Pharmacokinetics Flashcards
What is pharmacokinetics?
What the body does to the drug (ADME)
What is pharmacodynamics?
What the drug does to the body
What is the volume of distribution?
V is a measure of drug concentration in plasma
What are the important plasma proteins?
Albumin: carries acidic and neutral drugs
Alpha-1-acid glycoprotein (orosomucoid): Carries basic drugs, steroids, and protease inhibitors
What type of drugs are likely to need a loading dose?
Drugs with long half lives
What are the two routes of elimination?
Unchanged via the kidneys
Metabolised via the liver
What factors affect clearance?
Body weight Body surface area Cardiac output Drug-drug interactions Extraction ratio Genetics Hepatic and renal function Plasma protein binding
What is the elimination rate constant
K is the fraction of drug eliminated per unit time
The amount eliminated changes but the fraction is constant!
How many half lives are needed to reach steady state?
4-5 half lives
Dose independent pharmacokinetics
First order
Independent of C and dose
Half life, clearance, volume of distribution and K are all constant
Linear relationship
Dose dependent pharmacokinetics
Non linear Zero order Dependent on C and dose Half life, CL, and V depend on C or A One or more ADME processes are saturable
What is the normal GFR for an adult?
100ml/min
How is dose adjusted in renal impairment?
Croft-Gault equation
Define absorption
Process by which the unchanged drug moves from the site of administration to the site of measurement within the body
What factors affect drug distribution?
Body tissue characteristics Disease state Drug lipid solubility Physiological pH in various regions Extent of protein binding
What factors can decrease the concentration of Albumin?
RF Hepatic cirrhosis Burns Stress/trauma Pregnancy
What factors increase Alpha-1-glycoprotein?
RF Arthritis Surgery MI Stress/trauma
When can TDM be used?
High probability of therapeutic failure : low therapeutic index, pharmacokinetic variability, genetic factors, co-morbidities etc
When problems arise : non-compliance, unusually rapid elimination, pharmacodynamic resistance to drug, to confirm toxicity
No easily measurable physiological parameters
Give examples of drugs needing TDM
Gentamicin Vancomycin Digoxin Theophylline Phenytoin
Equation for loading dose
LD = (desiredC x V) / (S x F)
Equation for Volume of Distribution
V = Dose / InitialC
Equation for Rate of Elimination
CL x C = K x A
Equation for Total Body Clearance
CLmetabolic + CLrenal
Equation for Clearance
CL = K x V = (SFD) / Css x Dose Interval
Equation for Concentration at time t
Ct = InitialC x e^(-kt)
How does protein binding affect drug activity?
The unbound drug is active
Highly bound drugs are likely to have a narrow therapeutic index
