[5] Biotrans 1 - 2.5 Flashcards
Mechanism by which the body terminates the
action of some drugs.
(or eliminate them from our system)
DRUG METABOLISM
In some cases, it serves to activate “prodrugs”
(they are inactive so they need to be activated)
DRUG METABOLISM
Inactive drugs
PRODRUGS
PATHWAYS TO DRUG METABOLISM
(readily excreted by the kidneys)
1. Active —– inactive
2. Active —– active metabolites
3. Inactive — active (Prodrug)
- Active —– inactive
Administered to our body. Requires activation to our metabolic processes
PRODRUGS
THREE POSSIBLE PATHWAYS TO DRUG METABOLISM
- Active —– inactive
- Active —– active metabolites
- Inactive — active (Prodrug)
PATHWAYS TO DRUG METABOLISM
(a drug may be administered to our body which is already active)
1. Active —– inactive
2. Active —– active metabolites
3. Inactive — active (Prodrug)
meaning that they are able to interact with the receptors.
- Active —– inactive
Receptor binding requires specification as
to the structure of our drug
- Active —– inactive
- Active —– active metabolites
- Inactive — active (Prodrug)
some may need to add water
soluble groups or even some may
require unmasking of hydrophobic
or hydrophilic components of the
drug, so it will fit into the receptor.
- Active —– inactive
NOTE: So as we have said, some drugs are
already active when they are given to our
body and would have already reacted to the
receptors. Now what our body will do is to
inactivate them and they could be readily
excreted thru our kidneys.
PATHWAYS TO DRUG METABOLISM
other drugs are actually administered as active and when they are broken down
- Active —– inactive
- Active —– active metabolites
- Inactive — active (Prodrug)
they would also have active metabolites
for these types of drugs, the duration of
action would somehow be longer as
opposed to the first mechanism
- Active —– active metabolites
PATHWAYS TO DRUG METABOLISM
drug which is a prodrug - meaning that they are inactive
- Active —– inactive
- Active —– active metabolites
- Inactive — active (Prodrug)
- Inactive — active (Prodrug)
NOTE: some drugs that will not pass thru
the liver
PHASES OF METABOLIC ACTIONS
Non - synthetic reactions
PHASE 1
PHASES OF METABOLIC ACTIONS
Converts the parent drug to a more polar conjugate (water soluble) or more reactive product
more polar = more water soluble = more active
They intend to make a parent drug
whether active or inactive, more polar
PHASE 1
PHASES OF METABOLIC ACTIONS
- OXIDATION
- REDUCTION
- DEAMINATION
- HYDROLYSIS
These are what phase of metabolic actions:
Phase 1
PHASES OF METABOLIC ACTIONS
Introducing/inserting/unmasking a polar functional group. These include OH, SH, NH2 - hydroxyl, sulfidril, as well as amino group
These functional groups when they are
already present in our drug can be
unmasked, kung hindi naman they can be
inserted to the parent drug.
PHASE 1
NOTE: PHASE 1 normally precedes phase 2, but of
course we have some exceptions.
PHASES OF METABOLIC ACTIONS
Synthetic reactions
PHASE II
PHASES OF METABOLIC ACTIONS
Endogenous substrate is conjugated to the parent drug to make it more polar
Mas madali maeliminate because polar. Substrate coming from our metabolic reaction to the metabolic drug
PHASE II
intention: to make it polar for it to be
eliminated easier/readily
PHASES OF METABOLIC ACTIONS
- Glucuronidation - glucuronic acid - ADDITION of glucuronic acid
- Acetylation-acetyl COA - Adding acetyl group from acetyl coA
- Sulfation
- Methylation
- Glycine conjugation-glycine
- Glutathione conjugation – Addition of glutathione
- H2O conjugation
These are what phase of metabolic actions:
phase II
Common Route:
PHASE I ———- PHASE II (most drugs)
PHASE II ——— PHASE I (other drugs)
PHASE I ———- PHASE II (most drugs)
Isoniazid Acetylation ——- hydrolysis:
PHASE I ———- PHASE II (most drugs)
PHASE II ——— PHASE I (other drugs)
PHASE II ——— PHASE I (other drugs)
Recall: drugs which become (non-polar/polar)
are eliminated through the urine.
Polar
drugs that can not turn polar would be excreted through our ______.
biliary system.
