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Looking back on 60 years of DTB: antihypertensive drugs in 1962

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This year, Drug and Therapeutics Bulletin (DTB) is celebrating its 60th anniversary and to mark this occasion we are looking back at some of DTB’s early articles.

When DTB was first launched in 1962 there were no drug licensing laws, no formal controls of drug promotion or arrangements for pharmacovigilance, no summaries of product characteristics, and little recognition of the importance of scientific evidence to clinical practice.1 Doctors and drug companies went essentially unquestioned and there was little discussion with patients over details of their illness, treatment options or preferences.

At a time when there were very few independent sources of reliable information on the effects of medicines, DTB’s aim was—and continues to be—‘to provide clinicians with clear, reliable, usable, impartial and independent information to help ensure patients get the best deal’.1

In one of its early editions, DTB highlighted the challenge faced by clinicians in relation to new medicines and offered some advice: ‘to determine the effectiveness of a remedy is a difficult undertaking, and to anticipate the range, incidence and severity of harmful effects is impossible even with carefully controlled trials. For these reasons the physician should employ the greatest reserve in using new drugs, particularly when the risk of unknown toxicity is not offset by proved and significant superiority over older, standard remedies.’2 Despite developments in the regulation, manufacture and surveillance of medicines, DTB’s advice on the use of new medicines remains as important today as it did in 1962.

In May 1962, DTB (at that time published as a British edition of the US publication, The Medical Letter) discussed the evidence for using monoamine oxidase (MAO) inhibitors in the management of hypertension and concluded that ‘in the treatment of essential hypertension, the MAO inhibitors have no obvious advantages over other drugs which have been much more thoroughly studied, and their use in primary hypertension cannot be recommended at this time’.3 A month later, DTB reviewed the use of ganglion blocking drugs, including tetraethylammonium chloride (Beparon), mecamylamine hydrochloride (Inversine) and trimetaphan camphorsulphonate (Arfonad), for the treatment of hypertension.4 None of the six ganglion blocking drugs discussed are still licensed for use in the UK, and they all had significant serious adverse effects. The article noted that undesirable effects of these drugs ‘have been frequent and severe; they can cause fatal hypotension in persons with impaired renal, cerebral, or coronary circulation’. The article suggested that they should be reserved ‘for patients with accelerated and malignant hypertension, and for patients with less severe hypertensive disease whose prognosis is adversely affected by such factors as age, sex and family history’.

The role of guanethidine in the management of hypertension was covered in an article 2 weeks later.5 Guanethidine was regarded as being the preferred option in patients unable to tolerate ganglion blockers as it only blocks sympathetic nerve transmission, not the parasympathetic. So, while mydriasis, constipation and impotence were less common adverse effects compared with the ganglion blockers, diarrhoea was a problem. The DTB article suggested that orthostatic hypotension that occurred with this drug was ‘not a side effect but a feature of its therapeutic action’. The most recent Summary of Product Characteristics for guanethidine states that it is indicated for ‘control of hypertensive crises, and to obtain more rapid blood pressure control’, but the British National Formulary states that alternative treatments are preferred.6 7

It is worth remembering that in 1962 there was no evidence that drug treatment reduced risk of stroke or cardiovascular events in patients with ‘mild’ hypertension (defined at the time as a diastolic blood pressure of 90 to 109 mm Hg) and in an article in July 1962, DTB commented that chlorothiazide and other thiazide diuretics should be used with restraint in mild hypertension, suggesting that patients would do just as well ‘on nothing more than a weight-reducing diet and mild sedation’.8 Even in 1971, DTB highlighted the lack of evidence for treating mild uncomplicated hypertension and noted that further evidence was needed.9 It would not be until 1985 that the treatment of mild hypertension would be supported by evidence from the definitive Medical Research Council trial.10

References

Footnotes

  • Contributors Contributors DTB Team.

  • Provenance and peer review Commissioned; internally peer reviewed.