MEDICINE AND DRUG OPTION NOTE
D1. Pharmaceutical products
D1.1 List the effects of medicines and drugs on the functioning of the body.
+ Alters the physiological state, including consciousness, activity level or coordination.
+ Alters incoming sensory sensations.
+ Alters mood or emotions.
Placebo effect:
+ Therapeutic effect of an inert substance on the body and body is fooled into healing itself
naturally.
+ People are often responding positively to a substance that is not a drug.
Use of placebos in clinical trials:
+ Placebos refer substances that contain none of the compound being tested as drugs.
+ Placebo can “fool” the body into healing itself.
+ Placebo is used as a control to measure the effectiveness of a drug.
+ The methodology includes some of trial group being given placebo and some others being
given drug.
+ Patients and administrators should not know who gets a placebo and who gets a drug.
D1.2 Outline the stages involved in the research, development and testing of new
pharmaceutical products.
* Development of new pharmaceutical products
+ Drug is isolated from existing species or synthesized in the laboratory.
+ It is tested on animals to establish LD50.
+ It is then tested on humans and some of the group might be given a placebo.
* Effects of a drug which must be determined during clinical trials:
+ LD50 or ED50.
+ Risk : benefit ratio.
+ Side-effects.
+ Tolerance.
D1.3 Describe the different methods of administering drugs.
Several ways of administering drugs include:
+ Injection (parenteral).
+ Oral.
+ Rectal.
+ Inhalation.
+ Apply to skin.
For injection, there are 3 main ways by which drugs are injected into our bodies:
+ Intramuscular: into muscles.
+ Intravenous: into veins
+ Subcutaneous: into fat.
+ The method giving the fastest effect is intravenous because the drug is circulated or
transported quickly via the blood stream to various parts of the body.
D1.4 Discuss the terms therapeutic window, tolerance and side-effects.
+ Therapeutic window refers to the range over which a drug can be safely administered.
+ Therapeutic Index = LD50 / ED50 – Ratio of the lethal dose for 50% population and the
effective dose for 50% of population.
+ Tolerance refers to the state where a person needs to take ever larger quantities of a drug
to gain the original effect.
+ Tolerance is potentially dangerous to heroin users because in order to achieve the desired
effect, heroin users may reach the lethal dose and they are more likely to commit crimes to
pay for gradually increasing doses of the drug (taking account the fact that heroin is highly
expensive).
+ Side-effect refers to an unwanted/ undesired effect produced in addition to the one
intended.
Importance of therapeutic window in drug administration:
+ If concentration is too high it will have harmful side effects. This helps in the
determination of the lethal dose to 50 % of the population.
+ If concentration is too low it has little or no beneficial effect. This helps in the
determination of the effective dose to 50 % of the population.
+ For minor ailments a larger window is desirable, for serious conditions a smaller window
may be acceptable.
+ Therapeutic window depends on the drug, age, sex and weight.
+ A small therapeutic window means that an overdose is a high risk.
+ Wide therapeutic window indicates a large difference between effective dose and lethal
dose, which means drugs with wide therapeutic window are safer.
+ Narrow therapeutic window indicates a small difference between effective dose and lethal
dose; therefore, more attention needs to be paid when drugs with narrow therapeutic
window are administered.
D2. Antacids
D2.1 State and explain how excess acidity in the stomach can be reduced by the use of
different bases
+ Antacids are drugs used to neutralize excess stomach acid (hydrochloric acid HCl).
+ Examples of antacids: aluminium and magnesium compounds or sodium hydrocarbonate.
+ Reaction happening between antacid and stomach acid:
Al(OH)3(s) + 3HCl(aq)  2AlCl3(aq) + 3H 2 O(g)
Mg(OH) 2(s) + 2HCl(aq)  MgCl2(aq) + 2H 2O (g)
NaHCO3(s) + HCl(aq)  NaCl(aq) + H 2 O(l) + CO 2(g)
+ Among 3 of them, aluminium hydroxide can be said to be the most effective because one
mole of this antacid can neutralize 3 mole of stomach acid while the other can only
neutralize a smaller amount of stomach acid.
+ Antacids are often combined with alginates and with antifoaming agents such as
dimethicone.
+ Alginates not only help neutralize stomach acid but they also produce a neutralizing
layer.
+ This helps prevents heartburn or acid rising into the esophagus.
+ Anti-foaming agents help prevent flatulence or stomach bloating.
+ Sodium hydroxide or potassium hydroxide can’t be used as antacid because they are
strong bases whose corrosiveness can damage or destroy stomach lining.
D3 Analgesics
D.3.1 Describe and explain the different ways that analgesics prevent pain.
+ Analgesic is a substance that reduces pain.
+ Mild analgesics prevent the production of prostaglandins that cause pain.
+ Prostaglandins are involved in the transmission of pain impulses (to the brain)
+ They intercept pain at its source.
+ Meanwhile, strong analgesics bond to receptor sites in the brain.
+ Pain signals within brain (spinal cord) are blocked because strong analgesics prevent the
transmission of nerve impulses.
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).
Advantages
Disadvantages
Aspirin
prevents recurrence of heart
stomach bleeding when taking
attack or stroke
with alcohol.
anticoagulant
Irritates stomach lining.
reduces fever and antiallergic reaction.
inflammation
Reye’s syndrome,
hearing loss.
tinnitus (ringing in the ears).
gastrointestinal irritation (e.g.
heartburn, nausea).
Paracetamol
does not affect stomach,
may cause blood disorders
ulceration or bleeding.
kidney damage
does not give allergic reactions. overdose can cause serious liver
does not give Reye’s syndrome
damage
brain damage and death
does not reduce inflammation
D.3.3 Compare the structures of morphine, codeine and diamorphine (heroin, a semisynthetic opiate).
Morphine
Codein
Diamorphine
Phenol, ether, tertiary
Tertiary amine, alkene,
Tertiary amine, alkene,
amine, alkene, benzene
benzene ring, allylic
benzene ring, allylic alcohol,
ring, allylic alcohol.
alcohol, ether
ether, phenol, ester
D.3.4 Discuss the advantages and disadvantages of using morphine and its derivatives as
strong analgesics.
Advantage:
+ Antidiarrheal properties as it causes constipation
+ Reduces coughing.
+ Relieve acute pain.
+ Wide therapeutic window.
+ Reduce anxiety, improving quality of life.
+ Injected ntravenously causing faster distribution of drug.
Disadvantage:
+ Addiction, developing dependence.
+ Tolerance: increased risk of overdose upon prolonged use.
+ Causing euphoria, lack of self-control and dangerous behavior.
+ Causing kidney or renal failure.
+ Risks associated with intravenous drug administration.
D4 Depressants
D.4.1 Describe the effects of depressants.
+ At low doses a depressant may exert little or no effect.
+ At moderate doses the compound may induce sedation (soothing, reduction of anxiety).
+ At higher doses it may induce sleep and loss of consciousness.
+ At extremely high doses it may cause death.
+ Depressants are often described as antidepressants because they relieve depression.
D.4.2 Discuss the social and physiological effects of the use and abuse of ethanol.
Effects on family and cost to society:
+ Increased aggressiveness and hostility when intoxicated
+ A deterioration of relationships in the long term, and a general decrease in performance
in daily activities.
+ Lower productivity can cause job loss.
+ Loss of consciousness as a result of overconsumption might lead to criminal activities.
D.4.3 Describe and explain the techniques used for the detection of ethanol in the breath,
the blood and urine.
Breathalyzer:
+ The roadside breathalyzer test uses acidified potassium dichromate(VI) which reacts with
any ethanol present in the breath and converts it to ethanoic acid.
+ Potassium dichromate is reduced while ethanol is oxidized.
+ Color of solution changes from orange to green due to the presence of Cr3+ ion.
+ Reactions involved are shown below:
Oxidation:
C2H5OH + H2O → CH3COOH + 4H+ + 4e–
Reduction:
Cr2O72– + 14H+ + 6e– → 2Cr3+ + 7H2O
Overall this redox reaction:
3C2 H5OH  2Cr2O72  16H +  3CH 3COOH  4Cr 3+  11H 2O
Intoximeter:
+ Sample of breath passed into infrared spectrometer.
+ Ethanol in breath absorbs because of OH group.
+ Machine compares breath with air/reference sample with no breath.
+ (C-H bond in) ethanol causes radiation to be absorbed at a specific wavelength.
+ Amount of absorption depends upon the amount of ethanol in the breath.
Fuel cell:
+ Ethanol is oxidized; the reaction creates potential difference, which can be detected.
D.4.4 Describe the synergistic effects of ethanol with other drugs.
+ Ethanol has a synergistic effect with other drugs.
+ Ethanol can interact with other drugs, enhancing their effects.
+ Example when being consumed with aspirin, this combination will cause the bleeding of
the stomach lining.
+ Sometimes, alcohols might reduce the effectiveness of certain drug.
+ Alcohol depresses the central nervous system, causing sedative effects on CNS.
D.4.5 Identify other commonly used depressants and describe their structures.
+ Three other common depressants are diazepam (Valium), nitrazepam (Mogadon) and
fluoxetine hydrochloride (Prozac).
Valium
Modagon
Prozac
D5 Stimulants
D.5.1 List the physiological effects of stimulants.
+ Increase activity of central nervous system.
+ Increase glucose levels in blood.
+ Increase heart rate.
+ Increase in blood pressure.
+ Increase (mental) alertness or concentration.
+ Decrease appetite.
D.5.2 Compare amphetamines and epinephrine (adrenaline).
+ Amphetamines and epinephrine (adrenaline) are chemically similar in that both derive
from the phenylethylamine structure.
+ Amphetamines mimic the effects of epinephrine (adrenaline) and are known as
sympathomimetic drugs.
+ Short-term effects of amphetamines consumption: increased heart rate, increased blood
pressure, increased breathing rate, dilation of pupils, constriction of arteries, sweating,
increased alertness, increased concentration, and decreased appetite.
+ Long-term effects of consuming stimulants: weight loss, constipation and emotional
instability.
D.5.3 Discuss the short- and long-term effects of nicotine consumption.
Short-term effects
+ Increased heart rate, blood pressure and restriction of blood vessels.
+ Acts as an anti-diuretic, reducing urine output.
Long-term effects
+ Increased risk of heart disease or coronary thrombosis.
+ Risk of becoming addicted or physically dependent.
+ High cost.
+ Increased risk of lung, mouth, and throat cancer.
+ Increased risk of bronchitis/emphysema.
+ Reduce the capacity of blood to carry oxygen.
+ Withdrawal symptoms.
+ Negative effect during pregnancy.
+ Causing the formation of ulcers.
D.5.4 Describe the effects of caffeine and compare its structure with that of nicotine.
Symptoms associated with consumption of high dose caffeine:
+ Anxiety
+ Irritability and restlessness
+ Sleeplessness
+ Increase in urine output
+ Trembling
+ Increased heart rate
Comparing structure of caffeine and nicotine:
Caffeine
Nicotine
Structure
Functional groups
Amide, tertiary amine,
secondary amine, heterocyclic
group (benzene ring contains
both carbon and nitrogen atoms),
alkene group.
Tertiary amine, heterocyclic
group, alkene group.
D6 Antibacterials
D.6.1 Outline the historical development of penicillins.
+ Alexander Fleming, Howard Florey and Ernst Chain shared the Nobel Prize for “the
discovery of penicillin and its curative effect in various infectious diseases”.
+ Fleming discovered penicillin inhibited growth of bacteria and that penicillin has
antibiotic properties.
+ Florey and Chain produced penicillin in large quantity by discovering the synthetic
reaction of penicillin.
D.6.2 Explain how penicillins work and discuss the effects of modifying the side-chain.
Mode of action of penicillins:
+ Interfere with cell wall formation.
+ Prevent formation of cross-links within wall by inhibiting transpeptidase enzyme.
+ Size and shape of cell cannot be maintained.
+ Water freely enters the cell, building up the osmotic pressure which causes the cell to
burst.
Effects of modifying the side-chain of penicillin:
+ Penicillin becomes resistant to penicillinase enzyme which breaks the B-lactam ring of
penicillin.
+ This helps overcome the resistance that bacteria develop to existing antibiotics and
prevent penicillin from being destroyed by pencillinase enzyme.
+ Modifying side chain also helps develop resistance to the breakdown of penicillin by
stomach acid so it can be taken orally.
+ This also explains why it is important to develop semi-synthetic penicillins.
D.6.3 Discuss and explain the importance of patient compliance and the effect of penicillin
overprescription.
Causes of antibiotic resistance:
+ Overuse of antibiotics has increased proportion of resistant bacteria.
+ Use of penicillin in animal feedstock has introduced antibiotics into human food chain,
increasing proportion of resistant bacteria.
+ Patients not completing course of antibiotics increases proportion of resistant bacteria.
Effects of overprescription:
+ It makes penicillin less effective.
+ Penicillin can also destroy useful bacteria in our bodies.
+ Destroyed bacteria may be replaced by more harmful bacteria.
+ It allows resistant population to build up as resistant bacteria grow and pass on their
immunity to succeeding generations.
D7 Antivirals
D.7.1 State how viruses differ from bacteria.
+ Viruses do not have cellular structure.
+ Viruses do not have nucleus, cell wall and cytoplasm.
+ Bacteria are self-reproducing units while viruses need living hosts to survive.
+ Bacteria are able to grow, metabolize, feed and excrete while viruses lack metabolic
functions.
+ Bacteria contain various cell organelles (performing specific functions) while viruses
consist only of genetic material and protective coating.
+ Bacteria are (many times) larger than viruses.
+ Bacteria have more complex DNA than viruses do.
+ Viruses mutate much faster than bacteria do.
+ Viruses insert DNA/RNA into cells and rely on a host cell to reproduce.
+ Bacteria multiply by cell division: binary fission.
D.7.2 Describe the different ways in which antiviral drugs work.
+ They alter cells genetic material so that virus cannot use it to multiply.
+ They prevent viruses from multiplying by blocking enzyme activity within host cell.
+ They inhibit the synthesis of viral components by blocking enzymes (polymerase that
builds DNA) inside the cell.
+ They can sometimes become part of DNA of virus, inhibiting it from multiplying.
+ They prevent viruses from entering human cell and binding to cellular receptors on cell
membrane targeted by viruses.
+ They can alter the binding site on the cell wall.
+ They hinder the release of viruses from the cell.
+ In the case of HIV, antiviral can also prevent HIV from losing protein coat; block reverse
transcriptase to avoid converting the virus into a structure that can enter the nucleus of the
host cell; block the production of new viral RNA and proteins.
Normally, viral infections are generally harder to treat than bacterial infections because:
+ Compared to bacteria, viruses are more difficult to deal with because bacteria are much
more complex and thus can be targeted in more ways.
+ Viruses can mutate rapidly to adapt to the surrounding environment.
+ Bacteria can be killed by simple chemical agents while viruses cannot be killed and must
be targeted on genetic level.
+ Different types of bacteria employ similar metabolic processes and thus can be targeted
by common antibacterials while each kind of virus usually requires special drugs.
D.7.3 Discuss the difficulties associated with solving the AIDS problem.
+ HIV mutates rapidly
+ HIV metabolism linked to that of host cell; therefore drugs used will harm host cell as
well as HIV.
+ HIV destroys helper cells of the immune system.
+ Price of antiviral drugs is expensive and might not be affordable.
+ Sociocultural issues
Sociocultural issue
Details
availability cost
Condom use
cultural resistance
Cultural factors
Illegal activities
Resources / medical factors
Orphans
Devastation of family life
ignorance
wishful thinking
misinformation
social stigma
drug use
prostitution
impact of wars
availability of medical services
cost of drugs
condom use
resources / cost
devastation of family life
resources / cost
orphans
D8 Drug action
D.8.1 Describe the importance of geometrical isomerism in drug action.
+ Definition of geometrical isomerism: existence of compounds with the same molecular
formula but with atoms or groups arranged differently in space.
+ Example for this case is cisplatin:
+ Its geometrical isomer is:
+ Bonding presents in both isomers: covalent bonds and dative bond.
D.8.2 Discuss the importance of chirality in drug action.
+ Different enantiomers have different physiological effects in the body.
+ One example of this is thalidomide, which was used to treat morning sickness in pregnant
women.
+ Due to the presence of one chiral carbon (denoted by the star *), this drug has an optical
isomer, which can cause limb deformities in fetus.
Racemic mixture is not preferable because:
+ Racemic mixture means 50:50 mixture of two enantiomers
+ One enantiomer has beneficial effect while the other enantiomer might be potentially
harmful or require more clinical trials.
+ Example: thalidomide.
+ One thalidomide enantiomer relieves symptoms of morning sickness while the other
isomer can cause birth defects.
+ Second example is ibuprofen with one enantiomer much more effective.
D.8.3 Explain the importance of the betalactam ring action of penicillin.
+ Ring opens to allow penicillin to bond to enzyme which synthesizes bacterial cell walls
+ Therefore, it prevents cell wall or cell membrane from forming.
D.8.4 Explain the increased potency of diamorphine (heroin) compared to morphine.
+ Molecule of heroin is less polar while molecule of morphine is more polar because polar
OH groups in morphine are replaced with less polar/non-polar ester groups in heroin.
+ Less polar molecules cross the blood-brain barrier faster because heroin is more soluble in
non-polar environment of the CNS.
D9 Drug design
D.9.1 Discuss the use of a compound library in drug design.
+ A compound library is a collection of stored chemicals.
+ Each chemical in the library will have corresponding information: purity, chemical
structure, quantity and chemical properties that will be stored in an electronic compound
library database.
+ If a pharmaceutical chemist is in need of a chemical to perform a particular function, he
or she can search the electronic compound library database.
+ Any compounds that appear to have the required traits can be tested in the laboratory.
+ This eliminates the synthesizing and the individual evaluation in the laboratory of a
large number of related compounds which is a time consuming and expensive process.
+ Large numbers of related compounds can be created quickly.
+ As opposed to synthesizing and individually evaluating different compounds for biological
properties, this approach allows money and time to be saved.
D.9.2 Explain the use of combinatorial and parallel chemistry to synthesize new drugs.
+ Compared to the traditional method combinatorial chemistry and parallel synthesis are
used to synthesize a large number of different compounds and screen them for biological
activity.
+ A large number of similar related compounds are synthesized automatically using solid
phase techniques.
+ Same reaction sequence is applied at the same time to many compounds.
* Combinatorial chemistry:
+ Synthesis of large numbers of compounds using a variety of starting materials.
+ An automated process reacts a small number of compounds with a variety of reagents to
produce a large number of products.
+ Mix-and-split technique is used.
+ Small amounts of compounds are attached to resin.
+ Compound library consists of many different but related compounds.
+ Compounds are tested for biological activity.
* Compare combinatorial chemistry and parallel chemistry:
+ Parallel synthesis can produce smaller, more focused libraries.
+ Combinatorial synthesis produces larger, more diverse libraries while parallel synthesis
produces smaller, more focused libraries.
+ Combinatorial synthesis is performed in the same reaction vessel using mix and split
technique while parallel synthesis is performed in different reaction vessels.
* Solid-phase techniques:
+ Starting material covalently bonded to very small polystyrene beads.
+ Mix and split process used: beads are reacted together then split and reacted with new
substances so all combinations are made.
+ Products are purified by filtering of beads and washing.
D.9.3 Describe how computers are used in drug design.
+ Molecular modelling of receptors, pharmacophores, binding sites, potential drugs, drugreceptor interactions or virtual synthesis of drugs.
+ Facilitation of rational drug development, drug design, evaluation of effects of new drugs.
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.
+ Two examples you need to know are: aspirin and fluoxetine.
+ Their polarity can be increased by converting them into salts.
+ Converting them into salts has two advantages: increase their solubility in water and
facilitates their distribution inside the body.
+ Fluoxetine can be converted into salts by reacting with hydrochloric acid:
+ Aspirin can be converted into salts by reacting with sodium hydroxide:
(C6H4(OCOCH3)COOH + NaOH → C6H4(OCOCH3)COONa + H2O)
D.9.5 Describe the use of chiral auxiliaries to form the desired enantiomer.
+ A chiral auxiliary is itself an enantiomer, an optically active species.
+ It is bonded to the reacting molecule to create the stereochemical conditions
necessary to follow a certain pathway.
+ Further reaction will result in only one enantiomer being formed.
+ Once the desired enantiomer is formed, the auxiliary is removed.
+ Different enantiomers may have different biological effects, some of which may
be harmful.
+ It can cause genetic defects or deformities.
+ The advantage of using this is that it eliminates the need to carry out the separation of
the desired enantiomer from a racemic mixture.
D10 Mind-altering drugs
D.10.1 Describe the effects of lysergic acid diethylamide (LSD), mescaline, psilocybin and
tetrahydrocannabinol (THC).
Effects of taking LSD:
+ Extreme hallucinations
+ Magnified perception
+ Decreased judgment.
+ Relaxation and/or tension (depending on the user)
+ Dilated pupils
+ Increased heart rate.
+ Flashbacks.
Effects of psilocybin:
+ Mild hallucinations
+ Magnified perception
+ Relaxation.
+ 4-hour trip
Effects of taking mescaline:
+ Hallucinations or distortions in sound and visual perception.
+ Reduction of appetite, weight loss and insomnia.
Short term effect of THC:
+ Feelings of relaxation.
+ Enhanced auditory and visual perception
+ Loss of sense of time.
+ Confusion or emotional distress.
+ Increased risk of sedation with depressants.
D.10.2 Discuss the structural similarities and differences between LSD, mescaline and
psilocybin.
LSD
Mescaline
Psilocybin
Benzene ring, indole ring,
amide, tertiary and secondary
amine, alkene, heterocyclic
ring.
Primary amine, ether, benzene
ring.
Benzene ring, secondary
amine, phosphate group, ionic
end.
D.10.3 Discuss the arguments for and against the legalization of cannabis.
For:
+ Effective for certain named diseases. It can be used to relieve symptoms of AIDS or
cancer.
+ No more or less damaging than other drugs such as tobacco, alcohol.
+ Personal freedom argument: people who want to consume just have to pay more taxes.
+ It frees police to deal with more serious crimes due to the reduction of crime.
Against:
+ Some harmful effects e.g. increased risk of lung cancer, heart disease…
+ Many users move on to more damaging drugs.
+ Reduce the ability to drive safely.