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PRINCIPLES OF MANAGEMENT OF STIMULANT MISUSE DR ALISON BATTERSBY 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) Group of compounds • Amphetamine • Methamphetamine • Fenfluramine • Bupropion • Mephedrone • Synthesised in Germany in 1887 • Nasal decongestants until 1930’s • Medically tested on hospital workers in 30’s to create wellbeing and relieve fatigue • WW11 to combat fatigue • OTC in 50’s, POM in 60’s • Second most commonly injected drug 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 • Increased heart rate, BP • Palpitations • Dilated pupils • Dry mouth • Sweating • L-amphetamine greater cardiovascular effects Intoxication • Dizziness • Sweating • Chest pain • Palpitation • Hypertension • Cardiac arrhythmias • May increase body temp/convulsions 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 Physical Dependence • Disputed • After a “run” abrupt withdrawal “the crash” • Fatigue, depression, hunger • Irritability • Anxiety/agitation • ?normal reaction Psychological dependence • Definitely present • Intense craving • drug-seeking behaviour • Powerful reinforcer in animal experiments Adverse effects • Psychotic illness • Often persecutory in nature • Automatic stereotyped behaviour • Irritability • Paranoia • Aggression 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 Physical Sequelae • Cardiovascular, HT, Pulse, cardiomyopathy, aortic dissction • CNS ischaemic strokes, intracerebral haemorrhages, seizure, abnormal movements • Ischaemic colitis • Rhabdomyolysis • hepatotoxicity Methamphetamine • Common nicknames, ice, crystal meth, crank, glass, speed, shabu (philippines), tik (south africa) and ya ba (thailand) • Oral, snorting, smoking, injection 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 Effects • Desired: euphoria, alertness, concentration, self confidence, energy • Unwanted: aggression, agitation, irritability, paranoia, psychosis • Physical: anorexia, tachycardia, hypertension, constipation, palpitations, stroke, MI, convulsions Production • Combination of red phosphorus, pseudoephedrine and iodine • Extremely dangerous 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 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 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/SSRI’s when use stopped 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 • First isolated 1880’s • Oral consumption widespread • Used in tonics • Freud noted local anaesthetic and psychic effects • Recommended it for treatment opiate addiction Coca-cola (old-style) Manufacture • Illegal factories close to growth • Cocaine hydrochloride obtained • White powder • Easy to transport • Cut eg sugar, amphetamine, beta blockers Route of administration • Sniffing/snorting (line inhaled through straw) • Vasoconstriction of blood vessels • No rush, 20-40minute effect • Rhinitis/perforated nasal septum • Iv • Smoking • Cocaine hydrochloride unsuitable for smoking (decomposes high temps) • Alkaloid can be freed from hydrochloride by using ether, vaporises easily 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 • Reaches brain within seconds • Euphoria abates quickly • User feels restless and irritable • Marked craving • Use often escalates quickly to chase the high Effects • CNS stimulant • Increased energy, wakefulness, activity and confidence • Powerful euphoriant eg Brompton cocktail • Raised pulse, blood pressure, temperature • Dilated pupils • Local vasoconstriction Very high doses • Hypertension • Cardiac arrythmias • Convulsions • Death (cardiac/respiratory arrest) Tolerance • Some degree of tolerance with pure cocaine freebase • Ceiling tolerance level • No tolerance to reinforcing effect 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 Psychological dependence • Severe • Animal model, powerful reinforcer • Mechanism of action not fully understood • Specific cocaine receptors • Affects dopaminergic system, inhibit dopamine reuptake 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 Cocaine toxicity/psychosis • Anxiety, restlessness, apprehension, suspiciousness, hypervigilence, paranoid behaviour • Muscle twitching, nausea, vomiting • Increase pulse and blood pressure • Irregular respiration • convulsions Severe toxicity • Circulatory failure • Respiratory failure • Loss of reflexes • Unconsciousness • death Cocaine psychosis • Persecutory delusions • Stereotyped behviour • Auditory hallucinations • Tactile hallucinations (cocaine bugs) Treatment • Not as well defined as for opiate addiction • Psychosocial interventions using semistructured interviews • Acupuncture 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 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? 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 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 Questions please Go Home!
