Cholinergic Pharmacology of the ANS

Question 1

NAChR permeable to?

Answer 1

Na, K, Ca

Question 2

M2 vs M3 Receptors

Answer 2

M2 is Gi and in heart/smooth muscle. M3 is Gq in glands/smooth muscle.

Question 3

Synthesis of ACh

Answer 3

Choline taken up into terminal via cotransport with Na and Cl. Combined with acetyl-COA in ChAT and packaged.

Question 4

How is ACh signal stopped?

Answer 4

Acetylcholinesterase hydrolyzes ACh.

Question 5

Anticholinergic Drugs

Answer 5

Reduce transmission at cholinergic synapses.

Question 6

Physostigmine

Answer 6

Anticholinesterase. Prevents AChE from hydrolyzing ACh. Indirect ACh agonist.

Question 7

Effect of ACh on organs

Answer 7

Slows heart, decreases atrial contractile force, bronchoconstriction, increased secretions, increased GI motility, nearsightedness.

Question 8

ACh effect on vasculature?

Answer 8

Dilation, because muscarinic receptors on it. This is paradoxical.

Question 9

ACh effect on sweat glands?

Answer 9

Increased secretion, because sympathetic neurons that control sweating are cholinergic.

Question 10

Physostigmine toxidrome

Answer 10

GI pain, N&V, sweating

Question 11

Cholinesterase Poisoning (insecticides, nerve gases)

Answer 11

SLUDGE: Salivation, Lacrimation, Urination, Defecation, GI upset, Emesis. Killer B’s: Bradycardia, bronchospasm, bronchorrhea

Question 12

nAChR subtypes

Answer 12

N - ganglionic
M- skeletal muscle

Drugs can be selective for one over the other

Question 13

Nicotine

Answer 13

Direct agonist at both nAChRs. Stimulates both sympathetic and parasympathetic postganglionic neurons when given systemically.

Question 14

Nicotine effect on organs

Answer 14

Pushes towards dominant tone of organ

Question 15

Why do high levels of nicotine cause flaccid paralysis in skeletal muscle?

Answer 15

Due to depolarization blockade – Na+ channels remain inactivated, and can’t de-inactivate.

Question 16

Hexamethonium

Answer 16

Selective antagonist at Nn receptors. Will block transmission at all ganglia (P and S). Target organs are functionally denervated, so the effect is the opposite of the dominant tone for that organ. Causes baroreceptor reflex inhibition

Question 17

Effect of hexamethonium on baroreceptor reflex?

Answer 17

Severe problem with it. People frequently faint upon standing.

Question 18

Tubocurarine

Answer 18

Selective Nm receptor antagonist. Induces flaccid paralysis of skeletal muscle.

Question 19

Is acetylcholine used as a drug?

Answer 19

Yes, opthalmicly. When it’s administered IV, it activates muscarinic receptors, but is short acting because pseudocholinesterase in plasma and tissues degrades it quickly.

Question 20

Parasympathomimetics

Answer 20

Muscarinic Agonists, produce similar effects to anticholinesterase drugs like physostigmine (broncoconstriction, bradycardia, diaphoresis).

Question 21

One major difference between muscarinic agonists and physostigmine

Answer 21

Muscarinic agonists dilate vasculature and decrease diastolic BP because mAChRs exist on vasculature, they’re just not attached to anything.

Question 22

How does exogenous ACh dilate BVs?

Answer 22

Mediated by NO. Muscarinic receptors expressed on tunica intima. When activated by ACh, they release NO, causing vascular smooth muscle to relax via GC and cGMP.

Question 23

Atropine

Answer 23

Muscarinic antagonist. Causes dry mouth, trouble with near vision, tachycardia, heat, redness.