Option D: Medicines and drugs

D1 Pharmaceutical products

Assessment statement D.1.1 List the effects of medicines and drugs on the functioning of the body.

D.1.2 Outline the stages involved in the research, development and testing of new pharmaceutical products.

D.1.3 Describe the different methods of administering drugs.

D.1.4 Discuss the terms therapeutic window, tolerance and sideeffects.

Obj Answer 1 A medicine or drug is a chemical that: Alters the physiological state (consciousness, activity level or coordination), alters incoming sensory sensation and or alters mood and emotions. Although drugs and medicines can be helpful in aiding the body against invaders, the first line of defense and the most important is the human bodys natural system of defense. The first line of defense is barriers to prevent entry. These include the skin, mucous membranes, and closures and secretions of natural openings such as lips, eyelids and ear wax. Healing can also be achieved without the use of medicines or drugs. This can be done by the power of suggestion; this is called the placebo effect. The placebo effect occurs when a patient receives therapeutic and healing effects from medicines that are pharmacologically inert, when they believe they are taking an effective drug. 2 The stages involved in the research, development and testing of new pharmaceutical products are first discovery research. Discovery research usually takes up to 3 years and involves the identification of lead compounds, synthesis of analogues ( testing many chemically related compounds) and biological testing done on animals. The next step in developing a pharmaceutical product is developmental research. This step can take up to 6 years and involves human tests and is usually split up into three phases. Phase one involves 50-100 healthy volunteers. Phase 2 involved 200-400 patients. And phase 3 involves 300+ patients in which half are given the drug and the other half a placebo. In phase 3 neither the patient nor the doctor knows which preparation is being given. Sometimes all of these steps fail to detect an adverse side effect. An example of this is the thalidomide case which involved the drug thalidomide which causes birth defects. 2 The different methods of administering drugs are: Oral, which is taken by mouth. Examples of this are tablets, capsules, pills and liquids; Inhalation which is taken by vapor breathed in or by smoking. Examples of this are medications for respiratory conditions such as asthma and some drugs such as nicotine and cocaine; Skin patches, which are absorbed from the skin into the blood. Examples of this are hormone treatments; Suppositories, which are inserted into the rectum. Examples of this are treatments of digestive illnesses; Eye or ear drops, which are delivered directly into the opening. Examples of this are treatments of infections of the eye or ear; parenteral, which are taken by injection. Examples of this are vaccines, anesthetics and dental injections. Injections may be intravenous (the drug is injected directly into the blood stream), intramuscular (the drug is injected into a muscle) or subcutaneous (the drug is injected directly under the surface of the skin). 3 The ED50 of a drug is the dose required to produce the desired effect in 50% of test animals or patients. The ratio of LD50 (lethal dose) to ED50 (therapeutic dose) is known as the therapeutic window. For example a therapeutic window of 10 indicates an LD50 : ED50 ratio of 10 to 1. This

means that a ten-fold increase in the dose would result in a 50% death rate. Tolerance is when a higher dose of a drug is required to achieve the same effect that a lower dose initially had. An example of Tolerance is alcohol. A steady consummation of alcohol will build up tolerance. There are two different timeframes of tolerance. Acute tolerance and chronic tolerance. Acute tolerance occurs within a single exposure to the drug and chronic tolerance occurs when the drug is taken repeatedly. Side effects are any effects other than the intended effects. Side effects can vary from negative to positive.

D2 Antacids Assessment statement D.2.1 State and explain how excess acidity in the stomach can be reduced by the use of different bases.

Obj Answer 3 Factors such as alcohol, smoking, stress and some anti-inflammatory drugs, can cause excess production of gastric juice. This can lead to acid indigestion, heartburn and ulcers. This is where antacids come in. Antacids are weak bases which neutralize excess acid. Antacids work by neutralizing the hydrochloric acid and relieving the symptoms. Antacids react with the acid to produce salt and water. Examples of these reactions are Aluminum hydroxide Al(OH)3: Al(OH)3 (s) + 3HCl(aq)AlCl3(aq) + 2H2O(l). Another example of such reaction is Magnesium hydroxide Mg (OH)2: Mg(OH)2(s) + 2HCl(aq) MgCl2(aq) + 2H2O(l). Antacids are often combines with alginates (which produce a neutralizing layer, preventing acid in the stomach from rising into the esophagus and causing heartburn).

Option D: Medicines and drugs

D3 Analgesics Assessment statement D.3.1 Describe and explain the different ways that analgesics prevent pain. Obj Answer 3 There are many ways that analgesics prevent pain. Mild analgesics include aspirin and non-steroidal anti-inflammatory drugs such as ibuprofen. Mild analgesics act by preventing stimulation of the nerve endings at the site of pain. Mild analgesics promote the release of prostaglandins from the site of pain and relieve inflammation and fever. Strong analgesics such as the drugs related to morphine, known as the opioids work by binding to the opioid receptors in the brain which blocks the transmission of pain signals between brain cells and alters the perception of pain in the brain. Some side effects of strong analgesics can be drowsiness and possible change in behavior and mood. Strong analgesics are the most effective painkillers for severe pain but come with potential problems like independence. 2 IN 1860 the German Chemist Hermann Kolbe synthesized salicylic acid by reacting sodium phenoxide (C6H5O-Na) and carbon dioxide. Later on this was found to alleviate the symptoms of arthritis. Some of the advantages of using aspirin are that it has been found to be useful in preventing the recurrence of heart attacks and strokes. Some of the disadvantages of using aspirin include the development of ulcers and stomach bleeding, allergic reactions and Reyes syndrome in children. Reyes syndrome is a

D.3.2 Describe the use of derivatives of salicylic acid as mild analgesics, and compare the advantages and disadvantages of using aspirin and paracetamol

(acetaminophen).

D.3.3 Compare the structures 3 of morphine, codeine and diamorphine (heroin, a semi-synthetic opiate).

D.3.4 Discuss the advantages and disadvantages of using morphine and its derivatives as strong analgesics.

potentially fatal liver and brain disorder. The advantages of paracetamol are that paracetamol is very safe especially in children. In extreme cases paracetamol can cause blood disorders and kidney damage. Overdose on paracetamol can lead to serious liver damage, brain damage and death. The structure of morphine consists of a benzene ring, ether, alkene, alcohol, and tertiary amine. Morphine is obtained from raw opium ( 10%). The structure of codeine consists of a benzene ring, ether, alkene, alcohol and tertiary amine. The structure of diamorphine consists of a benzene ring, ether, alkene, ester-ethanoate and tertiary amine. The modification of morphine that results in the semisynthetic drug diamorphine is the added ester-ethanoate. Heroin causes the user to feel drowsy, warm and contented. Heroin is also one of the best painkillers. It also relieves stress and discomfort by creating a detachment from pain. One of the disadvantages is that users quickly become physically dependent and tolerant to the drug. This means that larger does must be taken to achieve the same state of euphoria. Withdrawal from high doses of heroin produces a variety of short term effects like symptoms similar to the flu. These effects last only for about a week. Long term effects can be the spread of diseases such as tetanus AIDS and Hepatitis. This is cause by the sharing of unsterilized needles. Dependency of the drug can lead to financial problems which can lead to crime.

D4 Depressants Assessment statement D.4.1 Describe the effects of depressants.

D.4.2 Discuss the social and physiological effects of the use and abuse of ethanol.

D.4.3 Describe and explain the techniques used for the detection of ethanol in the breath, the blood and urine.

Obj Answer 2 The effects of depressants depend on the dosage. At low doses a depressant may show little to no effect. At moderate doses the depressant can induce sedation (soothing, reduction of anxiety). At higher doses the depressant may induce unconsciousness (sleep). At extremely high doses it may cause death. 3 The effects of alcohol on society are considerable. There is a strong correlation between heavy drinking and diseases like: strokes, cirrhosis of the liver, suicide rates and all cancers, especially stomach cancers. A longterm effect of alcohol is that large quantities can lead to brain damage due to the alcohols dehydrating properties. In pregnant woman alcohol can lead to the baby being born with fetal alcohol syndrome where the baby is born underweight with brain damage. The use and abuse of ethanol can also cause changes in behavior. Some short-term effects of ethanol abuse include: Loss of self-restraint, loss of balance and judgment, violent behavior which can cause family brake down, dangerous risk taking, dehydration and at high doses vomiting. Some long-term effects causes by ethanol abuse include: alcoholism, liver disease, coronary heart disease, high blood pressure, fetal alcohol syndrome and permanent brain damage. 3 There are many different techniques used for the detection of ethanol in the breath, the blood and urine. One of the simpler techniques used for the detection of ethanol is a roadside breathalyzer. A road side breathalyzer contains crystals of potassium dichromate which are orange; these crystals are changes to green chromium (lll) in the presence of ethanol as they oxidize the ethanol into ethanol. The extent of this change can then be measured by a photocell and this can be used to determine the ethanol concentration. This test is not very accurate and most likely leads to more

D.4.4 Describe the synergistic effects of ethanol with other drugs.

D.4.5 Identify other commonly used depressants and describe their structures.

accurate tests. Another more accurate technique used for the detection of ethanol is the use of infrared spectroscopy in an apparatus called an intoximeter. An intoximeter works behind the idea that different molecules cause different absorption bands in the infrared part of the spectrum; as a result ethanol has a distinct band. The size of the peak can then show the ethanol concentration present when compared to the air stream. A different version of an intoximeter uses a fuel cell. Another technique that is used for the detection in ethanol is what is called gas-liquid chromatography; this technique has to be carried out in a laboratory. This works by injecting vaporized blood or urine into a stream of inter gas and then measuring the retention time. Ethanol has the potential to increase the activity of other drugs when taken at the same time. This effect is known as synergy. Some examples of how ethanol increases the effects of other drugs are: With aspirin, ethanol can cause increase risk of bleeding in the stomach and stomach ulcers; With depressants ethanol can cause heavy sedations and even lead to comas; With tobacco, ethanol can increase the chances for cancer especially in the liver and intestines; With other drugs alcohol can cause effects that the drug is not meant to do. Other commonly used depressants include diazepam marketed as Valium, nitrazepam marketed as Mogadon and fluoxetine hydrochloride marketed as Prozac. Both diazepam and nitrazepam contain both benzene rings and the diazepine structure, which are a seven-membered heterocyclic ring containing carbon and two nitrogen atoms. These molecules have high lipid solubility and can cross the brain-blood barrier easily.

Option D: Medicines and drugs

D5 Stimulants Assessment statement D.5.1 List the physiological effects of stimulants. Obj Answer 1 The physiological effects of stimulants are: increase heart rate and blood pressure, increase blood flow, increase air flow, increase mental awareness. Long term side effects such as that of nicotine can cause high blood pressure, increased heart disease risk, coronary thrombosis, increased levels of fatty acids in the blood which can lead to stroke and increased risk of peptic ulcers. 3 Amphetamines and adrenaline are chemically similar they are both derived from the phenylethylamine structure. Amphetamines mimic the effects of adrenaline. 3 Short-term effects of nicotine consumption include: Increased concentration, relieves tension and boredom, helps counter fatigue, increased heart rate and blood pressure, decrease in urine output. Some long term effects of nicotine include: high blood pressure, increases risk of heart disease, coronary thrombosis, increased level of fatty acids which can cause stroke and increased risk of peptic ulcers. Nicotine is a habit forming drug which quickly leads to dependence or addiction. One of the risks associated with smoking tobacco is the risk of lung cancer due to the chemicals released when a cigarette is burned. 3 Caffeine is present in many substances like coffee, tea, chocolate and colas. Caffeine reduces physical fatigue and restores mental alertness. Caffeine is a

D.5.2 Compare amphetamines and epinephrine (adrenaline). D.5.3 Discuss the short- and long-term effects of nicotine consumption.

D.5.4 Describe the effects of caffeine and compare its

structure with that of nicotine.

respiratory stimulant. When consumed in small amounts caffeine enhances mental energy but when consumed in large amounts caffeine can cause anxiety, irritability and insomnia. Both the structure of nicotine and caffeine contain heterocyclic rings and a tertiary amine group. In addition, caffeine contains two amide groups.

D6 Antibacterials Assessment statement D.6.1 Outline the historical development of penicillins. Obj Answer 2 Penicillins were first discovered in 1928 by Alexander Fleming who noticed that a fungus known as penicillium notatum had contaminated some of his cultures. Fleming then noticed that where the penicillium notatum had contaminated there were no cultures. Later work was done by Australian bacteriologist Howard Florey and Germany born biochemist Ernst Chain to successfully isolate penicillin. 3 Penicillins work by interfering with the chemicals that bacteria need to form normal cell walls. Penicillins inhibit the development of cross-links in bacterial walls therefore weakening the wall. Changing the side-chain results in penicillins that are more resistant to the penicillinase enzyme which is created by bacteria that have developed bacterial resistance. 3 Patient compliance insures that the drug is effective in what its treating. Patient compliance also lowers the drug exposure to the bacteria which lowers the chances for the bacteria to develop resistance to the drug. The effect of penicillin over prescription is that the bacteria develop resistance to penicillin. The use of penicillin in animal feedstock also contributes to the resistance problem.

D.6.2 Explain how penicillins work and discuss the effects of modifying the side-chain. D.6.3 Discuss and explain the importance of patient compliance and the effect of penicillin overprescription.

Option D: Medicines and drugs

D7 Antivirals Assessment statement D.7.1 State how viruses differ from bacteria. Obj Answer 1 Viruses differ from bacteria because they are such small and simple structures; they contain two components, have no cellular structure and are only capable of reproducing inside another living cell. Bacteria have a more complex cellular structure and have the ability to survive and reproduce independently from other living cells. 2 There are two ways that an antiviral drug works. The first way they work is by altering the cells genetic material so that the virus cannot use it to multiply. The second way they work is that they may prevent the viruses from multiplying by blocking enzyme activity within the host cell. 3 Some of the difficulties associated with solving the AIDS problem and developing a cure is that the virus destroys T helper cells, which are the cells that should be defending the body from the disease itself. Another difficulty associated with solving the AIDS problem is that the virus tends to mutate a lot. The virus also lays dormant which means that the immune system has nothing to respond to. All of these factors coupled with the high cost of antiretroviral agents and sociocultural issues make the Aids problem a tough problem to solve.

D.7.2 Describe the different ways in which antiviral drugs work. D.7.3 Discuss the difficulties associated with solving the AIDS problem.

D8 Drug Action Assessment statement D.8.1 Describe the importance of geometrical isomerism in drug action. Obj Answer 2 There are two different ways in arranging four ligands. The first way is the cis arrangement. This is when ammonia molecules are adjacent to one another. The other way of arranging is trans arrangement. This is when two ammonia molecules are opposite from one another. These types of arrangements can occur in inorganic complexes. Two different isomer arrangements can have different pharmacological effects. For example the cis isomer of [Pt(NH3)2Cl2] is used medically as an anti-cancer drug known as Cisplatin. But the trans isomer does not show any anti-cancer properties 3 Enantiomers that act as a drug have different biological properties because they bind with receptor molecules. These receptors are usually only capable of binding with the enantiomer that has a complementary structure. An example of a drug with two possible enantiomers is thalidomide. One enantiomer relieves morning sickness while the other causes deformities in the limbs of the fetus. 3 The importance of the betalactam ring action of penicillin is that this four membered ring is what is responsible for the antibacterial activity of penicillin. The ring opens up so that the penicillin becomes bonded to the enzyme thus blocking the synthesis of bacterial cell walls and inhibiting the enzyme from catalyzing any further reactions. 3 The increased potency of diamorphine is due to a polar alcohol group (-OH) has been converted to a less polar ethanoyl group. This group conversion results in an increased potency. This also makes it easier to transport into the non-polar part of the central nervous system.

D.8.2 Discuss the importance of chirality in drug action

D.8.3 Explain the importance of the betalactam ring action of penicillin.

D.8.4 Explain the increased potency of diamorphine (heroin) compared to morphine

D9 Drug Design
Assessment statement D.9.1 Discuss the use of a compound library in drug design. Obj Answer 3 In traditional drug design collection of related compounds are synthesized one at a time and evaluated. This approach is time consuming and costly. The chemical analogues constitute a compound library. Here the analogues will share common structural features but will have one or more different functional groups. For example various chemical analogues were retested until a suitable molecule with the best chemical, pharmacological and physical properties was obtained to make paclitaxel and docetaxel. This is better than the traditional method because now the makers of the drug dont have to go out there and find new analogues; they can now work from a library of analogues. 3 Combinatorial chemistry is the process by which a large number of new chemical structures are synthesized on a small scale using solid phase

D.9.2 Explain the use of combinatorial and

parallel chemistry to synthesize new drugs. D.9.3 Describe how computers 2 are used in drug design.

D.9.4 Discuss how the polarity 3 of a molecule can be modified to increase its aqueous solubility and how this facilitates its distribution around the body. D.9.5 Describe the use of 2 chiral auxiliaries to form the desired enantiomer.

chemistry. Combinatorial chemistry screens for biological activity. Parallel chemistry is used to synthesized smaller number of new chemical analogues but turns out more focused libraries. Computers aide in drug design by creating three-dimensional models which can be used for the virtual development and evaluation of the drug. Computers can also show if the drug is stable or not by performing energy minimization. Computers also offer the hope to developing drugs that will better attack the target sight. This is known as de novo drug design. The solubility of a drug in a polar and non-polar environment determines its abortion, distribution and excretion. Changing the polarity of the drug can improve its medical properties. For example a drug that contains a carboxylic acid functional group can be made more polar by converting them to a salt. An example of this is soluble aspirin which is the calcium or sodium salt of aspirin. Once the aspirin reaches the acidic environment in the stomach it changes back to the un-ionized form. A chiral auxiliaries is used to convert a non-chiral molecule into the desired enantiomer, this avoids the need to separate enantiomers from a mixture. It works by attaching itself to the non-chiral molecule and forces the reaction to follow a pre-determined path. Once the molecule has been formed the auxiliary can be taken off. An example of this is the synthesis of Taxol.

D10 Mind-Altering Drugs

Assessment statement D.10.1 Describe the effects of lysergic acid diethylamide (LSD), mescaline, psilocybin and tetrahydrocannabinol (THC). D.10.2 Discuss the structural similarities and differences between LSD, mescaline and psilocybin. D.10.3 Discuss the arguments for and against the legalization of cannabis. Obj Answer 2 The effects of LSD depend on the dosage, personality, mood of user and where it is being taken. The physical effects are dilated pupils, increased body temperature, increase in heart rate and blood pressure, sweating, tremors and sleeplessness. A large dosage of LSD produces hallucinations. LSD users may also experience depression. The effects of mescaline are the same as LSD but mescaline is considerably less potent. Psilocybin and tetrahydrocannabinol have similar effects as LSD including hallucinations but are less potent. 3 LSD, mescaline and psilocybin all contain the common structural feature that is an indole ring structure. Many hallucinogens are indole-amines and contain the indole ring. Although mescaline does not have an indole ring it has a very similar structure. The difference is the various functional groups attached to the indole skeleton which affects their solubility in fats and increase their potency. Non polar groups like (-CH3) enhance this effect. 3 One of the arguments for legalization of cannabis includes the ability of cannabis to relive and help patients with certain diseases. Like arthritis, cancer and HIV. One of the arguments against legalization includes the possible harmful effects and the fear of cannabis users to start using harder drugs.