stumulants

1. STIMULANTS BY: MOHAMMED JUNDA (C-II) APRIL,2018 E.C

2. OUTLINES • INTRODUCTION • EPIDEMOLOGY • NEUROPHARMACOLOGY • DIAGNOSIS AND CLINICAL FEATURE(S) • INTOXICATION AND WITHDRAWAL • PSYCHOTIC EFFECTS • MANAGEMENT

3. AMPHETAMINES • Amphetamines and amphetamine-like drugs are among the most widely used illicit substances, second only to cannabis, in the United States, Asia, Great Britain, Australia, and several other Western European countries. • Methamphetamine, a congener of amphetamine, has become even more popular in recent years.

4. Amphetamine sulfate (Benzedrine) • first synthesized in 1887, and in 1932 inhaler for the Rx of nasal congestion and asthma. • In 1937, tablets for the Rx of narcolepsy, post-encephalitic parkinsonism, depression, and lethargy. • In the 1970s, widespread amphetamine distribution. • The current U.S. FDA–approved indications • limited to attention-deficit/hyperactivity disorder (ADHD) and narcolepsy; • however, amphetamines are also used in the treatment of obesity, depression, dysthymia, chronic fatigue syndrome, multiple sclerosis, fibromyalgia, and neurasthenia.

5. Preparations • The major amphetamines currently available and used in the United States are • Dextroamphetamine(Dexedrine), • Methamphetamine(Desoxyn), • mixed dextroamphetamine-amphetamine salt (Adderall), and • amphetamine-like compound methylphenidate (Ritalin). • Street names as ice, crystal, crystal meth, and speed. • Other amphetamine-like substances are ephedrine, pseudoephedrine, and phenylpropanolamine (PPA). • PPA -can dangerously exacerbate hypertension, precipitate a toxic psychosis, cause intestinal infarction, or result in death.. • Methamphetamine: • inhale, smoke, or inject IV. • psychological effects last for hours and powerful.

6. Epidemiology • According to the National Association of Counties, • United States name methamphetamine as the primary drug problem. • On a global basis, according to a report from the United Nations Office on Drugs and Crime • use of amphetamine-type stimulants, including methamphetamine, is also a major concern, ranking as the second most widely used substance, following marijuana. • According to the 2010 National Survey on Drug Use and Health (NSDUH), • persons 12 years or older were current users of methamphetamine (0.1%).

7. Neuropharmacology • The classic amphetamines • release of catecholamines, particularly dopamine, from presynaptic terminals. • potent for the dopaminergic neurons projecting from the ventral tegmental area to the cerebral cortex and the limbic areas. • reward circuit pathway, and its activation is probably the major addicting mechanism for the amphetamines. • The designer amphetamines cause the release of catecholamines (dopamine and norepinephrine) and of serotonin, the neurotransmitter implicated as the major neurochemical pathway for hallucinogens.

8. Cont.. • Amphetamines • rapidly absorbed orally and have a rapid onset of action, usually within 1 hour when taken orally. • Intravenously - almost immediate effect • Users often overcome the tolerance by taking more of the drug..

9. CLINICAL FEATURES • elation, • euphoria, • heightened self-esteem, and • perceived improvement on mental and physical tasks

10. The MC causes of death related to amphetamine toxicity are arrhythmia, hyperthermia, and ICH.

12. Stimulant Withdrawal • After stimulant intoxication, a “crash” occurs with symptoms of anxiety, dysphoric mood, lethargy, fatigue, nightmares, headache, profuse sweating, muscle cramps, stomach cramps, and insatiable hunger. • peak in 2 to 4 days and resolved in 1 wk. • The most serious withdrawal symptom is depression • severe after the sustained use of high doses of stimulants • can be associated with suicidal ideation or behavior. • Experience powerful and intense cravings for cocaine • because taking cocaine can eliminate the unpleasant withdrawal symptoms.

14. Stimulant Intoxication Delirium • Associated with • high doses of a stimulant • sustained use • combination of stimulants with other substances • use of stimulants by a person with preexisting brain damage

15. Amphetamine-Induced Psychotic Disorder • Hallmark • the presence of paranoid delusions and hallucinations, which occurs in up to 50% of stimulant users. • Auditory hallucinations are also common, but visual and tactile hallucinations are less common than paranoid delusions. • Rx:- short-term use of an antipsychotic medication such as haloperidol (Haldol).

16. Amphetamine-Induced Psychotic Disorder • The positive symptoms of amphetamine-induced psychotic disorder and schizophrenia are similar, • amphetamine-induced psychotic disorder generally lacks the affective flattening. • only the resolution of the symptoms in a few days or a positive finding in a urine drug screen test eventually reveals the correct diagnosis.

17. Amphetamine-Induced Mood Disorder • In general, • intoxication is associated with manic or mixed mood features, • withdrawal is associated with depressive mood features. Amphetamine-Induced Anxiety Disorder • Onset:during intoxication or withdrawal. • Stimulants can induce symptoms similar to those seen in panic disorder, and phobic disorders, in particular.

18. Stimulant-Induced OCD • Onset: during intoxication or withdrawal. • After high doses of stimulants, some individuals develop time-limited stereotyped behaviors or rituals i.e., • picking at clothing, and arranging and rearranging items purposelessly.

19. Stimulant-Induced Sexual Dysfunction • High doses and long-term use are associated with erectile disorder and other sexual dysfunctions. • Stimulant-Induced Sleep Disorder • Can begin during either intoxication or withdrawal, • Stimulant intoxication can produce insomnia and sleep deprivation.

20. Adverse effects of Amphetamine physical • The most serious: • cerebrovascular, cardiac, and GI effects. • Life-threatening conditions are MI, severe HTN, cerebrovascular disease, and ischemic colitis. • Neurological symptoms associated with high doses • twitchingto tetany to seizures to coma anddeath • The non–life-threatening • flushing, pallor, cyanosis, fever, headache, tachycardia, palpitations, nausea, vomiting, bruxism (teeth grinding), shortness of breath, tremor, and ataxia.

21. Psychological • Restlessness, dysphoria, insomnia, irritability, hostility, and confusion. • Can also induce symptoms of anxiety disorders, such as GAD and panic disorder, as well as ideas of reference, paranoid delusions, and hallucinations.

22. TREATMENT AND REHABILITATIONAmphetamines • Individual, family, and group psychotherapy are usually necessary to achieve lasting abstinence. • Antipsychotic andanxiolytics may be necessary on a short-term basis. • In the absence of psychosis, diazepam (Valium) is useful to treat patients’ agitation and hyperactivity.

23. Treatment of Intoxication • Acute intoxication is treated by symptomatic measures, e.g. • hyperpyrexia (cold sponging, parenteral antipyretics), • seizures (parenteral diazepam), • psychotic symptoms (antipsychotics), and • hypertension (antihypertensives). • Acidification of urine (with oral NH4Cl; 500 mg every 4 hours) facilitates the elimination of amphetamines.

24. Treatment of Withdrawal Symptoms • The presence of severe suicidal depression may necessitate hospitalization. • The treatment includes symptomatic management, use of antidepressants and supportive psychotherapy. • The management of withdrawal syndrome is usually the first step towards successful management of amphetamine dependence.

25. KHAT • The fresh leaves of Catha edulis, a bush native to East Africa, have been used as a stimulant in the Middle East, Africa, and the Arabian Peninsula for at least 1,000 years. • Khat is still widely used in Ethiopia, Kenya, Somalia, and Yemen. • has cathinone± (S[-] aminopropiophenoneor S[-]2-amino-1-phenyl-1-propanone) been identified as the substance responsible. α-

26. Cathinone • converted in the plant to norephedrine and cathine (norpseudoephedrine), for their stimulant effects. • structurally and functionally closely similar to amphetamine • has most of the CNS and peripheral actions of amphetamine and • the same mechanism of action • releases catecholamaines from pre-synaptic storage sites resulting in CNS stimulation and a variety of peripheral sympathomimetic effects such as tachycardia and hypertension

27. Cathinone • Increased levels of energy, alertness and self-esteem, sensations of elation, decreases hunger, alleviates fatigue, enhanced imaginative ability and capacity to associate ideas. • It is also used to increase attention, and counteract the effects of alcohol. • At high doses, it can induce an amphetamine-like psychosis in humans.

28. Central stimulation by khat is manifested by euphoria, increased alertness, hyperactivity, excitement, aggressiveness, anxiety, elevated blood pressure, and manic behaviour. • The simulation lasts for about 3 hours.

29. Epidemology • Ethiopia • The overall khat chewing prevalence was 15.3% . • Regional variation was observed with the highest in Harar town (53.2%) and lowest in Tigrayregional state (1.1%). • The prevalence in Dire Dawa 44.9%, Oromiya 26.4% and Somali regional state 26.0%. (Analysis Using the 2011 Demographic and Health Survey)

30. THE PHARMACOKINETICS OF KHAT • Rapidly absorbed after oral administration • Lipophilic compounds that readily cross the BBB. • Has positive inotropic and chronotropic effects on the heart. • Cross-tolerance between d-amphetamine and d-cathinone. • At the cellular level cathinone has a similar effect to amphetamine atcentral dopaminergic synapses, as well as effects on other central and peripheral NTs.

31. Cont….. • The psychoactive substances in khat act on two main neurochemical pathways: dopamine and noradrenalin. • It has been suggested that cathinone, like amphetamine, releases serotonin in the CNS. • Both these substances induce the release of dopamine from CNS dopamine terminals thereby increasing the activity of dopaminergic pathways.

32. THE EFFECTS OF KHAT • Increases in temperature, BP and PR. • Transient facial and conjunctivalcongestion, and extra-systoles. • Increased diuresis, increased libidoand impotence. • Brownish staining of the teeth and mydriasiswith a staring gaze are considered pathognomonic signs of khatuse.

33. THE EFFECTS OF KHAT • Unwanted effects associated with khatare sleeplessness, nervousness, impotence and nightmares. • GIT- anorexia and constipation • LBW and inhibition of lactation • Divert their income into khatchewing, neglecting their families' needs. • Causal factor for family instability. • The concomitant use of alcohol to counteract the stimulant and insomniac effects of khat.

34. withdrawal symptoms • The most frequently reported withdrawal symptoms were feeling depressed, craving, and feeling fatigued. • increased appetite • irritability • hypersomnia • nightmares . • Usually felt the withdrawal symptoms for >10 hrs, the mean duration of 23.3 h. • Cause impairment in social, occupational, or other important areas of their functioning. • feeling hot all over, • feeling hot in arms and legs, • tremor of the tongue and hand, • tremor of the whole body • headache

35. Khat and psychosis • Exacerbate psychotic states in psychiatric pts. • Triggers the onset of schizophrenia in an individual with high vulnerability to the disease. • The behaviouralsensitization. • Khat consumption may affect the course of a psychotic disorder. • Usually paranoid delusions and hallucinationhave been seen. • Khatuse has the potential to develop into dependence.

36. REFERENCES

37. 10Q!