Antiadrenergic Drugs

Overview

Overview of the ANS ANS 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

The ANS ANS 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 is subdivided into the sympathetic and parasympathetic pathways. Both pathways contain 2 efferent Efferent Neurons which send impulses peripherally to activate muscles or secretory cells. Nervous System: Histology 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 in series known as the preganglionic and postganglionic 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.

Preganglionic neuron:

• 1st neuron in the series 
• The cell body originates in the CNS.
• Release acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS onto nicotinic cholinergic 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 in the autonomic ganglia
• In the adrenal gland, preganglionic 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 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 Chromaffin cells Cells that store epinephrine secretory vesicles. During times of stress, the nervous system signals the vesicles to secrete their hormonal content. Their name derives from their ability to stain a brownish color with chromic salts. Characteristically, they are located in the adrenal medulla and paraganglia of the sympathetic nervous system. Adrenal Hormones in the adrenal medulla Adrenal Medulla The inner portion of the adrenal gland. Derived from ectoderm, adrenal medulla consists mainly of chromaffin cells that produces and stores a number of neurotransmitters, mainly adrenaline (epinephrine) and norepinephrine. The activity of the adrenal medulla is regulated by the sympathetic nervous system. Adrenal Glands: Anatomy (instead of the sympathetic ganglia).

Postganglionic neuron: 

• Second neuron in the series 
• The cell body originates in the ganglion.
• May release:
  • 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 (NE) onto alpha- or beta-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 in target tissues:
    • Cardiac and smooth muscle
    • Gland cells
    • Nerve terminals
  • Acetylcholine Acetylcholine A neurotransmitter found at neuromuscular junctions, autonomic ganglia, parasympathetic effector junctions, a subset of sympathetic effector junctions, and at many sites in the central nervous system. Receptors and Neurotransmitters of the CNS onto muscarinic receptors Muscarinic Receptors Asthma Drugs in sweat glands Sweat glands Sweat-producing structures that are embedded in the dermis. Each gland consists of a single tube, a coiled body, and a superficial duct. Soft Tissue Abscess
  • 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 onto dopaminergic 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 in renal vascular smooth muscle
• In the adrenal gland, chromaffin cells Chromaffin cells Cells that store epinephrine secretory vesicles. During times of stress, the nervous system signals the vesicles to secrete their hormonal content. Their name derives from their ability to stain a brownish color with chromic salts. Characteristically, they are located in the adrenal medulla and paraganglia of the sympathetic nervous system. Adrenal Hormones act as modified postganglionic 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 and release epinephrine Epinephrine The active sympathomimetic hormone from the adrenal medulla. It stimulates both the alpha- and beta- adrenergic systems, causes systemic vasoconstriction and gastrointestinal relaxation, stimulates the heart, and dilates bronchi and cerebral vessels. Sympathomimetic Drugs (80%) and NE (20%) directly into the bloodstream.

Chemistry and Pharmacodynamics

Chemistry

• Catecholamines Catecholamines A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. Adrenal Hormones 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 Tyrosine A non-essential amino acid. In animals it is synthesized from phenylalanine. It is also the precursor of epinephrine; thyroid hormones; and melanin. Synthesis of Nonessential Amino Acids (a.a. Tyr).
• Most beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers) are structurally similar to the catecholamines Catecholamines A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. Adrenal Hormones.

Mechanisms of action

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

Alpha 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: 

• Alpha-1 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:
  • Alpha-1 stimulation:
    • Activates the enzyme phospholipase C Phospholipase C A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of glycerophospholipids. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of phosphatidylcholine, it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of phosphatidylinositols. Pseudomonas → 
    • Generates inositol triphosphate ( IP3 IP3 Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4, 5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1, 4, 5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell’s endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin. Second Messengers) and diacylglycerol Diacylglycerol Second Messengers ( DAG DAG Second Messengers) as secondary messengers → 
    • Causes ↑ calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes ion ( Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺) levels intracellularly → 
    • 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
  • Alpha-1 receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors antagonists: inhibit release of IP3 IP3 Intracellular messenger formed by the action of phospholipase C on phosphatidylinositol 4, 5-bisphosphate, which is one of the phospholipids that make up the cell membrane. Inositol 1, 4, 5-trisphosphate is released into the cytoplasm where it releases calcium ions from internal stores within the cell’s endoplasmic reticulum. These calcium ions stimulate the activity of B kinase or calmodulin. Second Messengers and DAG DAG Second Messengers → ↓ Ca CA Condylomata acuminata are a clinical manifestation of genital HPV infection. Condylomata acuminata are described as raised, pearly, flesh-colored, papular, cauliflower-like lesions seen in the anogenital region that may cause itching, pain, or bleeding. Condylomata Acuminata (Genital Warts)²⁺ release → smooth muscle relaxation
• Alpha-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 (primarily located at peripheral nerve endings):
  • Alpha-2- 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:
    • Inhibits the enzyme adenylyl cyclase → 
    • ↓ Levels of the secondary messenger 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 → 
    • Ultimately blocks the presynaptic release of NE → 
    • ↓ Adrenergic stimulation
  • Alpha-2 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 antagonists: block reduction in 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 → ↑ NE release → ↑ adrenergic stimulation
• Alpha 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 inhibitor binding may be:
  • Selective or nonselective for alpha-1 vs. alpha-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 
  • Reversible or irreversible

Beta 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: beta-1, beta-2, and beta-3 

• Beta 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: stimulates adenylyl cyclase → ↑ 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 → triggers target cell effects
• Beta 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 antagonists:
  • Competitively inhibit catecholamines Catecholamines A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. Adrenal Hormones at the beta-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 
  • ↓ Activation of adenylyl cyclase → inhibits target cell effects
  • Have minimal impact on patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship who are at rest
• Beta 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 partial agonists:
  • Partially activate the beta 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, though not as strongly as true catecholamines Catecholamines A general class of ortho-dihydroxyphenylalkylamines derived from tyrosine. Adrenal Hormones
  • Results in decreased effects when NE is ↑ and increased effects when NE is ↓

Physiologic effects

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 are located throughout the body and trigger Trigger The type of signal that initiates the inspiratory phase by the ventilator Invasive Mechanical Ventilation a wide variety of effects. The physiologic effects of antiadrenergic agents are to block whatever the typical response is of that particular 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. 

• Alpha-1 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:
  • Found in smooth muscle throughout the body (e.g., bronchial, vascular, intestinal, and bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess walls)
  • Play a major role in determining vascular tone
  • Alpha-1 receptor Receptor Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors antagonists cause:
    • Vasodilation Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs
    • Relaxation of bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess muscles → improved micturition 
• Beta-1 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:
  • Primarily located in the heart 
  • Play a major role in determining heart rate Heart rate The number of times the heart ventricles contract per unit of time, usually per minute. Cardiac Physiology (HR) and contractility
  • Beta-1 antagonists:
    • ↓ HR and contractility 
    • ↓ Myocardial O₂ demand
• Beta-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:
  • 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: Anatomy, and smooth muscle
  • Usually has effects opposite those of alpha-1 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 
  • Beta-2 antagonists:
    • ↓ HR, contractility, and myocardial O₂ demand
    • Bronchoconstriction (adverse effect)
    • Vasoconstriction Vasoconstriction The physiological narrowing of blood vessels by contraction of the vascular smooth muscle. Vascular Resistance, Flow, and Mean Arterial Pressure
    • ↓ Intraocular pressure Intraocular Pressure The pressure of the fluids in the eye. Ophthalmic Exam (IOP)
    • Metabolic effects 

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

• Beta-1-selective blockers:
  • Atenolol Atenolol A cardioselective beta-1 adrenergic blocker possessing properties and potency similar to propranolol, but without a negative inotropic effect. Class 2 Antiarrhythmic Drugs (Beta Blockers) 
  • Metoprolol
  • Esmolol
  • Nebivolol
• Beta-2-selective blocker: butaxamine (used only experimentally)
• Nonselective beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers):
  • Propranolol
  • Nadolol Nadolol A non-selective beta-adrenergic antagonist with a long half-life, used in cardiovascular disease to treat arrhythmias, angina pectoris, and hypertension. Nadolol is also used for migraine disorders and for tremor. Class 2 Antiarrhythmic Drugs (Beta Blockers)
  • Timolol Timolol A beta-adrenergic antagonist that is similar in action to propranolol; the levo-isomer is more active. Timolol has been proposed as an anti-hypertensive, anti-arrhythmic, anti-angina, and anti-glaucoma agent. It is also used in the treatment of migraine disorders and tremor. Class 2 Antiarrhythmic Drugs (Beta Blockers)
• Beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers) with partial agonist activity:
  • Pindolol
  • Acebutolol Acebutolol A cardioselective beta-1 adrenergic antagonist with little effect on the bronchial receptors. The drug has stabilizing and quinidine-like effects on cardiac rhythm, as well as weak inherent sympathomimetic action. Class 2 Antiarrhythmic Drugs (Beta Blockers)

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

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

• Carvedilol Carvedilol A carbazole and propanol derivative that acts as a non-cardioselective beta blocker and vasodilator. It has blocking activity for alpha 1 adrenergic receptors and, at higher doses, may function as a blocker of calcium channels; it also has antioxidant properties. Carvedilol is used in the treatment of hypertension; angina pectoris; and heart failure. It can also reduce the risk of death following myocardial infarction. Class 2 Antiarrhythmic Drugs (Beta Blockers)
• Labetalol Labetalol A salicylamide derivative that is a non-cardioselective blocker of beta-adrenergic receptors and alpha-1 adrenergic receptors. Subarachnoid Hemorrhage

Pharmacokinetics

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

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 Sildenafil A phosphodiesterase type-5 inhibitor; vasodilator agent and urological agent that is used in the treatment of erectile dysfunction and primary pulmonary hypertension. Phosphodiesterase Inhibitors) → 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 Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers) + loop diuretics Diuretics Agents that promote the excretion of urine through their effects on kidney function. Heart Failure and Angina Medication → 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 NSAIDS Primary vs Secondary Headaches may ↓ the efficacy of beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers).

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 Vasodilation The physiological widening of blood vessels by relaxing the underlying vascular smooth muscle. Pulmonary Hypertension Drugs and smooth muscle relaxation. They are frequently used in the treatment of:

• Prazosin:
  • 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 
  • Benign Benign Fibroadenoma prostatic hyperplasia Hyperplasia An increase in the number of cells in a tissue or organ without tumor formation. It differs from hypertrophy, which is an increase in bulk without an increase in the number of cells. Cellular Adaptation ( BPH BPH 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, 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. resulting in urinary retention Urinary retention Inability to empty the urinary bladder with voiding (urination). Delirium)
  • 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 Adrenal Medulla The inner portion of the adrenal gland. Derived from ectoderm, adrenal medulla consists mainly of chromaffin cells that produces and stores a number of neurotransmitters, mainly adrenaline (epinephrine) and norepinephrine. The activity of the adrenal medulla is regulated by the sympathetic nervous system. Adrenal Glands: Anatomy)
• Phentolamine:
  • 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 (ED)
  • Prevention or treatment of extravasation of IV NE 
  • Reversal of soft-tissue 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 from local anesthetics Anesthetics Agents that are capable of inducing a total or partial loss of sensation, especially tactile sensation and pain. They may act to induce general anesthesia, in which an unconscious state is achieved, or may act locally to induce numbness or lack of sensation at a targeted site. Anesthesiology: History and Basic Concepts containing a vasoconstrictor

Beta antagonists

Beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers) 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 Afib 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)
  • 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) (HF)
  • Post-MI
  • Angina
  • 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
• Other indications for propranolol:
  • Neuropsychiatric:
    • Essential tremor Tremor Cyclical movement of a body part that can represent either a physiologic process or a manifestation of disease. Intention or action tremor, a common manifestation of cerebellar diseases, is aggravated by movement. In contrast, resting tremor is maximal when there is no attempt at voluntary movement, and occurs as a relatively frequent manifestation of parkinson disease. Myotonic Dystrophies
    • 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 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
    • Anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder (especially performance anxiety Anxiety Feelings or emotions of dread, apprehension, and impending disaster but not disabling as with anxiety disorders. Generalized Anxiety Disorder)
  • GI: bleeding from esophageal varices (beta blockade ↓ portal vein Portal vein A short thick vein formed by union of the superior mesenteric vein and the splenic vein. Liver: Anatomy 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 Hypersecretion of thyroid hormones from the thyroid gland. Elevated levels of thyroid hormones increase basal metabolic rate. Thyrotoxicosis and Hyperthyroidism
• Specialized indications for other beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers):
  • Labetalol Labetalol A salicylamide derivative that is a non-cardioselective blocker of beta-adrenergic receptors and alpha-1 adrenergic receptors. Subarachnoid Hemorrhage: 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 The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
  • Timolol Timolol A beta-adrenergic antagonist that is similar in action to propranolol; the levo-isomer is more active. Timolol has been proposed as an anti-hypertensive, anti-arrhythmic, anti-angina, and anti-glaucoma agent. It is also used in the treatment of migraine disorders and tremor. Class 2 Antiarrhythmic Drugs (Beta Blockers) (good ocular penetration Penetration X-rays): 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 Half-Life The time it takes for a substance (drug, radioactive nuclide, or other) to lose half of its pharmacologic, physiologic, or radiologic activity. Pharmacokinetics and Pharmacodynamics): when steady-state infusions are required
  • Butoxamine (beta-2-selective antagonist): used for research Research Critical and exhaustive investigation or experimentation, having for its aim the discovery of new facts and their correct interpretation, the revision of accepted conclusions, theories, or laws in the light of newly discovered facts, or the practical application of such new or revised conclusions, theories, or laws. Conflict of Interest purposes 

Adverse Effects and Contraindications

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

Overdose

Presentation of beta-blocker toxicity Toxicity Dosage Calculation

Although beta-blockers Beta-blockers Drugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety. Class 2 Antiarrhythmic Drugs (Beta Blockers) are generally safe, overdose can produce symptoms of toxicity Toxicity Dosage Calculation, typically within 2 hours (almost always within 6). Symptoms include:

• 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
• Myocardial depression and cardiogenic shock Cardiogenic shock Shock resulting from diminution of cardiac output in heart disease. 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 Bronchospasm Asthma Drugs
• 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

Management

• Acute stabilization of the airway Airway ABCDE Assessment, breathing, and circulation Circulation The movement of the blood as it is pumped through the cardiovascular system. ABCDE Assessment (ABC):
  • Intubate if needed.
  • Isotonic Isotonic Solutions having the same osmotic pressure as blood serum, or another solution with which they are compared. Renal Sodium and Water Regulation 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 Atropine An alkaloid, originally from atropa belladonna, but found in other plants, mainly solanaceae. Hyoscyamine is the 3(s)-endo isomer of atropine. Anticholinergic Drugs to treat symptomatic 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
  • Glucagon Glucagon A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal glucagon-like peptides. Glucagon is secreted by pancreatic alpha cells and plays an important role in regulation of blood glucose concentration, ketone metabolism, and several other biochemical and physiological processes. Gastrointestinal Secretions
  • Calcium Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Electrolytes salts
  • Vasopressors Vasopressors Sepsis in Children
• 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 Dextrose Intravenous Fluids
• 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