Lecture 5 Flashcards
Name some physiologic changes during pregnancy
Changes in total BW and body fat composition
delayed gastric emptying and prolonged GI transit time
increase in extracellular fluid and total BW
increased CO, increased SV, and elevated material HR
decreased albumin conc with reduced protein binding
increased BF
increased GFR
Changed hepatic enzyme activity
Does bioavailability of drugs change during pregnancy?
No difference in bioavailability during pregnancy compared with postpartum
How is distribution affected in pregnancy?
Increase in volume of distribution - can result in decrease of Co (after a loading dose) and decrease in Cmax
if Cl decreased/ unchanged - can result in increased terminal elimination half-life
How is protein binding affected in pregnancy?
Albumin conc. decreases in 2nd trimester and declines throughout pregnancy
low extraction ratio drugs -doses monitored using total Cp
high extraction ratio drugs - narrow therapeutic window, non-oral routes. AUC unbound drug significantly increased when albumin is decreased
How is renal excretion affected during pregnancy?
GFR increased approx by 50% by the 1st trimester and continues to increase throughout pregnancy
What factors affect pathophysiology in pregnancy?
No significant difference in absorption between obese and lean subjects
affect drug distribution
high % of body fat
Lower % of lean tissue and BW
affect metabolism
higher CO and liver BF
enlarged liver with altered histologic studies
affect drug elimination
higher RBF
higher GFR
How is distribution affected in obesity?
Influence PK
weak or moderate lipophilicity - limited distribution in excess body fat
How is plasma protein binding affected in obesity?
may change in obesity without changing protein concentrations
How is renal function affected in obesity?
example, ciprofloxacin, lithium, and gentamicin -huge difference in CrCl between obese and those with a normal BW
vancomycin - huge increase in ClCr in morbidly obese patients
