ADME 2 Flashcards
What is biotransformation?
The conversion of one molecule to another via enzymatic process.
Most drugs that are part of Phase 1 or Phase 2 metabolism are modified when?
Prior to excretion by enzymatic reactions.
Enzymes involved in biotransformation are often involved metabolizing ___________ drug classes
Multiple
If the same enzyme is utilized in processing two drugs given simultaneously they can ________?
Produce drug interaction due to changes in metabolism rates.
Phase 1 metabolism involves?
Oxidation, re-education and hydrolysis which unmasks or inserts a more polar functional group.
Phase 2 metabolism involves?
reactions which add functional groups to alter the polarity of the molecule.
Examples of reactions for phase 2 metabolism
glucuronidation, methylation, sulphation and acetylation.
Enzymes mediating the reaction in phase 2 metabolism are called
Transferases
The goal of Phase 1 and 2 metabolism
is to produce more polar, hydrophilic molecules that can be excreted.
Most important enzymes in Phase 1 metabolism
is actually a group of similar enzymes classified as cytochrome P450 enzymes (CYP enzymes)
P450 or CYP enzymes are?
Oxidase that act to detoxify many organic compounds
CYP and p450 enzymes are _____ selectivity hence many drugs are modified by CYP.
Low
Other enzymes included for phase 1 metabolism
enzymes include the Flavin containing mono-oxegenases (FMOs) or hydrolytic enzymes such as epoxide hydrolases
Phase 2 has ________ enzymes
Conjugation
Key enzymes for phase 2 are?
Key enzymes are the uridine diphosphoglucuronosyltransferases, Sulfotransferases, Methyl transferases and N-acetyltransferases
Enzymes in phase 2 mediate what?
glucuronidation, suflation, methylation and N-acetylation respectively.
What are the primary routes of drug elimination?
Renal and Biliary
What are the factors that alter the ability for the drug to be eliminated by renal excretion?
include physiochemical properties such as molecular weight and hydrophilicity, Renal blood flow, binding of drug to other molecules such as plasma proteins and renal function.
Physiochemical properties are often altered by
Phase 1 and 2 metabolism
Renal blood flow can be altered by other ________
Medications
Poor renal function can produce poor elimination rates in some patients
True or false
True
Secondary routes of elimination include
exhalation or coughing (lungs), Saliva, Seat, Milk and Tears.
Cyp enzymes are found in
the ER and ER derived components of the cell (microsomes).
Why are CYP enzymes so important?
They are extremely important to drug metabolism since they are very non-selective but efficient oxidizers of organic compounds
drugs given simultaneously can compete with the same CYP catalytic sites and alter the pharmacokinetics of the drugs. This can lead to lethal drug/drug interactions, particularly for low therapeutic index drugs
True or false
True
Other factors that affect expression of CYP enzymes such as _________________________________________ can also impact metabolism and thus circulating drug concentrations.
age and other health conditions (ex: inflammation, kidney disease)
Drugs that are not efficiently eliminated can reach?
Toxic concentrations
Elimination of drugs from the body is directly related to their
efficiency of elimination from the body and their exposure to Phase 1 and Phase 2 reactions
Drugs that are rapidly biotransformed will be eliminated rapidly
thus reducing their half lives in circulation
Drugs that are slowly transformed will be
Eliminated more slowly
If two drugs compete for the same enzymes, such as CYP450,
they can dramatically alter each other’s pharmacokinetics
The drugs will be biotransformed more slowly thus increasing the circulating concentration and prolonging their time in the body.
If the drugs are taken at the normal dose, this would result in excessively high drug dosages, increasing the likelihood of adverse effects. This is an example of one type of drug interaction
Clearance is
the rate of drug elimination from the body
Renal clearance refers to
excretion through the kidney
hepatic clearance refers to excretion in the
bile (biliary).
Biliary clearance eliminates drugs through
excretion of the bile into the digestive track
Lung clearance indicates drugs are eliminated by
exhalation or by mucociliary mechanisms.
Most drugs under 500 MW that are hydrophilic are eliminated rapidly and
have high renal clearance.
