Autonomic Pharmacology Flashcards
Phenylephrine
Adrenergic Agonist: Direct Acting: Alpha1 Selective
Activates alpha adrenergic receptors in vascular sm: increases BP & TPR (reflex bradycardia)
Activates beta receptors only at much higher conc.
Clinical Indications: antihypotensive (orthostatic hypotension & shock), paroxysmal atrial tachycardia, nasal decongestant, mydriatic
Clonidine
Adrenergic Agonist: Direct Acting: Alpha2 Selective
Activates central alpha2 receptors (located on presynaptic nerve terminals) which decrease NT release & NE synthesis: decreases central sympathetic outflow: BP decreases. Also decreases aqueous humor production: decreased intraocular pressure
Uses: systemic hypertension and glaucoma
Adverse Effects: dry mouth, sedation, hypotension
Terbutaline
Adrenergic Agonist: Direct Acting: Beta2 Selective
Relax bronchial sm and decrease airway resistance, suppress release of leukotrienes & histamine from mast cells in lungs, enhance mucociliary function, decrease microvascular permeability, inhibit phospholipase A2
Not a substrate for methylation by COMT
Used for long-term tx of obstructive airway diseases, acute bronchospasm, emergyency tx of status asthmaticus (IV)
Fenoldopam
Adrenergic Agonist: Direct Acting: D1 Selective
D1»D2 Some stimulation of alpha2: feedback inhibition of NE release
Renal, mesenteric, peripheral, coronary vasodilation
RBF maintained & natriuresis promoted
Used during Hypertensive Crisis Side effect: hypotension
Isoproterenol
Adrenergic Agonist: Direct Acting: Non-Selective
Powerful Beta1&2 agonist, no effect on alpha
Decrease TPR, Increase HR, arrhythmias, myocardial contractility
Uses: bradycardia or complete heart block, particularly in torsade de pointes, CHF: as an inotropic agent, can be used in MI as an inotropic agent, high dose can cause myocardial necrosis
Dobutamine
Adrenergic Agonist: Direct Acting: Non-Selective
Stimulates alpha1, beta1&2, mainly acts on beta1 at therapeutic doses (considered selective)
Does not affect release of NE from nerve endings, does not affect dopaminergic receptors.
beta1 = +inotropic effect (>isoproterenol), +chronotropic effect: SA node automaticity, AV conduction
Does not change TPR b/c balance b/t alpha1&beta2
Used for: short-term tx of cardiac failure (post-cardiac surgery, CHF, MI) Stress Test: used in pts w/ coronary artery disease to assess exercise tolerance
Adverse Effects: Excessive increases in BP&HR, increased ventricular response rate in pts w/ AFib, entricular ectopic activity, my increase size of MI, tolerance may develop
Low Dose Epinephrine IV
Adrenergic Agonist: Direct Acting: Non-Selective
Epi stimulates everything: alpha1&2 beta1&2
In low dose IV: effects on beta1&2 predominate:
Beta1: increase pulse pressure, HR, SV, CO
Beta2: Decrease TPR, slight decrease in MAP, reflex tachycardia
Moderate Dose Epinephrine IV
Adrenergic Agonist: Direct Acting: Non-Selective
Epi stimulates everything: alpha1&2 beta1&2
In med dose IV: effects on beta1&2 and alpha1
Beta1: increase pulse pressure, HR, SV, CO
Beta2: Decrease TPR, slight decrease in MAP, reflex tachycardia
Alpha1: Increased TPR & BP
Final Effects = BP increased
High Dose Epinephrine IV
Adrenergic Agonist: Direct Acting: Non-Selective
Epi stimulates everything: alpha1&2 beta1&2
In high dose IV: predominant actions on alpha1 receptor causing an increase in TPR and BP w/ reflex bradycardia
Lesser effects on beta1&2 at high doses
Norepinephrine
Adrenergic Agonist: Direct Acting: Non-Selective
alpha1»beta1»»»beta2 (so no vasodilation)
Increase sBP, dBP, pulse pressure, coronary blood flow (coronary dilation and increased BP)
Unchanged or decreased CO d/t reflex bradycarida
Increase TPR, decrease renal, splanchnic hepatic blood flow
Limited therapeutic value. Can tx hypotension but dose titration usually required
Dopamine
Adrenergic Agonist: Direct Acting: Non-Selective
D1, D2, Beta1, Alpha1
Dose dependent (low dose is most common)
Diuretic effect: D2 receptors: increased Na+ filtration and decerased reabsorption = Na+ diuresis
Presynaptic D2 receptors: decrease NE release: vasodilation
Precaution: hypovolemia should aloways be corrected before dopamine use
Used in tx of severe CHF, particulary in pts w/ oliguria and low or normal peripheral vascular resistance. Cardiogenic/septic shock.
Ephedrine
Adrenergic Agonist: Mixed Acting
Directly activates adrenoceptors & indirectly releases NE
First orally active sypathomimetic drug, ma-huang, ↑bioavailability, long duration of action, mild CNS stimulant, decongestant (pseudoephedrine)
Amphetamine
Adrenergic Agonist: Indirect-Acting
CNS effects: releases biogenic amines from storage sties in nerve terminals, ↑medullary resp center, ↑cortex&reticular activating system which prevents fatigue and delays need for sleep. Decrease need for food.
CV effects: activates peripheral alpha/beta receptors, ↑s&dBP, HR, cardiac arrhythmias may occur, ↑bladder sphincter cx: used to tx enuresis/incontinence
Tyramine
Adrenergic Agonist: Indirect-Acting
Can be used to make NE & epi using indirect pathway
Destroyed by MAO in intestinal wall and liver
In pts using MAOIs, ingestion of fermented cheese (high tyramine levels) can cause dangerous ↑BP
Tyramine does not cross BBB = peripheral effects
Phenoxybenzamine
Alpha Adrenoceptor Antagonist (Alpha Blocker)
Irreversibly blocks alpha1&2, lowers BP, HR raises d/t indirect baroreflex activation
Tx: pheochromocytoma, high catecholamine states
T1/2>1day: orthostatic hypotension, tachycardia, MI
Prazosin (Terazosin, Doxazosin)
Alpha Adrenoceptor Antagonist (Alpha Blocker)
Blocks only alpha1, NOT alpha2
Lowers BP
Tx: HTN, BPH
Larger depressor effect w/ first dose may cause orthostatic hypotension (notable side effect)
Tamsulosin
Alpha Adrenoceptor Antagonist (Alpha Blocker)
slightly selectve for alpha1A, blockade may relax prostatic sm more than vascular sm
Used to tx: BPH, orthostatic hypotension may be less common than with prazosin
Propranolol (Nadolol, Timolol, Pindolol - has ISA, less bradycardia)
Beta Adrenoceptor Antagonist (beta blocker)
1st gen beta blocker - nonselective (blocks b1 = b2)
Effects: lower HR, BP, reduce renin
Tx: HTN, angina pectoris, arrhythmias, migrane, hyperthyroidism
Toxic: Bradycardia, worsened asthma, fatigue, vivid dreams, cold hands
Metoprolol (Atenolol, Esmolol, Alprenolol, Betaxolol, Acebutolol - has ISA, less bradycardia)
Beta Adrenoceptor Antagonist (beta blocker)
2nd gen beta blocker - selective (blocks b1»>b2)
Effects: lower HR, BP, reduce renin, may be safer in asthma pts d/t less b2 effects
Tx: angina pectoris, HTN, arrhythmias
Toxic: bradycardia, fatigue, vivid dreams, cold hands
Labetalol
Beta Adrenoceptor Antagonist (beta blocker)
3rd gen beta blocker - vasodilatory (b1=b2>=a1>a2)
Effects: lowers blood pressure w/ limited HR increase
Tx: HTN
This drug is commonly used like it’s one of the alpha blockers - it can lower BP with less reflex tachycardia than the other alpha blockers.
Alpha-Methyldopa
Alpha2 Adrenoceptor Agonist
Decrease BP in pregnency
Apraclonidine & Brimonidine
Alpha2 Adrenoceptor Agonist
Lover intraocular pressure only
Metaproterenol
Beta2 Adrenoceptor Agonist
Asthma, COPD, bronchospasm
Less used than albuterol & terbutaline
Albuterol
Beta2 Adrenoceptor agonist
For asthma
Ritodrine
Beta2 Adrenoceptor agonist
uterine relaxant
stop preterm labor
Cocaine
Reuptake Inhibitor
Indirect Adrenergic Agonist
Pargyline & Entacapone
MAO/COMT inhibitor
Indirecet Adrenergic Agonist
Phentolamine
Alpha1 & Alpha 2 Adrenoceptor Antagonist
Give to pts on MAOI who eat tyramine
Can cause orthostatic hypotension & tachycardia
Yohimbine (Rauwoscine, Torazoline)
Alpha 2 > Alpha 1 Adrenoceptor Antagonist
Increase NE release, Increase BP & HR
Use in male erectile dysfunction & hypotension
Carvedilol
Beta Adrenoceptor Antagonist (beta blocker)
3rd gen beta blocker - vasodilatory (b1=b2>=a1>a2)
Effects: lowers blood pressure w/ limited HR increase
Use to Tx Heart Failure
Acetylcholine
Prototype direct acting cholinoceptor agonist
Rapid destruction, not usually clinically used
Methacholine
Direct Acting Muscarinic Cholinoceptor Agonist
Dx asthma
Carbachol
Direct Acting Muscarinic Cholinoceptor agonist
Lower intraocular pressure
Use to tx glaucoma
Bethanechol
Muscarinic cholinoceptor agonist
Increase GI motility & bladder
Tx ileus & unobstructed urinary retention
Pilocarpine
Muscarinic cholinoceptor agonist
Miosis, glaucoma, xerostomia
test PANS dysfunction
Nicotine
Nicotinic cholinoceptor agonist
Muscle spasms, increased HR, peripheral vasoconstriction, increased gut motility & secretion, increased RR, nausea/vomiting
Tx smoking cessation
Edrophonium
Cholinesterase inhibitor (indirect agonist) Dx myasthenia gravis
Neostigmine & Pyridostigmine
Cholinesterase inhibitor (indirect agonist)
Doesn’t cross BBB
Tx ileus, myasthenia gravis, urinary retention, reverse depolarizing NM blockers
Physositmine
Cholinesterase inhibitor (indirect agonist) Crosses BBB Use in atropine overdose
Donepezil
Cholinesterase inhibitor (indirect agonist)
Crosses BBB
Tx Alzheimers
Organophosphates
Irreversible cholinesterase inhibitors
used in insecticides (malathion, prathion, sarin, echothiophate)
Cause Diarrhea, Urination, Miosis, Bradycardia, Bronchospasm, Excitation of skeletal muscles & CNS, Lacrimation, Sweating, Salivation (DUMBBELSS)
Treat with atropine
Atropine
Muscarinic receptor antagonist
Treat ACh intoxication (except E symptom)
Antisecratory (can lead to dry mouth, increased temperature, flushing, disorientation), causes mydrisasis & cycloplegia
Ipratropium
Muscarinic receptor antagonist
Decreases bronchoconstriction & bronchial secretions
Tx asthma & COPD
Benztropine
Muscarinic receptor antagonist
Tx Parkinson’s
Causes decreased GI motility & Increased HR
Hexamethonium & Mecamylamine
Nicotinic Receptor Antagonist (ganglion)
Decrease autonomic tone, prevent baroreceptor change in HR
Cause vasodilation, decreased BP, increased HR, mydriasis, cycloplegia, decreased GI motility, decreased sweat/saliva (xerostomia, anhidrosis), constipation & urinary retention
D-tubocurarine
Non-depolarizing Neuromuscular (Nm) blocker
Prevent chanel opening & decrease ACh release
Anesthesia, tracheal intubation, convulsions
Can cause hypotention, increased gastric & intraocular pressure, muscle pain, & hyperkalemia
Succinylcholine
Depolarizing Neuromuscular Blocking Drug
Causes depolarizing paralysis & later desensitization of chanels to depolarization
Anesthesia, tracheal intubation, convulsions
Can cause hypotention, increased gastric & intraocular pressure, muscle pain, & hyperkalemia
Muscarinic Antagonists
Atropine, Ipratropium, Benztropine
Direct Acting Cholinoceptor Agonists
Methacholine, Carbachol, Bethanechol, Pilocarpine
Indirect Acting (reversible) Cholinoceptor Agonists
Edrophonium, Neostigmine, Pyridostigmine, Physostigmine, Donepezil
Alpha receptor Antagonists
Prazosin, Phenoxybenzamine, Tamsulosin, Phentolamine, Yohimibine
Beta Receptor Antagonists
Propranolol, Metoprolol, Labetalol, Carvedilol
