Cocaine

Question 1

history of cocaine

Answer 1

Quechua called it kuka - was used to increase stamina and reduce altitude sickness.

Europeans that invaded south america discovered cocaine and it was first described by a european in 1565.

it was isolated from coca lead in 1855 and its history and use described by freud in 1884. same year it was identified to have local anaesthetic actions

Was used in tonics such as vin mariani (also contained alcohol, cocaine: 200mg/L)

Question 2

Cocaine vs crack

Answer 2

cocaine is hydrochloride salt that is commonly snorted with 80% bioavailability. can also be injected. Tmax = 45m

crack is the freebase of cocaine. bicarbonate neutralises the hydrochloride salt of cocaine. it is smoked due to low aqueous solubility with bioavailability of 60%. Tmax = 6m. much shorter duration of action 5-10 min vs 30 min

Question 3

Mechanism of action

Answer 3

Nav channel inhibition for LA effects.

DAT and NET blockade increase dopamine and noradrenaline levels in CNS and PNS

Question 4

effects and withdrawal

Answer 4

hyperstimulation, reduced fatigue, alertness.

vasoconstriction from NA at a1-AR, dilated pupils, hyperthermia, increased HR and BP

tolerance can occur. repeated use can reduce duration of highs.

binges are common, leading to increased irritability, restlessness and paranoia (possible psychosis). can cause cardiovascular complications (arrhythmia, HA, stroke), reduced appetite, and septum deterioration.

withdrawal causes dysphoria, depression, anxiety, pain, cravings

acute overdose deaths occur mostly through myocardial infarction.

Question 5

use with alcohol

Answer 5

use with alcohol causes the generation of cocaethylene through the action of carboxylesterase1.

more euphoric and cardio toxic than cocaine

Question 6

therapeutic alternatives

Answer 6

none approved by FDA

vaccines have been attempted since 1990 - would bind to cocaine and prevent its activity.

Humanised antibodies have been produced for acute detox.

CES1 has been produced. an enzyme based on butyrylcholinesterase to hydrolase cocaine.

Question 6

Prevalence of use

Answer 6

approx 10% of responders report having use cocaine. crack use is much lower in UK.
deaths.

1-2/100000 deaths a year in the USA. 2.2m regular users in the USA. 23m worldwide.