Unit 2 - Biological barriers & ADME 3 Flashcards
What can dyslipidaemias affect?
Metabolic capacity
- liver biotransformations
Pharmacological response
What effect does hyperlipidaemia have?
Increases sequestration of the lipophilic binding drugs
- more lipoproteins available for drug to bind to
How does blood flow through the liver?
Through sinusoids which surround the hepatocytes
- perfused on both sides
What is a bile canaliculus?
Small canal formed by opposed grooves in the surface of adjacent hepatocytes
What volume of plasma flows through the glomerulus per minute?
660 ml/min
What percentage of plasma is filtered through the glomerulus?
20%
What is the Glomerular Filtration Rate?
125 mL/min
Where are transporters found to secrete drugs into the nephron?
Proximal tubule epithelium
What are OAT?
Organic Anion Transporters
Where are OATs found?
Both surfaces of renal proximal tubule epithelium
- apical
- basolateral
Where are P-glycoproteins found?
Apical membrane of the renal proximal tubule epithelial cell
What GFR suggests chronic kidney disease?
< 60 ml/min
What can be used to calculate eGFR?
Serum creatinine
What is produced as a byproduct of muscle metabolism?
Creatinine
How is creatinine used as a measure of eGFR?
Creatinine is removed unchanged from the blood - glomerular filtration - mainly - proximal tubular secretion - small amount Little to no reabsorption occurs
What effect does kidney failure have on serum creatinine?
Serum creatinine levels rise
What assumptions can be made to calculate a drug’s renal clearance?
No reabsorption of drug back from the nephron to the blood
No active secretion of drug from blood into the nephron
Knowledge of fraction unbound
What are the implications of a drug pharmacokinetics being first order?
Concentration of drug in the body is proportional to dose
- a doubling of dose will see a doubling in concentration of drug in the body
Rate of elimination of drug from the body is proportional to concentration of the drug in the body
