Developing New Drugs

Plant Structure and Function

What is the purpose of drug testing?

To determine whether a new drug is effective, safe and suitable for use in patients.

Who was William Withering?

A British doctor and botanist who investigated the medicinal effects of foxgloves on patients with heart problems.

What are digitalis compounds?

Chemicals found in foxgloves that affect the beating and function of the heart.

What is oedema?

Swelling of tissues caused by the retention of excess fluid.

What condition was historically called dropsy?

Oedema caused by poor circulation, often associated with heart failure.

How did William Withering discover the potential medicinal effect of foxgloves?

He observed that a patient with a serious heart condition improved after taking a herbal remedy containing foxglove.

How did Withering investigate foxglove as a treatment?

He tested foxglove preparations on many patients and carefully recorded their effects and side effects.

What did Withering discover about the dose of foxglove?

Too much caused serious side effects, while the correct dose increased urine production and made the heartbeat stronger and more regular.

What side effects did excessive foxglove cause?

Nausea, vomiting and potentially death.

Why did foxglove help patients with oedema?

It improved heart function and increased urine production, helping the body remove excess fluid.

How did Withering prepare foxglove for treatment?

He used dried and powdered foxglove leaves to make a medicinal preparation.

Why was boiling foxglove leaves avoided?

Boiling reduced the effect of the active drug.

What modern drug is based on chemicals found in foxgloves?

Digoxin.

What is digoxin?

A drug based on a chemical found in foxgloves that improves heart function.

What properties should an effective new medicine have?

It should be effective, safe, stable, able to enter and leave the body appropriately, and suitable for large-scale manufacture.

What does it mean for a medicine to be effective?

It cures, prevents or relieves symptoms of the disease it is designed to treat.

What does it mean for a medicine to be safe?

It is non-toxic and does not cause unacceptable side effects.

Why must a medicine be stable?

So it can be stored for a suitable period and remain effective under normal conditions.

Why must a drug be able to enter and leave the body effectively?

It must reach its target and then be broken down or excreted safely after doing its job.

Why must medicines be suitable for large-scale manufacture?

So they can be produced in a pure form, in large quantities and at a reasonable cost.

Approximately how long can developing a new medicine take?

About 10 years.

Approximately how much can developing a new medicine cost?

Around £1.2 billion.

How can computer models help scientists discover new medicines?

They can model the shape of enzyme or receptor active sites and identify chemicals likely to bind to them.

What is the advantage of computer modelling during early drug development?

It helps identify promising compounds before expensive laboratory and clinical testing begins.

What happens when scientists identify a promising new compound?

It undergoes laboratory testing and, if successful, progresses through further development and trials.

Why are new drugs first tested on cells and tissues?

To determine whether they have the expected effect and identify potentially harmful effects.

Why do many potential drugs fail during early laboratory testing?

They may not work in living tissues or may have harmful effects.

What must be developed before a drug can be tested effectively in animals or humans?

A suitable delivery system, such as a tablet, injection or nasal spray.

Why must scientists check that a drug is stable before testing it?

To ensure it does not break down into toxic or inactive substances before reaching its target.

Why are potential drugs tested on animals?

To investigate their effects on a whole organism, including effectiveness, toxicity, metabolism and excretion.

Which animals are commonly used during initial drug testing?

Mice and rats.

Why are mammals used for drug testing?

Their biology is sufficiently similar to humans to provide useful information about how a drug may behave in the human body.

Why are animal experiments an ethical issue?

Animals may experience pain, distress or harm during experiments.

How is the use of animals in drug testing reduced?

Cell cultures and computer models are used where possible, animal numbers are minimised and procedures are refined to reduce distress.

Why can computer models and cell cultures not completely replace animal testing?

They cannot yet reliably show all the effects of a drug on a whole living organism.

What happens after successful animal testing?

The drug can progress to clinical trials in humans if regulators approve it.

What are clinical trials?

Controlled tests of a new medicine on human volunteers and patients to assess its safety and effectiveness.

What is a placebo?

An inactive substance resembling the drug being tested that is used as an experimental control.

Why are placebos used in clinical trials?

They allow researchers to determine whether improvements are caused by the drug rather than patients' expectations.

What is the placebo effect?

When a patient appears to improve because they believe they are receiving an effective treatment.

What happens during phase 1 clinical trials?

The drug is given to a small number of healthy volunteers to assess safety, dosage and unexpected side effects.

Who normally takes part in phase 1 trials?

A small number of healthy volunteers.

What is the main purpose of phase 1 trials?

To determine whether the drug behaves as expected in humans and identify potentially dangerous side effects.

What happens during phase 2 clinical trials?

The drug is given to patients with the target disease to assess effectiveness, dosage and side effects.

Approximately how many patients are involved in phase 2 trials?

About 100–500 patients.

Why are patients with the target disease used in phase 2 trials?

To determine whether the medicine actually treats the disease in real patients.

What is compared during phase 2 trials?

The new drug may be compared with a placebo or the current standard treatment.

What happens during phase 3 clinical trials?

The drug is tested on thousands of patients to confirm its effectiveness and safety and identify less common side effects.

Approximately how many patients may be involved in phase 3 trials?

Over 5000 patients.

Why are large numbers of patients used in phase 3 trials?

To provide reliable evidence of effectiveness and increase the chance of detecting uncommon side effects.

What is a double-blind trial?

A clinical trial in which neither the patient nor the doctor or scientist knows who receives the new treatment and who receives the control until the results are analysed.

Why are double-blind trials used?

To prevent expectations and unconscious bias from influencing the results.

Why are patients randomly allocated to treatment groups?

To reduce bias and make the groups as comparable as possible.

What can be used instead of a placebo when withholding treatment would be unethical?

The best-performing existing treatment.

Why might an existing treatment be used instead of a placebo?

To avoid denying patients effective treatment and to determine whether the new drug performs better than current treatment.

What information is collected during clinical trials?

Data on effectiveness, side effects, dosage and other responses to treatment.

Why are clinical trial results analysed statistically?

To determine whether differences between treatments are significant rather than due to chance.

Why might some patients stop taking part in a clinical trial?

They may experience side effects or fail to take the medicine regularly.

Why might a clinical trial be stopped early?

If strong evidence shows that the new treatment is highly effective or is causing unacceptable harm.

What happens after a drug successfully completes phase 3 trials?

The pharmaceutical company applies for regulatory approval and a licence to sell the drug.

What do regulatory authorities assess before approving a medicine?

They compare the potential benefits of the medicine with its possible harmful effects.

Why does a medicine need a licence?

To ensure there is sufficient evidence that it is safe, effective and suitable for use.

Does drug testing stop after a medicine is approved?

No. Its safety continues to be monitored while it is being used.

Why are medicines monitored after approval?

To identify rare or long-term adverse effects that may not have appeared during clinical trials.

What happens if adverse reactions occur after a drug is approved?

They are reported and recorded so the risks of the medicine can continue to be assessed.

What are the main stages of modern drug development?

Discovery and early testing → preclinical laboratory testing → animal testing → phase 1 trials → phase 2 trials → phase 3 trials → regulatory approval → continued monitoring.

How does Withering's investigation differ from modern drug testing?

Withering tested treatments directly on patients with limited controls, whereas modern drugs undergo laboratory and animal testing followed by carefully controlled clinical trials and regulatory approval.

What is one advantage of modern drug testing compared with historical methods?

It uses controlled, systematic testing to provide more reliable evidence about safety, effectiveness and dosage.