ADME 4- Tavalin Flashcards
What are the routes of drug excretion?
renal, liver/intestines, sweat, saliva, breast milk
What is the functional unit of kidney?
nephron
What are the three processes of a nephron?
glomular filtration - blood filted to kidney
tubular secretion - proximal tubule
tubular reabsorption - distal tubule and loop of Henle.
Is glomerular filtration rate saturable?
No. It is both passive and nonsaturable, depending entirely upon blood presentation and cardiac output.
Where in a nephron are low molecular weight (ions, glucose and peptides) molecules filted out of blood?
glomerulus
Where does most of the drug get reabsorbed?
almost 90% of what is filtered out in the glomerulus is reabsorbed by the tubules
What occurs in the proximal tubule?
reabsorption of water and active (ATP-dependent) secretion of weak electrolytes (especially acids). Significan t removal pathway for organic anions and cations as well as drugs.
What occurs in the distal tubules?
Water and Nonionized (lipid soluble) weak acids and bases are reabsorbed by passive diffusion and returned to general circulation. Lipids are extensively reabsorbed.
What effect would acidification of urine have on drug reabsorption?
Acidification of urine would facilitate removal of basic drugs, while alkalinization facilitates excretion of acidic compounds. (charged compounds excreted)
What is standard renal clearance of a drug that is filtered but not secreted or reabsorbed? What does it mean if renal clearance is less than this number? Higher?
about 120 mL/min in normal subjects.
If it is 120, then tubular secretion must be contributing to elimination process.
What is enterohepatic cycling?
drug is taken into circulation, in the liver it is metabolized and conjugated, then secreted with bile acids and salts into the intestines. There it undergoes hydrolysis back to parent compound (active metabolite) and is reabsorbed then sent back to liver to enter circulation and start cycle again. This prolongs drug presence in system.
Which type of drug would have a longer acting time in body: low or high molecular weight?
High molecular weight drugs will take longer to excrete so they will be in system longer.
Which type of drug would have a longer acting time in body: lipid or water soluble?
Lipid soluble will take longer to excrete so it will stay longer.
Which type of drug would have a longer acting time in body: low or high volume of distribution?
drugs with higher volumes of distribution will be more concentrated in one area, thus take longer to clear and stay in the system longer.
What does an extremely low volume of distribution suggest?
That the drug is extensively bound to plasma proteins such as albumin
