How disease affects drugs Flashcards
What are abosprtion paramters
F, Ka, AUC
what are distribution parameters?
free/unbound
VD
AUC
what are metabolism parameters
t1/2, Clint, Q, Cssavg
what are elimination parameters
Cl, Cssavg, AUC
what happens from a physiology perspective in hepatic disease?
- inflammation to the liver cause reduced function/death of hepatocytes
- decrease portal blood flow
- decreased plasma protein binding
- decreased clearance of bilirubin
Affects in relation to absorption liver failure
- increase bioavailability (F) bc diminshed first pass
- increased AUC
- reduction in portal blood flow (changes to Q effect high E drugs)
- reduction in number and activity of hepatic enzymes (affects Clint and low E drugs)
Affects in relation to distribution -liver failure
- increase free unbound (fu)
less albumin and alpha 1 glycoprotein
increase in endogenous compound such as bilirubin as liver can no longer clear them - increase in VD (ascites, increase in VD in water-soluble drugs)
affects in relation to metabolism - liver failure
- what metabolizer
- effects on clint, half life css
- decreased activity of CYP 450 enzymes so increased decreased Clint
- increase in half -life and Cssavg
what do we use for an estimaion of liver function?
and how do we suualy adjust?
Child-Pugh Classs
adjust by decreased dose or decreasing interval
Key Physiological changes in heart failure
- decreases cardiac output (decreased hepataic and reanl blood flow)
- edmea fluid in GI tract
- decreased blood flow to GI tract
- peripheral vasoconstriction (decrease ability to reach binding sites or target tissues - drugs remain in plasma)
affects on abosprtion in. HF
- GI edema interferes with absorption of drug (decreased blood flow to GI tract nad decreased bioavailability)
-
affect of distribution in HF
- Distribution (Vasoconstiction symtpathic activation interferes with drug distribution so decreased Vd - drug remains trapped in plasma)
Effects of Metabolism in HF
- decreases in hepatic blood flow (Q) so decreased metabolism for high E and intermediate E drugs
Effects of elimination in HF
Decreased renal blood flow, decreased renal clearance
- increased half life
takeways for patienst with HF
- incomplete drug respond when acutely ill ( maybe try IV)
- May be less responsive to high E drugs