stimulant drugs part 3 kim edward light, ph.d. professor, college of pharmacy university of arkansas...
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Stimulant DrugsPart 3
Kim Edward Light, Ph.D.
Professor, College of Pharmacy
University of Arkansas for Medical Sciences
Objectives part 3
Discuss prescription amphetamine products and uses.
Discuss other prescription stimulant drugs and their uses and problems.
Discuss use and abuse of cocaine. Identify the differences between cocaine
abuse and methamphetamine abuse. Discuss other illicit stimulants such as khat
and arecoline (betel).
Amphetamine Products
Adderall®
Adderall-XR®
Benzedrine®
Biphetamine®
Dexedrine®
Dexedrine Spansule®
Amphetamine - Uses
Treatment Attention Deficit Hyperactivity Disorder (ADHD) Narcolepsy Obesity
Extended or sustained release to reduce dosing frequency.
Amphetamine - Side Effects
Similar to methamphetamines but more cardiovascular
Abuse often leads to abuse of methamphetamine
Escalating use among college students as “study drug”
Other Stimulant Drugs
Treatment of ADHD Methylphenidate - Ritalin®
Atomoxetine - Strattera®
Treatment of Obesity Phenmetrazine – Preludin®
Phentermine – Fastin®
Fenfluramine - Pondimin®
Treatment of Narcolepsy Modafinil - Provigil® Methylphenidate - Ritalin®
Methylphenidate Ritalin®
Treatment of narcolepsy and ADHD Onset of action within one hour Duration of action is less than 4 hours.
Sustained or extended release preparations.
Used as a “study drug” Side effects similar to methamphetamine
and amphetamine May lead to abuse of methamphetamine
Phenmetrazine Preludin® Anorexiant drug for treatment of obesity
Sustained release preparation once daily - AM.
Tolerance development (within a few weeks). Actions, mechanisms, and adverse
consequences are similar to those of amphetamines and methylphenidate.
Less availability - less evident abuse Popular among medical professionals due to
their increased access
PhentermineFastin®
Anorexiant drug in treatment of obesity Sustained release preparation once daily - AM.
Actions and adverse consequences are similar Dosage escalation is a common feature Less availability - less evident abuse Also popular among medical professionals due
to increased access
FenfluraminePondimin®
Anorexiant drug in treatment of obesity Generally administered three times daily before meals Duration generally 4-6 hours Mechanism of action includes CNS serotonin systems Combined with phentermine → Phen-fen. Cardiovascular problems - palpitations, hypertension and
valvular heart disease led to discontinuation. Development of pulmonary hypertension Tolerance, dependence, and addiction
AtomoxetineStrattera®
Treatment of ADHD Administered once or twice daily Must take for several weeks before onset of
acceptable effect Classified as non-stimulant in 2004 but must carry
warning label for possible liver toxicity. Not stimulatory like amphetamines, although
increases in blood pressure heart rate weight loss
Modafinil Provigil®
Approved in 1999; Schedule IV drug, Once daily dosing Treatment of narcolepsy, obstructive sleep apnea and
excessive daytime sleepiness. Adverse effects may include hypertension, headache,
dizziness, agitation, and insomnia. Mechanism of action and effects are markedly different
from amphetamines, may enhance glutamate neurotransmission.
Cocaine - History
From the leaves of the plant Erytrhroxylon coca; grows in the Andes Mountains 1000-3000 m above sea level
Used by natives for suppression of appetite, thirst, and tiredness especially on long hunting trips
Inca civilizations used coca in religious rituals
Cocaine - History Sigmund Freud and Carl Koller introduced
cocaine into clinical practice Koller (an ophthalmologist) was intrigued by its
activity as a local anesthetic Freud, working as a neurologist (~1884), was
more interested in the stimulant effects
Cocaine - History Late 1800’s -- early 1900’s
ingredient in many products as an elixir, balm or other medicinal
Early 1900’s, awareness of problems resulted in a decrease in its availability
Passage of the Narcotics Tax Acts in 1914 further decreased its availability
Cocaine - Mechanism
Blocks reuptake of neurotransmitters - dopamine, norepinephrine, epinephrine, and serotonin.
Cocaine - Pharmacokinetics
Duration of action is minutes. Rapidly metabolized
esterase enzymes - in blood & tissues. Rapid metabolism results in
rapid decrease in euphoria intense craving or drug “hunger” results
Cocaine - Routes of Administration
Cocaine
Powder
Crack or Freebase
Cocaine – Binding Sites
VTA
NcA
Caudate
Cocaine - Adverse Effects
Tolerance & Sensitization Restlessness, irritability, anxiety, aggressiveness,
hypersexuality, and paranoia Acute toxicity and death
seizures or stroke in the brain arrhythmias or infarctions in the heart
Vasoconstriction may lead to necrosis and tissue death in the sinuses or injection sites.
Cocaine – Use Patterns
Binge Combination
Marijuana Benzodiazepines Heroin (“Speedball”) Alcohol
Cocaine + Ethanol Cocaethylene
Cocathethylene
Equipotent with cocaine atDA sites Less potent at serotonin sites. More euphorigenic and addictive. More toxic to the liver & heart.
Methamphetamine vs Cocaine
Origins Methamphetamine is man-made Cocaine is plant-derived
Common Methods of Use Smoked, injected intravenously, or snorted. Methamphetamine also is commonly ingested orally.
Methamphetamine vs Cocaine
Euphoria Intense pleasurable rush or high Duration of the high is major difference
Methamphetamine - 8 to 24 hours Cocaine - 20 to 30 minutes.
Methamphetamine vs Cocaine
Chronic Use Methamphetamine may result in more
violent behavior Methamphetamine withdrawal
drug hunger anhedonia.
Methamphetamine vs Cocaine
Methamphetamine Damage to the neurons that produce
dopamine and serotonin. Cocaine
No demonstrated damage to dopamine or serotonin neurons.
Transmission of HIV/AIDS
Intravenous injection of both contributes to transmission of HIV/AIDS
High-risk sexual behaviors and in exchange of drugs for sex
Other Stimulant Plants
Khat derived from Catha Edulis, a small tree/shrub that grows in East Africa and Arabian Peninsula
Arecoline derived from Betel nuts of the palm tree Areca catechu prevalent throughout southeast Asia
Khat - History
Cultivated in East Africa since the early 1300s.
Predates the use of coffee in the region 20th century - some countries in region
officially banned its use - seldom enforced. Increased publicity a result of the U.S.
efforts in Somalia during 1993.
Khat
Contains cathinone and cathine, Methcathinone is semisynthetic from
cathinone Cathine much less potent than cathinone or
methcathinone. Cathine is a Schedule IV drug; cathinone and
methcathinone are Schedule I drugs.
Cathine Cathinone Methcathinone
Khat - Use
Leaves and shoots are chewed, like tobacco, for the stimulation and appetite
suppression effects. Cathinone only present in fresh leaves
since it degrades within about 48 hours. Often refrigerated immediately upon
harvesting for transport.
Khat - Effects
Similar to amphetamines. mild euphoria and excitement reduced appetite increased HR & BP
Withdrawal symptoms lethargy depression nightmares and tremors.
Arecoline - History Widely used in India, Thailand,
Indonesia and other Asian countries. Used by more people in the world than
any other single plant. Traditionally used for intestinal worms
and as an antihelminthic in veterinary medicine.
Crushed betel nuts wrapped in pieces or leaves from the Piper betel vine along with lime and sometimes other flavorings including tobacco.
Arecoline - Mechanisms
Acts by stimulation of cholinergic neurotransmission in both CNS and ANS
May also act on other neurotransmitter systems (i.e. GABA)
Produces mild stimulation and euphoric not unlike tobacco
Increased risk of throat & mouth cancers.
Summary (part 3)
Amphetamine in therapeutics Methylphenidate, Phenmetrazine Phentermine, Fenfluramine Atomoxetine, Modafinil Cocaine Methamphetamine vs Cocaine Khat – cathine, cathinone
Methcathinone Arecoline – Betel nut