module 4 Flashcards
what is metabolism?
-enzyme-mediated alteration of drugsdrugs structure
what is metabolism also known as?
biotransformation
what are the sites of drug metabolism?
-liver
-intestine
-stomach (alcohol)
-kidney (contains enzymes)
-intestinal baacteria
why do we need metabolism?
to get rid of toxins etc
what are exogenous things?
-things that we put in our body that are naturally there to begin with
-potential to be toxic & this is why our body has enzymes to rid of it
-wine
-cigarettes
-steak
-vegetables
-coffee
what are endogonous things?
- same family of enzymes that is responsible from metabolizing drugs is also important in terms of endogenously regulated processes
- vit D synthesis, bilirubin, steroid hormones, bile acid
what happens to a drug after its been metabolized?
- increase water solubility to promote excretion
(lipophilic to hydrophilic)
-inactivate drugs
(active to inactive)
-increase drug effectiveness
(active to more active)
-activate prodrugs
(prodrugs are inactive until metabolized)
- increase drug toxicity
(non toxic to toxic)
what is first order kinetics?
MOST CLINICAL SITUATIONS
-the concentration of a drug is much lower than the
metabolic capacity of the body
-drug metabolism is directly proportional to the
the concentration of the free drug
-there is a constant FRACTION of the drug that it metabolized per unit time
- high drug concentration = high rate of metabolism
what is zero order kinetics?
-plasma concentration is much higher than the
metabolic capacity of the body
-drug metabolism is constant over time (this means that regardless of the concentration, the rate of drug metabolism doesn’t change)
-ethanol
what is first pass metabolism?
- PO drugs may undergo significant metabolism prior
to entering ciruclation
Where does first-pass metabolism occur?
hepatocytes
enterocytes
stomach
intestinal bacteria
what is the result of 1st pass metabolism?
decreased amount of parent drug that enters system circulation
degree of first pass metabolism can have a great degree on a drug action (if the drug is extensively metabolized in the liver, almost none of it will reach the systemic circulation and be available to act within the body)
what is the meaning of extraction ratio ?
the amount of metabolism on the first pass through the liver that determines a drugs bioavailibility
what are the characteristics of a drug with a high extraction ratio
-means there is a low bioavailability because liver
metabolizes alot of the drug on first pass
-PO dose must be higher than IV
-small changes in hepatic enzymes will produce large changes in bioavailability
-very susceptible to drug drug interactions
what characteristics does a drug with low ER have?
- high bioavailability (over 80)
- PO doses are similar to IV
-not suspectible to drug drug interactions
-takes many passes through the liver for the drug to be metabolized
-changes in hepatic enzyme will not have a big effect on bioavailability
when does first pass metabolism occur?
only with PO drugs!
drugs that are IV have 100% bioavailability and remained unchanged because they are already in the blood and do not need to pass through the liver to reach the systemic circulation
what happens in phase 1 of drug metabolism
-convert lipophilic to polar molecules
-involves oxidation, reduction and hydrolysis
-mediated by cytochrome p450
-metabolites formed can be more active, less active or
equally as active as the parent drug
what happens in phase 2 metabolism?
-increase the polarity by conjugation reactions
-addition of large water molecule
-conjugates include glucuronic acid, sulfate, acetyl
group or amino acids
-metabolites are less active than the parent drugs
types of drug metabolism
phase 1 - elimination
phase 1 - phase 2 - elimination
phase 2 - elimination
where does phase 1 metabolism occur
smooth endoplasmic recticulum
where does phase 2 metabolism occur
cytosol
EXCEPTION GLUCURONIDATION OCCURS IN THE SMOOTH ER
what are CYP enzymes
- used in phase 1 metabolism
-adds oxygen and water is a byproduct
-majority of metabolism is performed by CYP hepatic
-CYP is a large family of metabolizing enzymes
how many families of CYPs are there and how many are involved with the majority of drug metabolism?
-12 families
-3 major involvement
what decreases CYP activity?
-malnourisment
- deficiencies in iron, folic acid, protein and zinc
