Drug Abuse (1)

Drug abuse is inappropriate and usually excessive, self-administration of a psychoactive drug for non-medical purposes. Almost all abused drugs exert their effects in the CNS causing euphoria or alter perception. Drugs with high abuse potential have a tendency to induce compulsive drug- seeking behavior. It is a major problem in Western countries

Characteristics of drug abuse include: 1.Addiction (Psychological dependence): A state when drug-taking becomes compulsive, taking precedence over other needs. The individual becomes so obsessed with constantly obtaining and using a drug(craving for drug) aided by the positive reinforcing effects of drug in the CNS. The drug becomes a primary goal and disrupts the ability to function in family, social, or work. Any drug that activates the mesolimbic- dopamine system is liable for addiction. This system correlates with pleasure and reward. It is composed of ventral tegmental area (VTA) & nucleus accumbens .Its pathway runs via the medial forebrain bundle, from the VTA in the midbrain to the nucleus accumbens and limbic region to the prefrontal cortex causing the positive reinforcing effects . Addictive drugs increase the release of dopamine in the mesolimbic- dopamine system .

2.Dependance (Physical dependence): A state resulting from chronic use of a drug that has produced tolerance and so physical symptoms of withdrawal (withdrawal or abstinence syndrome)result from abrupt discontinuation or dosage reduction. e.g: anexity,r estlessness,bradycardia &weight gain associated with tobacco abstinence. 3.Tolerance : The decrease in a pharmacological effect on repeated administration of the drug so there is need to increase the dose to reach the same pharmacological effect. It is produced by use of drug over a long period ,it may be classified as: pharmacodynamic (tissue type) which results from either changes in receptor density (downregulation of receptors in the agonists) or changes in receptor sensitivity (desensitisation)

pharmacokinetic (auto-induction of enzymes responsible for drug metabolism, e.g., in barbiturates). The degree of tolerance is generally proportional to the drug dose and the duration of use. Cross-tolerance :occurs when repeated use of a drug in a given category confers tolerance not only to that drug but also to other drugs in the same structural and mechanistic category.

Aetiology of substance abuse: 1-Personal factors to obtain: a. Euphoria, pleasure, psycho-stimulation (energy, mood & concentration), “ rush(a sudden intense feeling) and flush”(warm feeling) effect b. Relaxation & well being. c. Sexual arousal & increased libido. d. Getting relief by drugs due to low tolerance for painful emotions (or to escape from reality) 2.Cultural factors like Smoking, Alcoholism & Khat. 3.Iatrogenic factors particularly for sedatives & analgesics due to patient insistence or request or due to repeated prescriptions. 4.Increase availability of drugs & decrease in price.  

Risks of drug abuse include: Social & legal implications. Individual’s health problems: bacterial infections, hepatitis B & HIV. Drug toxicity & overdose. Withdrawal syndromes. Teratogenic effects (Fetal alcohol syndrome; Small babies). Increased incidence of premature deaths(death in the youngs or middle age). Psychiatric symptoms are more closely linked to polydrug use.

Types of abused drugs: Opioids Originates from Poppy, Papaver somniferum L.,which is an annual herb native to Southeastern Europe and western Asia. Acts on µ, κ, δ opioid receptors. Drugs acting on µ receptors are more capable of addiction: morphine, heroin, codeine. µ opioids cause an inhibition of GABAergic inhibitory interneurons that leads eventually to a disinhibition of dopamine neurons. Their medical Use is for analgesia and anesthesia (fentanyl, oxymorphone, hydromorphone, and morphine), antitussive (codeine, hydromorphone). Dependence – strong both physical and psychological Withdrawal syndrome: dysphoria, nausea, muscle aches, sweating, diarrhea and fever.

opium poppy

Treatment The opioid antagonists: naloxone & naltrexone reverses the effects of a dose of morphine or heroin within minutes. This may be life-saving in the case of a massive overdose. In the treatment of opioid addiction, a long-acting opioid (eg, methadone) is often substituted for the shorter-acting, more rewarding, opioid (eg, heroin). For substitution therapy, methadone is given orally once daily.

2. CNS DEPRESSANTS Sedative/Hypnotics Benzodiazepines (eg, Diazepam, Lorazepam) Benzodiazepines are positive modulators of the GABAA receptor- coupled with chloride channels & increase response to the endogenous ligand -GABA. They are commonly prescribed as anxiolytics and sleep medications. They represent a moderate risk for abuse, which has to be weighed against their beneficial effects. Benzodiazepines are abused after their use as hypnotics, but may also abused after use for treatment of withdrawal from other drugs eg, to attenuate anxiety during withdrawal from opioids or alcohol. Barbiturates Barbiturates, are now largely obsolete but were previously the most commonly abused sedative hypnotics (after ethanol).They have principally the same mechanism of action as benzodiazepines.

Both groups (benzodiazepines & barbiturates) may induce psychological and physical type of dependence & tolerance(markedly more likely, severe and earlier onset in barbiturates). Withdrawal syndrome: nervousness, restlessness, tremor, anxiety, confusion, dizziness, delirium, convulsions. Risk of acute intoxication and respiratory depression is much greater with barbiturates. benzodiazepines are safer but severe cases often appear when they are combined with alcohol.

Alcohol (Alcoholism) Ethanol is one of the most widely abused substances in the world.. Excessive consumption of alcoholic beverages has been linked to as many as half of all traffic accidents, two-thirds of homicides, three-fourths of suicides, and it is a significant factor in other crimes, in family problems, and in personal and industrial accidents.

Tolerance and dependence: Tolerance : develops over 1-3 weeks of continuing administration. There is a cross- tolerance with many anaesthetics (e.g. halothan)& with benzodiazepines. Withdrawal syndrome: tremor, nausea, sweating, fever, occasionally hallucinations and epilepsy-like seizures. psychological dependence severe. physical dependence with prolonged heavy use.

Alcohol-related problems include: Social problems: unemployment, marital problems, child abuse, financial difficulties, problems with the law, police & traffic. Psychological & neurological problems: e.g.Depression, suicide, withdrawal syndrome, peripheral neuropathy, cerebral haemorrhage, Cerebellar degeneration. Sexual problems: impotence, sterility, testicular atrophy, gynecomastia. Liver: fatty changes, cirrhosis . CVS: Hypertension, cardiomyopathy . GIT: Gastritis ,oesophageal varices, cancers ,Pancreatitis. Fetal alcohol syndrome (retarded growth, mental retardation and behavioural abnormalities) Hyperuricaemia with precipitation of gout Vitamin deficiencies.

Treatment of alcoholism Disulfiram – blockade of aldehydedehydrogenase  acummulation of acetaldehyde causing nausea, flushing, tachycardia, hyperventilation, panic… Aim: to make alcohol consumption unpleasant and intolerable Acamprosate – anti-craving effects. It has structural similarity to both glutamate and GABA and appears to reduce the effect of excitatory amino acids such as glutamate, and modifies GABA neurotransmission. Naloxone – reduces alcohol-induced reward (unclear mechanism) The drugs used to alleviate the acute abstinence syndrome: benzodiazepines, clonidine (inhibits exaggerated neurotransmitter release) and propranolol (blocks excessive sympathetic activity).