BRITISH 1073 APRIL 20, 1963 TO-DAY'S DRUGS MEDICAL JOURNAL who has made a reasonable recovery from a cerebro- Current Practice vascular episode should also have his blood-pressure lowered; there is evidence that the persistence of hypertension is an important factor in determining the TO-DAY'S DRUGS subsequent prognosis.3 Once a patient has definite evidence of renal failure IYPOTENSIVE DRUGS (Continued) with a persistently raised blood urea potent hypotensive drugs should be used with extreme caution. If given in GENERAL CONSIDERATIONS the usual dose their effects can be catastrophic; once this stage is reached they do not prolong life and are Choice of Patient only symptomatically helpful. At the present time our views about the selection of patients for treatment with hypotensive drugs are in a state of change. At first it was the practice to give Choice of Drug these drugs only to patients with malignant hypertension From what has already been said it will be apparent or those who had definite signs of hypertensive disease. that none of the hypotensive drugs at present available As newer and better hypotensive agents have come into is ideal. When the decision to treat a patient has been use the scope of treatment has been broadened and now made a balance must be struck between the need to there are some who believe that.a patient with a raised lower the blood-pressure and the frequency and severity blood-pressure should be treated even if he has no of the side-effects of the hypotensive drug. In the symptoms. Those who advocate this policy do so on treatment of acute hypertensive emergencies, such as the grounds that the mortality statistics indicate that hypertensive encephalopathy or acute left ventricular such patients have a shortened life span and that they failure, there is an urgent need to lower the blood- die most often from conditions associated with hyper- pressure, and the second factor is unimportant. In these tension. Any consideration of this question must be circumstances the parenteral administration of a prefaced by two important points.' First, when treat- ganglion-blocking agent, as already described, is ment with potent hypotensive drugs is started it is recommended. probable that it will have to be continued for the rest For the patient with malignant hypertension also, the of the patient's life. Cases in which it has been possible necessity to lower the blood-pressure quickly must take to discontinue hypotensive treatment and the blood- precedence over the question of side-effects, and either pressure thereafter has remained normal have been pempidine or mecamylamine supplemented by an oral reported,2 but these are very rare. Secondly, this is diuretic is probably the best regime in the first instance. not a simple form of treatment; good results are It is exceptional to find a patient who does not show a achieved only when the doctor is prepared to spend time good immediate response to quite a small dose (2.5 mg. and care on the management, and when the patient is t.i.d.) of one of these drugs. This dose will have to be intelligent and co-operative. increased, but it is frequently possible to achieve good The most important indication for treatment is still control of the blood-pressure in such cases on a regime malignant hypertension; here treatment is a matter of of ganglion-blocking agent plus oral diuretic. Inevitably urgency, and, unless the patient already has evidence of this will be at the expense of the unpleasant side-effects renal failure, treatment should precede investigation as associated with parasympathetic blockade, but, once to the cause of the hypertension unless a phaeochromo- control of the blood-pressure has been obtained, it may cytoma is suspected. Other urgent indications are be possible to switch over to another drug with fewer hypertensive encephalopathy, acute left ventricular side-effects such as guanethidine. Guanethidine is at failure, and congestive cardiac failure, if hypertension present the drug of choice for most patients with is thought to be the main contributory cause. Most severe benign hypertension and it is preferred by some people would agree that patients with a high fixed authorities even for malignant hypertension. The initial diastolic pressure, evidence of cardiac enlargement, and dosage should be 10 mg. daily with increments of 10 mg. retinal haemorrhages or exudates should be treated, every three days until the desired effect (a standing although in these cases a short pre-treatment period for diastolic blood-pressure of 90-100 mm. Hg throughout assessment and investigation is permissible. The the day) is achieved. In most cases the addition of an decision is more difficult in those patients who are oral diuretic will enable this to be done more easily. symptom-free or have only mild symptoms, and in those Methyldolpa may become an acceptable alternative who have coronary artery disease or have had a stroke. to guanethidine for these cases. The choice of drug for In the first group a full investigation of the case to the patient with moderately severe hypertension is most exclude primary renal or other disease as a cause of the difficult. For these patients a drug is badly needed patient's hypertension must precede any decision about which will lower blood-pressure without causing severe treatment. The age and sex of the patient are postural hypotension or other side-effects. Reserpine important; most young males probably should receive has proved disappointing in these cases and has recently hypotensive therapy, but many middle-aged, obese been described4 as " a dangerous drug which should females are better off without drugs; their prognosis is, never be prescribed for the treatment of hypertension." on the whole, good, and they tolerate hypotensive drugs It is unlikely that methoserpidine will prove any better. poorly, often complaining bitterly of the side-effects. " Miopressin," a combination of rauwolfia with proto- Patients with hypertension who have coronary artery veratrine and phenoxybenzamine, an adrenolytic agent, disease should have their blood-pressure lowered has been advocated for this type of case, and although cautiously; the danger of precipitating myocardial some good results have been reported5 others are more infarction is probably real, but there is no doubt that sceptical of its value,4 and it is certainly not devoid of improvement in angina may follow when the blood- side-effects. For this group also methyldopa may prove pressure is reduced. Likewise a hypertensive patient a valuable drug. 1074 APRIL 20, 1963 Barriss TO-DAY'S DRUGS MEDICAL JOURNAL

For patients with less severe grades of hypertension Management such convincing proof of the beneficial effects of hypo- The object of treatment with hypotensive drugs is to tensive drugs is not yet available, although there are bring the patient's blood-pressure down to a level as some observations which suggest that even in these near normal as possible and to keep it there. This can milder cases treatment reduces the death rate. Apart often be achieved while the patient is in hospital, but it from the question of mortality rates, there is now a is much more difficult when he returns to his home considerable amount of evidence that the use of hypo- environment. There is no unanimity about the degree tensive drugs is followed by an improvement in those of blood-pressure control which is desirable for patients symptoms and signs which are considered to be due who are attempting to lead as normal a life as possible. mainly to the raised blood-pressure itself; regression of In the U.S.A. it is common practice for the patient or a retinopathy, relief of left ventricular failure with relative to be taught to record his blood-pressure at reduction in cardiac size, and improvement in the home so that frequent readings can be made, and control electrocardiographic signs of left ventricular strain are of treatment is based upon these. This is seldom done commonly observed to follow the institution of hypo- in this country. Most patients are controlled on the tensive therapy. The effect of treatment upon renal basis of one or two casual readings of the supine and failure is generally disappointing, and there is as yet no standing blood-pressure made on attendance at an out- convincing evidence that hypotensive drugs significantly patient clinic, and also on the basis of the maximum influence the incidence of either cardiac infarction or dose of the hypotensive drug which the patient can cerebrovascular accidents in hypertensive patients. tolerate without developing side-effects which interfere seriously with his activities. In many patients this means Conclusion that one has to be satisfied with diastolic blood-pressure readings of about 100 mm. Hg; attempts to maintain Although the new hypotensive drugs have revolu- lower levels than this are nearly always accompanied tionized the treatment of hypertension their use is still by episodes of postural hypotension which will only be only one aspect of the management of the patient with are potent accepted by a few intelligent and co-operative patients. high blood-pressure. Because these drugs Patients with severe hypertension whose treatment has therapeutic agents with side-effects which are often been started in hospital must be seen at frequent unpleasant and sometimes dangerous, it is extremely intervals after they are discharged. Only after they important that no patient should receive them until a have achieved a stable level of blood-pressure control thorough assessment has been made and it is certain for several weeks can they be allowed to remain Hypotensive Drugs unsupervised for a month or two. Patients who are Dose receiving ganglion-blocking or adrenergic-blocking Group Approved Name Other Names Daily(mg.) agents must be warned not to stand still-for example, Ganglion- Hexamethonium " Vegolysen" * at a bus-stop or looking into a shop window-for any blocking Pentolinium. " Ansolysen" * agents Chlorisondamine " Ecolid " 50-500 length of time. If they develop an intercurrent illness, Trimethidinium(U.S.) " Ostensin" 60-300 even a minor respiratory infection, they may become Pentacynium " Presidal" 200-800 Pempidine "Perolysen " 10-80 more susceptible to the hypotensive effects of these "Tenormal " in Mecamylamine "Inversine" 5-60 drugs and often require a reduction dosage. They Trimetaphan should be advised not to become or to continue as blood camphorsulphonate "Arfonad" t Phenacyl- donors. homatropinium "Trophenium" t their Patients with benign hypertension may have Adrenergic- Bretylium tosylate "Darenthin" 100-1,800 treatment started as out-patients, and the dose of the blocking Guanethidine "Ismelin" 10-300 hypotensive drug is then gradually increased at agents no a week; other drugs are added Rauwolfia Extracts of Rauwolfia Alseroxylon 2-4 intervals of less than compounds " Hypertane" 2-4 if necessary. With such patients the question of side- " Rauwiloid" 2-4 " Hypertensan" 50-200 effects is often critical. They frequently feel well in " Raudixin" 50-200 and it be difficult to Reserpine " Serpasil " 0-5-1 spite of their hypertension may Deserpidine " Harmonyl" 0-5-1-5 persuade them to accept even relatively minor side- Methoserpidine "Decaserpyl" 10-60 Syrosingopine "Singoserp" 0 5-3 effects for a benefit which they cannot readily to be though Diuretics Chlorothiazide "Saluric" 500-1,000 appreciate. They prefer happy Hydrochlorothiazide " Direma" 25-100 hypertensive than miserable from medication. " Esidrex" " HydroSalaric" " Hydrothide" Hydroflumethiazide " NaClex " 25-100 Results of Treatment " Di-ademil" " Hydrenox " A critical assessment of the results of treatment in a Bendrofluazide " Aprinox" 2 5-10 " Centyl " condition with so variable and unpredictable a course " Neo-Naclex" 100-200 as hypertension is extremely difficult. The most satis- Chlorthalidone "Hygroton" factory evidence would be a clear demonstration that Decarboxylase Methyldopa "Aldomet" 500-4,000 treatment with hypotensive drugs improved the prospects inhibitor survival. Such information is available only for the Veratrum Extracts of Veratrum Alkavervir 9-15 of compounds " Veriloid" malignant phase of the disease. There are now a Protoveratrines " Puroverine " 1-6 number of excellent papers in which it is shown that A and B the life of patients with malignant hypertension is pro- Hydrallazine " Apresoine " 50-200 and that the use of " longed by the hypotensive drugs, Mebutamate Capla 600-1,200 prospects for such a patient are better if he does not " renal failure when treatment is * These drugs are now given by injection only for the treatment of have evidence of hypertensive emergencies. t These are ultra-short-acting ganglion-blocking at started.5 6 agents used only by anaesthetists operations. APRIL 20, 1963 TO-DAY'S DRUGS B.rnsl- 1075 that treatment with hypotensive drugs is necessary. patients there is still a large group whose treatment even There are many patients with high blood-pressure who in the best hands is unsatisfactory, either from the do not require these drugs; the young adult who is patient's or from the physician's point of view. None symptom-free and has a blood-pressure of 150-160/ the less the evidence, at least in the more severe grades 90-95 mm. Hg requires explanation, reassurance, and of hypertension, that a reduction in blood-pressure is some sensible advice about his way of life; the middle- accompanied by an improved prognosis must encourage aged, slightly obese female whose casual blood-pressure us to persevere in the hope that newer and better hypo- is 210-220/110-120 is usually happy with her hyper- tensive drugs will be discovered. tension and should not be made miserable with drugs. For those in whom blood-pressure reduction is REFERENCES desirable the drugs now available offer a means of Rosenheim, M. L., Proc. roy. Soc. Med., 1962, 55, 278. achieving this but only at the expense of considerable 2 Dustan, H. P., and Page, I. H., Circulation, 1962, 25, 437. time and effort on behalf of both the physician and the Marshall, J., and Kaeser, A. C., Brit. med. J., 1961, 2, 73. 4 Turner, R. W. D., Proc. roy. Soc. Med., 1962, 55, 280. patient. It is important that the choice of drugs and 5 Pickering, G., Cranston, W. I., and Pears, M. A., The Treat- their combination should be related to the make-up of ment of Hypertension, 1961. Thomas, Springfield, Illinois. the patient and to his hypertensive disease. Although it 6 Harington, M., Proc. roy. Soc. Med., 1962, 55, 283. ' Hodge, J. V., McQueen, E. G., and Smirk, H., Brit. med. J., is now possible to maintain reasonable control of the 1961, 1, 1. blood-pressure in a considerable number of hypertensive Page, I. H., Ann. intern. Med.. 1962, 57, 96.

investigations such as air encephalography or carotid ANY QUESTIONS ? angiography will show any disorder that I advise against We publish below a selection of those questions and them. It would be better to refrain from the use of anti- answers which seem to be of general interest. It is regretted convulsant therapy and to re-examine the patient every few that it is not possible to supply answers to all questions months. submitted. In law the patient should not drive a car again, but most licensing authorities will grant a licence to a driver who has Prognosis in Treated Cardiac Arrest had fits, provided he has been free of fits for five years, Q.-What is the ultimate prognosis in unselected patients two of which have been without anticonvulsant therapy. with respiratory or cardiac arrest treated by cardiac massage What advice the doctor gives will depend upon many or continuous artificial respiration? Is there any recent considerations, including the amount the patient drives and review on this subject ? the circumstances in which she does so. I should think that A.-After successful resuscitation the ultimate prognosis in this particular case, with a single nocturnal fit, a year should be the same as if the respiratory or cardiac arrest without treatment would be adequate in common sense, if had never happened. The prognosis will be that of the not according to the law. causal illness and of any complications arising from the treatment itself, such as broken ribs after external compres- S.P.32 sion or sepsis after internal massage. When cardiac arrest Q.-I-Phenyl-2-pyrrolidinopentane hydrochloride is said occurs in an otherwise healthy person while under medical to have general tonic properties and to be an elevator of observation during a diagnostic procedure or in the operating mood. Is this true and are there any dangers in its use ? theatre, and is instantly recognized as it should be, resuscita- tion should nearly always be possible, and no neurological A.-Phenyl-pyrrolidinopentane, also known as S.P.32, is damage should ensue. Of course, cerebral and often renal the main constituent of the proprietary preparation damage may result if adequate restoration of ventilation "villescon," which also contains vitamin-B complex and and circulation is delayed. The effects of acute renal vitamin C.1 In large doses it causes convulsions. It is ischaemia are either fatal or reversible, so do not concern claimed to be of value as a general tonic, for the treatment us in the consideration of ultimate prognosis. However, of various states in which the patient complains of tiredness the brain, which is the organ most sensitive to anoxic or exhaustion, and as a stimulant in the elderly. Most of the insult, may be damaged and the final outcome be anything reports on the clinical use of the drug come from the between gross cerebral damage and the most subtle intel- Continent and are based mainly upon subjective assessments lectual defect. Minor cerebral syndromes may be recoverable on uncontrolled studies. In this country Laverty and Sinclair- over the short or long term. Gieben2 treated 44 patients with various affective disorders. There is now an abundant literature on the subject of This was a very small trial carried out over a relatively cardiac and respiratory arrest, and the questioner is referred short period, and in view of the fact that the results have to the publications listed below.`' to be assessed on subjective sensations one would like to have further confirmation of these findings before accepting REFERENCES this substance as a valuable addition to our list of drugs. 1 Brit. J. Anaesth., 1961, 33, 480. It is claimed that in therapeutic doses the drug is free of s Pampiglioni, G., Proc. roy. Soc. Med., 1962, 55, 653. 3 Artificial Respiration, Theory and Applications, 1962, ed. James L. side-effects, and none were noted in the trial mentioned Whittenberger. Harper and Row, London and New York. above. Its use is contraindicated in thyrotoxicosis. 4 Shipman, K. H., McCredy, W., and Bradford, H. A., Amer. J. Cardiol., 1962, 10, 551. REFERENCES I B SAt.med. J., 1961, 1, 1104. Nocturnal Fit in a Driver 2 Laverty, 5. 0., and Sinclair-Gieben, A. H., Scot. med. J., 1959. 4. 567. Q.-A woman driver, aged 44, had one epileptiform convulsion in the middle of the night, described as a Fat Under the Chin " typical one " by her husband. She also wet the bed Q.-I have a patient who has a pad of fat under the chin (which she has neven done before). An E.E.G. showed a but who is otherwise not unduly obese. What surgical practically normal reading. Should further investigations be technique can be used to benefit this ? done ? And for how should she stop ? long driving A.-Occasionally it is advisable to remove a pad of fat A.-If a person has a generalized convulsion without any from beneath the chin through a local incision, but this subsequent neurological signs, and an electroencephalogram operation may leave a rather obvious scar in the neck with is normal, it is so highly unlikely that more detailed an uneven contour. When there is a well-defined lipoma a