Drugs Affecting Cholinergic Neurotransmission Flashcards by Megan Carnahan

Which amino acid can be converted to make ACh?

serine

How well did you know this?

Not at all

Perfectly

Which 3 amino acids are involved in ACh metabolism?

Glu, His, Ser

How well did you know this?

Not at all

Perfectly

Muscarinic receptor

identified by the ability of the natural product muscadine to bind to the receptor
7 transmembrane domains, 5 subtypes
all are GPCR
important in drug therapy

How well did you know this?

Not at all

Perfectly

Nicotinic Receptor

identified by the ability of the natural product nicotine to bind to the receptor

How well did you know this?

Not at all

Perfectly

Which 3 amino acids are involved in muscarinic receptor domains?

Asp, Thr, Tyr

How well did you know this?

Not at all

Perfectly

General effects of muscarinic receptor activation

Diarrhea/Defecation
Urination
Miosis/ Constriction of pupil
Bradycardia (slow heart rate)
Bronchonconstriction
Excitation of CNS
Lacrimation
Salivation
Sweating
Abdominal Cramps/GI contraction

How well did you know this?

Not at all

Perfectly

PLC activation (increased IP3, DAG, Calcium, and PKC)
increase congnitive function and secretions
decrease dopamine release and locomotion

How well did you know this?

Not at all

Perfectly

PLC activation (increased IP3, DAG, Calcium, and PKC)
increased smooth muscle contraction and salivary gland secretion

How well did you know this?

Not at all

Perfectly

PLC activation (increased IP3, DAG, Calcium, and PKC)
facilitates dopamine release; augments drug seeking behavior and reward

How well did you know this?

Not at all

Perfectly

Inhibition of adenylyl cyclades and voltage gated calcium channels
decreased heart rate
increased smooth muscle contraction

How well did you know this?

Not at all

Perfectly

Inhibition of adenylyl cyclades and voltage gated calcium channels
facilitates dopamine release, inhibits transmitter release in the CNS

How well did you know this?

Not at all

Perfectly

Which receptors activate phospholipase C

odd numbered/ G alpha Q

How well did you know this?

Not at all

Perfectly

Which receptors are inhibitory and decrease cAMP

Gi/even numbered receptors

How well did you know this?

Not at all

Perfectly

Which receptors decrease voltage gated calcium channels?

Go / even numbered receptors

How well did you know this?

Not at all

Perfectly

What are the issues with using ACh as a drug?

non-selective
minimal bioavailability

How well did you know this?

Not at all

Perfectly

The positive nitrogen on ACh and muscarine is good for forming ionic bonds with receptors but poor for ?

absorption

How well did you know this?

Not at all

Perfectly

Methacholine

used for diagnostic tests
selective for muscarinic vs nicotinic receptors
equipotent with ACh but decreased rate of hydrolysis

How well did you know this?

Not at all

Perfectly

Carbachol

isosteric change to ACH
carbamate is not as easily hydrolyzed as an ester
used in ophthalmics

How well did you know this?

Not at all

Perfectly

Bethanechol

has carbamate and methyl group added on to ACh
used orally for urinary retention

How well did you know this?

Not at all

Perfectly

Pilocarpine

act as muscarinic agonist
natural alkaloid
used opthalmically and orally for dry mouth

How well did you know this?

Not at all

Perfectly

Cevimeline

synthetic muscarinic agonist
used orally for dry mouth

How well did you know this?

Not at all

Perfectly

Alzheimer’s disease

ACh deficiency; progressive degeneration of cholinergic neurons

How well did you know this?

Not at all

Perfectly

AChE inhibitors

indirect ACh agonists
will produce a non specific response
useful for glaucoma treatment- miosis, myasthenia gravis- incr ACh duration of action, Alzheimer’s- slow decline of memory, and to reverse mydriasis or effects of nondepolarizing neuromuscular blocking agents

How well did you know this?

Not at all

Perfectly

Myasthenia gravis

chronic autoimmune neuromuscular disorder
fluctuation weakness of voluntary muscle groups

How well did you know this?

Not at all

Perfectly

In pseudoirreversible inhibitors a carbamate is left on a Ser, what is the speed of hydrolysis ?

slow

Aryl Carbamates

have increased affinity for AChE, making them better inhibitors includes physostigmine, neostigmine, pyridostigmine, and rivastigmine

Order of rate of carbamylation of AChE

carbamic acid esters>methylcarbamic acid esters>dimethylcarbamic acid esters> methyl, ethyl

Neostigmine and pyridostigmine treat

myasthenia gravis

physostigmine treats

open-angle glaucoma

rivastigmine treats

alzheimer’s

Donepezil, Galantamine, and Ambenonium Chloride are?

Non-carbamoylating AChE inhibitors

Can quarternary salts cross the blood brain barrier?

A slower carbamylation leads to slower?

regeneration of AChE

Carbamylating agents may lead to ?

increased cholinergic effects

Irreversible AChE inhibitors

used in as low of a dose as possible used in a lot of insecticides

Symptoms of Organophosphate toxicity

increased GI peristalsis miosis, loss of ocular accomodation, ocular pain rhinorrhea chest tightness and wheezing increased lacrimation, salivation, and sweating bradycardia and hypotension confusion convulsions weakness, muscle paralysis, respiratory paralysis

What combination can reverse anti-AChE toxicities ?

atropine and pralidoxime

Pralidoxime Chloride

antidote to reverse muscle paralysis resulting from organophosphate AChE peticide poisoning it’s oxime has a higher affinity for phosphate as opposed to a hydroxyl group

Muscarinic receptor antagonists block?

muscarinic actions of ACh DUMBELLS

What are the 3 main stimulators of gastric acid release?

ACh, histamine, and gastrin

What are the first line drugs for treatment of COPD?

ipratropium and tiotropium

Alkaloid

nitrogen containing compound that is isolated from natural sources and possesses a pharmacological action

Ing’s Rule of 5

5-6: Agonist 7-8: Partial Agonist >9: Antagonist

When an active site is occupied and the auxiliary site is not used, then the receptor exists in a conformation that produces an?

agonist effect

When both active and auxiliary sets are occupied what kind of effect is produced?

Antagonist effect

Ipratropium, Tiotropium, and Aclidinium Bromide are all?

Bronchodilators quaternary ammonium anticholinergic agents

ACh action at M1 and M3 receptors causes bronchoxxx?

bronchoconstriction

Amino Alcohol Esters (Synthetic Antimuscarinic Drugs)

glyopyrroolate, propantheline, flavoxate, dicyclomine, cyclopentolate, and mepenzolate bromide

Amino Ethers (Synthetic Antimuscarinic Drugs)

diphenhydramine, bentropine, and orphenadrine

Amino Alcohols (Synthetic Antimuscarinic Drugs)

procyclidine, trihexyphenidyl, biperiden

Tropicamide and Tolterodine are ?

Synthetic Antimuscarinic Drugs

All synthetic anti muscarinic drugs are selective for?

the muscarine receptor

Where are nicotinic receptors located?

sympathetic and parasympathetic ganglia

How many ACh binding site are on the extracellular domain of each receptor molecule?

What kind of antagonists are nicotinic antagonists?

competitive

How can you reverse nicotinic antagonists ?

by administering an AChE inhibitor

Skeletal Neuromuscular Blocking Agent

used in anesthesia nicotinic antagonist

Ganglion is blocking agents

orphan drug for treatment of nicotine- responsive psychiatric disorders and nicotine and codein addiction nicotinic antagonist

What structural features do synthetic neuromuscular blocking drugs need

2 quaternary ammonium groups/ tertiary amines spread 10-12 atoms apart

Succinylcholine Chloride

ultrashort duration; depolarizing cannot be reversed by neostigmine used for rapid induction of muscle relaxation administered IV

Pancuronium Bromide

Long duration; competitive don’t use in patients with CAD

Vecuronium Bromide

intermediate duration; competitive

Rocuronium Bromide

intermediate duration; competitive

Atacurium Besylate

intermediate duration; competitive depends on renal elimination

Mivacurium Chloride

Short duration; competitive

Pancuronium Bromide, Vecuronium Bromide, and Rocuronium Bromide are all?

steroid based blocking drugs

Atacurium Beslyate and Mivacurium Chloride are ?

tetrahydroisoquinoline based blocking drugs

Adverse effects of neuromuscular blockers

hypotension, bronchospasm, cardiac disturbances, twitching before relaxation, histamine release