Unit 4 Pharmacology: Pharmacodynamics Flashcards
Pharmacodynamics is the study of:
Effect site concentration and clinical effect
Pharmacokinetics is the study of:
Drug dose and plasma concentration
Pharmacobiophasics is the study of:
Plasma concentration and effect site concentration
What 4 things affect pharmacokinetics?
Absorption
Distribution
Metabolism
Elimination
What 10 concepts are involved in pharmacokinetics
Volume of distribution Half-lives Metabolism Enzyme induction and inhibition Clearance Steady state Context sensitive half-time Degree of ionization Protein binding Ion trapping
What concept is involved in pharmacobiophasics?
Rate constants between the plasma and effect site
What 11 concepts are involved in pharmacodynamics?
Potency Efficacy Dose response curve Agonist Antagonist Partial agonist Inverse agonist ED50 LD50 Therapeutic index Stereochemistry
On the dose response curve the x-axis represent what?
Potency
Define potency
The dose required to achieve a given clinical effect
What 5 things is potency affected by?
Absorption Distribution Metabolism Elimination Receptor affinity
What is ED50? ED90?
They are measures of potency.
ED50: the dose required to achieve a given effect in 50% of the population
ED90: dose required to achieve given effect in 90% of population
What does it mean if the dose response curve has a left shift?
Increased affinity for receptor -> higher potency -> lower dose required
What does it mean if the dose response curve has a right shift?
Decreased affinity for receptor -> lower potency -> higher dose required
What is efficacy? Where is it on the dose response curve?
A measure of the intrinsic ability of a drug to elicit a given clinical effect.
The height of the plateau on the y-axis represents efficacy
What does the slope represent on the dose response curve? Steeper means what?
How many receptors must be occupied to elicit a clinical effect.
A steep slope implies that most of the receptors must be occupied before we observe the clinical response.
What is individual variability? What explain it?
A particular dose may provide excellent clinical effect in one patient, but not another.
It is explained by differences in pharmacokinetics and pharmacodynamics in patients
What is a agonist?
Binds to the receptor and turns on a specific cellular response
What does an agonist mimic?
An endogenous ligand
Continuous administration of an agonist may cause _______ of the target receptors.
Down-regulation - a decrease in the number of receptors making it less sensitive to the drug
What is a partial agonist?
Binds to a receptor but is only capable of partially turning on a cellular response. It is less efficacious than a full agonist.
What is another name for a partial agonist?
Agonist-antagonist
What unique effect occurs with the use of an agonist AND partial agonist?
The partial agonist can block the effects of an agonist by competing for biding sites
What is an antagonist?
It blocks the receptor from anything that could turn on a cellular response.
Which way is the dose response curve shifted with use of a competitive antagonist?
It is shifted right for the agonist. Giving more of the agonist can overcome the antagonist.
How does a non competitive antagonist bond? Can it’s effects be overcome?
Permanently, usually through covalent bonds.
The effects of a noncompetitve antagonist can only be reversed by producing new receptors.
Which way does a noncompetitive antagonist shift the dose response curve?
It shifts it DOWN, so that it resembles a partial agonist.
What is an inverse agonist?
Binds to the receptor and causes an opposite effect to that of a full agonist.
An inverse agonist has ___ efficacy.
Negative
Define addition:
Effect of 2 drugs given at the same time are added to each other
1 + 1 = 2
Define synergism:
Effects of 2 drugs given at the same time is greater than the sum of their individual effects.
1 + 1 = 3
Define potentiation:
Effect of one drug is enhanced by a drug that has no effect of its own.
1 + 0 = 3
Define antagonism:
Simultaneous administration of one drug cancels out the effect of a second drug.
1 + 1 = 0
Define ED50:
What is it a measure of?
Effective Dose 50: the dose that produces the expected clinical response in 50% of the population.
It is a measure of potency.
Define LD50:
Lethal Dose 50: the dose that will produce death in 50% of the population.
Define Therapeutic Index:
Equation:
A measure of drug safety. It is the ratio of the LD50 to the ED50
Therapeutic index = LD50 / ED50
What is stereochemistry?
The study of the 3-dimensional structure of molecules
What is chirality?
A division of stereochemistry that deals with molecules that have a center of 3-D asymmetry
What is an enantiomer?
Chiral molecules that are non-superimposable mirror images of one another
How are enantiomers distinguished from one another?
By the direction in which they rotate when exposed to polarized light. Dextrorotatory enantiomer (+) rotates clockwise Levorotatory enantiomer (-) rotates counterclockwise
What letters are used to describe the orientation of a specific stereocenter within a molecule?
R and S
D&L and R&S
What is a racemic mixture?
Mixture that contains 2 enantiomers in equal amounts
How common are enantiomers? Racemic mixtures?
About 1/3 of the dugs we administer are enantiomers, and just about all of them are racemic mixtures
Examples of enantiomers
ketamine Thiopental Methohexital Isoflurane Desflurane Mepivacaine Prilocaine Bupivacaine Morphine Methadone Ibuprofen Ketoralac
