Lecturio Medical Knowledge Essentials – Hypertension

Authors: Ahmed Elsherif ¹ ; Michelle Wyatt ²
Peer Reviewers: Stanley Oiseth ³ ; Joseph Alpert ⁴
Affiliations: ¹ Suez Canal University; ² Medical Editor at Lecturio; ³ Chief Medical Editor at Lecturio; ⁴ Tucson University, Arizona

This article is not intended to be a substitute for professional medical advice and should not be relied on as health or personal advice. Always seek the guidance of your doctor or other qualified health professional with any questions you may have regarding your health or a medical condition.

Definitions and Staging Classification

• A diagnosis of HTN requires integration of the measurements made in the clinic with home or ambulatory blood pressure monitoring (ABPM).[1]
• From the 2017 American College of Cardiology/ American Heart Association American Heart Association A voluntary organization concerned with the prevention and treatment of heart and vascular diseases. Heart Failure (ACC/AHA), the definitions and staging Staging Methods which attempt to express in replicable terms the extent of the neoplasm in the patient. Grading, Staging, and Metastasis of hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension are:
  • Normal systolic blood pressure ( SBP SBP Ascites) <120 mm Hg and diastolic blood pressure (DBP) <80 mm Hg
  • Elevated BP: SBP SBP Ascites 120–129 mm Hg and DBP <80 mm Hg
  • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, Stage 1 Stage 1 Trypanosoma brucei/African trypanosomiasis: SBP SBP Ascites 130–139 mm Hg or DBP 80–89 mm Hg 
  • Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, Stage 2: SBP SBP Ascites ≥140 mm Hg or DBP ≥90 mm Hg
  • Treated hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension: Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship on medication for hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, regardless of the BP
  • Note: The ACC/AHA stage is established by the higher value, if the  SBP SBP Ascites and DBP differ in stage.
• The ACC/AHA guidelines have been contested because some medical experts and other professional societies believe that the data is not definitive, that the risk of harm may outweigh the benefit in individual cases, and that the new guidelines are not practical to follow in low and middle-income countries since so many people with HTN in those countries already do not receive treatment at the higher thresholds.[9-11] A systematic review by the Cochrane Organization also noted: “For the general population of persons with elevated blood pressure, the benefits of trying to achieve a lower blood pressure target rather than a standard target (≤ 140/90 mm Hg) do not outweigh the harms associated with that intervention. Further research Research Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. Conflict of Interest is needed to see if some groups of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship would benefit or be harmed by lower targets. The results of this review are primarily applicable to older people with moderate to high cardiovascular risk. They may not be applicable to other populations.”[3] HTN was  defined in 2018 by the European Society of Cardiology and European Society of Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension (ESC/ESH), the International Society of Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension (ISH), and the National Institute for Health and Care Excellence (NICE guidelines), as follows: “ Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, using office-based blood pressure, is defined as: Systolic BP ≥140 mm Hg or diastolic BP ≥90 mm Hg.”[12]
• Recent guidelines continue to emphasize out-of-office blood pressure monitoring for diagnosis confirmation and personalized treatment approaches based on cardiovascular risk stratification. Despite this convergence Convergence Pupil: Physiology and Abnormalities, significant differences persist, particularly regarding the timing for initiating therapy. The key points from the 2023 ESH Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension Guideline Update were:
  • The 2023 ESH and the 2017 ACC/AHA guidelines both stress the importance of accurate blood pressure (BP) measurement, cardiovascular ( CV CV Vasculitides) risk evaluation, optimal lifestyle changes, and specific pharmacological management.
  • Both sets of guidelines suggest a lower BP target (<130/80 mm Hg) for high-risk adults to decrease the likelihood of cardiovascular events.
  • Significant differences include a lower diagnostic threshold Threshold Minimum voltage necessary to generate an action potential (an all-or-none response) Skeletal Muscle Contraction according to ACC/AHA criteria (<130/80 mm Hg) compared to ESH criteria (<140/90 mm Hg), as well as age-based treatment targets specific to ESH criteria.[26]
• This article is following the ACC/AHA guidelines.

Epidemiology

A person who has an actual measured high blood pressure and/or is taking antihypertensive medication is considered to have HTN.[1] In 2019, a global study using ≥140/90 mm Hg as the definition of HTN found that the prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of HTN in adults aged 30–79 years was 32% in women and 34% in men, which was similar to the 1990 levels. These percentages would have increased to an average of approximately 45% if the 2017 ACC/AHA lower cutoff level of ≥130/80 had been used, signifying a global burden of hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension of at least 1.8 billion people.[2] The prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency of HTN increases with age (70% of adults ≥65 years have hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension[13] and body weight. In the United States, the prevalence Prevalence The total number of cases of a given disease in a specified population at a designated time. It is differentiated from incidence, which refers to the number of new cases in the population at a given time. Measures of Disease Frequency is higher in Blacks than in Whites or Hispanics, and also higher in rural than in urban environments. Most people with HTN do not have adequate blood pressure control, even in high-income countries, but this is particularly pronounced in low and middle-income countries, where BP control is often very low, and many hypertensives remain undiagnosed. In high-income countries, only 37% of men and 43% of women have their HTN under control, while these percentages drop to 9% for men and 13% for women in sub-Saharan Africa and Oceania.

Etiology

Systemic arterial hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension (HTN) is divided into two types: primary hypertension Primary hypertension Hypertension that occurs without known cause, or preexisting renal disease. Associated polymorphisms for a number of genes have been identified, including agt, gnb3, and ece1. Hypertension (also known as “essential hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension” because at one time it was believed the high pressure was necessary to keep the vital organs perfused); and secondary hypertension Secondary hypertension Hypertension.[14-16]

Primary Hypertension Primary hypertension Hypertension that occurs without known cause, or preexisting renal disease. Associated polymorphisms for a number of genes have been identified, including agt, gnb3, and ece1. Hypertension ( PH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance)

This is hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension of unknown cause. Depending on the diagnostic method used, approximately 80–95% of hypertensive patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have PH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance, which is really the final manifestation of different underlying pathophysiologies. 60–70% of PH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance in adults has been attributed to being overweight or obese. Peripheral vascular resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing (PVR) is increased, and cardiac output Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics is normal or decreased in most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with long-standing PH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance; however, in younger patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship, the PVR may be normal, with increased cardiac output Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics. Plasma renin activity Plasma renin activity Renal Artery Stenosis ( PRA PRA Purine and Pyrimidine Metabolism) is increased in approximately 10–15% of individuals with PH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance (called “vasoconstrictor type” of HTN), while PRA PRA Purine and Pyrimidine Metabolism is decreased in ~ 25% (called “volume-dependent” or “low-renin hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension;” which is more common in African Americans). These underlying mechanisms help explain why not all PH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have the same response to the same medication: a person with high-renin HTN would likely respond to a vasodilator, and a low-renin HTN patient would likely respond to an aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia antagonist like spironolactone Spironolactone A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. Potassium-sparing Diuretics since aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia tends to be elevated in low-renin conditions. 

The risk factors associated with primary hypertension Primary hypertension Hypertension that occurs without known cause, or preexisting renal disease. Associated polymorphisms for a number of genes have been identified, including agt, gnb3, and ece1. Hypertension are:[17]

• Obesity Obesity Obesity is a condition associated with excess body weight, specifically with the deposition of excessive adipose tissue. Obesity is considered a global epidemic. Major influences come from the western diet and sedentary lifestyles, but the exact mechanisms likely include a mixture of genetic and environmental factors. Obesity and general weight gain (accounts for 60–70% of PH pH The quantitative measurement of the acidity or basicity of a solution. Acid-Base Balance; central adiposity is associated with higher risk)
• Age: advancing age is associated with weight gain, and especially associated with ↑ SBP SBP Ascites
• Family history Family History Adult Health Maintenance: Genetic factors can affect blood pressure increases by 30–50% [16]
• Race: HTN tends to be more common and more severe in people with African ancestry
• High-sodium diet: >3 g/day of sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes consumption increases the risk
• Excessive alcohol consumption
• Lack of exercise
• Reduced adult nephron Nephron The functional units of the kidney, consisting of the glomerulus and the attached tubule. Kidneys: Anatomy mass Mass Three-dimensional lesion that occupies a space within the breast Imaging of the Breast, from any cause—genetic/congenital, drugs, malnutrition Malnutrition Malnutrition is a clinical state caused by an imbalance or deficiency of calories and/or micronutrients and macronutrients. The 2 main manifestations of acute severe malnutrition are marasmus (total caloric insufficiency) and kwashiorkor (protein malnutrition with characteristic edema). Malnutrition in children in resource-limited countries, infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease

Secondary Hypertension Secondary hypertension Hypertension

• This category comprises 5% to 10% of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with HTN, and indicates an underlying and potentially reversible cause.[15] Many causes may coexist with primary hypertension Primary hypertension Hypertension that occurs without known cause, or preexisting renal disease. Associated polymorphisms for a number of genes have been identified, including agt, gnb3, and ece1. Hypertension and make adequate blood pressure control difficult to achieve. [1]
• Suspect if:
  • Unusual presentation of HTN (onset at < 30 or > 55 years; abrupt onset of HTN in a patient with previously normal BP; or elevation in blood pressure in a well-controlled hypertensive)
  • Drug-resistant hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
  • Clinical clues, e.g., such as an abdominal bruit Abdominal Bruit Abdominal Examination → may indicate possible renovascular hypertension Renovascular hypertension Hypertension due to renal artery obstruction or compression. Renal Artery Stenosis; low serum potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia → possible primary aldosteronism
• The Four Major Causes of Secondary Hypertension Secondary hypertension Hypertension:
  • Primary aldosteronism (PA) – Triad of hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia (only in 50%), metabolic alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis. Elevated ratio of plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia to plasma renin activity Plasma renin activity Renal Artery Stenosis; chronic licorice intake can mimic PA.
  • Renovascular hypertension Renovascular hypertension Hypertension due to renal artery obstruction or compression. Renal Artery Stenosis – often due to fibromuscular dysplasia Fibromuscular dysplasia Fibromuscular dysplasia (FMD) is a nonatherosclerotic, noninflammatory, medium-sized angiopathy due to fibroplasia of the vessel wall. The condition leads to complications related to arterial stenosis, aneurysm, or dissection. Fibromuscular Dysplasia in younger patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship and to atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis in older patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship; may have abdominal bruit Abdominal Bruit Abdominal Examination
  • Primary kidney disease – Acute or chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease
  • Obstructive sleep apnea Sleep apnea Repeated cessation of breathing for > 10 seconds during sleep and results in sleep interruption, fatigue, and daytime sleepiness. Obstructive Sleep Apnea ( OSA OSA Obstructive sleep apnea (OSA) is a disorder characterized by recurrent obstruction of the upper airway during sleep, causing hypoxia and fragmented sleep. Obstructive sleep apnea is due to a partial or complete collapse of the upper airway and is associated with snoring, restlessness, sleep interruption, and daytime somnolence. Obstructive Sleep Apnea): typical patient is obese man who snores loudly; > 50% of people with OSA OSA Obstructive sleep apnea (OSA) is a disorder characterized by recurrent obstruction of the upper airway during sleep, causing hypoxia and fragmented sleep. Obstructive sleep apnea is due to a partial or complete collapse of the upper airway and is associated with snoring, restlessness, sleep interruption, and daytime somnolence. Obstructive Sleep Apnea have HTN
• Less Common Cause of Secondary Hypertension Secondary hypertension Hypertension:
  • Medications, both prescription and over-the-counter: nonsteroidal antiinflammatory agents, especially if used chronically; oral contraceptives; antidepressants; corticosteroids Corticosteroids Chorioretinitis;decongestants; various weight-loss medications; sodium-containing antacids, if used chronically; stimulants Stimulants Stimulants are used by the general public to increase alertness and energy, decrease fatigue, and promote mental focus. Stimulants have medical uses for individuals with ADHD and sleep disorders, and are also used in combination with analgesics in pain management. Stimulants, including amphetamines Amphetamines Analogs or derivatives of amphetamine. Many are sympathomimetics and central nervous system stimulators causing excitation, vasopressin, bronchodilation, and to varying degrees, anorexia, analepsis, nasal decongestion, and some smooth muscle relaxation. Stimulants and methylphenidate Methylphenidate A central nervous system stimulant used most commonly in the treatment of attention deficit disorder in children and for narcolepsy. Its mechanisms appear to be similar to those of dextroamphetamine. Stimulants; erythropoietin Erythropoietin Glycoprotein hormone, secreted chiefly by the kidney in the adult and the liver in the fetus, that acts on erythroid stem cells of the bone marrow to stimulate proliferation and differentiation. Erythrocytes: Histology; cyclosporine Cyclosporine A cyclic undecapeptide from an extract of soil fungi. It is a powerful immunosupressant with a specific action on T-lymphocytes. It is used for the prophylaxis of graft rejection in organ and tissue transplantation. Immunosuppressants or tacrolimus Tacrolimus A macrolide isolated from the culture broth of a strain of streptomyces tsukubaensis that has strong immunosuppressive activity in vivo and prevents the activation of T-lymphocytes in response to antigenic or mitogenic stimulation in vitro. Immunosuppressants; atypical antipsychotics Atypical Antipsychotics Antiemetics; angiogenesis Angiogenesis Bartonella inhibitors; tyrosine Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids kinase inhibitors; and illegal drug use, especially methamphetamines and cocaine Cocaine An alkaloid ester extracted from the leaves of plants including coca. It is a local anesthetic and vasoconstrictor and is clinically used for that purpose, particularly in the eye, ear, nose, and throat. It also has powerful central nervous system effects similar to the amphetamines and is a drug of abuse. Cocaine, like amphetamines, acts by multiple mechanisms on brain catecholaminergic neurons; the mechanism of its reinforcing effects is thought to involve inhibition of dopamine uptake. Local Anesthetics
  • Endocrine disorders: hypothyroidism Hypothyroidism Hypothyroidism is a condition characterized by a deficiency of thyroid hormones. Iodine deficiency is the most common cause worldwide, but Hashimoto’s disease (autoimmune thyroiditis) is the leading cause in non-iodine-deficient regions. Hypothyroidism, hyperthyroidism Hyperthyroidism Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism, hyperparathyroidism Hyperparathyroidism Hyperparathyroidism is a condition associated with elevated blood levels of parathyroid hormone (PTH). Depending on the pathogenesis of this condition, hyperparathyroidism can be defined as primary, secondary or tertiary. Hyperparathyroidism, Cushing syndrome Cushing syndrome A condition caused by prolonged exposure to excess levels of cortisol (hydrocortisone) or other glucocorticoids from endogenous or exogenous sources. It is characterized by upper body obesity; osteoporosis; hypertension; diabetes mellitus; hirsutism; amenorrhea; and excess body fluid. Endogenous Cushing syndrome or spontaneous hypercortisolism is divided into two groups, those due to an excess of adrenocorticotropin and those that are acth-independent. Paraneoplastic Syndromes
  • Pheochromocytoma Pheochromocytoma Pheochromocytoma is a catecholamine-secreting tumor derived from chromaffin cells. The majority of tumors originate in the adrenal medulla, but they may also arise from sympathetic ganglia (also referred to as paraganglioma). Symptoms are associated with excessive catecholamine production and commonly include hypertension, tachycardia, headache, and sweating. Pheochromocytoma: 50% have paroxysmal hypertension Paroxysmal Hypertension Pheochromocytoma; others appear to be primary hypertension Primary hypertension Hypertension that occurs without known cause, or preexisting renal disease. Associated polymorphisms for a number of genes have been identified, including agt, gnb3, and ece1. Hypertension; rare cause
  • Coarctation of the aorta Aorta The main trunk of the systemic arteries. Mediastinum and Great Vessels: Anatomy: Major cause in young children, but also diagnosed in adults

The mechanism of renovascular hypertension Renovascular hypertension Hypertension due to renal artery obstruction or compression. Renal Artery Stenosis is mainly due to renal ischemia Ischemia A hypoperfusion of the blood through an organ or tissue caused by a pathologic constriction or obstruction of its blood vessels, or an absence of blood circulation. Ischemic Cell Damage. Renal artery Renal artery A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. Glomerular Filtration stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS) results in an increased level of renin Renin A highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system. Renal Sodium and Water Regulation and angiotensin I and II. These are associated with increased vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure, hence, hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension and an increased sympathetic tone. Aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia production is also increased in these patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship which results in increased retention of sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia. The increased retention of sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia is associated with increased water retention and can lead to extracellular blood volume. The interplay between these 2 mechanisms is the main cause of hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension in this group of patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.

Another type of arterial hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension is hypertensive disease of pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care. Risk factors include increasing maternal age and multifetal pregnancies.

Hypertensive disorders of pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care are divided into:

• Gestational hypertension Gestational hypertension A condition in pregnant women with elevated systolic (>140 mm hg) and diastolic (>90 mm hg) blood pressure on at least two occasions 6 h apart. Hypertension complicates 8-10% of all pregnancies, generally after 20 weeks of gestation. Gestational hypertension can be divided into several broad categories according to the complexity and associated symptoms, such as edema; proteinuria; seizures; abnormalities in blood coagulation and liver functions. Hypertensive Pregnancy Disorders ( hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension not associated with proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children)
• Preeclampsia Preeclampsia A complication of pregnancy, characterized by a complex of symptoms including maternal hypertension and proteinuria with or without pathological edema. Symptoms may range between mild and severe. Pre-eclampsia usually occurs after the 20th week of gestation, but may develop before this time in the presence of trophoblastic disease. Hypertensive Pregnancy Disorders ( hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension associated with proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children); it is a disorder of widespread vascular endothelial malfunction and vasospasm that occurs after 20 weeks’ gestation, and presents up to 4-6 weeks postpartum.
• Eclampsia Eclampsia Onset of hyperreflexia; seizures; or coma in a previously diagnosed pre-eclamptic patient (pre-eclampsia). Hypertensive Pregnancy Disorders (new onset of grand mal seizure activity and/or unexplained coma Coma Coma is defined as a deep state of unarousable unresponsiveness, characterized by a score of 3 points on the GCS. A comatose state can be caused by a multitude of conditions, making the precise epidemiology and prognosis of coma difficult to determine. Coma during pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care or postpartum in a woman with signs or symptoms of preeclampsia Preeclampsia A complication of pregnancy, characterized by a complex of symptoms including maternal hypertension and proteinuria with or without pathological edema. Symptoms may range between mild and severe. Pre-eclampsia usually occurs after the 20th week of gestation, but may develop before this time in the presence of trophoblastic disease. Hypertensive Pregnancy Disorders

Pathophysiology

Blood is delivered to the tissues and flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure occurs because of the pressure difference established by the pumping action of the heart. This relation between the pressure difference and the flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure can be described by the important equation: MAP = CO x PVR, where MAP = mean arterial pressure Mean Arterial Pressure Mean arterial pressure (MAP) is the average systemic arterial pressure and is directly related to cardiac output (CO) and systemic vascular resistance (SVR). The SVR and MAP are affected by the vascular anatomy as well as a number of local and neurohumoral factors. Vascular Resistance, Flow, and Mean Arterial Pressure (= diastolic pressure + ⅓ [systolic pressure – diastolic pressure]), CO = cardiac output Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics (= stroke volume Stroke volume The amount of blood pumped out of the heart per beat, not to be confused with cardiac output (volume/time). It is calculated as the difference between the end-diastolic volume and the end-systolic volume. Cardiac Cycle x heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology), and PVR = total peripheral resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing. At its basic level, this equation emphasizes that an elevation of mean blood pressure can only occur if there is an increase in cardiac output Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics (CO), an increase in total peripheral vascular resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing (PVR), or a combination of both. The main factors which determine blood pressure are the sympathetic nervous system Nervous system The nervous system is a small and complex system that consists of an intricate network of neural cells (or neurons) and even more glial cells (for support and insulation). It is divided according to its anatomical components as well as its functional characteristics. The brain and spinal cord are referred to as the central nervous system, and the branches of nerves from these structures are referred to as the peripheral nervous system. Nervous System: Anatomy, Structure, and Classification, the renin-angiotensin-aldosterone system Renin-angiotensin-aldosterone system A blood pressure regulating system of interacting components that include renin; angiotensinogen; angiotensin converting enzyme; angiotensin i; angiotensin ii; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to angiotensin II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal vascular smooth muscle, leading to retention of salt and water in the kidney and increased arterial blood pressure. In addition, angiotensin II stimulates the release of aldosterone from the adrenal cortex, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down bradykinin, a powerful vasodilator and component of the kallikrein-kinin system. Adrenal Hormones, and the plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products volume, which is mostly regulated by the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys: Anatomy. Increased peripheral vascular resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing (PVR) is the hallmark of established hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, but altered cardiac function also probably contributes to the raised blood pressure.[18] An increase in calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes intake slightly reduces both systolic and diastolic blood pressure in normotensive people, indicating a possible role in the prevention of hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension.[19] The underlying pathogenesis of primary hypertension Primary hypertension Hypertension that occurs without known cause, or preexisting renal disease. Associated polymorphisms for a number of genes have been identified, including agt, gnb3, and ece1. Hypertension is not well-understood, but many genetic and environmental factors are involved.

Clinical Features

Most people with hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension have no signs or symptoms, even with severe HTN; that is why it is often called “the silent killer.” Some people with severe HTN may have non-specific signs and symptoms, including headaches, shortness of breath Shortness of breath Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, nosebleeds Nosebleeds Bleeding from the nose. Granulomatosis with Polyangiitis, fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia, confusion, vision Vision Ophthalmic Exam alterations, chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, palpitations Palpitations Ebstein’s Anomaly, or hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma.

Subtypes and Variants

Special forms of arterial hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension are isolated office hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension and isolated ambulatory hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension.[1]

1. White-coat hypertension White-coat hypertension Phenomenon where blood pressure readings are elevated only when taken in clinical settings. Hypertension (“White-coat effect”)

• Defined as a BP which is consistently elevated by office readings only when in the physician’s office, while measurements taken at home and during ambulatory blood pressure monitoring are normal.
• Not true hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension

2. Isolated systolic hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension: 

• Defined as an increase in systolic blood pressure with diastolic blood pressure within normal limits
• Occurs commonly in the elderly due to decreased arterial elasticity Elasticity Resistance and recovery from distortion of shape. Skeletal Muscle Contraction/increased stiffness of the arteries Arteries Arteries are tubular collections of cells that transport oxygenated blood and nutrients from the heart to the tissues of the body. The blood passes through the arteries in order of decreasing luminal diameter, starting in the largest artery (the aorta) and ending in the small arterioles. Arteries are classified into 3 types: large elastic arteries, medium muscular arteries, and small arteries and arterioles. Arteries: Histology
• Having a high systolic blood pressure for a long period of time can increase the risk of strokes, heart disease and chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease.

3. Masked hypertension Masked hypertension Phenomenon where increased blood pressure readings taken in non-clinical settings (e.g., home blood pressure monitoring) do not replicate in clinical settings. Hypertension: This is BP that is consistently elevated by out-of-office measurements but normal at the office.

Diagnostics

Medical History and Physical Examination

Gathering a patient’s medical history is essential because it helps to discover risk factors, previous blood pressure measurements, and symptoms referable to hypertensive-related target organ damage, including ischemic heart disease Ischemic heart disease Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. Coronary Heart Disease, cerebrovascular disease, and chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease. It is very important to ask patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship about their current medications, previous illnesses, and family history Family History Adult Health Maintenance.

The patient’s physical examination should include checking the radial and the femoral pulses and performing abdominal auscultation Abdominal Auscultation Abdominal Examination which may help identify a bruit associated with renal artery Renal artery A branch of the abdominal aorta which supplies the kidneys, adrenal glands and ureters. Glomerular Filtration stenosis Stenosis Hypoplastic Left Heart Syndrome (HLHS), although this is not a sensitive test for RAS RAS Renal artery stenosis (RAS) is the narrowing of one or both renal arteries, usually caused by atherosclerotic disease or by fibromuscular dysplasia. If the stenosis is severe enough, the stenosis causes decreased renal blood flow, which activates the renin-angiotensin-aldosterone system (RAAS) and leads to renovascular hypertension (RVH). Renal Artery Stenosis.

Furthermore, it is essential to look for signs of heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) and left ventricular hypertrophy Ventricular Hypertrophy Tetralogy of Fallot. The fundi of the eyes should be examined as well to evaluate for possible hypertensive retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome, which will show progressively severe changes ranging from mild arteriolar narrowing → focal arteriovenous nicking Arteriovenous Nicking Hypertensive Retinopathy → retinal hemorrhages and exudates → papilledema Papilledema Swelling of the optic disk, usually in association with increased intracranial pressure, characterized by hyperemia, blurring of the disk margins, microhemorrhages, blind spot enlargement, and engorgement of retinal veins. Chronic papilledema may cause optic atrophy and visual loss. Idiopathic Intracranial Hypertension (grade IV hypertensive retinopathy Retinopathy Degenerative changes to the retina due to hypertension. Alport Syndrome).

Measuring Blood Pressure

Except for diagnostic severe hypertension Severe hypertension A confirmed blood pressure ≥ 180 mm Hg systolic and/or ≥ 120 mm Hg diastolic. Uncontrolled Hypertension ( SBP SBP Ascites ≥180 mm Hg and/or DBP ≥120 mm) or asymptomatic Stage 2 hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who have an elevated office blood pressure should have out-of-office blood pressure measurements for confirmation of the presence of true HTN. Automated and validated oscillometric BP monitors are preferred to stethoscope-based manual methods, both in the office and at home. For home measurements, the patient measures their BP once in the morning and once in the evening for 7 days. The first day of readings and the remaining 12 measurements are averaged. Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension is diagnosed if the mean home BP is ≥130 mm Hg systolic or ≥80 mm Hg diastolic. 24-hour ambulatory blood pressure monitoring (ABPM) is an alternative if adequate home blood pressures cannot be obtained or if there is doubt about the validity Validity Validity refers to how accurate a test or research finding is. Causality, Validity, and Reliability of home readings.

All individuals 18 years or older should be screened for HTN, with annual evaluation for those > 40 years old or those with risk factors for HTN. Younger adults with no risk factors should be evaluated every 3–5 years.

Laboratory Diagnostics

All patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with a new diagnosis of hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension should have the following tests:

• Electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes (including calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes) and serum creatinine (to calculate the estimated glomerular filtration rate Glomerular filtration rate The volume of water filtered out of plasma through glomerular capillary walls into Bowman’s capsules per unit of time. It is considered to be equivalent to inulin clearance. Kidney Function Tests and determine the presence of kidney disease)
• Fasting glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance (to check for diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus)
• Urinalysis Urinalysis Examination of urine by chemical, physical, or microscopic means. Routine urinalysis usually includes performing chemical screening tests, determining specific gravity, observing any unusual color or odor, screening for bacteriuria, and examining the sediment microscopically. Urinary Tract Infections (UTIs) in Children (moderately increased albuminuria Albuminuria The presence of albumin in the urine, an indicator of kidney diseases. Kidney Function Tests [previously called “microalbuminuria”] which is associated with an increased incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of cardiovascular disease)
• Complete blood count
• Thyroid-stimulating hormone Thyroid-stimulating hormone A glycoprotein hormone secreted by the adenohypophysis. Thyrotropin stimulates thyroid gland by increasing the iodide transport, synthesis and release of thyroid hormones (thyroxine and triiodothyronine). Thyroid Hormones
• Lipid profile Lipid profile Lipid Disorders 
• Electrocardiogram Electrocardiogram An electrocardiogram (ECG) is a graphic representation of the electrical activity of the heart plotted against time. Adhesive electrodes are affixed to the skin surface allowing measurement of cardiac impulses from many angles. The ECG provides 3-dimensional information about the conduction system of the heart, the myocardium, and other cardiac structures. Electrocardiogram (ECG) 
• Calculation of 10-year atherosclerotic cardiovascular disease (ASCVD) risk: https://tools.acc.org/ldl/ascvd_risk_estimator/index.html#!/calulate/estimator/ or the newer AHA PREVENT calculator (https://professional.heart.org/en/guidelines-and-statements/prevent-calculator): in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with stage 1 Stage 1 Trypanosoma brucei/African trypanosomiasis hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension, ASCVD risk assessment Risk assessment The qualitative or quantitative estimation of the likelihood of adverse effects that may result from exposure to specified health hazards or from the absence of beneficial influences. Preoperative Care can guide the need for treatment.

Extensive evaluation for secondary causes of HTN is not justifiable for all patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with primary hypertension Primary hypertension Hypertension that occurs without known cause, or preexisting renal disease. Associated polymorphisms for a number of genes have been identified, including agt, gnb3, and ece1. Hypertension, but rather only a targeted approach is recommended if there is an atypical presentation or there is a clinical clue that a secondary cause may be present.

Treatment

Non-pharmacological treatment (lifestyle modifications): alone or with antihypertensive drug therapy:

• Dietary salt restriction: can reduce SBP SBP Ascites/DBP by 4.8/2.5 mm Hg
• Potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia supplementation (best by dietary modification): unless chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease or using medications that reduce potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia excretion
• Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery: can reduce BP 0.5 to 2 mm Hg for every 1 kg lost
• Dietary Approaches to Stop Hypertension Dietary Approaches To Stop Hypertension Dietary recommendations that promote reduction in or prevention of high blood pressure. Recommendations include increasing intake of fruits and vegetables, and high-fiber, low-fat foods and reducing the intake of dietary sodium and high fat foods. Hypertension (DASH) diet: high in vegetables, fruits, low-fat dairy products, whole grains, poultry, fish FISH A type of in situ hybridization in which target sequences are stained with fluorescent dye so their location and size can be determined using fluorescence microscopy. This staining is sufficiently distinct that the hybridization signal can be seen both in metaphase spreads and in interphase nuclei. Chromosome Testing, and nuts and low in sweets, sugar-sweetened beverages, and red meat: can reduce SBP SBP Ascites/DBP by 6/4 mm Hg
• Exercise: Aerobic, dynamic resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing, and isometric resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing exercise at least 3–4 x per week of moderate-intensity aerobic exercise lasting approximately 40 minutes; can reduce SBP SBP Ascites/BP by 5/3 mm Hg
• Limited alcohol intake: Adult men and women with hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension should consume no more than two and one drinks/day respectively

Pharmacological Treatment

Blood pressure targets are based upon the patient’s risk for having a future cardiovascular event. In general, more aggressive blood pressure goals are indicated for higher-risk patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship. Treatment approach depends on the blood pressure stage and cardiovascular risk. For most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with stage 2 hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension (≥140/90 mmHg), initial combination therapy with 2 agents is recommended, preferably as single-pill combinations. Initial monotherapy is appropriate for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with stage 1 Stage 1 Trypanosoma brucei/African trypanosomiasis hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension who have cardiovascular risk factors or for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship at higher risk for adverse drug effects.

• Stage 1 Stage 1 Trypanosoma brucei/African trypanosomiasis Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension (130-139/80-89 mmHg):
  • Antihypertensive monotherapy for patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with established cardiovascular disease, diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus, chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease, age ≥65 years, or 10-year ASCVD risk ≥10%
  • Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship without these risk factors are managed with lifestyle modifications only.
• Stage 2 Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension (≥140/90 mmHg):
  • Combination therapy is recommended for most patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship, with single-pill combinations preferred over free equivalents to improve adherence and blood pressure control.

First-line medications include:

• Thiazide Thiazide Heterocyclic compounds with sulfur and nitrogen in the ring. This term commonly refers to the benzothiadiazines that inhibit sodium-potassium-chloride symporters and are used as diuretics. Hyponatremia diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Chronic Coronary Syndrome Medication
• Angiotensin-converting enzyme (ACE) inhibitors
• Angiotensin receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors blockers ( ARBs ARBs Agents that antagonize angiotensin receptors. Many drugs in this class specifically target the angiotensin type 1 receptor. Heart Failure and Chronic Coronary Syndrome Medication)
• Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blockers

While the above medications are considered as primary antihypertensives Antihypertensives The 1st-line medication classes for hypertension include thiazide-like diuretics, angiotensin-converting enzyme inhibitors (ACEis), angiotensin II receptor blockers (ARBs), and calcium channel blockers (CCBS). Contraindications, adverse effects, and drug-to-drug interactions are agent specific. Hypertension Drugs, they can still be combined. 

Preferred Drug Combinations: When combination therapy is indicated, the preferred combination is an ACE inhibitor or ARB with a dihydropyridine Dihydropyridine Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers) calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blocker. An alternative is an ACE inhibitor or ARB with a thiazide-like diuretic ( chlorthalidone Chlorthalidone A benzenesulfonamide-phthalimidine that tautomerizes to a benzophenones form. It is considered a thiazide-like diuretic. Thiazide Diuretics or indapamide Indapamide A benzamide-sulfonamide-indole derived diuretic that functions by inhibiting sodium chloride symporters. Hypertension Drugs preferred over hydrochlorothiazide Hydrochlorothiazide A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It is used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism. Thiazide Diuretics).

Secondary antihypertensives Antihypertensives The 1st-line medication classes for hypertension include thiazide-like diuretics, angiotensin-converting enzyme inhibitors (ACEis), angiotensin II receptor blockers (ARBs), and calcium channel blockers (CCBS). Contraindications, adverse effects, and drug-to-drug interactions are agent specific. Hypertension Drugs are used when primary medications do not work or when there are special indications such as in hypertensive patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who also have ischemic heart disease Ischemic heart disease Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. Coronary Heart Disease. 

Secondary antihypertensives Antihypertensives The 1st-line medication classes for hypertension include thiazide-like diuretics, angiotensin-converting enzyme inhibitors (ACEis), angiotensin II receptor blockers (ARBs), and calcium channel blockers (CCBS). Contraindications, adverse effects, and drug-to-drug interactions are agent specific. Hypertension Drugs include:

• Loop diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Chronic Coronary Syndrome Medication
• Potassium-sparing diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Chronic Coronary Syndrome Medication
• Beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers)
• Direct renin inhibitors Direct Renin Inhibitors Renin-Angiotensin-Aldosterone System Inhibitors
• Alpha-1 blockers
• Central alpha-2 blockers
• Direct vasodilators Vasodilators Drugs used to cause dilation of the blood vessels. Thromboangiitis Obliterans (Buerger Disease)

Diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Chronic Coronary Syndrome Medication

Primary sites of action [20]

Thiazide Thiazide Heterocyclic compounds with sulfur and nitrogen in the ring. This term commonly refers to the benzothiadiazines that inhibit sodium-potassium-chloride symporters and are used as diuretics. Hyponatremia Diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Chronic Coronary Syndrome Medication

• Excellent first-line therapy alone or in combination with other agents
• Mechanism: they bind BIND Hyperbilirubinemia of the Newborn the Cl − site of the Na+/ Cl − co-transport system in the distal convoluted tubule Distal convoluted tubule The portion of renal tubule that begins from the enlarged segment of the ascending limb of the loop of henle. It reenters the kidney cortex and forms the convoluted segments of the distal tubule. Gitelman Syndrome, thereby causing loss of sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia and chloride Chloride Inorganic compounds derived from hydrochloric acid that contain the Cl- ion. Electrolytes ions in the urine.
• The effect on blood pressure is limited because the contraction in blood volume stimulates  renin Renin A highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system. Renal Sodium and Water Regulation secretion Secretion Coagulation Studies, leading to angiotensin formation and aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia secretion Secretion Coagulation Studies, which raises blood pressure
• Generic and therefore inexpensive
• Shown to reduce cardiovascular-related events, for example, stroke, in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
• Examples: Chlorothiazide Chlorothiazide A thiazide diuretic with actions and uses similar to those of hydrochlorothiazide. Hypertension Drugs, chlorthalidone Chlorthalidone A benzenesulfonamide-phthalimidine that tautomerizes to a benzophenones form. It is considered a thiazide-like diuretic. Thiazide Diuretics, hydrochlorothiazide Hydrochlorothiazide A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It is used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism. Thiazide Diuretics ( HCTZ HCTZ A thiazide diuretic often considered the prototypical member of this class. It reduces the reabsorption of electrolytes from the renal tubules. This results in increased excretion of water and electrolytes, including sodium, potassium, chloride, and magnesium. It is used in the treatment of several disorders including edema, hypertension, diabetes insipidus, and hypoparathyroidism. Thiazide Diuretics), indapamide Indapamide A benzamide-sulfonamide-indole derived diuretic that functions by inhibiting sodium chloride symporters. Hypertension Drugs, metolazone Metolazone A quinazoline-sulfonamide derived diuretic that functions by inhibiting sodium chloride symporters. Hypertension Drugs

Adverse effects (AEs) of thiazide Thiazide Heterocyclic compounds with sulfur and nitrogen in the ring. This term commonly refers to the benzothiadiazines that inhibit sodium-potassium-chloride symporters and are used as diuretics. Hyponatremia diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Chronic Coronary Syndrome Medication:

• Hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia (low blood potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia level) is particularly a problem with chlorthalidone Chlorthalidone A benzenesulfonamide-phthalimidine that tautomerizes to a benzophenones form. It is considered a thiazide-like diuretic. Thiazide Diuretics (dose-related, may affect clinical outcome)
• Glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance intolerance ⇒ diabetic tendency
• Gout Gout Gout is a heterogeneous metabolic disease associated with elevated serum uric acid levels (> 6.8 mg/dL) and abnormal deposits of monosodium urate in tissues. The condition is often familial and is initially characterized by painful, recurring, and usually monoarticular acute arthritis, or “gout flare,” followed later by chronic deforming arthritis. Gout
• Kidney damage

Loop Diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Chronic Coronary Syndrome Medication

• Mechanism:
  • Act on the thick ascending limb Thick ascending limb Renal Sodium and Water Regulation, inhibiting the Na+/ K+/ 2Cl− carrier Carrier Vaccination in the lumenal membrane by combining with its Cl− binding site.
  • Initial vasodilator effect by unknown mechanism (s); intravenous administration of furosemide Furosemide A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for edema and chronic renal insufficiency. Loop Diuretics to patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema caused by acute heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) can be useful.
• Loop diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Chronic Coronary Syndrome Medication are the most powerful diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Chronic Coronary Syndrome Medication because they can cause the excretion of 15%–25% of the filtered Na+, which is delivered to the distal nephron Nephron The functional units of the kidney, consisting of the glomerulus and the attached tubule. Kidneys: Anatomy, causing loss of both H+ and K+. 
• The plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products concentration of HCO3− increases because plasma Plasma The residual portion of blood that is left after removal of blood cells by centrifugation without prior blood coagulation. Transfusion Products volume is reduced while HCO3− is not excreted, producing a form of metabolic alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis known as “ contraction alkalosis Contraction alkalosis Metabolic Alkalosis.”
• Examples: furosemide Furosemide A benzoic-sulfonamide-furan. It is a diuretic with fast onset and short duration that is used for edema and chronic renal insufficiency. Loop Diuretics (most commonly used), bumetanide Bumetanide A sulfamyl diuretic. Loop Diuretics and torsemide Torsemide A pyridine and sulfonamide derivative that acts as a sodium-potassium chloride symporter inhibitor. It is used for the treatment of edema associated with congestive heart failure; chronic renal insufficiency; and liver diseases. It is also used for the management of hypertension. Loop Diuretics; ethacrynic acid Ethacrynic acid A compound that inhibits symport of sodium, potassium, and chloride primarily in the ascending limb of henle, but also in the proximal and distal tubules. This pharmacological action results in excretion of these ions, increased urinary output, and reduction in extracellular fluid. This compound has been classified as a loop or high ceiling diuretic. Loop Diuretics (rarely) if there is allergy Allergy An abnormal adaptive immune response that may or may not involve antigen-specific IgE Type I Hypersensitivity Reaction to sulfonamides Sulfonamides A group of compounds that contain the structure so2nh2. Sulfonamides and Trimethoprim

Adverse effects of loop diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Chronic Coronary Syndrome Medication:

• Excessive Na+ and water loss—especially in elderly patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship—can cause
•   hypovolemia Hypovolemia Sepsis in Children and hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension. 
• Hypokalemia Hypokalemia Hypokalemia is defined as plasma potassium (K+) concentration < 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake. Hypokalemia and metabolic alkalosis Alkalosis A pathological condition that removes acid or adds base to the body fluids. Respiratory Alkalosis; can be serious. 
• Hyperuricemia Hyperuricemia Excessive uric acid or urate in blood as defined by its solubility in plasma at 37 degrees c; greater than 0. 42 mmol per liter (7. 0 mg/dl) in men or 0. 36 mmol per liter (6. 0 mg/dl) in women. Gout: can precipitate acute gout Acute Gout Gout 
• Hearing loss Hearing loss Hearing loss, also known as hearing impairment, is any degree of impairment in the ability to apprehend sound as determined by audiometry to be below normal hearing thresholds. Clinical presentation may occur at birth or as a gradual loss of hearing with age, including a short-term or sudden loss at any point. Hearing Loss: usually at high doses, may be worsened by concomitant use of other ototoxic drugs such as aminoglycoside antibiotics
• Hypomagnesemia Hypomagnesemia A nutritional condition produced by a deficiency of magnesium in the diet, characterized by anorexia, nausea, vomiting, lethargy, and weakness. Symptoms are paresthesias, muscle cramps, irritability, decreased attention span, and mental confusion, possibly requiring months to appear. Deficiency of body magnesium can exist even when serum values are normal. In addition, magnesium deficiency may be organ-selective, since certain tissues become deficient before others. Electrolytes: not often recognized

Antihypertensive Drugs: Hemodynamic Mechanism of BP Reduction

Renin-angiotensin Aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia System

The kidney is central to blood pressure control through the juxtaglomerular apparatus. Baroreceptors Baroreceptors Receptors in the vascular system, particularly the aorta and carotid sinus, which are sensitive to stretch of the vessel walls. Arginine Vasopressin Disorders (Diabetes Insipidus) in the arterial system inform the central nervous system Central nervous system The main information-processing organs of the nervous system, consisting of the brain, spinal cord, and meninges. Nervous System: Anatomy, Structure, and Classification about the level of blood pressure. The signals from baroreceptors Baroreceptors Receptors in the vascular system, particularly the aorta and carotid sinus, which are sensitive to stretch of the vessel walls. Arginine Vasopressin Disorders (Diabetes Insipidus) lead to changes in autonomic nervous system Autonomic nervous system The ANS is a component of the peripheral nervous system that uses both afferent (sensory) and efferent (effector) neurons, which control the functioning of the internal organs and involuntary processes via connections with the CNS. The ANS consists of the sympathetic and parasympathetic nervous systems. Autonomic Nervous System: Anatomy activity. Renin Renin A highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system. Renal Sodium and Water Regulation initiates a biochemical sequence that eventually converts angiotensinogen produced in the liver Liver The liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood. Liver: Anatomy into angiotensin, a strong vasoconstrictor. Angiotensin stimulates release of aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia from the adrenal gland which causes the kidney to retain salt (NaCl) and water. Angiotensin stimulates the release of antidiuretic hormone Antidiuretic hormone Antidiuretic hormones released by the neurohypophysis of all vertebrates (structure varies with species) to regulate water balance and osmolarity. In general, vasopressin is a nonapeptide consisting of a six-amino-acid ring with a cysteine 1 to cysteine 6 disulfide bridge or an octapeptide containing a cystine. All mammals have arginine vasopressin except the pig with a lysine at position 8. Vasopressin, a vasoconstrictor, acts on the kidney collecting ducts to increase water reabsorption, increase blood volume and blood pressure. Hypernatremia from the pituitary Pituitary A small, unpaired gland situated in the sella turcica. It is connected to the hypothalamus by a short stalk which is called the infundibulum. Hormones: Overview and Types gland which causes the kidney to retain water.

This system is part of the body’s defenses against dehydration Dehydration The condition that results from excessive loss of water from a living organism. Volume Depletion and Dehydration and/or blood loss. The purpose is to restore blood volume to normal as quickly as possible.

Angiotensin-converting enzyme inhibitors Angiotensin-converting enzyme inhibitors A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. Renin-Angiotensin-Aldosterone System Inhibitors ( ACEis ACEIs A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. Heart Failure and Chronic Coronary Syndrome Medication) and angiotensin receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors blockers ( ARBs ARBs Agents that antagonize angiotensin receptors. Many drugs in this class specifically target the angiotensin type 1 receptor. Heart Failure and Chronic Coronary Syndrome Medication) include:

• Captopril Captopril A potent and specific inhibitor of peptidyl-dipeptidase a. It blocks the conversion of angiotensin I to angiotensin II, a vasoconstrictor and important regulator of arterial blood pressure. Captopril acts to suppress the renin-angiotensin system and inhibits pressure responses to exogenous angiotensin. Hypertension Drugs — ACEi ACEi A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. Renin-Angiotensin-Aldosterone System Inhibitors
• Enalapril Enalapril An angiotensin-converting enzyme inhibitor that is used to treat hypertension and heart failure. Hypertension Drugs — ACEi ACEi A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. Renin-Angiotensin-Aldosterone System Inhibitors
• Lisinopril Lisinopril One of the angiotensin-converting enzyme inhibitors (ACE inhibitors), orally active, that has been used in the treatment of hypertension and congestive heart failure. Renin-Angiotensin-Aldosterone System Inhibitors — ACEi ACEi A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. Renin-Angiotensin-Aldosterone System Inhibitors
• Ramipril Ramipril A long-acting angiotensin-converting enzyme inhibitor. It is a prodrug that is transformed in the liver to its active metabolite ramiprilat. Hypertension Drugs — ACEi ACEi A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. Renin-Angiotensin-Aldosterone System Inhibitors
• Losartan Losartan An antagonist of angiotensin type 1 receptor with antihypertensive activity due to the reduced pressor effect of angiotensin II. Hypertension Drugs — ARB
• Candesartan — ARB
• Valsartan Valsartan A tetrazole derivative and angiotensin II type 1 receptor blocker that is used to treat hypertension. Hypertension Drugs — ARB

AE’s with ACEis ACEIs A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. Heart Failure and Chronic Coronary Syndrome Medication and ARBs ARBs Agents that antagonize angiotensin receptors. Many drugs in this class specifically target the angiotensin type 1 receptor. Heart Failure and Chronic Coronary Syndrome Medication — 1st line Rx

Aldosterone Antagonists Aldosterone antagonists Drugs that bind to and block the activation of mineralocorticoid receptors by mineralocorticoids such as aldosterone. Heart Failure and Chronic Coronary Syndrome Medication

• For resistant hypertension Resistant hypertension Blood pressure that remains uncontrolled despite concurrent use of 3 antihypertensive agents of different classes. Uncontrolled Hypertension despite potent diuretic therapy
• Mechanism of action: They block the effects of aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia on the renal distal convoluted tubule Distal convoluted tubule The portion of renal tubule that begins from the enlarged segment of the ascending limb of the loop of henle. It reenters the kidney cortex and forms the convoluted segments of the distal tubule. Gitelman Syndrome and collecting duct Collecting duct Straight tubes commencing in the radiate part of the kidney cortex where they receive the curved ends of the distal convoluted tubules. In the medulla the collecting tubules of each pyramid converge to join a central tube (duct of bellini) which opens on the summit of the papilla. Renal Cell Carcinoma, thereby decreasing sodium reabsorption Sodium reabsorption Tubular System and potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia excretion.

Aldosterone Aldosterone A hormone secreted by the adrenal cortex that regulates electrolyte and water balance by increasing the renal retention of sodium and the excretion of potassium. Hyperkalemia Inhibitors: Spironolactone Spironolactone A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. Potassium-sparing Diuretics and Eplerenone Eplerenone A spironolactone derivative and selective aldosterone receptor antagonist that is used in the management of hypertension and congestive heart failure, post-myocardial infarction. Potassium-sparing Diuretics

Spironolactone Spironolactone A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. Potassium-sparing Diuretics. However, eplerenone Eplerenone A spironolactone derivative and selective aldosterone receptor antagonist that is used in the management of hypertension and congestive heart failure, post-myocardial infarction. Potassium-sparing Diuretics is less potent and often requires twice-daily dosing (at 50 to 100 mg) to be as effective for blood pressure lowering. An eplerenone Eplerenone A spironolactone derivative and selective aldosterone receptor antagonist that is used in the management of hypertension and congestive heart failure, post-myocardial infarction. Potassium-sparing Diuretics dose of 50 mg once daily can be prescribed as an initial trial, with dose and frequency escalations undertaken as needed to achieve blood pressure control.

Adverse effects of aldosterone antagonists Aldosterone antagonists Drugs that bind to and block the activation of mineralocorticoid receptors by mineralocorticoids such as aldosterone. Heart Failure and Chronic Coronary Syndrome Medication

• Hyperkalemia Hyperkalemia Hyperkalemia is defined as a serum potassium (K+) concentration >5.2 mEq/L. Homeostatic mechanisms maintain the serum K+ concentration between 3.5 and 5.2 mEq/L, despite marked variation in dietary intake. Hyperkalemia can be due to a variety of causes, which include transcellular shifts, tissue breakdown, inadequate renal excretion, and drugs. Hyperkalemia: need to monitor potassium Potassium An element in the alkali group of metals with an atomic symbol k, atomic number 19, and atomic weight 39. 10. It is the chief cation in the intracellular fluid of muscle and other cells. Potassium ion is a strong electrolyte that plays a significant role in the regulation of fluid volume and maintenance of the water-electrolyte balance. Hyperkalemia levels!
• Spironolactone Spironolactone A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. Potassium-sparing Diuretics → gynecomastia Gynecomastia Gynecomastia is a benign proliferation of male breast glandular ductal tissue, usually bilateral, caused by increased estrogen activity, decreased testosterone activity, or medications. The condition is common and physiological in neonates, adolescent boys, and elderly men. Gynecomastia, breast tenderness, and erectile dysfunction Erectile Dysfunction Erectile dysfunction (ED) is defined as the inability to achieve or maintain a penile erection, resulting in difficulty to perform penetrative sexual intercourse. Local penile factors and systemic diseases, including diabetes, cardiac disease, and neurological disorders, can cause ED. Erectile Dysfunction (increases with higher doses) 
• Eplerenone Eplerenone A spironolactone derivative and selective aldosterone receptor antagonist that is used in the management of hypertension and congestive heart failure, post-myocardial infarction. Potassium-sparing Diuretics: more specific and without the side effects of spironolactone Spironolactone A potassium sparing diuretic that acts by antagonism of aldosterone in the distal renal tubules. It is used mainly in the treatment of refractory edema in patients with congestive heart failure, nephrotic syndrome, or hepatic cirrhosis. Its effects on the endocrine system are utilized in the treatments of hirsutism and acne but they can lead to adverse effects. Potassium-sparing Diuretics but less potent (may need twice-a-day dosing)

Beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers)

Beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers) reduce cardiac output Cardiac output The volume of blood passing through the heart per unit of time. It is usually expressed as liters (volume) per minute so as not to be confused with stroke volume (volume per beat). Cardiac Mechanics and decrease renin Renin A highly specific (leu-leu) endopeptidase that generates angiotensin I from its precursor angiotensinogen, leading to a cascade of reactions which elevate blood pressure and increase sodium retention by the kidney in the renin-angiotensin system. Renal Sodium and Water Regulation release by the kidney. They are considered as second-line antihypertensive agents, especially in people > 60 years of age, and include:

• Propranolol Propranolol A widely used non-cardioselective beta-adrenergic antagonist. Propranolol has been used for myocardial infarction; arrhythmia; angina pectoris; hypertension; hyperthyroidism; migraine; pheochromocytoma; and anxiety but adverse effects instigate replacement by newer drugs. Antiadrenergic Drugs
• Metoprolol Metoprolol A selective adrenergic beta-1 blocking agent that is commonly used to treat angina pectoris; hypertension; and cardiac arrhythmias. Antiadrenergic Drugs
• Atenolol Atenolol A cardioselective beta-1 adrenergic blocker possessing properties and potency similar to propranolol, but without a negative inotropic effect. Class 2 Antiarrhythmic Drugs (Beta Blockers)
• Carvedilol Carvedilol A carbazole and propanol derivative that acts as a non-cardioselective beta blocker and vasodilator. It has blocking activity for alpha 1 adrenergic receptors and, at higher doses, may function as a blocker of calcium channels; it also has antioxidant properties. Carvedilol is used in the treatment of hypertension; angina pectoris; and heart failure. It can also reduce the risk of death following myocardial infarction. Class 2 Antiarrhythmic Drugs (Beta Blockers)
• Bisoprolol Bisoprolol A cardioselective beta-1 adrenergic blocker. It is effective in the management of hypertension and angina pectoris. Class 2 Antiarrhythmic Drugs (Beta Blockers)
• Labetalol Labetalol A salicylamide derivative that is a non-cardioselective blocker of beta-adrenergic receptors and alpha-1 adrenergic receptors. Subarachnoid Hemorrhage

Adverse effects:

• May worsen heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) and asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma (so begin with very low doses) 
• Risk of bradycardia Bradycardia Bradyarrhythmia is a rhythm in which the heart rate is less than 60/min. Bradyarrhythmia can be physiologic, without symptoms or hemodynamic change. Pathologic bradyarrhythmia results in reduced cardiac output and hemodynamic instability causing syncope, dizziness, or dyspnea. Bradyarrhythmias and heart block as the dose is increased
• Impaired glucose Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Lactose Intolerance tolerance Tolerance Pharmacokinetics and Pharmacodynamics and an increased risk of new onset diabetes Diabetes Diabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance. Diabetes Mellitus 
• Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia and weakness: may resolve with time or by dose reduction

Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes Channel Blockers ( CCBs CCBs Calcium channel blockers (CCBS) are a class of medications that inhibit voltage-dependent L-type calcium channels of cardiac and vascular smooth muscle cells. The inhibition of these channels produces vasodilation and myocardial depression. There are 2 major classes of CCBS: dihydropyridines and non-dihydropyridines. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers))

• CCBs CCBs Calcium channel blockers (CCBS) are a class of medications that inhibit voltage-dependent L-type calcium channels of cardiac and vascular smooth muscle cells. The inhibition of these channels produces vasodilation and myocardial depression. There are 2 major classes of CCBS: dihydropyridines and non-dihydropyridines. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers) are first-line medications in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with abnormal kidney function. 
• They reduce peripheral resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing and blood pressure by dilating arterioles Arterioles The smallest divisions of the arteries located between the muscular arteries and the capillaries. Arteries: Histology (the resistance vessels Resistance vessels Arteries: Histology). 
• The mechanism of action involves inhibition of calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes influx into arterial smooth muscle cells. 
• There are two major classes of CCBs CCBs Calcium channel blockers (CCBS) are a class of medications that inhibit voltage-dependent L-type calcium channels of cardiac and vascular smooth muscle cells. The inhibition of these channels produces vasodilation and myocardial depression. There are 2 major classes of CCBS: dihydropyridines and non-dihydropyridines. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers):
  • Dihydropyridine Dihydropyridine Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers) CCBs CCBs Calcium channel blockers (CCBS) are a class of medications that inhibit voltage-dependent L-type calcium channels of cardiac and vascular smooth muscle cells. The inhibition of these channels produces vasodilation and myocardial depression. There are 2 major classes of CCBS: dihydropyridines and non-dihydropyridines. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers), e.g., amlodipine Amlodipine A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of angina pectoris and hypertension. Hypertension Drugs, nifedipine Nifedipine A potent vasodilator agent with calcium antagonistic action. It is a useful anti-anginal agent that also lowers blood pressure. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers)
    • Adverse effects:
      • Reflex tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children due to vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs and hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension, can worsen ischemic symptoms in angina due to an increase in myocardial oxygen demand Myocardial oxygen demand Stable and Unstable Angina
      • Can worsen proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children in patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with nephropathy
  • Non-dihydropyridine Non-Dihydropyridine Pulmonary Hypertension Drugs CCBs CCBs Calcium channel blockers (CCBS) are a class of medications that inhibit voltage-dependent L-type calcium channels of cardiac and vascular smooth muscle cells. The inhibition of these channels produces vasodilation and myocardial depression. There are 2 major classes of CCBS: dihydropyridines and non-dihydropyridines. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers)
    • Verapamil Verapamil A calcium channel blocker that is a class IV anti-arrhythmia agent. Pulmonary Hypertension Drugs: negative inotropic effect Negative Inotropic Effect Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers), minimal vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs
    • Diltiazem Diltiazem A benzothiazepine derivative with vasodilating action due to its antagonism of the actions of calcium ion on membrane functions. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers): negative inotropic effect Negative Inotropic Effect Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers) with vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs but less than dihydropyridine Dihydropyridine Pyridine moieties which are partially saturated by the addition of two hydrogen atoms in any position. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers) CCBs CCBs Calcium channel blockers (CCBS) are a class of medications that inhibit voltage-dependent L-type calcium channels of cardiac and vascular smooth muscle cells. The inhibition of these channels produces vasodilation and myocardial depression. There are 2 major classes of CCBS: dihydropyridines and non-dihydropyridines. Class 4 Antiarrhythmic Drugs (Calcium Channel Blockers)

Other Pharmacological Agents Occasionally used in the treatment of Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension 

• Minoxidil—very potent blood vessel dilator; also used for hair growth in cases of androgenic alopecia Alopecia Alopecia is the loss of hair in areas anywhere on the body where hair normally grows. Alopecia may be defined as scarring or non-scarring, localized or diffuse, congenital or acquired, reversible or permanent, or confined to the scalp or universal; however, alopecia is usually classified using the 1st 3 factors. Alopecia.
• Clonidine Clonidine An imidazoline sympatholytic agent that stimulates alpha-2 adrenergic receptors and central imidazoline receptors. It is commonly used in the management of hypertension. Sympathomimetic Drugs—blocks sympathetic activity in the brain Brain The part of central nervous system that is contained within the skull (cranium). Arising from the neural tube, the embryonic brain is comprised of three major parts including prosencephalon (the forebrain); mesencephalon (the midbrain); and rhombencephalon (the hindbrain). The developed brain consists of cerebrum; cerebellum; and other structures in the brain stem. Nervous System: Anatomy, Structure, and Classification and leads to decrease in vascular resistance Resistance Physiologically, the opposition to flow of air caused by the forces of friction. As a part of pulmonary function testing, it is the ratio of driving pressure to the rate of air flow. Ventilation: Mechanics of Breathing
• Peripheral sympathetic receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors blockers in vascular smooth muscle — alpha-blockers Alpha-blockers Drugs that bind to but do not activate alpha-adrenergic receptors thereby blocking the actions of endogenous or exogenous adrenergic agonists. Adrenergic alpha-antagonists are used in the treatment of hypertension, vasospasm, peripheral vascular disease, shock, and pheochromocytoma. Antiadrenergic Drugs

Possible Drug Combinations

Double combination options consist of administering a diuretic in combination with a beta-blocker, a long-acting calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blocker, ACE inhibitors ACE inhibitors Truncus Arteriosus, or ARBs ARBs Agents that antagonize angiotensin receptors. Many drugs in this class specifically target the angiotensin type 1 receptor. Heart Failure and Chronic Coronary Syndrome Medication.

An alternative is the combination of a calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blocker with a beta-blocker, ACE inhibitors ACE inhibitors Truncus Arteriosus (OR ARBs ARBs Agents that antagonize angiotensin receptors. Many drugs in this class specifically target the angiotensin type 1 receptor. Heart Failure and Chronic Coronary Syndrome Medication). Never use an ACE inhibitor ( ACEI ACEi A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. Renin-Angiotensin-Aldosterone System Inhibitors) and an angiotensin receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors blocker (ARB) together because their mechanisms target the same pathway, leading to overlapping effects. Both ACEIs ACEIs A class of drugs whose main indications are the treatment of hypertension and heart failure. They exert their hemodynamic effect mainly by inhibiting the renin-angiotensin system. They also modulate sympathetic nervous system activity and increase prostaglandin synthesis. They cause mainly vasodilation and mild natriuresis without affecting heart rate and contractility. Heart Failure and Chronic Coronary Syndrome Medication and ARBs ARBs Agents that antagonize angiotensin receptors. Many drugs in this class specifically target the angiotensin type 1 receptor. Heart Failure and Chronic Coronary Syndrome Medication interfere with the renin-angiotensin-aldosterone system Renin-angiotensin-aldosterone system A blood pressure regulating system of interacting components that include renin; angiotensinogen; angiotensin converting enzyme; angiotensin i; angiotensin ii; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to angiotensin II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal vascular smooth muscle, leading to retention of salt and water in the kidney and increased arterial blood pressure. In addition, angiotensin II stimulates the release of aldosterone from the adrenal cortex, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down bradykinin, a powerful vasodilator and component of the kallikrein-kinin system. Adrenal Hormones ( RAAS RAAS A blood pressure regulating system of interacting components that include renin; angiotensinogen; angiotensin converting enzyme; angiotensin i; angiotensin ii; and angiotensinase. Renin, an enzyme produced in the kidney, acts on angiotensinogen, an alpha-2 globulin produced by the liver, forming angiotensin I. Angiotensin-converting enzyme, contained in the lung, acts on angiotensin I in the plasma converting it to angiotensin II, an extremely powerful vasoconstrictor. Angiotensin II causes contraction of the arteriolar and renal vascular smooth muscle, leading to retention of salt and water in the kidney and increased arterial blood pressure. In addition, angiotensin II stimulates the release of aldosterone from the adrenal cortex, which in turn also increases salt and water retention in the kidney. Angiotensin-converting enzyme also breaks down bradykinin, a powerful vasodilator and component of the kallikrein-kinin system. Adrenal Hormones), which regulates blood pressure and fluid balance. Because both classes of drugs aim to reduce the effects of angiotensin II Angiotensin II An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the c-terminal by angiotensin converting enzyme. The amino acid in position 5 varies in different species. To block vasoconstriction and hypertension effect of angiotensin II, patients are often treated with ace inhibitors or with angiotensin II type 1 receptor blockers. Renal Sodium and Water Regulation, using them together does not provide additional benefits but rather increases the risk of adverse effects like hyperkalemia Hyperkalemia Hyperkalemia is defined as a serum potassium (K+) concentration >5.2 mEq/L. Homeostatic mechanisms maintain the serum K+ concentration between 3.5 and 5.2 mEq/L, despite marked variation in dietary intake. Hyperkalemia can be due to a variety of causes, which include transcellular shifts, tissue breakdown, inadequate renal excretion, and drugs. Hyperkalemia, hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension, and acute kidney injury Acute Kidney Injury Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury​. [24]Investigators involved in three large randomized controlled studies In lower-income countries concluded that fixed-dose combination treatment strategies substantially reduce the incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction, stroke, revascularization Revascularization Thromboangiitis Obliterans (Buerger Disease), and cardiovascular death in primary prevention of cardiovascular disease. These benefits were shown to be consistent irrespective of cardiometabolic risk factors. The combination pills, or polypills, included ≥2 blood pressure-lowering agents plus a statin, with or without aspirin Aspirin The prototypical analgesic used in the treatment of mild to moderate pain. It has anti-inflammatory and antipyretic properties and acts as an inhibitor of cyclooxygenase which results in the inhibition of the biosynthesis of prostaglandins. Aspirin also inhibits platelet aggregation and is used in the prevention of arterial and venous thrombosis. Nonsteroidal Antiinflammatory Drugs (NSAIDs).[7] If applied to all the people who live in low and middle-income countries, there would be a dramatic decrease in cardiovascular-related morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and mortality Mortality All deaths reported in a given population. Measures of Health Status, since most people with undiagnosed or uncontrolled hypertension Uncontrolled hypertension Although hypertension is defined as a blood pressure of > 130/80 mm Hg, individuals can present with comorbidities of severe asymptomatic or “uncontrolled” hypertension (≥ 180 mm Hg systolic and/or ≥ 120 mm Hg diastolic) that carries with it a significant risk of morbidity and mortality. Uncontrolled Hypertension live in those countries.[2]

In a study involving nearly 600 hypertensive patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship, a four-drug, single-pill combination containing low doses of irbesartan (an angiotensin II Angiotensin II An octapeptide that is a potent but labile vasoconstrictor. It is produced from angiotensin I after the removal of two amino acids at the c-terminal by angiotensin converting enzyme. The amino acid in position 5 varies in different species. To block vasoconstriction and hypertension effect of angiotensin II, patients are often treated with ace inhibitors or with angiotensin II type 1 receptor blockers. Renal Sodium and Water Regulation receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors blocker), indapamide Indapamide A benzamide-sulfonamide-indole derived diuretic that functions by inhibiting sodium chloride symporters. Hypertension Drugs (a thiazide-like diuretic), amlodipine Amlodipine A long-acting dihydropyridine calcium channel blocker. It is effective in the treatment of angina pectoris and hypertension. Hypertension Drugs (a calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blocker), and bisoprolol Bisoprolol A cardioselective beta-1 adrenergic blocker. It is effective in the management of hypertension and angina pectoris. Class 2 Antiarrhythmic Drugs (Beta Blockers) (a beta-blocker) was found to reduce 24-hour systolic blood pressure more effectively than a full dose of irbesartan alone (18 mmHg reduction versus 10 mmHg). Additionally, the combination pill achieved higher blood pressure control rates (77% compared to 50%). The incidence Incidence The number of new cases of a given disease during a given period in a specified population. It also is used for the rate at which new events occur in a defined population. It is differentiated from prevalence, which refers to all cases in the population at a given time. Measures of Disease Frequency of adverse effects was comparable between the two groups. Despite these promising results, the clinical experience with four-drug combination pills is still limited, and they are not yet recommended as an initial treatment option.[24]

Note: Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blockers of the non-dihydropyridine Non-Dihydropyridine Pulmonary Hypertension Drugs variety must not be administered in combination with beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers) as they may promote bradycardia Bradycardia Bradyarrhythmia is a rhythm in which the heart rate is less than 60/min. Bradyarrhythmia can be physiologic, without symptoms or hemodynamic change. Pathologic bradyarrhythmia results in reduced cardiac output and hemodynamic instability causing syncope, dizziness, or dyspnea. Bradyarrhythmias or an atrioventricular block Atrioventricular block Atrioventricular (AV) block is a bradyarrhythmia caused by delay, or interruption, in the electrical conduction between the atria and the ventricles. Atrioventricular block occurs due to either anatomic or functional impairment, and is classified into 3 types. Atrioventricular block (AV block) ( AV block AV block Atrioventricular (AV) block is a bradyarrhythmia caused by delay, or interruption, in the electrical conduction between the atria and the ventricles. Atrioventricular block occurs due to either anatomic or functional impairment, and is classified into 3 types. Atrioventricular block (AV block))!

Depending on the individual comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus, the respective medications may either gain or lose significance. A popular question in exams pertains to the following combinations: In case of hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension combined with heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR), diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Chronic Coronary Syndrome Medication are an option. ACE inhibitors ACE inhibitors Truncus Arteriosus may be used if there is heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR), diabetic nephropathy Diabetic nephropathy Kidney injuries associated with diabetes mellitus and affecting kidney glomerulus; arterioles; kidney tubules; and the interstitium. Clinical signs include persistent proteinuria, from microalbuminuria progressing to albuminuria of greater than 300 mg/24 h, leading to reduced glomerular filtration rate and end-stage renal disease. Chronic Diabetic Complications. Beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers) are also used for the treatment of heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR).

When choosing individual medications, side effects, individual tolerance Tolerance Pharmacokinetics and Pharmacodynamics, and interaction with other medications must be considered. If a two-drug combination is not effective, a third drug may be added. 

Isolated systolic hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension should be treated the same way as systolic and diastolic hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension. However, since ISH occurs mostly in older patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship, BP reduction should always be gradual (over 3–6 months) in these patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship. Ideally, maximal emphasis should be placed on nonpharmacologic therapy, particularly salt restriction and weight loss Weight loss Decrease in existing body weight. Bariatric Surgery in obese patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship, because antihypertensive drugs commonly cause orthostatic (postural) and/or postprandial hypotension Postprandial hypotension Hypotension in older hypertensive patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship.

Complications of Uncontrolled Hypertension

• Congestive heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR), both types: with reduced ejection fraction Ejection fraction Cardiac Cycle (systolic), and with preserved ejection fraction Ejection fraction Cardiac Cycle (diastolic) 
• Ischemic stroke Ischemic Stroke An ischemic stroke (also known as cerebrovascular accident) is an acute neurologic injury that occurs as a result of brain ischemia; this condition may be due to cerebral blood vessel occlusion by thrombosis or embolism, or rarely due to systemic hypoperfusion. Ischemic Stroke
• Intracerebral hemorrhage Intracerebral Hemorrhage Intracerebral hemorrhage (ICH) refers to a spontaneous or traumatic bleed into the brain parenchyma and is the 2nd-most common cause of cerebrovascular accidents (CVAs), commonly known as stroke, after ischemic CVAs. Intracerebral Hemorrhage 
• Left ventricular hypertrophy Ventricular Hypertrophy Tetralogy of Fallot 
• Ischemic heart disease Ischemic heart disease Coronary heart disease (CHD), or ischemic heart disease, describes a situation in which an inadequate supply of blood to the myocardium exists due to a stenosis of the coronary arteries, typically from atherosclerosis. Coronary Heart Disease, including angina and myocardial infarction Myocardial infarction MI is ischemia and death of an area of myocardial tissue due to insufficient blood flow and oxygenation, usually from thrombus formation on a ruptured atherosclerotic plaque in the epicardial arteries. Clinical presentation is most commonly with chest pain, but women and patients with diabetes may have atypical symptoms. Myocardial Infarction
• Chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease and end-stage kidney disease

High-yield fact:

Hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension is considered the most common cause of ascending aortic aneurysm Ascending aortic aneurysm Thoracic Aortic Aneurysms. On the other hand Hand The hand constitutes the distal part of the upper limb and provides the fine, precise movements needed in activities of daily living. It consists of 5 metacarpal bones and 14 phalanges, as well as numerous muscles innervated by the median and ulnar nerves. Hand: Anatomy, atherosclerosis Atherosclerosis Atherosclerosis is a common form of arterial disease in which lipid deposition forms a plaque in the blood vessel walls. Atherosclerosis is an incurable disease, for which there are clearly defined risk factors that often can be reduced through a change in lifestyle and behavior of the patient. Atherosclerosis is considered the most common cause of descending aortic aneurysm Descending aortic aneurysm Thoracic Aortic Aneurysms.

Prevention

Preventive approaches include the elimination Elimination The initial damage and destruction of tumor cells by innate and adaptive immunity. Completion of the phase means no cancer growth. Cancer Immunotherapy or reduction of hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension risk factors.

Review Questions

1. How is isolated systolic hypertension treated?
   1. Not at all 
   2. In the same way as systolic and diastolic hypertension Hypertension Hypertension, or high blood pressure, is a common disease that manifests as elevated systemic arterial pressures. Hypertension is most often asymptomatic and is found incidentally as part of a routine physical examination or during triage for an unrelated medical encounter. Hypertension
   3. With beta blockers only
   4. With ACE inhibitors ACE inhibitors Truncus Arteriosus only
   5. With diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Chronic Coronary Syndrome Medication only
2. What are not first-line antihypertensive medications?
   1. Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes channel blockers
   2. ACE inhibitors ACE inhibitors Truncus Arteriosus
   3. Alpha-1 receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors blockers
   4. Angiotensin receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors blockers
   5. Diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Chronic Coronary Syndrome Medication
3. Which of the following laboratory parameters must be determined first when first diagnosing hypertension?
   1. AST AST Enzymes of the transferase class that catalyze the conversion of l-aspartate and 2-ketoglutarate to oxaloacetate and l-glutamate. Liver Function Tests
   2. CRP
   3. eGFR
   4. ESR ESR Soft Tissue Abscess
   5. GPT

Answers: 1-2, 2-3, 3-3