med recon, formulation science, PKPD Flashcards
Order status and their meaning
1: Continue (correct)
2: Withheld, with documented reasons
3: Changed, with documented reasons
4: Changed, with no documented reasons
5: Not clerked, with no documented reasons
What is apparent volume of distribution?
Reflects how much the drug distributes into the tissues (fat, proteins, bone) rather than staying in the bloodstream
Low Vd (< 0.1 L/kg): Drug stays mostly in the plasma (e.g., warfarin, which is highly protein-bound).
Moderate Vd (~0.2–0.7 L/kg): Drug distributes into extracellular fluid (e.g., aminoglycosides like gentamicin).
High Vd (> 1 L/kg): Drug extensively distributes into tissues, often fat-soluble (e.g., propranolol, digoxin)
What are the clinical implications of a drug with high Vd vs low Vd
Drugs with a high Vd require larger doses to achieve therapeutic plasma levels.
Drugs with a low Vd are more affected by plasma protein binding (e.g., low albumin can increase the free active drug concentration).
What is enterohepatic cycling
1) Drug metabolised by the liver
2) Metabolite excreted into bile, which is released into the small intestine
3) Gut bacteria converts metabolite back into parent drug via B-glucuronidase
4) Drug is absorbed back into small intestine, exerting its therapeutic action again
What is oral bioavailability?
Fraction of oral drug that reaches systemic circulation after first pass metabolism
3 checkpoints
1) Fraction that enters the intestines
2) Fraction that passes through the intestines, into the hepatic portal vein
3) Fraction that escapes hepatic metabolism
What are primary PK parameters
4 primary PK parameters
Primary variables because directly affected by changes in physiologic variables
Bioavailability
(CLH) Hepatic clearance
(CLR) Renal clearance
(V) Volume of distribution
What are secondary PK parameters
What are the 2 types of secondary PK parameters, and what are they
Parameters that depend on primary PK parameters
1) Secondary PK parameters that depend on primary parameters only
- Elimination half life (t1/2 = Ln2 / k), where k is the elimination rate constant
- k (elimination rate constant)
k = CL / V (volume of distribution)
2) Parameters that depend on primary parameters and dose
AUC (area under curve)
= Dose / CL
Cmax
= Dose / Volume of distribution
What is extraction ratio
% or fraction of drug removed from blood or plasma, eg. 10%
High E (~1)
Means Flow limited or Perfusion limited Clearance = Dependent / limited by blood flow
The more blood flow reach kidney = the more drug is lost
Low E (~ 0.1)
Means Capacity limited Clearance
Drug is not extracted efficiently by organ
Limiting factor is the extraction process, becomes independent of blood flow
What is the difference between Therapeutic Index VS Therapeutic window
Therapeutic index is the ratio between the effective dose and the lethal dose of the drug
1) Gives us a rough estimate of how easy it is to overdose a drug
2) Not useful in clinical setting
Therapeutic window is the range of concentration that will produce therapeutic effect with minimal adverse effect
1) useful in clinical setting, can be used as target serum concentration of drug
What is the 2 compartment model made up of
Central compartment
More well perfused organs
Heart, brain, liver, kidneys, lungs
Peripheral compartment
Less perfused tissues
Muscle, Fat, Bone
How does the serum concentration of drug decrease in a 2 compartment model?
What is the clinical application of a 2 compartment model
Drug decreases fast initially
- Due to 1) Elimination + 2) Distribution to peripheral compartment
Then decreases slowly
- Elimination of drug mainly from peripheral compartment
Clinical application
- If draw samples from the initial phase, may think that drug is eliminated too quickly -> Will give too high dose next and overdose patient
Legal requirement of prescription
Name, address, signature of prescriber
Date of prescription
Total amount of drug, dose,
Number of repeats
“For dental treatment only” if dental prescription
