Individual Factors

Vocabulary flashcards covering the key factors altering drug response, tolerances, drug interactions, and precision medicine as described in the lecture notes.

Biological factors modifying drug response

age, body weight, gender, race, environment, time of administration, psych and emotional factors, genetic factors, idiosyncrasies, metabolic and pathologic disturbances, route of administration

Repeated administration of a drug modifying response

tolerance and tachyphylaxis

Concurrent administration of 2 drugs modifying response

synergism and antagonism

Idiosyncrasies

response to a drug in a different and unpredictable way, very rare; unknown etiology; classified as type B adverse drug reactions

Psychological Factors

some individuals may respond to administration of placebos

Genetic Factors

inherited differences in coagulation factors enhance DVT risk in women using oral contraceptives

Type B Adverse Reactions

malignant hyperthermia and neuroleptic malignant syndrome (NMS)

Malignant Hyperthermia

occurs with halothane and succinylcholine

Neuroleptic Malignant Syndrome (LMS)

occurs with haloperidol and other antipsychotics

Low Acidity Impact

decrease iron and aspirin absorption

Liver Disease Impact

increase bioavailability of drugs with high first pass metabolism

Renal Disease Impact

decrease excretion of drugs (like aminoglycosides), causing toxic effects

Diarrhea/Vomiting Impact

orally given drugs are ineffective

Tolerance

A slowly developing decrease in response to a drug with long-term use, often requiring higher doses; does not develop equally to all effects of a drugs; may be innate or natural, acquired, or cross tolerance

shifts dose response curve right, maximal response may be lower

Innate/Natural Tolerance

genetically determined lack of sensitivity to a drug; seen first time drug is given

example: Chinese tolerant to purgative action of castor oil

Acquired Tolerance

caused by repeated use of drug in an individual who was initially responsive; can be pharmacokinetic, pharmacodynamic, or acute/tachyphylaxis

Tachyphylaxis

Rapid decrease in response after repeated dosing over a short period; results from depletion of the intermediate required for response; maximum response reduced

example: indirectly acting sympathomimetics like epinephrine, amphetamine, and tyramine

Cross Tolerance

Tolerance that develops to other drugs within the same class

example: individuals tolerant to morphine may be tolerant to heroin and other opioids

Pharmacokinetic Tolerance

acquired tolerance; occurs when drug reduces absorption or enhances metabolism (microsomal enzyme induction) of its own or other co-administered drugs

example: alcohol and barbiturates

Pharmacodynamic Tolerance

acquired tolerance; results due to come type of adaptive changes that take place in the system after repeated drug administration

example: drug induced changes in receptor density

Tachyphylaxis vs Tolerance

tachyphylaxis: rarely seen in clinical practice, develops faster, original effect cannot be obtained by increasing dose

tolerance: seen in clinical practice, develops slowly from long term administration, original effect can be obtained by increasing dose

Effects of Concurrent Drug Administration

summation or addition, potentiation, synergism, antagonism

Potentiation

occurs when concurrent administration of potentiating agent increases potency or efficacy of agonist; potentiating agent does not produce response of its own

Synergism

interaction between drugs that each have an effect of its own; when drugs are given concurrently, combined effect is greater that sum of individual effects

example: levodopa and carbidopa in Parkinson’s treatment

Ways to Alter Receptors

receptor desensitization, receptor down regulation, receptor up regulation and supersensitivity

Desensitization

gradual reduction in receptor mediated response to drugs or hormones over second or minutes after reaching an initial high; usually reversible; self defense mechanism to avoid overstimulation of cells

Down-Regulation

Prolonged agonist exposure leads to fewer receptors on the cell surface; results from internalization or endocytosis of receptors

example: diminished responsiveness to albuterol over time in asthmatics

Up-Regulation

Prolonged antagonist exposure increases receptor numbers, increasing sensitivity; results from externalization of receptors on cell surface

Up-Regulation/Supersensitivity Examples

thyrotoxicosis leads to up-regulation and supersensitization of B1 adrenoceptors on the heart, causing tachycardia and palpitations

rebound hypertension after abrupt discontinuation of antihypertensive drugs, clonidine, and beta blockers

Summation/Addition

Combined effect equals the algebraic sum of individual drug effects.