OPTION D SL: MEDICINES AND DRUGS
D 1. Pharmaceutical products
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 side-effects.
Effects of medicines and drugs on the functioning of the body
A medicine or drug is any chemical that does one or more of the following to the human body, for better
or worse:
 alters the physiological state, including consciousness, activity level or coordination
 alters incoming sensory sensations
 alters mood or emotions
A medicine is a beneficial drug as it effects the body functions for the better. Each medicine has one (or
sometimes more) intended beneficial physiological effect that is called its therapeutic effect.
Physiological = to do with the functions in living organisms; physiological effects = effect on the
functioning of the living organism.
The types of medicines and drugs that we will study in this topic can be classified according to what
process or part they target in the human body:
Medicines and drugs
Analgesics, stimulants, depressants
Antacids
Antibacterials, antivirals
Target/aim
Nervous systems and brain; affect both sensory sensations and
mood
Target metabolic processes
Assist body’s ability to fight diseases
Stages in the development of a drug
1. Identify disease, could be new disease.
2. Identify a molecular target e.g. enzyme or gene which is necessary for disease to progress or a
receptor.
3. Identify ‘lead’ molecule that can act on gene/enzyme in the disease organism or host or on the
receptor – has pharmaceutical activity. Isolate the ‘lead’ molecule (e.g. from plants) or manufacture it
synthetically.
4. Preclinical trials: testing of ‘lead molecule’ in laboratory,
a. ‘in vitro’: the lead molecule is tested on animal/human cells and tissues which have been
removed from the body and are kept in an artificial environment.
b. ‘in vivo’: testing in live animals (usually 3 different species) to establish ED50 or LD50 which is
the amount which kills 50 % of the population.
5. Clinical trials
a. Testing of its effectiveness, its therapeutic window, tolerance and its side effects using the
placebo effect. This is a ‘blind trial’ in which half of the people/patients involved are given the
drug whilst the other half are given a similar substance that is not the drug (called ‘placebo’ but
none of the patients (or even their administering doctors) know which half they are in.
b. Structural modifications likely to be made to, for instance, improve effectiveness or reduce sideeffects.
6. Submission of reports on the drug and its trials to international or national regulatory bodies.
7. Monitoring of the drug after it has been launched; molecule might need further structural changes.
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Methods of administering drugs
 Oral: taken in by the mouth e.g. tablets, syrups, capsules;
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Advantages of taking it orally
Easily taken
No specialist equipment needed
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disadvantage
Can be destroyed by stomach acid
Slow to have an effect
Can cause stomach bleeding or vomiting
Only small amount of drug is absorbed
Patient needs to be conscious
 Parenteral – i.e. by injection, used when fast delivery is necessary.
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intravenous: into a vein of the blood stream – used for immediate impacts as it is the fastest
method; drug is immediately pumped around the body by the blood e.g. anaesthetics.
intramuscular i.e. into the muscles, e.g. many vaccines, antibiotics, usually used when a large
dose needs to be administered and it needs to act locally.
subcutaneous: in the layer of the skin directly below the cutis (dermis and epidermis) e.g. dental
injections, morphine, insulin. Slow absorption needed; also slow effect.
 Inhalation: e.g. medication for respiratory conditions such as asthma.
 Rectal: inserted into the rectum e.g. treatment for digestive illnesses, drug absorbed into the blood
stream.
 Skin patches: e.g. hormone treatments.
 Topical – applied to the skin: e.g. creams or ointments, also includes eye and ear drops.
Terms
Dosing regime = the amount of drug used for each dose i.e. how much drug should be taken in and its
frequency of administration e.g. three tablets every 4 hours.
Therapeutic window =
The therapeutic window is the range in amount or concentration over which a drug can be safely
administered to a typical population:
 The lowest level of concentration is the called the effective level (therapeutic level) or ED50; below this
level the drug loses its therapeutic effect.
 The highest level is the toxic or LD50 level (= the dose needed to kill 50 % of (animal) population)
above which adverse side-effects can occur.
wide therapeutic
window
narrow therapeutic
window
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low effective dose (ED50) and larger lethal dose (LD50) as a result there is a big
difference between effective and lethal dose.
for more common diseases
small difference between effective and lethal dose,
usually because lethal dose is small;
overdose is a high risk.
The therapeutic window depends on:
 The type of drug
 Age, sex and weight of the patient
 Diet
 Environment
Tolerance
Tolerance refers to the body’s reduced response to a drug i.e. its therapeutic effect is less than what it is
intended, usually as a result of taking the drug over a long period of time. As a result more of the drug
needs to be taken to achieve the same initial physiological effect with the danger of exceeding the lethal
dose.
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Side-effects =
Side-effects are physiological effects which are not intended and therefore undesired (intended =
therapeutic effects); these could be:
 beneficial e.g. protect against heart disease like aspirin.
 benign e.g. causing drowsiness, nausea constipation.
 adverse i.e. causing damage to other organs.
The extent of side effects determines who and when a medicine should be administered. Medicines with
severe side-effects should only be administered by qualified staff in medical emergencies.
Placebo effect
The placebo effect occurs when a person experiences a positive therapeutic (in particular with pain
killers) effect because they believe they have been given a medicine although the substance given is not
a medicine, instead a ‘placebo’ has been administered; the human body is fooled into healing itself
naturally. Placebo is used as a control to measure the real effectiveness of the drug which is the
difference between the effects experienced by the patients who took the drug and those patients who did
not.
Patients and administrators do not know which patients have taken the placebo.
D 2. Antacids
D 2.1 State and explain how excess acidity in the stomach can be reduced by the use of different bases.
Acid indigestion (discomfort in stomach) and heartburn (acid rising into oesaphagus) are conditions that arise
when excess hydrochloric acid is produced by the gastric glands in the walls of the stomach. The acid, which
creates an acidic environment of pH 0.3 to 1.2, is needed to:
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kill any bacteria in the food ingested and
provide the optimum pH environment for the digestive enzymes which act in the stomach.
Action of antacids
Antacids are substances (usually weak bases) which are used to neutralize excess hydrochloric acid in the
stomach so the pH level returns to the desired level.
Aluminium hydroxide, magnesium hydroxide, magnesium carbonate and sodium hydrogencarbonate are
commonly used as active ingredients in such antacids as they are weak bases. Aluminium hydroxide is the
most effective as it has 3 OH- per formula unit an can therefore neutralize three times as many H+ than sodium
hydrogen carbonate.
Sodium hydroxide or potassium hydroxide are not used as antacids because they are strong alkalis and are
too corrosive to the body tissue.
Equations
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Al(OH)3 (s) + 3HCl (aq)  AlCl3 (aq) + 3H2O (l)
Mg(OH)2 (s) + 2HCl (aq)  MgCl2 (aq) + 2H2O (l)
NaHCO3(s) + HCl (aq)  NaCl (aq) + H2O (l) + CO2(g)
MgCO3(s) + 2HCl (aq)  MgCl2 (aq) + H2O (l) + CO2(g)
Alginates
Some antacids also contain compounds called ‘alginates’ which prevent heartburn by
 producing a neutralizing layer on top of stomach contents and
 preventing acid in the stomach from rising into the oesophagus and causing heartburn (inflammation and
pain).
Anti-foaming agents
Antacids which use carbonates will also contain anti- foaming agents such as dimethicone which reduce the
bloating of the stomach as a result of the carbon dioxide production.
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D 3. Analgesics
D 3.1 Describe and explain the different ways that analgesics prevent pain.
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 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 .
Analgesics reduce pain.
How do analgesics prevent pain?
Mild analgesics, such as aspirin and paracetamol, function by stopping the transmission of pain from
source to brain as they intercept the pain stimulus at the source. They do this by interfering with or
suppressing the production of substances by injured tissues, such as prostaglandins, that stimulate pain
receptors that send pain impulses to the brain. Prostaglandins also cause pain, swelling or fever.
Strong analgesics such as morphine and diamorphine (heroin) work by temporarily bonding to receptor
sites to pain impulses in the brain or other parts of the central nervous system such as the spinal cord.
This prevents the transmission of pain impulses i.e. blocking the signal without depressing the central
nervous system.
Structures of some analgesics
Mild analgesics
Functional groups present in some mild analgesics:
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aspirin
phenyl/aromatic benzene
ester
carboxylic acid
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paracetamol
phenyl/aromatic benzene
hydroxyl
amide
carbonyl
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ibuprofen
phenyl/aromatic benzene
carboxylic acid
Some mild analgesics such as aspirin are derivatives of salicylic acid that was used as an analgesic in
the past but which was unpleasant to take and damaged the membranes in the mouth, gullet and
stomach. The structure of salicylic acid is shown below. A derivative = a new compound obtained from
another compound.
To convert salicylic acid into aspirin the hydrogen atom of
the OH group is replaced by a COCH3 group to form an
ester functional group which makes the compound less
irritating to the stomach and therefore easier to take.
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Strong analgesics (opiates)
Functional groups present in some strong analgesics:
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morphine
benzene ring
hydroxyl (2)
ether;
tertiary amine;
double bond/alkene;
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diamorphine/heroin
benzene ring
tertiary amine
alkene
ester (2)
ether
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codeine
benzene ring
hydroxyl/alcohol
ether (2)
alkene
tertiary amine
All three compounds are derived from opium which is an extract from poppy seeds. Both codeine and
diamorphine are derived from morphine and are called semi-synthetic opiate. An opiate is any chemical
that has the same physiological effect as morphine.
As the structures above show, heroin’s structure is only slightly different from morphine. Both the
hydroxyl or alcohol groups in morphine have been replaced with ester groups. This is achieved by
reacting the morphine with ethanoic acid; as a result an esterification occurs during which also water is
produced.
The amine in morphine, diamorphine and codeine is a tertiary amine as the nitrogen atom has three alkyl
groups bonded onto it.
Comparison of aspirin and paracetamol as mild analgesics
analgesic
aspirin
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paracetamol
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advantage
reduces fever more effectively –
antipyretic (=drug which reduces fever)
beneficial side-effects:
o preventing the recurrence of heart
attacks and strokes
o thins the blood
o reduces blood clotting
o also anti-inflammatory – reduces
inflammation or swelling
does not irritate stomach wall
suitable for children
allergic reactions rare
can be made in liquid form
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disadvantage
ulceration
stomach bleeding due to its acidic
properties
allergic reactions
Reye’s syndrome in children (a
potentially fatal liver and brain
disorder) so not suitable for children
can, in rare cases, cause blood
disorders and kidney damage.
easier to overdose and overdosage
can lead to serious liver damage,
brain damage and even death.
not a good anti-inflammatory
Advantages and disadvantages of using morphine and its derivatives
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advantage
strong analgesics and
therefore can relieve
extreme pain
wide therapeutic
window
relieves anxiety
induces relaxation
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disadvantage
euphoria, lack of self-control even dangerous behaviour
kidney failure.
addiction or physical dependence which leads to withdrawal
symptoms when drug is not taken e.g. restlessness, sweating, fever,
cramping, …
tolerance can become an issue with this type of drug as more of the
drug needs to be taken to achieve the same effect; in order to
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can be administered
intravenously which
results in faster
distribution of drug
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achieve the desired effect heroin users may take doses which exceed
the lethal dose
Social:
o heroin users are more likely to commit crimes to pay for
gradually increasing doses of the drug
o diversion of energy and money; loss of job
o when administered intravenously can lead to transmission of
dangerous infections e.g. AIDS.
o prostitution
D 4. Depressants
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.
D 4.4. Describe the synergistic effects of ethanol with other drugs.
D 4.5. Identify other commonly used depressants and describe their structures.
Depressants are often described as antidepressants (act against depression) because they relieve the
symptoms of (mental) depression by depressing (decreasing the activity of) the central nervous system.
They calm and relax the nervous system as they slow down the action of the brain, heart and other
organs.
Effects of depressants
dose
low
moderate
high
extremely high
effect
may exert little or no effect.
may induce sedation, soothing, reduction of anxiety, relaxes muscles, impaired
judgement, lowers heart rate,
may induce sleep, unconsciousness, slurred speech, altered perception
may cause organ failure, coma or death
Social and physiological effect of the use and abuse of ethanol
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Social
increased risk when driving or
operating machinery
involvement in violence or crime
relationship problems
taking time off work as a result of
sickness or death associated with
alcohol abuse
loss of income
hospital costs
lower economical production
cost of medical treatment to society
Physiological
Short term:
 reduces tension, anxiety and inhibitions
 impairs function of central nervous system
 dehydration
 high dose can cause vomiting, unconsciousness
Long term:
 liver damage/cirrhosis – liver disease
 increased blood pressure
 heart disease or stroke
 miscarriage and fetal abnormalities
 tolerance and physical dependence
Synergetic effect of ethanol with other drugs
Ethanol produces a synergic effect with other drugs i.e. their effect is enhanced in the presence of
alcohol which can be dangerous e.g. with aspirin it can increase risk of stomach bleeding. In the case of
sleeping tablets and other sedatives it can cause coma or death.
Techniques used for the detection of alcohol
Using potassium
dichromate
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Only used for detection in breath.
Ethanol is sufficiently volatile to pass into the lungs from the bloodstream which
is why it can be detected using a breathalyzer which contains potassium
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dichromate(VI).
In a positive result (i.e. presence of alcohol) the potassium dichromate changes
form orange to green when ethanol is present as the potassium dichromate is
reduced and the ethanol oxidized to ethanoic acid.
Equations:
oxidation: C2H5OH + H2O → CH3COOH + 4H+ + 4e−
reduction: Cr2O7 2− + 14H+ + 6e− → 2Cr3+ +7H2O
Overall: 3C2H5OH + 16H+ + 2Cr2O7 2− → 3CH3COOH + 2Cr3+ + 11H2O
intoximeter
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chromatography
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Used for breath, blood and urine.
Infrared radiation is passed through breath, blood or urine. The C–H bond in
ethanol causes radiation to be absorbed at a specific wavenumber (a wave
property proportional to frequency/energy) which is 2950 cm-1. The intoximeter
measures the amount of absorption at 2950 cm-1 which depends on the amount
of ethanol in the breath i.e. the more ethanol there is present the more IR is
absorbed. The concentration of ethanol is determined from the area under the
peak of the graph.
A fuel cell can also be used. Ethanol is oxidized to CO2 and H2O; the energy
released during this oxidation is converted into a voltage which can be used to
measure the concentration.
Used for blood and urine samples.
Ethanol is separated from the blood or urine using gas-liquid chromatography.
Accurate; area under ethanol peak on chromatogram indicates amount of
ethanol in blood or urine
Other commonly used depressants prescribed for stress relief: (see table 20 in data booklet)
depressant
Fluoxetine hydrochloride (Prozac®)
diazepam/Valium®;
nitrazepam/Mogadon®;
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Structure: functional groups
aromatic benzene, ether, fluorine, secondary amine, chloride
ion
amide
aromatic benzene
secondary amine
chlorine atom
amide
aromatic benzene
secondary amine
NO2
D 5. Stimulants
D 5.1 List the physiological effects of stimulants.
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.
Stimulants are drugs that act on the central nervous system as they increase the activity of the brain by
increasing the levels of neurotransmitters. They are the opposite to depressants.
Examples of stimulants
Caffeine, nicotine, amphetamines (synthetic drugs e.g. in diet pills). The intention of these drugs is to have
similar effects to adrenaline which is a natural stimulant that is released in times of stress e.g. pain, cold,
fear. The effects of adrenaline are increased heart beat, increased blood pressure, increased blood flow
to brain and muscles, increased air flow to lungs all resulting in an increased alertness to allow the
organism to deal with the stress or “fight or flight”.
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Amphetamines are synthetic drugs that have similar structures to epinephrine/adrenaline and therefore
mimic its effects of which is to stimulate the sympathetic nervous system. They are therefore known as
sympathomimetic drugs.
Physiological effects of stimulants
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Short term
Increased brain activity
increased heart rate,
increase breathing rate,
increased alertness and concentration
decreased appetite
shakes
sleeplessness
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Long term
increased risk of heart disease
increased blood pressure
coronary thrombosis (blood clots in blood vessels)
stomach ulcers.
tolerance: which leads to increased use as increased
amounts needed to produce same effect; increasing
amounts cause damage/death/overdose/lethal dose
Differences between amphetamines and epinephrine
Both have the phenylethylamine structure, C6H5CH2CH2-. Highlight this structure on the molecule of
amphetamine.
amphetamines
epinephrine
Functional groups:
 benzene ring
 primary amine
Functional groups:
 benzene ring
 secondary amine
 hydroxyl (3) can form more hydrogen bonds
and is therefore more soluble in water
Short and long term effects of nicotine consumption
A nicotine molecule contains the following functional groups: a tertiary amine in one ring, ring structures
with nitrogen atoms in them, and double bonds (alkene functional group). Label these groups on the
structure below.
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Short term effects
increased heart rate
increased blood pressure
reduced urine output
increased concentration
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Long term effects
increased risk of cancer or stroke
heart disease / thrombosis
stomach ulcers
emphysema
bronchitis
shortage of breath
coughing
bad breath
yellowing of teeth or fingers
adverse effect on pregnancy
addiction to tobacco
reduction in capacity of blood to carry oxygen;
withdrawal symptoms / weight gain (on quitting);
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Caffeine
Caffeine is a stimulant. When consumed in large amounts it can cause
anxiety, irritability and sleeplessness. It is a weak diuretic (=causes
increase in urine output).
Its structure is similar to nicotine as shown on the right; in this structure
highlight in blue the functional groups which both nicotine and caffeine
have: benzene ring and tertiary amine (caffeine has three of those) and in
red the group which caffeine has but not nicotine i.e. the amide group.
D 6. Antibacterials
D 6.1 Outline the historical development of penicillins.
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 .
Antibacterials are drugs that kill or inhibit the growth of bacteria that cause infectious diseases. Penicillins
are a group of compounds that are produced by micro-organisms and kill harmful micro-organisms; they
are therefore called antibiotics.
Examples of infectious diseases caused by bacteria: tuberculosis, syphilis, cholera, salmonella,
bronchitis, anthrax, meningitis, gonorrhea, chlamydia.
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”.
Scientist
Alexander Fleming
Howard Florey and Ernst Chain
Contribution to development of penicillin
Discovered by chance that penicillin inhibited growth or killed bacteria;
Fleming had left a bacteria culture and later found a clear zone in the
culture in which bacteria had been killed. That zone had been
contaminated by a mould called Penicillium notatum..
 overcame the problems associated with isolating and concentrating
penicillin as Penicillin G = main contribution
 showed that penicillin is harmless and effective on mice;
 first to use penicillin on a human;
 grew penicillin in large amounts;
 grew strains of penicillin in corn-steep liquor.
How do penicillins work?
Structure of the first penicillin to be used, penicillin G or C16H18O4N2S, is shown below.
Label functional groups A and B and any other functional groups you recognize.
Circle the side chain which is the benzene ring and CH2 to the left of the carbonyl group of the amide.
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Penicillins prevent the growth of bacteria. They do this by deactivating (the beta-lactam group does that)
the enzymes in the bacteria that are involved in developing cross-links in the cell wall of bacteria. As a
result the bacterial cell absorbs too much water which causes the cell to burst. Bacteria constantly
replace cell walls.
Administering of penicillins
There are two types of antibiotics:
 broad-spectrum antibiotics that are effective against a wide range of bacteria but can therefore also
kill useful bacteria.
 narrow-spectrum only attack a limited range of bacteria, usually administered when doctor has
identified type of infectious bacteria after taking samples of blood, urine, …
With some diseases, e.g. tuberculosis (TB), it is important to administer a “cocktail” of different
antibacterials because bacteria that cause TB are usually extremely resistant to penicillins so a mixture of
different antibiotics is used.
Increased resistance in bacteria to antibacterials
As a result of mutations, bacteria have become resistant to penicillins because of their misuse. Resistant
bacteria produce an enzyme, penicillinase, which causes the break up of the penicillin molecule (the beta
lactam ring to break open); these bacteria then reproduce and pass on their resistance to succeeding
generations.
Examples of misuse of antibiotics include:
1. Patient compliance
Refers to patients not completing the full course of antibiotics and this resuts in prolonging the disease as
not all bacteria are killed. By allowing the bacteria to live longer there can be more mutations eventually
producing bacteria with resistance. Patient compliance also allows disease to spread as bacteria are not
all killed.
2. Overprescription of antibacterials
Many doctors are too quick to prescribe antibiotics. Patients should be encouraged to fight an infection
using their own immune system. Overprescription can also result in allergic reactions by the patients and
also wipe out harmless bacteria.
3. Use of antibacterials in animal feedstock
Some antibiotics are also effective in animals but these antibiotics are sometimes administered without
the animals having any disease. These antibiotics end up in the food chain.
Modifying the side-chain of penicillin G to develop new semi-synthetic penicillins
Modern or semi-synthetic penicillins, such as ampicillin, are penicillin molecules that have been modified
by replacing the side-chain with other atoms or groups of atoms
For instance, in the case of ampicillin, the side chain now still contains a benzene or C6H5 ring but has a
hydrogen atom and an amine (-NH2) group instead of the CH2 group that was there.
Such modifications to the side-chain bring advantages such as:
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Reducing the occurence of penicillin resistant bacteria as the modified penicillins are able to
withstand the action of the enzyme, penicillinase, which is an enzyme produced by penicillin-resistant
bacteria and which causes the break down of penicillin.
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Resistance to breakdown or deactivation by stomach acid (so can be taken orally, e.g. ampicillin);
penicillin G had to be administered by injection because it was decomposed by stomach acid.
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D 7. Antivirals
D 7.1. State how viruses differ from bacteria.
D 7.2 Describe the different ways in which antiviral drugs work.
D 7.3 Discuss the difficulties associated with solving the AIDS problem.
Examples of diseases caused by viruses: AIDS, influenza, rabies, common cold, small pox, measles, …
Difference between bacteria and viruses
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Bacteria
bacteria are self-reproducing i.e. by cell division
– do not need a host
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bacteria are able to grow, feed and excrete
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bacteria contain organelles such as cytoplasm,
cell wall and a nucleus which all perform
specific functions
bacteria are (many times) larger than viruses
bacteria have more complex DNA
bacteria mutate/multiply slower than viruses;
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Viruses – need a host cell
viruses are not self-reproducing as they need a
host cell to multiply; viruses insert DNA into
host cells – after reproduction the host cell dies
viruses lack any metabolic functions so they do
not grow, feed or excrete
viruses consist only of genetic material and
protective coating, no cell wall, no nucleus and
no cytoplasm
viruses are smaller than bacteria
viruses have simpler DNA
viruses mutate/multiply (much) faster than
bacteria
Ways in which antiviral drugs work
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preventing viruses from entering host cell as it changes the cell membrane of the host cell
preventing the viruses from multiplying in the host cell:
o by blocking enzyme activity within the host cell.
o by altering genetic material in the host cell
preventing the release of viruses after reproduction from the cell
Viral infections are harder to treat than bacterial because
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viruses mutate much more quickly so:
o they can adapt to drugs or
o they can evade human immune system response
bacteria are more complex and thus can be targeted in more ways - viruses lack subunits/functions
which are normally targeted by antibacterials;
bacteria can be killed or their actions reduced by simple chemical agents but 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 whilst each kind of virus usually requires special drugs.
The treatment of AIDS by antiviral drugs is problematic because
HIV invades white blood cells or T4 cells.
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HIV viruses can mutate rapidly
antiretroviral drug target white blood cells which are meant to protect us against other pathogens
HIV lies dormant for a while
socioeconomic: high price of antiretroviral drugs, cost to state, access to drugs,
cultural issues: discrimination, stigma high price of antiretroviral drugs
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