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Stimulants

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.

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Stimulants

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  1. Stimulants Pearl Isaac & Anne Kalvik

  2. 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.

  3. CNS STIMULANTS • Nicotine • Caffeine • Cathinone (Khat)

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

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

  6. STIMULANTSCOCAINE • Powder • Crack (freebase) Some Street Names: C, coke, flake snow, rock

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

  8. 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.)

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

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

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

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

  13. 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

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

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

  16. 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

  17. COCAINE: PHARMACOLOGY • Blocks dopamine reuptake • Also NE and serotonin

  18. 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

  19. COCAINE: VIDEO PRESENTATION

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

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

  22. 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”

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

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

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

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

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

  28. 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

  29. 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”

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

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

  32. 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

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

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

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

  36. DEXTROAMPHETAMINE • Also prescribed for ADHD • Abuse similar to methylphenidate

  37. STIMULANT ABUSE What can a pharmacist do?

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

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