Treatment of Hypertension in Out-Patients: Mecamylamine, Bretylium and Guanethidine

Fife, Rose S.; Moran, F.; Prineas, John W.

doi:10.1177/003693306200701203

Cited by 3 publications

(4 citation statements)

References 17 publications

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“…In the patients who demonstrated a rise their therapy had to be discontinued in one only, a man who had chronic pyelonephritis. The incidence of raised blood ureas was similar to that found in this department with other anti-hypertensive agents (Fife et al, 1962).…”

Section: Discussionsupporting

confidence: 85%

Clinical Trial and Pharmacological Study of Compound 1029 ("Vatensol")

Lawrie¹,

Lorimer²,

McAlpine³

et al. 1964

BMJ

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The trial has shown that compound 1003 will lower the blood-pressure in severe and moderately severe hypertensives to a good level of control in 58 % and to a moderate level of control in 34X ; 8% remain poorly controlled. Not enough mild hypertensives have been treated to comment on these. The response in the renal and malignant hypertensives is good.No significant rise in the blood urea occurred during treatment with 1003 alone, although, as with other hypotensive drugs, there was often a rise on adding polythiazide, which in some cases returned to previous levels, but in others remained elevated.Clinically, the actions and side-effects of 1003 are similar to --thogeof guanethidine, but in some cases it has proved effective where guanethidine has failed, and in others has produced fewer side-effects.In 64 % of the out-patients polythiazide was given in addition to 1003 to help control ; this figure is similar in our experience to that in treatment with guanethidine and methyldopa.Lack of energy was the most troublesome side-effect; diarrhoea was also common initially, but was easily controlled with codeine phosphate and usually wore off with continued treatment. Postural and exertional dizziness and sexual symptoms occurred about as often as in guanethidine therapy. Nausea was troublesome in some patients but in only one case did the treatment have to be stopped because of it.There were two certain cases of drug reaction and a probable third out of 62 cases assessed. However, symptoms quickly settled on withdrawing the drug.The action of compound 1003 in depleting the hypothalamus and the adrenal medulla of pressor amines led us to look for any obvious differences from guanethidine in its mode of action in the clinical control of patients with hypertension; we found no very apparent difference, but attempts to correlate action in a particular area in the animal with the effect of lowering the blood-pressure in man are extremely difficult. At present this applies to most drugs used in the treatment of hypertension, since it is by no means clear which of their many pharmacological actions is responsible for lowering the blood-pressure.Compound 1003 has been shown to be a suitable drug for the treatment of patients with hypertension of moderate or severe degrees, whether associated with renal disease or not. This compound, designated 1029, is [(2-(2, 6-dichlorophenoxy) ethyl) amino I guanidine sulphate (" vatensol "), which has been shown to have the following pharmacological actions: (1) inhibition of dopamine beta-oxidase, (2) adrenergic neurone blockade, (3) depletion of noradrenaline in the C.N.S., and (4) depletion of peripheral tissue noradrenaline. In the adrenal medulla there was depletion of noradrenaline and, to a larger extent, adrenaline. Summary* Royal Infirmary, Glasgow.t Royal Alexandra Infirmary, Paisley. f Department of Pharmacology, Pfizer Ltd., Sandwich. Animal PharmacologyThe anti-hypertensive effect and modes of action of compound 1029 were demonstrated in animals and in vitro by the followin...

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Section: Discussionsupporting

confidence: 85%

Clinical Trial and Pharmacological Study of Compound 1029 ("Vatensol")

Lawrie¹,

Lorimer²,

McAlpine³

et al. 1964

BMJ

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show abstract

“…The variable incidences of side-effects which have been reported (Page et al, 1961 ;Leishman et al, 1961 ;Eagan and Orgain, 1961 ;Fife et al, 1962) are probably related to three factors: variations in (1) the type of patient treated,…”

Section: Discussionmentioning

confidence: 99%

“…Clinical details are given in Table I, which shows that these features indicate a fair cross-section of patients with severe hypertensive disease. Retinal changes were classified for convenience according to the criteria of Keith, Wagener, and Barker (1939), although this classification has disadvartages, as previously discussed (Turner, 1959). Criteria for the E.C.G.…”

Section: Methodsmentioning

confidence: 99%

Guanethidine in the Treatment of Hypertension

Lowther¹,

Turner²

1963

BMJ

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“…Criterion was based on symptoms, enzyme changes, ECG changes (Minnesota code)[16,17] and post-mortem findings defined in the WHO coding criteria[18] and the validity of the diagnosis was ensured by intra-observer studies[19]…”

Section: Methodsmentioning

confidence: 99%