Finals Misc Flashcards
What is the effect of obesity on absorption?
no significant impact on bioavailability and absorption
What is the effect of obesity on distribution? (3)
depends on drug lipophilicity and charge
tissue penetration may be reduced
increase in alpha-1 acid glycoprotein hence increased binding of basic drugs and lower serum drug conc
What is the effect of obesity on metabolism? (2)
possibly increased hepatic blood flow
increased phase II reactions
What is the effect of obesity on excretion?
increase weight = increase in CO
this may affect kidneys, causing glomerulopathy which can affect renal clearance
What is the effect of obesity on drug concentration?
conc = dose / vol
obese patients have disproportionate adipose/lean tissue relative to weight
drugs with low to mod Vd (hydrophilic) are likely to stay in plasma, weight based dosing will result in disproportionate increase in serum conc
↑↑dose / ↑vol
shld adopt more conservative dosing or dose based on IBW/LBW
What is the effect of CKD on absorption? (3)
may be impaired due to
- delayed gastric emptying from gastroparesis (DM)
- decreased gastric acidity from urea retention
- DDI w CKD-meds like phosphate binders, Fe and Ca supplements
What is the effect of CKD on distribution? (2)
can be affected due to:
- altered plasma protein binding (lower albumin)
- changes in fluid balance (edema/FO)
What is the effect of CKD on metabolism?
accumulation of metabolites due to reduced clearance
- toxic metabolites = toxic
- active metabolite = supratherapeutic
What is the effect of CKD on excretion?
as CKD progresses there is reduced renal perfusion
therefore prolonged elimination half life, reduced clearance
What is the effect of liver cirrhosis on absorption?
reduced hepatic flow and portosystemic shunting = lower FPE hence increased F and serum conc of drugs (esp for drugs w high extraction ratio, E) ( F = 1 - E )
What are high and low extraction ratios?
high > 0.7
low < 0.3
What are high and low extraction ratio drugs more affected by respectively, with regards to absorption in cirrhosis?
High E = drugs primarily affected by hepatic flow, F significantly affected by small changes in CL
Low E = affected more by plasma protein binding and CL(int)
What is the effect of liver cirrhosis on distribution? (2)
Decreased albumin = competition for protein binding sites = decreased plasma protein binging = higher free drug conc
presence of ascites and edema = increased ECF = increased Vd of hydrophilic drugs
What is the effect of liver cirrhosis on metabolism?
marked reduction in expression of CYP enzymes (affects phase I more)
What is the effect of liver cirrhosis on excretion?
hepatorenal syndrome = reduced renal perfusion = reduced clearance
