Autonomic pharmacology II Flashcards
what is the effect of M3 receptor activation on glands?
secretion - sweat, salivation, lacrimation
what is the effect of M3 receptor activation on sphincters?
mostly relaxation with the exception of lower esophageal sphincter
what is the effect of Nn receptor activation on the adrenal medulla?
secretion of EPI and NE
what is the effect of Nn receptor activation on the autonomic ganglia?
stimulation - net effects dependent on PANS/SNS innervation and dominance
what is the effect of Nm receptor activation on the neuromuscular junction?
stimulation - twitch / hyperactivity of skeletal muscle
what is the mechanism of direct acting cholinomimetics?
bind directly to and activate mucarinic or nicotinic cholinoceptors
what is the mechanism of indirect acting cholinomimetics?
produce their effects by inhibiting the action of AchE thus preventing destruction of endogenous Ach
what are the direct acting cholinoceptor agonists that act on M receptors (choline esters)?
- Ach
- methacholine
- carbachol
- bethanechol
how does the cationic quaternary ammonium group affect the choline ester metabolism?
- poor GI absorption
2. poor CNS distribution
how does the presence of methacholine’s methyl group affect its half life?
increase
how does the presence of carbachol’s and bethanechol’s amine group affect its metabolism?
insusceptible to cholinesterase
what is the clinical use for methacholine?
Dx - bronchial hyperactivity
what is the clinical use for carbachol?
Rx - glaucoma
what is the clinical use for bethanechol?
Rx - ileus, urinary retention
what are the muscarinic effects of Ach on the heart?
- vasodilation - reflex tachcardia (low doses)
2. bradycardia, decreased AV conduction, inotropy (high doses)
what are the muscarinic effects of Ach on the lungs?
- bronchial constriction
2. increased bronchial secretion
what are the muscarinic effects of Ach on glands?
salivary excretion, tears, sweat
what are the muscarinic effects of Ach on the bladder?
contraction
what are the muscarinic effects of Ach on the eye?
short lasting miosis
what are the nicotinic effects of Ach?
not normally seen - cannot penetrate fat surrounding skeletal muscle and autonomic ganglia
what are the clinical uses of Ach?
- eye surgery (short lasting miosis)
2. provocation testing in coronary angiography (Dx coronary vasospasm)
what are the clinical uses for methacholine?
diagnosis of bronchiolar hypersensitivity - excessive bronchoconstriction via M3 receptors in asthmatic patients
what are the effects of therapeutic doses of carbachol?
activate both nicotinic and muscarinic cholinoceptors
nicotinic effects on autonomic ganglia, adrenal medulla, skeletal muscle
what are the effects of high doses of carbachol?
cardiac arrest
what are the clinical uses of carbachol?
glaucoma
- contracts ciliary muscle
- enlarges Canal of Schlemm
- increases drainage of aqeuous humor
- decreases intraocular pressure
bethanechol acts primarily on what type of receptor?
M3
what is the effect of bethanechol on the GU system?
- increase detrusor tone
2. decrease outlet resistance of internal sphincter
what is the effect of bethanechol on the GI system?
increase motility and secretion
what are the effects of bethanechol on the heart (M2 receptors)?
weak / minimal effect
what are the indications for bethanechol use?
- gastric atony
- gastric emptying abnormalities
- urinary retention (in absence of obstruction)
what are the direct acting cholinoceptor agonists that act on M receptors (alkaloids)?
- muscarine
2. pilocarpine
what are the symptoms of muscarine poisoning?
- salivation, swear, lacrimation
- abdominal pain, nausea, diarrhea, blurred vision, dyspnea
- symptoms generally subside within 2 hours
- severe cases - cardiac and respiratory failure may lead to death
what are the primary effects of pilocarpine?
opthalmic
- contracts sphincter pupillae - miosis
- opens Canal of Schlemm
- enhances tone of trabecular network
- contracts ciliary muscle - accommodation
what are the clinical uses for pilocarpine?
- glaucoma Rx of choice
2. test on autonomic state
what are contraindications for direct acting cholinoceptor agonists?
- peptic ulcers
- GI tract disorders
- asthma
what are the main drug interactions with direct acting cholinoceptor agonists?
- quinidine - antiarrhythmics
- procainamide - antiarrhthmics
- tricyclic antidepressants
what are the direct acting cholinoceptor agonists that act on nicotinic receptors (alkaloids)?
- nicotine
2. succinylcholine
what are the effects of nicotine on Nm receptors?
- skeletal muscle contraction
- fasciculations, spasm
- depoloarizing blockade
what are the nicotinic effects of Nm receptor activation on the heart?
increased HR (mostly SNS)
what are the nicotinic effects of Nn receptor activation on the vasculature?
peripheral vasoconstriction (mostly PNS)
what are the nicotinic effects of Nn receptor activation on the GI system?
increased gut motility and secretion
what are the nicotinic effects of Nn receptor activation on the carotid bodies?
increased respiratory rate
what are the nicotinic effects of Nn receptor activation on the medullary emetic chemoreceptors?
nausea and vomiting
what are the clinical uses for edrophonium?
Dx - myasthenia gravis
what are the clinical uses for neostigmine and pyridostigmine?
Rx - ileus, urinary retention, myasthenia, reversal of non-depolarizing NM blockers
what are the clinical uses for physostigmine?
Rx - glaucoma, antidote in atropine overdose
what are the clinical uses for donepezil tacrine?
Rx - Alzheimer disease
what are the clinical uses for organophosphates?
Rx - glaucoma, insecticides, nerve gas
what are the symptoms of cholinesterase inhibitor toxicity?
DUMBBELSS
- Diarrhea
- Urination
- Miosis
- Bronchiolar constriction
- Bradycardia
- Excitement
- Lacrimation
- Sweating
- Salivation
what is the antidote for cholinesterase inhibitor toxicity?
atropine - muscarinic receptor antagonist
what is the function of pralidoxim?
regeneration of AchE following cholinesterase intoxication
