Download option d - chemistryatdulwich

OPTION D: 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 could be seen as a chemical which contains a useful drug.
A medicine or drug is any chemical that does one or more of the following to the human body.
 alters the physiological state, including consciousness, activity level or coordination
 alters incoming sensory sensations
 alters mood or emotions
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 which we will study in this topic can be classified according to what
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, mood
or sensations
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 target e.g. gene or enzyme which is necessary for disease to progress.
3. Identify ‘lead’ molecule that can act on gene/enzyme in the disease organism or host and isolate or
manufacture it.
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 LD50 which is the
amount which kills 50 % of population.
5. Clinical trials
a. Testing of its effectiveness and dose range on humans 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 which is not the drug but none of the patients know which half
they are in. All patients should/could experience placebo.
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.
IB option D
1
Methods of administering drugs
 Oral: taken in by the mouth e.g. tablets, syrups, capsules.
 Parenteral - by injection:
o
intravenous: into a vein of the blood stream – used for immediate impacts as its fastest
method; drug is immediately pumped around the body by the blood.
o
intramuscular i.e. into the muscles, e.g. many vaccines, local anaesthetics, usually used
when a large dose needs to be administered.
o
subcutaneous: in the layer of the skin directly below the cutis (dermis and epidermis) e.g.
dental injections, morphine, insulin. Slow.
 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.
Terms
Dosing regime = the amount of drug used for each dose i.e. how much drug should be taken in.
Therapeutic window =
The therapeutic window is the range over which a drug can be safely administered to a typical
population. It is the range in concentration in the blood within which an administered drug must remain;
 The lowest level of concentration is the called the effective 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
small effective dose (ED50) and larger lethal dose (LD50) as a result there is
a big difference between effective and lethal dose.
small difference between effective and lethal dose usually because lethal
dose is small.
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.
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.
 benign e.g. causing drowsiness, nausea constipation.
 adverse i.e. causing damage to other organs.
Placebo effect
The placebo effect occurs when a person experiences a positive therapeutic effect although a substance
which is not a drug has been administered; the human body is fooled into healing itself naturally
IB option D
2
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 which 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:
 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 which are used to neutralize excess hydrochloric acid in the stomach so the pH level
returns to the desired level.
Aluminium hydroxide, magnesium hydroxide and sodium hydrogencarbonate are commonly used as active
ingredients in such antacids as they are weak bases.
Sodium hydroxide or potassium hydroxide are not used as antacids because they are strong alkalis and are
too corrosive to the body tissue.
Equations

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)
Alginates
Some antacids also contain compounds called ‘alginates’ which:
 produce a neutralizing layer on top of stomach contents and
 prevent acid in the stomach from rising into the oesophagus and causing heartburn.
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.
Exercises
1. Compare the effectiveness of 1.00 g of sodium hydrogencarbonate to 0.50 g of magnesium hydroxide
in combating acidity in the stomach (M10)
2. Calcium carbonate can also neutralize stomach acid. The same amounts (in moles) of sodium
hydrogencarbonate and calcium carbonate are available. Deduce which antacid will neutralize the
greater amount of acid present in the stomach and explain your reasoning. (M09)
IB option D
3
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 3.3 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 the
production of substances, such as prostaglandins, that are produced by injured tissues and that 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:



aspirin
phenyl/aromatic benzene
ester
carboxylic acid




paracetamol
phenyl/aromatic benzene
hydroxyl
amide
carbonyl


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 made the compound less
irritating to the stomach and easier to take.
IB option D
4
Strong analgesics
Functional groups present in some strong analgesics:





morphine
aromatic benzene
hydroxyl (2)
ether;
tertiary amine;
double bond/alkene;





diamorphine/heroin
aromatic benzene
tertiary amine
alkene
ester (2)
ether





codeine
aromatic benzene
hydroxyl/alcohol
ether (2)
alkene
tertiary amine
On the diagram below of a morphine molecule indicate the different functional groups.
Diamorphine or heroin is a derivative of morphine or a semi-synthetic opiate. An opiate is a chemical
which has the same physiological effect as morphine.
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.
Also codeine is a morphine derivative.
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



paracetamol



IB option D
advantage
reduces fever more effectively –
antipyretic (=drug which reduces
fever)
also useful in preventing the
recurrence of heart attacks and
strokes and also thins the blood
(beneficial side-effects) and reduces
blood clotting
also anti-inflammatory – reduces
inflammation or swelling
reduces fever - antipyretic
very safe in the correct dose as it
does not upset the stomach or cause
bleeding
suitable for children
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
5
Advantages and disadvantages of using morphine and its derivatives
advantage
strong analgesics and therefore
can relieve extreme pain
wide therapeutic window
relieves anxiety
induces relaxation
can be administered
intravenously which results in
faster distribution of drug










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 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 loss of job
o diversion of energy and money
o when administered intravenously can lead to
transmission of dangerous infections e.g. AIDS.
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 because they relieve the symptoms of (mental)
depression by depressing the central nervous system. They calm and relax the nervous system as they
slow down the action of the brain, heat and other organs.
Effects of depressants
The effect on the individual of consuming depressants depends on the dose:
dose
low
moderate
high
extremely high
effect
may exert little or no effect.
may induce sedation, soothing, reduction of anxiety, impaired judgement
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




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
IB option D
Physiological
Short term:
 reduces tension, anxiety and inhibitions
 impairs function of central nervous system
 dehydration
 high dose can cause vomiting, unconsciousness
6



death associated with alcohol abuse
loss of income
hospital costs
lower economical production
Long term:
 liver damage/cancer
 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 damage to stomach and cause 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




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
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
intoximeter


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 wavelength which is 2950
cm. The intoximeter measures the amount of absorption which depends upon
the amount of ethanol in the breath i.e. the more ethanol there is present the
more IR is absorbed. The amount or peak is compared against a standard (e.g.
allowed amount)
chromatography



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 indicated amount of
ethanol in blood or urine
Other commonly used depressants
depressant
Fluoxetine hydrochloride (Prozac®)
diazepam/Valium®;
nitrazepam/Mogadon®;
IB option D

Structure: functional groups
aromatic benzene, ether, fluorine, amine, chloride ion





amide
aromatic benzene
secondary amine
chlorine
amide
7



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.
Examples of stimulants
Caffeine, nicotine, amphetamines. The intention of these drugs is to have similar effects to adrenaline which is a
natural stimulant. Amphetamines have similar structures to adrenaline.
Physiological effects of stimulants
Short term
 Long term increased heart rate, blood pressure,
breathing rate
 dilation of pupils
 constriction of arteries
 sweating
 increased alertness and concentration
 decreased appetite
 stimulating effects.




Long term
increased risk of heart disease,
coronary thrombosis
stomach ulcers.
tolerance: which leads to increased use as
increased amounts needed to produce same
effect; increasing amounts cause
damage/death/overdose/lethal dose
Amphetamines
Amphetamines mimic the effects of epinephrine or adrenaline which stimulates the sympathetic nervous
system and are therefore known as sympathomimetic drugs.
Adrenaline = hormone released in times of stress e.g. pain, cold, fear, …
Effects:
•increased heart beat/blood pressure
•Increased blood flow to brain and muscles
•Increased air flow to lungs
•Increased alertness
Nicotine is also a sympathometic drug.
Short and long term effects of nicotine consumption
A nicotine molecule contains the following functional groups: a tertiary amine, ring structures with
nitrogen atoms in them, and double bonds (alkene functional group). Label these groups on the structure
below.
IB option D
8




Short term effects
increased heart rate
increased blood pressure
reduced urine output
increased concentration













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);
Caffeine
Caffeine is a respiratory stimulant. When consumed in large amounts it can cause anxiety, irritability and
sleeplessness. It is a weak diuretic.
Its structure is similar to nicotine as shown below. In the structure below highlight in blue the functional
groups which both nicotine and caffeine have 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 (or antibiotics) are drugs that kill or inhibit the growth of microorganisms that cause
infectious diseases.
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
IB option D
Contribution to development of penicillin
discovered that penicillin inhibited growth or killed bacteria
 overcame the problems associated with isolating and concentrating
9




penicillin as Penicillin G
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 penicillin, C16H18O4N2S, is shown below
Label functional groups A and B and any other you recognize.
Penicillins work by interfering with the chemicals that a bacteria needs to form a cell wall. This prevents
the formation of cross-links within the cell wall. As a result the bacterial cell absorbs too much water and
bursts as the result of increased osmotic pressure.
Administering of antibiotics
There are two types of antibiotics
 broad-spectrum antibiotics are effective against a wide range of bacteria
 narrow-spectrum only attack a limited range of bacteria
With some diseases, e.g. tuberculosis (TB) it is important to administer a “cocktail” of different
antibacterials because bacteria which cause TB are usually extremely resistant to penicillins so a mixture
of different antibacterials is used.
Modifying side-chain of penicillin G
Modern or semi-synthetic penicillins, such as ampicillin, are molecules which have been modified from
the Penicillin G in which the side-chain R, an alkyl group indicated above, has been replaced and now
contains two functional groups: a benzene or C6H5 ring and an amine (-NH2) group
The different side-chain brings two advantages:
 resistant to penicillinase enzyme which is an enzyme which can break down penicillin G and which is
found in some bacteria; stops bacteria from destroying penicillin and becoming resistant to them
 resistance to breakdown by stomach acid (so can be taken orally).
Patient compliance
IB option D
10
Refers to not completing their course of peniciliin or antibiotics this allows bacteria to develop resistance
Effect of overprescription of antibacterials
The overuse of antibacterials has reduced their effectiveness as it



leads to resistance by the bacteria to penicillin which makes penicillin less effective; bacteria
produced penicillinase enzyme which destroys penicillin
resistant bacteria reproduce and pass on their to succeeding generations
useful bacteria may be killed
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.
Difference between bacteria and viruses

bacteria
bacteria are self-reproducing i.e. by cell division


bacteria are able to grow,feed and excrete


bacteria contain various cell subunits or
organelles such as cytoplasm and cell wall
which all perform specific functions
bacteria are (many times) larger than viruses
bacteria have more complex DNA
bacteria mutate/multiply slower than viruses;







viruses
viruses are not self-reproducing as they need a
host cell to multiply; viruses insert DNA into
host cells
viruses lack any metabolic functions so they do
not grow, feed or excrete
viruses consist only of genetic material and
protective coating
viruses are smaller than bacteria
viruses have simpler DNA
viruses mutate/multiply (much) faster than
bacteria
Ways in which antiviral drugs work




altering the host cell’s genetic material so that the virus cannot use it to multiply
preventing the viruses from multiplying by blocking enzyme activity within the host cell.
preventing viruses from entering host cell and binding to cellular receptors targeted by the viruses
preventing the release of viruses from the cell
Viral infections are harder to treat than bacterial because




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
IB option D
11
HIV invades white blood cells or T4 cells.





HIV viruses can mutate rapidly
HIV viruses have similar metabolism to the metabolism of the host cell host cells so any drug could
also damage host cell
high price of antiretroviral drugs
socioeconomic
cultural issues;
IB option D
12