allopurinol and Abnormalities--Drug-Induced

Allopurinol is widely used in the management of multiple disorders including gout, kidney stones and inflammatory bowel disease. Despite of long-term experience, its safety in pregnancy has been debated due to reports on possible teratogenicity. We aimed to review the literature on the safety of allopurinol in pregnancy and offspring. In animals, allopurinol induced species-specific reproductive toxicity. In humans, a total of 53 allopurinol exposed infants were reported in the literature. Major congenital malformations were reported in two cases with a comparable pattern of multiple abnormalities. Five other infants had minor birth defects. In conclusion, the association between allopurinol and teratogenicity appears to be weak and limited to two reports with uncertain causality. However, the available data are insufficient to make a certain judgement, and as allopurinol treatment evolves, report and prospective follow-up of all exposed infants (i.e. deviant and normal cases) should be encouraged.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Allopurinol; Animals; Female; Gout Suppressants; Humans; Maternal-Fetal Exchange; Pregnancy; Teratogens

The widely accepted standard therapy for cutaneous sarcoidosis includes corticosteroids, antimalarials, and methotrexate. However, a better understanding of the basic immunopathogenic properties of sarcoidosis has elucidated a number of steps critical to the persistence and progression of disease that may be vulnerable to treatment by targeted therapy. This article reviews both standard and newer therapeutic options for cutaneous sarcoidosis.

Topics: Abnormalities, Drug-Induced; Adrenal Cortex Hormones; Allopurinol; Animals; Anti-Inflammatory Agents; Antibodies, Monoclonal; Antigen Presentation; Antimalarials; Chlorambucil; Contraindications; Cyclosporine; Cytokines; Dermatologic Agents; Drug Therapy, Combination; Female; Humans; Immunosuppressive Agents; Infliximab; Isoxazoles; Laser Therapy; Leflunomide; Male; Melatonin; Methotrexate; Models, Immunological; Pentoxifylline; Pregnancy; Pregnancy Complications; Sarcoidosis; Skin Diseases; Tetracyclines; Th1 Cells; Thalidomide

Topics: Abnormalities, Drug-Induced; Alkylating Agents; Allopurinol; Alopecia; Antimetabolites; Antineoplastic Agents; Chemotherapy, Cancer, Regional Perfusion; Cyclophosphamide; Drug Synergism; Female; Fetus; Humans; Kidney Calculi; Kidney Diseases; Kidney Tubules; Mechlorethamine; Mercaptopurine; Neoplasms; Pregnancy; Pregnancy Complications; Uric Acid; Vincristine

We report on a case of a multiple congenital anomalies in a newborn infant whose mother was on allopurinol treatment through the pregnancy. The pattern of congenital anomalies that was noted in our patient was similar to the pattern described in a number of published reports following mycophenolate mofetil [CellCept®] treatment during pregnancy. The anomalies present in our patient include: diaphragmatic hernia, unilateral microtia and absence of external auditory canal, micrognathia, microphthalmia, optic nerve hypoplasia, hypoplasia of the corpus callosum, unilateral renal agenesis, pulmonary agenesis, and cleft lip and palate. Since both allopurinol and mycophenolate mofetil act by disrupting purine biosynthesis and given the similarities in anomalies seen after prenatal exposure, we suggest that allopurinol should also be considered a teratogen.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Allopurinol; Antimetabolites; Female; Humans; Infant, Newborn; Kidney Calculi; Male; Mycophenolic Acid; Pregnancy; Pregnancy Complications; Prenatal Exposure Delayed Effects; Purines; Teratogens

Day 9.5 rat embryos were exposed in culture to xanthine/xanthine oxidase generated active oxygen species. Growth and development were assessed after 46 hr of culture. The treatment induced abnormalities of the neural suture, the severity of which increased in a dose-related manner with the concentration of substrate or enzyme. Glutathione (10 mM) or catalase (50 micrograms/ml) either partially or completely abolished the effects of xanthine/xanthine oxidase, whereas the addition of superoxide dismutase (50 micrograms/ml) or desferrioxamine (1mM) did not reduce the number of malformed embryos. These findings suggest that hydrogen peroxide and/or hydroxyl radicals are responsible for the effects of xanthine and xanthine oxidase.

Topics: Abnormalities, Drug-Induced; Animals; Catalase; Deferoxamine; Embryo, Mammalian; Glutathione; Organ Culture Techniques; Oxygen; Rats; Rats, Inbred Strains; Superoxide Dismutase; Xanthine; Xanthine Oxidase; Xanthines

Topics: Abnormalities, Drug-Induced; Allopurinol; Barbiturates; Chromosome Aberrations; Drug-Related Side Effects and Adverse Reactions; Enzyme Induction; Estrogens; Female; Genetic Diseases, Inborn; Humans; Hyperbilirubinemia, Hereditary; Microsomes, Liver; Mutation; Neoplasms; Pharmaceutical Preparations; Pharmacogenetics; Uric Acid

Topics: Abnormalities, Drug-Induced; Allopurinol; Animals; Embryo, Mammalian; Female; Guanosine; Hypoxanthines; Injections, Intraperitoneal; Inosine Nucleotides; Maternal-Fetal Exchange; Mice; Pregnancy; Purines; Xanthine Oxidase