1. The first stage in the pharmacological screening of drug candidates, so called in vitro testing, is testing in animal tissue.

Two of these which are normally carried out are described as (i) Radioligand Binding

and (ii) Isolated Tissue testing.

For both of these methods, describe in detail the technique, what information can be derived from each and individual strengths and weaknesses of the testing.

2.    Answer ALL of the following parts.

Testing potential new drugs in live animals, so called in vivo testing, continues to be necessary in the development of safe and effective new treatments.

(a) Although earlier in vitro testing provides crucial data in drug development, explain why such testing is not sufficient for the drug to be used in man and why in vivo testing must be carried out (it is not expected that a review of invitro methods is discussed here).

(b) Approximately 80% of animals used in these experiments are rats and mice.

Explain the advantages and disadvantages of rodent use.

(c) Explain the term animal model (or disease model). Describe how conditions mimicking human disease can be induced in animals, giving two examples of human diseases for each model.

(d) Describe two methods by which analgesic drugs can be tested in animals.

Make particular reference to the control of the experiment to ensure that chance findings will not obscure the results, and the measures used to effectively compare different results and ensure that the results are statistically sound.

(a)    In vivo testing of a potential drug candidate in whole animals is mandatory in the development of a drug in order to examine its metabolism, safety and efficacy before progressing to studies in man.

There are three stages in the evaluation of the safety of a drug in animals and these are termed, acute, sub-acute and chronic toxicity tests. Define and describe each of these in terms of the length and type of dosing, the techniques which are used and the information which is gained. Describe at what stage in this process, given no overt signs of toxicity, the drug can begin to be tested in humans.

(b) The first exposure of the drug in man is termed Phase I testing. In this phase, describe in whom the testing is carried out and what is measured.