Restoration of Blood Flow after Pulmonary Embolism

J. A. Oates and his colleagues' observed the effects of guanethidine, methyldopa, and pargyline in 19 patients. They found less postural hypotension with methyldopa than with either of the other drugs, and fewer severe side-effects. V. Vejlsgaard and colleagues' carried out a double-blind trial of guanethidine, methyldopa, guanoclor, and guanoxan. They found that guanoclor produced more severe side-effects than the others and was extremely difficult to use. Methyldopa caused less postural hypotension and fewer side-effects than guanethidine or guanoxan. In that series' the dose of methyldopa was not limited by side-effects, but in four patients the blood pressure could not be controlled with this drug. The maximum dose used by Vejlsgaard and colleagues was much smaller than in the series reported this week by Sir Max Rosenheim and his team. Guanoxan caused fewer sideeffects than guanethidine in this trial, but there is evidence that it may impair liver function,5 6 and for this reason many will prefer to use other drugs. It thus seems clear that methyldopa has less postural effect on arterial pressure than the other sympathetic blocking agents with which it has been compared. This carries the implication that better control of blood pressure when the patient is supine should be achieved with this drug. But whether this is important in determining prognosis is unknown. Most patients with hypertension show a considerable fall of blood pressure with sleep,' and most of them should be able to live reasonably normal lives. Since most people lie down for long periods only when they are asleep, it might be expected that hypertensive patients are to some extent protected when in the supine position by the fall of blood pressure then. If this is generally true, control of blood pressure when supine may be less important than is at present believed. But it must be stressed that there is at present no evidence for this view. These comparisons of different drugs in the same patients can be performed only over relatively short periods of time. They give information about the ease of control of blood pressure and about early side-effects. They do not provide information about the development of tolerance to the drugs nor about delayed toxic effects, such as the appearance of positive Coombs tests and haemolytic anaemia with methyldopa.a They give a general indication of the likelihood that a given drug will control blood pressure in a group of patients. Oates and his colleagues' stress the importance of individual variations. Though one drug may, on average, cause fewer side-effects than another, many patients will be better controlled on the apparently " worse" drug. In the light of the evidence now available the first choice of a sympathetic blocking agent probably ought to lie betiveen methyldopa and bethanidine, with the proviso that debrisoquine (see p. 166) has not yet been compared with any of the other drugs of this kind. Guanethidine no longer seems to have a claim to be the first line of treatment in severe hypertension, but it must be retained because some patients may respond better to it than to other drugs. All the sympathetic blocking agents need to be used with care and patience. Small adjustments of dosage may alleviate disturbing side-effects without impairing control of the blood pressure. Experience in the use of a drug helps a great deal, and in view of the small differences shown between drugs in this trial there is a strong case for prescribing the one with which the doctor is most familiar.