chemistry in focus 3rd edition tro：重点介绍化学第三版

Chapter 17Drugs and Medicine: Healing, Helping, and Hurting,Love and Depression,Can feelings of love and depression have a molecular origin?LoveElevated phenylethylamine in the brainDepressionAbsence of serotonin (neurotransmitter)We are beginning to understand the connections between physical and psychological conditions and the molecules that cause them.,Serotonin,Aspirin: Relieving Pain, Reducing Fever, andLowering Inflammation,Aspirin is the most popular drug in the world.Analgesic (pain reliever)Antipyretic (fever reducer)Anti-inflammatory (lowers inflammation)Aspirin works on:Prostaglandins to mediate pain and feverHistamines to reduce inflammation,Aspirin Side Effects,Stomach irritationUlcer patients bewareBlood thinningLowers stroke and heart attack riskReyes syndromeChildren with chicken pox or flu should not take aspirin.Toxic in large dosesMore children are poisoned by aspirin than by any other drug.,Concept Check 17.1,What side effect of aspirin makes it unsuitable for use by children?,Concept Check 17.1 Solution,Aspirin has been linked to increased risk of Reyes syndrome.Aspirin is toxic in large doses. More children are poisoned by aspirin than by any other drug.,Aspirin Substitutes,AcetaminophenTylenol, Anacin-3Does not reduce inflammationIbuprofenAdvil, Nuprin, Motrin IBNaproxen Long-lasting effectAleve,Concept Check 17.2,Outline the structural similarities between naproxin and ibuprofen.,Concept Check 17.2 Solution,Structural similarities between naproxin and ibuprofen.,Antibiotics,Work by targeting the physiology of bacteria, selectively killing themBacterial infections were top causes of deathThis is still the case in many underdeveloped countries.,Common Antibiotic Categories,PenicillinsCephalosporinsTetracyclines,Penicillin,Accidental contamination with a fungus destroyed bacteriaPenicillins tried on humans by other researchersEffective in killing many pathogenic bacteriaAlmost no toxicity to humansMEDICAL MIRACLEBUT, resistant strains of bacteria discovered and others developed resistance over time,Alexander Fleming discovered penicillin.,Penicillin Development and Use,Oral administration or injectionMultiple penicillin choicesChemically related cephalosporins active against penicillin-resistant strainsCephalosporins modified to meet specific purposesPenicillin and cephalosporins both prevent normal development of bacterial cell walls.Tetracyclines inhibit protein synthesis.A completely antibiotic-resistant TB strain has developed since the 1980s.,Concept Check 17.3,A childs dose of the antibiotic Amoxicillin is 25 mg/kg per day. What is the correct Amoxicillin dose for a 35-pound child?,Concept Check 17.3 Solution,First, convert the mass of the child from pounds to kilograms:Now, multiply the mass of the child (15.9 kg) by the conversion factor, which is the daily dose of the drug per kilogram body weight:,Antiviral Drugs and AIDS,Viruses require a host cell for reproduction.Hard to attack them without also attacking healthy hostsViruses do not respond to antibiotics.,Vaccination,Introduction of an inactive virus into the bodyBody develops antibodies that remain to fight off the virus should it occurCommon coldNo vaccine, too many strains of cold virusAIDSNo vaccine, but research has led to the development of nucleoside analogs and protease inhibitors,Nucleoside Analogs,These are nucleotides without the phosphate groups.They work by fooling the enzymes that construct viral DNA.,Concept Check 17.4,AZT, the AIDS drug, is a replica of the nucleoside thymidine. How are AZT and thymidine similar and how are they different?,Concept Check 17.4 Solution,AZT and thymidine virtually identical except at C3, AZT has an N3 substituent where thymidine has an OH group.,Integrase Inhibitors,In 2007, the FDA approved the use of raltegravir, a new class of drugs called integrase inhibitors.Target HIV replicationWork by suppressing the an enzyme that HIV uses to insert its RNA into host cellsCan be used in combination with other drugs to lessen the chance of drug resistanceCan be given to patients that have already developed a resistance to other drugs,Protease Inhibitors,Attack virus replication at the stage when viral protein is produced.Proteases act as molecular scissors to cut viral proteins properly.Protease inhibitors jam the cutting site and prevent the replication of the virus.,Sex Hormones and the Pill,Sexual characteristics are governed by hormones.Testosterone is the most important of the male sex hormones called androgens.In females estrogen and progesterone are secreted in cyclical patterns.The birth control pill contains analogs that regulate the menstrual cycle and establish a state of false pregnancy.,Concept Check 17.5,What structural features are common between the hormones progesterone and testosterone?,Concept Check 17.5 Solution,Progesterone and testosterone are almost exactly the same structurally except the hydroxyl group in testosterone is replaced with an acyl group in progesterone.,New Developments,Mini-pillContains only progestin (a progesterone analog)Fewer side effectsSlightly less effective than the normal pillEfficacy dependent on regular dosesMifepristone (RU-486 )Terminates pregnancy within five weeks of conceptionBlocks progesterone necessary to sustain pregnancyControversial (when does life begin?),Steroids,Sex hormones are part of this larger class of compounds.,Adrenocortical Steroids,Used primarily for potent anti-inflammatory effectsUseful when inflammation causes pain Allergic reactionsRheumatoid arthritisColitisLeaves the patient subject to infectionSide effects include fluid retention, muscle loss, and osteoporosis.,Anabolic Steroids,Synthetic analogs of testosteroneUsed to increase muscle massSerious side effectsMalesLower sperm production and testicular atrophyFemalesPromotion of male secondary sex characteristicsBothLiver damage, stroke, and heart attack,Chemicals to Fight Cancer,Cancer cells are similar to normal cells but with a faster division rate.Several methods of action of cancer drugsAlkylating agentsAntimetabolitesTopoisomerase inhibitorsHormone treatmentChemotherapy is the administration of these drugs.Alone and often combined with other treatments, like surgery and radiationBone marrow, digestive tract, reproductive system, and hair follicles suffer most side effects,Alkylating Agents,Highly reactive compounds that add alkyl groups to other moleculesAdded to DNA, cell death resultsCyclophosphamide is called a “nitrogen mustard” because its structure is similar to WWI-era mustard gases.,Antimetabolites,Methotrexate (chemical imposter)Mimic normal compounds but do not behave in a way that allows DNA synthesis,Topoisomerase Inhibitors,Topoisomerase inhibitors are more specific in their action.Modify the action of topoisomerase, which normally pulls DNA apart during replicationCells die whenever they initiate replication.,Hormone Therapy,Some cancers are fueled by hormones.Hormone therapy to specific tissues is available for cancers of the breasts or sex organs.Estrogen positive breast cancers are treated with estrogen agonists, which compete for estrogen receptor sites and block estrogen from initiating/supporting tumor growth.Fewest side effects of chemotherapies,Concept Check 17.6,Alkylating agents and topoisomerase inhibitors work by affecting how DNA operates in a cell. How are their activities different in their use to fight cancer?,Concept Check 17.6 Solution,Alkylating agents react with DNA in a non-specific way to destroy its function. At this point, cellular mechanisms detect DNA damage and will usually kill the damaged cell to prevent DNA mutations from propagating through cell division.Topoisomerase inhibitors are more specific in their action by modifying the action of topoisomerase, which normally pulls DNA apart during replication. Topoisomerase inhibitors result in DNA damage and therefore in cell death during the action of topoisomerase. Effectively, these compounds cause cells to die whenever they initiate replication.,Depressants,Called tranquilizers or downersUsed medically to treat anxiety and insomnia, and as an anestheticAbused widely as recreational drugsAlcoholEthanol or grain alcoholLiver metabolizes at rate of one drink per hourDepresses the CNSModerate consumption may increase lifespanHeavy consumption definitely decreases lifespan,Depressants,Barbiturates and benzodiazepinesBarbituratesDepressant legally obtained through prescriptionFrom 19121960 used for anxiety and insomnia treatmentInduce physical and psychological dependenceBenzodiazepinesAnxiety and insomnia treatment todayFlumazil terminates the depressant effect of benzodiazepines.,Concept Check 17.7,What structural features are common in barbiturates?,Concept Check 17.8 Solution,Barbiturates differ by their substituents at the tetrahedral carbon on the six-membered ring.,Inhalants,AnestheticNitrous oxide: Displacesair and hypoxia can result in brain damage and suffocation.Enflurane: Used to anesthetize patients during major surgery.AbusedHousehold chemicals: Glue, pen solvents, and aerosol propellants. Brain damage, kidney and liver damage are common side effects.,Enflurane,Nitrous oxide,Narcotics,Drugs that act on the CNS to produce an analgesic and sedative effect; bind to opioid receptorsGreater ability to relieve pain and lower tendency to produce generalized sedation,Opium,Extracted from the opium poppyHas been used for thousands of yearsProduces euphoria, relieves pain, and induces sleep.Morphine is the primary component.Highly addictive,Morphine,Primary component of opiumDrug of choice to treat severe painProduces euphoria and feelings of well being, but user is left craving more1914 Harrison Narcotic Act: Banned nonmedical use,Codeine,Also found in opium, but only 1/10 as potent.Taken orally and administered with aspirin or ibuprofen to relieve moderate pain,Heroin and Fentanyl,HeroinProduced from morphine and reaches the brain fasterThree times more potent than morphineFentanylSynthetic drug more potent than morphineChina White,Drugs that Fight Narcotic Overdose and Addiction,Opioid antagonistsCancel the effect of the narcoticNaxaloneMethadone,Concept Check 17.8,What structural features are common between morphine, codeine, and heroin?,Concept Check 17.8,Morphine, codeine, and heroin and the same skeleton of carbon, nitrogen, and oxygen atoms. The differences occur with the substituents off the oxygen atoms (-OR groups).,Endorphins,Why do opioid receptors in the brain exist?Body produces its own opioid compounds: EndorphinsRunners high,Stimulants: Cocaine and Amphetamines,UppersIncreased alertness and energyDecreased appetite Fight or flight responseCocainePlant derivative indigenous to Peru, Bolivia, and EcuadorFreud advocated use to treat depressionUntil 1903, Coca-Cola contained 60 mg per serving.Psychological dependence is intenseControlled under the Harrison ActAmphetamineTreatment of narcolepsyMethamphetamine is the most abused amphetamine.,Caffeine: The Legal Stimulant,Blocks adenosine receptors, causing increases in dopamine and norepinephrine levels in the brain Effects felt at doses as low as 100 mg; ingestion of 10 g or more is lethalRelatively harmless, but withdrawal symptoms develop even for modest consumers,Nicotine,Found in cigarette smoke and chewing tobaccoInteracts with acetylcholine receptors in the CNSPowerful addictions; well-documented negative health effects,Concept Check 17.9,What do nicotine, caffeine, and cocaine have in common?,Concept Check 17.9 Solution,Nicotine, caffeine, and cocaine are nitrogen based organic compounds extracted from plants which belong to a class of compounds known as alkaloids. All three also act as stimulants and are highly addictive.,Hallucinogenic Drugs: Mescaline,Naturally occurring in the peyote cactusInhibits the filtering of sensory stimuli on the nervesUsed in sacramental and religious rites of the Aztec and Native American tribes,Designer Drugs,MDA, MMDA, MDMA (ecstasy)Mescaline-type actionNo physical addictionPsychological addiction is a concern.Potential brain damageIrreversible destruction,Concept Check 17.10,The designer drug MDMA has a structure similar to methamphetamine. Outline the structural similarities and predict one of MDMAs effects based on structural similarities.,Concept Check 17.10 Solution,MDMA and the stimulant methamphetamine have very similar structures. MDMA exerts the effect of a stimulant at small doses, with hallucinogenic effects at higher doses.,LSD,Dr. Albert Hoffman, 1938Personal experience with the effects of LSD“Acoustic perceptions were transformed into optical illusions”Believed to inhibit the filtering of sensory stimuli in the nerves.Exact