Clinical Pharmacology and Renal Disease Flashcards
What is the therapeutic index?
Quantitative measure - relative safety of the drug
Ratio comparison of the does that produces desired effect and which causes toxicity
What does it mean if the drug has a narrow therapeutic index?
Prescribe with care
Ratio is very close (largest non-toxic: minimum effective)
What is the measurement of clearance?
PK measurement
Volume of plasma from which the drug would be totally removed per unit time
What is low clearance equal to?
High systemic exposure
What is renal clearance mainly a function of?
Glomerular filtration
Tubular secretion
Reabsorption
What is filtration dependant on?
Drug must be free in plasma - Vd and protein binding
Kidney perfusion
Health of kidneys - specifically glomerulus
What is total renal clearance?
No secretion/ reabsorption
What is used to measure GFR?
Creatine and insulin
Explain active renal secretion
Mainly occurs in proximal tubule
Can clear drugs too large to filter
Weak acid/base, nucleoside P-glycoprotein transporters
Saturable
What drugs are actively secreted?
B-lactam antibiotics, frusemide, ranitidine, ribavirin and verapamil
What is secretion equal to?
When renal clearance more than GFR
Describe passive tubular reabsorption
Lipid solubility and conc. gradient
Depends on urine flow rate and pH
What can be used to increase clearance of weak acids (aspirin)?
Urinary alkalisation
More alkaline the tubular fluid pH the more likely the drug is ionised so more likely reabsorbed
Explain how volume of drug influences plasma conc.
Drugs with high Vd have longer elimination half life
Drug cleared from plasma redistributes from other tissues. Shift from compartments to plasma - plasma conc. maintained
What is half life equal to?
0.693 x (Vd/clearance)