Drugs That Act Directly on Nicotinic Receptors

Question 1

what is thought to be involved in drug seeking/reward behaviors?

Answer 1

rise of dopamine in nucleus accumbens (NAc)

aka anything that causes rise in dopamine in nucleus accumbens cause desire to repeat that experience

Question 2

what modulates dopamine release

Answer 2

acetylcholine releasing neurons that originate in the ventral tegmental area (VTA) modulate release of dopamine by activating Nn receptors on dopaminergic neurons in NAc

Question 3

side effects of nicotine

Answer 3

HA, nausea, diarrhea, nightmares, nicotine toxicity

Question 4

early/low dose toxic symptoms of nicotine

Answer 4

salivation, lacrimation, urination, defecation, sweating, nausea/vomiting, increased blood pressure (because no PSNS on it)

Question 5

what occurs if someone using a nicotine patch continues to smoke?

Answer 5

they will have nicotine toxicity, acute HTN, bradycardia, and SLUD

Question 6

MOA of varenicline (chantix)

Answer 6

partial nicotinic agonist causes minimal increases in central dopamine release AND competes with nicotine for Nn receptors on dopaminergic neurons

Question 7

what occurs if a person on chantix smokes again

Answer 7

TLDR: if person smokes, behaves like antagonist
if person doesn’t smoke, is partial agonist of dopamine release

nicotine from cigarette no longer causes rapid rise in dopamine in NAc because some nicotine receptors are being occupied by chantix so is acting like antagonist for nicotine.
BUT if no nicotine in the system, chantix partially stimulates dopamine release to NAc so person doesn’t have that craving.

Question 8

adverse effects of chantix

Answer 8

1. neuropsychiatric sx
2. sedation/insomnia, abnormal dreams
3. increased risk of cardiovascular events
4. serious allergic reaction

Question 9

what is succinylcholine

Answer 9

noncompetitive antagonist of Nm receptor

Question 10

MOA succinylcholine

Answer 10

works like ACh x2, and acetylcholinesterase can’t degrade it, so it stays bound…noncompetitive antagonism of Nm receptor – Na channel stays open, Na rushes in and K rushes out == desensitization blockade (too much ACh)

Question 11

what is seen first in succinylcholine

Answer 11

1st see muscle fasciculations because Na/K movement, increased K causes hyperkalemia, and this is followed by blockade

Question 12

MOA CURare derivatives

Answer 12

nondepolarizing competitive Nm antagonists

block Nm receptors (Nm antagonist) so ACh can’t activate them = non depolarizing competitive blockade (not enough ACh)

but can outcompete to reach Emax

Question 13

difference between CURare derivatives and succinylcholine

Answer 13

CURare are non-depolarizing competitive Nm antagonists (not enough ACh)

succinylcholine is depolarizing noncompetitive Nm antagonism (too much ACh)

Question 14

CURare derivative name

Answer 14

roCURonium (zemuron)

Question 15

use of CURare derivatives

Answer 15

intraoperative surgical relaxation, intubation, ventilation, control of peripheral manifestations of seizures

Question 16

note about CURare derivatives

Answer 16

patient will be paralyzed but not unconscious

Question 17

how to reverse CURare derivatives

Answer 17

increase ACh at Nm junction with ACh esterase inhibitors (because competitive antagonist)

Question 18

MOA of succinylcholine

Answer 18

binds to Nm causing initial depolarization, but stays bound so that ACh cannot bind (noncompetitive blockade of Na channels)

Question 19

how is succinylcholine degraded

Answer 19

plasma esterases

Question 20

pharmacogenomics of succinylcholine

Answer 20

some patients genetically deficient in plasma esterases so causes prolonged paralysis

Question 21

note about succinylcholine

Answer 21

pt are paralyzed but conscious

Question 22

what occurs if more ACh or AChE is added to succinylcholine

Answer 22

makes effects worse because noncompetitive antagonist

Question 23

adverse effects of succinylcholine

Answer 23

1. hyperkalemia (because when turns on Nm, Na rushes in and K out)
2. muscle pain (because of initial contraction)
3. increased intraocular pressure

Question 24

how to treat CURare derivatives

Answer 24

increase ACh levels at synapse with AChE inhibitor