Option D10: Mind-altering drugs

D.10.1 Describe the effects of lysergic acid diethylamide (LSD), mescaline, psilocybin and tetrahydrocannabinol

LSD

• Potent hallucinogen that creates distortions of the body and crawling geometric patterns
• Causes impaired judgement, hypertension, dilated pupils and changes to body temperature and heart rate
• Can cause unpredictable mood swings from euphoria to depression and panic

Mescaline

• About 1000-3000 times less potent than LSD; causes subjective hallucinations dependent on the individual
• Effects include anxiety, static tremors, and psychic disturbances with vivid hallucinations
• Abdominal pain, nausea and diarrhoea are also common.

Psilocybin

• Produces subjective hallucinations similar to mescaline but milder
• Some people experience a pleasant mood, others become apprehensive
• Compulsive movement and inappropriate laughter may occur; also vertigo and dizziness
• Numbness, muscle weakness and drowsiness are also common

Tetrahydrocannabinol (THC)

• It acts to depress the central nervous system and cause mental relaxation and euphoria
• Can lead to loss of inhibitions and an alteration of the perception of time and space
• Gives a loss of concentration, light-headedness, weakness and a sense of floating are commonly experienced
• Can cause depression of respiration and can lead to collapse 

D.10.2 Discuss the structural similarities and differences between LSD, mescaline and psilocybin

LSD

• Benzene ring
• Alkene
• Secondary amine
• Tertiary amine
• Tertiary amide

Mescaline

• Benzene ring
• Primary amine
• Ether

Psilocybin

• Benzene ring
• Secondary amine
• Tertiary amine ion
• Phosphate

D.10.3 Discuss the arguments for and against the legalization of cannabis

Option D9: Drug design

D.9.1 Discuss the use of a compound library in drug design

Once a target molecule has been identified for a particular drug, the next step is to find a lead compound - one that shows the desired pharmaceutical activity - which will be used as a start for the drug design and development process. In the past, this step involved the individual synthesis and testing of candidate molecules, which was an extremely slow and expensive process. The information derived from these syntheses and testing procedures led to the production of compound libraries, with details on the molecules' activities stored for possible future reference.

The increasing demand for more efficient ways of generating larger libraries of potential drug candidate molecule and screening these compounds for biologically relevant information has led to such major developments as combinatorial synthesis, parallel synthesis and high-throughput screening. While still relatively new approaches, they are widely used by all major pharmaceutical companies and it is hoped that this high-volume approach to the discovery of medicines will lead to an increase in the number of viable new products at an affordable cost.

D.9.2 Explain the use of combinatorial and parallel chemistry to synthesize new drugs

Combinatoral chemistry is a method for synthesizing groups of compounds known as combinatoral libraries simultaneously, rather than one by one as in the more traditional approach. Typical library sizes vary from 10000 to 500000 compounds.

By using specially designed machines that are largely automated, the synthesis reactions occur on a very small scale and generate a poll of chemically related compounds. The reactions take place in separate vessels, following a defined reaction route with a large variety of starting materials and reagents. Combinatoral chemistry in a sense mimics the natural process of random mutation and selection of the fittest - meaning in this case those with the best activity. Subsequent screening of the products for the desired activity will hopefully identify a useful lead compound.

A popular way of generating the different structures with the minimum number of steps is known as the mix and split method. Each of the three compounds is first linked to solid support (resin bead) and then the beads are mixed and split into three equal portions. Each portions is then reacted with a different building block, giving rise to dimers of which there will be nine possible structures.

A variation on this, known as parallel synthesis, carries out the reactions in such a way to produce a single product in each reaction flask. It generally produces libraries that are more focused and less diverse than those from combinatorial techniques.

Parallel synthesis usually involves the synthesis of a highly reactive intermediate via a series of simple steps, then its subsequent reactions with a number of different reagent.

Parallel rather than mixed syntheses are used in the research of structure-activity relationships and in drug optimizations, as these involve separate testing of each compound. Overall, the pharmaceutical industry is seeing an increase in multiple parallel syntheses, with a decline in mixed combinatorial syntheses.

D.9.3 Describe how computers are used in drug design

Computational chemistry has made huge strides in recent years, opening up a relatively new approach to drug design known as computer-aided design (CAD). Molecular-modelling software analyses the interaction between the drug and its receptor site, helping to design molecules that give an optimal fit. Progress in this field is largely possible due to increasing knowledge of the three-dimensional strcture of the biomolecular target obtained through methods such as X-ray crystallography and nuclear magnetic resonance (NMR) techniques.

D.9.4 Discuss how the polarity of a molecule can be modified to increase its aqueous solubility and how this facilitates its distribution around the body

Most drugs are transported in the blood. The term bioavailability is used to describe the percentage of a dose of a drug that reaches the bloodstream. Due to the fact that drugs may be misdirected or broken down before absorption, typically the figure is about 20%-40%. Once in the blood, drugs are transported in aqueous solution in the plasma. In general, drugs that are more polar or have ionic groups will dissolve more readily and hence be distributed to the target cells more efficiently. Some drugs can be modified to increase their solubility.

The structure of aspirin contains an ester group and a carboxylic group attached to a benzene ring. When it is reacted with a strong alkali, it forms a salt in which the carboxylic acid group is converted into its conjugate base, the acid anion. This increase the aqueous solubility of the compound; formulations containing the salt of the acid are known as soluble aspirin.

D.9.5 Describe the use of chiral auxiliaries to form the desired enatiomer

This is a chiral molecule which binds to the reactant, physically blocking on reaction site through steric hindrance, so ensuring that the next step in the reaction can only take place from one side. This effectively forces the reaction to proceed with a specified stereochemistry. Once the specific enatiomer of the new product has been set, the auxiliary can be taken off and recycled.

Option D8: Drug action

D.8.1 Describe the importance of geometrical isomerism in drug action

Many anticancer drugs work by disrupting the function of DNA (deoxyribonucleic acid) in the cancer cells thereby preventing cell division from occuring. DNA has a double helical structure, with two strands held together by hydrogen bonds between complementary base pairs. It carries a negative charge at cell pH and is found in the nucleus of all cells.

The compound cis-platin has a square planar geometry as this shape minimizes repulsive interactions between electrons in the d-orbtitals. Consequently it can exist as cis and trans isomers.

It does not work if the compound is trans-platin. This is because it no longer has the unique property of two chlorine on one side.


D.8.2 Discuss the importance of chirality in drug action

Although the two enationmers of a molecule usually have identical chemical properties, they can react differently in the presence of a chiral environment, such as with the enzymes and receptors in the body. Most enantiomers only have one that is biologically active and their physiological properties are very different.

The major impetus for this research activity in stereochemistry came from teh thalidomide tragedy. The drug was manufactured and sold as a racemic misture, It was discovered later that only the (R) isomer induced sleep and calmness in pregnant women, Its enantiomer, the (S) form, was teratogenic - it was able to cross the placenta and produce serious deformities in the fetus.

D.8.3 Explain the importance of the beta-lactam ring action of penicillin

The strucutre of penicillin, as determined by X-ray crystallography in 1945, contains a nucleus of a five-membered ring containing a sulfur atom known as thiazolidine, attached to a four-membered ring containing a cyclic amide group known as beta-lactam.

The bond angles in this ring are reduced to about 90 degree celcius despite the fact that because they have sp2 and sp3 hybridized atomic orbitals, the atoms in the ring seek to form bonds with angles of 120 and 109.5 respectively. This puts a strain on the bonds, effectively weakening them. Consequently, the ring breaks relatively easily and this is the key to the molecule's biological activity.

The action of these beta-lactam antibiotics is to disrupt the formation of cell walls of bacteria by inhibiting a key bacterial enzyme, transpeptidase, As the enzyme approaches the enzyme, the high reactivity of the amide group in the ring causes it to irreversibly bind near the active site of the enzyme as the ring breaks. Inactivation of the enzyme in this way blocks the process of cell wall construction within the bacterium because it prevents polypeptide cross-links forming between the mucopeptide chains. Without these strengthening links, the cell wall is unable to support the bacterium, which bursts and die.


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

Morphine, the principle drug derived from opium, is not able to cross the blood-brain barrier very effeciently due to its two polar -OH groups. Heroin (diamorphine), on the other hand, in which the two -OH groups have been replaced by ethanoate (ester) groups shown in green here, is much less polar.

This reduction in polarity of the molecule enables it to cross the blood-brain barrier more easily. Thus, heroin has a much greater potency than morphine; it reaches brain cells faster and in higher concentration. It is more active by a factor of two. Note that this also applies to its greater side-effects as well as to its characteristics of tolerance and dependence.

Option D (HL): Medicine and drugs

Option D of the IB HL Chemistry syllabus is the Medicine and drugs. IBO recommends to spend 22 hours on the whole topic.

This topic has an additional 3 sub-chapters: "Drug action", "Drug design" and "Mind-altering drugs". Each are separated with numerical values in order of mentioned.

These are all HL option syllabus statements, it is recommended to bring a Casio Graphical Calculator instead of Texas.

Option D7: Antivirals

D.7.1 State how viruses differ from bacteria

Viruses are such small and simple structures that there is debate about whether they can be classified as living organisms in their own right. They contain only the two components protein and nucleic acid (either RNA or DNA), have no cellular structure and are only capable of reproducing inside another living cell. In these ways, they are different from bacteria with their more complex cellular structure and ability to survive and reproduce independently from other living cells

Viruses are in fact the original hijackers - they literally take over the functioning of another cell (the host cell) and use it to carry out their own reproduction. The host cell's components are used in the assembly of new viral particles and in the process the cell eventually dies, releasing thousands of viral participle into the body.

D.7.2 Describe the different ways in which antiviral drugs work

Treating viral infections is a challenge because the viruses live within cells and so cannot be easily targeted. Lacking the cell structure of bacteria, they are not attacked by antibiotics. Another problem is the speed at which they can multiply, which means that they have often spread throughout the body by the time that symptoms appear, In addition, virus particles have a tendency to mutate rapidly and this changes their susceptibility to drugs. This is why, for example, different types of flu vaccine are developed each year according to the most abundant strain of virus around

Some antivirals work by altering the cell's genetic material (DNA) so that the virus cannot use it to multiply. Others block enzyme activity within the host cell, which prevents the virus from reproducing. In this case, the progression of the disease will be halted and there will be relief from symptoms, but not that the virus is not completely eradicated.

One reasonably effective antiviral drug is amadntadine, which causes changes in the cell membrane that prevent the entry of the virus into the cell. It is therefore used as a prophylactic treatment or given before the infection has spread widely.

D.7.3 Discuss the difficulties associated with solving the AIDs problem

The condition known as AIDs, caused by the human immunodeficiency virus (HIV), was first diagnosed in humans in 1981, AIDs is characterized by a failure of the immune system, so that the body falls prey to life-threatening opportunistic infections such as pneumonia and forms of cancer. The infection has spread at an alarming rate through the global population and it is estimated that 40 million people are currently HIV positive with a likelihood of developing AIDs.

There are three main reasons why HIV is proving even more challenging than other viruses to defeat.

• The virus destroys T-helper cells, the very cells in the immune system that should be defending the body against the virus
• The virus tends to mutate very rapidly even within a patient. It is thought that there is more variation in HIV in a single patient than in influenza virus worldwide in a year. These variations mean that the virus 'escapes' the immune response, because the patient has to make a response to the new virus
• The virus often lies dormant within host cells so the immune system has nothing to respond to

Drugs to help the fight against HIV, known as antiretroviral drugs, act at different stages in the HIV lifecycle. One target is to inhibit the enzyme reverse transcriptase, as this is specific to the virus and does not affect the host cell. The drug AZT, also known as zidovudine, works in this way and was the first antiretroviral drug approved for use in AIDs treatment. 

Option D6: Antibacterials

D.6.1 Outline the historical development of penicillin

The discovery of the chemicals known as penicillin truly revolutionized modern medicine, as this gave birth to drugs now known as antibiotics. These are chemicals, usually produced by microorganisms, which act as against other microorganisms. Their discovery is generally credited to Alexander Fleming, who was a Scottish microbiologist, working in 1928 on bacteria cultures. He noticed that a fungus (or mould) known as Penicillium notatum had contaminated some of his cultures. It created a clear region around it where no bacterial colonies were growing.

The Australian bacteriologist Howard Florey and German-born biochemist Ernst Chain, working in Oxford, England, picked up the research and successfully isolated penicillin as the antibacterial agent produced by the penicillin mold.


D.6.2 Explain how penicillin work and discuss the effects of modifying the side-chain

Its core structure is a four-membered ring consisting of one nitrogen and three carbon atoms and known as beta-lactam, This part of the molecule is known to be responsible for its antibacterial properties. By acting as an irreversible inhibitor of an enzyme, it prevents the development of cross-links in bacterial cell walls, so weakening the walls and causing the bacteria to rupture and die during their reproductive phase.

D.6.3 Discuss and explain the importance of patient compliance and the effect of penicillin overprescription

A major problem with the us of penicillin and other antibiotic is that of bacterial resistance. This was observed as early as the 1940s when penicillin proved to be ineffective against some populations of bacteria. It is now known that these resistant bacteria produced an enzyme, penicillinase, which can open penicillin's beta-lactam ring and render it inactive.

Antibiotic resistance arises by genetic mutation in bacteria and would normally account for a very small proportion of the population. But the number of resistance organisms increases dramatically with increased exposure to the antibiotic. The problem of resistance has been compounded by the wide use of penicillin in animal feeds to lower the incidence of disease in stock.

Option D5: Stimulants

D.5.1 List the physiological effects of stimulants

Stimulants are largely opposite to that of depressants, as they increase the activity of the brain and hence the person's state of mental alertness. They are used to prevent excessive drowsiness through the day and so allow greater concentration.

• They help facilitate breathing by causing relaxation of the air passages and are used in the treatment of respiratory infections such as severe bronchitis
• They may reduce appetite and so have been used as part of treatment for obesity
• They may cause palpitation or tremors to occur
• When used in excess, they can cause restlessness, sleeplessness, fits, delusions and hallucinations.

D.5.2 Compare amphetamines and epinephrine (adrenaline)

Adrenaline is a hormone that is released in times of stress and enables the body to cope with sudden demands such as those imposed by pain, shock, fear and cold. It is called the "fight or flight" reaction.

• increase the heart rate and blood pressure
• increase the blood flow to the brain and the muscle
• increase the air flow to the lungs
• increase mental awareness

The amphetamines are called sympathomimetic drugs. In small doses, amphetamines increase mental alertness and physical energy. Side-effects include dilation of the pupils and decreased appetite, as well as possible blurred vision and dizziness. Regular use of these drugs leads to the rapid development of both tolerance and dependence, coupled with serious long-term effects such as severe depression and reduce resistance to infection.

Modification to the amphetamine structure have produced some drugs that are very powerful and dangerously addictive. These include methamphetamine, known as speed and crystal meth, and the drug ecstasy.

D.5.3 Discuss the short- and long-term effects of nicotine consumption

Nicotine is one of the most widespread and abused stimulants. It is obtained from tobacco plants but is also found at low concentrations in tomato, potato, eggplant and green pepper plants. Usually it is taken in by inhalation of smoke from cigarette, cigars and pipe tobacco, but it can also be taken by chewing.

Short-term effects

• Increases concentration
• Relieves tension and boredom
• Helps to counter fatigue 
• Increases heart rate and blood pressure
• Decreases urine output

Long-term effects

• High blood pressure
• Increases risk of heart disease including angina
• Coronary thrombosis
• Increases the level of fatty acids in the blood which can lead to atherosclerosis and stroke
• Over-stimulation of stomach acids which can lead to increased risk of peptic ulcers

D.5.4 Describe the effects of caffeine and compare its structure with that of nicotine

Caffeine acts as a respirator stimulant increasing the rate of energy release within cells. It also intensifies and prolongs the effects of adrenaline. As with other drugs, higher consumption may lead to some negative effects.

Consumption of caffeine in small amounts

• Enhancement of mental energy alertness and ability to concentrate
• Acts as a diuretic, increasing volume of urine; can cause dehydration

Consumption of caffeine in large amounts

• Can cause anxiety, irritability and insomnia
• Can cause dependence; side-effects on withdrawal include headaches and nausea

In general, an intake of more than four cups of coffee per day may be considered non-beneficial. Pregnant woman are advised to limit their caffeine intake

Like, nicotine, caffeine contains heterocyclic rings (containing both carbon and nitrogen) and a tertiary amine group. In addition, caffeine contains two amide groups.

Option D4: Depressants

D.4.1 Describe the effects of depressants

Depressants are drugs that act on the brain and the spinal cord (known as the central nervous system or CNS). The action of these drugs changes the communication between brain cells by altering the concentration or the activity of chemicals called neurotransmitters.As a result they cause a decrease in brain activity that in turn influences the functioning of other parts of the body.

Low to moderate dose - calmness, relief from anxiety and very relaxed muscles

High dose - slurred speech, staggering gait, altered perception and sleep induced

Lethal dose - respiratory depression coma/death.

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

Short term effect of ethanol abuse

• loss of self-restraint; memory, concentration and insight are impaired
• loss of balance and judgment
• violent behaviour associated with domestic abuse and family breakdown
• dangerous risk-taking behaviour leading to many accidents involving motor vehicles and machinery
• dehydration caused by increased urine output leading to 'hangover' and loss of productivity
• at high doses, can cause vomiting, loss of consciousness, coma and death

Long-term effects of ethanol abuse

• dependence known as alcoholism, associated with withdrawal symptoms
• liver disease, cirrhosis, liver cancer
• coronary heart disease
• high blood pressure
• fetal alcohol syndrome
• permanent brain damage

Ethanol in alcoholic drinks is an important part of many diets and cultures, adding a sense of occasion to meals, rituals and festivities. In low doses, it can help to create a mild excitement and users become more talkative, confident and relaxed. There is also some evidence that low doses of ethanol might might have a beneficial effect on the circulation and diminish cardio-vascular diseases, perhaps owing to its mild anti-clotting effect.

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

Breath

Ethanol is a volatile compound and at body temperature in the lungs it establishes equilibrium between being dissolved in the blood and released into the air in the exhaled breath.

The equilibrium constant for this reaction has a fixed value at a particular temperature so measurement of the ethanol in the breath can be used to assess the blood alcohol concentration.

The simplest test involves a roadside breathalyser which contains crystals of potassium dichromate (VI) which are orange, but are changed to green chromium (III) Cr3+ ions as they oxidize the ethanol to ethanal and ethanoic acid.

A more accurate technique for breath analysis uses infrared spectroscopy in an apparatus called an intoximeter. The principle here is that different molecules cause different absorption bands in the infrared part of the spectrum as a result of vibrations of their particular bonds and functional groups. Hence ethanol has a characteristic absorption band at 2950 owing to its C-H bonds.

Blood and Urine

The most established method for ethanol analysis is gas-liquid chromatography, which must be carried out in a labouratory. In this technique, blood or urine is vaporized and injected into a stream of an inert gas (the mobile phase) over the surface of a non-volatile liquid (the stationary phase). The components of the vapour, including ethanol gas, move at different rates depending on their boiling points and relative solubility in the two phases. As a result, each leaves the column holding the liquid phase after a specific interval of time known as its retention time. So a peak at the retention time corresponding to ethanol can be used to confirm its presence in the vapour. The area under the peak is a measure of ethanol concentration relative to a known standard in the mixture such as propan-1-ol. The method allows for an accurate assessment of ethanol levels.

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

Ethanol has a the potential to increase the activity other drugs when taken at the same time. This effect is known as synergy. It means that care must be taken when consuming alcoholic drinks alongside other medications, as the synergistic effects can lead to very serious, even fatal, results. One of the problems is that because ethanol is such a widely consumed and socially available drug, many people do not consider its interaction with other prescription and non-prescription drugs.

• With aspirin, ethanol can cause increased bleeding of the stomach lining and increased risk of ulcers
• With other depressants such as barbiturates, including sleeping pills, ethanol can induce heavy sedation, possibly leading to coma
• With tobacco, ethanol appears to increase the incidence of cancers, particularly of the intestines and liver
• With many other drugs, ethanol can interfere with their metabolism by the liver, which can cause greater and more prolonged drug effects.

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

Benodiazepine are a major group of depressants. These drugs depress activity in the part of the brain that controls emotion and so are used as tranquilizers in the treatment of anxiety disorder and related insomnia. As well as being the most commonly used class of sleeping pill, they are also used as muscle relaxants. Although they are usually well tolerated by most people and cause relatively few side-effects, they can cause dependence. For this reason, they are used mostly in short-term treatments. Some widely used benzodiazepine drugs are diazepam, marketed as Valium and nitrazepam.

Option D3: Analgesics

D.3.1 Describe and explain the different ways that analgesics prevent pain

Mild analgesics, including aspirin and non-steroidal anti-inflammatory drugs (NSAID) such as ibuprofen, act by preventing stimulation of the nerve endings at the sit of the pain. They inhibit the release of prostaglandins from the site of injury and so give relief to inflammation and fever as well as to pain. (Paracetamol is an exception as it inhibits prostaglandin release int he brain rather than at the sit of the injury.) These analgesics do not interfere with the functioning of the brain, they are also known as non-narcotics.

Strong analgesics include the drugs related to morphine, known as the opioids. This refers to their ability to bind to so-called opioid receptors in the brain, which then blocks the transmission of pain signals between brain cells and so alters the perception of pain. Because these analgesics act on the brain, they may cause drowsiness and possible changes in behaviour and modd, so are also known as narcotics. They are the most effective pain killers for severve pain, but owing to their side-effects and potential problems with dependence, their usage must be monitored through medical supervision.

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)

Salicylic acid proved to be effective in treating pain but it tastes awful and caused the patient to vomit. The Bayer company in Germany made an Ester derivative of salicyclic acid, while still effective as an analgesic. It was named aspirin, which produces a similar compound.

Aspirin is widely used in the treatment of headache, toothache and sore throat. Also, because it is effective in reducing fever (an antipyretic) and inflammation, it is used to provide relief from rheumatic pain arthritis. Aspirin reduces the ability of the blood to clot and this makes it useful in the treatment of patients at risk from heart attacks and strokes. Negative side-effects include irritation and even ulceration of the stomach and duodenum, possibly leading to bleeding. This effect can be more acute when it is taken with ethanol in alcoholic drinks. A large number of people, especially those prone to asthma, are also allergic to aspirin, so it must be used with caution. It is not recommended for children under 12 because its use has been linked to Reye's syndrome, a rare and potentially fatal liver and brain disorder.

Paracetamol is much younger drug than aspirin, having been marketed only since 1953. Paracetamol is different from other mild analgesics as it is thought to act by reducing the production of prostaglandins in the brain, but does not affect prostaglandin production in the rest of the body. This means that it is not effective in reducing inflammation. It is one of the safest of all analgesics when taken correctly. It does not usually irritate the stomach and allergic reactions are rare. However, an overdose or chronic use of paracetamol can cause severe and possibly fatal damage to kidneys, liver and brain.

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

The narcotic drugs derived from opium are primarily morphine and its derivatives. We will consider three of these here: codeine, morphine and diamorphine, known as heroin. These are powerful analgesics, acting on the central nervous system to block the perception of pain.

Has benzene ring, 2 ethers, alkene, alcohol and tertiary amine functional groups. It is found in raw opium (0.5%).

Has benzene ring, ether, alkene, 2 alcohol and tertiary amine functional groups. It is found in raw opium (10%).

Has benzene ring, ether, alkene, 2 ester -ethanoate and a tertiary amine. It is found in opium but usually obtained by reaction of morphine, so is known as a semi-synthetic drug.


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

Codeine

Its therapeutic uses sometimes used in a preparation witha non-narcotic drug such as aspirin or paracetamol in the second stage of the pain management ladder. It is also used in cough medicine and in the short-term treatment of diarrhoea.

Morphine

It therapeutic uses are used in the management of severe pain, such as in advanced cancer. It also can be habit forming and can lead to dependence, so use must be regulated by a medical professional.

Diamorphine

Its therapeutic uses are used medically only in a few countries legally (Britain and Belgium) for the relief of severe pain. It has the most rapidly acting and is the most abused narcotic. It initially produces euphoric effects, but very high petential for causing addiction and increasing tolerance. Dependence leads to withdrawal symptoms and many associated problems.

Option D2: Antacids

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

The stomach is unusual in that it generates a pH as low as 1-2 by production of hydrochloric acid from structures in the lining of the walls, known as gastric glands. However, some factors, such as excess alcohol, smoking, stress and some anti-inflammatory drugs, can cause excess prdocution of this acidic secretion known as gastric juice.

Drugs to help combat such excess acid are known as antacids. They work by neutralizing the hydrochloric acid, hence relieving the symptoms. According to the dictum "no acid, no ucler", they do allow the stomach lining time to mend.

Aluminium hydroxide, magnesium hydroxide, sodium hydrogencarbonate and calcium carbonate are prime antacids that are used.

Option D1: Pharmaceutical products

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

The terms medicine and drugs are sometimes used interchangeably and sometimes have slightly different meanings in different parts of the world. They are most clearly defined as follows

Drugs are chemicals that affects how the body works. This includes changes for the better or the worse. The term is associated with substances which are illegal in many countries, such as cocaine, ecstasy and heroin.

Medicines are substances that improves health. Medicine, which may be natural or synthetic, therefore contain beneficial drugs. Synthetic medicines also contain other ingredients, which are non-active but help in the presentation and administration of the drug. The beneficial effect of a medicine is known as its therapeutic effect.

In general, the effects on the body of drugs include the following:

• alteration of the physiological state, including consciousness, activity level and coordination
• alteration of incoming sensory sensations
• alteration of mood or emotions

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

Pharmaceutical groups and research groups are constantly developing new drugs in response to the new diseases. The goal is usually to develop drugs that are more effective and have fewer toxic side-effects than pre-exisiting drugs for the same conditions, as well as drugs for new conditions such as SARS. The stages are split into 3 main stages: research, development and regulatory review.

Discovery Research

First stage in drug development involves identifying and extracting compounds that have been shown to have biological activity and are known as lead compounds. Lead compounds are often derived from plants.

Next, the effectiveness of lead compound is optimized by making and testing many chemically related compounds known as analogues. This process is often now fast-tracked by two relatively new techniques: combinatorial chemistry and high-throughput screening. Following extensive laboratory tests, a potenial medicine is then tested on animals, under strict legislative control.

Development research

There are usually three phases in subsequent human trials involving an increasing number of patients. The effectiveness of the drug is judged by the relative improvement in the patients who have received the real medication compared with those on a placebo in phase III.

Phase I - 50-100 healthy volunteer
Phase II - 200-400 patients
Phase III - 3000+ patients: half are given the drug under test, the other half a placebo; neither the doctor nor the patient knows which preparation is being given

Regulatory review

Regulators realized then that it was not sufficient only to establish the safety and effectiveness of a drug before it went on the market. An additional system was needed to track medications once the population had access to them, when effects in different groups of people, including long-term effects, become known.

D.1.3 Describe the different methods of administering drugs

The manner in which a drug is delivered to the patient's body depends on many factors. These include the chemical nature of the drug, the condition of the patient and the most effective way of getting the drug to the target organ.

Oral

This method is the most common example of medicine. Examples include tablets, capsules, pills and liquids.

Inhalation

This method of administration is done through vapour breathed in or smoking. Examples include medications for respiratory conditions such as asthma.

Skin patches

This method of administration is absorbed directly from the skin into the blood. Examples includes some hormone treatments like estrogen and nicotine patches

Suppositories

This method of administration is inserted into the rectum. It is used for treatment of digestive illness. Examples include hemorrhoids.

Eye or ear drops

This method of administration are liquids delivered directly to the opening. This is used for treatments of infection of the eye or ear.

Parenteral - by injection

There are three different methods of administration through injection. By intramuscular, intravenous or subcutaneous injection.

D.1.4 Discuss the terms therapeutic window, tolerance and side-effects

The dosing regime for a drug refers to the amount of drug used for each dose and the frequency of administration. Determining this is usually quite difficult as there are so many variable involved - for example the age, sex and weight of the patient, as well as factors such as diet and environment. The important thing is that the concentration in the blood stream must remain within a certain range: above this range, unacceptable side-effects may occur; below this range and there may not be effective therapeutic outcomes. This target range is referred to as the therapeutic window.

When a person is given repeated doses of a drug, it sometimes happens that tolerance develops, that is a reduced response to the drug. So higher doses are needed to produce the same effect and this increases the chances of there being toxic side-effects.

Side-effects are defined as physiological effects which are not intended and vary greatly from one drug to another, and with the same drug in different people. Sometimes side-effects may be beneficial, such as the fact that aspirin, taken for pain relief, helps protect against heart disease. Other times, the side-effects may be relatively benign, such as causing drowsiness, nausea or constipation.