Cocaine Flashcards
What arethe effects of psychostimulants?
- Alertness, wakefulness, and
locomotion
What are stimulants?
- Psychoactive drugs producing a
temporary increase in mental function
Name some psychomotor stimulants
Cocaine, amphetamines, caffeine, nicotine
Describe crack cocaine
Surge of ‘crack’ cocaine use in the
80’s described by many as an
epidemic
Describe the chemistry of cocaine
- Isolated as a water soluble HCl salt (cocaine HCl)
- Administered by oral, IV, or intranasal routes
- Can be recrystallized as a free base structure
- Can be precipitated by heating with baking soda
- ‘Crack’ cocaine
- Freebase and crack cocaine delivered by inhalation
Describe cocaine pharmacokinetics
Inhalation (smoking) or intranasal (snorting)
result in rapid access to the CNS.
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
Describe BBB permeability of cocaine
Cocaine is amphipathic– meaning it has both hydrophilic and lipophilic nature
Inhalation and intranasal admin both result in rapid uptake into brain and
pronounced psychoactive effects
Describe cocaine effects
Euphoria
Dysphoria
* anxiety
Psychosis
* Paranoia
* Formication
Describe psychomotor stimulation
Cocaine
administration results in marked locomotor
hyperactivity.
Cocaine administration results in stereotyped
behaviours. Common stereotypies include head
bobbing, pacing, repetitive rearing, excess
grooming.
Comparable effects in humans include
compulsive activities such as obsessive
cleaning, sorting, organizing.
Describe cocaine in animal models
Cocaine administration causes
hyperactivity in rodents – simple
measurement of intoxication
- Animals will self-administer to the
point of personal neglect, anorexia,
and increased mortality
Describe cocaine mechanism
- Cocaine is an SNDRI (serotonin, norepinephrine, and
dopamine reuptake inhibitor). - Cocaine blocks neurotransmitter reuptake such as at the
dopamine transporter (DAT). - Also causes decrease in monoamine synthesis through
presynaptic autoreceptors. - At elevated doses cocaine blocks Na+ channels and can
be used as a topical anaesthetic.
Describe tolerance
- Cocaine tolerance develops acutely and transiently
- Intermittent use produces sensitization rather than tolerance
- In animal models:
- 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 (esp.
amphetamines)
Describe cocaine withdrawal
- Three phases observed in binge users of cocaine:
- 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
Describe cocaine crash
- Many of the effects of withdrawal may in fact be psychological rather than physiological
as we cannot demonstrate dependence in animals - Acute withdrawal effects of a crash:
- Dysphoria, agitation, anxiety, and depression
- Gives way to fatigue after brief period (may be a few hours)
- Exhaustion results in hypersomnolence (prolonged sleep)
- Sleep can be interrupted by brief periods of waking and hyperphagia
Describe dysphoric syndrome symptoms
Gradual onset of a dysphoric syndrome – boredom, anergia, anhedonia, anxiety, and
increased craving
