12. Pharmacokinetics IIII Flashcards
Describe Cytochrome P450
-Important metabolism enzymes
-Membrane bound enzymes found mainly in the liver cells.
-All contain an Fe which is used to catalyse oxidation of the drug.
-large family of enzymes.
-Can be sped up, ex. Phenobarbital, or inhibited, ex Fluoxetine, by certain drugs
Describe the Brush border
lines hepatocyte cells has micro villi that increase surface area to pick up more drug.
Name the 5 types of Phase 2 conjugation reactions
- Glucuronidation
- Sulphation
- Acetylation
- Methylation
- Amino-acid conjugation
Describe the phase 2 Conjugation reaction Glucuronidation
-glucuronic acid C6H9O6 replaces the H to give water soluble inactive products.
Describe the phase 2 Conjugation reaction Sulphation
-A sulphur group So3- replaces the H to give a very water soluble inactive usually excretory product
Describe the phase 2 Conjugation reaction Acetylation
-Acetate CH3CO2- replaces the H to inactivate the functional group but no increase in water solubility.
Describe the consequences of drug metabolism
-Once the drug has been metabolised it is a different compound and the activity due to the parent drug is removed
-the metabolite is a different compound and may have:
- No activity, the usual case.
- Similar pharmacological activity.
- Different pharmacological activity.
- A toxicological action.
Describe Phase 1 metabolites
usually inactive, but may show a different change in activity. Frequently undergo phase 2 metabolism prior to excretion
Describe Phase 2 metabolites
nearly always inactive and are usually a lot more water soluble to be excreted easier.
Name 5 variables affecting Metabolism
-Species
-Genetics
-Environment
-Age
-Disease
Describe how Species will affect metabolism
rats and mice differ from humans. ex rats do not release bile from a gall bladder so rate of metabolism will be different
Describe how Genetics will affect metabolism
Certain metabolic Enzymes may be defective.
Describe how Environment will affect metabolism
other drugs taken may effect activity.
Describe how Age will affect metabolism
In the elderly the size of the liver and blood flow to it decrease slowing phase 1 metabolism
In the young certain drug metabolism enzymes are immature in neonatal livers so first pass metabolism is slowed or defective.
Describe how Disease will affect metabolism
Liver disease can cause changes that impair rapid uptake of lipid soluble drugs and lower activity of intracellular enzymes.
Describe the 3 routes of excreation
Lungs, volatile compounds only
Kidneys, urine, Low molecular weight and water soluble could be reabsorbed from kidneys
Bile, high molecular weight, Biliary metabolites may be metabolised in gut lumen and reabsorbed.
