Cholinergic Drugs Flashcards
bethanechol
Muscarinic Receptor Agonist
- choline ester
- Acetyl group of acetylcholine is replaced with a carbamyl. The N+ is permanently charged, reuslting in poor CNS absorption.
- Slowly hydrolized by AchE. Used topically for glaucoma.
carbachol
Muscarinic Receptor Agonist
- choline ester
- A carbamyl added to acetyl choline. The N+ is permanently charged, reuslting in poor CNS absorption. Reduce binding to nicotinic receptors; selective for muscarinic receptors
- Slowly hydrolized by AchE. Used to promote GI and urinary tract motility when non-obstructive cause. (Binds receptor that relaxes sphincters and constricts smooth muscles.
Methacholine
Muscarinic Receptor Agonist
- choline ester
- a beta-methyl group is added to acetocholine, reducing binding to nicotinic receptors. Selective for muscarinic receptors. Permanently charged = poor absorption into CNS.
- diagnosis of asthma.
pilocarpine
Muscarinic Receptor Agonist
- tertiary amine
- tertiary amine N is not charged so this can penetrate CNS. It is not an ester so It is not hydrolized by cholinesterase. Longer duration of action than Ach.
- Sialogogue (Cause salivation) and a mitotic agent (constricts pupil)
glycopyrrolate
Antimuscarinic
- quaternary amine
- poor CNS penetration
- Decrease oral secretions, GI Spasms, Treatment of saiallorrhea like in children with cerebral palsy. Treat peptic ulcer disease. Prevent bradycardia during surgical procedures.
Oxybutynin
Antimuscarinic
- tertiary amine, M3 selective
- relief of bladder spasm after urologic surgery
tolterodine
Antimuscarinic
- tertiary amine, M3 selective
- For urinary incontinence in Adults (M3 contracts smooth muscle and relaxes sphincters.)
darifenacin
Antimuscarinic
- tertiary amine, M3 selective
- For urinary incontinence in Adults (M3 contracts smooth muscle and relaxes sphincters.)
pirenzepine
Antimuscarinic
- tertiary amines, M1 selective
- inhibits gastric acid secretion. Little effect on smooth muscle or CNS
- used in peptic ulcer disease, but not so much anymore
tropicamide
Antimuscarinic
- tertiary amine
- mydriatic (pupil dilation), cycloplegic. Much shorter duration of action than atropine. (.25 days rather than a week)
cyclopentolate
Antimuscarinic
- tertiary amine
- mydriatic (pupil dilation), cycloplegic. Much shorter duration of action than atropine. (1 day rather than 1 wk)
Trimethophan
Nicotinic Receptor Antagonists
- Ganglion Blocking drug
- Treatment of hypertensive emergencies, rarely used bc of bad side effects. Used to produce controlled hypotension during surgery to decrease bleeding.
pancuronium
Nicotinic antagonist
- like steroid hormones, part of it mimics ach but bulkiness keeps the channel from opening.
- depolarizing blockade can be reversed by increasing concentration of normal transmitter, i.e. Ache
- Block access of Ach to receptor thereby preventing depolarization of membrane block channel in CLOSED position
tubocurarine
Nicotinic antagonist
- arrow poison
- depolarizing blockade can be reversed by increasing concentration of normal transmitter, i.e. Ache
- Block access of Ach to receptor thereby preventing depolarization of membrane block channel in CLOSED position
Succinylcholine
Neuromuscular Blocking Drug
- two acetylcholines connected together. ONLY depolarizing drug in use in US. Duration of action is five to ten minutes. Used in surgery.
- Phase I block: channel opens. Depolarized membranes remain depolarized and unresponsive to subsequent impulses. Flaccid paralysis results.
- Phase II block: desensitizing: continued exposure to the drug, depolarization decreases, membrane becomes repolarized some how, channels behave as though in a prolongued closed state even though they are in a prolongued open state.
Edrophonium
Indirect-acting Cholinomimetics -Acetylcholinesterase Inhibitors
- simple alcohol that non-covalently inhibits ACHE, short diration of action (Competes with Ach for binding)
- Use as a diagnostic test when patients exhibit muscle weakness. (It will mitigate weakness if blockade due to competitive Ach receptor antagonists or disease that affect NMJ)
- too asses adequacy of treatment for myaesthenia gravis.
neostigmine
Indirect-acting Cholinomimetics -Acetylcholinesterase Inhibitors
- carbomate: can modify AChE and stays on AChE longer than acetyl group would stay on in case of acetylcholine… basically binds up the enzyme and holds onto it for a while.
- charged, poorly absorbed, no distribution in CNS.
- MG, ileus, reversal of neuromuscular blockade
physostigmine
Indirect-acting Cholinomimetics -Acetylcholinesterase Inhibitors
- CAN GET INTO CNS - must be used carefully, used in overdose of antidepressants (?)
- well-absorbed from all sites
- glaucoma, reversal of neuromuscular blockade, used as a topical on the eye
pyridostigmine
Indirect-acting Cholinomimetics -Acetylcholinesterase Inhibitors
- Carbomate: can modify ACHE
- charged, poorly absorbed, no distribution in CNS.
- MG
malathion
thiophosphate insectisides
parathion
thiophosphate insectisides
tacrine
ache inhibitor
- symptomatic alz improvement ALZHEIMERS. Has hepatic toxicity
donepezil
ache inhibitor
symptomatic alz improvement
galantamine
ache inhibitor
symptomatic alz improvement
rivastigmine
ache inhibitor
symptomatic alz improvement
Botulinum Toxin
- Degrades synaptobrevin, preventing acetocholine vesicle fusion (prevents release of acetocholine)
- Induces flaccid paralysis, useful for treatment of spasms and dystonias
ipatropium
Antimuscarinic
- quaternary charged ammonium, synthetic analogue of atropine, acts locally
- Used by inhalation for asthma and COPD. Poorly absorbed which is good bc it stays in the lungs.
(M3 receptors constrict airways, so an antimuscarinic will dilate them)
benztropine
antimuscarinic
- tertiary amine (good CNS penetration).
- Used in therapy of Parkinsons which causes degradation of dopinergic neurons. Its also used to treat acute dystonias caused by antipsychotics.
scopalamine
antimuscarinic
similar to atropine
- Well absorbed from gut (no charges) and conjunctiva.
- Formulated as transdermal patch to decrease nausea for motion sickness and chemotherapy. Greater CNS effects than atropine; sedative. Dry as a bone, blind as a bat, red as a beet, mad as a hatter.
atropine
antidote for muscarine poisoning
- inhibit excess secretions during surgery, reverse sinus bradycardia, prevent vagal reflexes induced by surgical trauma, counteract muscarine poisoning.
pralidoxime
ACHE inhibitor
- prevents “aging” of modified enzyme ACHE when someone is exposed to organophosphates
- (keeps the ache intermediate from stabilizing
- use when you see cholinesterase inhibitor toxicity: DUMBBELSS: Diarrhea, urination, miosis, bronchoconstriction, bradycardia, excitation, lacrimation, salivation and sweating (you see direct effects on both muscarinic and nicotinic receptors.
echothiophate
organophosphate
- highly polar, very long duration of action
- used for glaucoma, lowers IOP. Not well absorbed (very polar)
4 Main effects of muscarinic Agonists
- cardiac slowing, decrease in cardiac output, vasodilation, fall in arterial pressure
- increase in GI peristalsis, contraction of bladder and bronchial smooth muscle
- stimulate secretions (sweat, lacrimation, salivation, bronchial)
- Contract ciliary muscle –> lower IOP in acute glaucoma
4 signs of Muscarinic AGONIST toxicity
- cutaneous vasodilation
- nausea, vomiting, diarrhea, bronchial constriction
- Sweating, salivation
- miosis
(Seen 15-20 min after eating mushroom. treat w atropine)
7 Major affects of atropine
- inhibition of secretions (salivary, lacrimal, sweat, bronchial)
- tachycardia (modest)
- mydriasis, cycloplegia
- inhibit GI motility (Large doses)
- relax smooth muscle - bronchial, biliary, urinary tract
- excite CNS
- Children: rise in body temperature exacerbated by losso f sweating *
5 major effects of muscarinic antagonists
- tachycardia
- relax gut, bladder, bronchial smooth muscles (contract sphincters)
- inhibit secretions (salivary, sweat, lacrimal, bronchial, gastric acid)
- mydriasis, cycloplegia
- CNS: antiemetic and antiparkinsonism
Topiramate
(Topomax)
antiepileptic
Valproate
(Depakote)
antiepileptic
Gabapentin
antiepileptic
Amitriptyline
tricyclic antidepressant
Nortiptyline
tricyclic antidepressant
Venlafaxine
SNRI
Duloxetine
SNRI
Propanalol, timolol
Beta-adrenergic blockers
Flunarizine
Calcium channel blockers
