Kruse Cholinergic Agonists and Antagonists DSA Flashcards
choline esters
examples
structure and CNS
how its broken down
eg. acetylcholine, carbachol, bethanechol, methacholine
- contain permanently charged quarternary ammonium groups = poor CNS absorption
- hydrolized in GI tract and less active when given PO
- all hydrolyzed by cholinesterase
most rapid to least rapid hydrolyzation of choline esters by acetylcholinesterase
acetylcholine>methacoline>carbachol = bethanechol
AMC Blockbuster
choline esters MOA
agonists on cholinergic receptors
alkaloids
examples
strucutre and absorption
anomalies with absorption
muscarine, nicotine, pilocarpine
agents are uncharged tertirary amines (except muscarine) that are well absorbed from most sites of administration
(nicotine can go through skin)
-although muscarine is quaternary amine, it is higly toxic when ingested and can enter the brain
excretion of alkaloid cholinergic drugs
excreted by kidneys, acidification of urine accelerates clearance
MOA of alkaloids
act as agonists on cholinergic receptors
what is the primary effect of muscarinic agonists on peripheral vasculature
reduces resistance
GI and genitourinary tracts direct acting cholinergic effects
what receptors and what function of them
increased glandular secretions more salivary and gastric
- M3 for contraction of smooth muscle
- M2 reduces cAMP formation and reduces relaxation caused by adrenergic effects
- sphincter relaxation is via NO signaling (M3 mACHRs)
the brain is richer in ____ ach receptors while the spinal cord contains predominantly __
muscarinic, nicotinic
excitatory mAChRs are involved in ___ while inhibitory mAChRs are involved in
learning and memory and seizure activity
tremors, hypothermia, and analgesia
nAChR causes receptor activation in _____ ___ and actions are similar in both ____
autonomic ganglia
symp, and parasymp ganglia
-initial response resembles simultaneous discharge of both parasymp and symp nervous systems
nAChR in CV system
nicotine is mainly sympathomimetic
nAChR in GI/GU
mainly parasympathomimetic (nausea, vomiting, diarrhea, voiding of urine)
clinical uses of direct acting cholinergic agonists
example of drug for one system
glaucoma
-musc stimulants cause contraction of cilirary body which = more outflow of aq humor and reduces intraocular pressure
accommodative esotropia in young children who are farsighted and overcompensate and eyes become crossed
GI/GU tract disorders
-postoperative ileus, atony or parlysis of stomoch or bowel after surgery, congenital megacolon, urinary retention, esophagueal reflux
- example is bethanechol
- as long as there is no obstruction or can cause perforation
what drugs are used to increase salivary secretion
pilocarpine and cevimeline
major contraindications to use mAChR agonists that are distributed systemically are
HACA
Hyperthyroidism
asthma
coronary insufficiency
acid-peptic disease
acute toxicity of nicotine
cns stimulation: convulsions progressing to coma and respiratory arrest
skeletal muscle end plate depolariztion leading to depol blockade and respiratory paralysis
hypertension
cardiac arrhythmias
treatment for acute toxicity
atropine for excess muscarinic stimulation from parasymp ganglia
anticonvulsants (diazepam) for CNS stimulation
chronic nicotine toxicity
increased risk vascular disease
sudden coronary death
ulcer recurrences in smokers with peptic ulcer
acetylcholine use
intraocular use during surgery and cuases miosis
methacholine use
inhalation for diagnosis of bronchial airway hyperreactivity in pts who don’t have clinically apparent asthma
bethanechol use
urinary retention and heartburn
selective mAChR
may produce UTI if sphincter fails to relax
carbachol use
nonspecific cholinergic agonist used for glaucoma or to produce miosis during surgery or eye exam
cevimeline use
oral tab used to treat xerostomia in pts with sjogren’s syndrome
metabolized via P450 pathway and eliminated in urine
