Autonomics II

Question 1

What are the multiple sites of action of ACh? Do AChmimetic drugs have diffuse or specific effects?

Answer 1

NN in ganglia and M1-5 in tissues that are innervated by both symp and parasymp fibers. DIFFUSE!

Question 2

Are Muscarinic receptors G protein coupled receptors or ligand-gated ion channels? Nicotinic Receptors?

Answer 2

GPCR, LGIC

Question 3

What is important about the M1-5 receptors with respect to medication?

Answer 3

Because they are different, there is potential for drug therapy with agonists/antagonists

Question 4

Which receptor controls pupil size reaction to light?

Answer 4

M3 receptor, parasympathetic

Question 5

Are M2 autoreceptors inhibitory or stimulatory?

Answer 5

inhibitory

Question 6

What receptor modulates/controls salivation?

Answer 6

M3 receptor, parasympathetic (eating), sympathetic (breathing)

Question 7

Which receptor is responsible for decreased heart rate?

Answer 7

M2 receptor via vagal stimulation

Question 8

How do M2 receptors modulate pupil constriction and salivation?

Answer 8

They don’t, fool.

Question 9

How do M2 and M3 receptors modulate bronchoconstriction?

Answer 9

Without M3 you cannot bronchoconstrict. Without M2, you get an even greater bronchoconstriction. M2 act as autoreceptors and limit the release of ACh. M3 is a GqCPR that allows for bronchoconstriction.

Question 10

Describe the mechanisms of muscarinic receptor agonists.

Answer 10

Trick question. Despite the differences between M1-5, muscarinic agonists do not exhibit any marked selectivity between the M receptors.

Question 11

Describe the mechanisms of Sympathetic Neuronal Nicotinic Receptor Agonists and Parasympathetic Nicotinic Receptor Agonists.

Answer 11

Trick question: Agonists for NNS and NNP are non-specific and will activate either receptor. There are however nicotinic agonists that are selective towards NNs rather than NMs.

Question 12

What are the two major groups of cholinoreceptor stimulants?

Answer 12

Direct-acting drugs and Indirect-acting drugs (AChesterase inhibitors)

Question 13

What are the two types of acting drugs?

Answer 13

Choline esters and non-ester alkaloids

Question 14

Name two choline esters, characteristics, and their targets

Answer 14

Direct acting drugs. Acetylcholine - quickly hydrolyzed and administered IV in large bolus effect of 5-20s or injection i.m. or s.c. with local effects. Non-specific. Will act on NM, NN, muscarinics; Bethanechol - Beta-methyl reduces potency for Nicotinics and BM along with carbamate groups make Bethanechol more resistant to degradation.

Question 15

Name 3 non-ester cholinomimetic drugs (alkaloids), characteristics and targets.

Answer 15

Direct acting drugs. Nicotine, Muscarine, Cevimeline; Non esters so not degraded by ACh. N - primarily nicotinic receptors, M - primarily muscarinic receptors, Cevimeline - primarily M3 receptors

Question 16

What are the effects of direct acting cholinoreceptor stimulants on M2? M3?

Answer 16

M2 Heart Suppression, M3 - glandular secretion, smooth muscle contraction, vasodilation and relaxation (special case)

Question 17

How do M3 receptors result in vasodilation?

Answer 17

Stimulated M3 receptors on endothelial cells increase Ca2+ and create NO. NO diffuses to smooth muscle surrounding vessel which results in vasodilation

Question 18

What are the classes of indirect-acting drugs and how do they work??

Answer 18

Cholinesterase inhibitors block AChesterase (synaptic) and psuedo/butyrylcholinesterase (extrasynaptic)

Question 19

Name 2 non-ester AChesterase inhibitors

Answer 19

Donepezil, Edrophonium

Question 20

Name 2 ester AChesterase inhibitors

Answer 20

Neostigmine, Physostigmine

Question 21

Name 2 organophosphate AChesterase inhibitors

Answer 21

Soman (Sarin gas), Echothiophate

Question 22

Describe the mechanism of Neostigmine

Answer 22

AChesterase inhibitor Similar mechanism to hydrolysis of ACh, just takes longer (.5-6 hrs)

Question 23

Describe the mechanism of Edrophonium

Answer 23

AChesterase inhibitor Creation of Enzyme-Inhibitor complex without covalent bonding

Question 24

Describe the mechanism of Soman

Answer 24

AChesterase inhibitor - Potent bonding to AChesterase

Question 25

How can one be saved from Soman poisoning?

Answer 25

Use of pralidoxime (PAM) which regenerates the enzyme

Question 26

Which drugs are less specific? Direct or indirect cholinoreceptor drugs?

Answer 26

Indirect because they raise ACh at neuronal junctions all over the body.

Question 27

What is myasthenia gravis? With what medication do you treat it? How do you dose the medication?

Answer 27

AutoAbs that attack the ACh receptors at the NMJ. Neostigmine. Use Edrophonium which has a very short half life. If you have underdosed the Neostigmine, Edrophonium will increase muscle strength. If you overdosed Neostigmine, Edrophonium will decrease muscle strength.

Question 28

What are the toxicities associated with direct and indirect AChesterase inhibitors.

Answer 28

SLUDGE - Salivation, Lacrimation, Urination, Defecation, GI distress, Emesis

Question 29

Tx for Direct-acting drug OD

Answer 29

Atropine - muscarinic antagonist that blocks receptors from increased ACh or AChmimetic

Question 30

Tx for Indirect-acting drug OD (Soman)

Answer 30

Atropine (muscarinic antagonist), Pralidoxime (if desperately needed to rescue ACh inhibitors; Must use before AChesterase ages)