Chemistry for Changing Times 11th Edition Hill and Kolb

Click to edit Master title style,Click to edit Master text styles,Second level,Third level,Fourth level,Fifth level,*,Chemistry for Changing Times12,th,Edition, Hill and Kolb,Chapter 19,Drugs: Chemical Cures, Comforts, and Cautions,Edited from,John Singer,Jackson Community College, Jackson, MI, 2010 Pearson Prentice Hall, Inc.,1,Chemical Cures, Comforts, and Cautions,Drugs, chemical substance that affects the functioning of living things and are used to relieve pain, treat illness, diagnose and prevent diseases, or improve state of health or wellbeing,Sources of drugs plants, microorganisms, marine organisms, and synthetic,Prescription vs. OTC,Brand vs. generic (price & effectiveness),Research and patent protection,Historical,Paul Ehrlich,(1904) found that certain chemicals are more toxic to disease organisms than to human cells.,He coined the term,chemotherapy,(chemical therapy) and was awarded the Nobel Prize in medicine/physiology in 1908,2,Some terminologies,Analgesic,Antipyretic and pyrogens,Anticoagulant,Anti-inflammatory,3,Pain Relievers: Nonsteroidal Anti-Inflammatory Drugs (NSAIDS),NSAIDS,relieve pain and reduce inflammation by blocking the over production of,prostaglandins,(the pain messenger). NSAIDS include aspirin, ibuprofen (Advil, Motrin), Naproxen (Aleve), Ketoprofen (Orudis),4,Pain Relievers: Nonsteroidal Anti-Inflammatory 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 mediator. Since NSAIDS block the production of prostaglandins, they help to reduce fever (do not cure what is causing the pain, merely kill the messenger).,Cycloxygenase (COX) enzymes catalyze the production of prostaglandins from arachidonic acid (C,20,). COX-1 is found in the stomach and kidney tissues, and COX-2 is found in tissues where inflammation occurs,Aspirin, Ibuprofen, and Naproxen block both COX enzymes. Blocking COX-1 enzyme leads to the side effects of excessive bleeding and stomach pain (gastrointestinal discomfort),5,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.,6,Pain Relievers: Nonsteroidal Anti-Inflammatory Drugs (NSAIDS),Aspirin (1893, acetylsalicylic acid, the most used drug),Analgesic, antipyretic, anti-inflammatory,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.,Cant be used after surgery,Aspirin is associated to “Reyes Syndrome” in children.,Regular dose = 325 mg, X-tra strength = 500 mg,Childrens dosage is of regular adult dosage,Buffered aspirin contains antacids,7,Pain Relievers: Nonsteroidal Anti-Inflammatory Drugs (NSAIDS),Acetaminophen (Tylenol),Acetaminophen 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.,Acetaminophen can be taken by those affected by aspirin side effects and children. However, when taken with alcohol it can cause liver and kidney damage.,Regular strength = 325 mg, X-tra strength = 500 mg,Childrens dosage is of regular adult dosage,Combination pain relievers,can include a number of different NSAIDS as well as caffeine, antihistamines, and other drugs. Excedrin and Anacin are familiar brands.,8,Antibacterial Drugs,In the first half of the 1900s, infectious disease was a leading cause of death in US,Compare life expectancy in the pre- and post- WWII era,What about in the late 1900s and 2000s?,9,Antibacterial Drugs,Sulfa drugs,were the first antibacterial drug (1935). Sulfanilamide acts by replacing,para,-aminobenzoic (PABA) acid that bacteria need to produce folic acid for growth (case of mistaken identity by bacterial enzymes),Used extensively during WWII,Tend to cause kidney damage by crystallizing there,Replaced by newer antibacterial agents,10,Antibacterial Drugs,Penicillins (Alexander Fleming, 1928),are antibiotics, 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 (interrupts the cross linking of the large molecules, e.g., mucoproteins),First human trial in 1941 (injected). Penicillin V can be taken orally. Amoxicillin is the most prescribed antibiotic in 1988 in USA. Overuse causes bacteria to grow resistance against the drug,11,Antibacterial Drugs,Cephalosporins,Scientists seek to develop new and more potent antibiotics to kill resistant bacteria. Penicillins have been partially replaced by cephalosporins such as cephalexin (Keflex). But some bacteria are resistant to this drug also.,12,Antibacterial Drugs,Tetracyclines,(1948) are,broad-spectrum,antibiotics,They act by binding to bacterial ribosomes inhibiting bacterial protein synthesis (do not bind with mammalian ribosomes),Can cause discoloration of the permanent teeth in children by the interaction of OH group and Ca during tooth development (caution for pregnant women). Milk and cheese can interfere the action of this medicine,13,Viruses and Antiviral Drugs,Viruses,are composed of nucleic acids and proteins. Viral diseases cannot be cured by antibiotics,Vaccination is often used against polio, mumps, measles, smallpox, cold, etc.,Viruses are composed of glycoprotein (membrane) and nucleic acids (genetic material), either DNA or RNA,14,Viruses and Antiviral Drugs,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.,Similarly,RNA viruses,enter the host cell and induce the synthesis of viral proteins. Some RNA viruses are,retroviruses,(reverse transcription) which synthesize new DNA in the host cell. HIV is one example of a retrovirus,15,Viruses and Antiviral Drugs,Worldwide, 35 million people were living with AIDS in 2007, of which 2.5 million were infected in that year. 1-1.2 million with HIV/AIDS infection in the US, with 37,000 new cases of infection each year,Acyclovir (Zovirax) controls chickenpox, shingles, cold sores, symptoms of genital herpes,Oseltamivir (Tamiflu ) to prevent influenza,Azidothymidine (AZT) slows down AIDS virus,Combination drugs work better,Highly toxic,16,Chemicals Against Cancer,Cancer is a much dreaded disease, 1.4 million new cases are diagnosed in the U.S. each year killing over 560,000 people,Some types of cancer have high cure rates (prostate) while others have a very low survival rate (lung). Treatment includes drug, radiation, and surgery,Dozens of anticancer drugs are used. However, drugs that kill cancer cells also damage normal cells,Anticancer drugs affect cells that undergo rapid replacement (lining of digestive tract and hair), causing nausea and hair loss to be common side effects,Anticancer agents (,antimetabolites,) interfere with physiological reactions with the substances essential to normal metabolism, such as DNA synthesis,17,Chemicals Against Cancer,Cisplatin, PtCl,2,(NH,3,),2,(1844, 1965) an alkylating agent, was used widely in the mid 80s for prostate cancer. It binds to DNA and blocks its replication (antimetabolite). It is also used to treat cancers of ovaries, testes, uterus, head, neck, breast, lung, and bladder,Other alkylating agents are mustard gas, nitrogen mustard are also used in cancer treatment,6-mercaptopurine (1954) substitutes adenine of the DNA and RNA, inhibiting their performance, providing 80% cure in child leukemia if treated early,5-fluorouracil blocks thymidine synthesis, essential for DNA replication (cancer of breast and digestive tract),18,Hormones: The Regulators,Hormones,are chemical messengers produced in the,endocrine glands,(pituitary, adrenal, prostate, ovary, thyroid, heart, liver, kidney, gut, and placenta),They regulate physiological activities (growth, metabolism, reproduction, etc.) even at remote parts of the body,19,Hormones: The Regulators,20,Hormones: The Regulators,Prostaglandins,are hormone-like lipids derived from a fatty acid, arachidonic acid (C,20,). 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. They are mediators of hormone action, an extremely small dose can produce marked changes in physiological actions.,21,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,22,Hormones: The Regulators,Cortisol, an adrenal hormone, acts to reduce inflammation, widely used for arthritis treatment. Repeated use has side effect,Prednisone, synthetic steroid, anti-inflammatory, replaced cortisone, effective in much smaller dose, less side effect,Cholesterol, a steroid that does not have any hormonal activity. 10% of brain is cholesterol, also makes nerve-cell membranes,Anabolic steroids, synthetic, used in some athletics for performance enhancement, illegal in some athletics,All hormones are steroids, but not all steroids are hormones,23,Hormones: The Regulators,24,Hormones: The Regulators,Sex hormones,are steroids,Androgens, male sex hormones, stimulate or control the development of male sexual organs and secondary sexual characteristics, e.g., voice and hair distribution. These are secreted by the testes. The most important androgen is,testosterone,Estrogens, female sex hormones, control female sexual functions, produced in the ovaries.,Estradiol,and,estrone,control female sexual functions (breast development, menstrual cycle, etc.).,Progesterone,prepares uterus for pregnancy,Testosterone has been used to treat breast cancer and estrogens are used to treat prostate cancer in males,25,Drugs for the Mind,Psychotropic drugs,affect primarily the human mind.,Alcohol, marijuana, opium, cocaine, peyot are from natural sources. In the market many are synthetic,These are divided into three classes:,Stimulants,such as cocaine and amphetamines which increase alertness, speed mental processes, and elevate mood,Depressants,such as alcohol, anesthetics, opiates, barbiturates, and tranquilizers reduce consciousness and reaction to stimuli, dull emotional responses,Hallucinogenic,drugs such as LSD and marijuana alter the perception to reality (mindbenders). Those inducing colorful vision are called,psychedelic,drugs,26,Chemicals Affecting the Nervous System,Selected neurotransmitters,27,Brain Amines: Depression and Mania,Biochemical theories of,mental illness,involve chemical imbalances of brain amines,Epinephrine, (synthesized from tyrosine) secreted by the adrenal glands under stress or fright,Tiny amounts can cause great increase in blood pressure, prepare body for the,fight or flight,Norepinephrine (NE),is a relative of epinephrine. Excess causes euphoria, large excess induces manic state. Deficiency can cause depression,Tyrosine, Dopa Dopamine Norepinephrine Epinephrine,Serotonin (synthesized from tryptophan) regulates sleep cycle, body temperature, memory, mood, etc.,Tryptophan xxxxxx xxxxxx Serotonin,28,Depressants - Anesthetics,Anesthetics,are substances that cause lack of feeling or awareness.,General anesthetics,produce unconsciousness and insensitivity to pain.,Local anesthetics,cause loss of feeling in part of the body.,List of some general anesthetics,29,Depressants - Anesthetics,Diethyl ether,is the first GA (introduced in 1842). Relatively safe, wide gap between effective dose and lethal dose. Gives nausea, highly flammable,Nitrous oxide, N,2,O (1844), laughing gas, used with oxygen, effective concentration is 50%. Lack of O,2, when mixed with air, can cause permanent brain damage,Chloroform, CHCl,3, is also a GA (1847). Not flammable, but have narrow safety margin (must be protected from oxygen during storage), effective dose is close to lethal dose, causes liver damage, and suspected carcinogen,30,Depressants - Anesthetics,Local anesthetics,often used for dental work or minor surgery while patient remains conscious,Cocaine was the first local anesthetic, isolated from the leaves of coca plant (1860). It is also a powerful stimulant and addictive,Dentists used procaine (Novocaine), takes long time to take and wears off too quickly,List of some local anesthetics,31,Depressants - Alcohol,Ethyl alcohol (ethanol),Fermentation of grain and fruit juice produces ethanol (5000 year old technology),Most used and abused drug in the world,It is a depressant, slows down both physical and mental activity. Moderate drinking (1-2 drink/day) increase longevity, due to relaxation effect,Moderate calorie (7 kcal/g) in alcoholic drinks cause fat deposit in the abdomen. Too much alcohol gives adverse effects: intoxication, sluggish muscular activity, raises dopamine levels in the brain (pleasure aspect), highway fatality, alcoholism (10 million people in the US are alcoholic), increased suicide rate (58x), fetal alcohol syndrome, birth defect,32,Depressants - Barbiturates,Barbiturates,are a family of related depressants, displaying a wide range of properties. They were once used as a mild sedative (few mg). In larger doses (100 mg) they induce sleep. Barbiturates are quite toxic, lethal dose is 1500 mg. Used as medicine to calm anxiety and as anticonvulsant for epileptics and brain-damaged people,Adolf von Baeyer (1864) synthesized barbituric acid from malonic acid (made from apples) and urea (occurs in urine),33,Depressants,Barbiturates, like alcohol, are intoxicating and addictive. Both are depressants. Taken together, they cause a,synergistic,effect, and can be deadly,A,synergistic,effect is an effect that is markedly greater than each drug taken individually,For instance, the depressant effect of barbiturates is enhanced up to 200 times when taken with ethanol,Habitual use of barbiturates lead to tolerance to the drug requiring ever-increasing doses,Side effects include hangover, drowsiness, dizziness, and headaches,Withdrawal symptoms include convulsions and delirium, can even cause death,34,Narcotics,Narcotics,are drugs that produce,narcosis,(stupor or general anesthesia) and,analgesia,(relief of pain),Many drugs produce these effects, but in the US only those that are also,addictive,are legally classified as,narcotics,. Their use is regulated by federal law,At lower doses many of these are classified as,non-narcotic,Opium and its derivatives (opiates) are common narcotics,35,Narcotics - Opiates,Opium,is the resinous juice of the unripe seeds of the oriental poppy. It contains more than 20 alkaloids, sugars, resins, waxes, and water,Morphine,is the principal alkaloid that makes up 10% of the weight of raw opium. Widely used in Am. Civil War (1861-65) as pain killer (battle wounds). One side effect is constipation, thus used against dysentery. Addiction from this usage came to ne known as “soldiers disease”,36,Narcotics,Codeine and Heroin,Codeine,(found 0.7 -2.5% in raw opium) can be made from morphine by the replacement of the phenolic hydroxyl (OH) group with the methoxy (OCH,3,) group by reacting with methanol. Less potent and less addictive. 2.2 mg/mL (cough syrup) is non-narcotic,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. Very addictive and harder to cure, illegal in US,37,Narcotics,Synthetic Narcotics,- search for pain killer as effective as morphine but less addictive,Methadone,is one such drug that is used to treat heroin addiction. It allows user to hold a productive job. It is also addictive,Demerol,does not cause nausea,Hydrocodone-acetaminophen,combination was the second most prescribed drug in 2006 in the US,38,Narcotics,Agonists and Antagonists,Morphine agonists,exhibit morphine-like activity by binding to receptors in the brain. Methadone is morphine agonist,Morphine antagonists,inhibit the action of morphine by blocking receptors. Naloxone is morphine antagonist, used to treating opiate addicts. Methadone is heroin antagonist,Natural Opiates,Endorphins,(endogenous morphines) are morphine-like peptide chains produced in response to pain that bind to the receptors in the brain that morphine reacts with. These are released during strenuous exercise as a response to pain.,39,Stimulant Drugs,Amphetamines,have been used in treating depression and narcolepsy,They increase pulse rate and blood pressure, induce excitability, restlessness, tremors, insomnia, dilated pupils, hallucination, and psychoses,Once they were used as a diet drug,They are used to treat ADD/ADHD (Ritalin) in children,Methamphetamine,has more psychological effect. Known as SPEED, ICE (free-base), gives abuser an euphoric rush,40,Stimulant Drugs,Cocaine, first used as a local anesthetic, also act as a powerful stimulant. It used to arrive in the US as the salt cocaine hydrochloride. It is now available as free base,crack cocaine,. Cocaine hydrochloride is readily absorbed through the mucus membrane of the nose. Crack cocaine is vaporized readily at the tip of burning cigarette reaching the brain in 15 sec. It acts by preventing the re-absorption of dopamine leaving high levels of dopamine to stimulate the pleasure centers of the brain. The effect is short-lived (1 hr) and its use is quickly followed by depression and craving for more.,41,Stimulant Drugs,Caffeine: Coffee, Tea, Cola,Caffeine is a mild stimulant. Effective dose is 200 mg (10- oz strong coffee or 3-5 cup strong tea),Addictive “morning grouch” syndrome,Vivarin, No-Doz 200 mg,Energy drinks upto 400 mg,42,Stimulant,Drugs,Nicotine, common stimulant, taken by smoking or chewing tobacco. Its initial stimulation is transient in nature thus is followed by depression. Smokers are able to keep a near-constant nicotine level in the blood by frequently smoking. Tar and other chemicals in the smoke causes many health hazard. Smokers pay upfront (tax) and later (health),SKOAL is pH balanced to enhance nicotine extraction by saliva,It is highly toxic to animals, used as contact insecticide in agriculture, lethal dose in human is 50 mg when injected,43,Hallucinogenic Drugs,Consciousness-altering substances that induces changes in sensory perceptions, often called,“mind-benders”,. Some are,psychedelic,as the produce colorful vision,Lysergic acid diethylamide, LSD,(Hoffman, 1943), is a semisynthetic, powerful psychedelic drug. It is synthesized by converting lysergic acid (from ergot, a fungus that grows on rye) to its diethylamide derivative,At small dose (10-100 g) it gives good effect, at high dose (mg) it gives various effect, lack of self control, extreme terror, schizophrenia, visual disturbances, etc.,44,Psychedelic Drugs,Marijuana,is prepared from the leaves, flowers, seeds, and stems of the,Cannabis sativa,plant. The major active ingredient is tetrahydrocannabinol (THC),Smoking marijuana increases pulse rate, distorts sense of time, impairs complex motor function, euphoric floatation sensation, heightened enjoyment of food, false impression of brilliance, etc.,Some users experience hallucination,Medical use reduction of eye pressure in glaucoma and nausea in cancer chemotherapy,45,Drug Problems,Drug abuse