Cholinergic agents

Question 1

what type of receptor and messenger to motoneurons use?

Answer 1

Nicotinic, Ach

Question 2

How does Ach stimulate both nicotinic and muscarinic receptors

Answer 2

its a two-sided molecule

Question 3

List seven direct acting parasympathomimetic drugs

Answer 3

Ach, Methacholine, bethanechol, pilocarpine, cevimeline, carbachol, muscarine

Question 4

Action of Ach at the SA node is an example of what kind of motif? What is the effect?

Answer 4

inhibitory signal transduction motif, agonists activate G proteins and produce effects w/in membrane and w/o 2nd messenger. increases gK, hyperpolarizing and slowing HR

Question 5

three actions of Ach at SA node

Answer 5

increase K current, inhibit I(funny), inhibit L-type Ca current

Question 6

how does Ach decrease BP?

Answer 6

via NO (endothelium derived relaxing factor or EDRF) which increases cGMP

Question 7

BP and HR: Ach alone

Answer 7

vasodilation results in decreased BP and reflex tachycardia

Question 8

BP and HR: Ach + Neostigmine

Answer 8

Huge drop in BP. Direct SA node effect overpowers baro reflex and HR drops

Question 9

BP and HR: Ach + Neostigmine + Atropine

Answer 9

Increases in BP and HR (due to stimulation of symp ganglia)

Question 10

methacholine: acts on what? clinical use?

Answer 10

Muscarinic receptors. Methacholine challenge for asthma (causes severe bronchoconstriction in asthma pts)

Question 11

bethanechol: unique features, clinical uses, administration routes

Answer 11

Muscarinic specificity, resistant to ester hydrolysis. Use to treat low bowel tone (adynamic ileus) and urinary retention. Never IV or IM

Question 12

Pilocarpine: uses

Answer 12

narrow angle glaucoma (uncrowds the angle and tones trabecular meshwork) and Sjogren’s syndrome (moistens dry mouth)

Question 13

Cevimeline

Answer 13

better than pilocarpine for Sjogrens dry mouth

Question 14

List 11 indirect parasympathomimetic agents (anticholinesterases)

Answer 14

edrophonium, neostigmine, physostigmine, pyridostigmine, DFP, Parathion, malathion, Sarin, VX, ambenonium, ecothiophate

Question 15

what are the two types of cholinesterases?

Answer 15

acetyl- (true, specific) and buytryl- (pseudo, non-specific)

Question 16

Four poisoning symptoms of anticholinesterases? due to what receptors?

Answer 16

Salivation, lacrimation, urination, defecation (SLUD). These four effects due to Muscuarinic receptors

Question 17

describe cycle of poisoning by irreversible CHE inhibitors: muscarinic and nicotinic

Answer 17

feedback cycle stimulate PREsynaptic nicotinic receptors resulting in more ACh. Nicotinic undergo phase 1 & 2 block, muscarinic do not (see sk mm twitching followed by faccid paralysis)

Question 18

Physostigmine: what happens on ingestion? Unique characteristics?

Answer 18

Reversible CHE inhibitor. Goes through 2 muscarinic receptors, leads to emesis. 3* so it gets into CNS

Question 19

Neostigmine

Answer 19

reversible CHE inhibitor. Rx for MG and to reverse non-depolarizing block

Question 20

edrophonium

Answer 20

used to test for MG (lasts 5-15 minutes)

Question 21

ACh hydrolysis by ChE

Answer 21

Anionic site is anchor, esteratic site has serine that gets acertylated and then regenerated via hydrolysis

Question 22

Reversible ChE inhibitors like neostigmine action

Answer 22

carbamylated esteratic site that is hydrolyzed slowly

Question 23

Mechanism of edrophonium

Answer 23

doesn’t bond to serine but rather histidine at esteratic site so inhibition is transient

Question 24

Mechanism of irreversible cholinesterase inhibitors

Answer 24

phosphorylate the serine at the esteratic site which doesn’t hydrolyze at all. Have to wait for ChE to regenerate

Question 25

DFP

Answer 25

irreversible cholineserase inhibitor

Question 26

Tabun or Sarin

Answer 26

irreversible ChE inhibitors

Question 27

Parathion

Answer 27

metabolized to paraoxon. irreversible ChE inhibitor

Question 28

Malathion

Answer 28

fish cannot detoxify but higher animals can. irreversible ChE inhibitor

Question 29

VX

Answer 29

deadliest nerve gas. Irreversible ChE inhibitor

Question 30

Rx of anti-ChE toxicity

Answer 30

heroic doses of Atropine, reactivate enzyme to tx SKM effects with 2-PAM

Question 31

Atropine: action, degree of amine, where found, uses

Answer 31

competitive inhibitor of ACh at muscarinic receptors. Tertiary. Jimsonweed.Mydriatic and cyclplegic for eye exam. Tx of colic. ^HR during surgery. Antidote. PARKINSONISM

Question 32

what is parkinsonism

Answer 32

too much ACh relative to dopamine along the nigro-striatal pathway

Question 33

Atropine toxicity (belladonna and jimsonweed). Antidote?

Answer 33

Dry as a bone, hot as a stove, red as a beet, blind as a bat, mad as a hatter. Physostigmine

Question 34

Scopolamine: what is it? three main actions?

Answer 34

like atropine but more CNS depression. Anti-emetic (motion sickness), sedation, amnesia

Question 35

Rx of overactive bladder

Answer 35

muscarinic blockers like TolTERODINE and sliFENACIN

Question 36

homatropine

Answer 36

used for ciliary spasm. prevents blurry vision and browache

Question 37

COPD tx

Answer 37

Ipratroprium (blocks M1 and M2 receptors). Tiotroprium (only blocks M1s)

Question 38

What system do ganglionic blockers work most on?

Answer 38

Parasymp since it has the normal major tone. effects similar to atropine. Except symp to vasculature and symp cholinergic