Pharmacokinetics 3 (Elimination) Flashcards
drug needs to be _____ polar to be excreted out successfully
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GI tract draining all of absorbing material into
liver
What is the advantage of GI tract draining all of absorbing material into liver
breaks bigger molecule into smaller molecules. then if molecules needs to go back into GI tract (e.g. if still too big).
hepatic artery > liver >
hepatic vein
s the name of the process when molecules goes back and fourth from GI to liver
hendro-hepatic recirculation
Mesenteric artery > liver >
hepatic portal vein
what is the most common site of action for drug metabolism
liver
can lipophilic drug be polar?
no
later on drug will be introduced in liver to make drug MORE
soluble and able to travel through liver
gut > liver (> kidney) >
site of action
Which enzymes facilitate the chemical process to make drugs more water soluble?
DMEs
Cytochrome P450
Alcohol dehydrogenase (ethanol)
Esterases
What are the two step process of drug metabolism?
Phase I = oxidation, reduction, hydrolysis
Phase II = conjugation
Phase 1 is catalysed by Cytochrome P450 (Haem-containing mono-oxygenase enzymes)
74 CYP gene families and multiple substrates
CYPs evolved to deal with environmental/nutritional toxins (e.g. plant alkaloids)
Some drugs or foods can increase the expression of specific CYPs (phenytoin, broccoli)
Some drugs or foods can inhibit the CYPs activity (grape fruit juice)
Metabolites could be more active than the drug (pro drugs)
What does phase 1 require?
oxygen and NADPH
Phase II is conjugation=
ADDITION of polar groups
(convert drugs more water soluble, that could most readily excreted by kidney)
examples of polar groups that can be added to drugs
OH (glucuronyl, methyl, sulphate)
NH2 (glucuronyl, acetyl)
COOH (glucuronyl, glycine)
the most common phase II catalysis is by…
Uridine-disphospho-glucuronyl transferases (UGTs)
Drug Excretion/Elimination
Water soluble molecules:
Urinary system (Kidneys)- Major site of drug eliminations (3 stages)
passive or not passive = glomerular filtration?
removal of [free] drugs
Tubular secretion = what kind of transport?
active transport
Reabsorption depends on _____ _______ & ___
lipid solubility & pH
Biliary system (entero-hepatic recirculation)
Large molecule
Describe the process of Drug Excretion/Elimination?
Active transport of large molecule into bile (glucuronides)
Excreted into gut
Redistribution of molecules into liver
Reabsorption can be blocked by activated charcoal (e.g. treatment method for drug poisoning)
Drug in blood continually changes with time because of
ADME