Drug Metabolism And Renal Excretion Flashcards
How are drugs usually excreted in
In the urine either unchanged or chemically transformed to a more polar compound
Excretion via the bile occasionally significant
What are xenobiotics
Compound ehich is forgein to the body
How does the body metabolise a xenobiotic
Convert parent drug to more polar metabolite that not readily abs by kidney
Conv drug to metabolite which is usually less active
- conv to inactiv prodrugs
- gain activty
- unchanged activity
- diff action possessed
What is the main organ of metabolism
Liver but GI tract, lungs and plasma have activity
What are the two phases of drug metabolism
Phase 1 - makes drugs more polar by adding chemical handle (oxi,red, hydrolysis)
Phase 2 - adds endogenous compound to increase polarity such as glucoronyl, sulphate, methyl, acetyl
What si the metabolism of aspirin
Drug - aspirin Phase 1 Derivative - salicylic acid Phase 2 Conjugate - glucoronide
Initial catabolism followed by anabolism
What are the cytochrome (p450) cyp family of monooxygenases
Haem protiens in the ER of liver hepatocytes
Mediate oxidation reactions involved in phase 1 drug metabolism of many lipid sol drugs
What si the formula for cytochrome p450 (CYP) monooxygenases
CYP3A4
3 - gene family
A - gene subfamily
4 - individaul gene
What si the important part of monooxygenate P450 cycle
Drug enters the complex cycle as drug substrate RH when 2 oxygens atoms are added which becomes hydroxyl and leaves and the other forms water
What are the phase 2 reactions
Result in inactive products
In liver
Involve conjugation of chem reactive subs
What is glucoronidation
Common reaction involving transfer of glucoronic acid to electron rich atoms of the substrate
Many endogenous subs are subject to this such as bilirubin and adrenal corticosteroids
What are the three basic processes of renal excretion
Glomerular filtration
Active tubular secretion
Passive reabs by diffusion across tubular epi
When does globular filtration occur freely for drugs
When drugs have a molecular weight less than 20000 and also not bound to plasma protein
Charge not imp
What do many drugs bind to in blood
Albumin and alpha1- acid glycoprotein and exist in the blood in an equilibrium between unbound and proetin bound forms
Only unbound molecules can
Enter filtrate via glomerular filtration
