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Dr Isa Naina MohamedDept. Of PharmacologyFaculty of Medicine, UKM.

[email protected]
http://images.google.com.my/imgres?imgurl=http://www.cbc.ca/gfx/photos/drug_injection.jpg&imgrefurl=http://www.cbc.ca/stories/2003/06/25/injection_030624&h=188&w=200&sz=5&tbnid=mlaxOsV0dg4J:&tbnh=93&tbnw=99&hl=en&start=7&prev=/images?q=drug+addicts+pictures&svnum=10&hl=en&lr=&rls=RNWE,RNWE:2004-43,RNWE:en&sa=N


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1. Dependence Psychologic dependence Compulsive drug-seeking behavior. Person repetitively usesdrugs for personal satisfaction, often fully aware of therisks. Deprivation will result in strong desire or craving. Physiologic physical) dependence Withdrawal of the drug produce physical signs and symptomsopposite to those sought by the user. 2. Withdrawal/abstinence syndrome The physical signs and symptoms seen when a drug that hasproduced physiologic dependence is suddenly withdrawn. 3.Addiction Imprecise term. Supposed to mean state of physiologic andpsychologic dependence.


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4. Tolerance Decreased response to the effects of the drug, necessitatingever larger doses to achieve the same effect. Metabolic tolerance - due to increased disposition of drug after chronic use Behavioral tolerance - ability to compensate for the drugs effects Functional tolerance - most common - due to compensatory changes in receptors, effectorenzymes, or membrane action of the drugs. 5. Rescidivism - return to abuse of agent


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1. CNS depressants Opioids, barbiturates/benzodiazepines/other sedative-hypnotics, alcohol 2. CNS stimulants Caffeine, nicotine, cocaine, amphetamine 3. Hallucinogens LSD, mescaline, psilocybin, PCP 4. Marijuana cannabis) 5. Inhalants 6. Steroids


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OPIOIDS Heroin Morphine Codeine Route of administration: Intravenous preferred) Intranasal Psychologic dependencerush euphoriatranquility, sleepiness Dose < 25mg effects last3-5 hrs Tolerance occurs withchronic use


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Physiologic dependence Withdrawal syndrome Acute phase: 7-10 days - increased activity of the autonomic nervous system - lacrimation, rhynorrhea, yawning, sweating - restless sleep, weakness, chills, gooseflesh cold

turkey), nausea, vomiting, muscle aches, involuntarymovements - hyperpnoea, hyperthermia, hypertension Secondary phase: 26-30 weeks - hypotension, bradycardia, hypothermia, mydriasis - decreased responsiveness of the respiratory center to CO2


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Pharmacological treatment of withdrawal syndrome a. Substitute a longer acting, orally active,pharmacologically equivalent drug from the samegroup, eg methadone Stabilize patient on substitute drug Gradual withdrawal b. Clonidine: centrally acting sympatholyticagent. Reduce sympathetic overactivity during withdrawal No narcotic action, non-addictive Other complications: Hepatitis B, AIDS Infections meningitis, osteomyelitis, abscesses Homicide, suicide, accidents


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Long-term treatment of opioid dependent persons a. Pharmacologic: opioid antagonis, eg naltrexone Long-acting, orally active pure antagonist Block effects of self-administered opioid Not popular with addicts 2. Non-pharmacologic Opioid rehabilitation program Psychosocial support Drug-free residential communities,group/individual psychotherapy, meditation etc.

OVERDOSE OF OPIOIDS: RESPIRATORY DEPRESSION


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BARBITURATES BENZODIAZEPINES ALCOHOL

Barbiturates and benzodiazepines Short and long-acting agents Short-acting agents more prone to abuse Benzodiazepines less abuse potential compared tobarbiturates


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Most of the dependence is psychologicPhysiologic dependence is rare with benzodiazepines Psychologic dependence Desired effect: sedation Other effects - initial disinhibition, followed by drowsiness - slurred speech, incoordination - similar to alcohol intoxication Therapeutic dose-dependence: Use of sedative hypnotics for insomnia or anxietydisorders can lead to dependence. Abruptwithdrawal may cause withdrawal syndrome.

Tolerance to sedative effects occur with bothbarbiturates and benzodiazepines. But more severewith barbiturates


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Withdrawal syndrome similar to alcohol withdrawal CNS overstimulation: - anxiety, tremors, twitches, nausea, vomitingfirst 16 hrs). - convulsions after 16-48 hrs - severe: delirium, hallucinations, psychosis Rx of withdrawal syndrome i. admin of long-acting sed-hypnotic, egchlordiazepoxide, diazepam gradual withdrawal ii. Propranolol, clonidine to suppresssympathetic overactivity

* Withdrawal syndrome more severe withbarbiturates than with benzodiazepines


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Treatment of chronic dependence 1. If short-acting sedative is abused, substitutewith Phenobarbital. Withdraw gradually

2. If long-acting sedative is abused, withdrawgradually. 3. Enroll patient in rehabilitation program Abuse of sedative-hypnotics is usually polydrugabuse + alcohol). Overdose with benzodiazepines only is not fatal,but overdose with barbiturates or polydrugcombination can cause respiratory depression anddeath


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ALCOHOL Most common sedative-hypnotic to be abused Psychologic dependence: Desired effect- sedation, relief of anxiety Tolerance occur after chronic use Other effects ataxia, slurred speech, impairedjudgement, disinhibited behaviour intoxication/drunkenness


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Physical dependence after chronic use Withdrawal syndrome - hyperexcitability, convulsions,psychosis, delirium tremens Management of alcohol withdrawal syndrome: i. Mild no pharmacological assistance ii. Severe - substitute with a long-actingbenzodiazepine - withdraw substitute drug gradually


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Long-term treatment of alcohol dependence1. DISULFIRAM

- inhibit aldehyde dehydrogenase Ethanol acetaldehyde acetate lcohol dehydrogen se ldehyde dehydrogen s disulfiram - accumulation of acetaldehyde flushing, throbbing, headache, confusion Discourage rescidivism Oral, rapid absorption Effect seen after 12 hrs May increase liver enzymes


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NALTREXONE Long-acting opioid antagonist - decrease rate of relapse and reduce alcoholcraving ? alcoholism associated with increase inendogenous opioids Oral, daily dose 50 mg Adverse effects: nausea, dizziness, headache High dose elevation in liver enzymes Naltrexone + Disulfiram = hepatotoxicity In opioid addicts, naltrexone will precipitatewithdrawal syndrome


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Criminal abuse of sedative-hypnotics: 1. Mickey Finn Chloral hydrate + ethanol alcohol) make person incapacitated helpless) 2. Flunitrazepam benzodiazepine) Anterograde amnesia Aid the criminal to commit crime robbery, rapeetc


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Amphetamines Methamphetamine Methedrine, speed) Methylenedioxymethamphetamine MDMA, ecstasy)

Cocaine Nicotine


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Dependence is mainly psychologic exceptcocaine Withdrawal increased appetite,exhaustion, mental depression Tolerance develops quickly


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Clinical aspectsAmphetamine 1. IV orgasm-like effect rush), mentalalertness, euphoria paranoid schizophrenia-like state, delusions exhaustion, withdrawal syndrome 2. Smoke crack) -- Similar to IV effectsCocaine Snuff/snort, smoke, IV euphoriaSpeedball Cocaine + heroin IV rush) Very dangerous False higher tolerance andcocaine is short acting


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Complications Hepatitis B, AIDS Amphetamines: Necrotizing arteritis brain hemorrhage, renalfailure Overdose amphetamines rarely fatal Cocaine: Vasoconstriction hypertension, myocardialinfarct, stroke


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Treatment 1. Subjects with psychosis treat with anti-psychotics haloperidol) 2. Subjects with depression antidepressants 3. Rehabilitation programs similar to opioidaddicts)

4. Nicotine dependence replacement with nicotinegum, transdermal patches


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Psychotomimetics, psychedelics Lysergic acid diethylamide LSD) semisynthetic Mescaline ] natural Psilocybin ] products Phencyclidine PCP) - synthetic


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LSD, mescaline, psilocybin Somatic, perceptual and psychologic effects 1. Somatic symptoms dizziness, weakness, tremors,nausea, paraesthesia 2. Perceptual symptoms blurring of vision, distortionof perspective, visual hallucinations, less discriminanthearing, change in sense of time 3. Psychologic symptoms impaired memory, difficulty inthinking, poor judgment, altered mood. 4. Overactivity of the sympathetic nervous system - mydriasis, tachycardia, mild hypertension, tremor,alertness Overdose non-fatal


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Toxicity Panic reactions large doses) Rx- sedation benzodiazepine) Acute psychotic/depressive reactions more commonwith PCP) Long-term treatment: Non-pharmacological, counselling etc


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MARIJUANA Cannabis/Ganja Preferred route inhalation smoking) Onset of effects20min Duration 3 hours Other routes oralsweets) Onset 3-4 hrs Duration 6-8 hrs


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Effects:1. Psychological: Euphoria, uncontrollable laughter, alteration oftime sense, depersonalization, sharpened vision Relaxed, dream-like state2. Physical signs: Tachycardia, red conjunctiva, postural hypotension Muscle weakness, tremors, unsteadiness Psychologic dependence ++ Tolerance +Treatment: Rehabilitation/Counselling


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Nitrous oxide Ether Chloroform Halothane Industrial solvents, eg toluene Aerosol propellants, eg fluorocarbons euphoria, exhilaration Organic nitrites, eg amyl nitrite sexual enhancer Toxicity liver, kidney, brain damage


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Anabolic steroids - increasing muscle mass and physical strength - athletes, body-builders etc. Side-effects Aggression, changes in libido and sexual function,mood changes, psychoses rare)

Acne, hirsutism females) gynaecomastia males) Edema, jaundice Withdrawal syndrome Fatigue, depression, craving for steroids Treatment: counselling


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