34 Section 1/ General Principles of Pharmacologymetabolism of a number of drugs like barbi-
turate induced sleeping time is prolonged in
thyroidectomized animals. Alloxan or
streptozotocin induced diabetes in rats also
reduced the metabolism of hexobarbitone
thus prolonging the sleeping time.
EFFECTS OF THE INTESTINAL
MICROFLORA
The metabolic transformation of
many drugs is catalysed by various
enzyme of the intestinal microflora. The
anaerobic microflora and colon are rich
in reductases which may be responsible
for a significant proportion of the
azoreductase and nitroreductase activity.
The enzymes and other factors that may
produce change in the nature of intestinal
microflora might also produce changes in
the metabolism pattern of the drugs.
GENETIC FACTOR – SPECIES
DIFFERENCES
Species differences in the metabolism
of drug may be due to the difference in
the rate of metabolism or in their metabo-
lites difference. Certain drugs have been
found safe and non-toxic in animals, but
when they were tested in human beings
severe toxic effects were observed. For
example, when sulfanilamide was tested
in dog it was found safe and non-toxic,
but when it was administered to human
being, certain toxic effects like the hema-
turia, renal failure were observed.
Likewise, in certain case it was opposite.
In human beings, phenacetin is generally
free from toxic side effects, but in dogs it
undergoes deacetylation.
PHARMACODYNAMIC FACTORS
Effects of Protein Binding
Acetylation of sulfonamides is reduced
by protein binding, but the formation of
glucuronide conjugates is unaffected.EXCRETION OF DRUGS
The excretion of drugs has been known to
take place through different routes mainly
kidneys, skin, lungs and alimentary tract.
Only few drugs are eliminated through skin
and via lungs (only for volatile drugs like
chloroform, ethyl alcohol, ether etc.). Drugs
which are poorly absorbed are excreted in
faeces. So kidneys serve as the primary and
major organ for removal of most drugs,
which is constituted by the microunits
called ‘nephron’. Three major processes
that are involved in the excretion of drugs
through kidneys are:
i. Glomerular filtration,
ii. Tubular secretion, and
iii. Passive diffusion.
Glomerular filtration: The rate of
drug filtration is determined by the glom-
erular filtration rate (GFR) by using a sub-
stance like ‘inulin’, which when injected
is filtered by the glomeruli and does not
undergo either reabsorption or secretion
by the renal tubules. The highly protein
bound drugs like phenylbutazone,
digoxin etc. are excreted slowly. Factors
affecting the GFR of drug also can influ-
ence the rate of drug clearance. For ex-
ample inflammation of the glomerular
capillaries may increase GFR. Molecular
configuration of drugs may also influence
the GFR.