Metabolism and Excretion Flashcards
What is Metabolism
- The enzymatic conversion of one chemical compound into another
- Mostly occurs in the liver (also occurs in lungs, kidney gut wall)
- Overall metabolic proccesses convert Drugs into a more water soluble compound by increasing the polarity so that the drug can be excreted as a fluid
What are the stages of Metabolism
- Hepatocytes (main functional cell of Liver) contain enzymes neccessary for drug metabolism
- The main enzymes involved in metabolism belong to Cytochrome CP450 Group and are housed in the Smooth ER of the cell
- Phase 1 = Reduction, Hydrolysis and Oxidation of Drug
- Phase 2 = Conjugation
What are the three metabolic functions of the liver
Take a:
Toxic substance - Convert to Non Toxic Metabolite
Pro Drug - Convert to Active drug
Active Drug - Convert to a Inactive metabolite/drug (Easier for excretion)
What are Active and Pro Drug
Pro Drug - A metabolically Inactive drug that becomes active after metabolism
Active Drug - A drug that has immediate biological effect without the requirement of metabolism
Explain Phase 1 Metabolism
CYP450 Enzymes act on a specific drug
They cause:
Oxidation reactions = loss of electrons, gain oxygen or loss of hydrogen
Reduction reactions = gain of electrons or hydrogen loss of oxeygen
Hydrolysis reactions = larger molecule broken into 2 smaller molecules using a water molecule
These procceses make a drug more polar and water soluble adding a chemically reactive group and permitting Conjugation or Phase 2 metabolism
Explain Phase 2 Metabolism
Phase 2 involves Conjugation
Conjugation is the attachment of an ionised group to the drug making it more water soluble to allow for excretion
Ionised groups can be:
* Methyl
* Acetyl
* Glutathione
* Sulphate
* Glucuronyl
What factors can affect liver metabolism
Disease - Disease that reduce hepatic blood flow i.e heart failure
Sex
Age - number of hepatocytes decreases
Diet - Dietry factors can inhibit or induce CP450 activity
Explain the clinical importance of factors which affect liver metabolism
A change in the factors affecting metabolism can alter the way a drug is metabolised
If metabolism is inhibited more drug stays in the bodies circulation for longer, increaseing the half life of the drug (Increase toxcicity)
If CP450 is induced to work harder the drug is broken down quicker which could affect the theraputic effect
Pro Drugs require metabolism to release the active drug/metabolite. If this is impared then lees drug will be available affecting the theraputic outcome.
What is Excretion
Excretion is the proccess in which a drug is removed from the body either as a Metabolite (product of Metabolism) Or unchanged
Primary method of excretion is renal (by the kidneys through urine)
Drugs are filtered out here or activley secreted in the nepheron filtering units
What is the clinical importance of excretion
Drugs are excreted unchanged or as active metabolites
Renal imparement can can compromise excretion meaning active drugs can recirculate producing high plasma concentrations.
Theraputic Index = Is the range of dose at which a drug is effective without being toxic.
For drugs with a narrow Theraputic index this renal imparment can cause toxicity.
What is the Theraputic Index
Theraputic Index = Is the range of dose at which a drug is effective without being toxic.
It compares the minimum effective drug concentration needed to produce a theraputive effect with the amount at which the drugs becomes toxic.
High theraputic Index = Are safer, there is a larger range between the minimum effective concentration and the concentration at which the drug is toxic
Low Theraputic Index = Is bad, there is a narrow range between the minimum effective concentration and the concentration at which the drug is toxic
What is the Half life of a Drug
The time it takes for the plasma drug concentration to reduce by Half
What is the collective word used to describe Metabolism and Excretion
Clearance/Elimination
What is the clinical importance of knowing the Clearance rate of a drug
Knowing the rate of removal allows the correct dosing interval to be calculated.
As the plasma concentration of the drug drops it can be topped up at each half life unitl a point at which the amount of drug cleared matches the amount put in (Steady State)
It takes 5 1/2 half lives to acheive Steady state
