Sympathomimetic Drugs

Chemistry and Pharmacodynamics

Sympathomimetic drugs, also known as adrenergic agonists, mimic the action of the stimulators of the sympathetic 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, specifically α, β, or dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS receptors Receptors 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:

Chemical structures

• Phenylethylamine (parent compound)
• 4 possible substitution sites:
  • Benzene ring: substitution by a hydroxyl group (-OH) at position 3 and 4 yields catecholamine ( dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS)
  • Terminal amino group (epinephrine)
  • Α or β carbons of the ethylamino chain (amphetamine and phenylephrine respectively)

Mechanism of action

• At the end of a neuron, terminal buttons (structures at the end of an axon) carry signals to neighboring neurons Neurons The basic cellular units of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. Nervous System: Histology (synapses), glands, or muscles.
• The synapses provide room for the chemical signal to travel and exert the effect.
• Sympathomimetics affect the adrenergic receptors Receptors 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 of epinephrine, norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS, or dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS to produce effects on α, β, or dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS receptors Receptors 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.

Classification

• Classification is based on the type of receptors Receptors 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 the drugs act on.
• Direct agonists (selective) act on 1 or more adrenergic (α and β) receptors Receptors 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:
  • Α agonists:
    • Nonselective: norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS
    • Α-1 selective: phenylephrine
    • Α-2 selective: clonidine
  • Β agonists:
    • Nonselective: epinephrine, isoproterenol
    • Β-1 selective: dobutamine
    • Β-2 selective: albuterol
• Indirect agonists:
  • 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: cause increased release of the endogenous neurotransmitter (e.g., 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)
  • Tricyclic antidepressants Tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants: inhibit reuptake of neurotransmitters → “ anticholinergic Anticholinergic Anticholinergic drugs block the effect of the neurotransmitter acetylcholine at the muscarinic receptors in the central and peripheral nervous systems. Anticholinergic agents inhibit the parasympathetic nervous system, resulting in effects on the smooth muscle in the respiratory tract, vascular system, urinary tract, GI tract, and pupils of the eyes. Anticholinergic Drugs” side effects
• Mixed:
  • Employ mechanisms of both direct and indirect activation
  • Ephedrine: acts on α and β receptors Receptors 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 to cause norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS release (used for anesthesia-related 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)

Physiologic effects

• Cardiovascular (e.g., epinephrine, norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS):
  • Increases heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology (positive chronotropy Chronotropy Chronotropy is the modulation of the heart rate at the level of the pacemaker cells. Cardiac Physiology)
  • Increases contractile force (positive inotropy)
  • Increases blood pressure by increasing 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
  • Isoproterenol (nonselective agent):
    • Increases 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 
    • Decreases blood pressure (opposite of epinephrine)
• Respiratory (e.g., albuterol):
  • Β-2 agonists relax smooth muscle → bronchodilation 
  • Albuterol is used for 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.
  • Epinephrine is used for anaphylaxis Anaphylaxis An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. Type I Hypersensitivity Reaction.
• Ocular:
  • 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. Pupil: Physiology and Abnormalities dilation ( mydriasis Mydriasis Dilation of pupils to greater than 6 mm combined with failure of the pupils to constrict when stimulated with light. This condition may occur due to injury of the pupillary fibers in the oculomotor nerve, in acute angle-closure glaucoma, and in adie syndrome. Glaucoma)
  • Accommodation Accommodation Refractive Errors is rarely affected.
  • Reduces intraocular pressure Intraocular Pressure The pressure of the fluids in the eye. Ophthalmic Exam
• Gastrointestinal:
  • Contracts smooth muscle in the splanchnic vessels
  • Low-dose dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS causes vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure.
• Renal:
  • Detrusor muscle Detrusor muscle Urinary Incontinence relaxation
  • Trigone Trigone Urinary Tract: Anatomy contraction
• Genital tract (women):
  • Β-2 agonists cause uterine relaxation.
  • Terbutaline Terbutaline A selective beta-2 adrenergic agonist used as a bronchodilator and tocolytic. Asthma Drugs is used to suppress 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.
• Genital tract (men):
  • Α-1 agonists cause prostatic smooth muscle contraction Smooth muscle contraction Smooth muscle is primarily found in the walls of hollow structures and some visceral organs, including the walls of the vasculature, GI, respiratory, and genitourinary tracts. Smooth muscle contracts more slowly and is regulated differently than skeletal muscle. Smooth muscle can be stimulated by nerve impulses, hormones, metabolic factors (like pH, CO2 or O2 levels), its own intrinsic pacemaker ability, or even mechanical stretch. Smooth Muscle Contraction (α blockers are used for benign Benign Fibroadenoma prostatic hypertrophy Hypertrophy General increase in bulk of a part or organ due to cell enlargement and accumulation of fluids and secretions, not due to tumor formation, nor to an increase in the number of cells (hyperplasia). Cellular Adaptation, which causes urinary outflow obstruction).
  • Ephedrine is sometimes used for urinary incontinence Urinary incontinence Urinary incontinence (UI) is involuntary loss of bladder control or unintentional voiding, which represents a hygienic or social problem to the patient. Urinary incontinence is a symptom, a sign, and a disorder. The 5 types of UI include stress, urge, mixed, overflow, and functional. Urinary Incontinence.

Pharmacokinetics and Indications

The primary drugs used as IV vasopressors Vasopressors Sepsis in Children in the hospital are dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS and norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS. Dobutamine is given IV as an inotrope. Albuterol is used via nebulizer or metered-dose inhaler for 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. Typical uses of certain medications include:

Routes of administration

Many routes are available:

• Oral:
  • Midodrine (used for orthostatic hypotension Orthostatic hypotension A significant drop in blood pressure after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm hg decrease in systolic pressure or a 10-mm hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include dizziness, blurred vision, and syncope. Hypotension)
  • Clonidine (a centrally acting antihypertensive agent)
  • Pseudoephedrine (nasal decongestant)
• Rectal: phenylephrine (vasoconstrictor suppositories Suppositories Medicated dosage forms that are designed to be inserted into the rectal, vaginal, or urethral orifice of the body for absorption. Generally, the active ingredients are packaged in dosage forms containing fatty bases such as cocoa butter, hydrogenated oil, or glycerogelatin that are solid at room temperature but melt or dissolve at body temperature. Large Bowel Obstruction for hemorrhoids Hemorrhoids Hemorrhoids are normal vascular cushions in the anal canal composed of dilated vascular tissue, smooth muscle, and connective tissue. They do not cause issues unless they are enlarged, inflamed, thrombosed, or prolapsed. Patients often present with rectal bleeding of bright red blood, or they may have pain, perianal pruritus, or a palpable mass. Hemorrhoids)
• Topical: eye drops for 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 (α agonists reduce intraocular pressure Intraocular Pressure The pressure of the fluids in the eye. Ophthalmic Exam)
• IV (pressors for 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 in hospitalized individuals):
  • Epinephrine
  • Dobutamine
  • Norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS
• Inhaled (for 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):
  • Albuterol (short-acting β agonist)
  • Salmeterol Salmeterol Asthma Drugs (long-acting β agonist (LABA))

Pharmacokinetics Pharmacokinetics Pharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body. Pharmacokinetics and Pharmacodynamics

Indications

Sympathomimetic drugs are used to augment endogenous catecholamines Catecholamines A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. Adrenal Hormones of 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 for therapeutic benefit.

Phenylephrine (α-1 selective agonist):

• Mechanism of action (MOA): activation of α-1 adrenoceptors → ↑ 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:
  • Does not stimulate cardiac adrenoceptors
  • ↑ TPR → induces reflex 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 (a counter-regulatory mechanism)
  • Contracts smooth muscle in the splanchnic vessels
• Indications:
  • IV vasopressor Vasopressor Acute Cholangitis to increase BP in 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 states
  • Used topically as a vasoconstrictor to relieve nasal congestion due to allergic rhinitis Allergic rhinitis An inflammation of the nasal mucosa triggered by allergens. Rhinitis
  • Used in topical ophthalmic preparations to promote mydriasis Mydriasis Dilation of pupils to greater than 6 mm combined with failure of the pupils to constrict when stimulated with light. This condition may occur due to injury of the pupillary fibers in the oculomotor nerve, in acute angle-closure glaucoma, and in adie syndrome. Glaucoma and conjunctival blood vessel constriction
  • An additive to topical hemorrhoid preparations to promote hemorrhoidal venous vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure

Isoproterenol (nonselective β agonist):

• MOA: activation of β-1 and β-2 adrenoceptors:
  • → ↑ Cardiac inotropy/ chronotropy Chronotropy Chronotropy is the modulation of the heart rate at the level of the pacemaker cells. Cardiac Physiology → ↑ CO → ↑ TPR
  • → Arteriolar smooth muscle relaxation → ↓ TPR
  • → Bronchial smooth muscle relaxation → ↓ bronchospasm Bronchospasm Asthma Drugs
  • ↑ CO + ↓ TPR compete for a net ↑ systolic BP / ↓ diastolic BP
  • Little-to-no α activity
• Indications:
  • Adjunctive IV vasopressor Vasopressor Acute Cholangitis to increase BP in 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 states (especially in the setting 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)
  • Used in the treatment of symptomatic bradyarrhythmias Bradyarrhythmias 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 blockage
  • Available aerosolized or in oral preparation for bronchospastic conditions (not commonly used)

Clonidine (α-2 selective agonist):

• MOA: α-2 adrenergic agonist → reduced sympathetic outflow from the CNS → ↓ TPR:
  • MOA in attention Attention Focusing on certain aspects of current experience to the exclusion of others. It is the act of heeding or taking notice or concentrating. Psychiatric Assessment deficit hyperactivity Hyperactivity Attention Deficit Hyperactivity Disorder disorder ( ADHD ADHD Attention deficit hyperactivity disorder is a neurodevelopmental disorder characterized by a pattern of inattention and/or hyperactivity-impulsivity that occurs in at least 2 different settings for more than 6 months. Although the patient has normal intelligence, the disease causes functional decline. Attention Deficit Hyperactivity Disorder) is unclear.
  • MOA in Tourette syndrome Tourette Syndrome A neuropsychological disorder related to alterations in dopamine metabolism and neurotransmission involving frontal-subcortical neuronal circuits. Both multiple motor and one or more vocal tics need to be present with tics occurring many times a day, nearly daily, over a period of more than one year. The onset is before age 18 and the disturbance is not due to direct physiological effects of a substance or another medical condition. The disturbance causes marked distress or significant impairment in social, occupational, or other important areas of functioning. Tics and Tourette Syndrome is unclear.
  • MOA in chronic pain Chronic pain Aching sensation that persists for more than a few months. It may or may not be associated with trauma or disease, and may persist after the initial injury has healed. Its localization, character, and timing are more vague than with acute pain. Pain Management is unclear.
  • Associated with rebound 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 
• Indications:
  • Administered transdermally ( patch Patch Nonpalpable lesion > 1 cm in diameter Generalized and Localized Rashes) for refractory hypertension Refractory hypertension Blood pressure that cannot be controlled even with maximally tolerated doses of ≥ 5 drugs. Uncontrolled Hypertension (though not a 1st-line drug 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)
  • Approved as an oral preparation for the treatment of ADHD ADHD Attention deficit hyperactivity disorder is a neurodevelopmental disorder characterized by a pattern of inattention and/or hyperactivity-impulsivity that occurs in at least 2 different settings for more than 6 months. Although the patient has normal intelligence, the disease causes functional decline. Attention Deficit Hyperactivity Disorder in children. 
  • Approved as an oral preparation for management of tics Tics Habitual, repeated, rapid contraction of certain muscles, resulting in stereotyped individualized actions that can be voluntarily suppressed for only brief periods. They often involve the face, vocal cords, neck, and less often the extremities. Examples include repetitive throat clearing, vocalizations, sniffing, pursing the lips, and excessive blinking. Tics tend to be aggravated by emotional stress. When frequent they may interfere with speech and interpersonal relations. Conditions which feature frequent and prominent tics as a primary manifestation of disease are referred to as tic disorders. Tics and Tourette Syndrome in Tourette syndrome Tourette Syndrome A neuropsychological disorder related to alterations in dopamine metabolism and neurotransmission involving frontal-subcortical neuronal circuits. Both multiple motor and one or more vocal tics need to be present with tics occurring many times a day, nearly daily, over a period of more than one year. The onset is before age 18 and the disturbance is not due to direct physiological effects of a substance or another medical condition. The disturbance causes marked distress or significant impairment in social, occupational, or other important areas of functioning. Tics and Tourette Syndrome.
  • May be administered as an adjunctive therapy for severe chronic pain Chronic pain Aching sensation that persists for more than a few months. It may or may not be associated with trauma or disease, and may persist after the initial injury has healed. Its localization, character, and timing are more vague than with acute pain. Pain Management (e.g., cancer, complex regional pain Regional Pain Complex Regional Pain Syndrome (CRPS) syndrome ( CRPS CRPS Complex regional pain syndrome (CRPS) is a chronic regional neuropathic pain condition characterized by excruciating pain (out of proportion to apparent tissue damage or inciting trauma), paresthesia, allodynia, temperature abnormalities, skin discoloration, edema, reduced range of motion, and bone demineralization. Complex Regional Pain Syndrome (CRPS)))

Dobutamine (β-1 selective agonist):

• MOA: β-1 adrenergic 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 agonist → ↑ inotropy and chronotropy Chronotropy Chronotropy is the modulation of the heart rate at the level of the pacemaker cells. Cardiac Physiology → ↑ 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:
  • Lesser agonist effects at peripheral α-1 and β-2 receptors Receptors 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 
  • The competing vasodilatory effects offset one another in the setting of ↑ 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 for a negligible effect on TPR.
• Indications:
  • Temporary IV inotropic support in cardiogenic shock Cardiogenic shock Shock resulting from diminution of cardiac output in heart disease. Types of Shock (until more definitive therapy can be undertaken)
  • IV to induce pharmacological stress during stress echocardiography Echocardiography Ultrasonic recording of the size, motion, and composition of the heart and surrounding tissues. The standard approach is transthoracic. Tricuspid Valve Atresia (TVA) for individuals unable to perform an exercise stress test

Albuterol (β-2 selective agonist):

• MOA: β-2 adrenergic 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 agonist → bronchial smooth muscle relaxation → attenuation of bronchospasm Bronchospasm Asthma Drugs:
  • β-2 stimulation also → ↑ intracellular cAMP cAMP An adenine nucleotide containing one phosphate group which is esterified to both the 3′- and 5′-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and acth. Phosphodiesterase Inhibitors →  attenuation of mast cells Mast cells Granulated cells that are found in almost all tissues, most abundantly in the skin and the gastrointestinal tract. Like the basophils, mast cells contain large amounts of histamine and heparin. Unlike basophils, mast cells normally remain in the tissues and do not circulate in the blood. Mast cells, derived from the bone marrow stem cells, are regulated by the stem cell factor. Innate Immunity: Phagocytes and Antigen Presentation → ↓ mediators of bronchospasm Bronchospasm Asthma Drugs
  • β-2 adrenergic receptors Receptors 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 also exist in the heart → cardiac side effects of 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 and palpitations Palpitations Ebstein’s Anomaly
• Indications:
  • Inhaled or nebulized for reversal of bronchospasm Bronchospasm Asthma Drugs in 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, bronchitis, and chronic obstructive pulmonary disease Pulmonary disease Diseases involving the respiratory system. Blastomyces/Blastomycosis ( COPD COPD Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD))
  • Inhaled for prophylaxis Prophylaxis Cephalosporins of exercise-induced bronchospasm Bronchospasm Asthma Drugs and reactive airway Airway ABCDE Assessment disease 
  • Also available as an oral preparation for the above indications (slower onset and rarely used)

Dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS (nonselective adrenergic agonist):

• MOA (works on different receptors Receptors 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 at different doses):
  • Low dose: stimulation of dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS receptors Receptors 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 (D1, D2, D3, D4, and D5):
    • Primarily located in the CNS
    • Functions in the extrapyramidal system to regulate movement (discussed separately)
    • Stimulation of peripheral D1 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 stimulation → vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs
  • Intermediate dose: direct stimulation of cardiac β-1 adrenergic receptors Receptors 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 ↑ inotropy and chronotropy Chronotropy Chronotropy is the modulation of the heart rate at the level of the pacemaker cells. Cardiac Physiology → ↑ 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
  • High dose: stimulation of peripheral α-2 adrenergic receptors Receptors 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 on sympathetic nerve terminals → release of norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS → α-1 mediated vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure
• Indications:
  • IV vasopressor Vasopressor Acute Cholangitis to increase BP in 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 states:
    • Low-dose infusion to maintain renal blood flow Renal blood flow The amount of the renal blood flow that is going to the functional renal tissue, i.e., parts of the kidney that are involved in production of urine. Glomerular Filtration (D1 mediated vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs)
    • Intermediate-dose infusion to support cardiac function (β-1 mediated ↑ inotropy/ chronotropy Chronotropy Chronotropy is the modulation of the heart rate at the level of the pacemaker cells. Cardiac Physiology)
    • High-dose infusion to support systemic BP (α-1 mediated ↑ TPR)
  • IV infusion during cardiac bypass to maintain organ perfusion

Epinephrine (mixed α and β agonist):

• MOA (multiple adrenergic 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 mediated effects):
  • β-1 mediated ↑ inotropy/ chronotropy Chronotropy Chronotropy is the modulation of the heart rate at the level of the pacemaker cells. Cardiac Physiology → ↑ 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
  • β-2 mediated bronchodilation and vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs → ↑ airway Airway ABCDE Assessment 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 and skeletal muscle perfusion
  • α-1 mediated vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure 
  • β-2 + α-1 vascular effects compete but generally lead to ↓ TPR (diastolic BP decreases, systolic BP may increase)
• Indications:
  • Subcutaneous injection for anaphylaxis Anaphylaxis An acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death. Type I Hypersensitivity Reaction and type 1 Type 1 Spinal Muscular Atrophy IgE-mediated reactions
  • IV vasopressor Vasopressor Acute Cholangitis to increase BP in 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 states
  • Used in advanced cardiac life support (ACLS) protocol for:
    • Sudden cardiac arrest Cardiac arrest Cardiac arrest is the sudden, complete cessation of cardiac output with hemodynamic collapse. Patients present as pulseless, unresponsive, and apneic. Rhythms associated with cardiac arrest are ventricular fibrillation/tachycardia, asystole, or pulseless electrical activity. Cardiac Arrest due to asystole Asystole No discernible electrical activity, flatline on electrocardiogram (P waves and QRS complexes are not present). Cardiac Arrest
    • Pulseless electrical activity Pulseless electrical activity Electrocardiogram (ECG) shows a cardiac rhythm without a palpable pulse. May be organized (with normal-appearing ECG complexes) or unorganized (no discernible complexes on ecg). From electromechanical dissociation, or no cardiac filling (“empty heart”). Cardiac Arrest
    • Ventricular fibrillation Ventricular fibrillation Ventricular fibrillation (VF or V-fib) is a type of ventricular tachyarrhythmia (> 300/min) often preceded by ventricular tachycardia. In this arrhythmia, the ventricle beats rapidly and sporadically. The ventricular contraction is uncoordinated, leading to a decrease in cardiac output and immediate hemodynamic collapse. Ventricular Fibrillation (V-fib)
    • Pulseless ventricular 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

Norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS (mixed α and β agonist):

• MOA (multiple adrenergic 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 mediated effects):
  • β-1 mediated ↑ inotropy/ chronotropy Chronotropy Chronotropy is the modulation of the heart rate at the level of the pacemaker cells. Cardiac Physiology → ↑ 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 (vagal influences may counterbalance chronotropy Chronotropy Chronotropy is the modulation of the heart rate at the level of the pacemaker cells. Cardiac Physiology, but inotropy is maintained)
  • Negligible effect on β-2 receptors Receptors 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
  • α-1 mediated vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure 
  • β1 + α1 vascular effects  → ↑ TPR (systolic and diastolic BP ↑)
• Indications:
  • IV vasopressor Vasopressor Acute Cholangitis to increase BP in 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 states
  • 1st-line IV vasopressor Vasopressor Acute Cholangitis in sepsis-mediated 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 unresponsive to adequate volume resuscitation Resuscitation The restoration to life or consciousness of one apparently dead. . Neonatal Respiratory Distress Syndrome

Amphetamine/ methamphetamine Methamphetamine A central nervous system stimulant and sympathomimetic with actions and uses similar to dextroamphetamine. The smokable form is a drug of abuse and is referred to as crank, crystal, crystal meth, ice, and speed. Stimulants (catecholamine augmentation):

• MOA:
  • Promotes the release of catecholamines Catecholamines A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. Adrenal Hormones ( dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS and norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS) from storage sites in the presynaptic nerve terminals
  • Blocks catecholamine reuptake by competitive inhibition Competitive inhibition Enzyme Inhibition (less significant)
• Indications:
  • Approved as an oral preparation for the treatment of attention Attention Focusing on certain aspects of current experience to the exclusion of others. It is the act of heeding or taking notice or concentrating. Psychiatric Assessment deficit disorder (ADD) and ADHD ADHD Attention deficit hyperactivity disorder is a neurodevelopmental disorder characterized by a pattern of inattention and/or hyperactivity-impulsivity that occurs in at least 2 different settings for more than 6 months. Although the patient has normal intelligence, the disease causes functional decline. Attention Deficit Hyperactivity Disorder
  • Used to promote alertness in narcolepsy Narcolepsy Narcolepsy is a neurological sleep disorder marked by daytime sleepiness and associated with cataplexy, hypnagogic hallucinations, and sleep paralysis. There are 2 types of narcolepsy: type 1 is associated with cataplexy and type 2 has no association with cataplexy. Narcolepsy
• Note:
  • High risk of abuse, dependency, addiction Addiction Substance use disorders are a significant cause of morbidity and mortality, especially among adolescents and young adults. A substance-related and addictive disorder is the continued use of a substance despite harmful consequences; these include significant impairment to one’s health or relationships or failure to fulfill major responsibilities at work, school, or home because of substance use. Substance-Related and Addictive Disorders, and overdose
  • High risk of diversion/recreational use 
  • Route of administration may be altered:
    • Smoked
    • Snorted
    • Suspended and IV administration

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 (catecholamine reuptake inhibition):

• MOA:
  • Inhibition of dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS, serotonin Serotonin A biochemical messenger and regulator, synthesized from the essential amino acid l-tryptophan. In humans it is found primarily in the central nervous system, gastrointestinal tract, and blood platelets. Serotonin mediates several important physiological functions including neurotransmission, gastrointestinal motility, hemostasis, and cardiovascular integrity. Receptors and Neurotransmitters of the CNS, and norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS reuptake
  • α-1, α-2, β-1, and β-2 adrenergic stimulation:
    • α-adrenergic stimulation → vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure in both cardiac and peripheral vasculature
    • β-adrenergic stimulation → increased HR → tachyarrhythmia Tachyarrhythmia A tachyarrhythmia is a rapid heart rhythm, regular or irregular, with a rate > 100 beats/min. Tachyarrhythmia may or may not be accompanied by symptoms of hemodynamic change. Tachyarrhythmias
• Indications:
  • Applied topically for local anesthesia Anesthesia A state characterized by loss of feeling or sensation. This depression of nerve function is usually the result of pharmacologic action and is induced to allow performance of surgery or other painful procedures. Anesthesiology: History and Basic Concepts/ vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure of vascular mucosa:
    • Useful in the nose Nose The nose is the human body’s primary organ of smell and functions as part of the upper respiratory system. The nose may be best known for inhaling oxygen and exhaling carbon dioxide, but it also contributes to other important functions, such as tasting. The anatomy of the nose can be divided into the external nose and the nasal cavity. Nose Anatomy (External & Internal), mouth, and throat Throat The pharynx is a component of the digestive system that lies posterior to the nasal cavity, oral cavity, and larynx. The pharynx can be divided into the oropharynx, nasopharynx, and laryngopharynx. Pharyngeal muscles play an integral role in vital processes such as breathing, swallowing, and speaking. Pharynx: Anatomy
    • Minor procedures (e.g., dental extraction, laceration Laceration Torn, ragged, mangled wounds. Blunt Chest Trauma repair, tonsillectomy Tonsillectomy Surgical removal of a tonsil or tonsils. Tonsillitis)
  • Applied topically for cessation of epistaxis Epistaxis Bleeding from the nose. Granulomatosis with Polyangiitis
• Note:
  • High risk of abuse, dependency, addiction Addiction Substance use disorders are a significant cause of morbidity and mortality, especially among adolescents and young adults. A substance-related and addictive disorder is the continued use of a substance despite harmful consequences; these include significant impairment to one’s health or relationships or failure to fulfill major responsibilities at work, school, or home because of substance use. Substance-Related and Addictive Disorders, and overdose
  • High risk of diversion/recreational use 
  • High risk of cardiovascular toxicity Toxicity Dosage Calculation:
    • Hypertensive emergency Hypertensive emergency A condition of markedly elevated blood pressure with diastolic pressure usually greater than 120 mm hg. Malignant hypertension is characterized by widespread vascular damage, papilledema, retinopathy, hypertensive encephalopathy, and renal dysfunction. Uncontrolled Hypertension
    • Ischemic/ hemorrhagic stroke Hemorrhagic stroke Stroke due to rupture of a weakened blood vessel in the brain (e.g., cerebral hemispheres; cerebellum; subarachnoid space). Subarachnoid Hemorrhage
    • 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

Adverse Effects and Contraindications

Sympathomimetics may produce a wide range of adverse effects resembling excessive stimulation of 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, including palpitations Palpitations Ebstein’s Anomaly, 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, and arrhythmias due to stimulation of cardiac β receptors Receptors 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.

Adverse effects

• Due to excessive adrenergic 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 activity
• IV extravasation of potent vasoconstrictors can cause local 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 if given via peripheral access (central line is preferred).
• Α-1 agonists (e.g., phenylephrine, norepinephrine Norepinephrine Precursor of epinephrine that is secreted by the adrenal medulla and is a widespread central and autonomic neurotransmitter. Norepinephrine is the principal transmitter of most postganglionic sympathetic fibers, and of the diffuse projection system in the brain that arises from the locus ceruleus. Receptors and Neurotransmitters of the CNS):
  • 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
  • Reflex 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
  • Piloerection
  • Urinary retention Urinary retention Inability to empty the urinary bladder with voiding (urination). Delirium
  • Vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure: may produce distal 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 and necrosis Necrosis The death of cells in an organ or tissue due to disease, injury or failure of the blood supply. Ischemic Cell Damage
• Α-2 agonists (e.g., clonidine):
  • Sedation
  • Respiratory depression
  • 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
  • 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 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
  • Miosis Miosis Pupil: Physiology and Abnormalities
  • Rebound 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
  • Xerostomia Xerostomia Decreased salivary flow. Sjögren’s Syndrome 
• Β-1 agonists (e.g., dobutamine):
  • 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/arrhythmias
  • High-dose IV → can cause mesenteric 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 
  • Acute coronary syndrome in individuals with underlying coronary artery Coronary Artery Truncus Arteriosus disease
• Β-2 agonists (e.g., albuterol, salmeterol Salmeterol Asthma Drugs):
  • Tremors
  • Agitation Agitation A feeling of restlessness associated with increased motor activity. This may occur as a manifestation of nervous system drug toxicity or other conditions. St. Louis Encephalitis Virus
  • Insomnia Insomnia Insomnia is a sleep disorder characterized by difficulty in the initiation, maintenance, and consolidation of sleep, leading to impairment of function. Patients may exhibit symptoms such as difficulty falling asleep, disrupted sleep, trouble going back to sleep, early awakenings, and feeling tired upon waking. Insomnia
  • 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
  • Hyperinsulinemia Hyperinsulinemia Diabetes Mellitus
  • Hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus
  • 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

Drug-drug interactions

• Βeta blockers: may antagonize the effects of β agonists → diminish the therapeutic effect
• Cannabinoid products: may enhance the tachycardic effect of sympathomimetics
• 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 (e.g., caffeine Caffeine A methylxanthine naturally occurring in some beverages and also used as a pharmacological agent. Caffeine’s most notable pharmacological effect is as a central nervous system stimulant, increasing alertness and producing agitation. Several cellular actions of caffeine have been observed, but it is not entirely clear how each contributes to its pharmacological profile. Among the most important are inhibition of cyclic nucleotide phosphodiesterases, antagonism of adenosine receptors, and modulation of intracellular calcium handling. Stimulants, 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): may enhance the adverse/toxic effect of sympathomimetics
• Α-1 blockers (e.g., doxazosin Doxazosin A prazosin-related compound that is a selective alpha-1-adrenergic blocker. Antiadrenergic Drugs, tamsulosin Tamsulosin A sulfonamide derivative and adrenergic alpha-1 receptor antagonist that is used to relieve symptoms of urinary obstruction caused by benign prostatic hyperplasia. Antiadrenergic Drugs):
  • May diminish the vasoconstrictive effect of dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS
  • Dopamine Dopamine One of the catecholamine neurotransmitters in the brain. It is derived from tyrosine and is the precursor to norepinephrine and epinephrine. Dopamine is a major transmitter in the extrapyramidal system of the brain, and important in regulating movement. Receptors and Neurotransmitters of the CNS may antagonize α-1 blocker mediated vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs.
• Serotonin-norepinephrine reuptake inhibitors Serotonin-Norepinephrine Reuptake Inhibitors Serotonin Reuptake Inhibitors and Similar Antidepressants ( SNRIs SNRIs Serotonin Reuptake Inhibitors and Similar Antidepressants):
  • May enhance the tachycardic and vasopressor Vasopressor Acute Cholangitis effects of α and β agonists
  • If coadministered → monitor for increased sympathomimetic effects (e.g., 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, chest pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways, or headache Headache The symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders. Brain Abscess)
• Tricyclic antidepressants Tricyclic antidepressants Tricyclic antidepressants (TCAs) are a class of medications used in the management of mood disorders, primarily depression. These agents, named after their 3-ring chemical structure, act via reuptake inhibition of neurotransmitters (particularly norepinephrine and serotonin) in the brain. Tricyclic Antidepressants:
  • May enhance the vasopressor Vasopressor Acute Cholangitis effect of the α and β agonists (avoid combining if possible)
  • Monitor for evidence of increased pressor effects and consider reductions in initial dosages of the α and β agonists.

Contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation for clinical use

• Sympathomimetics should be used with caution in individuals with cardiovascular disorders; however, many are used in life-threatening situations.
• Specific contraindications Contraindications A condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks). Noninvasive Ventilation to certain agents:
  • Extreme 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 (phenylephrine)
  • Hypertrophic obstructive cardiomyopathy Cardiomyopathy Cardiomyopathy refers to a group of myocardial diseases associated with structural changes of the heart muscles (myocardium) and impaired systolic and/or diastolic function in the absence of other heart disorders (coronary artery disease, hypertension, valvular disease, and congenital heart disease). Cardiomyopathy: Overview and Types (dobutamine)
  • 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) (isoproterenol)

Comparison of Medications