Nicotinics and AChE

Question 1

Where does ACh bind on Muscle nicotinic receptors

Answer 1

alpha - delta interface
or
alpha - epsilon interface

Question 2

How many molecules of ACh are required to open a nicotinic ion channel?

Answer 2

2

Question 3

Which nicotinic receoptor is Jim’s favorite?

Answer 3

Alpha7 homopentamer

Question 4

Where does ACh bind on neuronal AChRs?

Answer 4

Homomeric: Alpha-Alpha interface
Heteromeric: Alpha-Beta interface

Question 5

Alpha7 AChR homopentamer Ion selectivity and location

Answer 5

Ca++&raquo_space; Na+

Brain and Ganglia

Question 6

Alpha subunit primarily found in the brain

Answer 6

Alpha 2

Question 7

Alpha subunit primarily found in ganglia

Answer 7

Alpha 3

Question 8

Alpha subunit most common in CNS

Answer 8

Alpha 4

Question 9

Alpha subunit primarily found in skeletal muscle

Answer 9

Alpha 1

Question 10

Varenicline (Chantix)

Answer 10

Partial nicotinic agonist

Question 11

Bupropion (Wellbutrin; Zyban)

Answer 11

DAT/NET blocker

Question 12

Clonidine (Catapres)

Answer 12

Alpha2 agonist. Roll in smoking cessation?

Question 13

Chantix concerning side effect

Answer 13

Major sleep disruptions, bad dreams, etc.

Question 14

What makes a light cigarette?

Answer 14

More holes -> infuses more air -> less cough reflex -> deeper inhale

Question 15

If you want to increase nicotine receptor density in the brain, would you give nAChR agonist or antagonist?

Answer 15

Trick question you could use either.

Question 16

Current hypothesis for why nicotine (or agonist) can cause upregulation of receptor

Answer 16

Receptor homologously desensitized so chronic activation and desensitization leads to receptor synthesis

Question 17

Where are most neuronal nicotinic receptors located?

Answer 17

Presynaptic nerve terminals

Question 18

How doe presynaptic nerve terminal nAChRs facilitate nerotransmitter release?

Answer 18

Increased Ca++ levels; increased NT release

Question 19

Nicotine Withdrawl symptoms

Answer 19

Negative Mood
Depressed
Anxious
Inattentive
Hungry
Cognitively Impaired
Achy

Question 20

Skeletal muscle relaxants MOA

Answer 20

Indirect: Decrease ACh release in somatic NS

Direct acting: Block muscle nAChRs

Question 21

d-tubocurare (Tubarine) MOA

Answer 21

Direct antagonist. Binds nAChR orthosteric binding site

Question 22

How to reverse Curare

Answer 22

AChE inhibitors and mAChR antagonists

Question 23

Depolarizing neuromuscular blockers

Answer 23

Succinylcholine (Anectine)

Question 24

Succinylcholine (Anectine) MOA

Answer 24

Depolarizes NMJ initially, then produces long-lasting blockade

Question 25

Succinylcholine metabolism

Answer 25

Plasma cholinesterase

Question 26

Succinylcholine ADR

Answer 26

1. Postop muscle pain ( due to fasciculations) 2. Hyperkalemia 3. Malignant hyperthermia - number one cause of death during surgery

Question 27

Ganglionic Blocking Drugs

Answer 27

Mecamylamine (Inversine) Hexamethonium

Question 28

Mecamylamine (Inversine) MOA

Answer 28

Blocks nAChRs in ganglia -> decreased postganglionic release of NE -> decreased BP *Also blocks parasympathetic --> Anti-sludge ADR

Question 29

Mecamylamine (Inversine) Effects

Answer 29

- Decreased BP - Loss of cardiovascular reflexes - Severe orthostatic hypotension - Constipation, urinary retention, drymouth - Partial mydriasis

Question 30

AChEIs Use

Answer 30

- Recovery from NMJ blockers - Autoimmune myasthenia gravis - Atropine Poisoning (comp. musc. antag) - TCA overdose - Cognitive improvement in dementia

Question 31

Carbamates (AChEIs) that Cross the BBB

Answer 31

* *Donepezil (Aricept) * *Galanthanmine (Reminyl) - Physostigmine (Antilirium) - Tetrahydroacridine (THA) (Tacrine) - Rivastigmin (Exelon)

Question 32

Donepezil (Aricept) MOA

Answer 32

CNS AChEI -> increased central ACh activity

Question 33

Galanthamine (Reminyl) MOA

Answer 33

CNS AChEI -> increased ACh concentration | Also nAChR APL

Question 34

Carbamates that don't cross BBB

Answer 34

Pyridostigmine (Mestinon)

Question 35

Pyridostigmine (Mestinon) Use

Answer 35

Myasthenia Gravis and prophylaxis during the PGW

Question 36

ADRs of AChEIs

Answer 36

Indirect agonism of nAChRs and mAChRs | ANS+Somatic+CNS symptoms