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Chemistry for Changing Times 11th Edition Hill and Kolb Chapter 19 Drugs John Singer Jackson Community College, Jackson, MI © 2007 Prentice Hall Chemical Cures, Comforts, and Cautions Drugs are defined as any chemical substance that affects the function of living things and is used to relieve pain, treat illness, or improve health or wellbeing. Drugs can be obtained from plant sources, microorganisms, marine organisms, and synthetic sources. Scientific Drug Design Paul Ehrlich determined that certain drugs are more toxic to disease organisms than to human cells. He first coined the term chemotherapy and was awarded the Nobel Prize in medicine/physiology in 1908. Pain Relievers: Nonsteroidal AntiInflammatory Drugs (NSAIDS) NSAIDS relieve pain and reduce inflammation by blocking the production of prostaglandins. NSAIDS include aspirin, ibuprofen, acetominophen, etc. Pain Relievers: Nonsteroidal AntiInflammatory Drugs (NSAIDS) Aspirin for Heart Attack and Stroke Prevention NSAIDS block the production of prostaglandins, some of which are responsible for blood clotting. This is the source of their anticoagulant properties. Many adults take daily small doses of aspirin (81 mg) to help prevent heart attack and stroke. Pain Relievers: Nonsteroidal AntiInflammatory Drugs (NSAIDS) NSAIDS and Fever Reduction Fevers are caused by compounds called pyrogens that are released from leukocytes and other circulatory cells. Pyrogens often use prostaglandins as secondary messengers. Since NSAIDS block the production of prostaglandins, they help to reduce fever. Pain Relievers: Nonsteroidal AntiInflammatory Drugs (NSAIDS) How NSAIDS Work Cycloxygenase (COX) enzymes catalyze the production of prostaglandins from arachidonic acid. Two COX enzymes are known to exist: COX-1 found in the stomach and kidney tissues, and COX-2 found in tissues where inflammation occurs. Aspirin, ibuprofen, and naproxin block both COX enzymes. Blocking COX-1 enzyme leads to the side effects of excessive bleeding and stomach pain. Pain Relievers: Nonsteroidal Anti-Inflammatory Drugs (NSAIDS) How NSAIDS Work Newer NSAIDS only block the COX-2 enzyme and do not experience the side effects of the older NSAIDS. Unfortunately, some have side effects of increased risk of heart attack and stroke as well as allergic reactions and internal bleeding. Pain Relievers: Nonsteroidal AntiInflammatory Drugs (NSAIDS) Acetominophen Acetominophen helps reduce pain and fever. It is not anti-inflammatory and it is not an anticoagulant. It appears to act by blocking the COX-3 enzyme. Acetominphen can be taken by those affected by aspirin side effects and children. However, when taken with alcohol it can cause liver and kidney damage. Pain Relievers: Nonsteroidal AntiInflammatory Drugs (NSAIDS) Combination pain relievers can include a number of different NSAIDS as well as caffeine, antihistamines, and other drugs. Excedrin and Anacin are familiar brands. Chemistry, Allergies, and the Common Cold A variety of cold and allergy medications are available over-the-counter. Colds are caused by more than 200 different viruses. There are no effective cures. Most cold medications treat only the symptoms. Periodically the FDA reviews these medications for safety and effectiveness. Chemistry, Allergies, and the Common Cold Antihistamines relieve the symptoms of allergies caused by the actions of histamine. Histamines are released by certain cells when an allergen binds to its surface. Histamines cause redness, swelling, and itching. Chemistry, Allergies, and the Common Cold Cough suppressants (antitussives) include two narcotics: codeine and dextromethorphan. In addition, the antihistamine diphenhydramine has been found to be effective by the FDA. Chemistry, Allergies, and the Common Cold Expectorants help to bring up mucus from the bronchial passages. Only one expectorant, glyceryl guaiacolate (guaifensin), has been found to be marginally effective. Decongestants are inhaled through the nasal passage. They seem to be safe and effective for occasional use. They include oxymetaxoline, xylometaxoline, naphaxoline, and phenylephrine. Antibacterial Drugs In 1900, infectious disease was a leading cause of death. Antibacterial Drugs Sulfa drugs were the first antibacterial drug. Sulfanilamide acts by replacing para-aminobenzoic acid that bacteria need to manufacture folic acid. Antibacterial Drugs Penicillins are antibiotic substances. Antibiotics are soluble substances derived from molds or bacteria that inhibit the growth of other microorganisms. Penicillins work by inhibiting the enzymes that bacteria use to make their cell walls. Antibacterial Drugs Cephalosporins Bacteria have evolved resistances to certain antibiotics. Scientists are working to develop new and more potent antibiotics to kill resistant bacteria. Penicillins have been partially replaced by cephalosporins such as cephalexin (Keflex). Antibacterial Drugs Tetracyclines are broadspectrum antibiotics that act by binding to bacterial ribosomes inhibiting protein synthesis. Antibacterial Drugs Fluoroquinolones are broad-spectrum antibiotics first introduced in 1986. They act by inhibiting DNA replication through the interference with the enzyme DNA gyrase. Ciprofloxacin (Cipro®) is the leading fluoroquinolone. Viruses and Antiviral Drugs Viruses are composed of nucleic acids and proteins. Viral diseases cannot be cured by antibiotics. Viruses and Antiviral Drugs The genetic material of viruses is either DNA or RNA. DNA viruses enter the host cell where DNA is replicated and direct the production of viral proteins forming new viruses which invade other host cells and continue the process. RNA viruses enter the host cell and induce the synthesis of new proteins. Some RNA viruses are retroviruses, which synthesize new DNA in the host cell. HIV is one example of a retrovirus. Viruses and Antiviral Drugs Antiviral drugs have been developed which are effective against some viruses but do not provide cures. Viruses and Antiviral Drugs Antiviral Drugs Nucleoside analogs substitute an analog for the nucleoside in the viral DNA, effectively crippling it. Nonnucleoside reverse transcriptase inhibitors stop the reverse transcriptase enzyme from making more virus. Protease inhibitors block the enzyme protease so that new copies of the virus cannot infect new cells. Chemicals Against Cancer Cancer is a much dreaded disease. 1.3 million new cases are diagnosed in the U.S. each year. Some types of cancer have high cure rates while others have a very low survival rate. Dozens of anticancer drugs are used. However, drugs that kill cancer cells also damage normal cells. Chemicals Against Cancer Antimetabolites closely resemble a substance used in normal metabolism and interfere with the physiological reactions. 6-mercaptopurine (6-MP), 5-fluorouracil, and 5-fluorodeoxyuridine are incorporated into nucleotides and inhibit the formation of thymine-containing nucleotides during DNA synthesis. This slows the division and growth of cancer cells. Chemicals Against Cancer Antimetabolites resemble substances essential to metabolism and interfere with physiological reactions. Chemicals Against Cancer Nitrogen alkylating agents are relatives of the mustard gases used during WWI. They act by crosslinking DNA strands and hindering replication. Cyclophosphamide (Cytoxan) is used to treat Hodgkin’s disease, lymphomas, leukemias, and other cancers. Chemicals Against Cancer Miscellaneous Anticancer Reagents There are many other anticancer agents, including plant derivatives, certain antibiotics such as actinomycin, etc. Chemotherapy, surgery, and radiation therapy are the major tools in treating cancers. Hormones: The Regulators Hormones are chemical messengers produced in the endocrine glands. Hormones: The Regulators Hormones: The Regulators Prostaglandins are hormone-like lipids derived from a fatty acid. They are similar to hormones in that they react with target cells. However, they differ from hormones in that they act near where they are produced, can produce different effects in different tissues, and are rapidly metabolized. Prostaglandins are mediators of hormone action. Hormones: The Regulators Steroids are lipids with a definite 4-ring skeletal structure. Many drugs are based on steroids. Some are illegally used to enhance athletic performance, some are used to treat arthritis, asthma, dermatitis, and eye infections. Hormones: The Regulators Sex hormones are steroids. Androgens stimulate or control the development of masculine characteristics. Estrogens are compounds that control female sexual functions. Chemistry and Social Revolution: The Pill Progestin is any steroid hormone that has the effect of progesterone. They are effective for female birth control. They “fool” the body into acting as if it were already pregnant and blocking ovulation. Chemistry and Social Revolution: The Pill Emergency contraceptives are used to prevent pregnancy after unprotected intercourse. Emergency contraception pills (ECPs) can contain both estrogen and progestin or just progestin only. They disrupt the hormone patterns needed for pregnancy. Intrauterine devices (IUDs) interfere with sperm transport and fertilization. Mifepristone (RU-486) is the so-called medical abortion pill. It inhibits progesterone, preventing the body from maintaining pregnancy. Drugs for the Heart Drug treatments for the heart involve increasing blood supply, normalizing heart rhythm, lowering blood pressure, and prevention of lipid plaques. Drugs for the Heart Normalizing Heart Rhythm Arrhythmia is an abnormal heartbeat. Many drugs can treat this through a variety of actions. Fibrillation is a too-rapid heartbeat. It is treated with defibrillator devices that are available in many public places. Drugs for the Heart Treating Coronary Artery Disease Arteriosclerosis is blockage of the coronary arteries by lipid-containing plaque. It leads to angina pectoris (chest pain) and ultimately, heart attack. Nitroglycerin and amyl nitrite can be used to treat angina pectoris. They act by releasing nitric oxide (NO) which relaxes constricted blood vessels. Digitalis can be used to treat heart failure. Digitalis is a mixture of glycosides that release carbohydrates and steroids on hydrolysis. Drugs for the Mind Psychotropic drugs affect the human mind. They fall into three catagories: Stimulants such as cocaine and amphetamines which increase alertness, speed mental processes, and elevate mood. Depressants such as alcohol, anesthetics, opiates, barbiturates, and tranquilizers which reduce consciousness and reaction to stimuli. Hallucinogenic drugs such as LSD and marijuana which alter the way we perceive reality. Some Chemistry of the Nervous System The human nervous system is made up of about 12 billion neurons. The essential parts of the neuron are the cell body, axon, and dendrites. Some Chemistry of the Nervous System Messages are transmitted across the fluid-filled gaps called synapses by chemicals called neurotransmitters. Some Chemistry of the Nervous System Neurotransmitters Brain Amines: Depression and Mania Epinephrine is secreted by the adrenal glands. Tiny amounts lead to an increase in blood pressure and cause the fight-orflight syndrome. It has been implicated in some forms of mental illness. Brain Amines: Depression and Mania Biochemical Theories of Mental Illness Norepinephrine (NE) is a relative of epinephrine. It causes feelings of elation, and in excess, amounts leads to a manic state. Deficiency can cause depression. Brain Amines: Depression and Mania Biochemical Theories of Mental Illness Serotonin is another brain amine neurotransmitter. It is involved in the regulation of body temperature, sleep sensory perception, and pleasure sensation. Its metabolite is 5-HIAA. Research suggests reduced flow of serotonin can cause depression. Brain Amines: Depression and Mania NE agonists are stimulants that mimic or enhance the effects of NE. They can be used to treat depression, anxiety, and obsessive-compulsive disorder. NE antagonists are drugs that block the effects of NE. They can be used to treat hypertension, angina, or cardiac arrhythmia. Anesthetics Anesthetics are substances that cause lack of feeling or awareness. General anesthetics produce unconsciousness and block feelings of pain. Local anesthetics block feelings of pain in a specific part of the body. Anesthetics Anesthetics Modern anesthetics can include a variety of several drugs including: - a tranquilizer - an IV such as thiopental to cause unconsciousness - a narcotic pain killer, such as fentanyl - an inhalant anesthetic to keep the person unconsciousness and provide insensitivity to pain - a muscle relaxant like succinylcholine chloride Anesthetics Local Anesthetics Anesthetics Local Anesthetics Anesthetics Barbiturates are a family of related depressants. They were once used as a mild sedative. In larger doses, they induce sleep. Barbiturates are very toxic. Anesthetics Both alcohol and barbiturates are depressants. Taken together, they cause a synergistic effect. A synergistic effect is an effect greater than each drug taken separately. For instance, the depressant effect of barbiturates is enhanced up to 200 times when taken with ethanol. Narcotics Narcotics are drugs that produce narcosis (stupor or general anesthesia) and are analgesics (pain killers). In the United States, such drugs that are addictive are legally regulated and classified as narcotics. Narcotics Opium and Morphine Opium is the resinous juice of the unripe seeds of the oriental poppy. It contains more than 20 alkaloids, sugars, resins, and waxes. Morphine is an alkaloid that makes up 20% of the weight of opium. Narcotics Codeine and Heroin Codeine is a derivative of morphine. Replacement of the phenolic hydroxyl (OH) group with the methoxy (–OCH3) converts morphine to codeine. Heroin is made by converting both hydroxyl groups of morphine to acetate esters . This makes heroin less polar than morphine and makes it more soluble in fatty brain tissue. Narcotics Synthetic Narcotics Much research has been done to develop a pain killing drug as effective as morphine but less addictive. Methadone is one such drug that is used to treat heroin addiction. Narcotics Narcotics Morphine Agonists and Antagonists Morphine agonists exhibit morphine-like activity by binding to receptors in the brain. Morphine antagonists inhibit the action of morphine by blocking receptors. Pentazocine acts as both. It is less addictive than morphine and is effective at relieving pain. Naloxone is a pure antagonist. It can be used to treat opium addicts. Narcotics Natural Opiates Endorphins are morphine-like peptide chains produced in response to pain that bind to the receptors in the brain that morphine reacts with. It causes natural pain relief and the “runner’s high.” Antianxiety Agents A variety of drugs have been used to relieve the stress of modern living. One such class are the benzodiazepines. They are thought to act on the GABA receptor and are addictive. Antianxiety Agents Antipsychotic Agents In 1952, rauwolfia from the snakeroot plant was used to treat hypertension. That same year, reserpine (an active alkaloid) was isolated from rauwolfia and found to be an effective sedative as well as an antihypertensive agent. The following year, it replaced electroshock therapy for 90% of psychotic patients. Antianxiety Agents Phenothiazines Chlorpromazine (Thorazine®) was introduced in 1952 as an effective tranquilizer for psychotic patients in the U.S. Chlorpromazine is one of several phenothiazines. They act as dopamine antagonists by blocking the post-synaptic receptors for dopamine. They are effective at treating the symptoms of schizophrenia. Antianxiety Agents Antidepressant Drugs Selective serotonin reuptake inhibitors (SSRIs) are commonly used to treat depression. They enhance the effect of serotonin by blocking its reabsorption by nerve cells. Stimulant Drugs Amphetamines have been used in treating depression and narcolepsy. They increase pulse rate and blood pressure. They induce excitability and restlessness. At one time, they were used as a diet drug. They are used to treat ADD in children. Stimulant Drugs Cocaine is a powerful stimulant. It used to arrive in the U.S. as cocaine hydrochloride. It is now available as freebase crack cocaine. It acts by preventing the reabsorption of dopamine. This leaves high levels of dopamine to stimulate the pleasure centers of the brain. The effect is short-lived and its use is quickly followed by depression and craving for more. Stimulant Drugs Caffeine: Coffee, Tea, or Cola Caffeine is a mild stimulant. An effective dose is about 200 mg. Stimulant Drugs Nicotine is another common stimulant. It is taken by smoking or chewing tobacco. Its initial stimulant response is followed by depression. Smokers are able to maintain a near constant level of nicotine in their blood by regular smoking. Psychedelic Drugs Lysergic acid diethylamide (LSD) is a semisynthetic powerful psychedelic drug. It is synthesized by converting lysergic acid (from ergot) to its diethylamide derivative. Psychedelic Drugs Psilocybin and Mescaline Psilocybin is a psychedelic alkaloid found in several mushrooms with effects similar to LSD. Mescaline is a psychedelic drug found in the peyote cactus. Its effects last up to 12 hours. Psychedelic Drugs Marijuana is prepared from the leaves, flowers, seeds, and stems of the Cannibis sativa plant. One major active ingredient is tetrahydrocannabinol (THC). Drug Problems Drug abuse is the use of drugs for their intoxicating effects. It causes major problems for the abuser and society. Drug misuse is the use of drugs for the wrong purpose. An example is the use of antibiotics for viral illness. Antibiotics have no effect on viruses and such misuse contributes to antibiotic-resistant bacteria. The Placebo Effect A placebo is an inactive substance administered as a medication to a patient. Many patients demonstrate positive results when administered placebos. This demonstrates “mind-over-matter.” New Uses for Old Drugs The development of new drugs is very expensive. Many older drugs have been tested and approved for new uses.