ANS Drugs Flashcards
Botulinum toxin - mechanism
Blocks ACh release by cleaving SNARE proteins required for neurotransmitter release.
Botulinum toxin - Theraputic uses
long-term neuromuscular blockade for pts with blepharospam, strabismus, facial wrinkles, other issues related to spasm.
Botulinum action at target organs of parasympathetic NS
blocks cholinergic transmission – Tx of urinary incontinence.
Botulinum action at target organs of sympathetic NS
blocks cholinergic neurons that innervate sweat glands – blocks excessive sweating when administered in axilla.
Competitive blockers
competitive antagonists: inhibits the binding of ACh to the nAChR, blocking transmission
Prototype: tubocurarine
Succinylcholine mechanism
depolarizing blocker, partial agonist of nAChR - initially depolarizes endplate, causing muscle twitching, which interferes with nerve-evoked muscle contraction.
Persistent binding = desensitization of receptor to cholinergic agonists.
Succinylcholine uses
muscle relaxant/paralytic used during surgery/procedures
Succinylcholine side-effects/toxicity
can affect autonomic ganglia - arrhythmias, BP changes
can cause histamine release - bronchial spasm and hypotension
malignant hyperthermia
Toxic effects: overdose = cardiopulmonary failure d/t neuromuscular blockage, ganglion block, and histamine release
Acetylcholine - what receptors, what uses?
Agonist at both nicotinic and muscarinic receptors
causes meiosis (constriction of pupil) - used in extraction of cataracts
Methacholine - what is it, why is it different from ACh?
muscarinic agonist
choline ester of acetylcholine
more resistant to hydrolysis by acetylcholinesterase and plasma cholinesterase
very little nicotinic activity
Methacholine uses
diagnostic tool in its with asthma to determine airway hyperactivity - inhalation causes bronchoconstriction
Possible side-effects of non-subtype selective muscarinic receptors acetylcholine and methacholine?
hypotension - via vasodilation via mAChR on endothelial cells of vessels
bradycardia - via mAChR on heart
tachycardia - via hypotension-produced reflex increase in sympathetic tone
Cevimeline mechanism & use
M3 selective muscarinic agonist
used to treat dry mouth in pts with Sjogren’s syndrome
Atropine mechanism, uses, and side-effects
non-selective, competitive muscarinic antagonist for AChR
Blocks parasympathetic (rest and digest) stimulation at effector organs - affects many organs
Darifenacin
M3-selective antagonist that treats overactive bladder
AChE inhibitors
inhibit acetylcholinesterase (AChE), which hydrolyses ACH.
Increase lifetime of ACh and transmission of ACh signals
Edrophonium
Non-covalent reversible AChE inhibitor.
competitive enzyme inhibitor.
used in cardiac arrhythmias and in the diagnosis of myasthenia gravis (induces transient increase in strength.)
eliminated by kidneys rapidly - short duration of action
Pyridostigmine
covalent, slowly reversible AChE inhibitor.
Tx of Myasthenia Gravis - increases efficiency of NMJ by increasing ACh availability
Donepezil
noncompetitive AChE inhibitor
improves cognition/delays progression of Alzheimers
What are the naturally occurring catecholamines?
Epinephrine, norepinephrine, and dopamine
What is the main pathway for adrenergic for stopping adrenergic transmission?
Reuptake of norepinephrine back into the nerve terminal, metabolism by monoamine oxidase (MAO), extraneuronal catelchol-o-methytransferase (COMT)
Cocaine mechanism
Blocks the reuptake of catecholamines into the nerve terminal
Ephedrine
Mixed-acting (stimulates alpha and beta receptors) sympathomimetic (causes release of norepinephrine) and is an agonist for adrenergic receptors. Used to prevent hypotension during spinal anesthesia.
Indirect-acting sympathomometics
Act on the noradrenergic nerve terminal to cause release of norepinephrine – sympathetic effect.
Methyldopa
False transmitter (can be released in reponse to neuron stimulation). Stored in vesicles in adrenergic terminals
Alpha adrenergic versus beta-adrenergic responses
In alpha-adrenergic responses: potency EPI > NE»_space; ISO (isoprotenerol)
In beta-adrenergic responses: potency ISO > EPI > NE
Isoproterenol
High specificity for all 3 beta-receptors
Relaxes skeletal muscle vascular beds, decreasing blood pressure.
Also increases heartrate and cardiac output d/t decrease in peripheral resistance.
Dopamine
Activates vasodilatory dopamine receptors in mesenteric and renal vessels.
Phenylephrine
synthetic amine
stimulates alpha 1 adrenergic receptors & very little beta-receptor activity
increases blood pressure and peripheral resistance
decreases heart rate due to baroreceptor reflex
Midodrine
alpha 1 adrenergic agonist
prodrug - metabolically converted to the active form
increases blood pressure in pts with autonomic insufficiency and hypotension
Clonidine
selective alpha2 adrenergic agonist
Tx of hypertension
decreases BP by acting on a2 receptors in the CNS to decrease sympathetic outflow
Dobutamine
beta1 selective adrenergic agonist
increases cardiac output in conditions such as heart failure
Albuterol
Beta2 selective adrenergic agonists
bronchodilator - relaxes bronchial and other smooth muscle with little cardiac stimulation
Metoprolol
Beta1-selective agonist
Inhibits cardiac effects of sympathetic activity or adrenergic drugs - fewer effects on other organs
Propanolol
Non-selective beta blocker
Blocks all 3 beta receptors, decrease HR, cardiac output, BP. Can also block other beta-mediated effects
Uses for beta blockers
HTN
Angina
Cardiac arrhythmias
Glaucoma
Toxic effects of beta-blockers
Blockage of beta2 receptors causes bronchoconstriction in pts with respiratory system disorders
Bradycardia and hypotension – cold extremities and claudication from blocking beta2 receptors in skeletal muscle vasculature
Delay recovery from insulin-induced hypoglycemia in diabetics
Carvedilol
Combined adrenergic alpha and beta blocker
HTN and CHF Tx
