الفهرس 
material and methodsOnly 14 pages are availabe for public view
 |  | from | 199 |  |  |
| | | from | 199 | | |
Abstract
Epilepsy is one of the most common neurological disorders. It
IS a life long disease which requires a life long treatment. So, it is
very important to study the toxic effects of the used drugs to avoid
more suffer for the patient.
A major problem in the management of epileptic patients is
the possibility that certain antiepileptic drugs may cause
chromosomal abnormalities which may lead to birth defects and
also may be involved in the development of neoplasia. On the other
hand controversy still exists regarding the potential mutagenicity of
these drugs. Also, there is a shortage in knowledge about the
immuno toxicity of these drugs.
The present work was carried out to evaluate some of the
toxic effects of the most commonly used antiepileptic drugs namely
Phenytoin Sodium, carbamazepine, Clonazepam, and Sodium
valproate, specially their potential mutagenicity and
immunotoxicity in rats.
150 adult albino rats of both sexes weighing 200 - 220 gms
each were kept under the same conditions for 15 days, then they
were divided into 10 groups, 15 rats ofor each group. 8 groups were
used as test groups, each 2 groups of them received daily oral toxic
dose of one drug from the four tested antiepileptic drugs. The toxic
dose of each drug was considered as 3 folds its therapeutic dose.
(119)
Summary and Conclusion ....
The rats of one group from each 2 groups received the same drug
were sacrified after one month treatment, the rats of the other group
were sacrified after 3 months.
The last 2 groups of the 10 groups were used as control
groups treated in the same way given daily oral dose of distilled
water with no drugs. rats of one control groups were sacrified after
one month and the others after 3 months.
All sacrified rats either test or control rats were subjected to
toxicological evaluation, by the following studies:
(1) Biochemical study:
(a) Liver function tests : Liver affection was evaluated by
estimation of SOOT, SGPT, Alk.Ph.
(b) Kidney function tests : Kidney affection was evaluated by
estimation of blood urea, serum creatinine.
(2) Cytogenetic study:
Mutagenic effects was evaluated by studying the frequencies
of structural chromosomal abnormalities (Gaps, Break, Dicentric
chromosomes, Ring chromosomes, Minute fragments, and total
structural) and numerical chromosomal abnormalities
(Aneuploidies, polyploidies, total numerical) in rat bone marrow
cells.
(120)
Summary and Conclusion ....
(3) Immunologic study:
Evaluation of the immunotoxicity was done by studying the
degree of lymphocyte activation of splenic rat cells after being
cultured with the mitogen phytoheamagglutinin (P.H.A.).
Analysis of the results obtained revealed the following:
(l) Biochemical effects :
(a) Liver functions affection:
Affection of the liver function indicated by increased levels of
SGOT, SGPT, and Alk. Ph. to a varying degrees was observed with
chronic administration of all the four drugs with the observation
that sodium valproate was the most hepatotoxic drug used,
clonazepam was the least hepatoloxic one, while carbamazepine
and phenytoin sodium caused moderate hepatotoxicity.
(b) Kidney function affection:
Chronic administration of the 4 used drugs affected the renal
functions indicated by increased 0 levels of blood urea and S.
creatinine, to a varying degrees, with the observation that
carbamazepine was the most nephrotoxic drug, phenytoin sodium
was the least nephrotoxic one, while clonazepam and sodium
valproate were moderately nephrotoxic.
(2) Cytogenetic (Mutagenic) effects :
It was observed that, in rats treated with phenytoin sodium,
the frequencies of total structural and total numerical chromosomal
(121)
Summary and Conclusion ....
aberrations were significantly increased compared to the control
values after 1 and 3 months.
On the other hand, the frequencies of both Structural and
numerical chromosomal aberrations In rats treated with
carbamazepine, clonazepam and sodium valproate were not
significantly different from those in control rats.
(3) Immunologic (Immunotoxic) effects:
It was observed that chronic administration of phenytoin
sodium caused a significant depression in the. cell mediated
immune function, indicated by a significant decrease in the
percentage of lymphocytes transformed into blast cells when the
splenic rat cells were cultured with the mitogen
phytoheamagglutinin (P.RA).
On the other hand, it was observed that chronic
administration of carbamazepine, clonazepam, and sodium
valproate caused no significant change in the percentage of
lymphocytes transformed to blast cells when the splenic rat cells
were cultured with phytoheamagglutinin (P.H.A.)
In conclusion :
(I) The safest antiepileptic drugs, is clonazepam, which is neither
mutagenic nor immunotoxic, and have a little effect on liver and
moderate effect on kidney functions on chronic use.
(I 22)
Summary and Conclusion ....
(2) The most hepatotoxic drug, is sodium valproate, while the most
safe drug on the liver is clonazepam.
(3) The most nephrotoxic drug, is carbamazepine, while the most
safe drug on the kidney is phenytoin sodium.
(4) Phenytoin sodium is potentially mutagenic on chronic use,
while, clonazepam, carbamazepine and sodium valproate are
not.
(5) Phenytoin sodium has a potential immunotoxic effect on
prolonged administration, while clonazepam, carbamazepine
and sodium valproate have no effect on immune function.