Pearl Isaac & Anne Kalvik Stimulants Pearl Isaac & Anne Kalvik

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.

CNS STIMULANTS Nicotine Caffeine Cathinone (Khat)

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

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

STIMULANTS COCAINE Powder Crack (freebase) Some Street Names: C, coke, flake snow, rock

MEDICAL USES OF STIMULANTS COCAINE local anesthetic in ENT surgery AMPHETAMINES ADHD narcolepsy depression AMPHETAMINE-LIKE DRUGS appetite suppressant

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.)

WHY ARE THEY ABUSED? WHO ABUSES? CNS STIMULANTS WHY ARE THEY ABUSED? WHO ABUSES?

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

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

PHARMACOKINETICS OF COCAINE ABSORPTION snorted (limited by vasoconstriction) injected smoked (volatile, stable)

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 > 95% metabolized inactive metabolites excreted in urine

COCAINE: PHARMACOLOGICAL EFFECTS SHORT-TERM USE: LOW DOSE euphoria increased energy increased alertness decreased appetite increased heart rate and blood pressure

COCAINE: PATTERNS OF USE Intermittent Compulsive “Binge” use: “coke run”  until supplies run out, then “crash”

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

COCAINE: PHARMACOLOGY Blocks dopamine reuptake Also NE and serotonin

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

COCAINE: VIDEO PRESENTATION

COCAINE: LONG-TERM USE psychological dependence craving paranoid psychosis weight loss, malnutrition impotence sleep disturbances nasal congestion, septal perforation

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

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”

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

COCAINE: WITHDRAWAL PHASE 3: “EXTINCTION” episodic craving triggers to use craving extinguishes over time duration indefinite

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

COCAINE POLYSUBSTANCE ABUSE: e.g., “speedball”, benzodiazepines, alcohol, methadone clients

STREET STIMULANTS & OTCs Like cocaine and amphetamines but much weaker High doses Toxicity: alone and in combination “STREET STIMULANTS” availability restrictions OTC’S

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

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”

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

METHAMPHETAMINE WITHDRAWAL: NEUROTOXIN peak in 23 days abdominal distress, increased appetite, headaches, lethargy, depression, suicidal ideation NEUROTOXIN

METHYLPHENIDATE Well studied treatment for ADHD Abuse potential similar to cocaine and amphetamines Diversion: classmates, parents, etc. Crushed and snorted Injection possible (e.g.,“T’s & R’s”) Rapid onset (like cocaine) when snorted or injected Lasts about 6 hours

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

METHYLPHENIDATE Tolerance Withdrawal: user vs. “abuser” exhaustion, lethargy, depression

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

DEXTROAMPHETAMINE Also prescribed for ADHD Abuse similar to methylphenidate

What can a pharmacist do? STIMULANT ABUSE What can a pharmacist do?

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