Principles of Drug Action I & II

What is pharmacodynamics?

physiological effects of drugs; what the drug does to the body

What is pharmacokinetics?

drug absorption, distribution, binding, metabolism, elimination; what the body does to the drug

What is clinical pharmacology?

ensuring patients receive the correct drug at the right dose for an appropriate duration

What is the role of the clinical pharmacologist?

supervision and surveillance of a drug response, modifying and refining the dose regimen as deemed necessary

What is a dose?

amount of drug required to elicit a biological response

What is a dose-response relationship?

the intensity of the response elicited by a drug is proportional to the dose administered; sigmoidal

What is potency?

dose of a drug required to elicit a biological effect of a given intensity

How do we denote the clinical effectiveness of a drug?

potency and efficacy

What is an effective dose 50? (ED₅₀)

dose required to elicit 50% of the maximal effect or elicits a response in 50% of the population

What is efficacy?

the ability of the drug to elicit an effect

What is the limit of the dose-response curve on the response (y) axis?

efficacy

When is a drug considered potent?

if the dose required to elicit an effect is small

What is the margin of safety or therapeutic index?

dosage range between that which produces a lethal effect and the dose producing a pharmacologic effect

What is the equation for therapeutic index?

LD50/ED50 (lethal dose 50 over effective dose 50) OR TD50/ED50 (toxic dose)

What are the two types of biologic responses?

receptor mediated and non-receptor mediated effects

What is a ligand-gated ion channel?

membrane proteins with a structure similar to other ion channels; ligand binding (receptor) site (usually extracellular) that induces channel opening

What is an example of something that uses ligand-gated ion channels?

fast neurotransmitters (glutamate)

What is a G-protein coupled receptor?

7-transmembrane spanning receptors coupled to an intracellular effector system via a G protein; utilize a 2nd messenger system

What is an adrenergic receptor?

activation and inhibition of the same signaling pathway by two differing G proteins

What is a kinase-linked receptor? (Receptor tyrosine kinase)

membrane receptor responding mainly to protein mediators; extracellular ligand binding domain with enzymic (protein kinase) intracellular domain linked by single transmembrane helix

Tyrosine kinases are typically over-stimulated in cancers therefore what can be used to treat said cancers?

tyrosine kinase inhibitors (TKI) reduce cancer cell growth and spread

What is a nuclear receptor?

located in cytosol to regulate gene transcription, once activated moves to the nucleus to elicit a change in gene expression

What are other types of drug targets?

voltage-gated ion channels, enzymes, transporters, and non-cellular actions

What are non-cellular actions?

physical effects, chemical reactions, physicochemical mechanisms, and modification of the composition of body fluids

What is covalent binding?

binding in which electrons are shared

What is noncovalent binding?

reversible; ionic, hydrogen bonding, van der Waals attraction, and hydrophobic effect

What is ionic binding?

electrostatic attraction between charged ions

What is hydrogen bonding?

force of attraction between hydrogen and electronegative atoms

What is van der Waals attraction?

force of attraction between two dispersed electron clouds

What is a hydrophobic effect?

rearrangement of nonpolar and polar groups in a molecule; ex: nonpolar groups forced closer together in water

What is the weakest force of attraction between atoms?

van der Waals attraction

Drug response is _______ to percentage of receptors occupied.

proportional

What is an additive reponse?

response of treatment with two drugs A and B = response A + response B; two drugs act through the same or similar mechanisms biochemically

What is a synergistic response?

response of treatment with two drugs A and B is greater than response A + response B; two drugs like act through differing mechanisms that interact to elicit the same physiologic response

What is a less than additive response?

response of treatment with two drugs A and B is less that response A + response B; the two drugs likely antagonize one another

What is an agonist?

a drug with affinity and efficacy

What is an antagonist?

a drug that has affinity for a receptor but elicits no effect; this drug has affinity but no efficacy

What is a competitive antagonist?

competes with the agonist for the same receptor

What is a noncompetitive antagonist?

may bind to the same receptor or an associated molecule

How can a competitive antagonist be overcome?

increasing agonist concentration

How does a competitive antagonist effect the dose-response curve?

displaces to the right but does not alter maximal efficacy

How can a noncompetitive antagonist be overcome?

cannot be overcome by increasing agonist concentration

How does a noncompetitive antagonist effect the dose-response curve?

displaces to the right; maximal efficacy is decreased which prevents the agonist at any concentration from reaching maximal efficacy