1. Drug development  Recognise the use of plants as sources of medicines.  Describe the drug development process.  Compare historic drug testing with contemporary drug testing protocols, e.g. William Withering’s digitalis soup; double blind trials; placebo; three-phased testing.

2. Starter activity Read the section on p 222-3 Extracting the active ingredient. Read the section on p 222-3 Extracting the active ingredient. Answer question 1. Answer question 1.

3. Foxgloves - Digitalis purpurea The leaves are poisonous when eaten by humans and animals. They have a stringyy, bitter taste as a warning. The leaves are poisonous when eaten by humans and animals. They have a stringyy, bitter taste as a warning. Symptoms of poisoning: Symptoms of poisoning: Dizziness Dizziness Vomiting Vomiting Diarrhoea Diarrhoea Hallucinations Hallucinations Heart failure – irregular heart beat rate Heart failure – irregular heart beat rate This effect on heart beat rate meant that it was use in moderation as a remedy for dropsy. This effect on heart beat rate meant that it was use in moderation as a remedy for dropsy.

4. Dropsy (odema) The accumulation of fluid in the bodies tissues when circulation begins to fail. The accumulation of fluid in the bodies tissues when circulation begins to fail. A painful condition that can result in a slow death. A painful condition that can result in a slow death. Caused by heart and kidney problems it results in an increased blood pressure. Caused by heart and kidney problems it results in an increased blood pressure. This means tissue fluid fails to return to the capillaries and so builds up in patients feet, legs and organs. This means tissue fluid fails to return to the capillaries and so builds up in patients feet, legs and organs. Eventually the patient dies by drowning due to fluid accumulation on the lung. Eventually the patient dies by drowning due to fluid accumulation on the lung.

5. William Withering William Withering had heard of foxgloves curative properties for dropsy, but here was no evidence to prove this until he began his investigations into the plants medicinal properties after meeting a wise woman called Mrs Hutton. William Withering had heard of foxgloves curative properties for dropsy, but here was no evidence to prove this until he began his investigations into the plants medicinal properties after meeting a wise woman called Mrs Hutton. Mrs Hutton used foxglove as one ingredient in her “special tea” which seemed to treat the symptoms of dropsy. Mrs Hutton used foxglove as one ingredient in her “special tea” which seemed to treat the symptoms of dropsy. Withering proposed that it was the foxglove which contained the active ingredient. Withering proposed that it was the foxglove which contained the active ingredient. He began making his own version of the tea which proved successful in treating one patient but nearly killed another and so he gave up. He began making his own version of the tea which proved successful in treating one patient but nearly killed another and so he gave up.

6. The story continues… Withering move to Birmingham hospital which saw a great number of dropsy cases and Withering was persuaded to restart his investigations. By determining and recording the side- effects of the digitalis, Withering discovered that the dosage was vitally important in the success of the medicine. Withering move to Birmingham hospital which saw a great number of dropsy cases and Withering was persuaded to restart his investigations. By determining and recording the side- effects of the digitalis, Withering discovered that the dosage was vitally important in the success of the medicine. He would administer the patient with increasing amounts until diarrhoea and vomiting was induced and then reduce the dosage slightly from that point, this enabled him to find the correct dosage for each patient. He would administer the patient with increasing amounts until diarrhoea and vomiting was induced and then reduce the dosage slightly from that point, this enabled him to find the correct dosage for each patient. After 10 years of studying the medicinal properties of the digitals Withering wrote a book. Withering helped to change the face of the medical practice for ever. After 10 years of studying the medicinal properties of the digitals Withering wrote a book. Withering helped to change the face of the medical practice for ever. We now know the active ingredient in the foxglove to be a chemical called digitalin. We now know the active ingredient in the foxglove to be a chemical called digitalin.

7. Task: The work of William Withering Read p223 and answer Question 2 p223. Read p223 and answer Question 2 p223.

8. Drug testing today Potential new drugs now undergo a series of rigorous tests before they can be developed into a new product. Potential new drugs now undergo a series of rigorous tests before they can be developed into a new product. Refer to p225. Refer to p225. ?What five characteristics must a new medicine have? It typically takes 10 to 12 years and costs over 1 billion US dollars. It typically takes 10 to 12 years and costs over 1 billion US dollars.

9. Stages in drug testing Pre-clinical testing Pre-clinical testing animal and laboratory studies on cells and tissues so assess safety and effectiveness of the compound animal and laboratory studies on cells and tissues so assess safety and effectiveness of the compound Clinical trials phase I Clinical trials phase I small group of volunteers normally healthy are given the drug to see if it is absorbed, distributed and excreted by the body by the predicted mechanisms. small group of volunteers normally healthy are given the drug to see if it is absorbed, distributed and excreted by the body by the predicted mechanisms. Clinical trials phase II Clinical trials phase II a small group of people with the disease are treated to look at drugs effectiveness. a small group of people with the disease are treated to look at drugs effectiveness.

10. Drug trialling Clinical trials phase III Clinical trials phase III large group of patients is used split into two groups one given a placebo and the others given the active drug. This is done as a double-blind randomised controlled trail, neither the patients nor the doctors know who has been given what. If statistically significant results come back showing the drug has worked. If all goes well the drug can then be licensed and marketed. large group of patients is used split into two groups one given a placebo and the others given the active drug. This is done as a double-blind randomised controlled trail, neither the patients nor the doctors know who has been given what. If statistically significant results come back showing the drug has worked. If all goes well the drug can then be licensed and marketed. After licensing – trials continue collecting data on the effectiveness and safety. After licensing – trials continue collecting data on the effectiveness and safety.

11. Tasks Read p 224 – 227. Answer the questions on p227. Read p 224 – 227. Answer the questions on p227. ?Why is it important to: ?Randomly assign patients to treatments? ?Have double blind trials? ?What is a placebo? ?How do Withering’s methods compare to the modern day methods? ?In what ways do you think the modern system is safer and more reliable?