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Biomedical subjects

W D Cooper

Publications and source records attributed to W D Cooper.

At least 19 recordsLinked to original sources
PubMed1989

Headache and blood pressure: evidence of a close relationship.

Although headache is sometimes regarded as a symptom of severe hypertension, its relationship to blood pressure is not clear. In 11,710 patients with mild to moderate essential hypertension we have found that headache was common and may be reduced by treatment. We found a clear relationship between the frequency of reports of headache and both systolic and diastolic blood pressure irrespective of treatment or the type of drug used to treat hypertension. Calcium antagonists appeared most likely to be a cause of headache in hypertensive patients.

Blood Pressure↗
PubMed1988

Clinical profile of angioedema associated with angiotensin converting-enzyme inhibition.

Based on data from three studies with complete recording of adverse events in about 12,000 patients each, we determined that angioedema in association with the angiotensin converting-enzyme inhibitor enalapril maleate occurred during the first week of therapy at the rate of one case per 3000 patients per week. Thereafter, the incidence was 14-fold lower, without evidence of a temporal trend in incidence beyond the first week of therapy. The cumulative incidence was one case per 1000 patients treated (0.1%). An additional 138 case reports consistent with the diagnosis of angioedema were obtained from our overall controlled and marketed experience using enalapril in more than 1.2 million patients. These reports were examined to further characterize the reaction. The cases generally were mild, and they resolved on discontinuation of drug therapy. Seven patients experienced angioedema or urticaria in association with both enalapril and captopril, a structurally different angiotensin converting-enzyme inhibitor. This further suggested that the side effect is mechanism based. If angioedema is suspected, therapy with any angiotensin converting-enzyme inhibitor should be interrupted promptly, respiratory distress should be treated appropriately, and subsequent therapy should be initiated with an agent from an alternative class of medication.

Angioedema↗
PubMed1988

Pharmacokinetics of lisinopril, enalapril and enalaprilat in renal failure: effects of haemodialysis.

1. Lisinopril and enalapril were administered as 2.5 mg single doses and as eight single daily 2.5 mg doses to separate groups of six patients with chronic renal failure. Patients were receiving regular haemodialysis. 2. In the absence of haemodialysis, the decline in plasma concentrations of lisinopril and enalaprilat was extremely slow and plasma concentrations were generally high. 3. Haemodialysis had large effects on plasma concentrations of lisinopril and enalaprilat. A 4 h period reduced plasma concentrations of both drugs by around one-half and often by significantly more than this. Even 1 or 2 h of haemodialysis had significant effects. 4. Haemodialysis plasma clearance was similar for both drugs with mean values of the order of 40 ml min-1. Clearance did not markedly differ when measured after 1, 2 or 4 h of haemodialysis or after single or multiple doses of lisinopril or enalapril. 5. The design of dosage regimens of both lisinopril and enalapril for patients with severe renal impairment or chronic renal failure should take into consideration the use and effects of haemodialysis.

Adult↗
PubMed1988

Symptoms in hypertensive patients: the effect of treatment withdrawal.

We have evaluated the effect of withdrawal of antihypertensive drugs on the frequency of symptoms over a 2-week period in 11,710 hypertensive patients. Previously untreated patients complained most frequently of headache, dizziness and chest pain, whereas most other symptoms occurred more often in previously treated patients. With the exception of headache, which rose in frequency, most symptoms showed a significant reduction following therapy withdrawal. The burden of symptoms reported by treated hypertensive patients is probably the result of a combination of their disease, drug-related adverse effects and inappropriate use of drugs in certain patient groups.

Antihypertensive Agents↗
PubMed1987

Lisinopril in hypertension associated with renal impairment.

The antihypertensive efficacy and safety of lisinopril, a long-acting angiotensin-converting enzyme inhibitor, were assessed in 23 patients with hypertension associated with impaired renal function (glomerular filtration rate 60 ml/min or less) in an open study of 12 weeks' duration. Lisinopril was given orally in single daily doses. The starting dose was 2.5 mg in patients with glomerular filtration rate (GFR) of less than 30 ml/min and 5 mg in all other patients. This was titrated to a maximum of 40 mg daily according to blood pressure response. A diuretic was then added if blood pressure was not controlled. Mean sitting and standing blood pressures were significantly reduced by lisinopril treatment. The median dose of lisinopril taken was 10 mg daily (range 2.5-40 mg), and only three patients required the addition of a diuretic. The mean glomerular filtration rate was unchanged during the study (38 +/- 16.4 ml/min at baseline, 41 +/- 21.0 ml/min after 12 weeks of treatment). Twenty-two patients completed the study. One patient was withdrawn because of nausea and vomiting due to reflux oesophagitis which was probably not drug related. Another patient had transient mild angioneurotic oedema and continued on lisinopril. No clinically significant haematological or biochemical changes were observed. In conclusion, lisinopril provided effective blood pressure control and was well tolerated in this group of hypertensives who are typically difficult to treat.

Adult↗
PubMed1987

Lisinopril treatment of hypertension in patients with impaired renal function.

Lisinopril is a new, long-acting, nonsulfhydryl angiotension-converting enzyme (ACE) inhibitor that is excreted unchanged by the kidney. The antihypertensive efficacy and safety profiles of lisinopril were assessed in 24 patients (15 men, 9 women; mean age 52.3 years; range 21-75 years) with hypertension associated with impaired renal function (glomerular filtration rate GFR 60 ml/min or less), in an open study of 12 weeks' duration. Previous antihypertensive drugs were discontinued at entry into the study. Lisinopril was given orally once daily; the starting dose was 2.5 mg in patients with a GFR of less than 30 ml/min, and 5 mg in all other patients. The dosage of lisinopril was titrated upward to 40 mg daily according to BP response. A diuretic could then be added if hypertension was inadequately controlled. Twenty-three patients completed the study. Mean sitting BP was reduced from 177 +/- 21.2/106 +/- 9.1 mm Hg (mean +/- SD) at entry to the study to 145 +/- 21.4/88 +/- 8.3 mm Hg after 12 weeks of treatment (p less than 0.001). The median dose of lisinopril used was 10 mg (range 2.5-40 mg) and only 4 patients had a diuretic added to the lisinopril. Overall GFR was unchanged during the study: mean baseline value was 37 +/- 16.4 ml/min (range 10-60 ml/min) at the beginning of the study and 40 +/- 21.0 ml/min at the end. As in a previous pharmacokinetic study in similar patients, a tendency toward drug accumulation was noted only in those patients with the most severe renal impairment.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Influence of age on blood pressure response to enalapril.

Based on prevailing hypotheses about the role of renin in essential hypertension, both Laragh and Buhler independently predicted that angiotensin-converting enzyme (ACE) inhibitors would become less effective with increasing age, as elderly hypertensive patients tend to have low plasma renin activity. We have investigated this situation in a large postmarketing surveillance study with enalapril. Following a 2-week no-treatment period, a total of 11,710 patients with essential hypertension received 10-20 mg of enalapril once daily for 6 weeks. BP was measured on two occasions prior to enalapril treatment, and on two occasions during enalapril treatment (after 2 and 6 weeks). Enquiry for symptom events was also made on each of these four occasions. Systolic BP (SBP) prior to enalapril treatment rose steeply with increasing age, whereas diastolic BP (DBP) rose only very slightly with age and reached a plateau by the 5th decade. The fall in SBP in response to enalapril increased with increasing age, but DBP was relatively uninfluenced by age. However, when corrected for initial BP, the percentage changes in both SBP (13%) and DBP (14%) were not different across the age range studied. Prior to receiving enalapril, 67.8% of patients were reporting symptoms, and this showed a positive correlation with age. During enalapril therapy, the overall level of symptom events reported fell significantly in all age groups (35.0%) but more so in the elderly, such that at the end of the study no significant age-related difference was detected. In all age groups, more than half of the events reported during enalapril therapy were of an improvement in general well-being.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Post-marketing surveillance of enalapril: experience in 11,710 hypertensive patients in general practice.

Post-marketing surveillance in general practice represents an important part of the monitoring of adverse events associated with newly introduced drugs. Such a study of the angiotensin-converting enzyme inhibitor enalapril maleate has been undertaken in 11 710 patients with essential hypertension. Serious adverse events occurred in 1.7% of patients, though most of these were not thought to be related to the treatment. The incidence rates of death (0.09%), stroke (0.11%) and myocardial infarction (0.15%) were compatible with rates predicted from age, sex and blood pressure considerations. Other events reported were hypotension (0.3%), angioneurotic oedema (0.03%), rash (0.5%), taste disturbance (0.2%) and cough (1.0%). The degree of blood pressure reduction attained was similar to that previously reported from pre-marketing development studies, as was the overall nature and frequency of both serious and non-serious adverse events. The most frequently reported event during enalapril therapy was of an improvement in well-being (19.8%).

Adolescent↗
PubMed1986

Pharmacokinetics of enalapril in normal subjects and patients with renal impairment.

The pharmacokinetics of enalaprilat were studied after administration of single and multiple doses of enalapril maleate to people with normal and impaired renal function. Renal impairment was associated with higher serum concentrations of enalaprilat, longer times to peak concentrations, slower decline of serum concentrations and with reduced urinary elimination. Urinary elimination of enalaprilat was closely related to renal function. In patients with severe renal impairment (GFR values below 30 ml min-1 1.73 m-2) significantly smaller doses of enalapril maleate will be required than in patients with normal or less severely impaired renal function.

Adult↗
PubMed1986

Enalapril in moderate to severe hypertension: a comparison with atenolol.

Patients with moderate to severe essential hypertension (mean untreated supine blood pressure 190/112 mm Hg) received once daily enalapril 20-40 mg or atenolol 50-100 mg, supplemented if required by hydrochlorothiazide 25-100 mg, in a randomized observer-blind trial. Both regimens produced a highly significant reduction in supine and standing blood pressure. There was no significant difference in the antihypertensive effects of enalapril and atenolol when they were used as monotherapy. After hydrochlorothiazide was added to patients not achieving 'target' blood pressure, the fall in systolic pressure was significantly greater in the enalapril group than in the atenolol group, despite similar dosage of hydrochlorothiazide in the two groups. At the end of 6 months' treatment, a supine diastolic blood pressure of 90 mm Hg or below was achieved in 74% of patients on enalapril plus hydrochlorothiazide and 56% of patients on atenolol plus hydrochlorothiazide. This difference was not statistically significant. A small rise in plasma urea and creatinine was observed in the enalapril group and a small rise of urea only in the atenolol group. These changes were statistically significant but of uncertain clinical importance. This study confirms that once daily enalapril and atenolol, both alone and in combination with hydrochlorothiazide, are effective drugs in the management of moderate to severe hypertension.

Adolescent↗
PubMed1985

Enalapril in the treatment of hypertension associated with impaired renal function.

This pilot study was undertaken to examine the safety and efficacy of enalapril in the treatment of hypertension associated with impaired renal function. Forty-one patients with glomerular filtration rate (GFR) < or = 50 ml/min received enalapril for up 12 weeks. Blood pressure, renal function, biochemistry and haematology were monitored weekly for 4 weeks and then monthly. Blood pressure was effectively reduced within 4 weeks; this reduction was maintained for at least 12 weeks. Renal function remained stable and there was no significant sustained alteration in any biochemical or haematological parameter. Requirement for additional antihypertensive drugs was reduced during enalapril therapy. These data suggest that enalapril may have a useful role in the management of hypertension associated with renal impairment.

Adult↗
PubMed1984

Reduced peripheral vascular symptoms in elderly patients treated with alpha-methyldopa--a comparison with propranolol.

A multicentre study of 6-10 weeks duration was performed in 60 ambulant hypertensive patients aged over 60 years to compare the efficacy of methyldopa and propranolol with particular reference to the occurrence of cold extremities and sleep disturbances. Blood pressure was effectively controlled by both drugs being reduced from a mean of 180/108 mmHg to 161/93 with methyldopa and 180/108 to 162/94 with propranolol. More patients treated with methyldopa (74%) achieved the target diastolic blood pressure of 95 mmHg or below compared with those treated with propranolol (58%). Side effects were more frequent in the propranolol group necessitating the withdrawal of four patients from the study. Only one patient on methyldopa was withdrawn. The incidence of cold extremities was significantly greater with propranolol. The occurrence of sleep disturbances was similar in both groups. In this group of elderly patients methyldopa was better tolerated than propranolol.

Aged↗
PubMed1984

Cardiac arrhythmias following acute myocardial infarction: associations with the serum potassium level and prior diuretic therapy.

The relationship between the initial serum potassium level and the incidence of cardiac arrhythmias following myocardial infarction has been reviewed in a coronary care unit setting. The incidence of arrhythmias in general, and ventricular fibrillation, ventricular tachycardia and frequent ventricular ectopic beats in particular, were inversely related to the initial serum potassium level. Hyperkalaemia was also significantly associated with ventricular fibrillation and ventricular tachycardia. Hypokalaemia was significantly more common in patients previously treated with diuretics, though most patients with hypokalaemia had not been so treated. The occurrence of an acute hypokalaemic syndrome, independent of, but exacerbated by, diuretic therapy, is further supported by these results.

Arrhythmias, Cardiac↗
PubMed1984

Factors affecting the reporting of symptoms by hypertensive patients.

Patients diagnosed as hypertensive have a high complaint rate, both on and off treatment and this has been postulated to be due to either their disease process, their being labelled as hypertensive, or to their treatment. Data from 6637 hypertensive patients being entered into clinical trials in general practice have been analysed to determine the relationship between the patient's age, sex, concurrent illnesses, concurrent medication, whether they were on antihypertensive treatment and the frequency of their reporting symptoms. The analysis was conducted using a multivariate technique. The frequency of reporting symptoms was greater in females than males. Those receiving antihypertensive therapy reported more symptoms than those who were not. This was notable with those receiving a beta-adrenoceptor blocker (47% of such patients complaining). Patients receiving concurrent medication were more likely to report a symptom than those not (48 compared to 37%). This was particularly noticeable if central nervous system-acting drugs were prescribed where the prevalence of symptoms was 52%. Patients already on antihypertensive treatment were more likely to be taking other medication for other conditions (37 vs 31%) than those not receiving antihypertensive treatment. Females were more likely to be taking other tablets than males (38 compared to 30%). The only symptoms which were less prevalent in those receiving treatment were headache, dizziness and breathlessness. All other symptoms were increased or unchanged in patients on antihypertensive therapy. This study indicates that present treatment for hypertension produces a high complaint rate from patients and that, when patients so complain, the possibility of their symptoms being due to their concurrent medication should be considered.

Antihypertensive Agents↗