Pharmacology

Question 1

Define the term “drug receptor” and describe a drug receptor’s major functions

Answer 1

A drug receptor is a cellular macromolecule that interacts with a drug and in doing so initiates a series of biochemical events that result in the characteristic action of the drug
Functions of the receptor:
1. Recognition - the receptor binds a drug or endogenous ligand
2. Transduction - transfer of information

Question 2

Describe in very general terms the major mechanisms of receptor mediated signal transduction

Answer 2

1. G-protein coupled receptors (GPCRs) are expressed by the third largest family of genes and represent the most common drug receptor group. GPCRs regulate “2nd messengers” such as cAMP, cGMP, Ca2+, diacylglycerol (DAG), and inositol trisphosphate (IP3).
2. Modulate ligand-gated ion channels (both cationic & anionic)
3. Intrinsic enzyme activity phosphorylates diverse effector proteins
4. Regulation of gene transcription

Question 3

List the major attributes of drug receptor mediated processes

Answer 3

A. Highly compartmentalized; confers drug specificity

B. Self-limiting (most; excepting intracellular hormone receptors); potential basis for drug tolerance

C. Organized into opposing systems; another potential basis for drug tolerance as well as possible drug-drug interactions.

D. Create opportunities for signal amplification

E. Operate through a relatively small number of 2nd messenger systems; another potential basis for drug-drug interactions (essentially an expansion of attribute C).

Question 4

List some non-receptor modes of drug action

Answer 4

A. Some drugs interact with small molecules or ions, e.g. EDTA, dimercaprol

B. Agents that act by physicochemical mechanisms, e.g. mannitol, MgSO4

C. Drugs that target rapidly dividing cells (e.g., chemotherapeutic agents)

1. Cell cycle specific drugs
2. Cell cycle nonspecific drugs that act on dividing cells as well as cells at rest

Question 5

Define drug occupancy theory in terms of its two underlying assumptions

Answer 5

It assumes that effect is proportional to receptor occupancy and that interaction is monovalent.

Question 6

affinity

Answer 6

Affinity, characterized as 1/KD, describes the ability of a drug to form a complex with a receptor

Question 7

ED50

Answer 7

the dose of drug producing 50% of the maximal response.

Question 8

Differentiate between graded and quantal log dose-response curves in terms of the information they do and do not provide

Answer 8

D. Quantal dose-effect curves provide information on variability in the response of a population (from the observed log-normal distribution) and can be used to judge a drug’s potency relative to that of another drug.

E. Quantal dose-effect curves DO NOT provide information on a drug’s KD value or its maximum efficacy.

Question 9

1. Compare and contrast the major mechanisms responsible for transport of drugs across biological membranes

Answer 9

Passive Diffusion: Does not saturate, Not inhibited by structurally similar analogs, Passive diffusion is largely limited to nonionized lipid soluble drugs

Filtration
1. Bulk flow of fluids through channel

Endocytosis

1. Active bulk flow through the membrane - invagination of membrane engulfs local fluid
2. Nonselective or selective

Facilitated Diffusion

1. Transport of large, water-soluble molecules, including both ionized and nonionized molecules, e.g. glucose and amino acids
2. Movement DOWN a concentration gradient
3. Carrier mediated
4. Selective and inhibited by closely related chemicals
5. Saturates at high substrate concentrations

Active Transport

1. Transport of large, water soluble molecules, and both ionized and nonionized molecules, e.g. secretion of organic acids and bases by renal proximal tubule and by liver into bile
2. Movement UP a concentration gradient
3. Carrier mediated
4. Requires energy; can distinguish primary (ATP hydrolysis) and secondary (coupled to another compound’s electrochemical gradient) mechanisms
5. Selective and inhibited by closely related chemicals
6. Saturates at high substrate concentrations