Amphetamine and Related Disorders(khat.pptx

Amphetamine and Related Disorders(khat.pptx

1. Amphetamine and Related Disorders( khat ) Prepared by- Abdirahman T Modulator- Dr. Girma Mamo (Psychiatrist )

2. Outline Introduction Epidemiology Neuropharmacology Physical and psychological adverse effects Amphetamine related disorders Treatment and rehabilitation

3. Amphetamine most widely used illicit substances, second only to cannabis Referred as sympathomimetics , analeptics, stimulants and psychostimulants Used to increase performance and induce euphoric feeling Addictive drug,less than cocaine Orally, inhaled, smoked or injected IV have certain therapeutic uses: ADHD, Narcolepsy, Depression,Obesity etc

4. Epidemiology Life time prevalence of amphetamine dependence and abuse is 1.5% (DSM-IV-TR) M: F ratio is 1 7.1 % of persons (12 years of age and older) reported lifetime nonmedical use of stimulants The highest rates of use were among 18- to 25-year-olds, followed by 12- to 17-year-olds. Occur in all socioeconomic groups

5. Neuropharmacology All the amphetamines - rapidly absorbed orally ,rapid onset of action(1hr) Primary effects- cause release of catecholamines (dopamine) and serotonin from presynaptic terminals. Potent for the dopaminergic neurons projecting from the ventral segmental area to the cerebral cortex and the limbic areas.

6. Physical adverse effects most serious - cardiac, cerebrovascular , and GI effects life-threatening conditions - MI, severe HTN, CVD, and ischemic colitis. IV use of amphetamines – HIV, hepatitis, lung abscesses, endocarditis , and necrotizing angiitis . Pregnancy – baby with LBW, small head circumference, early gestational age, and growth retardation.

7. Clinical effects of Amphetamine Psychological Physical Enhanced cognitive functions Elevated mood Over activity Over – talkativeness Increased confidence, self-esteem and sociability Insomnia. Reduced sense of fatigue Reduced appetite (anorexia) Dilated pupils Tremor In high doses / prolonged use: Restlessness, irritability Paranoid psychosis Aggressiveness, hostility In high doses / prolonged use: Nausea, vomiting, cardiac arrhythmia. Severe hypertension, cerebrovascular accident, seizures, dizziness, hyperthermia, respiratory distress, cyanosis

8. DSM-IV-TR Amphetamine (or Amphetamine-like)-Related Disorders Amphetamine use disorders Amphetamine dependence Amphetamine abuse Amphetamine-induced disorders Amphetamine intoxication Amphetamine withdrawal Amphetamine induced psychiatric disorders Amphetamine related disorder NOS

9. Amphetamine use disorders Amphetamine dependence maladaptive pattern of amphetamine use, leading to clinically significant impairment or distress and manifest in psychological & physical dependence DSM-IV-TR Diagnostic Criteria for Amphetamine Dependence A. manifested by three (or more) of the following, occurring at any time in the same 12-month period: 1. Tolerance 2. Withdrawal 3. the substance is often taken in larger amounts or over a longer period than was intended

10. .............. Con’t 4.there is a persistent desire or unsuccessful efforts to cut down or control substance use 5.a great deal of time is spent in activities necessary to obtain Amphetamine, use Amphetamine or recover from its effects 6. important social, occupational, or recreational activities are given up or reduced because of Amphetamine use 7. Amphetamine use is continued despite knowledge of having a persistent or recurrent physical or psychological problem that is likely to have been caused or exacerbated by it

11. .............. con’t Amphetamine abuse characterized by the presence of at least one specific symptom indicating that amphetamine use has interfered with the person’s life. DSM-IV-TR Criteria for Amphetamine Abuse one (or more) of the following, occurring within a 12-month period: recurrent use resulting in a failure to fulfill major role obligations at work, school, or home recurrent use in situations in which it is physically hazardous recurrent Amphetamine-related legal problems continued use despite having persistent or recurrent social or interpersonal problems caused or exacerbated by the effects of Amphetamine The symptoms have never met the criteria for Substance Dependence for this class of substance

12. Amphetamine induced disorders Amphetamine Intoxication Recent use of amphetamine or a related substance Clinically significant maladaptive behavioural or psychological changes (e.g., euphoria or affective blunting; changes in sociability; impaired judgment; or impaired social or occupational functioning) that developed during, or shortly after, use of amphetamine or a related substance.

13. C . Two (or more) of the following, developing during, or shortly after, use of amphetamine or a related substance: tachycardia or bradycardia pupillary dilation elevated or lowered blood pressure perspiration or chills nausea or vomiting evidence of weight loss psychomotor agitation or retardation muscular weakness, respiratory depression, chest pain, or cardiac arrhythmias confusion, seizures, dyskinesias , dystonias , or coma D . The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder. Specify if: With perceptual disturbances

14. ................. con’t Amphetamine withdrawal A. Cessation of (or reduction in) amphetamine (or a related substance) use that has been heavy and prolonged. B. Dysphoric mood and two (or more) of the following physiological changes, developing within a few hours to several days after Criterion A: fatigue vivid, unpleasant dreams insomnia or hypersomnia increased appetite psychomotor retardation or agitation C. The symptoms in Criterion B cause clinically significant distress or impairment in social, occupational, or other important areas of functioning. D. The symptoms are not due to a general medical condition and are not better accounted for by another mental disorder.

15. ................ con’t Amphetamine-Induced Mood Disorder Can happed during intoxication or withdrawal . Intoxication- manic or mixed mood features, Withdrawal- depressive mood features. Manic and hypomanic symptoms- rarely (if ever) persist beyond the period of drug use Hypophoria , anhedonia , and depressive symptoms - persist well beyond the period of withdrawal

16. ................ con’t Amphetamine-Induced Anxiety Disorder during intoxication or withdrawal. can induce symptoms similar to OCD, with repetitive, stereotyped behaviors, panic disorder and phobic disorders. symptoms do not persist beyond the period of drug intoxication and rarely merit a distinct diagnosis.

17. ................ con’t Amphetamine Induced Psychotic Disorder Hallmark- presence of paranoia. Predominant visual hallucinations, appropriate affects,hyperactivity , hypersexuality , confusion and incoherence, and little evidence of disordered thinking Lacks the affective flattening and alogia of schizophrenia Resolution of the symptoms in a few days Positive finding in a urine drug screen test (>=in 2-3 days) Rx-short-term use of an antipsychotic medication such as haloperidol

18. ................ con’t Amphetamine-Induced Sleep Disorder Amphetamine intoxication- insomnia and sleep deprivation Amphetamine withdrawal- hypersomnolence and nightmares.

19. ................ con’t Amphetamine-Induced Sexual Dysfunction antidote to the sexual side effects of serotonergic agents such as fluoxetine (Prozac) misused by persons to enhance sexual experiences. High doses and long-term use are associated with erectile disorder and other sexual dysfunctions. Amphetamine-Related Disorder Not Otherwise Specified disorders associated with the use of amphetamine (or a related substance) that are not classifiable under the above disorders

20. Treatment and Rehabilitation Abstinence from the drug Inpatient setting and the use of multiple therapeutic methods (individual, family, and group psychotherapy) Treatment of specific amphetamine-induced disorders with specific drugs may be necessary on a short-term basis Treat comorbid conditions Bupropion ( Wellbutrin ) may be of use after patients have withdrawn from amphetamine. It has the effect of producing feelings of well-being as these patients cope with the dysphoria that may accompany abstinence.

21. KHAT

22. Objective To know What Khat is and its constituents The pharmacology and pharmacokinetics of Khat The effect of Khat The investigation of Khat The treatment of Khat related problems

23. Contents Introduction Epidemiology Pharmacology Pharmacokinetics Tolerance and withdrawal Adverse effects Detection Treatment of it’s problems References

24. Introduction Khat is derived from the fresh leaves of Catha edulis , a species belonging to the plant family Celastraceae ; a bush native to East Africa. The leaves have an aromatic odour , astringent taste and slightly sweet. It is usually packaged in plastic bags or wrapped in banana leaves to retain its moistness and freshness. Ingested by chewing(mainly), making drink from dried leaves and rarely by smoking dried leaves

25. ................ con’t Other names for Khat :- Qat , Kat, Chat, Kus-es-Salahin , Mirra , Tohai , Tschat , Catha, Quat , Abyssinian Tea, African Tea, and African Salad . Ethiopia is thought to be the country of origin of khat use The earliest mention was during the time of king Amde Tsion in the 14 th century. traditionally it has been used to treat various ailments including depression , colds, body pains and arthritis .

26. Epidemiology of khat use Mainly grown in Ethiopia, Kenya, Yemen, Somalia, Sudan, South Africa and Madagascar In Somalia found that more men habitually chewed than women: 75% of men chewed khat regularly compared with only 7–10% of women In the last decades, the khat ‘habit’ has spread to other African countries and to Europe, to Australia and to the United States .

27. .............. con’t Khat is freely available in Ethiopia and is a highly valued export commodity. According to the EDHS 2011 11% of women and 28% of men reported that they had ever chewed khat . Among both women and men, this proportion increases with age. Among women, khat consumption is higher in rural areas than in urban areas (12% vs 7%), while among men there is no marked difference by place of residence. The percentage of respondents who ever chewed khat is lowest in Tigray (1% of women and 4% of men) and highest in Harari (39% of women and 82 % of men). The percentage who ever chewed khat is highest among women with no education(14 %) and among men with more than secondary education (32%).

28. Common Reasons for Chewing Khat Is a social and a culture-based activity. To enhance social interaction , playing a role in ceremonies such as weddings. Some believe that chewing facilitates contact with Allah when praying. To improve performance , stay alert and to increase work capacity To stay awake and postpone fatigue

29. Pharmacology of khat Contains more than 40 alkaloids, glycosides, tannins, amino acids, vitamins and minerals Most of the effect come from two phenylalkylamines – cathinone and cathine

30. ............... con’t cathinone a ‘natural amphetamine’ the most active ingredient of khat Its effects have been shown to be similar to amphetamine, but with a lower potency Estimated to be 7–10 times more potent than cathine .

31. ............... con’t Cathine Has a milder psychostimulant action than cathinone The effects last for only a short time, so the user must chew leaves almost continuously Responsible for the unwanted systemic effects.

32. ................ con’t Modes of action Exert their effects on two main neurochemical pathways: dopamine and noradrenalin. Both cathinone and amphetamine induce release of dopamine from central nervous system dopamine terminals and thus increase the activity of the dopaminergic pathways. Cathinone has a releasing effect on noradrenalin storage sites, which supports the conclusion that cathinone facilitates noradrenalin transmission.

33. Pharmacokinetics Pharmacokinetics Absorption from the oral mucosa Cathinone The effect is maximum after 15–30 minutes. Metabolism is rapid,occurring mainly during first passage through the liver. Only a small fraction (about 2%) appears unchanged in the urine. Most is metabolised to norephedrine and is excreted in this form. The rate of inactivation is about the same as the rate of absorption, which limits blood levels attainable by chewing.

34. ............... con’t Cathine has a slower onset of action, with a serum half-life in humans of about 3 hours. Is excreted unchanged in the urine within about 24 hours . There is pharmacological synergism with drinks containing methylxanthines (e.g. tea and cola), which therefore enhances the effects of khat .

35. Addiction, Tolerance and Withdrawal Cathinone is the dependence-producing constituent of khat leaves Tolerance to khat practically does not occur; if it does, the doses are increased only very slowly. Tolerance may be due to the intrinsic properties of khat or to the physical limits on the amount that can be consumed There are conflicting opinions regarding the existence of a withdrawal syndrome.

36. ................ con’t Physical withdrawal symptoms are documented, including physical or mental worriness , lack of energy, nightmares and slight trembling,which appear several days after ceasing to chew. Depressive disorder, sedation and hypotension are sometimes seen after withdrawal of khat . In one study only 0.6% of khat chewers continued to use in order to prevent withdrawal symptoms

37. Adverse effects of khat Psychological sequelae A feeling of well-being, a sense of euphoria, excitement ↑ energy levels , alertness , and ability to concentrate Improvement in self-esteem and ↑ in libido An enhanced imaginative ability and capacity to associate ideas An improvement in the ability to communicate and a subjective improvement in work performance.

38. ..................... con’t After chewing ceases : Insomnia, numbness, lack of concentration and low mood. Anxiety, tension, restlessness and hypnagogic hallucinations Minor reactions include over-talkativeness, overactivity , anxiety, irritability, agitation and aggression.

39. ............. Con’t Physical sequelae CVS - Tachycardia, arrythimia , palpitation, hypertension, vasoconstriction,MI , pulmunary edema, cerebral haemorrhag e Respiratory - Bronchitis, tachypnoea , dyspnoea , TB GIS -Dry mouth, polydypsia , dental caries, periodontal disease, chronic gastritis, gastric ulcer, constipation, paralytic ileus , anorexia weight loss, increased risk of upper GI malignancy Hepatobiliary -fibrosis,cirrhosis GUS - Spermatorrhoea , impotence, libido change, urinary retention Obstetric effects -LBW, still birth, impaired lactation Metabolic and endocrine effects -Hyperthermia, perspiration, hyperglycemia CNS -Dizziness , impaired concentration, insomnia, headache, mydriasis , impaired motor coordination, fine tremor

40. 4/26/2013 Acute effects Long term effects relief of fatigue, increased alertness, reduced sleepiness malnutrition mild euphoria and excitement; improved ability to communicate, loquacity psychotic reactions after chronic use; depressive reactions tachycardia, hypertension irritative disorders of the upper gastro-intestinal tract (gastritis, enteritis ) moderate hyperthermia cardiovascular disorders mydriasis , blurred vision hemorrhoids anorexia, dry mouth, constipation impaired male sexual function, spermatorrhoea , impotence psychotic reactions at high doses irritability and depressive reactions at the end of a khat session periodontal disease, mucosal lesions ( keratosis ) lethargy and sleepy state (next morning)

41. Psychiatric Complications When the amount chewed per day was greater than two bundles , morbidity was significantly increased many researchers consider that khat precipitates a psychotic illness in those who are already predisposed The main psychiatric manifestations short-lived schizophreniform psychotic illness mania and more rarely, depression On occasions these presentations are associated with episodes of self-harm or harm to others.

42. ..................... con’t Psychoses The characteristics of psychoses following the use of khat describes two main types a paranoid or schizophreniform psychosis (similar to an amphetamine-like psychosis) and a manic psychosis.

43. ..................... con’t Schizophreniform psychosis The patients typically present with: paranoid delusions fear, a hostile perception of the environment auditory hallucinations (frequently of a persecutory or threatening type) ideas of reference, thought alienation and a tendency to isolate themselves, or alternatively displaying aggressive behaviour to wards others. Consumption is ceased, resolution occurs 3–11 days but there is a tendency for the psychosis to recur if chewing is restarted.

44. ..................... con’t 2. Manic psychosis The patient presented with : hyperactivity, shouting, pressure of speech grandiose delusions with flight of ideas and tangential thought processes, and a labile mood varying from euphoria to anger. Symptoms subsided spontaneously within about 8 hours of chewing

45. ..................... con’t Depression Arises on cessation of use. This has, on occasions, been associated with self-harm and suicide. Self-harm, suicide and violence Rare, documented during both chewing and the subsequent intoxication phase.

46. ..................... con’t Socio-economic effects Decreased productivity - loss of work hours, decreased economic production, malnutrition and diversion of money Family and marital problems - neglect, dissipation of family income and inappropriate behaviour

47. Detection of khat Urinalysis Initially, a rapid screen by immunoassay detects amphetamine-related compounds Then gas chromatography mass spectrometry is performed(presence of norephedrine ) The test will give a positive result for up to about 48 hours after consumption of khat .

48. Management of psychiatric problems 1. Cessation of use 2 .Pharmacological management Antipsychotics- thioridazine at doses of 300–600 mg per day for 1 week and haloperidol (doses not specified) 3 . ECT 4 . Psychotherapy

49. References Kaplan and sadock , synopsis of psychiatry,10 th edition,2007 WHO, 2006 a. Assessment of khat ( Catha edulis Forsk ), WHO Expert Committee on Drug Dependence, 34 ECDD 2006/4.4. internet

50. Thank you very much