الخميس، 14 أكتوبر 2010

Nutrient-Drug Interactions


Nutritional Status and Nutrient-Drug Interactions: Severe psoriasis has been associated with nutritional deficiencies because of an accelerated loss of nutrients from the hyperproliferation and desquamation of the epidermal layer of skin. Furthermore, an elevated requirement of some nutrients such as antioxidants may occur.

Beside the disease-related risk of poor nutritional status, patients with chronic diseases are often regular drug users. Therefore they are at particular risk for drug-nutrient interactions. In psoriasis, especially systemic therapy can be associated with alterations of the nutritional status. About 30% of patients with psoriasis have symptoms that are severe enough to require systemic therapy. On the other hand, dietary factors can affect a drug's pharmacokinetics and pharmacodynamics. One systemic treatment in patients with psoriasis is the folic acid antagonist methotrexate which is used at low doses. It is hepatotoxic, leads to loss of appetite and its use is contraindicated in patients with poor nutritional status. Patients with psoriasis who received low-dose methotrexate therapy (25 mg weekly) had significantly higher fasting plasma homocysteine and lower plasma folate levels than age matched controls. This finding is supported by studies in patients with rheumatoid arthritis on methotrexate therapy.

Homocysteine is derived from methionine and is used as a sensitive marker of folate status. Elevated homocysteine concentrations are associated with an elevated risk of atherosclerosis and may increase the risk of dementia. Homocysteine can be degraded through two enzymatic pathways: the remethylation of homocysteine to methionine is catalysed by the methionine synthetase. In this reaction 5-methyl tetrahydrofolic acid is involved as a methyl group donor, while vitamin B12 is the intermediate acceptor of the methyl group.

In folate deficiency, plasma homocysteine rises. In the trans-sulphuration pathway, homocysteine forms cysteine, but this degradation pathway is not sufficient to normalize homocysteine concentrations in folate deficiency. Homocysteine can be used as a sensitive marker of folate status in patients with psoriasis receiving methotrexate. Folic acid supplements should be prescribed routinely to these patients. In order to reduce side-effects, 5 mg of folic acid two to five times weekly is commonly given to patients receiving methotrexate.

Another systemic therapy in psoriasis is ciclosporin, an immunosuppressive agent. Owing to downregulation of the cytochrome P450 3A4 enzyme in the intestinal wall, the oral bioavailability of ciclosporin increases by more than 60% when taken with grapefruit juice. Patients should be advised to avoid the consumption of grapefruit juice when taking ciclosporin.

Retinoids such as etretinate are synthetic analogues of retinoic acid (vitamin A). Systemic retinoids can induce symptoms of hypervitaminosis A including headache, weakness and anorexia. Patients taking retinoids should be advised to avoid food sources rich in vitamin A, particularly liver. Retinoids can also induce hyperlipidaemia. Thus regular monitoring of this side-effect is necessary. Serum triglycerides can be significantly lowered by a diet low in saturated fatty acids and high in n-3 fatty acids from fish such as salmon, herring or fish oil supplements. Furthermore, alcohol intake and dietary monosaccharides should be reduced.

Dithranol is the most common therapeutic agent. The therapeutic effect is based on the generation of reactive oxygen intermediates and anthrone radicals produced in the skin. As superoxide dismutase and α-tocopherol acetate were effective in inhibiting cytokine elevation induced by dithranol, systemic antioxidant administration may reduce dithranol-associated side-effects.

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