POSTGRAD. MED. J. (1966), 42, 195.

THE TREATMENT OF HYPERTENSIONM. HAMILTON, M.D., M.R.C.P.

From the Chelmsford Group of Hospitals.Selection of Patients for TreatmentANY PATIENT who knows that he or she hasa raised blood pressure requires treatment.For the majority, this will consist only ofsimple measures, e.g. weight reduction,reassurance and perhaps sedation to allayapprehension. However, the minority willrequire treatment with potent hypotensivedrugs, and the selection of patients for suchtreatment remains difficult. Iln exercising suchselection, two points are important:

(a) once started, treatment with a potentdrug will be required for the rest ofthe patient's life, except in a smallproportion of those treated, and

(b) the more time and care devoted by thedoctor, and the more co-operative thepatient, the better will be the resultsobtained.

Within a very few years of the introductionof hexamethonium, the benefits of hypotensivetherapy were clearly established. The sideeffects produced by ganglion-blocking agentswere so severe, that their administration wasvirtually restricted to the treatment of thecomplications of hypertension. However, sincethe introduction of thiazides, adrenergicblocking agents, and methyldopa, it has beenpossiible to control hypertension with produc-tion of only minor side-effects from drugadministration, so that the indications fortreatment have broadened.

This is demonstrated by Table 1, whichillustrates the increasing proportion of patientsreferred to a clinic on account of a raisedblood pressure, in whom treatment is startedwithin the first three months after referral.This increase in the proportion of patientstreated is partly due to the increasing apprecia-tion of the prophylactic value of early bloodpressure reduction, and partly to that of thevalue of thiazides used as a hypotensive agent.In my own series, the proportion of patientsstarting treatment with thiazides has risen from25%/0 in 1957 and 1958, to 59% in 1964(Table 2).

Treatment of ComplicationsAlthough the indications for treatment have

extended, priority in respect of treatment mustfirst be given to the presence of certain

complications of hypertension, some of whichare of sufficient severity as to require immediateblood pressure reduction, and consisting of:-

(a) the malignant phase(b) hypertensive encephalopathy(c) cardiac asthma.The presence of papilloedema, due to hyper-

tension, constitutes the sole physical sign toindicate that the hypertension has entered themalignant phase. This diagnosis should beregarded as a medical emergency demandingimmediate introduction of hypotensive therapy,which in this instance should precede investi-gation into the aetiology of the raised bloodpressure. There is one exception to this dogma,viz: that should a -phaeochromocytoma beseriously considered as the cause of the hyper-tension, investigation should precede treatment.I personally still employ parenteral therapy inthe initiation of treatment in such cases, usingparenteral pentolinium, in order to establishcontrol of the blood pressure within 36 hoursof diagnosis.

Hypertensive encephalopathy is a diagnosiswhich is frequently abused. I think that thereare physicians who still maintain that a stroke,occurring during the course of hypertension,constitutes a contraindication to the use ofhypotensive drugs, yet who employ suchtreatment, justifying their decision by diagnos-ing a stroke as an encephalopathic attack. Iconfine the diagnosis of encephalopathy toan attack of confusion and severe headache,often with minor focal neurological signs,proceeding to epileptiform fits and coma. Thedistinction from cerebral haemorrhage can bedifficult, and in my experience, often madeonly in retrospect, following the patient'sdramatic recovery with reduction of the bloodpressure.The relief of pulmonary oedema due to

'hypertensive 'left ventricular failure, byparenteral pentolinium or methyldopa, can bequite dramatic.The significance of the soft retinal exudate

must now be accepted as indicating thedevelopment of hypertensive vascular damage(Hodge and Dollery, 1964). If therefore, thefinding of papilloedema constitutes an indica-

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TABLE 1

PERCENTAGE OF TOTAL NUMBER OF (HYPERTiENSIVE PATIENTS STARTING TREATMENTWITHIN THREE MONTHS OF IREFERRAL

1957/58 1959/60 1961/62 1963 1964

Total number 123 116 135 110 111

Number treated 55 51 96 68 79

Percentage oftotal treated 46 44 71 62 71

TABLE 2

PROPORTI)ON OF IPATIENTS STARTING TREATMENT WITH THIAZIDES

1957/58 1959/60 1961/62 1963 I964Total number treated 55 51 96 68 79

Number treated withThiazides 14 15 53 36 47

Percentage of totaltreated withThiazides 25 29 55 53 59

tion for immediate blood pressure reduction,the finding of evidence of vascular damageprovides little less urgency. The appearance ofretinal exudates in a patient previously withoutretinopathy, or the finding of soft exudates ina newly-examined hypertensive, constitutes aneed for blood pressure reduction, no lessurgent than that presented by the finding ofpapilloedema.Many publications have established heart

failure as the main single cause of deathamong untreated hypertensives, accounting forbetween 40%/ and 50% of the total mortality,but one which should now no longer beconsidered a cause of death among treatedpatients. (Smith and Fowler, 1955; Smirk,1957). Therefore, the presence of heart failuremust be considered an absolute indication forblood pressure reduction, the urgency withwhich treatment is introduced being determinedsolely by the severity of the manifestation ofthe failure.The association of Hypertensive and

Ischaemic ,Heart Disease perhaps requiresspecial mention. Eleven years ago Doyle andKilpatrick (1954) demonstrated the relief ofangina which such patients can experience,as a result of blood pressure reduction, andthis is now a commonplace observation. Inmy own cases, over 50% of hypertensivepatients with angina obtained sufficient reliefby blood pressure reduction alone, to dispense

entirely with trinitrin, upon which they hadpreviously been dependent for their normalconduct of life. I consider therefore, that thepresence of angina provides an added indicationfor the introduction of hypotensive therapy.It is furthermore my practice to recommendsuch reduction of blood Ipressure in patientswith persistent hypertension following cardiacinfarction. To do so appears logical; althoughI have no evidence of 'benefit from this policy,I am convinced that it does not provokefurther coronary thrombosis.

Treatment has so far been recommendedsolely for the treatment of complications ofhypertension, but obviously evidence ofdeterioration in the patient's condition shoulddemand treatment before such complicationsbecome established. Thus the appearance ofretinal lesions, or of clinical, radiological, orcardiographic changes of ventricular hyper-trophy, or the onset and progression ofdyspnoea, require that the Iblood pressure 'levelbe reduced in order to prevent the develop-ment of cardiac failure or deterioration intothe malignant phase.The relief of headache, due to hypertension,

by blood pressure reduction, is dramatic.Admittedly, it has 'been shown that suchheadaches can be relieved by a placebo in themajority of patients (Stewart, 1953). However,if a patient is suffering severe headaches asa result of hypertension, and if such headaches

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are interfering with the patient's life, or work,or sleep, I do not consider it justifiable towithhold hypotensive therapy, even if nocomplications are present. If headaches arenot rapidly relieved by simple measures, e.g.sedation, weight reduction and reassurance,then the blood pressure must be reduced inorder to procure relief. I see no reason todepart from accepted principles of therapeutics,viz: that whenever possiible it is preferable totreat the disease causing symptoms, ratherthan give symptomatic treatment which hasno effect upon the cause of the underlyingdisease.The decision to treat symptomless, uncom-

plicated hypertension, is one which should notbe taken lightly. It is no longer adequatemerely to reassure such patients as to theabsence of complications. Full investigation isobligatory, aimed at the exclusion of a remedialcause for the raised iblood pressure. If no suchremedial cause is found, then one must decidewhich patients will require treatment in orderto prevent the advent of complications andwhether, in fact, the evidence at presentavailable justifies the decision to embark onhypotensive itherapy, in the absence ofsymptoms or complications, in order to preventsuch complications from arising.

Wihen the blood pressure is raised as aresult of renal disease-chronic glomerulo-orpyelonephritis-I believe that early reductionof blood pressure can retard the progress ofrenal failuire, and (Moyer, Heiden, Bevey andFord (1958) have produced evidence supportingthis contention.Prevention of ComplicationsThe position in respect of the administration

of hypotensive drugs to a patient followinga stroke, is still undefined. I do not believethat there is evidence to show that bloodpressure reduction, unless excessive, causescerebral thrombosis. Of 67 patients startingtreatment following a cerebral thrombosis,there have been only 15 deaths, nine of whichwere due to stroke, five of these beingthrombotic. I consider that a cerebral throm-bosis is an added indication for blood pressurereduction, provided that the -stroke has leftno appreciable residua.l physical or mentaldeterioration. However, the greater problemis whether iblood pressure control willl preventthe development of stroke if provided earlyin the course of the disease. For 'many years,the prognosis of 'hypertension in respect ofstroke remained uncertain. Leishman (1959,

1963), 'by comparing consecutive series ofpatients, provided convincing proof of im-proved prognosis in this respect, but studyof consecutive cases is always open to somedoubt. In an attempt to resolve this prognosticdilemma, my colleagues and I (Hamilton,Thompson and Wisniewski, 1964), conducted atherapeutic trial, the object being to determinewhether blood pressure reduction influencedthe incidence of complications, includingstrokes, in patients with essential hypertension.

It was essentiall to include only such patientsin the trial w'ho were hypertensive, but inwhom atherosclerosis was not a dominantfeature, as judged by the crude criteria availableto the clinician. Thus, subjects included in thetrial were all aged under 60 years. None hadsymptoms of arterial disease-i.e. all deniedangina, claudication, rest pain in the limbs,or transient symptoms suggestive of cerebro-vascular insufficiency. 'In alil, the carotid andfoot pullses were palpable, no bruits wereaudible over the carotid or femoral arteries,and none had cardiographic changes to suggestthe presence of cardiac infarction.

It was imperative that all subjects shouldshow a sustained manometric hypertension,and those included all maintained a diastolicblood pressure of at least 110 mm. Hg. overa period of three months' outpatient observa-tion, entailing at least three visits to -the elinic.In view of the difficulties of accurate recordingof iblood pressure, Ail readings were made tothe nearest 5 mm. of mercury.

It is clearly indefensi-ble to include in sucha trial any patient with complications of hyper-tension, or severe symiptoms which demandtreatment, at the time of their reference tothe Out-patient Clinic. Thus, all the patientslhad been referred because of symptomlesshypertension, which was in all cases consideredto be essential; known causes of secondaryhypertension were excluded 'by routineinvestigation, including, if necessary, renalarteriography. None showed complications ofthe disorder, such as papilloedema, exudates,or haemorrhages on retinal examination; therewere none with clinical, radiological, or cardio-graphic signs of cardiac enlargement, andnone had albumen or casts in the urine, onurinalysis; 'al had normal level of serum-urea.

T'hus, all patients were under 60, withsymptomless uncomplicated benign essentialhypertension. The trial was conducted over aperiod of six years, and no cases were includedduring the last two, so that all treated cases

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received a minimum of two and a maximumof six years' therapy.

After dlinical examination and investigationto exclude (a) the need for immediate treatmentof the hypertension on account of symptomsor complications of the disease, and (b) thepresence of some other condition known to beassociated with a.raised arteria pressure, caseswere included in the trial, and admitted to atreated or control group ailternately, in orderto maintain an equal number in each group.At the conclusion of the trial, three cases wererejected after perusal of their notes; one wasfound to have been 62 years of age at thetime of his inclusion, and in the other twothere were some doubt regarding the aetiologyof the hypertension. Hence the numbers inthe two groups do not exactly balance.No indication was made in the patients'

clinical notes of their inclusion in the trial,and the list of all particilpants was kept remotefrom the clinics and wards. This was donedeliberately, in order to avoid prejudice againstintroducing treatment in a patient includedin the control series. It was thought that if suchinformation were available when the patientsattended the clinic, it might weigh against otherconsiderations for the introduction of hypo-tensive therapy should the development ofsymptoms or complications make such therapydesirable.

Thus, we were able to include in the trialsixty-one patients under 60 years of age, withsevere, sustained, symptomless, uncomplicatedbenign essential hypertension, who showed nodetectable evidence of atherosclerosis. Thesepatients comprised thirty-nine females, andtwenty-two males. Twenty females and tenmales constituted ithe treated series, and nine-teen females and twelve males the controlseries. Despite the slight discrepancy in numbersbetween the groups, there was no significantdifference for either sex between the treatedand control groups in respect of age, weight,or blood pressure.

In assessing the efficacy of blood pressurecontrol in the treated series, the followingcriteria were maintained:-Good Control implies a diastolic pressure

consistently below 100 mm.Hg.Fair Control implies the diastolic pressure

maintained below 110 mm. Hg.Poor Control the diastdlic pressure consis-

tently over 110 mm. Hg.To consider first the ma'le patients-all were

severely hypertensive, with no significant

difference in respect of age, weight or bloodpressure between the treated and controlgroups. In all of the ten treated males, thedegree of blood pressure control was consideredadequate, being good in nine, and fair in one.None suffered a stroke or other complicationsof the disease. Of the twelve untreated males,four suffered a stroke; in one this provedfatal and necropsy showed a cerebralhaemorrhage. Three other patients developeda hemiplegia: Two of these made a completeobjective recovery and were ultimately ableto resume work, but the third was left withslight dysarthria and weakness of one hand,which unfortunately prevented his return to'his former occupation of schoolmaster.Although the incidence of four strokes amongtwelve subjects appear high, the numbersare small and the difference between the twogroups is not statistically significant. Of theremaining eight untreated patients, one hada coronary thrombosis, with a subsequent fallin blood pressure to normal levels, anotherbegan to have headaches of increasing severityand intensity, which required hypotensive drugsfor their control, and in two more clinical andcardiographic signs of increasing left ventricularhypertrophy developed, following whichhypotensive therapy was considered necessaryin order to prevent the development ofhypertensive cardiac failure. Thus, eight oftwelve untreated -patients showed complicationsof hypertension during the course of the trial,as compared with none of ten treated patients,and this difference is highly significant atmore than the 2.5% 'level.There were nineteen females in the control

group, of whom three suffered a stroke-twomade a full objective recovery from apresumed cerebral thrombosis; one died fromrupture of an intracranial aneurysm fifteenmonths after starting treatment introduced tocontrol headache of increasing severity. In'five others, complications arose, consisting ofcoronary thrombosis in two, both with sub-sequent blood pressure fall; and increasing leftventricular hypertrophy in three, all of whomstarted treatment on this account. Thus, eightof the nineteen patients developed complica-tions.

There were twenty females in the treatedseries, of whom five developed complicationsof the disease; consisting of a stroke in three(two cerebral thrombosis with recovery, andone fatal cerebral haemorrhage); coronarythrombosis in one, and increasing heart size in

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March, 1966 HAMILTON: Treatment of Hypertension 199

one. Thus, 'five of this series developedcomplications compared with eight in thecontrol group, and clearly this difference isnot significant.However, in four of the treated group, the

blood pressure control was considered poor,i.e. the diastolic pressure was never controlledbelow 110 mm. Hg., which was the originalcriterion for inclusion in the trial. If, therefore,we consider the females, not in respect oftreatment, ibut in respect of the adequacy oftreatment, there were sixteen patients withadequate Iblood pressure control with onlyone complication i(increasing L.V.), whereasof twenty-three with inadequate control(nineteen control series plus four inadequatelytreated) there were twelve complications,including six strokes, and this difference bothin respect of the incidence of strokes andoverall incidence of complications, becomeshighly significant.

Thus, there is no doubt from the trial thatadequate blood pressure control, maintainingthe diastolic pressure below 110 mm. Hg., inyounger patients, reduces the overall incidenceof complications, including stroke. Theseresults justify the decision to extend the indica-tion for treatment of hypertension, so as toinclude patients of younger age groups in whomcomplications of the disease have not appearedat the time of starting treatment, in order toprevent, or delay, the appearance of suchcomplications.Although symptomless, all patients treated

in this trial maintained a substantial hyper-tension, with severe diastolic pressures of over

130 mm. Hg. The decision to treat a sustainedmanometric hypertension of this magnitude,even though symptomless and uncomplicated,is not difficult to accept. But the decision totreat less severe degrees of hypertension is onewhich is more difficult to take. Is it in factjustifiable to treat patients with lesser gradesof hypertension? Will any benefit follow theintroduction of treatment in a young person,in the second or third decade of life, whomaintains a diastolic blood pressure of 90-100mm. Hg.? I have as yet no evidence to offeron this aspect, although it has been suggestedthat such patients be selected according tothe level of diastolic pressure, treating thosewhose pressure persists at levels associatedwith a known increased mortality. Thus,Pickering, Cranston and Pears (1964) quotethe following levels of diastolic pressure whichjustify hypotensive therapy.

Age Male FemaleUnder 40 years 106 115Over 40 years 110 120

Certainly, in pregnancy, I believe that greaterlatitude is justified in respect of the introductionof therapy. The presence of maternal hyper-tension imposes a greatly increased risk offoetal death. Prior to the introduction ofmethyldopa, I was not successful in maintainingadequate control of blood pressure in anypregnant woman who was severely hyper-tensive. My facilities in this respect arerestricted, but during the past three years Ihave been able to treat seven young womenduring pregnancy. All were hypertensive beforepregnancy-in one the raised blood pressure

TABLE 3

INFLUENCE OF BLOOD IPRESSURE CONTROL UPON COURSE OF PREGNANCY IN SEVENHYPERTENSIVE PATIENTS

Greatest Duration BirthAge tiology B.P before Number of No. of Mis- Birth Present Weight Fate ofYears O yper- pegncy pregnancies carriages Weight Pregnancy Child Child

lbs. ozs. (Weeks) lbs. ozs.41 Essential 190 120 Five 1 7 12 38 6 13 Live25 Pyelo-

nephritis 180 110 Two 2 - 38 7 1 Live23 Pyelo- 5 12 Live

nephritis 160 120 - - 3642 Essential 220 130 Nine 3 7 8 36 6 15 Live21 Essential 220 140 - - - 37 5 15 Live

Pyelo-25 nephritis 150 115 Four 2 7 4 38 5 14 Live21 Vascular 220 130 - - - 36 6 1 Live

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was atributed to renal vascular disease; in threeto pyelonephritis, and the remaining threewere considered to ibe suffering from essentialhypertension. In all the iblood pressure wasmaintained throughout pregnancy at a diastolic-level not exceeding 90 mm. Hg. Alli thepregnancies were induced between thethirty-sixth and thirty-eighth week, and allwere productive of a live infant of satisfactorybirth weight (Table 3).In conclusion, therefore, while therapy

retains prior place in the treatment of compli-cations of hypertension, the recent introductionof new drugs capdble of achieving bloodpressure control with few side-effects hasbroadened the indications for the use of suchdrugs, so that the role of treatment in theprevention of complications of the disease isnow firmly established.

The Choice of Drug for Use in TreatmentHaving decided which patient requires

hypotensive therapy, the choice of drug touse presents certain problems. I do not believethat any comprehensive scheme can be givenwhereby the treatment selected is determinedby the level of blood pressure, even thoughthis is a commonly 'preached dogma. It is myconviction that the most useful drug is thatwith which the particular physician is mostfamiliar. All the many drugs now available-for use possess certain peculiarities in respectof the method, extent and speed of the bloodpressure reduction obtained, and the compli-cations produced. Familiarity in the use ofa drug can do a great deal to achieve a smoothand early response, with the production ofminimal side-effects, thus making the patient'slife more tolerable, and improving the prospectof continued treatment.For the younger patient, under 40 years of

age, with a mild manometric hypertension,there is at present no evidence to indicatebenefit resulting from blood pressure reduction.In the absence of such evidence, it is notjustifiable to commit a symptomless individualto a lifetime of drug therapy. 'However, thisdoes not imply the negation of responsibility.If overweight, the achievement of weight losswill provide a reduction of blood pressure inexcess of that attributable to reduction ofarm circumference (Fletcher 1954). Although'light sedation, e.g. with phenobarbitone, iscommonly prescribed as a routine treatmentfor such patients with mild hypertension, thereis no evidence that it 'produces any reduction

in the level of blood pressure. However, manysuch patients experience symptoms due toanxiety induced by the knowledge that theirblood pressure is raised, and apprehensionregarding its outcome, and such sedation willfrequently relieve the symptoms, through reliefof anxiety. In such patients, reassurance bythe physician is obligatory, and furthersupervision desirable in order to observe theadvent of any objective evidence of deteriora-tion, so that treatment can be institutedbefore complications become established orirreparable.The need for immediate reduction of blood

pressure, in the presence of certain complica-tions of hypertension, has already beenemphasised. In patients suffering fromhypertensive encephalopathy, or pulmonaryoedema due to hypertensive left ventricularfailure, immediate reduction of blood pressurecan only be achieved by parenteral preparations.In such instances I still prefer to use parenteralpentolinium (Ansolysen) given with the headof the bed elevated, in order to make full useof the postural hypotension which characterisesthe action of the ganglionklocking agents. Inthe case of malignant hypertension, the needfor such dramatic reduction of blood pressureis less urgent, but as the renal failure, in suchcases, can progress with alarming speed, it ismy choice to rely on parenteral pentoliniumfor the initiation of treatment in such cases.Using increasing doses of pentolinium, givenby subcutaneous injection, if neoessary everytwo hours, it is possible to reduce the bloodpressure within six to eight hours, and tomaintain a reasonable degree of controlthroughout the 24 'hours, within 18 to 24 'hours.Once the blood pressure has been reducedto, and maintained at, safe levels, even thoughthe control is usually uneven with pentolinium,other oral preparations can be introduced ata later date, once the urgent complications ofthe disease have been overcome.The use of thiazides, as a sole hypotensive

agent, is becoming increasingly widespread,and a mode of treatment which I am using inan increasing number of patients. I personallyuse, purely from habit, large doses ofhydroflumethiazide, giving 100 mg. twice daily,combined with 'potassium supplement tocompensate for the increased urinary loss ofpotassium induced by this group of drugs.The individual dose of potassium requiredvaries from 1 to 4 g. 'potassium chloride ortartrate daily; the dose required being that

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March. 1966 HAMILTON: Treatment of Hypertension 201

which maintains a normal level of serumpotassium.Of over 150 patients treated with this drug

alone, the average reduction of systolic anddiastolic pressure has Ibeen of the order of25% of the pre-treatment level, e.g. a meanpre-treatment 'blood pressure of 200/120 hasbeen reduced to one of 150/90, and maintained,in some cases, for up to six years withoutalteration in the dose of thiazide. Unfortunately,the response to this group is unpredictable-a small proportion having shown no bloodpressure response at all-so that I do not usethis method of treatment for patients withestablished complications of hypertension.However, it is simple to administer, productiveof few side effects and, in my opinion, anexcellent choice of drug for the elderly patientwith hypertension complicated by cardiacfailure, in whom the presence of extensivearterial disease is inevitable and profoundfalls or wide fluctuation in blood pressureare undesirable.

Reserpine is undoubtedly an effectivehypotensive agent, its effect being producedmainly by noradrenaline depletion (Burn andRand, 1957), possibly supplemented by some"central action" (McQueen, Doyle and Smirk,1955). Although effective, reserpine causesmany side effects, some of which are merelyunpleasant, e.g. nasal congestion, nightmares,tremor, mental apathy, biliary colic andlactation, but two of which are extremelyserious, namely, the production of sodiumand fluid retention, which might precipitatecardiac failure, and the production of mentaldepression, which can be of such insidiousonset and progression as to escape recognitionbefore the tragedy of certification or suicide.For these reasons, I prefer to avoid the useof this drug entirely, even though, used insmall doses, not exceeding 0.3 mg. a day, inconjunction with more potent hypotensiveagents, it does facilitate treatment, and usedin such doses, the risk of mental depressionis small.The choice of the more potent drugs is

certainly one of individual preference. I con-sider the ganglion blocking agents as themost potent available, but the severity ofside effects resulting from parasympatheticblock make their administraition unpleasant forthe patient. However, in cases in Which I cannotmaintain adequate control over the bloodpressure, with more recently introduced agents,I still resort to the use of mecamylamine or

pempidine combined with thiazide diuretics.The hypotensive drugs made available in thepast five or six years all achieve their effectmainly by the depletion of noradrenaline storesfrom the vessel walls. This alters the reaction ofthe vessels so thait an impulse, normally vaso-constrictor, no longer produces this effect, butinstead causes vasodilatation. I personallyhave never used guanethidine with appreciablesuccess. The side effects, Iprincipally muscleweakness and diarrhoea, -together with thevariable control over the blood pressure,which I obtain, has led me to largely abandonits use. I prefer methyldopa, which is easyof administration, effective in achieving controlover the blood pressure, and productive offew side effects, apart from drowsiness whichpresents a major problem to some patients(Hamilton and Kopelman, 1963). Unfortun-ately, I am becoming worried by the increasingproportion of patients treated with this drug,who are developing late tolerance, as predictedby Bayliss and Harvey-Smith (1962). Severalpatients, whose blood pressure has remainedwell controlled by a fixed dose of methyldopa,over periods of eighteen to thirty-six months,suddenly escape from control, and requirerestabilisation on an alternative routine. Morerecently, Bethanidine (Johnston et al, 1964)and Envacar (Peart and McMahon, 1964) havebeen reported as maintaining effective controlof the blood pressure, with the production ofcomparatively few side effects, and both appearto be drugs of some considerable promise.However, my personal experience of Iboth istoo limited for comment.

REFERENCESBAYLISS, R. I. S., and HARVEY-SMITH, E. A. (1962):Methyldopa in the Treatment of Hypertension,Lancet, i, 763.

BURN, J. H., and RAND, M. J. (1957): Reserpine andNoradrenaline in Artery Walls, Lancet, ii, 1097.

DOYLE, A. E., and KILPATRICK, J. A. (1954):Methonium Compounds in the Angina of Hyper-tension, Lancet, i, 905.

FLETCHER, A. P. (1954): The Effect of WeightReduction upon the Blood-Pressure of ObeseHypertensive Women, Quart. J. Med. N.S., 89,331.

HAMILTON, M., and KOPELMAN, H. (1963): Treatmentof Severe Hypertension with Methyldopa, Brit. med.J., i, 151.

HAMILTON, M., THOMPSON, E. N., and WISNIEWSKI,T. K. M. (1964): The Role of Blood-pressureControl in Preventing Complications of Hyper-tension, Lancet, i, 235.

HODGE, J. V., and DOLLERY, C. T. (1964): RetinalSoft Exudates, Quart. J. Med. N.S., 129, 117.

LEISHMAN, A. W. D. (1959): Hypertension-Treatedand Untreated. A Study of 400 Cases, Brit. med.J., i, 1361.

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LEISHMAN, A. W. D. (1963): lMerits of ReducingHigh Blood-pressure, Lancet, i, 1284.

MCQUEEN, E. G., DOYLE, A. E. and SMIRK, F. H.(1955): The Circulatory Effects of Reserpine,Circulation, 11, 161.

MOYER, J. H., HEIDER, C., PEVEY, K., and FORD,R. V. (1958): The Effect of Treatment on theVascular Deterioration Associated with Hyper-tension, with 'Particular Emphasis on RenalFunction, Amer. J. Med., 24, 177.

PICKERING, G. W., CRANSTON, W. I., and PEARS, M.A. (1964): The Treatment of Hypertension. p. 124.Springfield, Illinois: Charles C. Thomas.

SMIRK, F. H. (1957): High Arterial Pressure p. 693.Oxford: Blackwells.

SMITH, K. S., and FOWLER, P. S. B. (1955):Prevention and Treatment of Hypertensive Heart-failure by Ganglion-blocking Agents, Lancet, i, 417.

STEWART, I. McD. G. (1953): Headache and Hyper-tension, Lancet, i, 1261.

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