548 ACUTE REACTION TO PENTAGASTRIN
AMANTADINE-INDUCED HEART-FAILURE
SIR,-Amantadine alone or in combination with levodopa is of benefit in the treatment of Parkinson’s disease. A number of adverse effects, however, complicate the use of this drug; one of the commonest is ankle oedema. This appears to be of little significance and is unassociated with cardiac, renal, or hepatic disease. Its appearance does not usually necessitate the withdrawal of treatment. There have, in addition, been isolated reports 1suggesting that heart-failure may follow or be exacerbated by the use of amantadine. We wish to report a further patient who had severe cardiac failure after he had received 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 treated with levodopa alone, but in October, 1971, amantadine 100 mg twice a day and orphenadrine 50 mg three times a day were also prescribed. The patient remained in good health and was able to enjoy a regular round of golf until August, 1975, when he became increasingly short of breath and bilateral ankle oedema developed; his exercise tolerance fell to 20 m. He was admitted to hospital in September, 1975. On examination there was pitting oedema up to the knees, the jugular venous pressure was raised 5 cm and basal crepitations were heard. Congestive cardiac failure was diagnosed and this was confirmed radiologically (cardiothoracic ratio 17/30). Throughout the illness the electrocardiograms showed non-specific T-wave changes, and serial biochemical profiles were normal. Because of the possibility that amantadine might have precipitated the heart-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 pulmonary embolism, but made a satisfactory recovery. A year later there was no clinical or radiological evidence of cardiac failure (cardiothoracic ratio 15/30) and he no longer required diuretics. His extrapyramidal symptoms were well controlled by orphenadrine and levodopa. In 1970 Parkes et al.’ described a patient who had oedema and mild cardiac enlargement while receiving amantadine. Walker et all have reported two further patients with this complication during a clinical trial. The first had cardiac failure during the placebo period which worsened when she was given levodopa and amantadine. The failure responded poorly to diuretics and the withdrawal of anti-parkinsonian therapy, and she died. The second patient had ankle oedema while receiving amantadine. After completion of the trial paroxysmal noctural dyspnoea developed. His symptoms lessened on digoxin and diuretics and the withdrawal of amantadine, but he died from a probable pulmonary embolism. It would seem reasonable to conclude that our patient also had an amantadine-induced cardiomyopathy since no other cause for the sudden development of severe cardiac failure could be elicited. Parkes et al. have suggested that oedema in patients on amantadine is due to a peripheral fluid shift in the legs, probably from muscles into skin and subcutaneous tissues. They found no evidence of a change in total body water or sodium. The mechanism whereby amantadine induces cardiac failure is unknown though animal studies have shown that when it is given in high dosage there is a significant decrease in myocardial contractility.4 We recommend that amantadine should be prescribed with caution to patients with a history of myocardial disease. The American pharmaceutical literature carries this warning. Guy’s Hospital,
J. A. VALE
London SE1 9RT
K. S. MACLEAN
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. ArzneimittelForsch. 1975, 25, 891. 1.
report the first major reaction to we have observed in our unit that pentagastrin (’Peptavlon’) where we have used this drug daily in thousands of gastricfunction tests over the past 10 years. We had previously observed only the well-recognised minor side-effects, but one other severe reaction has been reported.’1 A man of 56 with a chronic duodenal ulcer, but otherwise healthy, attended our gastric clinic, fasting. He was semirecumbent on a couch with a nasogastric tube in place and an infusion of saline through a butterfly needle into a forearm vein 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 (concentration 6 jjLg/kg in 47 ml water), and not more than 40 p.g had been infused when the patient fainted and became cold and white with no radial pulse palpable for 3 min. Once the pulse returned he had a severe bradycardia of 35/min. Intravenous promethazine 50 mg produced some temporary improvement of his pulse but 5 min later the pulse weakened and 100 mg hydrocortisone succinate was given intravenously. 10 min later he was conscious and rational but cold and shivering with pulse 65/min and blood-pressure 110/60 mm Hg. The test was stopped and he recovered completely after 60 min. A subsequent electrocardiogram was normal. Despite the bradycardia there was no suggestion that this was a vasovagal episode, since the patient was comfortable and unaware of the start of the pentagastrin infusion. LC.L’s medical department tell us: "We have had several reports of acute reactions characterised by sweating, hypotension and bradycardia following the administration of TeptavIon’. Investigations have not succeeded in throwing any light on their nature and I suppose they must be ascribed to an idiosyncrasy or an acute hypersensitivity. In some cases we have been able to recover the batch from which the ampoule in question was taken and invariably it has been demonstrated on analysis that no fault can be detected in the formulation".
Sm,—We would like
We thank Dr
to
J. A. Waycott, medical department, I.C.I. for his com-
ments.
Department of Surgery,
Royal Postgraduate Medical School, Hammersmith Hospital,
R. F. MCCLOY J. H. BARON
London W12
ŒSOPHAGEAL ULCERATION DUE TO EMEPRONIUM BROMIDE
SIR,-We were interested to read the three cases reported by Dr Kavin (Feb. 19, p. 424). We have seen a similar incident in an otherwise healthy woman of 18 who had been prescribed
emepronium bromide (’Cetiprin’) for urinary-tract symptoms. 2 days after starting treatment she had very severe retrosternal pain. She had considerable dysphagia for both solids and fluids on account of the pain. Barium-swallow examination revealed no abnormality. At resophagoscopy there was an area of acute over 2 or 3 cm, in the region of the There was contact bleeding and superficial ulceration. The distal oesophagus was normal. She made a good recovery on intravenous fluids and analgesics. Later she said that she had taken the emepronium immediately before going to bed and without any drink. Ulceration of the gums and mouth has occurred with this compound, according to the manufacturers, in elderly patients who are probably liable to hold the tablets in their mouths for prolonged periods, but cesophageal ulceration is not widely known.
inflammation, extending
mid-cesophagus.
Ashford
SIMON KENWRIGHT
Hospital,
A. D. C. NORRIS
Ashford, Kent TN23 1LX
1.
Aylward, M., Bourke, J.
B. Lancet,
1969, ii, 267.
AMANTADINE-INDUCED HEART-FAILURE
SIR,-Amantadine alone or in combination with levodopa is of benefit in the treatment of Parkinson’s disease. A number of adverse effects, however, complicate the use of this drug; one of the commonest is ankle oedema. This appears to be of little significance and is unassociated with cardiac, renal, or hepatic disease. Its appearance does not usually necessitate the withdrawal of treatment. There have, in addition, been isolated reports 1suggesting that heart-failure may follow or be exacerbated by the use of amantadine. We wish to report a further patient who had severe cardiac failure after he had received 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 treated with levodopa alone, but in October, 1971, amantadine 100 mg twice a day and orphenadrine 50 mg three times a day were also prescribed. The patient remained in good health and was able to enjoy a regular round of golf until August, 1975, when he became increasingly short of breath and bilateral ankle oedema developed; his exercise tolerance fell to 20 m. He was admitted to hospital in September, 1975. On examination there was pitting oedema up to the knees, the jugular venous pressure was raised 5 cm and basal crepitations were heard. Congestive cardiac failure was diagnosed and this was confirmed radiologically (cardiothoracic ratio 17/30). Throughout the illness the electrocardiograms showed non-specific T-wave changes, and serial biochemical profiles were normal. Because of the possibility that amantadine might have precipitated the heart-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 pulmonary embolism, but made a satisfactory recovery. A year later there was no clinical or radiological evidence of cardiac failure (cardiothoracic ratio 15/30) and he no longer required diuretics. His extrapyramidal symptoms were well controlled by orphenadrine and levodopa. In 1970 Parkes et al.’ described a patient who had oedema and mild cardiac enlargement while receiving amantadine. Walker et all have reported two further patients with this complication during a clinical trial. The first had cardiac failure during the placebo period which worsened when she was given levodopa and amantadine. The failure responded poorly to diuretics and the withdrawal of anti-parkinsonian therapy, and she died. The second patient had ankle oedema while receiving amantadine. After completion of the trial paroxysmal noctural dyspnoea developed. His symptoms lessened on digoxin and diuretics and the withdrawal of amantadine, but he died from a probable pulmonary embolism. It would seem reasonable to conclude that our patient also had an amantadine-induced cardiomyopathy since no other cause for the sudden development of severe cardiac failure could be elicited. Parkes et al. have suggested that oedema in patients on amantadine is due to a peripheral fluid shift in the legs, probably from muscles into skin and subcutaneous tissues. They found no evidence of a change in total body water or sodium. The mechanism whereby amantadine induces cardiac failure is unknown though animal studies have shown that when it is given in high dosage there is a significant decrease in myocardial contractility.4 We recommend that amantadine should be prescribed with caution to patients with a history of myocardial disease. The American pharmaceutical literature carries this warning. Guy’s Hospital,
J. A. VALE
London SE1 9RT
K. S. MACLEAN
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. ArzneimittelForsch. 1975, 25, 891. 1.
report the first major reaction to we have observed in our unit that pentagastrin (’Peptavlon’) where we have used this drug daily in thousands of gastricfunction tests over the past 10 years. We had previously observed only the well-recognised minor side-effects, but one other severe reaction has been reported.’1 A man of 56 with a chronic duodenal ulcer, but otherwise healthy, attended our gastric clinic, fasting. He was semirecumbent on a couch with a nasogastric tube in place and an infusion of saline through a butterfly needle into a forearm vein 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 (concentration 6 jjLg/kg in 47 ml water), and not more than 40 p.g had been infused when the patient fainted and became cold and white with no radial pulse palpable for 3 min. Once the pulse returned he had a severe bradycardia of 35/min. Intravenous promethazine 50 mg produced some temporary improvement of his pulse but 5 min later the pulse weakened and 100 mg hydrocortisone succinate was given intravenously. 10 min later he was conscious and rational but cold and shivering with pulse 65/min and blood-pressure 110/60 mm Hg. The test was stopped and he recovered completely after 60 min. A subsequent electrocardiogram was normal. Despite the bradycardia there was no suggestion that this was a vasovagal episode, since the patient was comfortable and unaware of the start of the pentagastrin infusion. LC.L’s medical department tell us: "We have had several reports of acute reactions characterised by sweating, hypotension and bradycardia following the administration of TeptavIon’. Investigations have not succeeded in throwing any light on their nature and I suppose they must be ascribed to an idiosyncrasy or an acute hypersensitivity. In some cases we have been able to recover the batch from which the ampoule in question was taken and invariably it has been demonstrated on analysis that no fault can be detected in the formulation".
Sm,—We would like
We thank Dr
to
J. A. Waycott, medical department, I.C.I. for his com-
ments.
Department of Surgery,
Royal Postgraduate Medical School, Hammersmith Hospital,
R. F. MCCLOY J. H. BARON
London W12
ŒSOPHAGEAL ULCERATION DUE TO EMEPRONIUM BROMIDE
SIR,-We were interested to read the three cases reported by Dr Kavin (Feb. 19, p. 424). We have seen a similar incident in an otherwise healthy woman of 18 who had been prescribed
emepronium bromide (’Cetiprin’) for urinary-tract symptoms. 2 days after starting treatment she had very severe retrosternal pain. She had considerable dysphagia for both solids and fluids on account of the pain. Barium-swallow examination revealed no abnormality. At resophagoscopy there was an area of acute over 2 or 3 cm, in the region of the There was contact bleeding and superficial ulceration. The distal oesophagus was normal. She made a good recovery on intravenous fluids and analgesics. Later she said that she had taken the emepronium immediately before going to bed and without any drink. Ulceration of the gums and mouth has occurred with this compound, according to the manufacturers, in elderly patients who are probably liable to hold the tablets in their mouths for prolonged periods, but cesophageal ulceration is not widely known.
inflammation, extending
mid-cesophagus.
Ashford
SIMON KENWRIGHT
Hospital,
A. D. C. NORRIS
Ashford, Kent TN23 1LX
1.
Aylward, M., Bourke, J.
B. Lancet,
1969, ii, 267.
