Change in cough reflex after treatment with enalapril and ramipril.
OBJECTIVE
To find out whether enalapril or ramipril causes the sensitivity of the cough reflex to change or symptomatic cough to develop in patients with hypertension.


METHODS
Prospective, placebo controlled, double blind, randomised crossover study.


METHODS
Academic units of clinical pharmacology and medicine.


METHODS
20 Patients (nine men and 11 women) who needed to take angiotensin converting enzyme inhibitors to control hypertension.


METHODS
All patients received enalapril 10 mg daily, ramipril 10 mg daily, or placebo daily for one week in random order, with a washout period of at least one week between treatments. For assessment of sensitivity of the cough reflex the patients inhaled various concentrations of capsaicin solution in random order.


METHODS
Measurement of the doses of capsaicin required to cause two or more and five or more coughs or the development of a symptomatic cough.


RESULTS
Blood pressure, symptoms of cough, and the sensitivity of the cough reflex to inhaled capsaicin were recorded at the start of the study and before and at the end of each treatment period. Plasma urea and creatinine concentrations and angiotensin converting enzyme activity were measured at the start of the study and the end of each treatment period. Data were analysed by two way analysis of variance. Mean blood pressure was 159/97 mm Hg at the start of the study and 152/92, 143/88, and 147/86 mm Hg after treatment with placebo, enalapril, and ramipril respectively. Mean (SE) plasma angiotensin converting enzyme activity was 2.2 (0.2) mmol/l/h after treatment with placebo and fell significantly to 1.3 (0.1) mmol/l/h and to 0.4 (0.1) mmol/l/h after treatment with enalapril and ramipril respectively. No patient complained of cough while taking placebo but three women complained of cough when taking both enalapril and ramipril. The mean (95% confidence interval) lowest dose of capsaicin causing two or more coughs was 2.4 (1.5 to 4.0), 1.8 (1.12 to 2.82), and 2.2 (1.7 to 3.0) nmol after treatment with placebo, enalapril, and ramipril respectively; none of these changes were significant. The lowest dose of capsaicin causing five or more coughs was 18.9 (13.9 to 25.8), 14.4 (8.4 to 24.5), and 15.3 (10.8 to 21.2) nmol respectively; none of these changes were significant. The three patients who complained of cough had normal sensitivity to capsaicin after treatment with placebo but had a considerably increased sensitivity after treatment with enalapril and ramipril.


CONCLUSIONS
Both enalapril and ramipril increase the sensitivity of the cough reflex appreciably in patients who complain of cough during treatment, but they do not change the se
McEwan
J R
JR
Department of Clinical Pharmacology, Royal Postgraduate Medical School, London.
Choudry
N
N
Street
R
R
Fuller
R W
RW
D000328:Adult; D000368:Aged; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001643:Bridged Bicyclo Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D001952:Bridged-Ring Compounds / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D003371:Cough / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D004311:Double-Blind Method; D004656:Enalapril / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D006973:Hypertension / Q000097:blood / Q000517:prevention & control; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood; D011446:Prospective Studies; D017257:Ramipril; D011897:Random Allocation; D012018:Reflex / Q000187:drug effects*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001643:Bridged Bicyclo Compounds; D001952:Bridged-Ring Compounds; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A; D017257:Ramipril