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” • caffeine • ephedrine • PPA (phenylpropanolamine) • OTC STIMULANTS • Caffeine • Pseudoephedrine (Sudafed) • Ephedrine • Herbals (e.g. mahuang, guarna)
CNS STIMULANTS • AMPHETAMINES • dextroamphetamine (Dexedrine) • methamphetamine • AMPHETAMINE-LIKE DRUGS • methylphenidate (Ritalin) • diethylpropion (Tenuate) • phentermine (Ionamin) • (“Phen-Fen”) • “Ecstasy” (MDMA)
STIMULANTSCOCAINE • 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 • ADHD • 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.)
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 35 minutes (nasal); within 1 minute for IV and inhaled use • half-life 3090 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 • 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: • peak in 23 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 • user vs. “abuser” • Withdrawal: • exhaustion, lethargy, depression
METHYLPHENIDATE • How to treat those with a history of substance and ADHD?
DEXTROAMPHETAMINE • Also prescribed for ADHD • Abuse similar to methylphenidate
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
