Smooth m relaxants part 2

Question 1

Cholinesterases

Answer 1

• Butyrylcholinesterase- found in plasma and liver

- ACE

Question 2

AChE inhibitors

Answer 2

• Alcohols
• Carbamic acid esters
• organophosphates

Question 3

AChE inhibitors- alcohols

Answer 3

-edrophonium

Question 4

AChE inhibitors- carbamic acid esters

Answer 4

-neostigmine, pyridostigmine, physostigmine, carbaryl

Question 5

AChE inhibitors- organophosphates

Answer 5

• echothophate, parathion, malathion (insecticides), sarin, soman, and tuban (n gases)
• irreversible

Question 6

AChE inhibitors- moa

Answer 6

• inhibit AChE

- ACh accum throut body- act of nAChRs and mAChRs

Question 7

AChE inhibitors- duration of action

Answer 7

• alcohols short (2-10 min)
• carbamic acid esters- 2-step hydrolysis (30 m- 6 hrs)
• organophosphates- very long

Question 8

AChE inhibitors- CNS

Answer 8

• CNS- low conc- diffuse act on EEG

- high conc- generalized convulsions

Question 9

AChE inhibitors- eye, resp tract, GI tract, urinary tract

Answer 9

-innervated by mAChRs (parasymp)

Question 10

AChE inhibitors- CV

Answer 10

• inc activity of symp and parasymp ganglia (n and mACHRs) supplying the heart and at mAChRs on cardiac cells
• parasymp tone dominates- CO dec
• modest bradycardia, dec in CO, modest dec in BP
• toxic doses- marked bradycarida, hypotension

Question 11

AChE inhibitors- NMJ

Answer 11

• prolong and intensify actions of ACh- inc strength of contraction
• fibrillation of m fibers and fasciculations- high conc
• continued inhibition of ACHE- progression of depolarizing neuromuscular blockade to nondepolarizing blockade

Question 12

AChE inhibitors- therapeutic uses

Answer 12

• glaucoma, accommodative esotropia
• postop atony, neurogenic bladder)
• MG, curare-induced neuromuscular paralysis
• central atrial arrhythmias
• Alzheimer dz

Question 13

MG- tx

Answer 13

-pyridostigmine, neostigmine, ambenonium (AChE inhibitors)- dont cross BBB!!

Question 14

dx agent for MG

Answer 14

Edrophonium test

• admin of edrophonium (short-acting)- relieves ptosis, diff speaking and swallowing, extremity weakness
• not used anymore- dangerous!!!- use ice pack test (2-3 min)- inhibits cholinesterase activity

Question 15

Myasthenic vs cholinergic crisis

Answer 15

• Myasthenic crisis- weakness from acquired MG that is severe enough to necessitate intubation
• cholinergic crisis- SE of excessive ACHE inhibitors
• to distinguish b/w the 2- edrophonium test!- if in myasthenic crisis, sx’s will improve!
• should be assumed that pts w MG in crisis are in myasthenic crisis unless it is known t hat the doses of ACHE inhibitors exceed the daily allowable limits

Question 16

ACHE inhibitors- reversal of pharmacologic crisis

Answer 16

• reverse the paralysis induced by neuromuscular blocking drugs
• can treat paralytic ileus, atony of urinary bladder, and congential megacolon

Question 17

ACHE inhibitors- glaucoma

Answer 17

(inc intraocular P)

-reduce intraocular P by stim mACHRs of ciliary body- causes contraction- outflow of aqueous humor

Question 18

ACHE inhibitors- dementia

Answer 18

-Alzheimers- def of intact cholinergic neurons

Question 19

ACHE inhibitors- antidote

Answer 19

• intoxication of anticholinergic agents- cutaneous vasodilation, anhidrosis, nonreactive mydriasis, delirium, hallucinations, reduction to urinate
• physostigmine!!- crosses BBBB

Question 20

ACHE inhibitors- drug-drug interactions

Answer 20

• nondepolarizing NM blocking agents- combo- dimishes NM blockade; exception is mivacurium
• succinylcholine- enhance phase 1 block, and antagonise phase 2 block
• cholinergic agonists- enhance effects
• B-blockers- enhance bradycardic effects
• systemic corticosteroids- enhance m weakness seen in pts w MG

Question 21

ACHE inhibitors- acute intoxication

Answer 21

• mACHR stim- miosis, salivation, sweating, bronchial constriction, vomiting, diarrhea
• after ingestion- GI sx’s 1st
• percutaneous abs- sx’s of sweating and m fasciculations nearby

Question 22

ACHE inhibitor poisoning- tx

Answer 22

• atropine!!!! (mACHR antagonist)

- pralidoxime- cholinesterase regenerator

Question 23

prophylaxis in ACHE inhibitor poisoning

Answer 23

-pyridostigmine