19 Anti-cholinergics

Question 1

Anti-muscarinic absorption

Answer 1

Tertiary: well-absorbed in gut and conjunctiva
Quaternary: poor absorption orally

Question 2

Anti-muscarinic distribution

Answer 2

Atropine and tertiary agents: widely distributed (30mins-1hr)
Quaternary agents: poorly taken up by brain, no CNS effect at low dose

Question 3

Anti-muscarinic metabolism and excretion

Answer 3

atropine: 2 phase elimination (2h rapid phase, 13h slow phase)

Question 4

Anti-muscarinic pharmacodynamics

Answer 4

Atropine: reversible cholinomimetic actions at M receptors (M selective); prevents IP3 release and adenylyl cyclase inhibition; stops sweating

Antimuscarinic = inverse agonist

Question 5

M1, M2, M3

Answer 5

M1 and 3 = IP3 and DAG
M2 = CAMP and K

pirenzepine = m1
oxybutynin = m3

Question 6

CNS effects

Answer 6

Scopolamine/hyoscine (motion sickness, can cause sedation and dry mouth)

prevents/reverses vestibular disturbances (motion sickness)
drowsiness and amnesia

Question 7

CNS - parkinsons

Answer 7

parkinsons = excess cholinergics + low dopamine, need antimuscarinic with doopamine

treatment: benzotropine
- M receptor antagonist in basal ganglia

Question 8

Eyes effects

Answer 8

EFFECT: mydriasis

Tropical atropine: mydriasis + cycloplegia (loss of accommodation), reduced lacrimal secretion

Optha exam: mydriasis to see optic cup and disc ATROPINE
Prevent synechia (adhesions) HOMATROPINE

Question 9

CVS

Answer 9

EFFECTS:
SA node
AV node
Effects: low dose (bradycardia), moderate-high dose (tachycardia), block vasodilation

Toxic: intraventricular conduction block, cutaneous vasodilation

Question 10

Indicators for atropine for CVS

Answer 10

MI with pain from reflex vagal discharge + depression of SA/AV node = atropine to block vagal discharge

Hyperactive carotid sinus reflexes

Prevent PANS action by M2 autoantibodies

Question 11

Respi

Answer 11

EFFECT: bronchodilation and reduced secretion (M3)

COPD and asthma: ipratropum (short action), aclidinium and glycopyrrolate, tiotropium and umeclidinium (longer action)

Preanesthetics: scopolamine (amnesia, pregnant), toxic effects (urinary retention and intestine hypomotility)

Question 12

GI

Answer 12

EFFECT: dry mouth, dec peristalsis > dec gastric secretions, dec pancreatic/intestinal secretions

Gastric secretions: pirenzepine, telenzepine
Hypomotility: hyoscine/scopolamine, hyoscyamine, dicyclomine

Question 13

GU

Answer 13

EFFECT: slow voiding/urinary incontinence

Bladder: oxybutynin (M3 selective; urologic surgery, meningomyelocele), trospium

Question 14

Skin

Answer 14

EFFECT: suppress thermoregulatory sweating = hyperthermia

Hyperhidrosis: glycopyrronium, oxybutynin, botox

Question 15

Cholinergic poisoning

Answer 15

Antimuscarinic therapy: atropine (counteracts cholinergic effects)

Cholinesterase regenerator compounds: given before aging; oximes (high affinity for P); pralidoxime (PAM), diacetylmonoxime (DAM), obidoxime

Pyridostigmine: blocks Ach binding sites vs organophosphates

Question 16

Anti-muscarinic toxicity

Answer 16

Adverse effects: mydriasis, cycloplegia, block PANS,

Question 17

Atropine overdose symptoms

Answer 17

Constipation
Urinary retention
Mydriasis
Bronchodilation
cycloplegia
Tachycardia
Dry mouth
dec Sweat
Disorientation
inc Temp
Flushed skin

Treatment: Physostigmine

Question 18

Anti-ganglionic agents pharmacokinetics

Answer 18

Tetraethylammonium
Hexamethonium
Decamethonium
Mecamylamine

Question 19

Anti-ganglionic pharmacodynamics

Answer 19

Blocks Nn receptors

Question 20

Neuromuscular blockers

Answer 20

Mechanism of action: competitively block nicotinic receptors
Use: muscle relaxant for anes
Adv: less cardiorespi effects

Question 21

Neuromuscular blockers

Answer 21

1 Nondepolarizing (motor weakness -> flaccid): Rocuronium (rapid onset), cisatracurium (long effect 25-45mins), tubocurarine/atracurium (anaphylactic shock), pancuronium, vecuronium

2 Depolarizing (contraction -> flaccid): <10 mins, succinylcholine, side effects

Question 22

Malignant hyperthermia correlate

Answer 22

Succinylcholine and halothane (volatile anes)

Abnormal release of Ca from skeletal muscle -> contraction -> kidney problem

Treatment: Dantrolene

Question 23

Reversal of neuromuscular blockade

Answer 23

Treats flaccid state

Neostigmine and pyridostigmine: reverse Nm blockade indirectly (inhibit AChE)

Sugammadex: reverses rocuronium and vecuronium