548

AMANTADINE-INDUCED HEART-FAILURE

SIR,-Amantadine alone or in combination with levodopa isof benefit in the treatment of Parkinson’s disease. A numberof adverse effects, however, complicate the use of this drug;one of the commonest is ankle oedema. This appears to be oflittle significance and is unassociated with cardiac, renal, orhepatic disease. Its appearance does not usually necessitate thewithdrawal of treatment. There have, in addition, been iso-lated reports 1 suggesting that heart-failure may follow or beexacerbated by the use of amantadine. We wish to report afurther patient who had severe cardiac failure after he hadreceived amantadine for 4 years.The patient was a man of 65 who had been diagnosed as

having Parkinson’s disease in 1970. He was at first treatedwith levodopa alone, but in October, 1971, amantadine 100mg twice a day and orphenadrine 50 mg three times a day werealso prescribed. The patient remained in good health and wasable to enjoy a regular round of golf until August, 1975, whenhe became increasingly short of breath and bilateral ankleoedema developed; his exercise tolerance fell to 20 m. He wasadmitted to hospital in September, 1975. On examinationthere was pitting oedema up to the knees, the jugular venouspressure was raised 5 cm and basal crepitations were heard.Congestive cardiac failure was diagnosed and this was con-firmed radiologically (cardiothoracic ratio 17/30). Throughoutthe illness the electrocardiograms showed non-specific T-wavechanges, and serial biochemical profiles were normal. Becauseof the possibility that amantadine might have precipitated theheart-failure, the drug was stopped forthwith and diuretic

therapy was prescribed with dramatic alleviation of symptoms.3 weeks after admission the patient had a major pulmonaryembolism, but made a satisfactory recovery. A year later therewas no clinical or radiological evidence of cardiac failure (car-diothoracic ratio 15/30) and he no longer required diuretics.His extrapyramidal symptoms were well controlled byorphenadrine and levodopa.

In 1970 Parkes et al.’ described a patient who had oedemaand mild cardiac enlargement while receiving amantadine.Walker et all have reported two further patients with thiscomplication during a clinical trial. The first had cardiac fail-ure during the placebo period which worsened when she wasgiven levodopa and amantadine. The failure responded poorlyto diuretics and the withdrawal of anti-parkinsonian therapy,and she died. The second patient had ankle oedema whilereceiving amantadine. After completion of the trial paroxysmalnoctural dyspnoea developed. His symptoms lessened on

digoxin and diuretics and the withdrawal of amantadine, buthe died from a probable pulmonary embolism.

It would seem reasonable to conclude that our patient alsohad an amantadine-induced cardiomyopathy since no othercause for the sudden development of severe cardiac failurecould be elicited. Parkes et al. have suggested that oedema inpatients on amantadine is due to a peripheral fluid shift in thelegs, probably from muscles into skin and subcutaneous tis-sues. They found no evidence of a change in total body wateror sodium. The mechanism whereby amantadine induces car-diac failure is unknown though animal studies have shownthat when it is given in high dosage there is a significant de-crease in myocardial contractility.4 We recommend that aman-tadine should be prescribed with caution to patients with a his-tory of myocardial disease. The American pharmaceuticalliterature carries this warning.

Guy’s Hospital,London SE1 9RT

J. A. VALEK. S. MACLEAN

1. Parkes, J. D., Zilkha, K. J., Marsden, P., Baxter, R. C. H., Knill-Jones,R. P. Lancet, 1970, i, 1130.

2. Walker, J. E., Potvin, A., Tourtellotte, W., Albers, J., Repa, B., Henderson,W., Snyder, D. Clin. Pharmac. Ther. 1972, 13, 28.

3. Parkes, J. D., Baxter, R. C. H., Curzon, G., Knill-Jones, R. P., Marsden,C. D., Tattersall, R., Vollum, D. Lancet, 1971, i, 1083.

4. Van Ackern, V. K., Deuster, J. E., Mast, G. J., Schmier, J. Arzneimittel-Forsch. 1975, 25, 891.

ACUTE REACTION TO PENTAGASTRIN

Sm,—We would like to report the first major reaction topentagastrin (’Peptavlon’) that we have observed in our unitwhere we have used this drug daily in thousands of gastric-function tests over the past 10 years. We had previouslyobserved only the well-recognised minor side-effects, but oneother severe reaction has been reported.’ 1A man of 56 with a chronic duodenal ulcer, but otherwise

healthy, attended our gastric clinic, fasting. He was semi-recumbent on a couch with a nasogastric tube in place and aninfusion of saline through a butterfly needle into a forearmvein for one hour. The reaction occurred 3-6 min after the

syringe pump had been changed to a pentagastrin infusion.The syringe contained 680 g pentagastrin (concentration6 jjLg/kg in 47 ml water), and not more than 40 p.g had been in-fused when the patient fainted and became cold and white withno radial pulse palpable for 3 min. Once the pulse returned hehad a severe bradycardia of 35/min. Intravenous prometha-zine 50 mg produced some temporary improvement of hispulse but 5 min later the pulse weakened and 100 mg hydro-cortisone succinate was given intravenously. 10 min later hewas conscious and rational but cold and shivering with pulse65/min and blood-pressure 110/60 mm Hg. The test was

stopped and he recovered completely after 60 min. A sub-sequent electrocardiogram was normal. Despite the brady-cardia there was no suggestion that this was a vasovagal epi-sode, since the patient was comfortable and unaware of thestart of the pentagastrin infusion.

LC.L’s medical department tell us: "We have had severalreports of acute reactions characterised by sweating, hypoten-sion and bradycardia following the administration of Teptav-Ion’. Investigations have not succeeded in throwing any lighton their nature and I suppose they must be ascribed to an idio-syncrasy or an acute hypersensitivity. In some cases we havebeen able to recover the batch from which the ampoule inquestion was taken and invariably it has been demonstrated onanalysis that no fault can be detected in the formulation".

We thank Dr J. A. Waycott, medical department, I.C.I. for his com-ments.

Department of Surgery,Royal Postgraduate Medical School,Hammersmith Hospital,London W12

R. F. MCCLOY

J. H. BARON

ŒSOPHAGEAL ULCERATION DUE TOEMEPRONIUM BROMIDE

SIR,-We were interested to read the three cases reported byDr Kavin (Feb. 19, p. 424). We have seen a similar incidentin an otherwise healthy woman of 18 who had been prescribedemepronium bromide (’Cetiprin’) for urinary-tract symptoms.2 days after starting treatment she had very severe retrosternalpain. She had considerable dysphagia for both solids and fluidson account of the pain. Barium-swallow examination revealedno abnormality. At resophagoscopy there was an area of acuteinflammation, extending over 2 or 3 cm, in the region of themid-cesophagus. There was contact bleeding and superficialulceration. The distal oesophagus was normal. She made agood recovery on intravenous fluids and analgesics. Later shesaid that she had taken the emepronium immediately beforegoing to bed and without any drink. Ulceration of the gumsand mouth has occurred with this compound, according to themanufacturers, in elderly patients who are probably liable tohold the tablets in their mouths for prolonged periods, butcesophageal ulceration is not widely known.

Ashford Hospital,Ashford, Kent TN23 1LX

SIMON KENWRIGHTA. D. C. NORRIS

1. Aylward, M., Bourke, J. B. Lancet, 1969, ii, 267.