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Drug Abuse. 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.
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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,restlessness,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 factorslike Smoking, Alcoholism & Khat. 3.Iatrogenic factorsparticularly 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, PapaversomniferumL.,which is an annual herb native to Southeastern Europe and western Asia. • Acts on µ, κ, δopioid 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 physicaland psychological • Withdrawal syndrome: dysphoria, nausea, muscle aches, sweating, diarrhea and fever.
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-actingopioid (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 ,oesophagealvarices, 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 aldehydedehydrogenaseacummulation 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).
3.CNS Stimulants • Amphetamines: • Amphetamines (e.g.Amphetamine, methamphetamine)are a group of synthetic, indirect-acting sympathomimetic drugs that cause the release of endogenous biogenic amines, such as dopamine • They are taken orally, sniffed, smoked or injected. • Amphetamines are neurotoxic & can cause tachycardia ,dysrhythmias & hypertensive crisis. • Withdrawal consists of dysphoria, drowsiness (in some cases, insomnia), and general irritability. • Khat (Catha edulis) chewing leaves present in Yemen, Ethiopia & Somalia. Khat contains amphetamine-like agents (cathine & cathinone) with psychostimulant effects. It produces sense of well being, improvement of socialization, increase libido & increase work performance. It increases incidence of oral cancer.
Cocaine: • The prevalence of cocaine abuse has increased greatly over the past decades and now represents a major public health problem worldwide. Cocaine is highly addictive • Cocaine is an alkaloid found in the leaves of E. coca. It was used as a local anesthetic and to dilate pupils in ophthalmology • Cocaine blocks the uptake of dopamine, noradrenaline, and serotonin. • Given IV or by sniffing: a rapid stimulating effects similar to amphetamine. • It causes toxic psychosis & ulceration of the nasal mucosa& Other serious side effects.
Nicotine: • Nicotine is selective agonist of the nicotinic acetylcholine receptor . • In terms of numbers affected, addiction to nicotine exceeds all other forms of addiction. • Nicotine exposure occurs primarily through smoking of tobacco, which causes associated diseases that are responsible for many preventable deaths. The chronic use of chewing tobacco and snuff tobacco is also addicting. • Smoking-associated diseases :include lung cancer, heart disease, atherosclerosis, laryngeal cancer, oral cancer, oesophageal cancer, COPD, intrauterine growth retardation & low birth weight.
Tolerance: very quick perhaps due to desensitization of receptors. • withdrawal syndrome: craving ! increased irritability, anxiety, impaired performance of psychomotor tasks, aggressiveness ,sleep disturbances, headache and increased appetite. • highly addictive with the very strong psychological component.
Treatment of nicotine dependence • Most smokers would like to quit but few succeed • Combination of psychological and pharmacological treatment achieve success rate about 25% (after 1 year). • Nicotine replacement therapy: Nicotine in patches (controlled release), chewing gums, nasal sprays several times daily (short effect) • Adjunct therapy: • Bupropion: an antideprssant that reduces the severity of nicotine cravings and withdrawal symptoms .It inhibits the reuptake of dopamine and so increase dopamine activity in nucleus accumebens. Treatment course lasts for seven to twelve weeks. • Clonidine – rarely used due to the side-effects (hypotension, drowsiness…).
Cannabis and Cannabinoids • Extracts of the hemp plant (Cannabis sativa,Canabisindica) • Cannabis mostly smoked produces a sensation of relaxation & well-being. • Cannabis contains chemicals called cannabinoids .One of these, delta-9-tetrahydrocannabinol (THC), is believed to be responsible for most of the characteristic psychoactive effects of cannabis. • Marijuana: (dried leaves and flower heads) is one of the most frequently encountered illicit(illegal) drug worldwide. • Hashish: consists of the THC-rich resinous material of the cannabis plant, which is collected, dried, and then compressed into a variety of forms, such as balls, cakes. • Their CNS effects are combination of psychotomimetic & depressant effects eg: relaxation, well-being and euphoria ,uncontrolled laughing ,a feeling sharpened sensory awareness, with tastes, sounds and sights more intense and fantastic ,impairment of motor coordination (driving), impaired short-term memory and judgement, increased appetite ,analgesic effect,antiemetic effect.
Mechanism of action is through cannabinoid(CB) receptors (CB1- brain ) highly abundant in: hippocampus (memory), cerebellum (loss of coordination), and substantianigra (motor disturbances), hypothalamus (appetite) and mesolimbicdopaminergic pathway (reward) and cortex. • The synthetic 9-THC analog dronabinol is approved cannabinoid agonist currently marketed in the USA and some European countries for the treatment of anorexia in AIDS patients, as well as for refractory nausea and vomiting of patients undergoing chemotherapy. Nabilone, an older 9-THC analog used as an antiemetic and as an adjunct analgesic for neuropathic pain. • Tolerance and physical dependence occur only to a minor degree in heavy users. Withdrawal syndrome: weak and usually mild irritability, restlessness, confusion, sweating tremor and sleep disturbances. • Rimonabant is selective CB1receptor blocker used as an anorectic anti-obesity drug It can opposite effects of cannabinoids.
5.Hallucinogens • Hallucinogens are substances produce changes in perception, thought and mood. • Thoughts and perceptions tend to become distorted and dream-like, colours and sounds are more sharp. Different kind of hallucinations (visual, auditory, tactile and olfactory) appear. • Thought process tend to be illogical and disconnected • Lysergic acid diethylamide (LSD) is the most potent hallucinogen (agonist at 5-HT2 receptors) .Others include: Psilocybin,Mescaline( agonists at 5-HT2 receptors) MDMA(Methylenedioxymethamphetamine) (Ecstasy)called as "street" or "party" drug. It is an amphetamine derivative which acts mainly by inhibiting 5-HT uptake and has powerful psychostimulant effects typical of amphetamines, as well as psychotomimetic effects. • Phencyclidine called as “angel dust” and ketamine are antagonists at NMDA(N-methyl-D-aspartic acid)-type glutamate receptors.
6.Inhalants • Inhalants are a diverse group of substances that include volatile solvents, gases, and nitrites that are inhaled. • These substances are found in common household products like glues, lighter fluid, cleaning fluids, and paint products. • The chronic use of inhalants has been associated with a number of serious health problem: • Sniffing glue and paint thinner causes kidney abnormalities, while sniffing the solvents toluene and trichloroethylene cause liver damage. • Memory impairment, attention deficits, and diminished intelligence • Deaths resulting from heart failure, asphyxiation, or aspiration have occurred.
7.Anabolic steroids • A type of steroid that mimics the male sex hormone testosterone. • Medical uses of anabolic steroids include replacement of inadequate levels of testosterone resulting from a reduction or absence of functioning testes,& also for certain kinds of anemia and breast cancer. • Bodybuilders and athletes often use anabolic steroids to build muscles and improve athletic performance. But using them this way is not legal or safe. • Anabolic steroids have many psychological and physical side effects Including: • Liver damage and cancer • Sterility, reduction of the size of the testes and breast enlargement in men. • Increased facial hair ,a deeper voice and decreased breast size in women. • Acne. • Permanently stunted growth in adolescents. • Aggressive behavior, mood swings, depression. • Hypertension. • High cholesterol. • Injuries to tendons and muscles.
General Management of drug abuse: • Stopping the use of the substance. • 2.Pharmacotherapy : as use of antidotes e.g: Naloxone for opioid abuse. • or substituting agents e.g:a long acting opioid (e.g:methadone) for shorter acting one(e.g:heroin) &use of chewed or transdermal nicotine. • 3.Long term support, rehabilitation & Psychosocial therapies.
