-
biotransformation reactions are significant
because
- they are often the first step in eliminating drugs
- from the body
-
Enzymes are also responsible for
Metabolism or biotransformation
-
xenobiotics
- The metabolism (biotransformation) of foreign drugs
- from the body
-
What are the 2 primary ways drugs are excreted
from the body?
2
1.) Urine/Feces --> Unexcreted
2.) Metabolized/biotransformed then excreted
-
What are other ways that drugs can be excreted
after being metabolized or biotransformed?
2
Sweating
Respriation
-
Most drugs are biotransformed when and why
prior to excretion because they are not polar enough
ie not water soluble enough
-
What is the major object of biotransformation?
- Make non polar drugs more polar to be more readily
- excreted
-
Drugs are biotransformed by what
Enzymes
-
The products of biotransformation results in
what
- a compound that is less active or inactive that
- the parent drug
-
Biotransformation makes a drug more soluble or
less soluble?
Makes the drug more soluble for excretion
-
After biotransformation what is produced that is
no longer of therapeutic value
a metabolite
-
Prodrugs
- the biotransformation creates the metabolite that
- produces the therapeutic response
-
Prodrugs
Biotransformation produces the active drug
-
Where does biotransformation primarily occur
in the liver, but other places as well
-
1.
Other
places biotransformation can occur
KGSL
o Kidneys
o GI Tract
o Skin
o Lungs
-
How are drugs ingected orally entered into the
bloodstream?
Absorbed in the GI Tract to enter the bloodstream
-
What is the primary organ for biotransformation
the liver
-
How are drugs transported to the liver
hepatic portal vein
-
Once the drugs are absorbed into the
bloodstream, are the drugs directly or indirectly delivered to the liver and
how
directly delivered
via the hepatic protal vein
-
First pass effect
- the percentage loss of how much a drug is loss due to
- absorption into the GI tract
-
Possible Pathways of Elimination for a Drug
1) excreted unchanged,
- 2) biotransformed (structurally
- modified) to metabolites that are:
- a) excreted
- b) further biotransformed.
-
Prodrugs take advantage of what to produce a
therapeutic effect
the metabolism
-
Prodrugs are the same or different as drugs
the same, just use metabolism to produce effect
-
Only between prodrugs and drugs
prodrugs are activated by the metabolic process
-
1.
Properities
of Metabolites
PHIL
- Polar
- Hydrophilic
- Inactive
- Less Active
-
Drugs are AKA
Xenobiotics
-
heme-containing membrane proteins
cytochrome P450 enzymes
-
cytochrome P450 enzymes are found in high
concentrations where
the liver
-
1.
cytochrome
P450 enzymes are found in lower concentrations where?
BLIK
- Brian
- Lungs
- Intestine
- Kidneys
-
most important enzymes for drug metabolism are
cytochrome P450 monooxygenases
-
1.
cytochrome
P450 are capable of catalyzing what type of reactions
7
- Aromatic and aliphatic hydroxylations
- N-, O-, and S- dealkylation
- N-oxidation
- Sulfoxidation
- N-hydroxylation
- Deamination
-
CYP 450 interactions generally result from what
of two processes
II
Induction
Inhibition
-
Induction
a drug stimulates the synthesis of the enzyme OR
- reduces its degradation and the metabolic capacity for the isoenzyme is
- increased
-
reduces its degradation and the metabolic
capacity for the isoenzyme is increased
Induction
1 of the 2 processes of P450 Enzyme
-
Inhibition
Competitive binding at an enzyme's binding sites(s)
- A drug with a high affinity for an enzyme with SLOW the
- metabolism of any low affinity drug that produces a particular enzyme
-
A drug with a high affinity for an enzyme with SLOW the metabolism of any low affinity drug that produces a particular enzyme
Inhibition
-
designed to take advantage of absorption or
metabolic properties to provide more optimal drug therapy
Prodrugs
-
Prodrugs
- designed to take advantage of
- absorption or
- metabolic properties to provide
- more optimal drug therapy
-
an inactive compound that is administered and
then transformed into an active substance by either chemical or metabolic means
Prodrugs
-
designed to take advantage of absorption or
metabolic properties to provide more optimal drug therapy
Prodrugs
-
Prodrugs
- designed to take advantage of
- absorption or
- metabolic properties to provide
- more optimal drug therapy
-
Biotransformation Reactions are broken into what
two groups
Phase I Rxns
Phase II Rxns
-
Phase I rxns are
Functionalization Rxns
-
How do Phase I rxns work?
make a compound more hydrophilic
by introducing or exposing a polar functional group
-
reactions that introduce or expose a functional
group on a compound
Phase I Rxns
-
Phase I Rxns
reactions that introduce or expose a functional group on a compound
-
in some cases, these reactions enhance or retain
the activity of the parent compound.
Phase I Reactions
-
biosynthetic reactions
Phase II Rxns
-
result in covalent linkage between a functional group on the parent drug and a highly polar conjugate.
Phase II Rxns
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