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

Drugs are chemicals which effect how the human body functions, for better or for worse. A medicine is a beneficial drug as it effects the body functions for the better. Each medicine has one (or more) intended beneficial physiological effect(s) which is called its therapeutic effect.

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 / Target/aim
Analgesics, stimulants, depressants / Nervous systems and brain; affect both sensory sensations and mood
Antacids / Target metabolic processes
Antibacterials, antivirals / 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.
  1. 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.
  1. Preclinical trials: testing of ‘lead molecule’ in laboratory,
  2. ‘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.
  3. ‘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.
  1. Clinical trials
  2. 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.
  3. Structural modifications likely to be made to, for instance, improve effectiveness or reduce side-effects.
  1. Submission of reports on the drug and its trials to international or national regulatory bodies.
  2. Monitoring of the drug after it has been launched; molecule might need further structural changes.

Methods of administering drugs

  • Oral: taken in by the mouth e.g. tablets, syrups, capsules.
  • Parenteral – i.e. by injection, used when fast delivery is necessary.
  • 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.
  • intramuscular i.e. into the muscles, e.g. many vaccines, local anaesthetics, usually used when a large dose needs to be administered.
  • 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 and its frequency of administration e.g. three tablets every 4 hours.

Therapeutic window =

The therapeutic window is the range in amount over which a drug can be safely administeredto 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 (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 / low effective dose (ED50) and larger lethal dose (LD50) as a result there is a big difference between effective and lethal dose.
narrow therapeutic window / 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

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.

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 effect although asubstance which is not a medicine (a ‘placebo’) has been administered; the human body is fooled into healing itself naturally. Placebo is used as a control to measure 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.

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 (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 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 prevent heartburn by

  • producing a neutralizing layer on top of stomach contentsand
  • 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.

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 or suppress 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 / paracetamol / ibuprofen
  • phenyl/aromatic benzene
  • ester
  • carboxylic acid
/
  • phenyl/aromatic benzene
  • hydroxyl
  • amide
  • carbonyl
/
  • 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. Aspirin

/ 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.

Strong analgesics (see table 20 in data booklet

Functional groups present in some strong analgesics:

morphine / diamorphine/heroin / codeine
  • aromatic benzene
  • hydroxyl(2)
  • ether;
  • tertiary amine;
  • double bond/alkene;
/
  • aromatic benzene
  • tertiary amine
  • alkene
  • ester (2)
  • ether
/
  • aromatic benzene
  • 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 a chemical which 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 / advantage / disadvantage
aspirin /
  • reduces fever more effectively – antipyretic (=drug which reduces fever)
  • beneficial side-effects:
  • preventing the recurrence of heart attacks and strokes
  • thins the blood
  • reduces blood clotting
  • also anti-inflammatory – reduces inflammation or swelling
/
  • 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

paracetamol /
  • reduces fever - antipyretic
  • very safe in the correct dose as it does not upset the stomach or cause bleeding
  • 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

advantage / disadvantage
  • 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
/
  • euphoria, lack of self-control even dangerous behaviour
  • kidney failure.
  • addiction or physical dependence which leads to withdrawal symptoms when drug is not takene.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:
  • heroin users are more likely to commit crimes to pay for gradually increasing doses of the drug
  • diversion of energy and money; loss of job
  • when administered intravenously can lead to transmission of dangerous infections e.g. AIDS.
  • prostitution

D 4. Depressant

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 / effect
low / may exert little or no effect.
moderate / may induce sedation, soothing, reduction of anxiety, relaxation,impaired judgement
high / may induce sleep, unconsciousness, slurred speech, altered perception
extremely high / may cause organ failure, coma or death

Social and physiological effect of the use and abuse of ethanol

Social / Physiological
  • 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
/ Short term:
  • reduces tension, anxiety and inhibitions
  • impairs function of central nervous system
  • dehydration
  • high dose can cause vomiting, unconsciousness

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: Cr2O72−+ 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 wavenumber (a wave property proportional to frequency/energy) which is 2950 cm-1. The intoximeter measures the amount of absorption at 2950 cm-1which depends on the amount of ethanol in the breath i.e. the more ethanol there is present the more IR is absorbed. The amount of absorption or peak is compared against a standard (e.g. allowed amount of ethanol in the blood).

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 (see table 20 in data booklet)

depressant / Structure: functional groups
Fluoxetine hydrochloride (Prozac®) /
  • aromatic benzene, ether, fluorine, amine (ammonium structure), chloride ion

diazepam/Valium®; /
  • amide
  • aromatic benzene
  • secondary amine
  • chlorine atom

nitrazepam/Mogadon®; /
  • 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; they are the opposite to depressants.

Examples of stimulants

Caffeine, nicotine, amphetamines. The intention of these drugs is to have similar effects to adrenaline which is a natural stimulant which is released in times of stress e.g. pain, cold, fear. The effect of adrenaline are increased heart beat, 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.

Amphetamines have similar structures to adrenaline.Amphetamines mimic the effects of epinephrine or adrenaline which stimulates the sympathetic nervous system and they are therefore known as sympathomimetic drugs.

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.
/
  • increased risk of heart disease
  • increased blood pressure
  • 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

Differences between amphetamines and epinephrine

amphetamines / epinephrine
Functional groups:
  • aromatic benzene
  • primary amine
/ Functional groups:
  • aromatic benzene
  • secondary amine
  • hydroxyl (3)

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.