Drug Excretion Flashcards
What are the primary routes by which drugs are excreted from the body?
Renal and hepatic are the primary routes. Secondary includes pulmonary, salivary and mammary. Secondary routes are quantitatively insignificant but can have a clinical role in assessment of drug exposure.
What are the key processes and anatomical location involved in renal excretion?
Filtration (glomerulus) , active tubular secretion (PCT) and tubular reabsorption (Loop of Henle) are the most important mechanisms. With rare exception, biotransformation in the liver is quantitatively insignificant.
How do the physicochemical properties of a drug influence its filtration, secretion, and reabsorption by the kidney?
Glomerular filtration is largely influences by molecular size and plasma protein.
Drugs that undergo active tubular secretion exhibit saturation at high concentration and are subject to competitive interactions with other drugs that undergo transport by the same renal transporters.
Most tubular reabsorption is passive, it is therefore driven by concentration gradient. Increasing urine flow will decrease reabsorption (meaning there is more drug eliminated in the urine) of drugs. The reabsorption of ionizable drugs is sensitive to changes in urine pH.
What is the relationship between molecular weight and renal clearance?
Lower molecular weight compounds can be passively reabsorbed before entering the bile duct and be excreted by the kidneys. Large molecules are eliminated in the bile/liver.
What is the relationship between dose and urinary excretion rate for a drug that undergoes filtration only and one eliminated primarily through renal secretion?
For filtration only, as you increase the dose, you get a proportional (linear) increase in urinary excretion rate. For renal secretion (active tubular secretion) early on the relationship is linear as you between dose and urinary excretion rate but then it begins to saturate and approach a maximal value. This is because active tubular secretion involves a carrier mediated process (has a limited number of transport protein).
What is the relationship between molecular weight and percent of drug excreted in bile?
Large polar molecules, which include many drug metabolites, are mostly eliminated in the bile. As molecular weight increases, percent of drug excreted in bile increases linearly.
What is the impact of enterohepatic recirculation on drug half-life in the body?
Interruption of the enterohepatic recirculation reduces drug half-life in the body.
