Pharmacology - chapter 4 - Cholinergic agonists Flashcards
In Ach synthesis Acetyl CoA is supplied by?
the mitochondria
rate-limiting step in Ach synthesis?
uptake of choline by sodium/choline co-transporter
What drug inhibits the Na/Choline co-transporter?
Hemicholonium
How is Ach stored?
In the vesicles of presynaptic neurons, together with ATP and proteoglycans
Degradation of Ach occurs…. ?
in the synaptic cleft by acetylcholinesterase and butyrylcholinesterase in plasma
What is muscarine?
an alkaloid present in certain poisonous mushrooms
Locations of muscarinic receptors?
Ganglia of peripheral nervous system and on effector organs such as smooth muscle, brain, heart, exocrine glands etc..
What kind of G-protein are M1 and M3 receptors coupled with?
Gq - protein that activates Phospholipase C
Pirenzepine … ?
is a tricyclic anticholinergic drug that inhibit M1 muscarinic receptors
Darifenacin is … ?
a competitive muscarinic blocker with affinity for M3 receptors. Used for treating overactive bladders.
One action that limits the clinical usefulness of direct acting cholinergic agonists?
They show little specificity
Bethanecol … ?
have strong muscarinic activity. Primarily working on intestinal motility and tone, and on the detrusor muscle of the bladder. Used in post-partum urinary obstruction.
Carbachol?
have both nicotinic and muscarinic actions. Profound effects on cardiovascular and GI systems. Used as miotic agent to treat glaucoma.
Pilocarpine.. ?
Muscarinic activity. One of the most postent stimulators of secretions(secretagogue), and therefor used to treat xerostomia and Sjøgrens yndrome. Stable to AChE.
Pilocarpine in glaucoma?
drug of choice in the emergency lowering of intraocular pressure of both open-angle and closed-angle glaucoma. Mechanism: opens the trabecular meshwork around the canal of schlem.
Indirect-acting cholinergic agonists?
work by inhibiting Acetylcholinesterases
two broad classes of AChE inhibitors?
short acting and long acting
Edrophonium.. ?
short-acting AChE inhibitor used in the diagnosis of myasthenia gravis. Duration of action is 10-20 minutes.
antidote in a cholinergic crisis?
atropine
Physostigmine…?
Intermediate-acting indirect inhibitor of AChE. work on both muscarinic and nicotinic receptors, as well as the NMJ. Also used in treatment of anticholinergic overdoses with atropine, phenothiazines and trycylic antidepressants.
Neostigmine.. ?
Synthetic compound. More polar and therefor absorbed poorly from the GI-tract. Used to stimulate the detrusor muscle and as antidote for tubocurarine poisoning.
donepezil, rivastigmine and galantamine are used to treat…?
Alzheimer disease
What is the pathomechanism regarding ACh in Alzheimer?
Loss of cholinergic neurons in the nucleus basalis of maynert
Echothiophosphate..?
Bind covalently to a serine -OH group at the active site of AChE.
What is “aging”?
When irriversible AChE inhibitors bind to AChE, the enzyme slowly loses an alkyl group, rendering it useless
Pralidoxime..?
reactivate inhibited AChE. This must occur before aging has happened
Pralidoxime and CNS?
naut. Pralidoxime cannot penetrate BBB.
AChE inhibitors are typically associated with ………. bowel activity
AChE inhibitors are typically associated with increased bowel activity
what is cycloplegia?
paralysis of the ciliary muscle with problem focusing on near objects.
which one is more toxic in humans, parathion or malathion?
Parathion
Describe the difference in the molecular structure of neostigmine and physostigmine?
Neostigmine is a quarternary(charged) substance and cannot enter CNS
Physostigmine is a tertiary(uncharged) substance and readily enters CNS
