PRINCIPLES OF MANAGEMENT OF STIMULANT MISUSE

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PRINCIPLES OF MANAGEMENT OF STIMULANT MISUSE

• DR ALISON BATTERSBY

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Amphetamine

• Class of synthetic drugs similar effect to
  adrenalin
• Act by releasing noradrenalin and dopamine and
  inhibiting reuptake.
• D and L forms (D twice as powerful as a central
  stimulant)

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Group of compounds

• Amphetamine
• Methamphetamine
• Fenfluramine
• Bupropion
• Mephedrone

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• Synthesised in Germany in 1887
• Nasal decongestants until 1930s
• Medically tested on hospital workers in 30s to
  create wellbeing and relieve fatigue
• WW11 to combat fatigue
• OTC in 50s, POM in 60s
• Second most commonly injected drug

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Effects

• Elevated mood
• Feel more energetic, alert and self-confident
• Improved task performance
• Decreased fatigue and hunger
• May be more talkative, restless or agitated
• Increased libido

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• Increased heart rate, BP
• Palpitations
• Dilated pupils
• Dry mouth
• Sweating
• L-amphetamine greater cardiovascular effects

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Intoxication

• Dizziness
• Sweating
• Chest pain
• Palpitation
• Hypertension
• Cardiac arrhythmias
• May increase body temp/convulsions

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Tolerance

• To some but not all aspects
• To gain euphoric effect may need to escalate dose
• Cardiovascular effects
• Appetite suppression
• Used therapeutically for narcolepsy and
  hyperkinetic disorders

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Physical Dependence

• Disputed
• After a run abrupt withdrawal the crash
• Fatigue, depression, hunger
• Irritability
• Anxiety/agitation
• ?normal reaction

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Psychological dependence

• Definitely present
• Intense craving
• drug-seeking behaviour
• Powerful reinforcer in animal experiments

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Adverse effects

• Psychotic illness
• Often persecutory in nature
• Automatic stereotyped behaviour
• Irritability
• Paranoia
• Aggression

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Mode of Action Dopamine and Serotonin

• Causes presynaptic dopamine vesicles to release
  dopamine into cytosol
• Causes reversal of the DAT (dopamine active )
  transporters so it transports Dopamine into the
  cleft
• Reversal of the SERT (serotonin) transporter
  particularly in mesocorticolimbic pathways
  increasing glutamatergic neurons

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Physical Sequelae

• Cardiovascular, HT, Pulse, cardiomyopathy, aortic
  dissction
• CNS ischaemic strokes, intracerebral
  haemorrhages, seizure, abnormal movements
• Ischaemic colitis
• Rhabdomyolysis
• hepatotoxicity

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Methamphetamine

• Common nicknames, ice, crystal meth, crank,
  glass, speed, shabu (philippines), tik (south
  africa) and ya ba (thailand)
• Oral, snorting, smoking, injection

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Pharmacology

• ½ life 9-15 hrs excreted by kidney
• Lipid soluble, fast entry to brain
• Resistance to MAO degradation
• Causes reversal of dopamine, NA uptake enzymes
• Tolerance occurs partially due to transmitter
  depletion
• Neurotoxic to dopamine and serotonin neurons

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Effects

• Desired euphoria, alertness, concentration, self
  confidence, energy
• Unwanted aggression, agitation, irritability,
  paranoia, psychosis
• Physical anorexia, tachycardia, hypertension,
  constipation, palpitations, stroke, MI,
  convulsions

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Production

• Combination of red phosphorus, pseudoephedrine
  and iodine
• Extremely dangerous

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Long term effects

• Meth mouth, dry mouth, grinding teeth
• Injecting related problems
• Unsafe sex
• Withdrawal excessive sleeping, increased
  appetite and depression, often accompanied by
  anxiety and drug craving

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Amphetamine psychosis

• 309 regular amphetamine users
• 13 screened positive for psychosis
• 23 clinically significant symptoms of
  suspiciousness, unusual thought content or
  hallucinations in the past year
• Swift onset
• Delusions and hallucinations may mimic bipolar or
  schizophrenia
• Abates within days with restoration of sleep and
  cessation of amphetamines

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Treatment of Amphetamine Dependence

• Mainly semi-structured psychosocial interventions
• Substitution therapies, evidence is equivocal or
  poor quality
• Occasional use of modafinil, baclofen,
  mirtazapine and naltrexone
• High dose venlafaxine/SSRIs when use stopped

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Cocaine

• Alkaloid prepared from coca bush
• Erythroxylum coca
• Central and south america
• Leaves chewed alleviate fatigue, hunger and cold
• Incas religious ceremonies, social and medicinal

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• First isolated 1880s
• Oral consumption widespread
• Used in tonics
• Freud noted local anaesthetic and psychic effects
• Recommended it for treatment opiate addiction

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Coca-cola (old-style)
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Manufacture

• Illegal factories close to growth
• Cocaine hydrochloride obtained
• White powder
• Easy to transport
• Cut eg sugar, amphetamine, beta blockers

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Route of administration

• Sniffing/snorting (line inhaled through straw)
• Vasoconstriction of blood vessels
• No rush, 20-40minute effect
• Rhinitis/perforated nasal septum
• Iv

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• Smoking
• Cocaine hydrochloride unsuitable for smoking
  (decomposes high temps)
• Alkaloid can be freed from hydrochloride by using
  ether, vaporises easily

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Crack

• Cooking cocaine with baking powder and water
• Baking powder precipitates impurities
• Pure crystalline cocaine
• Usually smoked in pipe or sprinkled on cigarette
• Sudden intense high

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• Reaches brain within seconds
• Euphoria abates quickly
• User feels restless and irritable
• Marked craving
• Use often escalates quickly to chase the high

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Effects

• CNS stimulant
• Increased energy, wakefulness, activity and
  confidence
• Powerful euphoriant eg Brompton cocktail
• Raised pulse, blood pressure, temperature
• Dilated pupils
• Local vasoconstriction

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Very high doses

• Hypertension
• Cardiac arrythmias
• Convulsions
• Death (cardiac/respiratory arrest)

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Tolerance

• Some degree of tolerance with pure cocaine
  freebase
• Ceiling tolerance level
• No tolerance to reinforcing effect

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Physical dependence

• Withdrawal
• Crash thirty minutes after a binge
• Social withdrawal, depression, tremor, muscle
  pain, disturbance of sleeping, eating
• Dysphoria, intense craving
• Extinction phase 3-12 months

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Psychological dependence

• Severe
• Animal model, powerful reinforcer
• Mechanism of action not fully understood
• Specific cocaine receptors
• Affects dopaminergic system, inhibit dopamine
  reuptake

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Long-term use

• Excessive dopamine metabolised
• Therefore reduced dopamine concentration
• Then changes in post-synaptic receptors (craving)
• Also acts on NA and 5HT systems inhibiting
  reuptake

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Cocaine toxicity/psychosis

• Anxiety, restlessness, apprehension,
  suspiciousness, hypervigilence, paranoid
  behaviour
• Muscle twitching, nausea, vomiting
• Increase pulse and blood pressure
• Irregular respiration
• convulsions

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Severe toxicity

• Circulatory failure
• Respiratory failure
• Loss of reflexes
• Unconsciousness
• death

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Cocaine psychosis

• Persecutory delusions
• Stereotyped behviour
• Auditory hallucinations
• Tactile hallucinations (cocaine bugs)

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Treatment

• Not as well defined as for opiate addiction
• Psychosocial interventions using semi-structured
  interviews
• Acupuncture

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Ketamine

• Developed 1962 by Pfizer
• Used as a general anaesthetic or in pain relief
• NMDA (Glutamate) receptor antagonist
• Action particularly in the prefrontal cortex and
  hippocampus
• At higher levels binds opioid receptors, partial
  D2 agonist and inhibits dopamine reuptake

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Illicit use

• Sold in powder or liquid
• Can be sniffed, injected or swallowed
• Significant first pass metabolism so larger
  amounts needed if swallowed
• Class C drug
• Dependence rare, tolerance develops reasonably
  quickly, no abstinence syndrome?

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Effects

• Dissociative amnesia k-hole
• Feelings of detachment from the world
  depersonalisation/derealisation
• Spiritual experiences
• Feeling connected to others
• Visual hallucinations, other perceptual
  abnormalities
• Changes in time
• Lasts about 2 hours

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Health consequences

• Bladder problems- BMJ 2008 case series of 9
  patients dose-related
• Severe urinary frequency, urgency, macroscopic
  haematuria, suprapubic pain
• Changes in cognition, heavy users worse verbal
  short-term memory and visual memory
• Occasional users no different from controls
• Overdose, commonly from iv use

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Questions please
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