Stimulants

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Stimulants

• Pearl Isaac Anne Kalvik

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LEARNING OBJECTIVES

• 1. Develop an understanding of the effects and
  toxicity of stimulant drugs.
• 2. Become familiar with the issues surrounding
  stimulant (especially cocaine) abuse including
  dependence and current treatment approaches.

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CNS STIMULANTS

• Nicotine
• Caffeine
• Cathinone (Khat)

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CNS STIMULANTS

• STREET STIMULANTS
• caffeine
• ephedrine
• PPA (phenylpropanolamine)
• OTC STIMULANTS
• Caffeine
• Pseudoephedrine (Sudafed)
• Ephedrine
• Herbals (e.g. mahuang, guarna)

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CNS STIMULANTS

• AMPHETAMINES
• dextroamphetamine (Dexedrine)
• methamphetamine
• AMPHETAMINE-LIKE DRUGS
• methylphenidate (Ritalin)
• diethylpropion (Tenuate)
• phentermine (Ionamin)
• (Phen-Fen)
• Ecstasy (MDMA)

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STIMULANTSCOCAINE

• Powder
• Crack (freebase)
• Some Street Names
• C, coke, flake snow, rock

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MEDICAL USES OF STIMULANTS

• COCAINE
• local anesthetic in ENT surgery
• AMPHETAMINES
• ADHD
• narcolepsy
• depression
• AMPHETAMINE-LIKE DRUGS
• ADHD
• appetite suppressant

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MEDICAL USES OF STIMULANTS

• CAFFEINE
• Augmentation of analgesia
• Mild stimulant to stay awake
• By injection for apnea in newborns
• OTC STIMULANTS
• Nasal decongestion
• Symptomatic relief of asthma
• Appetite suppression (U.S.)

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CNS STIMULANTS

• WHY ARE THEY ABUSED?
• WHO ABUSES?

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STIMULANT ABUSE

• SIGNS OF USE
• irritability
• restlessness
• insomnia
• panic, confusion
• weight loss
• paranoia

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STIMULANT ABUSE

• SIGNS OF OVERDOSE
• hypertension
• cardiac arrhythmia
• chest pain, myocardial infarction
• convulsions
• cerebral hemorrhage
• coma
• death

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PHARMACOKINETICS OF COCAINE

• ABSORPTION
• snorted (limited by vasoconstriction)
• injected
• smoked (volatile, stable)

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PHARMACOKINETICS OF COCAINE

• DISTRIBUTION, METABOLISM, ELIMINATION
• penetrates brain rapidly
• euphoria in approx 3?5 minutes (nasal) within 1
  minute for IV and inhaled use
• half-life 30?90 minutes
• gt 95 metabolized
• inactive metabolites excreted in urine

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COCAINE PHARMACOLOGICAL EFFECTS

• SHORT-TERM USE LOW DOSE
• euphoria
• increased energy
• increased alertness
• decreased appetite
• increased heart rate and blood pressure

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COCAINE PATTERNS OF USE

• Intermittent
• Compulsive
• Binge use coke run ? until supplies run out,
  then crash

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COCAINE PHARMACOLOGICAL EFFECTS

• SHORT-TERM USE HIGH DOSE
• intensified high
• increased BP heart rate
• increased temperature
• anxiety, muscle twitching, insomnia
• bizarre/erratic behaviour, psychosis
• seizures
• arrhythmias, MI

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COCAINE PHARMACOLOGY

• Blocks dopamine reuptake
• Also NE and serotonin

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Effects of Cocaine on Dopaminergic Activity
Chronic cocaine use
Normal (no cocaine)
Presynaptic neuron
Presynaptic neuron
Dopamine release
Dopamine release
Reuptake carrier
Normal amount of dopamine in synapse
Dopamine in synapse
Reuptake carrier
Cocaine blockade
Postsynaptic neuron
Postsynaptic neuron
Decreased postsynaptic receptors
Postsynaptic receptors
Cocaine withdrawal
Acute cocaine use
Presynaptic neuron
Presynaptic neuron
Dopamine release
Dopamine release
Reuptake carrier
Increased dopamine in synapse
Decreased dopamine in synapse
Reuptake carrier
Cocaine blockade
Postsynaptic neuron
Postsynaptic neuron
Decreased postsynaptic receptors
Postsynaptic receptors
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COCAINE VIDEO PRESENTATION
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COCAINE LONG-TERM USE

• psychological dependence
• craving
• paranoid psychosis
• weight loss, malnutrition
• impotence
• sleep disturbances
• nasal congestion, septal perforation

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COCAINE TOXICITY

• SUDDEN DEATH
• arrhythmias, hypertension
• seizures
• brain hemorrhage, stroke
• OTHER MEDICAL COMPLICATIONS
• heart disease
• respiratory complications
• acute renal failure
• psychiatric

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COCAINE WITHDRAWAL

• PHASE 1 THE CRASH
• lasts up to 4 days
• profound decrease in mood and energy
• craving, agitation, anxiety, paranoia
• followed by hunger, fatigue, sleepiness
• cocaine blues

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COCAINE WITHDRAWAL

• PHASE 2 WITHDRAWAL DYSPHORIA
• prolonged dysphoria, anhedonia, lack of
  motivation/energy
• increased craving
• lasts 1 to 10 weeks
• high risk of relapse

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COCAINE WITHDRAWAL

• PHASE 3 EXTINCTION
• episodic craving
• triggers to use
• craving extinguishes over time
• duration indefinite

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COCAINE TREATMENTS

• bromocriptine
• antidepressants
• anticonvulsants
• neuroleptics
• vaccine
• vigabatrin ????
• NO EFFECTIVE PHARMACOLOGICAL TREATMENT YET
• treat co-morbid disorders

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COCAINE

• POLYSUBSTANCE ABUSE
• e.g., speedball, benzodiazepines, alcohol,
  methadone clients

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STREET STIMULANTS OTCs

• Like cocaine and amphetamines but much weaker
• High doses
• Toxicity alone and in combination
• STREET STIMULANTS
• availability
• restrictions
• OTCS

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METHAMPHETAMINE

• crystal, ice, speed, meth
• increasing trend
• precursors (e.g., OTCs)
• internet recipes and supplies
• manufacture home-made labs
• smoked, injected, snorted, swallowed
• effects on presynaptic release of dopamine
• some effects on serotonin norepinephrine

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METHAMPHETAMINE

• rapid onset (similar to cocaine)
• LASTS 10 -12 HOURS
• intense high (rush)
• alertness, well-being
• decreased appetite
• like buzz of 1000 cups of coffee

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METHAMPHETAMINE

• Toxic Effects
• irritability, insomnia, high BP, palpitations
• chest pain,MI, death possible
• hyperthermia, seizures
• Paranoia, hallucinations, formication
• violent behaviour

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METHAMPHETAMINE

• WITHDRAWAL
• peak in 2?3 days
• abdominal distress, increased appetite,
  headaches, lethargy, depression, suicidal
  ideation
• NEUROTOXIN

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METHYLPHENIDATE

• Well studied treatment for ADHD
• Abuse potential similar to cocaine and
  amphetamines
• Diversion classmates, parents, etc.
• Crushed and snorted
• Injection possible (e.g.,Ts Rs)
• Rapid onset (like cocaine) when snorted or
  injected
• Lasts about 6 hours

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METHYLPHENIDATE

• UNDESIRABLE EFFECTS
• loss of appetite, anxiety insomnia, hypertension,
  headache, psychosis
• chest pain, tremors, seizures, paranoia,
  formication (coke bugs)
• stroke, MI, death

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METHYLPHENIDATE

• Tolerance
• user vs. abuser
• Withdrawal
• exhaustion, lethargy, depression

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METHYLPHENIDATE

• How to treat those with a history of substance
  and ADHD?

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DEXTROAMPHETAMINE

• Also prescribed for ADHD
• Abuse similar to methylphenidate

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STIMULANT ABUSE

• What can a pharmacist do?

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STIMULANT ABUSE

• Refer for treatment
• Monitor prescriptions for methylphenidate and
  other stimulants
• Monitor OTC sales
• Remember polysubstance abuse