organic chem

Question 1

structure of tropane

Answer 1

• fused bicyclic heterocycle
• contain basic N
• alkaloid

Question 2

properties of tropane

Answer 2

• rapidly absorbed by mucous membrane
• paralyse peripheral ends of sensory nerves by blocking neuronal membrane ion channels

Question 3

physicochemical properties of cocaine

Answer 3

pKa 8.6 (basic)

• higher than physiological pH so will be < 50% protonated
  ** if drug is > 50% protonated then can permeate neuronal membrane
  ** if drug is < 50% protonated then need to be +ve charge to bind to Na+ ion channel

Question 4

doing questions about ‘which is more soluble’

Answer 4

basically j convert and see how much of the drug is in 1mL, more means more soluble

Question 5

analgesic properties of cocain

Answer 5

• permeate across neuronal membrane -> block Na channel -> prevent generation of action potential
• essential components

1) aromatic carboxylic acid ester
2) basic amino group
3) lipophilic hydrocarbon ring

Question 6

SE of cocaine

Answer 6

allergy, addiction, withdrawal, tissue irritation, poor stability in aq solution

Question 7

structural modifications to cocaine

Answer 7

1) benzoyltropine

• remove carboxymethyl group -> eliminate addiction liability

2) benzocaine

• lesser local and systemic toxicity, stronger local anesthetic
• lower water solubility (lone pair of e- in N delocalise into benzine ring -> less able to form H bond)

3) procaine

• simplification: indole ring open up, carbonyl group inserted

Question 8

characteristics of procaine

Answer 8

• less allergenic
• more stable in water (ortho methyl group block access of water, amide group)
• good local anaesthetic agent (longer duration of action than benzocaine)

Question 9

essential components of cocaine-derived local anaesthetic

Answer 9

1) lipophilic portion

• facilitate permeation
• essential for LA activity

2) intermediate chain

• ester/amide linkage + 1-3 C chain
• amide group more resistant to hydrolysis -> longer duration of action

3) hydrophilic portion

• sec/tert amine or N in heterocycle
• amide group basic and ionisable to give cation

(LA w higher lipid solubility + lower pKa -> faster onset and lower toxicity cuz permeate quickly and higher percentage is unionised)

Question 10

ideal characteristic for local anaesthetic

Answer 10

1) usually basic

• good balance between lipophilicity and pKa

2) reversible
3) selective for sensory neuron, no effect on motor neuron
4) rapid onset, sufficient duration of action
5) chemically stable when sterilised
6) no systemic toxicity, wide margin of safety
7) compatible with co-administered drugs
8) cheap

Question 11

organic chem of morphine

Answer 11

• basic structure + weak acid phenolic OH
• metabolised in body to

1) morphine-3-O-glucuronide: more effective, longer lasting than morphine
2) morphine-6-O-glucuronide: antagonistic to morphine

Question 12

organic chem of codeine

Answer 12

• hydroxyl group of morphine converted into 3-O-methyl ether
• effectively decrease cough centre -> raise threshold for sensory cough impulses

Question 13

other morphine derivatives

Answer 13

1) pholcodeine

• effective and reliable antitussive
• SN2 nucleophilic substitution: alkylation of morphine w N-(chloroethyl)morphine

2) dihydrocodeine

• reduced form of codeine (double bond)

3) diamorphine/heroin

• diacetate of morphine
• increased lipophilic character, highly addictive and hypnotic

Question 14

types of synthetic opioid drugs

Answer 14

1) pentazocine
2) pethidine
3) fentanyl
4) alfentanil, remifentanil
5) tramadol

Question 15

pentazocine

Answer 15

1) modifications

• ether bridge removed from morphine
• cyclohexene ring replaced by simple methyl group

2) general

• good analgesic, non additive
• can induce withdrawal symptoms

Question 16

pethidine

Answer 16

1) modifications

• only benzene ring and piperidine systems required

2) general

• less potent but less constipating than moprhine
• short term analgesia

Question 17

fentanyl

Answer 17

1) modification

• 4-anilino rather than 4-phenyl-piperidine structure

2) general

• higher lipophilicity = better transport and absorption = way more potent
• rapid acting

Question 18

alfentamil, remifentanil

Answer 18

• rapid acting
• used during operation

Question 19

tramadol

Answer 19

• enhanced serotonergic and adrenergic pathway w few opioid side effect

Question 20

methadone

Answer 20

• diphenylpropylamine rather than piperidine structure
• less euphoric, longer duration of action

Question 21

other morphine derivatives

Answer 21

have agonistic-antagonistc properties

1) nalbuphine

• mixed agonist-antagonist due to charged N-methyl group
• similar agonist activity as moprhine but lesser SE and less abuse

2) naloxone

• potent antagonist at opiate receptors
• used for opiate poisoning

3) naltrexone

• potent antagonist at opiate receptors