W3- Lecture 15.2- Pharmacokinetics Flashcards
Name the three routes of elimination
Renal excretion
Liver metabolism
Chemical transformation
What two types of compounds are not metabolised and almost exclusively cleared by
glomerular filtration
Some complex carbohydrates
Why do lipophillic drugs need to be metabolised ?
They are not excreted by the kidney so if they were not metabolised they could just be endlessly recycled
Named the three phases of metabolism
Phase I metabolism - Functionalisation reactions
Phase II metabolism - Conjugation reactions
Phase III metabolism - Formation of xenobiotic- macromolecule adducts
Where can you find the majority of drug metabolism and drug metabolising enzymes
In the liver
What is first pass metabolism
The drug has to pass the liver directly after administration (before major absorption )
Why do we need to consider first pass metabolism when admistrating drugs ?
Because oil can decrease bioavailability of drugs
How can we bypass the first pass metabolism
But giving drugs parenerally (aside from intestine )
e.g may cross epithelium (e.g. skin, lung)
may avoid epithelium (e.g. subcutaneous, intramuscular, intrathecal(spinal chord ), intraperitoneal injection(abdominal ))
Drug metabolism mainly occurs in to sub cellecular compartments which two are these ?
Smooth Endoplasmic Reticulum that form microsomes
And the mitochondria
Are are a variety of metabolic enzymes in the microsomes, mitochondria and the cytosol
Describe phase 1/ Functionalisation reactions
Addition or removing of functional polar group
E.g oxidation, deduction, hydrolysis
not so common (hydration & isomerism )
This deactivated the drug
Describe Phase II or conjugation reaction
Addition of a group or groups to a drug molecule
Addition of polar group catalysed by transferase
With a cofactors donor
Describe the properties of a drug metabolising enzyme
Low substrate specificity
Low reaction specificity (may catalyse diff reactions )
Lower catalytic rates
Present in high concentrations
Substrates usually lipophilic(converts to more polar substances)
Enzymes are inducible ()
Describe an inducible enzyme
I responded to high activity , activation of production of more enzymes
Describe the reaction of cytochrome P450
Reactacts NADPH H+ O2 RH(oxidisable substrate )
Goes to
NADP+
H20
ROH - now able to be excerpted by kidneys (water soluble )
Name 5 factors Microsomal drug metabolism is modified by
Competition between substrates, e.g. warfarin / tolbutamide.
Inhibition of enzymes by drugs, e.g. cimetidine, erythromycin.
Induction of enzyme systems, e.g. phenobarbital. (gene expression) Metabolism of drug substrates increases (eg warfarin, oral contraceptives), and those drugs become less effective
Age, nutritional status, liver disease.
Genetic polymorphism. Individuals or population groups may have less/more activity of particular enzymes & show slower/faster rates of metabolism (e.g. codeine)
