3.5.3 Intro to Hepatocyte Pharmokinetics Flashcards
How can liver disease effect drug distribution?
↓ liver function → ↓ albumin → drugs can’t get to target tissues
What are the general roles of the Liver in drug metabolism? (5)
Inactivates the drug
Makes it more water soluble
Can make drug more active or toxic
Can be divided into phase I and phase II reactions
primarily carried out by the hepatocyte
How can hepatocytes affect distribution of drugs?
drugs commonly bind to albumin, if liver malfunctioning, ↓ albumin → ↓ drug transport
What is pharmacokinetics?
What the body does to the drug
How can cirrhosis affect the metabolism of a drug?
less functional liver tissue also lead to portal HTN
What is pharmacodynamics?
Effect of drug on the body
What are the characteristics of Phase III Metabolism of drugs?
drug transport to various tissues, also occurs before phases 1 and 2, ABC transporters
What is absorption?
The process by which drugs enters the body
What is metabolism is regards to drugs?
enzymes modify drug to make it water soluble or activate it
What are the major principles of pharmacokinetics and pharmacodynamics?
Absorption
Distribution
Metabolism
Excretion
How can liver disease effect excretion of a drug?
Excretion – cholestatic liver disease, abnormal bile levels inhibits drug excretion
What is first pass metabolism?
drugs taken orally goes through liver before reaching target tissues, metabolism limits bioavailability of drug
What is excretion is regards to drugs?
removal from body via bile or serum, mostly by kidneys
How can liver disease affect absorption of a drug?
decreased first pass effect
How can liver disease affect metabolism of a drug?
capacity of hepatocytes is diminished, shunts → possible toxicity
What is the role of hepatocytes in drug excretion?
Hepatocytes can secrete the drug metabolite into the bile for excretion
What is distribution?
Delivery of drug from systemic circulation to tissue
What are the characteristics of Phase II drug metabolism?
Involved conjugation, such as glucuronic acid, which combines with the drug or phase I metabolite to form conjugate with high polarity
What are the characteristics of phase I drug metabolism?
Consists of oxidation, reduction and hydrolysis reactions
Typically results in more polar
How can portal HTN affect drug metabolism?
portal HTN → shunts around liver, loss of fenestrations → drug can’t enter hepatocytes
What are the enzymes that carry out phase I drug metabolism in the liver?
Cytochrome p450
Flavin containing mono-oxidases
epoxide hydrolases
