pmcol 305 cocaine

3 main consumable forms of cocaine

1. coca leaves

2. cocaine hydrochloride

3. free-base cocaine = crack

how is insufflation of cocaine absorved + bioavailibility

mucous membranes, 35%

dissolution of cocaine creates

HCl → nasal structure corrosion

onset and peaks of cocaine insufflation

onset= 3-5 min

peaks: bimodal at 10 and 45 min

duration of cocaine being snorted

30-40 min

inhalation of cocaine (onset and duration)

onset: 6-10sec

duration: 5-30 minutes but intense

why is cocaine designed to be smoked

cocaine HCl pyrolyzes (breaks down) before it vapourizes @195C

crack vapourizes at 98C

injection of cocaine onset and duration

onset: 10-15 sec

duration 10-20 min

what is cocaine primarily metabolizzed by

CYP3A4

major metabolite of cocaine

benzoylecgonine

bhenzoulecgoning

cocaine metabolite in which 40% is spontaneously produced by hydrolysis within 4 hours of use

ecgonine methylester

liver/plasma esterases generated

combines with alcohol to make cocaethylene metabolite

what is a by product of pyrolysis when cocaine is administered with alcohol

methylecgonidine

cocaine is detectable in urine up to how many days and how is it excreted

4 days, 2 weeks in chronic users ; kidneys

percentage of cocaine degraded by esterases vs hydrolysis

30-50% vs 40%

acute effects of cocaine

sympathommimetic

when your blood vessels are constricted are you more likely to form blood clots or no

yes

cocaine in blocking Na channels

anesthetic, blocks NT, no pain

in heart = dysthythmias

excess what result in sympathomimetic effects in cocaine

DA, 5HT, NE, EP

6 effects of excess NT from cocaine

inc HR, BP

anorexia, insomnia, agitation, hyperthermia

brain regions affected during cocaine use + how

basal ganglia: repetitive compulsive movements

PFC: problem solving, plannning, social

NAc: reward

medulla: respiratory and circulatory failure

excess DA here

mechanisms of cocaine

blocks DAT = prolonged stimulation

5HT excess underlies what

mood, sleep, appetite, temp

NE excess underlies what

sympathommimetic effects

VTA sensitivity to Glu and reward

formification

adverse effect of acute cocaine use

feeling of bugs crawling

acute cocaine use on GIT

inc. acute infections in GIT, dec. blood flow = tissue death

cocaine injection sites cause what

allergic reactions. HIV

why is cocaine in combination with alcohol so bad

altered metabolism to make cocaethylene = potent vasoconstrictor

how do scientists know that not only DA was involved in cocaine use

exclusive DAT blockers do not mimic cocaine effects

cardiovascular effects of cocaine due to

blockages of NE (hypertension) + EP (hear rate) reuptake

tolerance of cocaine

reduced euphoria due to dec DA, and increase DAT efficiency

D1 and D2 are internalized rapidly

after 2 weeks of D1 and D2 receptor internalizetion, what might be upregulated

D1

altered opioid-ergic signaling results in what during cocaine use (tolerance)

striatal dynorphin expression is induced

what type of tolerance does cocaine cause

reverse tolerance: hyperthermia, convulsions, sterotyped movments

intermittent use of cocaine is associated with

strong behavioural sensitization, increased locomotor activity

long term DAT efficiency (increase, decrease stay the same) after cocaine use

increase

are cocaine withdrawls bad

no they are mild when compared to others

dependence of cocaine

mild physical dependence, intense psychological

but most do not become addicted

ways to treat acute cocaine intoxication

1. benzos + nitroglycerine

2. supply heart with oxygen

3. ice bath

   1. gutyrylcholinesterase

benzos for cocaine

control agitation and over stimulation

decrease BP, HR by decreasing NT release

nitroglyverine on cocaine

evokes NO production, counteracts vasoconstriction

supply heart with oxygen

butyrylcholinesterase

iv treatment cause paid elimation of cocaine

longterm consequence of cocaine use

cardiovasular disease → arryhtmia due to inhib Na

constricted vessels = organ death

psychosis = brain ageing

rhabdomyolysis break down muscle du to hyperthermia

myoglobinurina + kidney failure

increase blood coagulation, decreae fibrinolysis = increase stroke risk