Pharmacokinetics Liver + Renal Dysfunction Flashcards
What is biliary excretion?
Secretion of endogenous + exogenous drugs/substances from hepatocytes into bile
What can impaired bile secretion be due to?
Bile duct stones
Sclerosing cholangitis
Cancer of biliary tree
Pancreas
What can bacteria in GI do?
Reform drug again
= go back to liver
Describe liver structure
Central in the middle
Triads are on each corner
What flows between the triads?
Rich O2
What is triad made up of?
Bile duct
Hepatic artery
Portal vein
Where is there low oxygen?
At central
= hepatic vein is draining
= low O2
Where does Phase II happen?
Between cells
= requires lots of oxygen
What is compensated liver damage?
Body cannot compensate for it = puffer cells activated
What does liver damage do?
Put pressure on pathway
= restrict flow
= body can’t compensate
What are some common liver diseases?
Alcohol-related liver disease
Non-alcoholic fatty liver disease
Hep A, B, C
Haemochromatosis
Primary biliary cirrhosis
What is liver cirrhosis?
Scarring of liver caused by long-term damage
What can liver cirrhosis ead to?
Reduce hepatic blood flow = higher serum levels
Impaired renal excretion = increased serum conc
Hypoalbuminemia = reduce protein binding = higher serum conc of free drug
Bowel edema = impaired absorption
Reduced cytochrome activity = reduced 1st-pass/clearance
What happens to bilirubin in the body?
It is recycled
What are the different types of bilirubin?
Bilirubin-albumin
Bilirubin-diglucuronide
Bilirubin-glucuronide
How long would it take to see no more albumin if liver stopped functioning?
t1/2 X 5
= 20 days = 100 days
What are the intracellular things?
AST
ALT
GGTP
Alkaline phosphatase
= if seen in the blood = PROBLEM
What does increased ALT indicate?
Liver damage
How is INR calculated?
Centrifuge
Ca2+ added to serum
Gel forms
Time taken = prothrombin time
INR = PT test
—————
PT normal
What is Phase I?
CYP enzymes
Oxidative
What is Phase II?
Transferases
Conjugate drug
Describe competitive inhibition
Inhibitor competes for active sites
= stretches the curve
Describe non-competitive inhibition
Reduces enzyme activity BUT does not bind to active site
= reduces Vmax
What happens if we have no blood flow to enzymes?
Mimics “competitive inhibition”
Is Phase II less affected by liver dysfunction?
YES until decompensation
How do you calculate AUC hepatic function?
AUC total
