Chapter 7: Cholinoceptor-Activating & Cholinesterase-Inhibiting Drugs

Question 1

may be considered the prototype of drugs with acetylcholine-like effects (cholinomimetics) that acts directly at both muscarinic and nicotinic receptors.

Answer 1

Acetylcholine

Question 2

_____ is a prototype for the indirect-acting cholinesterase inhibitors.

Answer 2

Neostigmine

Question 3

Muscarinic receptors are G protein-coupled receptors (GPCRs). Gq protein coupling of M1 and M3 muscarinic receptors to phospholipase C, a membrane-bound enzyme, leads to the release of the second messengers:

1. _____
2. _____

Answer 3

1. diacylglycerol (DAG)

2. inositol-1,4,5-trisphosphate (IP3)

Question 4

_____ is a nicotinic partial agonist. It appears to reduce craving in persons addicted to nicotine through a nonautonomic action.

Direct- acting nicotinic agonist used in medicine to assist smoking cessation

Answer 4

Varenicline

Question 5

Direct- acting nicotinic agonists are used in medicine produce skeletal muscle paralysis

Answer 5

Succinylcholine

Question 6

Muscarine and similar alkaloids are found in certain mushrooms (_____ & _____) and are responsible for the short-duration type of mushroom poisoning, which is characterized by nausea, vomiting, and diarrhea.

Answer 6

Inocybe species and Amanita muscaria

Question 7

The much more dangerous and potentially lethal form of mushroom poisoning from _____ and related species involves initial vomiting and diarrhea but is followed by hepatic and renal necrosis.

It is not caused by muscarinic agonists but by amanitin and phalloidin, RNA polymerase inhibitors.

Answer 7

Amanita phalloides

Question 8

CNS stimulation is common with organophosphate and physostigmine overdosage and includes convulsions, followed by respiratory and cardiovascular depression. The spectrum of toxicity includes:

Answer 8

Can be remembered with the aid of the mnemonic DUMBBELSS

D - diarrhea
U - urination
M - miosis
B - bronchoconstriction
B - bradycardia
E - excitation of SkM and CNS
L - lactimation
S - salivation
S - sweating

Question 9

Direct-acting, muscarinic agonist

Activates muscarinic (M) receptors –> increases IP3 and DAG

Use: Bladder and bowel atony, for example, after surgery or spinal cord injury

Answer 9

Bethanechol

Question 10

Direct-acting, muscarinic agonist

Activates muscarinic (M) receptors –> increases IP3 and DAG

May also activate EPSPs via M receptors in ganglia

Use: Sjögren’s syndrome (increases salivation); was used in glaucoma (causes miosis, cyclospasm)

Answer 10

Pilocarpine

Question 11

Direct-acting, muscarinic agonist

Activates muscarinic (M) receptors –> increases IP3 and DAG

Use: Alkaloid found in mushrooms

Answer 11

Muscarine

Question 12

Direct-acting, nicotinic agonists

Activates all nicotinic (N) receptors –> opens Na -K channels in ganglia and neuromuscular end plates

Use: Smoking cessation (also used as insecticide)

Tox: Generalized ganglionic stimulation: hypertension, tachycardia, nausea, vomit- ing, diarrhea

Answer 12

Nicotine

Question 13

Direct-acting, nicotinic agonists

A partial agonist at N receptors

Use: Smoking cessation

Tox: Hypertension, sweating, sensory disturbance, diarrhea, polyuria, menstrual disturbance

Answer 13

Varenicline

Question 14

Direct-acting, nicotinic agonists

Use: Muscle relaxation

Tox: Initial muscle spasms and postoperative pain • Prolonged action in persons with abnormal butyrylcholinesterase

Answer 14

Succinylcholine

Question 15

Indirect-acting, alcohol

Inhibitor of cholinesterase • amplifier of endogenously released ACh

Use: Reversal of NM block by nondepolarizing drugs • diagnosis of myasthenia gravis

Answer 15

Edrophonium

Question 16

Indirect-acting, carbamates

Inhibitor of cholinesterase • amplifier of endogenously released ACh, plus small direct nicotinic agonist action

Use: Reversal of NM block, treatment of myasthenia

Answer 16

Neostigmine

Question 17

Indirect-acting, carbamates

Inhibitor of cholinesterase • amplifier of endogenously released ACh

Use: Treatment of myasthenia

Answer 17

Pyridostigmine

Question 18

Indirect-acting, carbamates

Inhibitor of cholinesterase • amplifier of endogenously released ACh

Use: Reversal of severe atropine poison- ing (IV) • occasionally used in acute glaucoma (topical)

Answer 18

Physostigmine

Question 19

Indirect-acting

Cholinesterase inhibition plus variable other poorly understood effects

Use: Alzheimer’s disease

Answer 19

Rivastigmine
Galantamine
Donepezil