Outline and chapter notes to accompany chapter 14 DRUGS AND ADDICTION Dec., 2003 A. DRUGS ARE CHEMICALS THAT ALTER BIOLOGICAL PROCESSES DRUGS AND THEIR ACTIVITY: Drug: any chemical substance that produces a physiological effect other than as food. Psychoactiuve drug: any drug that alters consciousness, mood, or perception. Dose: the amount of a drug taken on one occasion. Therapeutic dose: the amount of a drug which has a healthful effect. Toxic dose: the amount of a drug that impairs health. Lethal dose: the amount of a drug that causes death. Margin of safety: ratio (or other comparison) between toxic dose and therapeutic dose. ROUTES OF ENTRY INTO THE BODY: by inhalation (via lungs and respiratory passages) by mouth (orally) by insertion into another body cavity (as a suppository) by injection (intravenous or other types) topically (applied to a surface) to a fetus through the placenta to a nursing infant through the mother's milk DISTRIBUTION OF DRUGS THROUGHOUT THE BODY: Most drugs are distributed throughout the body by the circulatory system, regardless of their route of entry. Exception: many topical medications remain where they are put and do not spread. ELIMINATION OF DRUGS FROM THE BODY: Some drugs are metabolized by the body (broken down chemically). Alcohol is an example. Metabolic elimination of alcohol can easily be exceeded by intake. Other drugs are excreted unchanged. Some drugs (or their breakdown products) are exhaled as gases, others are excreted in sweat. The majority of drugs are excreted in the urine by the kidneys. Half-life is the time for a drug to reach one-half its original concentration in the body. A drug with a long half- life may interact with another drug taken later. DRUG RECEPTORS AND DRUG ACTION ON CELLS Some drugs enter cells directly and have effects inside. Most drugs do not enter cells, but achieve their effects via receptors on cell surfaces. These receptors bind to a chemical (such as a drug) and then initiate some cellular activity. Most drug receptors are membrane proteins embedded in the cell membrane with their binding site facing the environment outside the cell. The specificity of the drug depends on the unique shape of the receptors. The tissues that respond to a drug are those whose cells have receptors for that drug. An agonist is a substance that elicits a response or stimulates a receptor; an antagonist inhibits a response, often by inhibiting receptors. SIDE EFFECTS AND DRUG INTERACTIONS Effects other than the intended effect are called side effects. They may be beneficial or harmful; they may also vary from barely noticeable to severe. DRUG INTERACTIONS: The effects of two or more drugs may be: - additive (same as the sum of their independent effects) - synergistic (greater than the sum of their independent effects) - antagonistic (less than the effect of either drug alone) The probability of drug interaction increases rapidly with the number of drugs used. A threshhold is the minimum dose of a drug for which some effect is detectable. Some drugs may lower or raise threshholds of activity for other drugs. DRUG SAFETY In industrialized countries, drugs sold over the counter (OTC) and drugs sold by prescription are tested for safety and efficacy. Herbal remedies are usually sold without testing. Amounts of active ingredients (and of other, potentially harmful ingredients) may vary greatly. In the United States, anything sold as a "food supplement" can be sold without testing and with little or no regulation. Many advertising claims are unsupported by any research. B. PSYCHOACTIVE DRUGS AFFECT THE MIND OPIATES AND OPIATE RECEPTORS Opiates include heroin, morphine, codeine, and other chemicals derived from opium poppy. All opiates are narcotics: they can induce drowsiness or sleep. Opiates in low doses are pain killers (analgesics) and can cause euphoria (feeling good). Opiates are highly addictive. Opiates produce their effects by binding to specific opiate receptors. The brain produces its own endogenous opiates, called endorphins and enkephalins. MARIJUANA AND THC RECEPTORS Marijuana contains many psychoactive drugs, of which the most potent is called THC or delta-9-tetrahydrocannabinol. Brain cells contain specific THC receptors, which cause the release of norepinephrine. No endogenous chemical has yet been found which binds to these receptors. NICOTINE AND NICOTINIC RECEPTORS Nicotine stimulates nicotinic receptors in the cerebral cortex and the sympathetic nervous system. Elsewhere in the body, nicotine produces increased heart rate, increased blood pressure, and blood vessel constriction, and it impairs the action of the cilia that cleanse the respiratory tract. AMPHETAMINES: AGONISTS OF NOREPINEPHRINE Amphetamines stimulate the central nervous system by: - increasing the activity of the reticular formation (a brain region that regulates our level of awareness), and by - mimicking the effects of norepinephrine by binding to norepinephrine receptors. Amphetamines also inhibit the enzyme MAO and block the reuptake of norepinephrine. LSD: AN AGONIST OF SEROTONIN LSD can mimic the effects of serotonin by binding to serotonin receptors. LSD alters perception of stimuli and also frequently causes hallucinations. Even short-term use can cause permanent brain damage. CAFFEINE: A GENERAL CELLULAR STIMULANT Caffeine enters cells and increases their rate of metabolism by inhibiting the breakdown of cyclic AMP. In the brain, it increases activity of the reticular formation. ALCOHOL: A CNS DEPRESSANT Unlike most other drugs, alcohol is not receptor-mediated. Because it is soluble both in water and in membrane lipids, alcohol readily dissolves in cell membranes, changing their properties. Alcohol depresses the activity of the entire nervous system, especially the reticular formation. Alcohol impairs judgement, lessens all defensive reactions, and slows reaction time. At higher doses, alcohol interferes with vision, speech, muscular control, and balance, and it may cause unconsciousness and death. C. MOST PSYCHOACTIVE DRUGS ARE ADDICTIVE ADDICTION, DEPENDENCE AND WITHDRAWAL Addictive drugs are those which can cause the following effects: Dependence, meaning that the person can no longer function normally (physiologically or psychologically) without the drug; Withdrawal symptoms, unpleasant physiological and behavioral changes that occur when the drug is withdrawn, and Tolerance, meaning that an increased dose is needed to produce the same physiological effect that was formerly produced by a smaller dose. Conditioned withdrawal syndrome: context cues (such as people or places) can bring about physiological withdrawal symptoms, even unconsciously, since they have become associated with the drug via classical conditioning. BRAIN REWARD CENTERS AND DRUG-SEEKING BEHAVIORS One theory of addiction is that it is an attempt to avoid unpleasant stimuli (a negative reinforcement). A newer theory is that addiction results from stimulation and positive reinforcement of the brain's positive reward centers, particularly those in the ventral tegmental area (VTA) of the midbrain. DRUG TOLERANCE means that, after repeated use, the former physiological effect can only be achieved by increasing the dose. The increased doses usually have harmful side effects. D. DRUG ABUSE IMPAIRS HEALTH Drug use that has negative health consequences is called drug abuse or substance abuse. DRUG EFFECTS ON THE HEALTH OF DRUG USERS may be either acute (reversible once the drug wears off), or else chronic (permanent damage resulting from excessive use, usually over a long period of time). EXAMPLES: Chronic effects of alcohol abuse include permanent damage to the brain, liver, and heart. Alcohol also interferes with many beneficial drugs including antibiotics, anti-diabetic drugs, and some vitamins. Caffeine can cause chromosomal damage, respiratory difficulties, and heart and circulatory problems. Tobacco (including passive smoke) impairs respiratory health and causes many cancers. Other effects include greater risk of heart attacks and a depressed immune system. Marijuana also impairs respiratory health, impairs reproductive hormones, and depresses the immune system. Steroids can damage reproductive organs and the heart. "Designer drugs" are dangerous because their effects are unpredictable. Two designer drugs caused hundreds of younger users to develop Parkinsonism. Over-the-counter (OTC) drugs may be harmful if they interact with prescription medications or with other drugs. Drug contaminants and additives are often harmful; their presence and concentration is unpredictable in street drugs. DRUG EFFECTS ON EMBRYONIC AND FETAL DEVELOPMENT Many drugs can cross the placenta and impair the health of the fetus. For example, alcohol can cause fetal alcohol syndrome, including various birth defects. Caffeine and nicotine are also harmful to fetuses. DRUG ABUSE: PUBLIC HEALTH AND SOCIAL ATTITUDES Different societies have different cultural values and thus different attitudes towards the use of various drugs. Some of these attitudes can change and have changed over decades. Laws regulating drug use vary around the world. Many European countries treat drug abuse as a public health problem and attempt to reduce the amount of harm caused to the user and to society, a strategy called harm reduction. The U.S. has relied upon arresting people who use or abuse certain restricted drugs. Some very harmful drugs, such as alcohol, are not regulated in this way, however. Education works: Drug abuse does decrease when public perception of drug harm increases. People's attitudes differ regarding the degree of legal restriction that should be placed on drug use and abuse, as well as the consequences that should be imposed on violators. ---------------------------------- Dec., 2003 PERMISSION IS HEREBY GRANTED to instructors who have adopted the book BIOLOGY TODAY for classroom use to download, modify, and use these notes as needed to aid them in in their teaching. Students of such instructors may likewise use and modify these notes as study aids.