Cholinergic Inhibitors

Question 1

Name the two naturally occurring muscarinic antagonists.

Answer 1

atropine and scopolamine; found in plants

Question 2

Name the three (semi)synthetic muscarinic antagonists. They’re all tertiary amines and used for peripheral applications.

Answer 2

dicyclomine, tropicamide, and tolterodine

Question 3

Name the three (semi)synthetic muscarinic antagonists that are quaternary amines used in asthma.

Answer 3

ipratropium, tiotropium, and benztropine

Question 4

What’s the main difference caused by quaternary vs tertiary amine?

Answer 4

Tertiary amines are generally better absorbed and penetrate the CNS better; they therefore typically have more central effects than quaternary.

Question 5

Are the muscarinic antagonists selective?

Answer 5

No; they’re essentially non-selective and don’t discriminate well between the five receptor sub-types

Question 6

Effects and MOA of muscarinic antagonists in the CNS.

Answer 6

receptor sub-type unknown; sedation, anti-motion sickness, antiparkinson, amnesia, delirium

Question 7

Effects and MOA of muscarinic antagonists in the eye.

Answer 7

M3; cycloplegia, mydriasis (paralysis of ciliary muscle and dilation)

Question 8

Effects and MOA of muscarinic antagonists in the bronchi.

Answer 8

M3; bronchodilation (especially if constricted)

Question 9

Effects and MOA of muscarinic antagonists in the GI tract.

Answer 9

M1, M3; relaxation, slowed peristalsis

Question 10

Effects and MOA of muscarinic antagonists in the GU tract.

Answer 10

M3; relaxation of bladder wall, urinary retention

Question 11

Effects and MOA of muscarinic antagonists in the heart.

Answer 11

initial bradycardia (esp low doses) from block of inhibitory presynaptic receptors; tachycardia from block of M2 in SA node

Question 12

Effects and MOA of muscarinic antagonists in the blood vessels.

Answer 12

M3 on endothelial cells; block of muscarinic vasodilation (only manifests if a muscarinic agonist is present)

Question 13

Effects and MOA of muscarinic antagonists in the glands.

Answer 13

M1, M3; marked reduction of salivation, moderate reduction of lacrimation and sweating, less reduction of gastric secretion

Question 14

Effects and MOA of muscarinic antagonists in the skeletal muscle.

Answer 14

none!

Question 15

Use of benzotropine.

Answer 15

CNS; treat manifestations of Parkinsons

Question 16

Use of scopolamine.

Answer 16

CNS; prevent or reduce motion sickness

Question 17

Use of atropine.

Answer 17

eye; produce mydriasis and cycloplegia

Question 18

Use of tropic amide.

Answer 18

eye; produce mydriasis and cycloplegia

Question 19

Use of ipratropium and tiotropium.

Answer 19

bronchodilation in asthma, COPD

Question 20

Use of dicyclomine

Answer 20

GI tract; reduce transient hypermotility

Question 21

Use of tolterodine.

Answer 21

GU tract; treat transient cystitis, postop bladder spasms, incontinence

Question 22

What’s the pneumonic for the toxicity/overdose of atropine?

Answer 22

dry as a bone, blind as a bat, red as a beet, mad as a hatter

Question 23

Explain dry as a bone.

Answer 23

reduced sweating, lacrimation, salivation

Question 24

Explain blind as a bat.

Answer 24

blockade of accommodation and excessive pupillary dilation

Question 25

Explain red as a beet.

Answer 25

dilation of cutaneous vessels in upper body (atropine flush)

Question 26

Explain mad as a hatter.

Answer 26

inhibitions of CNS receptors - series of complex consequences

Question 27

What's the most important atropine side effect that's potentially lethal in children?

Answer 27

atropine fever, hyperthermia; results from blockade of thermoregulatory sweating`

Question 28

Name and mechanism of a ganglion-blocking drug.

Answer 28

hexamethonium; non-depolarizing; competitively inhibits Nn receptors in both sympathetic and parasympathetic ganglia (non-selective); very rarely used

Question 29

What's the largest effect of hexamethonium and what's the only clinical use?

Answer 29

blood pressure effect is marked (large reduction in vascular tone); used in hypertensive emergencies and to produce hypotension for 'bloodless field' surgery

Question 30

Contrast depolarizing and non-depolarizing NMJ blockers.

Answer 30

non-depolarizing - prevent the opening of the channel | depolarizing - super agonists; persistently occupy receptor and cause persistent depolarization

Question 31

Name three NMJ blockers and whether they're depolarizing or non-depolarizing.

Answer 31

succinylcholine - depolarizing | tubocurarine, mivacurium - non-depolarizing

Question 32

Use of tubocurarine and mivacurium. Which lasts longer?

Answer 32

cause flaccid paralysis of skeletal muscle necessary for surgery without depressant effects of deep anesthesia; tubocurarine lasts 30-60 min; mivacurium is shorter acting because it's hydrolyzed more rapidly

Question 33

Use and duration of action of succinylcholine.

Answer 33

causes flaccid paralysis quickly and is effective only for a few minutes; used for brief procedures such as tracheal intubation

Question 34

Toxic effects of NMJ blockers?

Answer 34

respiratory paralysis and disturbance of autonomic function (interact with Nn to a lesser extent) (pancuronium, non-depolarizing, is a component in lethal injections for capital punishment)

Question 35

Effects of cholinesterase inhibitors on NMJ blockers.

Answer 35

effective at blocking effects of non-depolarizing blockers; depolarization blockers unaffected or increased effect

Question 36

MOA of botulinum toxin A

Answer 36

degrades SNAP-25, which mediates fusion of synaptic vesicles with presynaptic terminal membrane (blocks release of Ach)

Question 37

Use of botulinum toxin A

Answer 37

treatment of diseases associated with increased muscle tone: reduce frown lines and wrinkles achalasia (abnormal esophageal contractions) strabismus (misalignment of eyes) oromandibular dystonia (continuous spasms of face, jaw, neck, etc)