Topic 19: Cocaine Flashcards
What are stimulants, psychostimulants, and psychomotor stimulants?
psychoactive drugs producing a temporary increase in mental function
alertness, wakefulness, and locomotion
cocaine, amphetamines, caffeine, nicotine
What is cocaine?
psychoactive alkaloid isolated from the leaves of the coca shrub Erythroxylum coca
primary psychoactive component has moderate bioavailability by oral administration
cocaine is sensitive to acid hydrolysis
coca leaves traditionally chewed with lime to decrease acid hydrolysis in the GI
What is the history of cocaine?
popularized in Europe in the 19th century with development of various alcoholic tonics
Coca-cola was first developed as a non-alcoholic alternative to tonic wines due to the growing temperance movement in the USA
recreational use of cocaine became re-popularized in the 70s-90s
What is the chemistry of cocaine?
isolated as a water soluble HCl salt (cocaine HCl): administered by oral, IV, or intranasal routes, susceptible to breakdown by heating
can be recrystallized as a free base structure: extraction with an organic solvent, highly dangerous as solvents are hard to remove from finished product
can be precipitated by heating with baking soda: “crack” cocaine, heating leaves distinct traces that can be identified in urine
freebase and crack cocaine delivered by inhalation
What is the purification of illicit cocaine?
cocaine is purified by acid-base extraction
illicit cocaine is purified by partially drying leaves
leaves are coarsely chopped, mixed with an alkali (powdered cement or lime)
alkali mix is soaked in solvent (gasoline) for 24 hours and pressed to create a crude extract
free base cocaine is phase extracted by neutralization with an acid (battery acid)
cocaine is then precipitated with caustic soda (NaOH)
yields a dried paste of 40-60% pure cocaine that is reprocessed and recrystallized at specialized labs after sale
What are the pharmacokinetics of cocaine?
inhalation (smoking) or intranasal (snorting) result in rapid access to the CNS
half-life circulation ~30-90 minutes
metabolized by esterases, CYP450 in liver
cocaethylene is an active metabolite formed in the presence of alcohol - longer lasting than cocaine and greater cardiotoxic effects
methylecgonidine is produced by pyrolysis (heating) of cocaine and is detectable in urine
What is the blood brain barrier permeability of cocaine?
cocaine is amphipathic - meaning it has both hydrophilic and lipophilic nature
subsequently cocaine is very rapidly absorbed across the BBB and measurement of cocaine in circulation does not effectively convey the psychoactive levels
inhalation and intranasal admin both result in rapid uptake into brain and pronounced psychoactive effects
rapid uptake into brain and short duration of “high” (5-30 minutes) thought to contribute to addictive potential
What are the euphoric effects of cocaine?
euphoria
increased alertness: insomnia
increased energy: hyperactivity
increased self-confidence: inflated self esteem
increased sociability: pressure of speech
heightened sexual interest/performance
motor stereotypes
anorexia
What are the dysphoric effects of cocaine?
irritability, hostility, anxiety: anger, verbal aggression
psychosis: paranoia, formication
impulsivity
increased heart rate
increased blood pressure
hyperthermia
seizures
stroke/intracranial haemorrhage
What is psychomotor stimulation in cocaine use?
stimulant effects of cocaine are readily demonstrable in animal models, cocaine administration results in marked locomotor hyperactivity
cocaine administration results in stereotyped behaviors, common stereotypes include head bobbing, repetitive rearing, excess grooming
comparable effects in humans include compulsive activities such as obsessive cleaning, sorting, organizing
What are animal models of cocaine?
animal models will rapidly acquire self-administration of cocaine
cocaine administration causes hyperactivity in rodents - simple measurement of intoxication
animals will self-administer to the point of personal neglect, anorexia, and increased mortality
What is the mechanism of cocaine?
cocaine is an SNDRI (serotonin, norepinephrine, and dopamine reuptake inhibitor)
cocaine blocks neurotransmitter reuptake such as at the dopamine transporter (DAT)
this leads to accumulation of neurotransmitters in the synapse and excessive downstream signalling
also causes decrease in monoamine synthesis through presynaptic autoreceptors
at elevated doses cocaine blocks Na+ channels and can be used as a topical anaesthetic
What is cocaine tolerance?
cocaine tolerance develops acutely and transiently
subjective and cardiovascular effects develop tolerance quickly
intermittent use produces sensitization rather than tolerance
What are animal models of cocaine tolerance?
continuous infusion via minipump results in tolerance to the effects of cocaine
daily use (intermittent) sensitizes the psychomotor and reinforcing effects
both animals and humans show cross-sensitization to other stimulants (especially amphetamines)
What are the three phases of cocaine withdrawal observed in binge users?
binge use refers to episodic use for extended periods (hours or days) without interruption (or sleep)
- Crash (15-30 minutes following final dose)
- Withdrawal (hours-days after final dose)
- Extinction
