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The Pharmaceutical Journal Vol 267 No 7161 p217-221
18 August 2001

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Iron for ACE inhibitor-induced cough

Iron supplements might prevent angiotensin-converting enzyme (ACE) inhibitor-induced dry cough, researchers in Korea suggest.

Persistent dry cough is the most troublesome and frequent side effect of ACE inhibitor therapy, occurring in up to 39 per cent of patients, say Dr Sang Chol Lee, Sungkyunkwan University school of medicine, Seoul, and colleagues.

Although the mechanism that causes ACE inhibitor-induced cough is not fully understood, it is known that administration of ACE inhibitors increases nitric oxide generation, they say. Nitric oxide (which has inflammatory effects on bronchial epithelial cells) is generated by the haem-related enzyme, nitric oxide synthase. Activity of this enzyme is reduced by an increased concentration of iron.

The researchers tested the hypothesis that iron supplementation would reduce ACE inhibitor-induced cough in 19 patients. After a two-week observation period, patients received either 256mg ferrous sulphate or placebo for four weeks. They recorded the severity of cough in a diary using a scoring system graded from 0 (no cough) to 4, (severe cough that interferes with daily life and sleep).

Mean daily cough score was significantly reduced by iron supplementation from 3.07&mn;0.7 in the observation period to 1.69&mn;1.10 at the end of the treatment period (p<0.01). No significant change was found in the placebo group.

“This dramatic effect of iron supplementation on dry cough may require further explanation, but according to our hypothesis and the results of previous studies, iron may be the key element in the control of the dry cough mechanism,” the researchers conclude (Hypertension 2001;38:166).

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