Drugs PDF

Drugs  Chemical Cures, Comforts, and Cautions Drugs – chemical substance that affects the function of living things and is used to relieve pain, treat illness, diagnose and prevent diseases, or improve health or wellbeing Sources of drugs – plants, microorganisms, m...

Drugs  Chemical Cures, Comforts, and Cautions Drugs – chemical substance that affects the function of living things and is used to relieve pain, treat illness, diagnose and prevent diseases, or improve health or wellbeing Sources of drugs – plants, microorganisms, marine organisms, and synthetic Prescription vs. Generic (same active ingredients) Brand vs. OTC (cost vs. effectiveness) Patent protection  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 (chemical therapy) and was awarded the Nobel Prize in medicine/physiology in 1908.  Some terminologies Analgesic (painkillers) Antipyretic (reduces fever) and pyrogens (produces a rise in temperature) Anticoagulant (prevents coagulation) Anti-inflammatory (reduces inflammation or swelling)  Pain Relievers: Nonsteroidal Anti- Inflammatory Drugs (NSAIDS) NSAIDS relieve pain and reduce inflammation by blocking the production of prostaglandins. Prostaglandins are a group of lipids with hormone-like actions that your body makes primarily at sites of tissue damage or infection.  Pain Relievers: Nonsteroidal Anti- Inflammatory Drugs (NSAIDS) NSAIDS include aspirin, ibuprofen, acetaminophen, etc.  Pain Relievers: Nonsteroidal Anti- Inflammatory Drugs (NSAIDS) Aspirin (acetylsalicylic acid) 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. Can’t be used after surgery. Aspirin is associated to “Reye’s Syndrome” in children. (disorder that affects all organs of the body brain and the liver) Regular dose = 325 mg, X-tra strength = 500 mg  Pain Relievers: Nonsteroidal Anti- Inflammatory Drugs (NSAIDS) Other Aspirin-Like Drugs including diclofenac, ibuprofen, ketoprofen, meloxicam, naproxen, and oxaprozin. Ibuprofen and naproxen are available in both prescription and over-the-counter (OTC) versions. The doses in OTC ibuprofen (Advil and Motrin) or naproxen (Aleve) are about half the doses of prescription versions.  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 messengers. Since NSAIDS block the production of prostaglandins, they help to reduce fever.  Pain Relievers: Nonsteroidal Anti- Inflammatory Drugs (NSAIDS) How NSAIDS Work Cycloxygenase (COX) enzymes catalyze the production of prostaglandins from arachidonic acid (C20). COX-1 is found in the stomach and kidney tissues, and COX-2 is found in tissues where inflammation occurs.  Pain Relievers: Nonsteroidal Anti- Inflammatory Drugs (NSAIDS) How NSAIDS Work Aspirin, Ibuprofen, and Naproxen 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 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.  Pain Relievers: Nonsteroidal Anti- Inflammatory Drugs (NSAIDS) Combination pain relievers can include a number of different NSAIDS as well as caffeine, antihistamines, and other drugs. Excedrin (Acetaminophen, aspirin and caffeine) and Anacin (Caffeine and Paracetamol) are familiar brands.  Prescription Medications Typical prescription pain relief medicines include opioids and non-opioid medications. Types of prescription opioid medications morphine, which is often used before and after surgical procedures to alleviate severe pain oxycodone, which is also often prescribed for moderate to severe pain  Prescription Medications codeine, which comes in combination with acetaminophen or other non-opioid pain relief medications and is often prescribed for mild to moderate pain hydrocodone, which comes in combination with acetaminophen or other non-opioid pain relief medications and is prescribed for moderate to moderately severe pain Prescription Medications  Drugs and Infectious Diseases An infectious disease is any disease caused by the direct effect of a pathogen. A pathogen may be cellular (bacteria, parasites, and fungi) or acellular (viruses, viroids, and prions).  Antibacterial Drugs In 1900s, infectious disease was a leading cause of death in US. What about in the 2000s?  Antibacterial Drugs Sulfa drugs were the first antibacterial drug. Sulfanilamide acts by replacing para- aminobenzoic (PABA) acid that bacteria need to manufacture folic acid.  Antibacterial Drugs Used extensively in WWII. Tend to cause kidney damage by crystallizing there. Replaced by newer antibacterial agents.  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 broad- spectrum antibiotics that act by binding to bacterial ribosomes inhibiting protein synthesis. They can cause discoloration of the permanent teeth in children by interaction of –OH group and Ca2+.  Antibacterial Drugs Inhibition of protein synthesis by erythtomycin, teracycline, streptomycin, and chloramphenicol.  Viruses and Antiviral Drugs Viruses are composed of nucleic acids and proteins. Viral diseases cannot be cured by antibiotics. Vaccination is often used against mumps, measles, smallpox, cold, etc.  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 Acyclovir (Zovirax) controls chickenpox, shingles, cold sores, symptoms of genital herpes.  Viruses and Antiviral Drugs Azidothymidine (AZT) slows AIDS virus. Combination drugs work better. Highly toxic.  Viruses and Antiviral Drugs Prevention of Viral Diseases with Vaccination While we do have limited numbers of effective antiviral drugs, such as those used to treat HIV and influenza, the primary method of controlling viral disease is by vaccination, which is intended to prevent outbreaks by building immunity to a virus or virus family. Vaccines may be prepared using live viruses, killed viruses, or molecular subunits of the virus  Viruses and Antiviral Drugs Prevention of Viral Diseases with Vaccination Live viral vaccines are designed in the laboratory to cause few symptoms in recipients while giving them protective immunity against future infections.  Viruses and Antiviral Drugs Prevention of Viral Diseases with Vaccination The danger of using live vaccines, which are usually more effective than killed vaccines, is the low but significant danger that these viruses will revert to their disease-causing form by back mutations. Live vaccines are usually made by attenuating (weakening) the “wild-type” (disease-causing) virus by growing it in the laboratory in tissues or at temperatures different from what the virus is accustomed to in the host.  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 Chemotherapy is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents) as part of a standardized chemotherapy regimen. Chemotherapy may be given with a curative intent (which almost always involves combinations of drugs), or it may aim to prolong life or to reduce symptoms (palliative chemotherapy).  Chemicals Against Cancer Chemotherapy is one of the major categories of the medical discipline specifically devoted to pharmacotherapy for cancer, which is called medical oncology. The available anticancer drugs have distinct mechanisms of action which may vary in their effects on different types of normal and cancer cells.  Chemicals Against Cancer There are very few demonstrable biochemical differences between cancerous cells and normal cells. For this reason the effectiveness of many anticancer drugs is limited by their toxicity to normal rapidly growing cells in the intestinal and bone marrow areas. A final problem is that cancerous cells which are initially suppressed by a specific drug may develop a resistance to that drug. For this reason cancer chemotherapy may consist of using several drugs in combination for varying lengths of time.  Chemicals Against Cancer Chemotherapy drugs, are sometimes feared because of a patient's concern about toxic effects. Their role is to slow and hopefully halt the growth and spread of a cancer. There are three goals associated with the use of the most commonly-used anticancer agents.  Chemicals Against Cancer 1. Damage the DNA of the affected cancer cells.  Chemicals Against Cancer 2. Inhibit the synthesis of new DNA strands to stop the cell from replicating, because the replication of the cell is what allows the tumor to grow.  Chemicals Against Cancer Stop mitosis or the actual splitting of the original cell into two new cells. Stopping mitosis stops cell division (replication) of the cancer and may ultimately halt the progression of the cancer.  Chemicals Against Cancer Categories of Chemotherapy Drugs In general, chemotherapy agents can be divided into three main categories based on their mechanism of action.  Chemicals Against Cancer Stop the synthesis of pre DNA molecule building blocks "Antimetabolites« methotrexate (Abitrexate®), fluorouracil (Adrucil®), hydroxyurea (Hydrea®), mercaptopurine (Purinethol®) thioguanine.  Chemicals Against Cancer This product acts as an antimetabolite by inhibiting the synthesis of 2-deoxythymidine because the carbon - fluorine bond is extremely stable and prevents the addition of a methyl group in the 5- position. The failure to synthesize the thymidine nucleotide results in little or no production of DNA.  Chemicals Against Cancer Directly damage the DNA in the nucleus of the cell "Alkylating agents, antibiotics, topoisomerase inhibitors and intercalating agents. cisplatin (Platinol®) 7) daunorubicin (Cerubidine®), doxorubicin (Adriamycin®) etoposide (VePesid®).  Chemicals Against Cancer cis-platin was used widely in the mid 80’s for prostate cancer. Interferes DNA synthesis (antimetabolite). Hair loss and nausea is expected. Toxic, affects normal cells too. 6-mercapto purine can substitute adenine.  Chemicals Against Cancer Effect the synthesis or breakdown of the mitotic spindles "Mitotic disrupters« Vinblastine (Velban®), Vincristine (Oncovin®) Pacitaxel (Taxol®).  Chemicals Against Cancer Paclitaxel (taxol) was first isolated from the from the bark of the Pacific Yew (Taxus brevifolia). Docetaxel is a more potent analog that is produced semisynthetically.  Hormones: The Regulators Hormones are chemical messengers produced in the endocrine glands. They regulate physiological activities (growth, metabolism, reproduction, etc.) at remote parts. Hormones: The Regulators  Hormones: The Regulators Types of Hormones The hormones of the human body can be divided into two major groups on the basis of their chemical structure.  Hormones derived from amino acids include amines, peptides, and proteins.  Those derived from lipids include steroids These chemical groups affect a hormone’s distribution, the type of receptors it binds to, and other aspects of its function.  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 Cortisone, an adrenal hormone, acts to reduce inflammation, used for arthritis treatment. Repeated use has side effect. Prednisone, replaced cortisone, is effective in much smaller dose, less side effect. Cholesterol is a steroid that does not have any hormonal activity. Hormones: The Regulators  Hormones: The Regulators Sex hormones are steroids. Androgens stimulate or control the development of masculine characteristics. They are secreted by the testes. The most important androgen is testosterone. Estrogens are compounds that control female sexual functions, produced in the ovaries. Estradiol and estrone control female sexual functions, progesterone prepares uterus for pregnancy.  Drugs for the Mind Psychotropic drugs affect the human mind and result in alterations of mood, thinking, perception, and/or behavior. Psychoactive drugs may be used for many purposes, including therapeutic, ritual, or recreational purposes. Besides caffeine, other examples of psychoactive drugs include cocaine, LSD, alcohol, tobacco, codeine, and morphine.  Drugs for the Mind Psychoactive drugs may be legal prescription medications (e.g., codeine and morphine), legal nonprescription drugs (e.g., alcohol and tobacco), or illegal drugs (cocaine and LSD).  Drugs for the Mind They fall into three categories according to their pharmacological effects Stimulants Depressants Hallucinogenic  Drugs for the Mind 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 (mindbenders).  Drugs for the Mind Mechanisms of Action Each drug tends to have a specific action on one or more neurotransmitters or neurotransmitter receptors in the brain. Generally, they act as either agonists or antagonists.  Drugs for the Mind Mechanisms of Action Agonists are drugs that increase the activity of particular neurotransmitters. They might act by promoting the synthesis of the neurotransmitters, reducing their reuptake from synapses, or mimicking their action by binding to receptors for the neurotransmitters. Antagonists are drugs that decrease the activity of particular neurotransmitters. They might act by interfering with the synthesis of the neurotransmitters or by blocking their receptors so the neurotransmitters cannot bind to them.  Drugs for the Mind Chemistry of the Nervous System Neurons, also called nerve cells, are electrically excitable cells that are the main functional units of the nervous system. Their function is to transmit nerve impulses. They are the only type of human cells that can carry out this function.  Drugs for the Mind Chemistry of the Nervous System Neurotransmission is the process by which signaling molecules called neurotransmitters are released by the axon terminal of a neuron (the presynaptic neuron), and bind to and react with the receptors on the dendrites of another neuron (the postsynaptic neuron) a short distance away.  Drugs for the Mind Chemistry of the Nervous System Synapses are functional connections between neurons, or between neurons and other types of cells. The synaptic cleft —also called synaptic gap— is a gap between the pre- and postsynaptic cells that is about 20 nm (0.02 μ) wide. The small volume of the cleft allows neurotransmitter concentration to be raised and lowered rapidly.  Drugs for the Mind Biochemical Theories of Brain Diseases The lack or excess of specific neurotransmitters can be associated with depression, anxiety, bipolar disorder, or schizophrenia. Other disorders or health conditions, namely Attention Deficient Hyperactivity Disorder (ADHD) and Parkinson's Disease have also been linked with varying levels of neurotransmitters. Some Chemistry of the Nervous System Neurotransmitters  Drugs for the Mind Biochemical Theories of Brain Diseases Mental health conditions can result from a person's life experiences and/or genetics. Sometimes, drug usage or brain trauma can trigger mental illness. It is important to note all health conditions that are present in your family tree (biological). Also, recognizing emotional trauma and then seeking counseling/medical treatment is important for navigating a mental health condition.  Drugs for the Mind Depression symptoms Can be short or long-term. Experience-sadness, sleeping and eating issues, withdrawal, feelings of hopelessness, loss of interest/pleasure, lack of energy, feelings of worthlessness/guilt, slowed processing, trouble concentrating, frequent thought of suicide/death, anxiety, and unexplained health problems.  Drugs for the Mind Antidepressant Medications  Drugs for the Mind Anti Depressants Monoamine Oxidase Inhibitors Monoamine oxidase inhibitors (MAOIs) were the first effective antidepressants used. The monoamine oxidase inhibitors comprise a chemically heterogeneous group of drugs that have in common the ability to block oxidative deamination of naturally occurring monoamines.  Drugs for the Mind Anti Depressants Serotonin Serotonin (5-hydroxytryptamine or 5-HT) is a monoamine neurotransmitter found in cardiovascular tissue, in endothelial cells, in blood cells, and in the central nervous system.  Drugs for the Mind Anti Depressants Tricyclic Anti-depressants Imipramine, amitriptylin, and other closely related drugs are among the drugs currently most widely used for the treatment of major depression. Because of there structure they are often referred to as the tricyclic antidepressants.  Drugs for the Mind Anti Depressants Selective Serotonin Reuptake Inhibitors In recent years, selective serotonin reuptake inhibitors (SSRIs) have been introduced for the treatment of depression. Prozac is the most famous drug in this class.  Depressants - Anesthetics Anesthetics are substances that cause lack of feeling or awareness.  Depressants - Anesthetics General anesthetics produce unconsciousness and block feelings of pain. Diethyl ether is the first GA. Gives nausea, highly flammable. Nitrous oxide, N2O, laughing gas, effective concentration is >50% with O2. Lack of O2 can cause brain damage. Chloroform, CHCl3 is also a GA. Not flammable, but have narrow safety margin.  Depressants - Anesthetics Local anesthetics block feelings of pain in a specific part of the body (dental work or minor surgery). Cocaine was the first local anesthetic. It is also a powerful stimulant and addictive. Dentists use procaine (Novocain).  Depressants - Alcohol Ethyl alcohol (ethanol) Most used and abused drug in the world. It is a depressant. Moderate drinking increase longevity, due to relaxation effect. Too much alcohol use gives adverse effects: intoxication, loss of motor function, highway fatality, alcoholism, increased suicide rate, fetal alcohol syndrome, birth defect.  Depressants - Barbiturates Barbiturates are a family of related depressants. They were once used as a mild sedative (few mg). In larger doses (~100 mg) they induce sleep. Barbiturates are very toxic, lethal dose is 1500 mg. Used as medicine to calm anxiety and as anticonvulsant for epileptics and brain-damaged people.  Depressants 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. At lower doses many of these are classified as non-narcotic.  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 10% of the weight of raw opium. Widely used in Am. Civil War as pain killer. Gives constipation. Addiction from the usage was called “soldier’s disease”.  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. Less potent and less addictive. Less than 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.  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. It allows user to hold a productive job. It is addictive. Demerol does not cause nausea.  Narcotics Morphine 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. 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.”  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 Methamphetamine has more psychological effect.  Stimulant Drugs Cocaine is a powerful stimulant. It used to arrive in the U.S. as cocahydrochloride. It is now available as free-base ine crack cocaine. It acts by preventing the re-absorption of dopamine. This leaves 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.  Stimulant Drugs Caffeine: Coffee, Tea, or Cola Caffeine is a mild stimulant. Effective dose is ~200 mg (1- 2 cup strong tea or coffee). Addictive – “morning grouch” syndrome. Vivarin – 200 mg. No-Doz – 100 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. Smokers pay upfront (tax) and later (health). It is highly toxic to animals, used as insecticide in agriculture, lethal dose in human is 50 mg when injected.  Psychedelic Drugs These are called “mind-benders” Lysergic acid diethylamide (LSD) is a semisynthetic powerful psychedelic drug. It is synthesized by converting lysergic acid (from ergot) to its diethylamide derivative. At small dose (10-100 µg) it gives good effect, at high dose (mg) it gives various effect, lack of self control, extreme terror, schizophrenia, visual disturbances, etc.  Psychedelic Drugs Marijuana is prepared from the leaves, flowers, seeds, and stems of the Cannabis sativa plant. One major active ingredient is tetrahydro- cannabinol (THC). Marijuana increases pulse rate, distorts sense of time, impairs complex motor function, etc.  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.” Placebo test vs. double blind test.  New Uses for Old Drugs The development of new drugs is very expensive. Many older drugs have been tested and approved for new uses.