ANS Drugs

Question 1

Botulinum toxin - mechanism

Answer 1

Blocks ACh release by cleaving SNARE proteins required for neurotransmitter release.

Question 2

Botulinum toxin - Theraputic uses

Answer 2

long-term neuromuscular blockade for pts with blepharospam, strabismus, facial wrinkles, other issues related to spasm.

Question 3

Botulinum action at target organs of parasympathetic NS

Answer 3

blocks cholinergic transmission – Tx of urinary incontinence.

Question 4

Botulinum action at target organs of sympathetic NS

Answer 4

blocks cholinergic neurons that innervate sweat glands – blocks excessive sweating when administered in axilla.

Question 5

Competitive blockers

Answer 5

competitive antagonists: inhibits the binding of ACh to the nAChR, blocking transmission

Prototype: tubocurarine

Question 6

Succinylcholine mechanism

Answer 6

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.

Question 7

Succinylcholine uses

Answer 7

muscle relaxant/paralytic used during surgery/procedures

Question 8

Succinylcholine side-effects/toxicity

Answer 8

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

Question 9

Acetylcholine - what receptors, what uses?

Answer 9

Agonist at both nicotinic and muscarinic receptors

causes meiosis (constriction of pupil) - used in extraction of cataracts

Question 10

Methacholine - what is it, why is it different from ACh?

Answer 10

muscarinic agonist

choline ester of acetylcholine

more resistant to hydrolysis by acetylcholinesterase and plasma cholinesterase

very little nicotinic activity

Question 11

Methacholine uses

Answer 11

diagnostic tool in its with asthma to determine airway hyperactivity - inhalation causes bronchoconstriction

Question 12

Possible side-effects of non-subtype selective muscarinic receptors acetylcholine and methacholine?

Answer 12

hypotension - via vasodilation via mAChR on endothelial cells of vessels

bradycardia - via mAChR on heart

tachycardia - via hypotension-produced reflex increase in sympathetic tone

Question 13

Cevimeline mechanism & use

Answer 13

M3 selective muscarinic agonist

used to treat dry mouth in pts with Sjogren’s syndrome

Question 14

Atropine mechanism, uses, and side-effects

Answer 14

non-selective, competitive muscarinic antagonist for AChR

Blocks parasympathetic (rest and digest) stimulation at effector organs - affects many organs

Question 15

Darifenacin

Answer 15

M3-selective antagonist that treats overactive bladder

Question 16

AChE inhibitors

Answer 16

inhibit acetylcholinesterase (AChE), which hydrolyses ACH.

Increase lifetime of ACh and transmission of ACh signals

Question 17

Edrophonium

Answer 17

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

Question 18

Pyridostigmine

Answer 18

covalent, slowly reversible AChE inhibitor.

Tx of Myasthenia Gravis - increases efficiency of NMJ by increasing ACh availability

Question 19

Donepezil

Answer 19

noncompetitive AChE inhibitor

improves cognition/delays progression of Alzheimers

Question 20

What are the naturally occurring catecholamines?

Answer 20

Epinephrine, norepinephrine, and dopamine

Question 21

What is the main pathway for adrenergic for stopping adrenergic transmission?

Answer 21

Reuptake of norepinephrine back into the nerve terminal, metabolism by monoamine oxidase (MAO), extraneuronal catelchol-o-methytransferase (COMT)

Question 22

Cocaine mechanism

Answer 22

Blocks the reuptake of catecholamines into the nerve terminal

Question 23

Ephedrine

Answer 23

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.

Question 24

Indirect-acting sympathomometics

Answer 24

Act on the noradrenergic nerve terminal to cause release of norepinephrine – sympathetic effect.

Question 25

Methyldopa

Answer 25

False transmitter (can be released in reponse to neuron stimulation). Stored in vesicles in adrenergic terminals

Question 26

Alpha adrenergic versus beta-adrenergic responses

Answer 26

In alpha-adrenergic responses: potency EPI > NE >> ISO (isoprotenerol) In beta-adrenergic responses: potency ISO > EPI > NE

Question 27

Isoproterenol

Answer 27

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.

Question 28

Dopamine

Answer 28

Activates vasodilatory dopamine receptors in mesenteric and renal vessels.

Question 29

Phenylephrine

Answer 29

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

Question 30

Midodrine

Answer 30

alpha 1 adrenergic agonist prodrug - metabolically converted to the active form increases blood pressure in pts with autonomic insufficiency and hypotension

Question 31

Clonidine

Answer 31

selective alpha2 adrenergic agonist Tx of hypertension decreases BP by acting on a2 receptors in the CNS to decrease sympathetic outflow

Question 32

Dobutamine

Answer 32

beta1 selective adrenergic agonist increases cardiac output in conditions such as heart failure

Question 33

Albuterol

Answer 33

Beta2 selective adrenergic agonists bronchodilator - relaxes bronchial and other smooth muscle with little cardiac stimulation

Question 34

Metoprolol

Answer 34

Beta1-selective agonist Inhibits cardiac effects of sympathetic activity or adrenergic drugs - fewer effects on other organs

Question 35

Propanolol

Answer 35

Non-selective beta blocker Blocks all 3 beta receptors, decrease HR, cardiac output, BP. Can also block other beta-mediated effects

Question 36

Uses for beta blockers

Answer 36

HTN Angina Cardiac arrhythmias Glaucoma

Question 37

Toxic effects of beta-blockers

Answer 37

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

Question 38

Carvedilol

Answer 38

Combined adrenergic alpha and beta blocker | HTN and CHF Tx