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Companion Animal Posters
Anticonvulsant drugs, such as phenobarbital, are a known cause of
hepatic cirrhosis and have been
studied throughout the years
regarding their possible association
with organ degeneration and tumor
development (1, 2). It is essential that
clinicians inform the owners that
long term side effects are to be
expected with anticonvulsant therapy. Educating the
owners is an important step in ensuring a prompt and
effective response to all situations, and in improving
the patient’s quality of life and life expectancy.
The case presented pertains to the necropsy of a
14-year-old dog with a history of epilepsy and carcinoma of the bladder. The cadaver exhibited enlarged
variegated liver, with superficial irregularity. Discrete
bilateral hydronephrosis and a bladder nodule were
observed, as well as prostatic hypertrophy and irregularity. Histological lesions were early stage cirrhosis
and chronic nephritis; a prostatic transitional cell carcinoma with vesical metastization was diagnosed, as
well as an early stage ependymoma in the lateral
ventricles.
Continuous exposure to phenobarbital has been
proven to cause cirrhosis in dogs and humans (1, 3).
Additional side effects of long term treatment with
phenobarbital may include decreased muscle tonus in
the ureters and bladder, disruption of testicular function, changes in thyroid function and anemia (3-7). The
drug has also been associated with impaired brain
development in infants treated for early onset epilepsy
and febrile seizures (8, 9). A connection between long
term barbiturate intake and bladder tumors was once
suspected in humans and the possibility has not yet
been refuted (10-12). The idea that these drugs may
play a role on bladder tumor promotion in dogs is plausible, although unproven.
Abstracts European Veterinary Conference Voorjaarsdagen 2011
This case rekindles the debate around long term effects
of treatment with anticonvulsants and the need to
acquire information that can serve both clinician and
owner and, ultimately, benefit the patient.
1. Bunch SE, Castleman WL, Hornbuckle WE, Tennant BC. Hepatic
cirrhosis associated with long-term anticonvulsant drug therapy in dogs. J Am Vet Med Assoc. 1982 Aug 15;181(4):357-62.
2. Foster JR. Spontaneous and drug-induced hepatic pathology
of the laboratory beagle dog, the cynomolgus macaque and
the marmoset. Toxicol Pathol. 2005;33(1):63-74.
3. Phenobarbital Tablets, USP CIV [database on the Internet]. U.S.
National Library of Medicine. 2010 [cited 2010 January 10].
Available from: http://dailymed.nlm.nih.gov/dailymed/fda/
fdaDrugXsl.cfm?id=19791&type=display.
4. Chen SS, Shen MR, Chen TJ, Lai SL. Effects of antiepileptic
drugs on sperm motility of normal controls and epileptic
patients with long-term therapy. Epilepsia. 1992 JanFeb;33(1):149-53.5. Gaskill CL, Burton SA, Gelens HC, Ihle SL,
Miller JB, Shaw DH, et al. Changes in serum thyroxine and thyroid-stimulating hormone concentrations in epileptic dogs
receiving phenobarbital for one year. J Vet Pharmacol Ther.
2000 Aug;23(4):243-9.
6. Muller PB, Wolfsheimer KJ, Taboada J, Hosgood G, Partington
BP, Gaschen FP. Effects of long-term phenobarbital treatment
on the thyroid and adrenal axis and adrenal function tests in
dogs. J Vet Intern Med. 2000 Mar-Apr;14(2):157-64.
7. Chauvet AE, Feldman EC, Kass PH. Effects of phenobarbital
administration on results of serum biochemical analyses and
adrenocortical function tests in epileptic dogs. J Am Vet Med
Assoc. 1995 Nov 15;207(10):1305-7.
8. Bittigau P, Sifringer M, Genz K, Reith E, Pospischil D, Govindarajalu S, et al. Antiepileptic drugs and apoptotic neurodegeneration in the developing brain. Proc Natl Acad Sci U S A. 2002
Nov 12;99(23):15089-94.
9. Calandre EP, Dominguez-Granados R, Gomez-Rubio M,
Molina-Font JA. Cognitive effects of long-term treatment with
phenobarbital and valproic acid in school children. Acta Neurol Scand. 1990 Jun;81(6):504-6.
10. Morimoto S. Alteration of intercellular communication in a
human urothelial carcinoma cell-line by tumor-promoting
agents. Int J Urol. 1996 May;3(3):212-7.
11. Wihlborg A, Johansen C. Incidences of kidney, pelvis, ureter,
and bladder cancer in a nationwide, population-based cancer
registry, Denmark, 1944-2003. Urology. 2010 May;75(5):1222-7.
12. Diwan BA, Ohshima M, Rice JM. Promotion by sodium barbital
of renal cortical and transitional cell tumors, but not intestinal
tumors, in F344 rats given methyl(acetoxymethyl)nitrosamine,
and lack of effect of phenobarbital, amobarbital, or barbituric
acid on development of either renal or intestinal tumors. Carcinogenesis. 1989 Jan;10(1):183-8.
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CHAPTER 5
Lo n g - t e r m e f f e c t s o f lo n g - t e r m
t r e at m e n t w i t h P h e n o b a r b i ta l a n d
NSAID s : a c a s e r e p o r t
Rute M Noiva, Msc, DVM, Ana M Santos, DVM, Maria C
Peleteiro, PhD
Centro de Investigação Interdisciplinar em Sanidade
Animal (CIISA), Faculdade de Medicina Veterinária,
Universidade Técnica de Lisboa, Avenida da Universidade
Técnica, 1300-477 Lisboa
Portugal
Email: [email protected]