Antiadrenergic Drugs

Antiadrenergic agents are drugs that block the activity of catecholamines, primarily norepinephrine (NE). There are 2 major types of adrenergic receptors–alpha and beta receptors—and there are several subtypes of each. Antiadrenergic drugs can be classified according to their specificity for the different receptors, with the major classes including selective beta-1 receptor blockers, nonselective beta-blockers, mixed alpha- and beta-blockers, selective alpha-1 receptor blockers, and nonselective alpha-blockers. There are many beta receptors in the heart, so these medications are primarily used for cardiac indications, including MI MI 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, angina, heart failure (HF) (stable), and 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 (as an alternative agent). Alpha receptors are prominent in smooth muscle, especially in the vasculature. Alpha-blockers cause significant vasodilation and are indicated in 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 benign prostatic hyperplasia Benign prostatic hyperplasia Benign prostatic hyperplasia (BPH) is a condition indicating an increase in the number of stromal and epithelial cells within the prostate gland (transition zone). Benign prostatic hyperplasia is common in men > 50 years of age and may greatly affect their quality of life. Benign Prostatic Hyperplasia (BPH). Significant adverse effects are possible.

Last update:

Editorial responsibility: Stanley Oiseth, Lindsay Jones, Evelin Maza

Table of Contents

Share this concept:

Share on facebook
Share on twitter
Share on linkedin
Share on reddit
Share on email
Share on whatsapp

Overview

Overview of the ANS

The ANS is subdivided into the sympathetic and parasympathetic pathways. Both pathways contain 2 efferent neurons in series known as the preganglionic and postganglionic neurons.

Preganglionic neuron:

  • 1st neuron in the series 
  • The cell body originates in the CNS.
  • Release acetylcholine onto nicotinic cholinergic receptors in the autonomic ganglia
  • In the adrenal gland, preganglionic neurons synapse Synapse The junction between 2 neurons is called a synapse. The synapse allows a neuron to pass an electrical or chemical signal to another neuron or target effector cell. Synapses and Neurotransmission directly with chromaffin cells in the adrenal medulla (instead of the sympathetic ganglia).

Postganglionic neuron: 

  • Second neuron in the series 
  • The cell body originates in the ganglion.
  • May release:
    • Norepinephrine (NE) onto alpha- or beta-adrenergic receptors in target tissues:
      • Cardiac and smooth muscle
      • Gland cells
      • Nerve terminals
    • Acetylcholine onto muscarinic receptors in sweat glands
    • Dopamine onto dopaminergic receptors in renal vascular smooth muscle
  • In the adrenal gland, chromaffin cells act as modified postganglionic neurons and release epinephrine (80%) and NE (20%) directly into the bloodstream.
Overview of the ans

Overview of the ANS
ACh: acetylcholine
N: nicotinic receptor
M: muscarinic receptor
α and β: α and β adrenergic receptors
NE: norepinephrine
D: dopamine
D1: dopamine receptor
Epi: Epinpehrine

Image by Lecturio.

Chemistry and Pharmacodynamics

Chemistry

  • Catecholamines are derived from the amino acid Amino acid Amino acids (AAs) are composed of a central carbon atom attached to a carboxyl group, an amino group, a hydrogen atom, and a side chain (R group). Basics of Amino Acids tyrosine (a.a. Tyr).
  • Most beta-blockers are structurally similar to the catecholamines.

Mechanisms of action

Antiadrenergic drugs work by inhibiting the postganglionic adrenergic receptors. These are G-protein-coupled receptors.

Alpha receptors: 

  • Alpha-1 receptors:
    • Alpha-1 stimulation: 
      • Activates the enzyme phospholipase C → 
      • Generates inositol triphosphate (IP3) and diacylglycerol (DAG) as secondary messengers → 
      • Causes ↑ calcium ion (Ca2+) levels intracellularly → 
      • Smooth muscle contraction
    • Alpha-1 receptor antagonists: inhibit release of IP3 and DAG → ↓ Ca2+ release → smooth muscle relaxation
  • Alpha-2 receptors (primarily located at peripheral nerve endings):
    • Alpha-2- receptor stimulation: 
      • Inhibits the enzyme adenylyl cyclase → 
      • ↓ Levels of the secondary messenger cAMP → 
      • Ultimately blocks the presynaptic release of NE → 
      • ↓ Adrenergic stimulation
    • Alpha-2 receptor antagonists: block reduction in cAMP → ↑ NE release → ↑ adrenergic stimulation
  • Alpha receptor inhibitor binding may be:
    • Selective or nonselective for alpha-1 vs. alpha-2 receptors 
    • Reversible or irreversible

Beta receptors: beta-1, beta-2, and beta-3 

  • Beta receptor stimulation: stimulates adenylyl cyclase → ↑ cAMP → triggers target cell effects
  • Beta receptor antagonists: 
    • Competitively inhibit catecholamines at the beta-adrenergic receptors 
    • ↓ Activation of adenylyl cyclase → inhibits target cell effects
    • Have minimal impact on patients who are at rest
  • Beta receptor partial agonists:
    • Partially activate the beta receptors, though not as strongly as true catecholamines
    • Results in decreased effects when NE is ↑ and increased effects when NE is ↓

Physiologic effects

Adrenergic receptors are located throughout the body and trigger a wide variety of effects. The physiologic effects of antiadrenergic agents are to block whatever the typical response is of that particular receptor. 

  • Alpha-1 receptors: 
    • Found in smooth muscle throughout the body (e.g., bronchial, vascular, intestinal, and bladder walls)
    • Play a major role in determining vascular tone
    • Alpha-1 receptor antagonists cause: 
      • Vasodilation
      • Relaxation of bladder muscles → improved micturition 
  • Beta-1 receptors: 
    • Primarily located in the heart 
    • Play a major role in determining heart rate (HR) and contractility
    • Beta-1 antagonists:
      • ↓ HR and contractility 
      • ↓ Myocardial O2 demand
  • Beta-2 receptors: 
    • Located throughout the body, including heart, lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs, and smooth muscle
    • Usually has effects opposite those of alpha-1 receptors 
    • Beta-2 antagonists:
      • ↓ HR, contractility, and myocardial O2 demand
      • Bronchoconstriction (adverse effect)
      • Vasoconstriction
      • ↓ Intraocular pressure (IOP)
      • Metabolic effects 
Table: Physiologic effects of antiadrenergic medications
System Organ Receptors Physiologic actions from receptor stimulation (agonism) Physiologic effects from receptor blockade (antagonism)
Eye Iris radial muscle α1 Contraction → pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil's size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Physiology and Abnormalities of the Pupil dilation Relaxation → pupil Pupil The pupil is the space within the eye that permits light to project onto the retina. Anatomically located in front of the lens, the pupil's size is controlled by the surrounding iris. The pupil provides insight into the function of the central and autonomic nervous systems. Physiology and Abnormalities of the Pupil constriction
Ciliary muscle β Relaxes → flattens lens → better for long-range focus ↓ Relaxation → rounder lens → short range focus
Ciliary epithelium Epithelium The epithelium is a complex of specialized cellular organizations arranged into sheets and lining cavities and covering the surfaces of the body. The cells exhibit polarity, having an apical and a basal pole. Structures important for the epithelial integrity and function involve the basement membrane, the semipermeable sheet on which the cells rest, and interdigitations, as well as cellular junctions. Surface Epithelium β ↑ Production of aqueous humor ↓ Secretion of aqueous humor → ↓ IOP
Cardiovascular system SA β1, β2 Acceleration (↑ HR) ↓ HR
Ectopic pacemakers β1, β2 Acceleration (↑ HR) ↓ HR
Contractility of atria and ventricles β1, β2 ↑ Contractility ↓ Contractility
Vascular wall smooth muscle α1 Vasoconstriction Vasodilation → may cause orthostatic 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 reflex tachycardia
β2 Vasodilation Vasoconstriction → ↑ peripheral resistance
Pulmonary smooth muscle Bronchiolar smooth muscle β2 Bronchodilation Bronchoconstriction (especially with 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)
GI tract smooth muscle Intestinal walls α2, β2 Relaxation (↓ motility) ↑ Motility → may lead to diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
Sphincter muscles α1 Contracts (prevents chyme from passing through) Sphincter relaxation → ↑ risk of heartburn
Genitourinary smooth muscle Bladder wall β2, β3 Relaxes ↓ Resistance to urine flow
Urethral sphincters α1 Contracts ↓ Resistance to urine flow → ↑ risk of incontinence
Pregnant uterus α Uterine contraction Uterine relaxation
β2 Uterine relaxation Uterine contractions → labor Labor Labor is the normal physiologic process defined as uterine contractions resulting in dilatation and effacement of the cervix, which culminates in expulsion of the fetus and the products of conception. Normal and Abnormal Labor/ preterm labor Preterm labor Preterm labor refers to regular uterine contractions leading to cervical change prior to 37 weeks of gestation; preterm birth refers to birth prior to 37 weeks of gestation. Preterm birth may be spontaneous due to preterm labor, preterm prelabor rupture of membranes (PPROM), or cervical insufficiency. Preterm Labor and Birth
Penis Penis The penis is the male organ of copulation and micturition. The organ is composed of a root, body, and glans. The root is attached to the pubic bone by the crura penis. The body consists of the 2 parallel corpora cavernosa and the corpus spongiosum. The glans is ensheathed by the prepuce or foreskin. Penis and seminal vesicles α Ejaculation Difficulty with ejaculation
Metabolic functions 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 α, β2 Gluconeogenesis Gluconeogenesis Gluconeogenesis is the process of making glucose from noncarbohydrate precursors. This metabolic pathway is more than just a reversal of glycolysis. Gluconeogenesis provides the body with glucose not obtained from food, such as during a fasting period. The production of glucose is critical for organs and cells that cannot use fat for fuel. Gluconeogenesis, glycogenolysis ↓ Glycogenolysis → may impair recovery from hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia
Adipose tissue Adipose tissue Adipose tissue is a specialized type of connective tissue that has both structural and highly complex metabolic functions, including energy storage, glucose homeostasis, and a multitude of endocrine capabilities. There are three types of adipose tissue, white adipose tissue, brown adipose tissue, and beige or "brite" adipose tissue, which is a transitional form. Adipose Tissue β3 Lipolysis Inhibition of lipolysis
Kidney β1 Renin release Suppression of renin release
IOP: Intraoccular pressure
SA: Sinoatrial node
HR: heart rate

Classification

Alpha-blockers

  • Alpha-1-selective blockers:
    • Prazosin
    • Doxazosin
    • Terazosin
    • Tamsulosin
  • Alpha-2-selective blocker: yohimbine (currently not FDA approved) 
  • Nonselective alpha-1 and alpha-2 blockers:
    • Phenoxybenzamine
    • Phentolamine

Beta-blockers

  • Beta-1-selective blockers:
    • Atenolol 
    • Metoprolol
    • Esmolol
    • Nebivolol
  • Beta-2-selective blocker: butaxamine (used only experimentally)
  • Nonselective beta-blockers:
    • Propranolol
    • Nadolol
    • Timolol
  • Beta-blockers with partial agonist activity: 
    • Pindolol
    • Acebutolol

Mixed Alpha- and Beta-blockers

These drugs have inhibitory effects at both the beta and alpha-1 receptors 

  • Carvedilol
  • Labetalol

Pharmacokinetics

Differences in pharmacokinetics can help determine which medication in a particular class is optimal for a given clinical scenario.

Table: Pharmacokinetics of antiadrenergic drugs
Drug Absorption Distribution Metabolism Excretion
Prazosin (selective α1-blocker) Onset: 2‒4 hrs
  • VD: 0.5 L/kg
  • Protein binding: 97%
Extensive hepatic via demethylation and conjugation
  • Fecal
  • Half-life: 2‒3 hrs
Phentolamine (nonselective α-blocker
  • Poor oral absorption
  • Onset:
    • IM: 15‒20 min
    • IV: 1‒2 min
Widely distributed Hepatic
  • Urine
  • Half-life: approximately 20 min
Propranolol (nonselective β-blocker)
  • Rapid complete oral absorption
  • Onset:
    • By mouth: 1‒2 hrs
    • IV: < 5 min
  • VD 4 L/kg
  • Cross BBB
  • Protein binding: approximately 90%
Extensive 1st-pass hepatic metabolism
  • Urine (as metabolites)
  • Half-life: 3‒6 hrs
Atenolol1-selective β-blocker)
  • Rapid incomplete oral absorption (approximately 50%)
  • Onset (by mouth): < 1 hr
  • VD: approximately 75 L
  • Does not cross BBB
  • Protein binding: approximately 10%
Minimal hepatic metabolism
  • Feces: 50%
  • Urine: 40%
  • Half-life: 6‒7 hrs (up to 35 hrs in ESRD)
Metoprolol1-selective β-blocker)
  • Rapid complete oral absorption
  • Onset:
    • By mouth: 1‒2 hrs
    • IV: 20 min
  • VD: approximately 4 L/kg
  • Crosses BBB
  • Protein binding: approximately 10%
Extensive 1st-pass hepatic metabolism
  • Urine
  • Half-life: 3‒4 hrs (↑ in hepatic impairment)
Carvedilol (mixed α and β blockade)
  • Rapid complete oral absorption
  • Onset (by mouth):
    • α blockade: 30 min
    • β blockade: 1 hr
  • VD: 115 L (distributes in extravascular space)
  • Protein binding: 98%
Extensive 1st-pass hepatic metabolism
  • Feces
  • Half-life: 7‒10 hrs
IM: intramuscular
IV: intravenous
BBB: blood–brain barrier
ESRD: end-stage renal disease
VD: volume of distribution

Drug interactions

Drug interactions are also important for several medications within this class.

  • Alpha-blockers + medications for 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 (e.g., sildenafil) → may cause significant 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
  • Beta-blockers + loop diuretics Loop diuretics Loop diuretics are a group of diuretic medications primarily used to treat fluid overload in edematous conditions such as heart failure and cirrhosis. Loop diuretics also treat hypertension, but not as a 1st-line agent. Loop Diuretics → may result in 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
  • NSAIDs may ↓ the efficacy of beta-blockers.

Indications

Alpha antagonists

While Alpha-2 antagonists have few clinical uses, alpha-1 and nonselective alpha antagonists are used for their ability to cause vasodilation and smooth muscle relaxation. They are frequently used in the treatment of:

  • Prazosin:
    • Hypertension 
    • Benign prostatic hyperplasia (BPH, enlargement of the prostate Prostate The prostate is a gland in the male reproductive system. The gland surrounds the bladder neck and a portion of the urethra. The prostate is an exocrine gland that produces a weakly acidic secretion, which accounts for roughly 20% of the seminal fluid. Prostate and other Male Reproductive Glands resulting in urinary retention)
    • Off-label use: nightmares in PTSD PTSD Posttraumatic stress disorder is a psychiatric illness characterized by overwhelming stress and anxiety experienced after exposure to a life-threatening event. Symptoms last more than 1 month and involve re-experiencing the event as flashbacks or nightmares, avoiding reminders of the event, irritability, hyperarousal, and poor memory and concentration. Posttraumatic Stress Disorder (PTSD)
  • Phenoxybenzamine: 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 (catecholamine-secreting tumors of the adrenal medulla)
  • Phentolamine: 
    • Erectile dysfunction (ED)
    • Prevention or treatment of extravasation of IV NE 
    • Reversal of soft-tissue anesthesia Anesthesia Anesthesiology is the field of medicine that focuses on interventions that bring a state of anesthesia upon an individual. General anesthesia is characterized by a reversible loss of consciousness along with analgesia, amnesia, and muscle relaxation. Anesthesiology: History and Basic Concepts from local anesthetics Local anesthetics Local anesthetics are a group of pharmacological agents that reversibly block the conduction of impulses in electrically excitable tissues. Local anesthetics are used in clinical practice to induce a state of local or regional anesthesia by blocking sodium channels and inhibiting the conduction of painful stimuli via afferent nerves. Local Anesthetics containing a vasoconstrictor

Beta antagonists

Beta-blockers have a variety of indications. They are frequently used for their negative inotropic and chronotropic effects in the heart. 

  • Cardiovascular indications: 
    • Atrial fibrillation Atrial fibrillation Atrial fibrillation (AF or Afib) is a supraventricular tachyarrhythmia and the most common kind of arrhythmia. It is caused by rapid, uncontrolled atrial contractions and uncoordinated ventricular responses. Atrial Fibrillation (AFib)
    • Congestive heart failure Congestive heart failure Congestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction. Congestive Heart Failure ( CHF CHF Congestive heart failure refers to the inability of the heart to supply the body with normal cardiac output to meet metabolic needs. Echocardiography can confirm the diagnosis and give information about the ejection fraction. Congestive Heart Failure)
    • Post- MI MI 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
    • Angina
    • Hypertension
  • Other indications for propranolol:
    • Neuropsychiatric
      • Essential tremor
      • Migraine headache Migraine Headache Migraine headache is a primary headache disorder and is among the most prevalent disorders in the world. Migraine is characterized by episodic, moderate to severe headaches that may be associated with increased sensitivity to light and sound, as well as nausea and/or vomiting. Migraine Headache
      • Anxiety (especially performance anxiety)
    • GI: bleeding from esophageal varices (beta blockade ↓ portal vein pressure in cirrhosis Cirrhosis Cirrhosis is a late stage of hepatic parenchymal necrosis and scarring (fibrosis) most commonly due to hepatitis C infection and alcoholic liver disease. Patients may present with jaundice, ascites, and hepatosplenomegaly. Cirrhosis can also cause complications such as hepatic encephalopathy, portal hypertension, portal vein thrombosis, and hepatorenal syndrome. Cirrhosis
    • Endocrine: hyperthyroidism Hyperthyroidism Thyrotoxicosis refers to the classic physiologic manifestations of excess thyroid hormones and is not synonymous with hyperthyroidism, which is caused by sustained overproduction and release of T3 and/or T4. Graves' disease is the most common cause of primary hyperthyroidism, followed by toxic multinodular goiter and toxic adenoma. Thyrotoxicosis and Hyperthyroidism
  • Specialized indications for other beta-blockers:
    • Labetalol: 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 pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care
    • Timolol (good ocular penetration): glaucoma Glaucoma Glaucoma is an optic neuropathy characterized by typical visual field defects and optic nerve atrophy seen as optic disc cupping on examination. The acute form of glaucoma is a medical emergency. Glaucoma is often, but not always, caused by increased intraocular pressure (IOP). Glaucoma
    • Esmolol (very short half-life): when steady-state infusions are required
    • Butoxamine (beta-2-selective antagonist): used for research purposes 

Adverse Effects and Contraindications

Antiadrenergic medications must be used with caution and titrated slowly to avoid side effects.

Table: Adverse effects and contraindications of anti-adrenergic medications
Drug Adverse effects Contraindications
Beta-blockers
  • Bradycardia
  • Bronchospasm (due to beta-2 blockade with nonselective beta-blockers)
  • HF
  • Hypotension
  • Syncope Syncope Syncope is a short-term loss of consciousness and loss of postural stability followed by spontaneous return of consciousness to the previous neurologic baseline without the need for resuscitation. The condition is caused by transient interruption of cerebral blood flow that may be benign or related to a underlying life-threatening condition. Syncope and/or dizziness
  • Impotence/ejaculatory failure
  • Diarrhea
  • Heartburn
  • Fatigue
  • Hyperglycemia
  • Mask signs of hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia in diabetics
  • Blurred vision
  • Absolute contraindications:
    • Asthma
    • Uncompensated HF and/or cardiogenic shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock
    • 2nd- or 3rd-degree heart block
  • Relative contraindications:
    • Individuals prone to hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia
    • Diabetes
    • Hypotension
    • PVD
    • 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 or kidney disease
    • Pheochromocytoma (untreated with alpha blockade)
    • MG
    • Hyperthyroidism
Alpha-1 blockers (prazosin)
  • Orthostatic 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
  • Syncope Syncope Syncope is a short-term loss of consciousness and loss of postural stability followed by spontaneous return of consciousness to the previous neurologic baseline without the need for resuscitation. The condition is caused by transient interruption of cerebral blood flow that may be benign or related to a underlying life-threatening condition. Syncope and/or dizziness
  • Headache
  • Fatigue
  • Nasal congestion
  • GI distress
  • Edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
  • Priapism (prolonged erection)
Known hypersensitivity to the drug
Nonselective alpha antagonists (phenoxybenzamine, phentolamine)
  • Same as alpha-1 antagonists, especially orthostatic 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
  • Reflex tachycardia (due to additional alpha-2 blockade, which causes ↑ NE release)
  • Breastfeeding Breastfeeding Breastfeeding is often the primary source of nutrition for the newborn. During pregnancy, hormonal stimulation causes the number and size of mammary glands in the breast to significantly increase. After delivery, prolactin stimulates milk production, while oxytocin stimulates milk expulsion through the lactiferous ducts, where it is sucked out through the nipple by the infant. Breastfeeding
  • Cardiovascular conditions that cannot tolerate 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:
    • CHD
    • Angina
    • MI MI 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
    • HF
HF: Heart failure
PVD: Peripheral vascular disease
MG: Myasthenia gravis Myasthenia Gravis Myasthenia gravis (MG) is an autoimmune neuromuscular disorder characterized by weakness and fatigability of skeletal muscles caused by dysfunction/destruction of acetylcholine receptors at the neuromuscular junction. MG presents with fatigue, ptosis, diplopia, dysphagia, respiratory difficulties, and progressive weakness in the limbs, leading to difficulty in movement. Myasthenia Gravis
CHD: Coronary heart disease Coronary 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

Overdose

Presentation of beta-blocker toxicity

Although beta-blockers are generally safe, overdose can produce symptoms of toxicity, typically within 2 hours (almost always within 6). Symptoms include:

  • Bradycardia
  • Hypotension
  • Myocardial depression and cardiogenic shock Shock Shock is a life-threatening condition associated with impaired circulation that results in tissue hypoxia. The different types of shock are based on the underlying cause: distributive (↑ cardiac output (CO), ↓ systemic vascular resistance (SVR)), cardiogenic (↓ CO, ↑ SVR), hypovolemic (↓ CO, ↑ SVR), obstructive (↓ CO), and mixed. Types of Shock
  • Ventricular dysrhythmias
  • Mental status changes (e.g., delirium Delirium Delirium is a medical condition characterized by acute disturbances in attention and awareness. Symptoms may fluctuate during the course of a day and involve memory deficits and disorientation. Delirium, 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, seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures)
  • Bronchospasm
  • Hypoglycemia

Management

  • Acute stabilization of the airway, breathing, and circulation (ABC):
    • Intubate if needed.
    • Isotonic fluid to treat 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 
  • Reverse the cardiotoxic effects:
    • Atropine to treat symptomatic bradycardia
    • Glucagon
    • Calcium salts
    • Vasopressors
  • Avoid hypoglycemia Hypoglycemia Hypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features. Hypoglycemia: IV dextrose
  • Treat seizures Seizures A seizure is abnormal electrical activity of the neurons in the cerebral cortex that can manifest in numerous ways depending on the region of the brain affected. Seizures consist of a sudden imbalance that occurs between the excitatory and inhibitory signals in cortical neurons, creating a net excitation. The 2 major classes of seizures are focal and generalized. Seizures: benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines

Comparison of Medications

Table: Comparison of medications
Medication Mechanism Physiologic effects Indication
Metoprolol Selective β1-blocker
  • ↓ HR
  • ↓ Contractility
  • Less effect on bronchial smooth muscle
  • MI MI 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
  • HF with ↓ EF (stable)
  • Angina
  • Hypertension (not 1st line)
  • AFib
Propranolol Nonselective β-blocker
  • ↓ HR
  • ↓ Contractility
  • ↓ Blood pressure
  • Higher risk of bronchospasm
  • MI MI 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
  • AP
  • Hypertension (not 1st line)
  • Migraine Migraine Migraine headache is a primary headache disorder and is among the most prevalent disorders in the world. Migraine is characterized by episodic, moderate to severe headaches that may be associated with increased sensitivity to light and sound, as well as nausea and/or vomiting. Migraine Headache prophylaxis
  • Essential tremor
  • Performance anxiety
  • PTSD PTSD Posttraumatic stress disorder is a psychiatric illness characterized by overwhelming stress and anxiety experienced after exposure to a life-threatening event. Symptoms last more than 1 month and involve re-experiencing the event as flashbacks or nightmares, avoiding reminders of the event, irritability, hyperarousal, and poor memory and concentration. Posttraumatic Stress Disorder (PTSD)
  • Thyrotoxicosis Thyrotoxicosis Thyrotoxicosis refers to the classic physiologic manifestations of excess thyroid hormones and is not synonymous with hyperthyroidism, which is caused by sustained overproduction and release of T3 and/or T4. Graves' disease is the most common cause of primary hyperthyroidism, followed by toxic multinodular goiter and toxic adenoma. Thyrotoxicosis and Hyperthyroidism
Carvedilol Nonselective α- and β-blocker
  • ↓ HR
  • ↓ Contractility
  • Vasodilation
  • ↓ Renin release
  • HF with ↓ EF (stable)
  • Angina
  • AFib
Prazosin Selective α1-blocker
  • Vasodilation of 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 and veins Veins Veins are tubular collections of cells, which transport deoxygenated blood and waste from the capillary beds back to the heart. Veins are classified into 3 types: small veins/venules, medium veins, and large veins. Each type contains 3 primary layers: tunica intima, tunica media, and tunica adventitia. Veins
  • ↓ Blood pressure
  • Relaxation of bladder muscles
  • Hypertension (not 1st line)
  • BPH
  • PTSD PTSD Posttraumatic stress disorder is a psychiatric illness characterized by overwhelming stress and anxiety experienced after exposure to a life-threatening event. Symptoms last more than 1 month and involve re-experiencing the event as flashbacks or nightmares, avoiding reminders of the event, irritability, hyperarousal, and poor memory and concentration. Posttraumatic Stress Disorder (PTSD) (off-label use)
Phentolamine Nonselective α-adrenergic antagonist
  • Vasodilation
  • ↓ Blood pressure
  • ↑ HR
  • Pheochromocytoma
  • Prevention or treatment of extravasation of IV NE
  • Reversal of soft-tissue anesthesia Anesthesia Anesthesiology is the field of medicine that focuses on interventions that bring a state of anesthesia upon an individual. General anesthesia is characterized by a reversible loss of consciousness along with analgesia, amnesia, and muscle relaxation. Anesthesiology: History and Basic Concepts from local anesthetics Local anesthetics Local anesthetics are a group of pharmacological agents that reversibly block the conduction of impulses in electrically excitable tissues. Local anesthetics are used in clinical practice to induce a state of local or regional anesthesia by blocking sodium channels and inhibiting the conduction of painful stimuli via afferent nerves. Local Anesthetics containing a vasoconstrictor
HF: heart failure
AFib: atrial fibrillation
AP: angina pectoris
BPH: benign prostatic hyperplasia Benign prostatic hyperplasia Benign prostatic hyperplasia (BPH) is a condition indicating an increase in the number of stromal and epithelial cells within the prostate gland (transition zone). Benign prostatic hyperplasia is common in men > 50 years of age and may greatly affect their quality of life. Benign Prostatic Hyperplasia
NE: norepinephrine

References

  1. Katzung, BG. (2012). Introduction to autonomic pharmacology. In Katzung, BG, Masters, SB, & Trevor, AJ. (Eds.), Basic and Clinical Pharmacology. 12th Ed. pp. 79–95. McGraw-Hill.
  2. Robertson, D, & Biaggioni, I. (2012). Adrenoceptor antagonist drugs. In Katzung, BG, Masters, SB, & Trevor, AJ. (Eds.), Basic and Clinical Pharmacology. 12th Ed. pp. 151–165. McGraw-Hill.
  3. Podrid, PJ. (2020). Major side effects of beta blockers. UpToDate. Retrieved September 1, 2021, from https://www.uptodate.com/contents/major-side-effects-of-beta-blockers
  4. Farzam, K, & Jan, A. (2021). Beta blockers. StatPearls. Retrieved August 31, 2021, from https://www.statpearls.com/articlelibrary/viewarticle/18241/ 
  5. Nachawati, D, & Patel, J. (2021). Alpha blockers. StatPearls. Retrieved August 31, 2021, from https://www.statpearls.com/articlelibrary/viewarticle/17401/ 
  6. Lexicomp Drug Information Sheets (2021). In UpToDate. Retrieved August 31, 2021:
  7. Wang, J, Gareri, C, & Rockman, HA. (2018). G-protein-coupled receptors in heart disease. Circ Res. 123(6), 716–735. https://doi.org/10.1161/CIRCRESAHA.118.311403 
  8. Westfall, TC, Macarthur, H, & Westfall, DP. (2018). Neurotransmission: The autonomic and somatic motor nervous systems. Adrenergic Agonists and Antagonists. In Brunton, LL, et al. (Eds.). Goodman & Gilman’s: The Pharmacological Basis of Therapeutics 13e. New York, NY: McGraw-Hill. 
  9. Gorodetzky, CW, et al. (2017). A phase III, randomized, multi-center, double-blind, placebo-controlled study of safety and efficacy of lofexidine for relief of symptoms in individuals undergoing inpatient opioid withdrawal. Drug Alcohol Depend. 176, 79–88. https://doi.org/10.1016/j.drugalcdep.2017.02.020 
  10. Sarma, AV, Wei, JT. (2012). Benign prostatic hyperplasia and lower urinary tract symptoms. N Engl J Med. 367(3), 248–57. https://doi.org/10.1056/NEJMcp1106637 
  11. Wolraich, ML, et al. (2019). Clinical practice guideline for the diagnosis, evaluation, and treatment of attention-deficit/hyperactivity disorder in children and adolescents. Pediatrics. 144(4), e20192528. https://doi.org/10.1542/peds.2019-2528 
  12. Campbell, RJ, et al. (2019). Evolution in the risk of cataract surgical complications among patients exposed to tamsulosin: A population-based study. Ophthalmology. 126(4), 490–496. https://doi.org/10.1016/j.ophtha.2018.11.028 
  13. The definition of orthostatic hypotension, pure autonomic failure, and multiple system atrophy. (1996). J Auton Nerv Syst. 58(1–2), 123–4. https://doi.org/10.1016/0165-1838(96)90001-6 
  14. Griebenow, R, et al. (1997). Low-dose reserpine/thiazide combination in first-line treatment of hypertension: efficacy and safety compared to an ACE inhibitor. Blood Press. 6(5), 299–306. https://pubmed.ncbi.nlm.nih.gov/9360001/
  15. Li, S, Liu, X, & Li, L. (2020). A Multicenter retrospective analysis on clinical effectiveness and economic assessment of compound reserpine and hydrochlorothiazide tablets (CRH) for hypertension. Clinicoecon Outcomes Res. 12, 107–114. https://www.ncbi.nlm.nih.gov/pubmed/32104022
  16. Shamon, SD, Perez, MI. (2016). Blood pressure–lowering efficacy of reserpine for primary hypertension. Cochrane Database Syst Rev. 12, CD007655. https://www.ncbi.nlm.nih.gov/pubmed/27997978
  17. Khakurel, S, Sapkota, S, & Karki, AJ. (2019). Analgesic effect of caudal bupivacaine with or without clonidine in pediatric patient. J Nepal Health Res Counc. 16(41), 428–433. https://www.ncbi.nlm.nih.gov/pubmed/30739935
  18. Bello, M, et al. (2019). Effect of opioid-free anesthesia on postoperative epidural ropivacaine requirement after thoracic surgery: A retrospective unmatched case-control study. Anaesth Crit Care Pain Med. 38(5), 499–505. https://pubmed.ncbi.nlm.nih.gov/30731138/
  19. Pelayo, R, & Yuen, K. (2012). Pediatric sleep pharmacology. Child Adolesc Psychiatr Clin N Am. 21(4), 861–83. https://pubmed.ncbi.nlm.nih.gov/23040905/
  20. Drugs for ADHD. (2020). Med Lett Drugs Ther. 62(1590), 9–15. https://pubmed.ncbi.nlm.nih.gov/31999670/

Study on the Go

Lecturio Medical complements your studies with evidence-based learning strategies, video lectures, quiz questions, and more – all combined in one easy-to-use resource.

Learn even more with Lecturio:

Complement your med school studies with Lecturio’s all-in-one study companion, delivered with evidence-based learning strategies.

User Reviews

0.0

()

¡Hola!

Esta página está disponible en Español.

🍪 Lecturio is using cookies to improve your user experience. By continuing use of our service you agree upon our Data Privacy Statement.

Details