Pharmacokinetics Flashcards
What factors influence pharmacokinetics
Bioavailability
Half-life
Drug elimination
Intra-subject variability
Drug-drug interactions
What is bioavailability and what affects it
Bioavailability - measure of drug absorption into a body compartment where it can be used
All non-IV routes are referenced as a fraction of IV
Bioavailability is affected by:
- Absorption - affected by formulation, age, food, vomiting, malabsorption
- First pass metabolism
What factors influence drug distribution
Blood flow and capillary structures - highly or poorly vascularised, endothelial structure, slit junctions
Lipophilicity and hydrophilicity - lipophilic drugs readily cross cell membranes
Protein binding
Volume of distribution
How does drug-protein binding affect distribution
Drugs only able to interact and cause a response if in free form
Displacement of a drug from a binding site can result in protein binding drug interaction
Drug-protein binding is important if: drug highly protein bound, narrow therapeutic index, low Vd
If a second drug displaces a first drug from binding proteins, the free concentration of the first drug increases meaning there is more drug to elicit a response
What is volume of distribution and what equation is used to calculate it
The volume of fluid required to contain the total amount of drug in the body at the same concentration as in the plasma
Smaller Vd suggests drug is confined to the plasma
Larger apparent Vd suggests drug is distributed throughout tissue
Vd ~ Dose/[Drug]plasma
t1/2 is proportional to Vd
Name some factors which can affect CYP450s
Endogenous and exogenous compounds inducing or inhibiting CYPs
Age
Hepatic disease
Blood flow
Alcohol
Cigarette smoking
Where are the routes of drug excretion
Kidneys
Pulmonary
Biliary
Faecal sweat
Genital secretions
Savlia
Breast milk
What factors affect elimination through the kidneys
If drug/molecule is particularly water soluble
GFR and protein binding
Competition for transporters
Lipid solubility
pH
Flow rate
What is half-life and what is it effected by
Half-life is the time in which the concentration of a drug in the plasma decreases by half
It is inversely proportional to clearance
Half-life is affected by: age (muscle mass), pathological fluid space, adipose tissue among others
What will cause the half-life of a drug to become increased
Clearance is compromised
Renal or hepatic stenosis
Haemorrhage
Reduced metabolism
Reduced plasma drug extraction
Drug-drug interactions
What is 1st order kinetics and what is zero order kinetics
1st order/linear kinetics - rate of elimination is proportional to [drug]
Zero order kinetics - rate of elimination is constant
Why must drugs be monitored
Pharmacokinetics
Zero order kinetics - can occur if drug dose is too high
Narrow therapeutic window
Long half-life of some drugs
Reported or expected toxic effects
Is the therapeutic effect seen the response expected/desired
What is the difference between pharmacokinetics and pharmacodynamics
Pharmacokinetics is how the drug is handled by the body
Pharmacodynamics is the required pharmacological effect. The effects of the drug on the body
When is therapeutic benefit optimal and how long does this take to occur
Therapeutic effect is optimal once [drug] is at the steady state plasma concentration
At this point the overall intake of the drug is in dynamic equilibrium with its elimination
CpSS is usually reached after about 5 half-lives
If a drug’s CpSS takes a long time to come into affect, what can be done?
Can give a loading dose to get the drug into the therapeutic range
Or can give another drug that takes a short time to come into affect while you give the drug that takes a long time to come into affect
