PK, PD, Genomics Flashcards
Sources of variability drug exposure
renal/hepatic function gastric ph drug-drug interactions drug metabolism polymorphisms medication compliance
sources of variability drug response
placebo effect
drug receptor or enzyme polymorphisms
tolerance, tacyphylaxis
gender, race,
Variables Determining Drug Response
affinity for site of action (phamacodynamics) x Drug concentration at site of action (pharmacokinetics) x underlying biology of patient (genetics, age, disease, enviornment)
Pharmacodynamics
what the drug does to the body
Pharmacokinetics
what the body does to the drug
PD concepts
• Dose response curve (potency, slope, efficacy, variability)
• Receptor mechanisms (agonist, antagonist, partial agonist)
• Therapeutic index (median effective dose “ED50”, median
lethal dose “LD50”
Dose-Response Cure
• Helps illustrate the relationship between the dose administered and the
degree of response it produces
• Usually an “S” shape when plot log dose vs intensity of effect
• Can help estimate response and safety, or compare profiles of drugs
Many (not all!) drugs exert
t their pharmacologic actions via receptormediated mechanisms
Agonist =
substance that interacts with a receptor and produces an
effect
- Indirect (Do not bind directly to a receptor. Affect formation,
release, inactivation, or reuptake of a neurotransmitter.)
- Direct
Antagonist =
substance that interacts with a receptor, but has no action
of its own. Prevents agonists, such as neurotransmitters, from acting.
Agonist are not
as perfect as a fit. It will interact with a receptor but not all sub types
Most perfect fit is the
hormone or neurotransmitter these interact with all subtypes.
Neurotransmitter Dopamine (DA) – a
D2 agonist
Aripiprazole (APZ) – a
D2 partial agonist
First Generation Antipsychotic (FGA) – a
D2 antagonist
Overall effect of a
partial agonist may be as a
“functional” agonist or “functional” antagonist depending on surrounding levels of naturally occurring neurotransmitter
increase in dopamine is related to
positive symptoms