Exam 4 - Lecture 40, Medicinal Chemistry of Muscaranic Antagonist & Neuromuscular Blockers

Question 1

Muscarinic Agonist effects

Answer 1

SLUDGEM

Salivation, Lacrimation, urination, defecation, GI secretion/mortality, Emesis, Miosis or muscle spasm

Question 2

Muscarinic antagonists

Answer 2

Antispasmodics, anticholinergics, antimuscarinic, cholinergic blockers or parasympatholytics

Side effects: Dry mouth, blurred vision, difficulty in urination

Question 3

Atropine

Answer 3

1st muscarinic antagonist, pKa 9.8

2 main uses: bradycardia an preoperative agent to reduce secretion before surgery

Contraindicated in glaucoma

used to decrease muscarinic cholinergic action in case of poisoning by organophosphate nerve agents and insecticides

racemic mixture

Question 4

Scopolamine

Answer 4

greater ability to cross BBB than atropine, has an epoxide in ring allowing that

only (-) form present

pKa ~ 7.6

Question 5

molecules with permanently charged N…

Answer 5

cannot enter BBB

Question 6

molecules without permanently charged N…

Answer 6

can enter BBB

Question 7

peripherally acting Muscarinic antagonists

Answer 7

have quaternary ammonium functional group, not well absorbed from the GI tract.

Primarily used in the treatment of ulcers, and other conditions in which a reduction in gastric secretion and reduced motility of the GI tract is desired

Question 8

centrally acting Anticholinergic agents

Answer 8

lipophilic agents derived from amino alcohols and ethers possessing 3 amine.

readily cross the BBB and proven particularly beneficial in treatment of Parkinson’s disease

Question 9

QNB, quinuclidinylbenzilate

Answer 9

radio labeled QNB instrumental in development of muscarinic receptor labeling technique as well as discovery of subtypes of receptors

used as incapacitating agent by military

Physostigmine, which increases the conc of ACh in synapses and in neuromuscular junctions is antidote

Question 10

Pirenzepine and telenzepine

Answer 10

exhibit high M1 subtype selectivity and reduce gastric acid secretion with fewer side effects than atropine and other less selective agents

Question 11

AFDX-116

Answer 11

selective for cardiac m2 receptors

Question 12

Two subclasses of NM blocker

Answer 12

skeletal neuromuscular blocking agents

ganglionic blocking agents

Question 13

NM blockers therapeutic applications

Answer 13

1st block muscle which produce rapid movements, include muscle of face/eyes/neck

muscle of limbs/chest/abdomen are affected next with diaphragm being affected last

primary use as adjunct in general anesthesia

Question 14

NM blockers side effects

Answer 14

hypotension
bronchospasm
histamine-release
membrane depolarization leading to muscle fasciculations (twitching) and cardiac disturbances

Question 15

Depolarizing NM blocking agents

Answer 15

act by depolarizing the plasma membrane of skeletal muscle fiber, persistent depolarization makes the muscle fiber resistant to further stimulation by ACh

Question 16

Non-depolarizing NM blocking agents

Answer 16

majority of clinically relevant blocks

Act by blocking the binding of ACh to its receptors

Question 17

nAChRs possessed two…

Answer 17

anionic-binding sites, both of which had to be occupied for neuromuscular blocking effect

Question 18

in amino steroids if 3,17 groups are chopped,,,,

Answer 18

then metabolite is inactive. if one is chopped but one remains then it’ll still remain active

Question 19

Hoffman elimination

Answer 19

spontaneous but by reversing ester you prevents it from occurring

Question 20

Metocurine vs d-Tubocurarine

Answer 20

Metocurine 4 fold more potent

Question 21

Tetrahydroisoquioline based

Answer 21

Mivacurium Chloride = shortest acting (double bond O different sides)

Atracurium besylate = intermediate acting (Double bond O, ester same side)

Doxacurium Chloride = longest acting