Drugs That Act Directly on Nicotinic Receptors Flashcards
what is thought to be involved in drug seeking/reward behaviors?
rise of dopamine in nucleus accumbens (NAc)
aka anything that causes rise in dopamine in nucleus accumbens cause desire to repeat that experience
what modulates dopamine release
acetylcholine releasing neurons that originate in the ventral tegmental area (VTA) modulate release of dopamine by activating Nn receptors on dopaminergic neurons in NAc
side effects of nicotine
HA, nausea, diarrhea, nightmares, nicotine toxicity
early/low dose toxic symptoms of nicotine
salivation, lacrimation, urination, defecation, sweating, nausea/vomiting, increased blood pressure (because no PSNS on it)
what occurs if someone using a nicotine patch continues to smoke?
they will have nicotine toxicity, acute HTN, bradycardia, and SLUD
MOA of varenicline (chantix)
partial nicotinic agonist causes minimal increases in central dopamine release AND competes with nicotine for Nn receptors on dopaminergic neurons
what occurs if a person on chantix smokes again
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.
adverse effects of chantix
- neuropsychiatric sx
- sedation/insomnia, abnormal dreams
- increased risk of cardiovascular events
- serious allergic reaction
what is succinylcholine
noncompetitive antagonist of Nm receptor
MOA succinylcholine
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)
what is seen first in succinylcholine
1st see muscle fasciculations because Na/K movement, increased K causes hyperkalemia, and this is followed by blockade
MOA CURare derivatives
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
difference between CURare derivatives and succinylcholine
CURare are non-depolarizing competitive Nm antagonists (not enough ACh)
succinylcholine is depolarizing noncompetitive Nm antagonism (too much ACh)
CURare derivative name
roCURonium (zemuron)
use of CURare derivatives
intraoperative surgical relaxation, intubation, ventilation, control of peripheral manifestations of seizures
note about CURare derivatives
patient will be paralyzed but not unconscious
how to reverse CURare derivatives
increase ACh at Nm junction with ACh esterase inhibitors (because competitive antagonist)
MOA of succinylcholine
binds to Nm causing initial depolarization, but stays bound so that ACh cannot bind (noncompetitive blockade of Na channels)
how is succinylcholine degraded
plasma esterases
pharmacogenomics of succinylcholine
some patients genetically deficient in plasma esterases so causes prolonged paralysis
note about succinylcholine
pt are paralyzed but conscious
what occurs if more ACh or AChE is added to succinylcholine
makes effects worse because noncompetitive antagonist
adverse effects of succinylcholine
- hyperkalemia (because when turns on Nm, Na rushes in and K out)
- muscle pain (because of initial contraction)
- increased intraocular pressure
how to treat CURare derivatives
increase ACh levels at synapse with AChE inhibitor
