57. Phase 1 and Phase 2 Metabolism Flashcards
what does ADME stand for
Absorption, Distribution, Metabolism and Excretion
what is drug metabolism
drug transformation by metabolism by the liver and other tissues
the enzymatic conversion of the drug to another chemical entity
which organ is the most important for drug metabolism
liver
Metabolism in the liver (and/or gut) reduces the ‘………..’of drugs when administered by the enteral (oral) rout
Bioavailability
what has 100% bioavailability
Intravenous administration
what is bioavailability
The amount of drug that eventually reaches systemic circulation (and hence is available for drug action on the target) of an administered dose of the drug
what is the bioavailability equation
(Bioavailability) F= quantity of drug reaching systemic circulation/quantity of drug administered (DOSE)
AKA
Amount of drug in systemic Circ
F= ——————————————–
Quantity of drug administered
what is first pass metabolism
Occurs with oral administration;
The drug is absorbed in the gut and transported to the liver,
Reducing bioavailability.
This may require higher doses or alternative routes of administration
systemic metabolism occurs in ….. phases
2
Phase one and two mainly take part where?
the liver
Phase 1 of systemic metabolism is (3)
oxidation, reduction and hydrolysis
Phase 2 of systemic metabolism is
Conjunction with polar molecules to form water soluble metabolites
explain phase 1 oxidation
by cytochrome P450 enzymes, incorporation 1 atom of O2 to the drug to form a hydroxyl group
explain phase 1 reduction
this reaction occurs less than oxidation.
explain phase 1 hydrolysis
Ester and amide bonds are hydrolyzed, occurring in plasma and other tissues.
Usually forms chemically reactive metabolites that can be active or toxic.
so oxidation phase one can produce good metabolites?
No, they are harmful
what is an example of harmful oxidation of drugs in metabolism 1
paracetamol
cytochrome P450 2E1 causes NAPQI which is a toxic metabolite of paracetamol
Cytochrome P450 enzymes are ‘…….’ proteins
Haem
Name some CYP (Cytochrome P450) gene families involved in drug metabolism in the liver
CYP1, CYP2, CYP3
P450 activity is genetically determined so when people lack this activity it leads to
higher drug plasma levels
P450 activity is genetically determined so when people have very high levels of this activity it leads to
lower plasma levels (reduced drug action)
what are you blood plasma levels
When you take a drug, it enters your bloodstream and is carried throughout your body. The blood plasma level is the amount of the drug present in the liquid part of your blood (plasma) at any given time.
Why Are Blood Plasma Levels Important? 2 reasons
Effectiveness: The drug needs to reach a certain level in your blood to be effective. If the level is too low, the drug might not work. If it’s too high, it could be toxic.
Timing: Understanding how long a drug stays in your blood helps determine how often you need to take it.
drugs can induce or inhibit P450 activity, which ……
affects drug metabolism.
