Cocaine Flashcards
Cocaine
- was used as anesthetic (still is rarely in eye surgeries)
- Freud popularized it
- used to be part of OTC remedies and drinks
- natural product of the coca plant (grows in south america)
- locals chew leaves mixed with very basic substances (lime to increase extraction)
- cocaine=benzoylmethylecgonine
- smuggled by “mules”
Cocaine production
-leaves dumped in makeshift trench
-500 kg for leaves for 1 kg paste
-kerosene or gasoline added to extract active ingredients (stomp on it)
-after drying (so gasoline evaporates) obtain
paste (about 75% cocaine but heavily contaminated with solvent)
-workers health issues and paid in cocaine paste (dependency and neurological issues)
Cocaine hydrochloride
- refinement of paste can result in a salt
- easier to transport (polar, soluble in water)
- often cut with other white powders to max profit (eg milk, baby laxative, lidocaine or benzococaine)
Consequences of cutting
- eg levamisole
- anti-helminthic drug given to cattle (shown to mildly increase DA)
- purpura leading to necrosis of tissue due to vasculitis
Administration
- Insufflation (snorting): cocaine hydrochloride, onset 3-5 min, lasts 30-40 min, absorption through mucous membranes, can lose cartilage in chronic uses
- Intravenous injection: onset 15-30 sec, effects last 10-20 min, vasoconstriction & necrosis if goes into artery (prevention of NA uptake and nitric oxide production)
- smoking: freebase & crack cocaine, onset 6-10 secs, intense but short duration, repeated dose
Freebase cocaine
-hydrochloride burn before produces vapours so converted into freebase form when being smoked
-dissolve cocaine hydrochloride in water, add base (usually ammonia), extract with ether (flammable), evaporate to dryness
-hard to get ether, dangerous to make
Coc-H+Cl- + NH3 -> Coc + NH4Cl
Crack cocaine
-crackles when smokes
-dissolve low purity cocaine in water, add sodium bicarbonate (baking soda) to neutralize hydrochloride, heat, freebase will precipitate and can be purified (less pure than true freebase)
Coc-H+Cl- + NaHCO3 -> Coc+H20+CO2+NaCl
Metabolism
- metabolized by carboxylesterase enzymes in blood and liver
- benzoylegonine: major metabolite, appears within 4 hours of using cocaine t1/2 6hrs
- cocaethylene: if taken with alcohol (damaging it heart tissue, may enhance euphoria)
- methylecgonidine: cocaine was smoked
- ecigonidine methyl…: minor metabolite no matter what form
Psychological Effects
-extreme euphoria, energy, hyperactivity, hypersexuality, confidence, makes mundane more pleasurable, can develop psychosis
Physiological effects
- local anesthetic actions (blocks sodium channels, prevents nerve conduction)
- sympathetic system is stimulated (due to excess NT in synapse, HR and BP increase, anorexia, insomnia)
Mechanism
- blocks the action of transporter proteins (DAT) that normally remove NTs, get accumulation of DA in synapse thus prolonged stimulation of post synaptic receptors (cocaine binds to DAT and inhibit)
- results in large DA accumulation at the NAcs
- takes a while to resupply sufficient amount of DA (why feel depressed)
- similar effects at NA and 5HT transporters
- DA not entirely responsible for effects
What happens to DAT with chronic use?
- -experiment in notes
- DAT activity increases
- brain adapts by increase number and activity of DAT
- why users may report depressed state b/c have hyperactive proteins that clear dopamine fast, don’t get as much pleasure from everyday things
Damage from Cocaine
- high acute dose can lead to effects on the medulla (respiratory and circulatory failure)
- hyperactivity combined with vasoconstriction can lead to hyperthermia (this can lead to rhabdomyolosis and myoglobinuria leading to kidney failure)
- psychosis in chronic users of high doses
Cardiac effects of Cocaine
- in 1st hour risk of myocardial infarction increases 24 fold
- numerous routes that can kill you eg:
- > NaCL channels damaged so inconsistant rhythms
- > inability to supply sufficient O2 to tissue get infarction
Withdrawal
- fairly mild
- depression most prominent (“let down occurs within 30 minutes after use)
