nicotinic drugs

ion channel
5 subunits
bind ACh > open ch > Na+ IN

Nn neuronal: ganglionic nico receps or CNS
Nm muscle: NMJ, present on motor endplate

feature of nACh receptor; can become unresponsive to cont exposure to agonist
OR
response to agonist becomes variable (sometimes inhib sometiems excite)

NOT behind BBB > exposed to anything systemic
nAChR in both sns pns
alter activity of nACh in ganglia > effects of blocking both SNS and PNS

AchE inhibitors:
neostigmine (no BBB)
physostigmine (BBB!!!!)

direct agonist of ganglionic stim
at recreational doses: modest ^ HR, BP, respiratory rate, GI activity, CNS stim
long term: tolerance and dependence

partial/full agonist at nACh receptor
tx: smoking cessation therapy
sfx: MTWThF

muscarine xs: anticholinergic (atropine)
NMJ blockage : mechanical respiration
CNS: anticonvulsant (diazepam)

AID of NMJ
tx: neostigmine (this is indir agonist, which inc ACh, can have sfx from ganglia and effector organs)

neostigmine has direct (stim receptor) and indirect (inhibit AChE) effects

add peripheral anticholinergic agent

cholinergic is activation of PNS
antichol inhibition of PNS

prevent Nm activation by ACh, preventing endplate depolarization
aka paralytics or muscle relaxants

indication: Intubation, pts on mechanical ventilation, muscular relaxation for a surgical procedure, orthopedics

short acting: succinylcholine
interm: rocuronium
long: tubocurarine

d-tubocurarine (curare); will compete with ACh to bind to receptor
flaccid, relaxed paralysis
sfx at non NMJ: ganglia and musc blocking, histamine release > hypotension, tachycard, bronchospasm

this can be reversed by AChE inhibitors like neostigmine/physostigmine

--

rocuronium
fast onset
good w sugammadex, encapsule ron > dont intr with nAChR > rapid reversal and shorten duration of action

apnea (no respiration)
ganglionic blockade and histamine release from tubocurarine, which can in turn cause hypotension

AChE inhibitors

succinylcholine
two phases of block, 1 most relevant clin

p1: membrane depol, transient fasiculations and paralysis

NMJ BLOCK CANNOT BE REVERSED BY ACHE INHIBITOR

less effect than curare, fast onset, brief duration

metabolized by psuedocholinesterase

succinylcholine is the NMB

pts with atypical pseudocholinesterase: no enzyme or altered, can be paralyzed for hours

hyperkalemia: burn pts have more nACh recept > more plasma K+ > cardiac arrest

malignant hyperthermia: more likely with halothane; some drugs with succinylcholine cause Ca++ release > tachycardia, dysrhythmia, muscle rigid, inc body temp

dantrolene

can be synergistic with some agents

CaCh blockers

aminoglycoside abx

certain general anesthetic (halothane)