Flashcards in Concepts in Drug Elimination Deck (19):
What is the driving force of glomerular filtration?
The hydrostatic pressure of blood flowing in capillaries
What is used to estimate GFR?
What is the GFR (ml/min) often used as a threshold to diagnose first stage chronic kidney disease?
What 3 things do we assume when using GFR as a measure of renal clearance for a drug?
1.) That no drug is reabsorbed back from the nephron (proximal tubule) into the blood
2.) That no drug is actively secreted into the nephron from the blood
3.) We know the Fu
Why do we use Creatinine to estimate GFR?
1.) IT is removed unchanged from the blood primarily by GFR (only a small amount by proximal tubule secretion)
2.) Little or no tubular reabsorption occurs
If filtration in the kidney is deficient, do serum creatinine levels rise or fall?
Why is GFR important?
It is a measure of renal function
Why would creatinine clearance be different in males and females?
Because creatinine is a byproduct of muscle metabolism and so would expect to see higher muscle mass in males.
Name two ways that a drug administered IV would enter the liver.
1.) from circulation via hepatic artery
2.) perfuse into small intestine and drain into liver via portal vein
Name the two components of hepatic elimination
1.) Metabolism within hepatocytes
2.) Secretion into bile
How is bile recycled?
via the enterohepatic circulation i.e. the bile in the small intestines is returned to the liver via the hepatic portal vein.
Where are cytochrome p450 enzymes expressed?
In the endoplasmic reticulum of cells that undertake a vast array of oxidation reactions. The liver has the highest conc and broadest range of CYP450 enzymes.
What is the aim of metabolism?
To make xenobiotics (substances that weren't produced in the body) more polar so that they can be easily excreted by the body.
Name 2 phase one CYP reactions
Epoxidation, Hydroxylation, oxidation (N,S), deamination, dealkylation (N,O,S)
Name 2 phase one non-CYP reactions
Name two conjugations
What is the name of the amino acid that conjugates with the toxic metabolite NAPQI in paracetamol metabolism?
What happens in paracetamol overdose?
More paracetamol is shunted to the phase 1 (CYP450) pathway to produce NAPQI. The liver's supply of glutathione becomes depleted and so NAPQI isn't converted into its non-toxic form. It reacts with cellular membrane molecules of hepatocytes and causes liver damage (necrosis) or even death by acute liver failure.