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Brought to you by:
Stephanie Andrus,
Kimberly Bernosky
and Steve Marshall
General Effects of
Psychomotor Stimulants:
• Increase in behavioral and motor activity
• Increase in alertness and disruption of sleep
• Pupil dilation, shift in blood flow from skin and
organs to muscle, increased body temp.
• Increase in blood pressure and heart rate
• Increased O2 and glucose levels in the blood
• Side effects of anxiety, insomnia and irritability
• Effects synaptic action of dopamine, serotonin &
Forms of Cocaine
• Coca leaves contain 0.5-1% active ingredient of
cocaine (benzomethylecognone)
• Coca paste contains 60-80% cocaine, then is
treated with HCl to produce H2O soluble salt.
One line of cocaine = 25 mg
• This salt is injectable, but decomposes with heat
• Freebase (crack cocaine) is not H2O soluble, but
it is soluble in alcohol, acetone & ether.
• Freebase is relatively heat tolerant, so it can be
smoked. One dose of crack = 250–1000 mg
Pharmacokinetics of Cocaine: Absorption
• Absorption through mucous membranes
(snorting): Cocaine’s vasoconstrictive property
limits its own absorption (20-30% absorbed).
Peak reached in 30-60 minutes
• Inhalation of freebase smoke:
Onset of effect in 8-10 seconds.
6-32% reaching plasma.
Peak plasma levels reached at 5 minutes,
persisting for 30 minutes.
• Intravenous Administration:
Onset of effect in 30-60 sec
Pharmacokinetics of Cocaine:
Distribution & Metabolism
• Penetrates BBB rapidly, initial brain
concentration far exceeds plasma concentration
• Removed slowly from brain
• Half-life in plasma = 30-90 minutes
• Rapid enzymatic breakdown
• Detectable for 12+ hrs after use (metabolites
detectable up to 2 weeks after use)
• Freely crosses placental barrier
Neurotransmitter Actions
of Cocaine
• Potentiates synaptic action due to actively blocking
the reuptake of DA, NE & serotonin
• Exerts inhibitory effect on postsynaptic dopamine
• Blocks the presynaptic transporter protein for DA
• Increases levels of DA at the synaptic cleft, creating
a euphoric sensation
• Serotonin binding provides additional reinforcement
Physiological Effects of Short-term LowDose Cocaine Use
• Low dose is hard to maintain due to
increasing tolerance (progressively higher
doses needed)
• Appetite repression
• See Slide 2: General effects of psychomotor
stimulants (increased BP, HR, body temp
Psychological Effects of Short-term
Low-dose Cocaine Use
Euphoria, giddiness, boastfulness, selfconsciousness (lasting 30 minutes) then mild
euphoria, anxiousness (lasting 60-90 minutes)
Then cocaine craving & rebound depression
Eventually, loss of coordination, tremors &
Increased interest in sex & increased sexual
Effects of Long-term
High Dose Cocaine Use
• Toxic Paranoid Psychosis – anxiety, sleep
deprivation, hypervigilance, paranoia,
• Hyperreactivity, impulsiveness, aggression,
homicidal tendencies
• Withdrawal can result in hallucinations
Treatment of Cocaine Addiction
• Obstacles – rewarding nature of cocaine,
tendency towards relapse, presence of other
• Areas of Need – antiwithdrawal agents,
anticraving agents (blocking dopamine
receptors), treatment of comorbid disorders
• New types of treatment – ritalin & tricyclic
Mechanism of Action
CNS effects are caused by release of NE
and DA from presynaptic storage sites in
the nerve terminals, increasing the
amounts available at the postsynaptic
receptor (see attached Figure 7.2, page
186 in the text)
Pharmacological Effects
• Response intensity and duration varies w/type of
drug, dose & route of administration
• Low dose: typical psychomotor stimulation
• Moderate dose: tremors, insomnia, agitation,
increased respiration
• Continuous high doses: repetitive activity,
aggression, delusions, anorexia
• Detectable in urine for 48 hours
Analogous to crack cocaine
Highly abused illicit substance
Easily synthesized from obtainable chemical
Methamphetamine HCl is used orally, IV & by
snorting, but breaks down at the temperatures
needed for smoking
• ICE does not break down at these temperatures,
so it is smoked.
• Absorption through lungs & mucous membranes
can be faster than IV administration of Meth. HCl
ICE: Pharmacokinetics
• Near immediate absorption into plasma
with additional absorption over the next
four hours
• Half-life ≈ 12 hours (intense, persistent
drug action)
• 60% slowly metabolized in the liver
• Metabolized & unmetabolized ICE
excreted through kidneys
ICE: Effects & Toxicity
• Effects are nearly indistinguishable from those of
• Repeated high doses result in long-lasting,
irreversible decreases in DA and serotonin in the
• Change in sleep patterns, depression,
movement disorders, sexual dysfunction &
schizophrenic psychoses can result from these
chemical changes
• Fatalities occur in cases of high cardiac toxicity,
resulting in pulmonary edema or heart failure
Behavioral Stimulants
• Differ from amphetamines in that they lack
the basic amphetamine nucleus
• Have similar effects to amphetamines
• Include ephedrine (ma-huang) which is
used among athletes as a stimulant and is
found in some OTC weight loss treatments
Behavioral Stimulants:
Used in Weight Loss
• Sibutramine (Meridia)
• Serotonin and norepinephrine reuptake inhibitor
• Does not appear to have properties lending it to
compulsive misuse
• Causes significant increases in heart rate and
blood pressure, limiting its use
• Orlistal (Xenical) can be used as an alternative
Treatment of ADHD:
Non-Amphetamine Behavioral Stimulants
• Methylphenidate (Ritalin)
• Used in treatment of ADHD to calm hyperactivity
and improve attention (prescribed in 90% of
• Half-life ≈ 2-4 hours
• Variable absorption rates, but generally a rapid
onset with short duration (multiple
administrations needed over the course of a
Treatment of ADHD:
Non-Amphetamine Behavioral Stimulants
• Methylphenidate (continued)
• No currently available susatained-release
• Low-abuse potential
• Increases syn. conc. of DA by blocking the
presyn. DA transporter (like cocaine) and
increases the release of DA (like
Treatment of ADHD:
Non-Amphetamine Behavioral Stimulants
• Pemoline (Cylert)
• Structurally dissimilar to amphetamine &
• Decreases ADHD symptoms by potentiating
dopaminergic transmission
• May cause hepatitis-like liver damage
• Modafinil
• Potentiates glutamate neurotransmission, and inhibits
activity of GABA neurons in the nucleus accumbens
and cerebral cortex
• Used in treatment of ADHD, narcolepsy and causes
cognitive improvement in Alzheimer’s patients
Treatment of ADHD:
• Dextroamphetamine (Dexedrine) and an
amphetamine mixture (Adderall)
• A one-time dose of Adderall is similar in
effect to the typical two daily doses of
Treatment of ADHD
• Stimulants improve behavior and learning in 6080% of correctly diagnosed children
• 10-30% of ADHD individuals are treatment
resistant (little to no response to treatment)
• Alternatives: antidepressants like fluoxetine
(Prozac), buproprion (Welbutrin) and buspirone
• With antidepressants, rare cases of high cardiac
toxicity have been found