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 ActivityNormal (no cocaine)

Postsynaptic receptors

Reuptake

carrier

Dopamine insynapse

Presynaptic neuron

Postsynaptic neuron

Dopamine release

Chronic cocaine use

Decreased postsynaptic

receptors

Reuptake carrier Normal amount of

dopamine in synapse

Presynaptic neuron

Postsynaptic neuron

Dopamine release

Cocaine blockade

Acute cocaine use

Postsynaptic receptors

Reuptake carrier

Presynaptic neuron

Postsynaptic neuron

Dopamine release

Cocaine blockade

Increased dopamine in

synapse

Cocaine withdrawal

Decreased postsynaptic

receptors

Reuptake carrier

Presynaptic neuron

Postsynaptic neuron

Dopamine release

Decreased dopamine in

synapse

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