fumarates and Abnormalities--Drug-Induced

The recent approval of several oral disease-modifying drugs (DMDs) for multiple sclerosis (MS) brings promise of improved clinical effectiveness as well as greater drug compliance compared to the existing non-oral DMDs, and substantially increases patient choice and therapeutic options in the effective management of MS. However, for men and women with MS of childbearing age, concerns about the effect of oral DMDs on pregnancy and the fetus may arise. Some limited data from animal reproductive studies of oral DMDs suggest a potential increased risk of early pregnancy loss, impaired growth and birth defects. Although active surveillance mechanisms exist, there is limited data to inform clinical practice. Using existing information from published clinical trials and drug monographs, as well as recent conference proceedings, this review summarizes the mechanism of action (in relation to embryogenesis and pregnancy) and existing animal or human pregnancy-related data for approved (fingolimod, teriflunomide and dimethyl fumarate) and investigational (laquinimod and firategrast) oral DMDs for MS.

Topics: Abnormalities, Drug-Induced; Administration, Oral; Animals; Crotonates; Dimethyl Fumarate; Female; Fingolimod Hydrochloride; Fumarates; Humans; Hydroxybutyrates; Immunologic Factors; Multiple Sclerosis; Nitriles; Pregnancy; Pregnancy Outcome; Prenatal Exposure Delayed Effects; Propylene Glycols; Sphingosine; Toluidines

Psoriasis, a chronic common immune-mediated disease with frequent remitting/relapsing courses, has a high negative impact on the quality of life, especially in patients moderately or severely affected by the disease. It is also associated with various co-morbidities resulting in a decreased life expectancy and remarkable socioeconomic costs. At least one third of the patients who suffer from it has moderate or severe psoriasis and require continuous treatment to control disease activity. The therapeutic approach in daily practice is usually determined by the severity of the disease. Whether the definition of disease severity is not always clear, there is a considerable number of patients requiring systemic treatment to control the symptoms of psoriasis. The treatment options available for the management of moderate-severe psoriasis have dramatically increased over the past decade, and now range from phototherapy to traditional systemic treatments to biologics. Available data from clinical trials and growing number of patients treated with biologics shows that this new agent are effective and relatively safe to control psoriasis, and are coupled with improved tolerability, convenience and improvement in quality of life. This review shortly presents the characteristics, safety and efficacy profile of the conventional and newer systemic drugs used in moderate-to-severe psoriasis.

Topics: Abnormalities, Drug-Induced; Alefacept; Antibodies, Monoclonal; Clinical Trials as Topic; Contraindications; Cyclosporine; Etanercept; Female; Fumarates; Hematologic Diseases; Humans; Hypertension; Immunoglobulin G; Immunosuppressive Agents; Kidney Diseases; Male; Methotrexate; Photochemotherapy; Pregnancy; Pregnancy Complications; Psoriasis; Receptors, Tumor Necrosis Factor; Recombinant Fusion Proteins; Retinoids; Severity of Illness Index; Tumor Necrosis Factor-alpha

Angiotensin (Ang) II plays important roles in the development of hypertension and cardiovascular and renal injury. Pharmaceutical approaches to block its activity led to the development of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers. Numerous trials have documented their efficacy in controlling blood pressure, minimising left ventricular remodelling, preventing progression to heart failure, ameliorating proteinuria and retarding renal disease progression. Although they are considered safe in general, there remain concerns about the potential for adverse events in certain target populations. Recently, several novel, low molecular weight renin inhibitors without the extended peptide-like backbone of previous renin inhibitors were developed with favourable pharmacokinetic properties. They have been shown to successfully reduce Ang II levels in normal volunteers and to lower blood pressure in patients with mild-to-moderate hypertension. In this review, the authors summarise current knowledge about these renin inhibitors.

Topics: Abnormalities, Drug-Induced; Amides; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Clinical Trials as Topic; Fumarates; Humans; Hyperkalemia; Hypertension; Hypotension; Inappropriate ADH Syndrome; Male; Mice; Renin

Topics: Abnormalities, Drug-Induced; Animals; Animals, Newborn; Cycloheptanes; Female; Fumarates; Mice; Parasympatholytics; Pregnancy; Pregnancy, Animal; Propylamines; Rabbits; Rats

Topics: Abnormalities, Drug-Induced; Animals; Cycloheptanes; Dogs; Fumarates; Mice; Rabbits; Rats