02 - Anticholinergics Flashcards
What is the moa of M1,3,5 recpeotrs
signal via Gq to incr IC Ca2+ and PKC
What are the locations of M1 and M3 receptors
M1: CNS, symp postganglionic cells
presynaptic cytes
M3: SM, lungs, eyes, effector cell membranes
What is the moa of M2, M4 receptors?
Gi/o signallingn to decrease cAMP and decrease cAMP-dep PK activity
what are the locations of M2 and M4 receptors?
M2: myocardium, SM, presynaptic sites (K+ channel linked = slow HR)
M4: located in CNS
What are the clinical uses of anticholinergics?
ocular exams:
mydriasis (M3 pupilly constrictor muscle), cycloplegia (M3, ciliary muscle)
incontinence: bladder relaxation (M3, contraction of bladder and M2 -- inhib relaxation)
IBS: GI tract paralysis, reduce secretion
Pre-op anti-sec
COPD–bronchodilation, red secr
motion sickness
Parkinson’s disease adjunct
What are the long-lasting tertiary amines that are antimuscarinic? what is their selectivity? What are they used to treat?
atropine
scopalomine
M1/M2/M3 non-selective
used to treat GI/urinary conditions, COPD, Motion sickness, adjunct for Parksinons
Can affect CNS.
scopolamine has higher CHS penetration (more drowsiness-halluciation)
What are the short-acting antimuscarinic tertiary amines? what is their selectivity? What are they used to treat?
homatropine, tropicamide
used in optical applications: cycloplegia and mydrasis
M1,2,3 nonselective
homatropine less toxic but tropicamide has shorter doa
What antimuscarinic tertiary amine are used for Parkinson’s disease?
benztropine (Cogentin)
sedative activity
adjunct w L-DOPA to achieve better balance btw dopaminergic and cholinergic neurotransmission
What antimuscarinic quaternary amines are used for GI disorders?
glycopyrrolate propantheline brome (Probanthine)
tx of GI spasms, peptic ulcers
charged N maks crossing gut difficult
What antimuscarinic quaternary amines are used for COPD?
ipratropium bromide
M3 receptors mediate bronchiolar SM constriction so this drug blocks Ach-mediatde contstriction of bronchial smooth muscle constriction
–> enhances beta-adrenergic agonist therapy in COPD
What are the signs of anticholinergic toxicity?
How should it be treated?
dry as a bone (mouth, sweat, thirst)
blind as a bat (dilated)
hot as firestone
mad as a hatter (hallucinations, delirium)
others include rapid pulse, ataxia, coma
Treat with AChEI to help compete away the antagonist.
What are clinical uses of nicotinic receptor antagonists?
–> cause muscle paralysis
muscle relaxation during surgery
tracheal intubation
control of ventilation
tx of convulsions (status epilepticus, local anesthetic,)
**these drugs don’t penetrate BBB
What are the two modes of action of nicotinic receptor antagonists?
(1) depolarizing competitive
(2) nondepolarizing
Describe the moa of depolarizing nicotinic receptor antagonists?
phase I: depolarization, open ion channel and depolarize motor end plate
II: densensitization, depolarization decreases and end plate repolarizes but membrane still can’t be dpepolarized (unknown mechanism similar to nondepolarizing)
Which neuromuscular blocker is depolarizing?
Describe its duration of action. What is it used for? What is a possible ADR?
succinylcholine
SHORT 5-10 min d/t hydrolysis by plasma pseudocholinesterase
use: intubation
–can cause arrythmias d/t stimulating all autonomic ACh receptors
