Cholinergic Agonists Flashcards
Action of direct cholinergic agonists
activate cholinoceptors
Action(s) of indirect cholinergic agonists
- stimulate release of acetylcholine
- inhibit acetylcholinesterase
What tissues are Nm receptors found in, what is the response, what is the mechanism?
skeletal muscle; depolarization and contraction; ligand-gated opening of Na/K channel
What tissues are Nn receptors found in, what is the response, and what is the mechanism?
Found in the ganglions (post-ganglionic); depolarization; ligand-gated opening of Na/K channel
Found in adrenal medulla; catecholamine secretion; ligand-gated opening of Na/K channel
What type of receptor does acetylcholine have the highest affinity for?
Muscarinic» Nicotinic
What tissues are M1 receptors found in , what is the response, and what is the mechanism?
Post-ganglionic receptors, depolarization, Gq
What tissues are M2 receptors found in, what is the response, and what is the mechanism?
Heart, inhibition, Gi (activates K+ channels)
What tissues are M3 receptors found in, what is the response, and what is the mechanism?
smooth muscle, exocrine glands, epithelium; contraction, secretion, and relaxation; Gq
What is the endogenous neurotransmitter for Muscarinic receptors?
acetylcholine
Main structural components of acetylcholine?
Acetyl group (ester) + choline group (charged quaternary amine)
exogenous cholinergic neurotransmitters
muscarine & nicotine
muscarine poisoning symptoms
bradycardia, nausea, cramps, vomiting, diarrhea, bronchoconstriction, salivation, visual disturbances, sweating, hypotension
can muscarine cross the BBB?
no
Direct acting cholinergic agonist classes
Choline esters, alkaloids
Indirect acting cholinergic agonist classes
reversible & irreversible; organophosphates & stigmines
Muscarinic agonist effect in the heart
M2 activation = decreased HR, conduction, and force
Muscarinic agonist effect in exocrine glands
M3 activation = increase in secretion
Muscarinic agonist effect in smooth muscles
M3 activation = increase in contraction
Muscarinic agonist effect in sphincters
M3 activation = relaxation
Muscarinic agonist effect in CNS
only by M1 activation = tremor, hypothermia, locomotor activity, improved cognition
Carbachol class
direct acting cholinergic receptor agonist; esters
methacholine class
direct acting cholinergic receptor agonist; esters
bethanechol class
direct acting cholinergic receptor agonist; esters
What receptors are ACh and carbachol active on?
both n and m
What is the effect of B substitutions on acetylcholine?
reduce AChE activity; more selective for Muscarinic
What is the effect of a substitutions on acetylcholine?
selective for Nicotinic
What is the effect of carbamate group on ACh?
resistant to AChE
Alkaloids
muscarine, nicotine, pilocarpine
pilocarpine indication & effects
glaucoma; promotes sweating, urination, urination, and salivation
Pilocarpine receptor & clinical use
M3 agonist; promotes outflow of aqueous humor (glaucoma), xerostomia
Bethanechol clinical use
GI stimulation; treatment of urinary retention
methacholine clinical use
test for hyperreactive airways
carbachol clinical use
ocular (surgery, glaucoma)
Side effects of muscarinic receptor direct agonists
DUMBBELS- diarrhea, urination, miosis, bradycardia, bronchoconstriction, emesis, lacrimation, salivation, sweating
muscarinic receptor direct agonist contraindications
asthma, coronary insufficiency, peptic ulcer
nicotinic receptor locations
skeletal muscle endplate (Nm), Autonomic ganglia (Nn), Brain (CNS) (Nn)
varenicline indication (chantix)
smoking cessation
Varenicline MOA
Nicotinic receptor partial agonist (CNS)
Bupropion (wellbutrin) Indication
smoking cessation (nicotinic receptor partial agonist)
What does AChE do?
hydrolyzes (inactivates) ACh using catalytic triad; has an anionic site and esteratic site to bind to ACh
reversible anticholinesterase agents (categories)
alcohol, carbamates, other (donepezil)
irreversible anticholinesterase agents
organophosphates
Edrophonium
Quaternary ammonium alcohol
pralidoxime action
hydrolyzes organophosphate & regenerates AChE
pralidoxime clinical use
used for organophosphate poisoning (pesticide + nerve gas)
Atropine class/ action
muscarinic receptor antagonist (especially in CNS)
Atropine clinical use
used in conjunction with pralidoxime for organophosphate poisoning; helps with overstim. of cholinergic receptors.
Donepezil class/action
AChE inhibitor
Donepezil clinical use
Treats symptoms of alzheimers; crosses the BBB
Rivastigmine/Epastigmine class/action
reversible AChE inhibitor
crosses the BBB
Rivastigmine/ Epastigmine clinical use
Alzheimer’s Disease
Galantamine class/action
Reversible competitive AChE inhibitor, may be a nicotinic receptor agonist
Galantamine clinical use
Treatment of Alzheimers
Memantine class/action
NMDA receptor antagonist (not cholinergic)
Memantine clinical use
Slows progression of Alzheimers; often used with donepezil
edrophonium clinical use/ action
Reversible AChE inhibitor; diagnostic for myasthenia gravis
neostigmine clinical use/action
Reversible AChE inhibitor; Myasthenia gravis, bladder distension, used in surgery
physostigmine clinical use/action
reversible AChE inhibitor; glaucoma, alzheimers, antidote to anticholinergic overdose
Donepezil clinical use/action
reversible AChE inhibitor; Alzheimer’s disease
Echothiophate clinical use/action
irreversible AChE inhibitor; glaucoma
Cholinergic Agent side effects
SLUD- salivation, lacrimation, urination, defecation
Treatment for Cholinergic Agent side effects
cholinergic receptor antagonist (Atropine)
for irreversible AChE inhibitor, (Pralidoxime)
Contraindications to parasympathomimetic drugs
Asthma and COPD, coronary deficiency, peptic ulcer, obstruction of urinary or GI tract, epilepsy
atropine action
competitive muscarinic receptor antagonist
atropine selectivity
Muscarinic»_space; Nicotinic
active at M1, M2, and M3
Classes of Muscarinic Antagonists
Tertiary Amines, Quaternary Amines
What are tertiary amine muscarinic antagonists used for clinically?
Ocular and CNS applications
What are quaternary amine muscarinic antagonists used for clinically?
GI tract and peripheral (no BBB access)
Atropine/Scopolamine -ine’s
Muscarinic antagonists; used for motion sickness
Ipratropium/ tiotropium
derivative of belladonna alkaloids – muscarinic antagonist
benztropine
tertiary amine; used for parkinson’s disease (side effect: sedative activity)
Ipatropium
COPD and asthma (M3 antagonist; opens the airway)
glycopyrrolate use
Pre-op to reduce secretions (anti-muscarinic)
Tolterodine
used for overactive bladder; M3 antagonist (M3 selective)
M3 selective muscarinic antagonists for OAB
Solifenacin, Oxybutynin, and Darifenacin
Neuromuscular blocking drugs
anti-nicotinic; look like ACh
