Lecture 11: Cholinergics / ANS: Parasympathetic

Question 1

M1, M3, M5 act through which pathway

Answer 1

Gq - excitatory

Question 2

M2, M4 acts through which pathway

Answer 2

Gi - inhibitory
inhibit AC and decrease cAMP

Question 3

location of M1 R

Answer 3

ganglia
gastric, parietal, salivary glands

Question 4

location of M2 R

Answer 4

heart
smooth muscle
autonomic nerve terminal (auto and heteroreceptors)

Question 5

location of M3 R

Answer 5

smooth muscle
gastric and salivary glands
bladder, vascular smooth muscle

Question 6

location of M4 R

Answer 6

auto and heteroreceptor

Question 7

Location of M5 R

Answer 7

low level of expression - seen in cerebral artery VSM

Question 8

pilocarpine

Answer 8

natural directly acting cholinergic drug (mimics ACh structure)
- used for glaucoma to decrease IOP

Question 9

bethanechol

Answer 9

natural directly acting cholinergic drug (mimics ACh structure)
- used to make someone pee after surgery
- activates muscarinic receptors in detrusor muscle of bladder

Question 10

reversible cholinesterase inhibitors (3)

Answer 10

physostigmine - crosses BBB, for glaucoma (decreases IOP)

neostigmine - quaternary ammonium compound, also doesn’t cross the BBB, taken po for myasthenia gravis

edrophonium - short-acting and given IV to diagnose myasthenia gravis

Question 11

pralidoxime

Answer 11

2-PAM
- used to rescue irreversible inhibition of ACh-esterase at the early phosphorylation stage

Question 12

echothiophate

Answer 12

irreversible acetylcholinesterase inhibitor
- organophosphate
- long action >100 hr
- used to treat glaucoma
- other side FX treated with atropine (musc. blocker) or 2-PAM

Question 13

Anti-muscarinic agents for bronchodilation

Answer 13

LOW DOSE atropine - nonselective for musc Ach R Ant. Antagonizing M3 causes bronchodilation (M3 is Gq, blocking this = less calcium = less contraction), also decreases mucus

Selective M2 and M3 antagonists
- tiotropium
- ipratropium bromide (can be a rescue med)

less effective than beta2 agonists but used as adjunct in acute episodes or for beta 2 nonrespnders

Question 14

pharmacological effects of atropine

Answer 14

non selective musc ach r blocker
- decreased secretions from gastric, bronchiole, salivary, sweat glands
- causes retention of urine
- dose-dependent changes in HR -> low dose causes bradycardia through CNS effects and high dose causes tachycardia through vagal block
- causes pupil dilation (mydriasis) (blocks musc. receptors on iris muscles)
- disorientation at high doses

Question 15

red as a beet, dry as a bone, blind as a bat, mad as a hatter, hot as a hare, and full as a flask

Answer 15

Anticholinergic clinical presentation

refers to the symptoms of flushing, dry skin and mucous membranes, mydriasis (pupil dilation) with loss of accommodation, altered mental status (AMS), fever, and urinary retention

Question 16

Plants that atropine can be found in

Answer 16

atropa belladonna
- deadly nightshade

datura stramonium
- jimsonweed
- jamestown
- stinkweed
- thorn-apple
- devil’s apple

Question 17

therapeutic uses of atropine

Answer 17

• IV for acetylcholinesterase inhibitor poisoning (supportive)
• drops/ointment (CONTRAINDICATED in narrow angle glaucoma)
• low dose bronchodilation

duration of action is a couple hours, no tolerance in CV or eye. Long term use may cause urinary retention.

Question 18

scopolamine

Answer 18

AKA hyoscine
- similar peripheral effects to atropine but also causes sedation so can be used for agitated patients
- used in surgery
- also used to prevent motion sickness (transdermal patch) to reduce GI motility

Question 19

anti-muscarinics for urinary retention

Answer 19

darifenacin and tolterodine

both antagonize M3 in the detrusor muscle of the bladder - reduce contractility and urgency to urinate

Question 20

three nicotinic Ach R agonists

Answer 20

• nicotine
• lobeline (less potent than nic)
• arecoline (has euphoric effects, similar to nicotine, toxic effects are CV, resp, GI, musc) - not used therapeutically

Question 21

ganglionic blockers block what receptor?

Answer 21

nicotinic receptor (antagonize it) at the ganglion (between pre and postganglionic fibres of ANS)
- nicotine (an agonist) can also act as a blocker at high doses if it desensitizes

Question 22

hexamethonium

Answer 22

gangalionic blocker - blocks nicotinic acetylcholine receptor at the ganglia

Question 23

pharmacological effects of ganglionic blockers

Answer 23

depends on tone of the target tissue (PS vs S) and location of the receptor subtypes, but generally:

because of reduced Symp tone
- decreased blood pressure

because of reduced PS tone
- dilated pupils aka mydriasis
- less GI secretions and motility
- some bronchiole dilation, less secretions (but this is also under symp tone)
- dry and flushed skin

Question 24

Trimethaphan camsylate

Answer 24

nAChR ganglia blocker
- IV infusion for rapid reduction in BP in hypertensive crisis