College of Medicine and Health Sciences: St. Lucia

Neuropharmacology

Unit I Introduction to Pharmacology

Objectives

Reading Assignments

            Katzung: Chapters 1, 2, 3, 4 and 5.

            Mycek: Chapters 1 and 2.

Introduction to Pharmacology

1.      Define each of the following terms: pharmacology, drug, toxicology, drug receptor, pharmacokinetics, and pharmacodynamics.

2.      Recognize the basic nature of drugs.

3.      Compare and contrast aqueous and lipid diffusion of drugs.

4.      Explain Fick’s law.

5.      Describe the basis of aqueous and lipid solubility for weak acids and bases.

Pharmacodynamics

1. 1.            Explain what determines the quantitative reaction between dose or concentration of a drug and the pharmacologic effect.
2. 2.            Describe how receptors are responsible for selectivity of drug action and for the action of an antagonist?
3. 3.            Describe the concentration effect curve and compare it to the Michaelis Menton curve for an enzyme catalyzed biochemical reaction.
4. 4.            Describe a “partial” agonist and compare and contrast it with a “full” antagonist.
5. 5.            Compare and contrast competitive and irreversible (non- competitive) antagonists.
6. 6.            Describe other mechanisms of drug antagonism.
7. 7.            List the five basic mechanisms transmembrane signaling.
8. 8.            Describe the mechanism of action of the intracellular receptor of lipid soluble agents using the mechanism of action of glucocorticoid as a model.
9. 9.            Describe the mechanism of action of the ligand regulated transmembrane enzyme using the mechanism of action of epidermal growth factor (EGF) as a model.
10. 10.        Describe the mechanism of action of the cytokine receptor.
11. 11.        Describe the mechanism of action of the ligand gated channel receptor.
12. 12.        Explain the role of G protein and second messengers with emphasis on the serpentine receptor.
13. 13.        Explain the phenomenon of receptor regulation.
14. 14.        Describe the possible fates of internalized receptor.
15. 15.        Describe the role to each of the following second messengers: cAMP, calcium and phosphoinositide, and cGMP.
16. 16.        Distinguish between the potency and the efficacy of a drug.
17. 17.        Define each of the following terms: maximum efficacy, EC50, ED50.
18. 18.        Explain the significance of dose - response curves.
19. 19.        Define each of the following terms: TD50, LD50, and therapeutic index.

         Pharmacokinetics

1. 1.            Compare and contrast the following methods of drug administration: intravenous, oral, intramuscular, subcutaneous, buccal, lingual, rectal, inhalation, topical, and transdermal.
2. 2.            Describe the determinants of drug distribution.
3. 3.            Define volume of distribution of a drug.
4. 4.            Recognize the various body compartments into which a drug can distribute.
5. 5.            Compare and contrast first order kinetics and second order kinetics of drug elimination.
6. 6.            Define drug clearance and distinguish between organ specific types of clearance.
7. 7.            Define half life.
8. 8.            Define steady state concentration of a drug and explain how it is maintained.
9. 9.            Define ‘maintenance dose” and explain the various factors that must be taken into consideration in determining it.
10. 10.        Define “loading dose”.
11. 11.        Given the appropriate pharmacokinetic and pharmacodynamic parameters, calculate maintenance dose.
12. 12.        Given the appropriate pharmacokinetic and pharmacodynamic parameters, calculate loading dose.
13. 13.        Explain the basic strategy involved in maintaining target concentration of a drug using multiple dosing schedules.

Biotranformation

1. 1.            Explain the critical role of biotransformation in terminating the biological activity of a drug.
2. 2.            Explain the role of biotransformation in the disposition of a drug.
3. 3.            Describe where most drug biotransformation occurs and relate this to the first pass effect.
4. 4.            Describe Phase I biotransformation and the role of the microsomal mixed function oxidase system.
5. 5.            Explain the role of enzyme induction in Phase I biotransformation.
6. 6.            Explain how some drugs inhibit phase I biotransformation.
7. 7.            Describe Phase II reactions of biotransformation and its role in the excretion of drugs.
8. 8.            Explain the consequences of metabolism of drugs into toxic substances.
9. 9.            Describe the role of each of the following clinically relevant variables in drug biotransformation: individual variation, genetic factors, diet, environmental factors, age, and gender.
10. 10.        Describe drug-drug interactions that may complicate biotransformation.
11. 11.        Explain how presence of a disease state may affect drug metabolism.

Drug Development and Testing

• 1.            List the ways that new drug candidates are developed.
• 2.            Define each of the following terms: drug screening, pharmacological profile, and lead compound.
• 3.            Explain the process of pre-clinical safety and toxicity testing of a drug including each of the following: acute toxicity, subacute toxicity, chronic toxicity, effect on reproductive performance, carcinogenic potential, mutagenic potential, and investigative toxicity.
• 4.            Explain the pitfalls associated with human clinical trials.
• 5.            Relate the major legislative acts and federal agencies that control drugs in the U.S,
• 6.            Describe in detail the three phases of clinical trials that each drug must go through prior to being cleared for use.
• 7.            Explain the ongoing evaluations (Phase 4) that a drug receives after approval.
• 8.            Define “orphan drug” and explain the significance of the Orphan Drug Act.
• 9.            Describe the elements used to evaluate a clinical drug trial.