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PRINCIPLES OF MANAGEMENT OF STIMULANT MISUSE DR ALISON BATTERSBY.

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Presentation on theme: "PRINCIPLES OF MANAGEMENT OF STIMULANT MISUSE DR ALISON BATTERSBY."— Presentation transcript:

1 PRINCIPLES OF MANAGEMENT OF STIMULANT MISUSE DR ALISON BATTERSBY

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

4 Group of compounds Amphetamine Amphetamine Methamphetamine Methamphetamine Fenfluramine Fenfluramine Bupropion Bupropion Mephedrone Mephedrone

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

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

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

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

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

10 Physical Dependence Disputed Disputed After a “run” abrupt withdrawal “the crash” After a “run” abrupt withdrawal “the crash” Fatigue, depression, hunger Fatigue, depression, hunger Irritability Irritability Anxiety/agitation Anxiety/agitation ?normal reaction ?normal reaction

11 Psychological dependence Definitely present Definitely present Intense craving Intense craving drug-seeking behaviour drug-seeking behaviour Powerful reinforcer in animal experiments Powerful reinforcer in animal experiments

12 Adverse effects Psychotic illness Psychotic illness Often persecutory in nature Often persecutory in nature Automatic stereotyped behaviour Automatic stereotyped behaviour Irritability Irritability Paranoia Paranoia Aggression Aggression

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

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

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

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

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

19 Production Combination of red phosphorus, pseudoephedrine and iodine Combination of red phosphorus, pseudoephedrine and iodine Extremely dangerous Extremely dangerous

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

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

23 Treatment of Amphetamine Dependence Mainly semi-structured psychosocial interventions Mainly semi-structured psychosocial interventions Substitution therapies, evidence is equivocal or poor quality Substitution therapies, evidence is equivocal or poor quality Occasional use of modafinil, baclofen, mirtazapine and naltrexone Occasional use of modafinil, baclofen, mirtazapine and naltrexone High dose venlafaxine/SSRI’s when use stopped High dose venlafaxine/SSRI’s when use stopped

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

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

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30 Coca-cola (old-style)

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

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

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

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

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

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

38 Very high doses Hypertension Hypertension Cardiac arrythmias Cardiac arrythmias Convulsions Convulsions Death (cardiac/respiratory arrest) Death (cardiac/respiratory arrest)

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

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

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

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

43 Cocaine toxicity/psychosis Anxiety, restlessness, apprehension, suspiciousness, hypervigilence, paranoid behaviour Anxiety, restlessness, apprehension, suspiciousness, hypervigilence, paranoid behaviour Muscle twitching, nausea, vomiting Muscle twitching, nausea, vomiting Increase pulse and blood pressure Increase pulse and blood pressure Irregular respiration Irregular respiration convulsions convulsions

44 Severe toxicity Circulatory failure Circulatory failure Respiratory failure Respiratory failure Loss of reflexes Loss of reflexes Unconsciousness Unconsciousness death death

45 Cocaine psychosis Persecutory delusions Persecutory delusions Stereotyped behviour Stereotyped behviour Auditory hallucinations Auditory hallucinations Tactile hallucinations (cocaine bugs) Tactile hallucinations (cocaine bugs)

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

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

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

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

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

52 Questions please

53 Go Home!


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