Substance- Related Disorders

1. Substance- Related Disorders Prepared by Assist Prof Dr Sirwan K Ali College of Medicine (2012-2013)

3. Introduction • A primary, chronic, neurobiological disease, with genetic, psychosocial, and environmental factors influencing its development and manifestations

4. Introduction Addiction 5 C’s • Chronic • Compulsiveuse, not associate with willpower • Control-impaired--unable to limit intake • Craving--desire for the drug when it is absent • Continued use despite harm—irrational pursuit of mood change/high at expense of family, job, emotional well-being, and health

5. SUBSTANCE ABUSE • DIAGNOSIS AND DSM-IV CRITERIA Abuse is a pattern of substance use leading to impairment or distress for at least 1 year with one or more of the following manifestations: 1. Failure to fulfill obligations at work, school, or home 2. Use in dangerous situations (i.e., driving a car) 3. Recurrent substance-related legal problems 4. Continued use despite social or interpersonal problems due to the substance use

6. Substance Dependence • A maladaptive pattern of substance use leading to clinically significant impairment or distress, manifested by 3 or more of the following occurring at any time within the same 12 month period: • Tolerance -need for more to achieve the same effect -decreased effect with same amount • Withdrawal -Characteristic withdrawal syndrome -Using substance to avoid withdrawal Sx

7. Substance Dependence cont. • Substance taken in larger amount or for longer time than intended • Persistent unsuccessful attempts to cut down or control use • Great deal of time spent obtaining, using, or recovering from use • Important social, occupational, recreational activities given up or reduced • Use is continued despite knowledge that has persistent or recurrent physical or psychological problems that were caused or exacerbated by use

8. Learning and Physiological Basis for Dependence • Reinforcing behaviors / Pleasure Circuit/ reward circuit/ hippocampal and limbic memory circuit • acute increases of levels of neurotransmitters in the brain • Increased Dopamine (DA) in the limbic areas (ventral tegmental DA neurons synapsing on the nucleus accumbens neurons is very rewarding. • Some drugs also increase serotonin and/or norepinephrine.

9. Learning and Physiological Basis for Dependence • Reinforcing behaviors / Pleasure Circuit/ reward circuit/ hippocampal and limbic memory circuit • acute increases of levels of neurotransmitters in the brain • Ex. Increased Dopamine (DA) in the limbic areas (ventral tegmental DA neurons synapsing on the nucleus accumbens neurons is very rewarding. • Some drugs also increase serotonin and/or norepinephrine.

10. EPIDEMIOLOGY • Lifetime prevalence of substance abuse or dependence in the United States: Approximately 17% • More common in men than women

11. Alcohol and other drugs are associated with: • Up to 50% spousal abuse • 50% traffic accidents • 49% murders • 68% manslaughter charges • 69% drownings • 38% child abuse • 52% rapes • 62% assaults • 20-35% suicides (Johnson-1997)

12. Cost to Business & Industry • 100 million annually • 40% industrial fatalities • 47% workplace injuries • 50% of motor vehicle fatalities(2005)

13. Estimated Economic Cost to Society from Substance Abuse and Addiction: • Illegal drugs: $181 billion/year • Alcohol: $185 billion/year • Tobacco: $158 billion/year Total: $524 billion/year Surgeon General’s Report, 2004; ONDCP, 2004; Harwood, 2000.

14. Classes of Psychoactive Substances • Alcohol • Amphetamines and related substances • Caffeine • Cannabis • Cocaine • Hallucinogens • Inhalants • Nicotine • Opioids • Phencyclidine and related substances • Sedatives, hypnotics, or anxiolytics

15. Categories of Drugs Stimulants - “uppers” - stimulate the central nervous system - amphetamines, amyl nitrite, cocaine, crack, ecstasy - “downers” Depressants - depress the central nervous system - alcohol, barbiturates, benzodiazepines Analgesics - powerful painkillers - from opium poppy or synthetically produced Hallucinogens - dramatically alter perception - LSD, psilocybin, cannabis, ecstasy

16. Predisposing Factors Biological Factors • Genetics: apparent hereditary factor, particularly with alcoholism Biochemical: alcohol may produce morphine-like substances in the brain that are responsible for alcohol addiction Psychological Factors • Developmental influences: • Punitive superego • Fixation in the oral stage of psychosexual development • Personality factors:certain personality traits suggested to play a part in both development and maintenance of alcohol dependence, including • Low self-esteem • Frequent depression • Passivity • Inability to relax or defer gratification • Inability to communicate effectively

17. Sociocultural Factors • Social learning: children and adolescents more likely to use substances with parents who provide model for substance use • Use of substances may also be promoted within peer group • Conditioning: pleasurable effects from substance use act as a positive reinforcement for continued use of substance • Cultural and ethnic influences: some cultures are more prone to the abuse of substances than others

18. Alcohol

19. ALCOHOL (EtOH) • Alcohol activates gamma-aminobutyric acid (GABA) and serotonin receptors in the central nervous system (CNS) and inhibits glutamate receptors. GABA receptors are inhibitory, and thus alcohol has a sedating effect. • Alcohol is the most commonly abused substance in the United States. 7 to 10% of Americans are alcoholics, (also in our community)

20. Alcohol: Patterns of Use or Abuse Alcohol Abuse and Dependence Patterns of Use or Abuse • Phase I: Pre-alcoholic phase: characterized by use of alcohol to relieve everyday stress and tensions of life • Phase II: Early alcoholic phase:begins with blackouts: brief periods of amnesia that occur during or immediately following a period of drinking; alcohol is now required by the person. • Phase III: The crucial phase:person has lost control; physiological dependence clearly evident • Phase IV: The chronic phase: characterized by emotional and physical disintegration; person is usually intoxicated more often than sober

21. SCREENING FOR ABUSE • The CAGE questionnaire is used to screen for alcohol abuse. Two or more “yes” answers are considered a positive screen; one “yes” answer should arouse suspicion of abuse: • 1. Have you ever wanted to cut down on your drinking? • 2. Have you ever felt annoyed by criticism of your drinking? • 3. Have you ever felt guilty about drinking? • 4. Have you ever taken a drink as an “eye opener” (to prevent the shakes)?

22. DSM-IV Alcohol Dependence Maladaptive drinking leading to clinically significant impairment or distress, shown by 3+ of the following in the same 12-month period: • Drinking more or longer than intended • Persistent desire or unsuccessful efforts to cut down or stop • A great deal of time spent on drinking or getting over its effects • Important activities given up or reduced because of drinking • Continued drinking despite knowledge of a serious physical or psychological problem • Tolerance • Withdrawal, or drinking to avoid or relieve drinking

23. DSM-IV Alcohol Abuse Not dependent, and maladaptive drinking leading to clinically significant impairment or distress, shown by 1 + of the following: • Continued use despite social/interpersonal problems • Hazardous use (e.g., driving when impaired by alcohol) • Frequent drinking leading to failure to function in major roles • Legal problems

24. What is the safe level of alcohol? A widely accepted measure is the term of units of alcohol One unit is a 8 grams of ethanol, correspond to half a pint of beer, a wine glass of wine..etc Safe level; Men; up to 21 units per week. Women: up to 14 units per week. Dangerous level; Men: over 50 units per week. Women: over 35 units per week.

25. Mental Disorders Due to Use of Alcohol • Acute intoxication: • euphoria, flushed face, ataxia, slowed reaction time, impaired motor performance, slurred speech, poor concentration; in higher doses behavioural changes – disinhibition of sexual and aggressive impulses, increased suicidal and homicidal behaviour • Pathological intoxication: • sudden change of consciousness with aggressive behaviour and amnesia • Harmful use: • physical complications – hypertension, arteriosclerosis, heart infarction, cardiomyopathy, brain stroke, liver cirrhosis, fatty liver, gastritis, etc. • psychic complications - depression

26. DIFFERENTIAL DIAGNOSIS • Hypoglycemia, hypoxia, mixed EtOH–drug overdose, ethylene glycol or methanol poisoning, hepatic encephalopathy, psychosis, and psychomotor seizures • DIAGNOSTIC EVALUATION Serum EtOH level or an expired air breathalyzer can determine the extent of intoxication. A computed tomographic (CT) scan of the head may be necessary to rule out subdural hematoma or other brain injury.

27. TREATMENT • Intoxication (Acute) Ensure adequate airway, breathing, and circulation. Monitor electrolytes and acid–base status. Obtain finger-stick glucose level to exclude hypoglycemia. • Thiamine (to prevent or treat Wernicke’s encephalopathy), naloxone (to reverse the effects of any opioids that may have been ingested), and • folate are also administered. • The liver will eventually metabolize alcohol without any other interventions provided that a reliable airway is maintained; • a severely intoxicated patient may require intubation while he or she is recovering. • Gastrointestinal evacuation (e.g., gastric lavage and charcoal) has no role in the treatment of EtOH overdose but may be used in mixed EtOH–drug overdose.

28. Dependence (Long Term) 1. Alcoholics Anonymous—self-help group 2. Disulfiram (Antabuse)—aversive therapy; inhibits aldehyde dehydrogenase, causing violent retching when the person drinks 3. Psychotherapy and selective serotonin reuptake inhibitors (SSRIs) 4. Naltrexone—though an opioid antagonist, helps reduce cravings for alcohol.

29. Alcohol Withdrawal • The pathophysiology of the alcohol withdrawal syndrome is poorly understood. • Patients experiencing mild withdrawal may be irritable and complain of insomnia. Those in more severe withdrawal may experience fever, disorientation, seizures, or hallucinations. • The signs and symptoms of the alcohol withdrawal syndrome include insomnia , anxiety, tremor, irritability, anorexia, tachycardia, hyper-reflexia, hypertension, fever, seizures, hallucinations, and delirium.

30. Delirium tremens (DTs) • Delirium tremens (DTs) is the most serious form of EtOH withdrawal and often begins within 72 hours of cessation of drinking. • In addition to delirium, symptoms of DTs may include visual or tactile hallucinations, gross tremor, autonomic instability, and fluctuating levels of psychomotor activity.

31. DIAGNOSTIC EVALUATION • Accurate and frequent assessment of vital signs is essential, as autonomic instability may occur in cases of severe withdrawal and DTs. • Careful attention must be given to the level of consciousness, and the possibility of trauma should be investigated. • Signs of hepatic failure (e.g., ascites, jaundice, coagulopathy) may be present.

32. DIFFERENTIAL DIAGNOSIS Alcohol-induced hypoglycemia, acute schizophrenia, drug-induced psychosis, encephalitis, thyrotoxicosis, anticholinergic poisoning, and withdrawal from other sedative–hypnotic type drugs • TREATMENT Tapering doses of benzodiazepines (chlordiazepoxide, lorazepam) Thiamine, folic acid, and a multivitamin to treat nutritional deficiencies Magnesium sulfate for post with-drawalseizures

33. Long-Term Complications of Alcohol Intake • Wernicke–Korsakoffsyndrome is caused by thiamine (vitamin B1) deficiency resulting from the poor diet of alcoholics. Wernicke’s encephalopathy is acute and can be reversed with thiamine therapy: 1. Ataxia 2. Confusion 3. Ocular abnormalities (nystagmus, gaze palsies) • If left untreated, Wernicke’s encephalopathy may progress into Korsakoff’s syndrome, which is chronic and often irreversible. 1. Impaired recent memory 2. Anterograde amnesia 3. +/− Confabulation • Confabulation: Making up answers when memory has failed

34. Discussion

35. CNS Stimulant Abuse and Dependence • A profile of the substance • Amphetamines • Nonamphetamine stimulants • Cocaine • Caffeine • Nicotine • Patterns of use and abuse • Effects on the body • CNS effects • Cardiovascular effects • Pulmonary effects • GI and renal effects • Sexual functioning

36. Cocaine Powder Cracked cocaine cocaine

37. COCAINE • Cocaine blocks dopamine reuptake from the synaptic cleft, causing a stimulant effect. Dopamine plays a role in behavioral reinforcement (“reward” system of the brain). • Cocaine Intoxication CLINICAL PRESENTATION • Cocaine intoxication often produces euphoria, increased or decreased blood pressure, tachycardia or bradycardia, nausea, dilated pupils, weight loss, psychomotor agitation or depression, chills, and sweating. It may also cause respiratory depression, seizures, arrhythmias, and hallucinations (especially tactile). • Cocaine’s vasoconstrictive effect may result in myocardial infarction (MI) or cerebrovascular accident (CVA).

38. DIFFERENTIAL DIAGNOSIS Amphetamine or phencyclidine (PCP) intoxication, sedative withdrawal • DIAGNOSTIC EVALUATION Urine drug screen (positive for 3 days, longer in heavy users) • TREATMENT Intoxication 1. For mild-to-moderate agitation: Benzodiazepines 2. For severe agitation or psychosis: Haloperidol 3. Symptomatic support (i.e., control hypertension, arrhythmias) • Dependence 1. Psychotherapy, group therapy 2. Tricyclic antidepressants (TCAs) 3. Dopamine agonists (amantadine, bromocriptine)

39. Cocaine Withdrawal • Abrupt abstinence is not life threatening but produces a dysphoric “crash”: malaise, fatigue, depression, hunger, constricted pupils, vivid dreams, psychomotor agitation or retardation • TREATMENT: Usually supportive—let patient sleep off crash.

40. Methamphetamine S p e e d shabu I C E

41. AMPHETAMINES • Classic amphetamines: Dextroamphetamine (Dexedrine), methylphenidate(Ritalin), methamphetamine (Desoxyn, ice, speed, “crystal meth,” “crack”) • Substituted (“designer”) amphetamines: MDMA (ecstasy), MDEA (eve) • Classic amphetamines release dopamine from nerve endings, causing a stimulant effect. They are used medically in the treatment of narcolepsy, attention deficit hyperactivity disorder (ADHD), and depressive disorders. • Designer amphetamines release dopamine and serotonin from nerve endings and have both stimulant and hallucinogenic properties.

42. Amphetamine Intoxication • CLINICAL PRESENTATION Amphetamine intoxication causes symptoms similar to those of cocaine. • DIFFERENTIAL DIAGNOSIS Cocaine or PCP intoxication. schizophrenia. • DIAGNOSTIC EVALUATION Urine drug screen (positive for 1 to 2 days). A negative routine drug screen does not rule out amphetamine use, since most assays are not of adequate sensitivity. A negative drug screen can never completely rule out substance abuse or dependence. • TREATMENT Similar to cocaine • Amphetamine Withdrawal Similar to cocaine withdrawal

43. CAFFEINE: • Is the most commonly used psychoactive substance usually in the form of coffee or tea. • Caffeine acts as an adenosine antagonist , causing increased cyclic adenosine monophosphate (cAMP) and a stimulant effect via the dopaminergic system. • One cup of coffee :100 to 150 mg caffeine. • One cup of tea : 40 to 60 mg caffeine.

44. Caffeine intoxication & withdrawal: • May occur with consumption of over 250 mg of caffeine. • Signs and symptoms include anxiety, insomnia, twitching, rambling speech, flushed face, GI disturbance and restlessness. • Consumption of more than 1 g of caffeine may cause tinnitus , sever agitation and cardiac arrhythmias. • In excess of 10g death may occur secondary to seizures and respiratory failure. • Treatment: supportive and symptomatic.

45. Caffeine intoxication & withdrawal: Caffeine withdrawal: -resolve within 1 week and include headache, nausea/vomiting, drowsiness, anxiety or depression. Treatment : taper consumption of coffee containing products , use analgesia to tx headache , rarely short course of benzadiazepines may be indicated to control anxiety.

46. Nicotine: - is derived from the tobacco plant and stimulate nicotinic receptors in autonomic ganglia of the sympathetic and parasympathetic nervous systems. • Cigarette smoking leads to many health risks and nicotine is rapidly addictive through its effect on the dopaminergic system.

47. Nicotine intoxication & withdrawal: • Act as a CNS stimulant and may cause restlessness, insomnia, anxiety, and increased GI motility . • Tobacco users report improved attention, improved mood and decreased tension. • Treatment: cessation. Nicotine withdrawal: • Withdrawal causes intense craving, dysphoria, anxiety, increased appetite, irritability and insomnia.

48. Nicotine intoxication & withdrawal: Treatment: smoking cessation with the aid of : • Behavioral counseling. • Nicotine replacement therapy (gum, patch). • Clonidine. • antidepressant that help reduce cravings. relapse after abstinence is common!!

50. Sedatives-hypnotics: -these drugs are highly abused since they are more readily available than other drugs such as cocaine or opioids. -benzodiazepines are commonly used in the treatment of anxiety disorders and are therefore obtained easily via prescription. -they potentiate the effects of GABA by increasing the frequency of chloride channel opening. *Barbiturates are used in the tx of epilepsy and as anesthetics , and they potentiate the effects of GABA by increasing the duration of chloride channel opening .