cholinergic agent Flashcards
acetylcholine has a higher affinity for the ______ receptor than the ______ receptor
muscarinic
nicotinic
choline is transported into the presynaptic nerve terminal by a _____
-sodium-dependent choline transporter (CHT)
-this transporter can be inhibited by hemicholinium
ACh is synthesized from choline and acetyl- CoA by the enzyme
-choline acetyltransferase (ChAT)
ACh is then transported into the storage vesicle by a second carrier, the ________ this can be inhibited by ______
-vesicle-associated transporter (VAT)
-vesamicol
Release of transmitter occurs when an action potential opens__________ and increases the intracellular____. Fusion of vesicles with the surface membrane results in release of ACh. This step can be blocked by ______
-voltage sensitive calcium channel
-calcium
-botulinum toxin (botox)
ACh binds to _____ on the postsynaptic cell
cholinoceptors
ACh ‘s actions is terminated by metabolism by the enzyme ______
acetylcholinesterase (AChE)
parasympathmimetic actions (agonists)
-direct agonist: activates cholinoceptors
-indirect agonist: stimulate acetylcholine release, inhibit acetylcholinesterase (AChE) for ACh degradation
parasympatholytic actions (antagonists)
direct or indirect
-many drugs exhibit anticholinergic side-effect
muscarinic agonist effect on the heart
M2 activation leads to decrease in HR, conduction and force (bradycardia)
Muscarinic agonist effects on the endocrine glands
M3 increase secretion of lachrymal, tracheobronchial, salivary, digestive, sweat glands
muscarinic agonist effect on the smooth muscles
M3 increases contraction (M2 inhibit relaxation)
muscarinic agonist effect on sphincters
M3 relaxation
muscarinic agonist effect on CNS
-not all muscarinic agonist able to access CNS
-CNS effects mainly mediated by M1 receptors
-produce tremor, hypothermia, increased locomotor activity, improved cognition
cholinoceptors agonist (muscarinic agonist)
acetylcholine
methacholine
carbachol
bethanecol
muscarine
pilocarpine
muscarinic agonist (mushroom poisoning) PSNS
-bradycardia
-nausea, cramps, vomiting, diarrhea
-bronchoconstriction
-salivation
-visual disturbances
muscarinic agonist (mushroom poisoning) SNS
sweating
-hypotension: uninnervated muscarinic receptors in blood vessel endothelium cells mediating vasodilation via NO
xerostomia
-dry mouth, cottonmouth
-pilocarpine is used for the treatment of xerostomia that
follows head and neck radiation treatments (M3 receptor)
pilocarpine hypofunction of salivary glands
xerostomia and sjogren syndrome
sjogren’s syndrome
-an autoimmune disorder occurring primarily in women
-secretions from the salivary glands are reduced
Pilocarpine is useful in increasing secretions
clinical use of pilocarpine
open-angle glaucoma; dry mouth due to hypofunction of salivary
glands e.g. Sjogren’s or cancer radiotherapy (“xerostomia”)
clinical use of methacholine
Provocative test for hyperreactive airways
clinical use of bethanechol
GI stimulation or treatment of urinary retention
clinical use of carbachol
ocular (surgery, glaucoma)
muscarinic receptor agonist side effects
-PSNS effects such as DUMBBELS
-SNS effects sweating
-Use with caution in patients with asthma, coronary insufficiency, or peptic ulcer
-Cardiovascular
-Respiratory
