Feb 28, 1987 - Churchill Livingstone, 1979:192. Adenosine: an importance .... write: Dr Susan M Wood and her colleagues (10. January, p 92) described 13 ...
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Points The potential and benefits of advanced prehospital care
BRITISH MEDICAL JOURNAL
established therapeutic importance in the manipulation of ductal blood flow in the neonate. Pharmacological treatment has been described both to contract the patent ductus arteriosus3 and to dilate the vessel when ductal patency is desirable, as in neonates with certain aortic arch abnormalities.4 Adenosine antagonists and agonists have yet to be evaluated under such circumstances. Whatever the clinical importance of these observations, it remains an interesting possibility that, at least in the fetus, circulating adenosine may give rise to specific vasodilator effects, as well as its autoregulatory action on blood vessels local to its site of release.
Mr WILLIAM RUTHERFORD (Department of Health and Social Service, Northern Ireland) writes: It is unfortunate that the study by Mr I W R Anderson and colleagues (24 January, p 278) should have become available only after decisions have already been taken about the nature and scope of advanced training for ambulancemen. A strong case could be made for concentrating primarily on making defibrillation 1 Mentzer RM, Ely SW, Lasley RD, Mainwaring RD, Wright available in all emergency ambulances and leaving EM, Berne RM. Hormonal role of adenosine in maintaining other aspects of advanced training until the rewards of patency of the ductus arteriosus in fetal lambs. Ann Surg this move have been reaped. It seems unlikely that this 1985;202:223-30. could be negotiated at this stage. This makes it all the 2 Kovalcik V. The response of the isolated ductus arteriosus to oxygen and anoxia. J Physiol 1963;169:185-97. more urgent to ensure that good studies are planned and executed to monitor the effect of the new training. 3 Kitterman JA. Patent ductus arteriosus: current clinical status. Arch Dis Child 1980;55:106-9. Although objective measurement is not easy, it is not 4 Heymann MA, Berman W, Rudolph AM. Dilation of the ductus impossible. arteriosus by prostaglandin E2 in aortic arch abnormalities. Circulation 1979;59:169-73.
Dr C J WRIGHT (St James's University Hospital, Leeds LS9 7TF) writes: While practical resuscitation is a major component of the extended training of ambulance staff (Mr I W R Anderson and others (24 January, p 228)), training in clinical examination and observation and the underlying physiology and disease is equally important. This information should be of great benefit to the medical teams taking over the care of a particular case. In our first six months of experience with our first three ambulance staff who had undergone extended training, of 148 cardiac patients, only 115 required an electrocardiograph recording, and of the remainder, 49 were said to require basic ambulance skills, with only nine actually requiring defibrillation. No doubt figures will soon become available to confirm or refute the predictions of Mr Anderson and coworkers, but ambulance staff who have undergone extended training will clearly improve survival in many patients, particularly those with head injuries, for whom the maintenance of an unobstructed airway is paramount. It is also clear that such staff contribute to the smooth transfer of seriously ill patients to regional specialist centres. The extended training of 40-50 ambulance staff yearly in West Yorkshire takes 0 34% of the county's expenditure on ambulance services, which I suggest will prove a wise investment. Many ambulance cadets now have qualifications that several years ago would have been adequate for entry to medical school.
The increase in molluscum contagiosum Dr C B S SCHOFIELD (Newcastle General Hospital, Newcastle upon Tyne NE3 4YN) writes: Dr M A Waugh (7 February, p 373) should consider treating molluscum contagiosum lesions with an up to date non-touch technique, such as cryotherapy,' using a liquid nitrogen spray. This is much more hygienic and effective than the archaic thumbnail method of removal, which he believes to be "usually done" in outpatient departments. I Schofield CBS. Sexually transmitted diseases. 3rd ed. Edinburgh:
Churchill Livingstone, 1979:192.
Adenosine: an importance beyond ATP Dr GORDON C S SMITH (Institute of Physiology, The University, Glasgow G12 8QQ) writes: There was one important omission from the otherwise extensive article by Drs A H Watt and P A Routledge (6 December, p 1455)-namely, the recent study by Mentzer et al on the role of circulating adenosine in maintaining patency of the fetal ductus arteriosus in utero.' The authors described in vivo reversal of oxygen induced contracture of the ductus arteriosus by adenosine, as shown in vitro by Kovalcik in 1963.2 Furthermore, fetal plasma adenosine values decreased in a dose dependent way in relation to increasing arterial oxygen tensions when the fetus was ventilated with 100% oxygen. Thus circulating adenosine may have a role (a) in maintaining patency of the ductus arteriosus in utero and (b) by its (relative) absence in ductal closure in early neonatal life. There is a well
Drug points Syrup of ipecacuanha Drs I M ANDERSON and C WARE (Warneford Hospital, Oxford OX3 7JX) write: The evidence cited by Dr J A Vale and others (22 November, p 1321) on the superiority of activated charcoal over ipecacuanha suggests that the combination of gastric lavage and activated charcoal may be the treatment of choice in antidepressant poisoning. We describe a case illustrating a costly and avoidable complication of this treatment. A A2 year old man with hypochondriacal delusions during a depressive illness was admitted two hours after a serious suicide attempt by self poisoning with 85 x25 mg amitriptyline and 50x50 mg chlorpromazine tablets. He was deeply unconscious though breathing spontaneously and after intubation received gastric lavage followed by 50 g activated charcoal (Carbomix). Over the next 36 hours he was given 300 g of activated charcoal. He recovered and was transferred to a psychiatric unit. Over the next 10 days he was mobile and maintained a good fluid input. He received small doses of trifluoperazine and temazepam but no further antidepressants. He was treated with danthron (Dorbanex) for constipation without effect and was severely constipated before receiving more vigorous treatment consisting of sodium picosulphate (Picolax), suppositories, enemas, and an attempted manual evacuation, all without success. By the 12th day he was in great discomfort with spurious diarrhoea secondary to faecal impaction. He was transferred to a surgical unit for an anal stretch and manual evacuation under general anaesthetic. The impacted mass mainly consisted of charcoal resembling a barbecue briquette. We concluded that the combination of the anticholinergic action of both drugs taken in overdose together with 3/4 lb of high residue charcoal led to this result. It is important to be aware of this complication, and consideration should be given to using a preparation of activated charcoal reported to cause diarrhoea (Medicoal) rather than the constipation which has been associated with Carbomix.1 Furthermore, the early and vigorous treatment of constipation may help to prevent surgical intervention. I Proudfoot AT, Vale JA. Acute poisoning: an update. Prescribers
Joumnal 1986;26:78-87.
Alfacalcidol and hypercalcaemia Dr B T MARSH (Leo Laboratories, Aylesbury, Bucks HP17 9RR) writes: I endorse the plea of Dr Mark Ardron (10 January, p 125) for careful biochemical monitoring during treatment with alfacalcidol. This drug is widely used in place of vitamin D in various conditions. Two of its main advantages are the rapid response to its administration and the fact that any overdose can be quickly reversed over a few days. Vitamin D intoxication, on the other hand, may last for
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several months with an irreversible hypercalcaemia during this time. Indeed, Mawer et al have stated that it is difficult to recommend pharmacological doses of vitamin D in the management of vitamin D resistant conditions when treatment with the newer derivatives of vitamin D such as alfacalcidol are effective.' We would emphasise the need for regular biochemical monitoring of all patients receiving alfacalcidol as indicated in our data sheet. We also recommend a starting dose of 0 5 ,ug rather than 1 [tg in the elderly. The dose can then be adjusted according to the biochemical response. I MawerEB, HannJT, BerryJL, DaviesM. Vitamin D metabolism in patients intoxicated with ergocalciferol. Clin Sci 1985;68: 135-41.
Angio-oedema and urticaria associated with enalapril Professor W H W INMAN and Dr N S B RAWSON (Drug Safety Research Unit, Southampton S03 2BX) write: Dr Susan M Wood and her colleagues (10 January, p 92) described 13 reports of angio-oedema associated with the use of enalapril that were submitted to the Committee on Safety of Medicines. Six cases occurred after the first dose and seven within five days of starting treatment. The committee cannot estimate the incidence of adverse reactions, so it may be useful to provide an estimate based on our study of this drug by prescription event monitoring, which is complementary to the yellow card system. Our study is still in progress, but to date 10500 adequately documented cases have been assembled. All have been followed up for at least one year. Nine cases of angio-oedema have been reported, of which two occurred three and eight months after the patient had stopped taking the drug; another had suffered from chronic angio-oedema for several years. Of the remaining six, one patient developed it on the second day and the five others three to 11 months after starting treatment. We have also heard of three other patients developing "facial oedema" during the first two days of treatment. Thus of nine possible cases of angio-oedema, only four occurred early in treatment, while in the other five the probability of a link with enalapril appears to be small. Our results suggest that the overall incidence may be about one per 1000 patients per year, while the attributable incidence may be about half this. Although there has been some concern that enalapril might cause anaphylactic shock, we have encountered no case in this study or in an earlier study in about 2500 patients in which we used prescription event monitoring to test that particular hypothesis.
Nephrotoxic drug interaction between metolazone and cyclosporin Drs P CHRISTENSEN and M LESKI (Division de
Nephrologie, Departement de Medecine, H6pital Cantonal Universitaire, 1211 Geneve 4, Switzerland) write: A 39 year old man whose second renal cadaver transplant was followed by subnormal renal function (creatinine 235 [tmol/l) and severe hypertension (220/130 mm Hg) required the introduction of atenolol (100 mg/day) and minoxidil (15 mg/day). Then appeared ankle oedema resistant to increasing doses of frusemide (up to 500 mg/day and then 750 mg/day). The addition of low doses of metolazone (2-5 mg/day) for two weeks caused the increase of serum creatinine concentrations from 193 to 449 ,umol/l. There was no other change in treatment, significant reduction in body weight, or change in whole blood cyclosporin values (321-329 ,tg/l). Stopping only the metolazone resulted in a return of serum creatinine concentration to the previous value. There was neither graft rejection nor hypovolaemia to explain the deterioration of renal function. Furthermore, the metolazone did not alter the bioavailability of cyclosporin. It thus seems that there was a toxic drug interaction at the level of the kidney. We have found no mention of such an interaction in published reports or from the manufacturer. This interaction may be important in view of the therapeutic indications of cyclosporin-for example, in the nephrotic syndrome and in renal transplantation with hypertension necessitating minoxidil.
