W7: Pharmalcology Flashcards
(51 cards)
Large/narrow therapeutic index (TI) is safe (what is TI?)
Large (big gap between effectiveness and toxicity)
TI is ratio: TD50/ED50
Define pharmacokinetics and name what ADME stands for.
what body does to drug;
ADME – absorption, distribution, metabolism, excretion
What is quantal dose-response (d-r) curve? Describe its components:
X and Y axis
ED50
TD50
LD50
graph used to quantify quantal response to a drug (quantal - all or none; yes or no)
X - dosage each person took
Y - % of people who responded to the drug
Median effective dose (ED50) - dosage at which 50% responded favorably
Median toxic dose (TD50) - toxic dosage for 50% of participants
Median lethal dose (LD50) - dosage at which 50% found lethal
What is graded dose-response (d-r) curve ?
X and Y axis?
What are 2 important information you can get?
D-R curve is a graphical representation between quantity of drug and a graded biological effect
X - drug concentration
Y - % maximal response
efficacy and potency
Magnitude of a response is called __.
Efficacy
EC50 is used to compare the potency/efficacy of two drugs.
Potency
Therapeutic window is utilized in quantal/graded dose-response to gauge the effective plasma drug concentration range.
graded
competitive/non-competitive antagonist reduces the EC50 (efficacy/potency) of the original drug.
competitive, potency
Non-competitive antagonists reduces the efficacy/potency of the original drug which can/cannot be overcome with increased [original drug].
efficacy, cannot
Define concept of spare receptors. How was this discovered?
Idea that when maximal response is reached, not all receptors are activated
Experiment: When agonist + irreversible antagonist are added, maximal response was still achieved.
Conclusion: Max response can be achieved with less than 100% of receptors (because spare receptors are present)
difference between EC50 and Kd?
EC50 describes potency of the drug action.
Kd describes the binding affinity of drug/ligand to receptor.
What is the difference between occupancy theory and the two state receptor model?
occupancy: one ligand, one receptor (receptor inactive if no ligand)
two state: presence of constitutively active receptor and inactive receptor that needs to be bound to a ligand (receptor can be spontaneously active in absence of ligand)
Draw a dose x drug activity graph indicating the terms below:
constitutive activity full agonist partial agonist antagonist inverse agonist
constitutive activity - activity (y axis) > 0 (all graphs start here)
full agonist - sigmoidal, max activity
partial agonist - sigmoidal, less than max activity
*antagonist = constitutive
(two state receptor model)
inverse agonist - decrease to zero from constitutive
3 targets of drug
- receptor (potency, efficacy)
- enzyme (affinity, efficacy)
- transporters (blockers)
Two factors that influence absorption of drug into plasma are __ and __, which both determine the __ of drug.
route of administration, membrane penetration;
bioavailability
Differentiate therapeutic index and therapeutic window and their parameters (X vs. Y).
TI: range of safe dose for general population
(X - dose; Y - % of people who responded to the drug)
TW: - range of doses that produce a therapeutic response without unacceptable side effects
(X - time; Y - PLASMA drug concentration)
Calculation for oral bioavailability (%)
AUC (area under the curve)
iv does is 100% bioavailability (plasma absorption)
oral dose AUC/ iv dose AUC
Enteral/Parenteral administration of drug means via the GI tract.
Enteral
__ is the disadvantage of oral administration of drug, subjecting drug to degradation/alteration in __ and __ prior to reaching the systemic circulation (blood).
First Pass Effect;
liver and intestine
Trajectory: oral –> GI –> vasculature –> portal vein –> liver (metabolism) –> hepatic vein –> systemic circulation (absorption)
3 ways drug enters cell/tissue (distribution)
- Diffusion (partition coefficient)
- Carrier-mediated transport
- Endocytosis
What determines the diffusion of drug into cell/tissue?
Jx = Px A (Co – Ci)
Px - partition coefficient
A - area of membrane
(Co – Ci) - concentration gradient
__ is measure of solubility of drug in lipid.
Partition coefficient
[Drug] lipid phase / [Drug] aqueous phase
Drug distribution to tissue is influenced by 3 factors (list them), determining the __.
ion trapping, protein binding, tissue barrier;
volume of distribution
Drug-protein binding in the plasma functions as a
__ of drugs in the circulation. The fraction of bound (drug-protein complex) to total drugs in plasma remains constant.
reservoir
