Option D – Medicine and Drugs

Option D – Medicine and Drugs IB Chemistry Outline of this option Pharmaceutical products ( definitions, categories, placebo effect, body's defenses, research, Thalidomide, administration of drugs, toxicity, tolerance) Antacids Analgesics ( mild - aspirin, acetaminophen, ibuprofen strong (opiates) - morphine, codeine, heroin) Depressants ( tranquilizers - alcohol, "other") Stimulants (adrenaline (epinephrine) amphetamines - ecstasy, pheylethylamine, dopamine, "speed") Antibacterials (penicillin) Antivirals (AIDS)

What is a medicine or drug? · A substance that alters one or more of the following: ·Incoming sensory sensations ·Mood or emotions ·Physiological state ·Consciousness ·Activity level ·Co-ordination

D.1 Pharmaceutical Products A drug or medicine is any chemical which: Alters sensory sensations Alters mood or emotions Alters physiological state (consciousness, activity level, or coordination) Drugs: chemicals that affect how the body works. Used to describe substances both legal and illegal. Medicines: substances that improve health. Can be natural or synthetic. The beneficial effects of medicines are known as the therapeutic effect.

Categories of medicines ·Infection fighters ·Antiseptics ·Antibiotics ·Antivirals ·Affecting metabolism ·Hormones ·Vitamins ·Affecting central nervous system ·Stimulants ·Depressants ·Analgesics ·Anaesthetics

·Placebo effect: ·A pharmacologically inert substance (often a sugar pill) produces a significant reaction because the patient expects, desires, or was told it would happen ·Used as a control in clinical trials ·Highlights the body’s natural healing powers and power of suggestion

Body’s Lines of Defense ·First line defense: ·Skin, mucous membranes, closures and secretions (lips, eyelids, ear wax, etc.) ·Second line defense: ·White blood cells, blood clotting, inflammatory response ·Third line defense: ·Antibodies, memory cells

Research on new products ·1. Tests on animals ·Dose, side effects ·2. Clinical trial (phase 1) ·Safety, dose range ·3. Clinical trial (phase 2) ·Response, investigator bias, statistics ·4. Clinical trial (phase 3) ·Extended evaluation

·D.1.2 Research and Development: ·Development of a new drug is a very costly, lengthy process controlled by the government: ·In 1970, 3620 drugs were tested. 16 came on the market at an average cost of $20 million ·Only 1 in 2000 drugs eventually make it to the market ·Phase I: Initial clinical trials on volunteers after the drug has proven safe when given to animals ·Phase II: Thorough clinical investigation to eliminate investigator bias ·Phase III: Extended clinical evaluation

Thalidomide Early 1960’s given to pregnant women to treat morning sickness Later found to cause major birth defects One isomer controls morning sickness, the other leads to birth defects (optical isomer)

Administration of drugs ·Oral ·convenient, effect varies because absorption is affected by stomach content and drug concentration ·absorbed at small intestines ·Rectal ·Effective if a drug cannot be taken orally or if a drug is pH sensitive ·when not able by mouth or destroyed by acids ·Inhalation ·rapid due to extensive network of blood vessels in lungs ·anaesthesia ·Parenteral / Injection ·Subcutaneous (dental, slow) ·Intramuscular (vaccinations, large V) ·Intravenous (fast, practical)

·Parenteral (injection) ·Subcutaneous ·Beneath the skin ·Slow absorption ·Intra-muscular ·Used when immediate response is not required ·Used for large volumes of drug injection ·Intravenous ·Near instantaneous effect ·Concentration not affected by stomach content

·More about drugs ·Fat-soluble drugs are more easily absorbed, since blood vessels contain a fatty layer ·Capillaries of brain are denser and prevent diffusion of many substances into the brain (blood-brain barrier) ·Drugs are broken down by the kidneys and liver ·Half-life is the time required for half of the drug to be eliminated

·Toxicity ·LD50 is the dose (in mg of substance per kg of body mass) that is lethal to 50% of laboratory animals ·The lower the LD50, the more toxic the substance ·Lowest LD50 rating known as of yet: botulism toxin (BoTox) – most toxic substance known LD50 of roughly 0.005-0.05 µg/kg ·ED50 – the effective dose where 50% of the population shows a noticeable effect. The smaller the ED50, the more effective the substance Examples: aspirin 55

Examples: (mg/kg) aspirin rat: 200 rabbit: 1000 nicotine rat: 50 ethanol rat: 9000

Therapeutic window = the ratio of LD50 over ED50 The wider the window, the safer the substance Examples: aspirin therapeutic window = 200/55

D.1.4 Terms to Know ·Therapeutic window: physiological effects that are intended when prescribed. It is also the concentration in the blood where the drug becomes effective but below the level where it would be toxic. ·Side effects: physiological effects which are not intended. They can vary greatly from drug to drug. ·Tolerance: what occurs when a drug becomes less effective over time. Higher doses are then needed to have the desired effect.

Drug effect ·Main effect (desired) ·Side effects (unwanted responses) ·Drug effects are relative!! ·Morphine: ·For pain relief, constipation is side effect ·For diarrhoea, pain relief is side effect

Tolerance and Dependence Drugs may result in physical or psychological dependence Tolerance means that over time, an individual requires an increased amount of the drug to achieve the same physiological effect

ANTACIDS ·Why is stomach acidic? ·How can we neutralize it? ·What are the most common antacids? ·What are the neutralizing reactions? ·With what can the antacids be combined?

D.2 Antacids ·Bases (metal oxides, metal hydroxides, metal carbonates, or metal hydrogen carbonates) that react with excess stomach acid to adjust pH ·Often combined with alginates and anti-foaming agents to prevent reflux ·Consumption of too much antacid results in alkalosis (basic stomach) ·Stomach acid (gastric juice) is secreted from gastric glands which line the stomach. The acid (HCl) helps suppress growth of harmful bacteria and aids in digestion by creating a better environment for certain enzymes to work.

·The following antacids produce a salt, water and carbon dioxide. This can lead to bloating and flatulence. ·Anti-foaming agents (e.g. dimethicone) are added to help reduce this. CaCO3(s)+ 2HCl(aq)-->H2O(l) +CO2(g) +CaCl2(aq) NaHCO3(s) +HCl(aq) -->H2O(l) + CO2(g) +NaCl(aq) ·Some antacids also contain alginates. They float on top of the stomach contents, creating a barrier, preventing reflux into the esophagus.

Neutralization Reactions ·Aluminum hydroxide and magnesium hydroxide react with the acid to produce a salt and water. ·Reactions: ·Al(OH)3(s) + 3 HCl(aq) -->AlCl3(aq) + 3H2O(l) ·Mg(OH)2(s) + 2 HCl(aq) -->MgCl2(aq) + 2H2O(l)

ANALGESICS ·What are soft and strong analgesics? ·How do they prevent pain? ·Aspirin versus paracetamol? ·Morphine versus heroin/codeine? ·Advantages – disadvantages?

Definition of analgesics and categories Analgesics are drugs that relieve pain. These are: Mild analgesics: used for relief of mild pain. (aspirin, acetaminophen) Strong analgesics: used for relief of very severe pain. (morphine, heroin, codeine) Local anesthetics: used as pain killers in localized areas. (lidocaine, procaine) General anesthetics

D.3 Analgesics ·Pain receptors in our bodies are nerves that transmit pain. These are free nerve endings located in various body tissues that respond to thermal, mechanical and chemical stimuli. When stimulated, these pain receptors generate an impulse. The pain results of various impulses arriving at the spinal cord and the brain. ·When tissues become injured, they release chemicals called prostaglandins and leukotrienes that make the pain receptors more sensitive and thus causing pain.

D.3.1 Analgesics ·Pain relievers act by interfering with pain receptors ·The brain sends nerve impulses through pain receptors and nerve pathways. ·Mild analgesics work by interfering with the pain stimulus at the source. One way is by blocking the production of prostaglandins. These are released when cells are damaged by thermal, mechanical, or chemical energy. ·Prostaglandins: ·Constrict blood vessels ·Affect hypothalamus (region of brain controls heat regulation and hence fever can result) ·Increase permeability of capillaries to allow for swelling (inflammatory response)

Mild analgesics They work by blocking the enzyme-controlled synthesis of prostaglandins. The main effects prostaglandins are: 1) The constriction of blood vessels, which helps increase the body temperature. 2) Direct effect on the body’s heat regulating centre, hypothalamus, which produces fever. 3) Increase of the permeability of capillaries which allows water to pass to the tissue and cause pain and swelling.

·D.3.2 Mild analgesics ·Aspirin (acetyl salicylic acid or ASA) produced from salicylic acid (relatively strong acid, difficult to take) ·Addition of acetyl group lowers acidity – less irritating to stomach ·ASA is called a prodrug: a less active form that is converted to the active form after administration ·ASA can also be used to produce alka-seltzer and other drugs by further modification

Natural painkillers They are produced naturally in the body. Endorphins and enkephalinsare the natural opiates found in the part of the brain and the spinal cord that transmit pain impulses. They are able to bind to neuroreceptors in the brain and produce relief from pain. The temporary loss of pain immediately after an injury is associated with the production of these chemicals.

·Uses of salicylic acid and its derivatives:· ·Relief from minor aches and pains ·Fever reduction (antipyretic) ·Anti-inflammatory agent ·Anti-clotting agent As mild analgesic for minor aches and pains. As an antipyretic. As an anti-inflammatory agent when there is swelling from injuries. As an anti-clotting agent in the prevention of abnormal blood clotting and as an anti clotting agent after heart surgery.

Disadvantages of aspirin: ·Can cause upset stomach and ulceration ·Risk of severe gastrointestinal bleeding following alcohol consumption ·Small risk of allergy (.5% of population) ·Accidental infant poisoning; small correlation to Reye’s syndrome in children (a fatal liver and brain disorder with the symptoms of vomiting, lethargy, irritability and confusion.)

·Salicylic acid was widely used as a fever reducer However, it is relatively strong acid so it was unpleasant to take orally and it damaged the membranes lining the mouth, esophagus and stomach. ·Sodium salicylate (its salt) was used but it was also highly irritating to the stomach. ·Its ester called Acetyl Salicylic Acid (ASA) named aspirin retains the beneficial properties of salicylic acid but is less irritating to the stomach. ·ASA is relatively tasteless so it can be taken orally.

·D.3.2 Aspirin substitutes ·Acetaminophen ( paracetemol) ·Does not upset stomach or cause bleeding ·NOT an anti-inflammatory ·Safe in correct dose, but overdose ( >20 tablets) can cause serious liver damage, brain damage, and death) ·Ibuprofen ·Many of the same effects as aspirin but fewer stomach problems ·It is an anti-inflammatory drug.

D.3.3 ·Strong analgesics work by binding to receptors in the brain ·Prevents transmission of pain impulses without depressing the central nervous system ·The opium alkaloids: ·Opiate: it is a natural or synthetic drug that exerts actions on the body similar to those induced by morphine. ·Narcotic: is a term generally used for drugs that have both a narcotic and analgesic action.

morphine, heroin and codeine Morphine is the principal alkaloid and makes up about 10% by mass of raw opium. Codeine makes up about 0.5% by mass of raw opium. Heroin is usually synthesized from morphine and thus is a semi-synthetic drug and it is obtained by relatively simple structural modification of morphine or codeine.

Opium plant Morphine

·Strong analgesics ·Opiates (narcotics) ·Opium alkaloids (morphine, heroin, codeine) ·Belong to “opiate” class (drug that exerts actions on the body similar to morphine) or “narcotics” (drug that produces a narcotic (sleep-inducing) effect as well as an analgesic (pain relieving) effect) Morphine is principal alkaloid, making up about 10% by mass of raw opium ·Codeine is about .5% of raw opium ·Heroin (diamorphine)is synthesized from morphine (semi-synthetic drug) via a simple acetylation

·Note: All three share the following functional groups; benzene ring, ether, alkene, amine (tertiary). ·Codeine and morphine also have a hydroxyl group while heroin has ester functional groups.

Structures

·D.3.3 Advantages of Opiates: ·Pharmacological effects ·Major effects on: ·Nervous system ·The eye ·GI tract gastrointestinal tract (the digestive system) ·Uses: ·Strong analgesic for relieving severe pain ·Treatment of diarrhea (produces constipation) ·Cough suppressant ·Constriction of the pupil ·Narcotic effects

·Disadvantages: ·Psychological effects ·Drowsiness, mood change, mental fogginess, nausea and vomiting ·Anxiety, fear, lethargy, sedation, lack of concern, inability to concentrate ·Effects increase from codeine to morphine to heroin (highest) ·Tolerance and Dependence ·Cross-tolerance can occur (users tolerant to one opiate will be tolerant to other opiates) ·Users may not function properly without the drug, experience withdrawal symptoms (addiction)

Tolerance appears due to the induction of drug metabolizing enzymes in the liver and also to the adaptation of neurons in the brain to the presence of the drug. The users that became tolerant to one opiate will also exhibit a tolerance to all other opiates.

Narcotic Effects ·Short-Term: ·Feelings of well-being and contentment ·Dulling of pain and lessens fear and tension ·Euphoria ·Long-Term: ·Constipation and reduced libido ·Loss of appetite and poor nutrition ·Dependence, Tolerance and Withdrawal

·Tolerance appears due to the induction of drug metabolizing enzymes in the liver and also to the adaptation of neurons in the brain to the presence of the drug. ·The users that became tolerant to one opiate will also exhibit a tolerance to all other opiates.

The opiates (in general) They are extremely potent and valuable drugs for the treatment of pain They have the capacity of inducing a state of euphoria and relief from physiological pain The opiates induce profound tolerance and physiological dependence They are important both medically and sociologically as the user is difficult to treat and must frequently resort to crime to support the habit and reach a source of supply.

Summary of the effects of opiates ·Short term effects ·Sedation and stupor ·Euphoria ·Reduced tension, worry and fear ·Reduced coughing reflex ·Occasional death from overdose ·Long term effects ·Loss of appetite ·Sterility ·Withdrawal illness, loss of job, crime ·Diversion of energy and money ·Risk of dangerous infections due to shared needles

Option D – Medicine and Drugs