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Chapter 14 The Chemistry of Drugs. The medicinal use of plants has been discovered more than 2000 years ago. Greek physician Dioscorides described the.

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Presentation on theme: "Chapter 14 The Chemistry of Drugs. The medicinal use of plants has been discovered more than 2000 years ago. Greek physician Dioscorides described the."— Presentation transcript:

1 Chapter 14 The Chemistry of Drugs

2 The medicinal use of plants has been discovered more than 2000 years ago. Greek physician Dioscorides described the use of opium, in which morphine is the main component. In 1806, morphine was isolated from opium. In 1820, quinine was isolated from the bark of the cinchona tree. In 1860s, Pasteur discovered bacteria and phenol and related compounds started to be used to prevent bacteria infection. In 1930s, sulfur-containing compounds known as surfa drugs were developed. In 1939, penicillin (antibiotic) was found. Today, there are more than 25,000 prescription drugs ( 处方药 ) and 300,000 nonprescription drugs ( 非处方药 ).

3 14.1 Drugs are classified by safety, social acceptability, origin, and biological activity Classified according to safety and social acceptability Most drugs exhibit a broad spectrum of activity. Aspirin relieves pain, reduces fever and inflammation, thins the blood, causes ringing in the ears. U.S. Drug Enforcement Agency Classification of Drugs ClassificationDescriptionExamples Over-the-counter (OTC) drugs Available to anyoneAspirin, cough medicines Permitted nonmedical drugsAvailable in food beverage and tobacco productsAlcohol, caffeine, nicotine Prescribe drugsRequires physician authorizationAntibiotics, birth control pills Control substance Schedule 1No medical use, high abuse potentialHeroine, LSD, mescaline, marijuana Schedule 2Some medical use, high abuse potentialAmphetamine, cocaine, morphine, codeine Schedule 3Prescription drugs, abuse potentialBarbiturates, valium

4 Classified according to origin Table 14.2 The Origin of Some Common Drug OriginDrugBiological Effect Natural productCaffeine Reserpine Vincristine Penicilline Morphine Nerve stimulant Hypertension reducer Anticancer agent Antibiotic analgesic Chemical derivative of natural product Prednisone Ampicillin LSD Chloroquinine Ethynodiol diacetate Antirheumatic Antibiotic Hallucinogenic Antimalarial Contraceptive SyntheticValium Benadryl Allobarbital Phencyclidine methadone Antidepressant Antihistamine Sedative-hypnotic Veterinary anesthetic analgesic

5 14.2 The Lock-and-Key Model guides chemists in synthesizing new drugs all drugs that act like morphine have the same basic three-dimensional shape as morphine T-shaped three dimensional structure found in all opioids morphine codeineheroine

6 Fig 14.2 many drugs act by fitting into receptor sites on molecules found in the body, much as a key fits in a lock Drug molecule (morphine) Receptor site Lock Key

7 Most new medicinal drugs are still discovered instead of designed. Fig 14.3 ethnobotanists directed natural-products chemists to the yellow coating on the root of the African Bobgunnua tree. Indigenous people have known for many generations that this coating has medicinal properties. From extracts of the coating, the chemists isolated a compound that is highly effective in treating fungal infections. This compound, produced by the tree to protect itself from root tot, shows much promise in the treatment of the opportunistic fungal infections that plague those suffering from AIDS

8 Another important method of drug discovery is the random screening of vast numbers of compounds. Taxol Fig 14.4 originally isolated from the bark of the pacific yew tree, Taxol is a complex natural product useful in the treatment of various forms of cancer

9 Combinational Chemistry ( 组合化学 ) Tiny well or test tube in which reagents B and 4 are mixed. Fig 14.5 (a) eight hypothetical starting materials A through D and 1 through 4 can be combined in various ways to yield 16 products, each of which may have some biological activity not found in any of the starting materials. (b) A multitude of products are thus immediately available to be screened for medicinal activity.

10 14.3 Chemotherapy cures the host by killing the disease The use of drugs that destroy disease-causing agents without destroying the animal host is known as chemotherapy. It works by taking advantage of the ways a disease-causing agent, also known as a pathogen ( 病原体 ), is different from a host. Sulfa drugs (磺胺类药物) and antibiotics (抗生素) treat bacteria infections Humans can use folic acid ( 叶酸 ) from outside sources, but bacteria have to synthesize from PABA. PABA Folic acid Several steps Bacterial enzyme Fig 14.6 bacterial enzymes use para-aminobenzoic acid (PABA) to synthesize folic acid.

11 No folic acid bacterial die PABA sulfanilamide Bacterial enzyme Fig 14.7 sulfa drugs are metabolized to sulfanilamide, which binds to the bacterial enzymes and keeps them from doing their job.

12 Antibiotics Penicillin and related compounds (cephalosporins, 头孢 霉素 ) kill bacteria by inactivating an enzyme responsible for strengthening the bacteria cell wall. Fig 14.8 Penicillins, such as penicillin G, and cephalosporin, such as cephalexin, as well as most other antibiotics, are produced by microorganisms that can be mass-produced in large vats. The antibiotics are then harvested and purified penicillin Gcephalexin

13 Chemotherapy can inhibit the ability of viruses to replicate Fig 14.9 viruses are much smaller than bacteria and many times smaller than animal cells, (Notice the small dot representing the virus.) the smallest of all pathogens, viruses consist mostly of nucleic acids enclosed in a protein coat.

14 Figure 14.10 before a nucleoside, such as guanosine. Can be incorporated into RNA or DNA, it must be activated by having three phosphate groups attached to it Figure 14.11 Acyclovir (zovirax) is a derivative of the nucleoside deoxyguanosine. And zidovudine (AZT) is a derivative of the nucleoside deoxythymidine 3 phosphate group enzyme

15 Acquired immune deficiency syndrome (AIDS) Protease inhibitors ( 蛋白酶抑制剂 ) together with nucleoside antiviral agents ( 核苷抗病毒剂 ) have been used. (a) the small green bodies cover this white blood cell are human immunodeficiency viruses (b) the anatomy of HIV

16 the protease inhibitor nelfinavir

17 Cancer chemotherapy attacks rapidly growing cells At present mortality rate, one in six of us will die of cancer. Chemotherapy is most effective at the early stage of cancer because drugs work best on cells when they are in the process of dividing. A variety of chemicals may be used to selectively kill cells that are in the process of dividing by attacking DNA. S-fluorouracil cycphosphamide cis-platin Figure 14.15 These anticancer agents all kill dividing cells by targeting the cell’s DNA Uracil

18 14.5 The nervous system is a network of neurons central nervous system( brain and spinal cord) peripheral nervous system sensory neurons motor neurons Involuntary (conduct signals from CNS to cardiac nuscles, smooth muscles, glands) Voluntary (conduct signals from CNS to skeletal muscles) Stress (promote emergency functions) Maintenance (promote nonemergency functions) fig 14.20 the two major divisions of the human nervous system are the central nervous system and the peripheral nervous system

19 Neurotransmitters ( 神经传递 介质 ) include norepinephrine (去甲肾上 腺素), acetylcholine (乙酰 胆碱), dopamine (多巴 胺), serotonin (血清素), and GABA ( γ- 氨基丁酸) The primary neurotransmitter for stress neurons is norepinephrine. The primary neurotransmitter for maintenance neurons is acetylcholine. Figure14.21 The chemical structures of the stress neurotransmitter norepinephrine and the maintenance neurotransmitter acetylcholine norepinephrine acetylcholine

20 Dopamine plays a significant role in activating the brain’s reward center, located in the hypothalamus ( 下丘脑 ), giving a pleasurable sense. Serotonin Gamma aminobutytic acid (GABA) Figure 14.22 the chemical structures of three neurotransmitters important to the central nervous system Dopamine

21 Frontal lobe Spinal cord hypothalamus cerebellum Figure 14.23 The human brain

22 14.6 Psychoactive drugs alter the mind or behavior Stimulants ( 兴奋剂 ), Hallucinogens ( 致幻觉剂 ), depressants ( 抑制剂 ), antipsychotics ( 安定药 ), antidepressants ( 抗抑郁剂 ) Stimulants activate the stress neurons Stimulants mimic many of effects of neurotransmitter. They also boost the levels of these neurotransmitters in a synaptic cleft by blocking their removal. Figure 14.24 Amphetamines are a family of compounds structurally related to the neurotransmitters morepinephrine and dopamine. Amphetamines morepinephrine dopamine

23 Fig 14.25 1) neurotransmitters bind to their postsynaptic receptors. 2)neurotransmitters are reabsorbed by the presynaptic neuron that released them through proteins embedded in the presynaptic membrane. 3) A drug that interferes with re-uptake causes a buildup of neurotransmitters in the synaptic cleft

24 Cocaine Figure 14.26 The south American coca plant has been used by indigenous cultures for many years in religious ceremonies and as an aid to staying awake on long hunting trips. Leaves are either chewed or ground to a powder that is inhaled nasally

25 Fig 14.27 cocaine affects dopamine levels in the synaptic clefts of the brain’s reward center 1) High levels of dopamine remain active in the synaptic cleft as cocaine blocks dopamine re-uptake sites. This causes cocaine’s euphoric effect. 2) Dopamine is metabolized and deactivated as it loiters in the synaptic cleft awaiting re- uptake 3)After cocaine is metabolized and deactivated, dopamine re- uptake is no longer blocked, but there is very little dopamine in the synaptic cleft or in the neurons and the cocaine user experiences extreme depression

26 Caffeine Caffeine can be found in coffee beans, teas, kolanuts, and cocoa beans. Caffeine facilitates the release of norepinephrine into synaptic clefts. Caffeine can be well dissolved in carbon dioxide. caffeine Fig14.28 a coffee with its ripening caffeine-containing beans

27 Nicotine Nicotine has a similar chemical structure to acetylcholine, and can depress the maintenance neurons, leading to relaxation and increased digestion. But depressed maintenance neuron favors the stress neurons, leading to increased blood pressure. The lethal dose of nicotine in humans is about 60 mg. acetylcholinenicotine Fig14.29 nicotine is able to bind to receptor sites for acetylcholine because of structural similarities

28 Hallucinogens and cannabinoids alter perceptions LSD is the most famous hallucinogen and was synthesized in 1938 by Albert Hoffmann. Serotonin Figure 14.31 The side chain of serotonin can rotate into a number of conformations. Upon binding to a receptor site. However, the side chain is likely to be a held in conformation 3. Note how the LSD molecule can be superimposed on structure 3. LSD may therefore be thought of as a modified serotonin molecule in which the side chain is held in the ideal conformation for receptor binding Lysergic acid diethylamide

29 Cannabinoids are the psychoactive components of marijuana ( 大麻 ). Figure 14.34 The major psychoactive component marijuana is Δ 9 -tetrahydrocannabinol. Δ 9 -tetrahydrocannabinol.

30 Depressants inhibit the ability of neurons to conduct impulses Alcohol, barbiturates ( 巴比妥酸盐 ), benzodiazepines Alcohol mimics the effect of GABA by binding to GABA receptor sites, allowing chlorine ions to enter the neuron. Cl - Ethyl alcohol Channel open Cl - Channel open Chloride ion channel protein GABA receptor site Outside neuron inside neuron Channel closed Fig 14.38 (a) when GABA binds to its receptor site, a channel opens to allow negatively charged chloride ions into the neurons. The high concentration of negative ions inside the neuron prevents the electric potential from reversing from negative to positive. Because that reversal is necessary if an impulse is to travel through a neuron, no impulse can move through the neuron. (b) ethyl alcohol mimics GABA receptor sites Neuron cell membrane

31 Antipsychotics and antidepressants boost synaptic-cleft concentrations of neurotransmitters Fig 14.39 the receptor sites for barbiturates and benzodiazepines are adjacent to GABA receptor sites. (a ) Barbiturates open up chloride-ion channels on their own. (b) benzodiazepines can not. (c) rather, benzodiazepines help GABA in its channel- opening task Cl - Benzodiazepine receptor site Barbiturate receptor site GABA

32 14.7 Pain relievers inhibit the transimission or perception of pain Anesthetics ( 麻醉剂 ) prevent neurons from transmitting sensations to the CNS. Local anesthetics Aromatic ring Intermediate chain Amine group Fig 14.43 local anesthetics have similar structural features, including an aromatic ring, an intermediate chain, and an amine group. Ask your dentist which ones he or she uses for your treatment

33 General anesthetics Figure 14.44 The chemical structures of sevoflurane and nitrous oxide. sevofluranenitrous oxide

34 Analgesics ( 止痛药 ) No prostaglandin enzyme Over- the- counter analgesic bound to enzyme Arachidonic acid prostaglandin Fig 14.45 (a) prostaglandins, which cause pain signals to be sent to the brain, are sunthesized by the body in response to injury. The starting material for all prostaglandin is arachidonic acid, which is found in the plasma membrane of all cells. Arachidonc acid is transformed to prostaglandin with the help of an enzyme. There are a variety of prostaglandins, each having its own effect, but all have a chemical strucrure resembling the one shown here, (b) analgesics inhibit the synthesis of prostaglandin by binding to the arachidonic acid receptor site on the enzyme. With no prostaglandins, no pain signals are generated. (a) (b)

35 Figure 14.46 Aspirin, ibuprofen, and naproxen block the formation of prostaglandins responsible for pain, fever, and inflammation. Acetaminophen blocks the formation only of prostaglandins responsible for pain and fever. Aspirin ibuprofen naproxenAcetaminophen

36 Opioid analgesics Opioids mimic the action of endorphin ( 内啡肽 ). Heroin Fig 14.48 the structure of methadone superimposed on that of morphine Methadone/morphine

37 14.8 Drugs for the heart open blood vessels or alter heart rate arteriosclerosis ( 动脉硬化 ) leads to arrhythmia ( 心律失常 ) and clogging of blood vessel. Vasodilators ( 血管扩张药 ) expand blood vessels by releasing NO. Figure 14.49 The vasodilators nitroglycerin and amyl nitrite. nitroglycerinamyl nitrite

38 Beta blockers ( 干扰素 ) and calcium-channel blockers lower the blood pressure. Figure 14.50 Propranolol is a beta blocker, and nifedipine is a calcium-channel blocker Propranolol(inderal) Nifedipine


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