Cocaine

Question 1

What arethe effects of psychostimulants?

Answer 1

• Alertness, wakefulness, and
  locomotion

Question 1

What are stimulants?

Answer 1

• Psychoactive drugs producing a
  temporary increase in mental function

Question 2

Name some psychomotor stimulants

Answer 2

Cocaine, amphetamines, caffeine, nicotine

Question 3

Describe crack cocaine

Answer 3

Surge of ‘crack’ cocaine use in the
80’s described by many as an
epidemic

Question 4

Describe the chemistry of cocaine

Answer 4

• 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

Question 5

Describe cocaine pharmacokinetics

Answer 5

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

Question 6

Describe BBB permeability of cocaine

Answer 6

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

Question 7

Describe cocaine effects

Answer 7

Euphoria

Dysphoria
* anxiety

Psychosis
* Paranoia
* Formication

Question 8

Describe psychomotor stimulation

Answer 8

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.

Question 9

Describe cocaine in animal models

Answer 9

Cocaine administration causes
hyperactivity in rodents – simple
measurement of intoxication

• Animals will self-administer to the
  point of personal neglect, anorexia,
  and increased mortality

Question 10

Describe cocaine mechanism

Answer 10

• 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.

Question 11

Describe tolerance

Answer 11

• 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)

Question 12

Describe cocaine withdrawal

Answer 12

• Three phases observed in binge users of cocaine:
• Binge use refers to episodic use for extended periods (hours or days)
  without interruption (or sleep)

1. Crash (15-30 minutes following final dose)
2. Withdrawal (hours-days after final dose)
3. Extinction

Question 13

Describe cocaine crash

Answer 13

• 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

Question 14

Describe dysphoric syndrome symptoms

Answer 14

Gradual onset of a dysphoric syndrome – boredom, anergia, anhedonia, anxiety, and
increased craving

Question 15

Describe cocaine toxicity

Answer 15

• Acute overdose results from several main effects:
• Reduced seizure threshold
• Due to general increase in neurotransmitter release
• Cardiovascular effects
• Increased heart rate and blood pressure can increase risk of stroke, cerebral hemorrhage, tachycardia
  and arrhythmia
• Hyperthermia