VPT 311: General and Systemic Veterinary Pharmacology (2+1)

DRUG SCREENING

• Drug screening refers to a sequence of experiments and characterization using a variety of biologic assays at the molecular, cellular, organ system, and whole animal levels to define the activity and selectivity of the drug. For example, anti- infective drugs may be tested against a variety of infectious organisms some of which are resistant to standard agents.
• The molecule will also be studied for a broad array of other actions to establish the mechanism of action and selectivity of the drug. This will reveal any suspected and unsuspected toxic effects.
• Occasionally, an unexpected therapeutic action is discovered by chance.. It becomes very important to develop suitable preclinical in vitro and in vivo models to predict drug action.
• During drug screening, studies are performed to define the pharmacologic profile of the drug at the molecular, cellular, system, organ, and organism levels.
• At the molecular level the drug would be tested for receptor binding activity to target recptors, metabolizing enzymes etc.
• At the cellular level, the drug would be studied to determine whether it stimulates or inhibits the cellular function.
• At the organ level the pharmacologic activity and selectivity for the organ studied would be studied. Isolated organ studies esp. smooth muscles and other in vitro preparations can be used.
• Whole animal studies are generally necessary to determine the effect of the drug on organ systems and disease models. Cardiovascular and renal function studies of all new drugs are generally first performed in normal animals.
• Where appropriate, studies on disease models would be performed. Evidence would be collected on duration of action and efficacy following oral and parenteral administration.
• If the agent possessed useful activity, it would be further studied for possible adverse effects on other major organ systems, including the respiratory, gastrointestinal, endocrine, and central nervous systems.
• These studies might suggest the need for further chemical modification to achieve more desirable pharmacokinetic or pharmacodynamic properties. For example, oral administration studies might show that the drug was poorly absorbed or rapidly metabolized in the liver; modification to improve bioavailability might be indicated.
• If the drug was to be administered long-term, an assessment of tolerance development would be made. For drugs related to or having mechanisms of action similar to those known to cause physical dependence, abuse potential would also be studied. For each major action found, a pharmacologic mechanism would be sought.
• The outcome of this screening procedure is called a lead compound, i.e., a leading candidate for a successful new drug.