organic chem Flashcards
structure of tropane
- fused bicyclic heterocycle
- contain basic N
- alkaloid
properties of tropane
- rapidly absorbed by mucous membrane
- paralyse peripheral ends of sensory nerves by blocking neuronal membrane ion channels
physicochemical properties of cocaine
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
doing questions about ‘which is more soluble’
basically j convert and see how much of the drug is in 1mL, more means more soluble
analgesic properties of cocain
- 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
SE of cocaine
allergy, addiction, withdrawal, tissue irritation, poor stability in aq solution
structural modifications to cocaine
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
characteristics of procaine
- 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)
essential components of cocaine-derived local anaesthetic
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)
ideal characteristic for local anaesthetic
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
organic chem of morphine
- 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
organic chem of codeine
- hydroxyl group of morphine converted into 3-O-methyl ether
- effectively decrease cough centre -> raise threshold for sensory cough impulses
other morphine derivatives
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
types of synthetic opioid drugs
1) pentazocine
2) pethidine
3) fentanyl
4) alfentanil, remifentanil
5) tramadol
pentazocine
1) modifications
- ether bridge removed from morphine
- cyclohexene ring replaced by simple methyl group
2) general
- good analgesic, non additive
- can induce withdrawal symptoms