Transcript Slide 1
III. Drug Metabolism
The
aim
of
drug
metabolism is to convert
lipid soluble (non polar)
drugs to polar metabolites
easily excreted in urine.
The liver is the principle
organ of drug metabolism.
The drug metabolite may be:
Inactive: metabolism results in termination of drug
action e.g. most drugs.
Active like the parent drug: e.g. diazepam (sedative
and hypnotic).
Active and the parent drug is inactive: (prodrug)
e.g. methotrexate
IV. Drug Excretion
Kidney is the major rout of
excretion of drugs or their
metabolites.
Other
channels
of
excretion include the lungs,
intestine, skin and milk.
Drugs are eliminated from
the body either unchanged
as the parent drug or as
metabolites (a changed form
of the drug).
Since drugs are small particles dissolved in the blood,
they are usually filtered into the kidneys and then
reabsorbed back into the bloodstream.
In order for the kidney to eliminate drugs from the
body, the drug must somehow be prevented from
being
reabsorbed
from
the
urine
into
the
bloodstream.
The drug must be chemically changed into a
compound that is less fat-soluble and therefore less
capable of being reabsorbed.
Drug Product (Delivery system):
The dosage form that contains the therapeutically
active agent (s), generally but not necessarily in
association with inactive ingredients (e.g. tablet,
capsule, suspension, ….. ).
Drug product selection:
The process of selecting dosage form in which the
drug product will be manufactured.
The duration of drug therapy:
The time necessary for the treatment of a disease
with a drug.
Dosage regimen:
Is the manner in which a drug is taken.
It comprises calculation of the required dose (size
of the dose) and adjusting dosing interval (dosing
frequency) for patients.
Therapeutic Objective:
It may be either the treatment, mitigation or the
prevention of the disease.
It is evident that both the duration of drug
therapy and the dosage regimen depend on the
therapeutic objective.
Minimum Effective Concentration (MEC):
Many drugs have no demonstrable therapeutic
effect or do not produce a desired degree of
pharmacologic response unless a minimum
concentration is reached at the receptors (sites of
action).
The MEC represents the minimum concentration
of a drug needed at the sites of action (receptors)
to produce the desired pharmacologic effect.
Minimum Toxic Concentration (MTC):
conc.
It reflects the drug
concentration
at
Toxic
MTC
which a toxic effect
will appear.
Therapeutic
MEC
Ineffective
time
Therapeutic concentration range
(Therapeutic window):
It is the range of drug concentration between the
MEC and the MTC.
In other words, it is a region associated with
therapeutic effect.
An optimal dosage regimen might be defined as
one that maintains the plasma concentration of a
drug within its therapeutic window.
Drug with narrow therapeutic window:
These drugs require
conc.
Therapeutic drug
Toxic
concentration monitoring.
Examples:
Therapeutic Window
e.g.1 Digoxin
e.g.2 Warferin
e.g.3 Theophylline
Ineffective
time
Therapeutic effectiveness:
Is the difference between effective therapy and
toxic effects.
Biopharmaceutics:
Is
the study of the effect of various
pharmaceutical formulation variables on the
delivery of the drug to the body under normal and
pathologic conditions (impaired physiological
function).
Bioavailability:
Is the rate (amount/time) and extent (total
amount) to which the active drug ingredient or
therapeutic moiety is absorbed from a drug
product and becomes available at the receptor
(site of action).
When a medication is administered intravenously,
its bioavailability is 100%.
However when a medication is administered via
other routes (orally), its bioavailability generally
decreases (due to incomplete absorption and firstpass metabolism) or may vary from patient to
patient.
Bioavailability
must
be
considered
when
calculating dosages for non-intravenous routes of
administration.
Pharmaceutic equivalents:
These are drug products that are identical in:
Active drug ingredient
Strength or concentration
Dosage form
Route of administration
They may differ in some characteristics e.g.
colour, shape, packing, expiration time and
inactive ingredients.
Bioequivalent drug products:
These are pharmaceutical equivalents whose rate
and extent of absorption are not different (i.e.
have similar bioavailability).
When given in the same concentration (molar
dose) under similar experimental conditions).
Pharmaceutic alternatives:
These are drug products that contain the same
therapeutic moiety but not necessarily as the
same chemical structure.
e.g.1 Betamethasone Acetate and Betamethasone
Valerate
e.g.2 Tetracyclin Hydrochloride and Tetracyclin
Phosphate
Also, different dosage forms containing the same
active ingredients and produced by a single
manufacturer are pharmaceutic alternatives.
e.g.1 Sustained-release dosage form (Olfen SR)R
versus
a
standard
immediate-release
drug
product of the same ingredient (Olfen)R.
e.g.2 Diclofenac Sodium (Declophen)R ampoule
and Diclofenac Sodium (Declophen)R tablet.