ANS and Cholinergic pharmacology

Question 1

Only has one motor neuron in PNS

Answer 1

Somatic

Question 2

Two neurons in PNS

Answer 2

Autonomic

Question 3

Describe neuroeffector junction of autonomic nervous system

Answer 3

Beads line post-ganglionic branches, are sites of neurotransmitter synthesis, storage, and release

Target tissues may be innervated by many post-ganglionic neurons

Post-synaptic receptors are widely distributed on the target tissues- no specialized region of receptors like end plate

Question 4

is sympathetic or parasympathetic more restricted in terms of location. How so?

Answer 4

parasympathetic. Parsympathetic only goes to viscera not vasculature smooth muscle

Question 5

Location of Preganglionic and postganglionic cell bodies for sympathetic nervous system

Answer 5

Preganglionic: Lateral horn of spinal cord T1-L2/3 Postganglionic: Paravertebral ganglia OR pre-aortic ganglia

Question 6

Location of preganglionic and postganglionic nearons for parasympathetic nervous system

Answer 6

Preganglionic: CN 3, 7, 9, 10 AND S2-S4

Postganglionic: Near the target organ

4 specific ones: ciliary, pterygopalatine, submandibular, and otic ganglion

Question 7

Identify the classic neurotransmitters released by pre- and postganglionic sympathetic neurons and the types of receptors found on their effector organs.

Also note the sweat gland exception

Identify the classic neurotransmitters released by pre- and postganglionic parasympathetic neurons and the types of neurotransmitter receptor found on their effector organs.

Answer 7

Note: sweat glands have sympathetic cholinergic activation

Question 8

Cells of adrenal medulla that preganglionic sympathetic neurons go to

Answer 8

chromaffin cells

Question 9

chromaffin cells make

Answer 9

mostly epi (80%)

20% norepi

Question 10

name a tumor of adrenal medulla

Answer 10

pheochromocytoma. makes mostly norepi. sxs: panic attack and HTN and cold hands/feet but also feels hot

Question 11

Classify Muscarinic Receptors into two subgroups based on numbering and on basic G protein mechanism

Answer 11

M1: M1, M3, M5. G-alpha-i. Inhibit Adenylate Cyclase. Lower cAMP.

M2: M2, M4. G-alpha-q. Via Phospholipase C, IP3 and raising Ca ++

Question 12

M3 contracts (constricts as approp.) these tissues

Answer 12

Bronchioles

Smooth muscle in GI tract

Smooth muscle in walls of urinary bladder

Question 13

parasympathetic influence on SA node: receptor and action

sympathetic influence on SA node: receptor and action

Answer 13

M2; decreases heart rate

Beta 1; increases heart rate

Question 14

GI tract innervation:

1. Parasympathetic receptor and action for i. smooth muscle of tract and ii. sphincters
2. Sympathetic receptor and action i. smooth muscle of tract and ii. sphincters

Answer 14

1. i. Smooth muscle wall: M3; contracts
   ii. Sphincters: Mostly M2, some M3; relaxes
2. i. Smooth muscle wall: Alpha 2, Beta 2; relaxes
   ii. Sphincters: Alpha 1; contracts

Question 15

Urinary tract innervation

1. Parasympathetic receptor and action for i. smooth muscle of bladder and ii. bladder sphincter
2. Sympathetic receptor and action i. smooth muscle of bladder and ii. bladder sphincter

Answer 15

1. i. M3; contracts ii. Mostly M2, some M3; relaxes
2. i. Beta 2; relaxes ii. Alpha 1; contracts

Question 16

Salivary secretion innervation

Parasympathetic and sympathetic sources (and which is larger contribution)

Answer 16

Parasympathetic larger contribution: M3, salivation.

Sympathetic lesser contribution: Beta 1, salivation

Question 17

Innervation and receptor: Radial (dilator pupillae), iris

Answer 17

Sympathetic: Alpha 1. Dilates pupils by contracting dilator muscles

Question 18

Innervation and receptor: Sphincter (constrictor pupillae), iris

Answer 18

Parasympathetic. M3. Constricts.

Question 19

Sweat glands innervation and receptor

Answer 19

Sympathetic.

Eccrine: M3; increases secretion

Apocrine: Alpha; increases secretion

Question 20

Erector pili innervation and receptor

Answer 20

sympathetic. alpha 1. erects hairs.

Question 21

lacrimal gland innervation and receptor

Answer 21

parasympathetic, M3 receptor, secretion

Question 22

liver innervation and receptor

Answer 22

Sympathetic: Alpha 2, beta 2; gluconeogenesis, glycogenolysis

Question 23

explain the difference between nicotinic and muscarinic receptor structure/fxn in 1 sentence

Answer 23

nicotinic receptors are ligand gated ion channels while muscarinic receptors are GPCRs

Question 24

list two areas where muscarinic receptors are

Answer 24

parasympathetic post-ganglionic synapse (effector organ)

sympathetic sweat gland innervation (post ganglionic)

Question 25

what is the receptor and innervation of adrenal medulla?

Answer 25

N2. Sympathetic.

Question 26

describe direct acting cholinomimetic agents using words like M and N receptor and specificity

Answer 26

Can agonize either M or N. Can have good discrimination between M and N and WITHIN N. BUT Within M no good specificity.

Question 27

describe indirect acting cholinomimetics

Answer 27

AcH esterase inhibitors. Nonspecifically raise ACH concentration at ANY (M or N) type of cholinergic synapse to which the drug has access.

Question 28

two classes of muscarinic agonists and name drugs within each that are exclusively M and no N xreactivity

Answer 28

class one: choline esters. exclusive: bethanechol

class two: cholinomimetic. exclusive: muscarine and pilocarpine

Question 29

Atropine target and effects

toxidrome

Answer 29

antagonist to M1-M5 (all muscarine receptors)

Hot as a hare. Dry as a bone. Red as a beet. Blind as a bat. Mad as a hatter. +RAPID PULSE

Question 30

name two more muscarinic antagonists besides atropine:

Answer 30

scopolamine and Pirenzepine

Question 31

MOA and duration of edrophonium

Answer 31

Directly and reversibly inhibits AchEsterase. SHORT halflife of minutes.

Question 32

Name a differentiating use of edrophonium

Answer 32

Differentiate between MG and LE

Question 33

MOA and duration of carbamate esters (-stigmine). Name a condition treated with these drugs

Answer 33

Reverisbly and directly inhibit AcH esterase by acting as pseudosubstrate. 2-4 hour half life. Treatment for MG

Question 34

Side effects of overdose on -stigmine rational

Answer 34

since ACH esterase -stigmine increase ACH at both the N and M ach receptors.

Question 35

fnxal group that makes malathion “irreversible”

non-clinical uses

Answer 35

phosphorylated active site that is very stable

insecticides and chemical warfare

Question 36

describe treatment for nerve gas poisoning

(2 drugs + 1 intervention)

Answer 36

pralidoxime (strong nucleophile to displace phosphate group from ach esterase) + Atropine (to counter muscarinic effects) + mechanical ventilation

Question 37

MOA and target of succinylcholine and decamethonium

adverse rxn

Answer 37

Target: nicotinic ach receptors

MOA: activate receptor and cause it to remain open, cause continual depolarization

hyperkalemia

Question 38

competitive nicotinic receptor blockers

MOA:

Answer 38

Rocuronium (an Ammonio Steroid) and Turbocurarine (a Benzylisoquinoline)

occupy ACH binding site on nicotinic receptor therefore the receptor can’t be opened

Question 39

what drugs can reverse competitive nicotinic receptor blockers?

Answer 39

ACH esterase inhibitors can reverse it by raising ACH lvl to compete with blockers

Question 40

why use both an acetylcholinesterase inhibitor and a muscarinic antagonist in the reversal of neuromuscular blockade performed with a drug like rocuronium

Answer 40

Roundabout way of increasing ACh at only Nicotinic AChRs, but not Muscarinic AChRs (this is impossible to do directly)