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Acute Upper Extremity Ischemia during Concomitant Use of Ergotamine Tartrate and Ampicillin
Acute Upper Extremity Ischemia during Concomitant Use of Ergotamine Tartrate and Ampicillin Sumio Fukui, MD, Marc Coggia, MD, and Olivier Goe¨au-Brissonnie`re, MD, PhD, Boulogne, France
Individual hypersensitivity to the vasoconstrictor effects of ergotamine tartrate has been observed even at doses within recommended limits. Hypersensitivity can be induced by concomitant use with other drugs. The best-documented example of drug-induced hypersensitivity to ergotamine tartrate involves antibiotics of the macrolides class. The mechanism underlying this interaction appears to be interference with metabolism of ergotamine tartrate by the liver. In the present report we describe a case of upper extremity ischemia during concomitant use of ergotamine tartrate and ampicillin. The fact that the effect was not dose-dependent, disappeared when administration of ampicillin was discontinued, and reappeared when administration of ampicillin was resumed suggests that the underlying mechanism in our patient was immunologic. Since immunologic hypersensitivity to the vasoconstrictor effects of ergotamine tartrate is unpredictable, great caution and close surveillance is advisable when ergotamine tartrate is used in association with other drugs. (Ann Vasc Surg 1997;11:420-424.)
Preparations containing ergotamine tartrate are used mainly for treatment of migraine. Even at normal therapeutic doses ergotamine tartrate can induce vascular spasm and lead to ischemic manifestations.1–4 Concomitant use of ergotamine tartrate with some drugs, especially antibiotics of the macrolides class, can induce ischemic manifestations even when ergotamine tartrate is administered at doses within the recommended limits. 5–7 The mechanism underlying this drug interaction has not been firmly established, but interference with metabolism of ergotamine tartrate by the liver is the most widespread hypothesis.8 In the present report we describe a case of upper extremity ischemia during concomitant use of ergotamine tartrate and an antibiotic from another class, i.e., ampicillin. The From the Service de Chirurgie Vasculaire, Hoˆpital Ambroise Pare´, Boulogne, France. Correspondence to: O. Goe¨au-Brissonnie`re, MD, PhD, Service de Chirurgie Vasculaire, Hôpital Ambroise Paré, 9, avenue du Ge´ne´ral de Gaulle, 92104 Boulogne Cedex, France. 420
mechanism underlying this reaction was not related to metabolism by the liver.
CASE REPORT A 54-year-old woman was hospitalized for subacute right upper extremity ischemia of 3 weeks duration. The patient was a chronic migraine sufferer and during attacks regularly took 3 to 4 tablets of Migwelt (ergotamine tartrate 2 mg, caffeine 91.5 mg, cyclizine chlorhydrate 50 mg). She did not smoke and had never experienced Raynaud’s syndrome. Three weeks before hospitalization the patient had taken two tablets of Bacampicinet (bacampicillin 400 mg) for sore throat. She experienced palpations, coldness, and pallor of the right upper extremity which disappeared spontaneously. Several days later the patient took the antibiotic again and re-experienced the same symptoms. Sensing a connection between intake of the antibiotic and the symptoms, the patient discontinued Bacampicinet but continued to take Migwelt. However subacute right upper extremity ischemia persisted and the patient was hospitalized. Upon admission examination revealed bilateral loss of humeral, radial, and cubital pulses. Axillary pulse was
Vol. 11, No. 4, 1997
present. On the right the hand was pale and cold with paresthesia and pain in digits but without motor deficit. On the left there was loss of pulses but no ischemic manifestations. Pulses were present in the lower extremities and all other clinical findings were normal. Arteriography of the upper extremities was performed. The right subclavian and axillary arteries were normal (Figs. 1A and 2A) but there were several short stenoses in the circumflex artery and a long tight stenosis in the brachial artery. The deep brachial artery was not opacified. Findings on the left (Figs. 3A and 4A) were the same as those on the right. Diagnosis was ergotamine intoxication in association with concomitant use of ampicillin. Migwel* was discontinued and heparin was administered intravenously with vasodilators (buflomedil 50 mg and pentoxifylline 300 mg, twice a day). The patient improved rapidly. Pain disappeared, warmth returned to the hand, and radial and cubital pulses reappeared in both extremities. The patient was discharged from the hospital after 11 days. Control arteriography was performed three weeks later. Findings (Figs. 1B, 2B, 3B, and 4B) were normal in all upper extremity arteries except the digital arteries of the second and third right fingers which showed occlusion (Fig. 5).
DISCUSSION Vascular complications due to ergotamine intoxication have been recognized since the Middle Ages when they were referred to as Saint Anthony’s fire.9 Ischemia of the extremities is due to vascular spasm and can lead to gangrene. The offending agent which has been isolated from rye ergot and identified as the sclerotium of the fungus Claviceps purpurea is found in poor quality bread. Currently derivatives of rye ergot (ergotamine tartrate) are used pharmacologically as ocytocics10 and antimigraine agents.11 Ergotamine tartrate contains an amino acid alkaloid radical that induces vasoconstriction by acting as an antagonist and partial agonist of adrenergic and tryptaminergic receptors.9,12 Ischemic manifestations can occur anywhere including the carotid,13 coronary,14 renal,15 and mesenteric16 arteries but the most frequent sites are in the extremities, especially the lower extremities.17 Involvement of the upper extremities is more uncommon.18 Vascular side-effects of ergotamine tartrate have been observed during long-term administration within recommended dose limits, overdosage, and acute administration in hypersensitive subjects.19 Ischemic complications have usually occurred during chronic administration.20 Several predisposing factors have been implicated in ergotamine tartrate intoxication including severe infection, coronary heart disease, hepatic disease, kidney insufficiency, thyrotoxicosis, arterial hypertension, pregnancy,
Case reports
421
and chronic occlusive arterial disease.21 Druginduced hypersensitivity has been reported not only with antibiotics of the macrolides class but also with oral contraceptives22 and beta-blockers.23 The exact mechanism underlying these drug interactions is unclear, but the most widespread hypothesis is interference with liver metabolism. Adverse effects during concomitant use of macrolides seems to be due to inhibition of metabolism of ergotamine tartrate by the liver. As a result, caution has been advised when prescribing drugs metabolized by the liver in association with ergotamine tartrate.8 To our knowledge, this is the first report of hypersensitivity to ergotamine tartrate during concomitant use of ampicillin. Bacampicillin is a prodrug of ampicillin that is rapidly and completely hydrolyzed in ampicillin. The only difference with ampicillin is bioavailability.24 Interference with liver metabolism is a less likely hypothesis than with macrolides since the major organ of excretion of ampicillin is the kidney, biliary excretion accounting for only 20% of the total clearance. This suggests the possibility that an immunologic mechanism may be involved in the induction of hypersensitization to the vasoconstrictor effects of ergotamine tartrate by ampicillin. This hypothesis is supported by the fact that the effect was not dosedependent, disappeared when ampicillin was discontinued, and immediately reappeared when ampicillin was resumed. Regardless of the underlying mechanism, the present case underlines the unpredictability of vascular complications and thus the need for close surveillance when prescribing another drug in association with ergotamine tartrate. Treatment depends mainly on discontinuing ergotamine tartrate.25,26 However, vasoconstrictor effects can persist for several days due to accumulation of the drug in the smooth muscle of arteries.27 Some authors have proposed administration of heparin alone or in combination with a vasodilator, the most effective being sodium nitroprusside.28–30 In the present report, heparin was effective. Heparin diminishes intraarterial thrombus which can persist even after spasm has disappeared as demonstrated in our patient by the absence of opacification of digital arteries. Prostacyclin has also been successfully used by some authors.31
CONCLUSIONS Prescription of preparations containing ergotamine tartrate require close surveillance due to the danger of ischemic manifestations. Concomitant use of other drugs increases the need for caution due to possible drug interactions. In addition to drugs me-
422
Case reports
Annals of Vascular Surgery
Fig. 1. Arteriograms showing A upper right arm before treatment, B upper right arm after treatment. Fig. 2. Arteriograms showing A lower right arm before treatment, B lower right arm after treatment.
Fig. 3. Arteriograms showing A upper left arm before treatment, B upper left arm after treatment. Fig. 4. Arteriograms showing A lower left arm before treatment, B lower left arm after treatment.
424
Case reports
Fig. 5. Arteriogram of digital arteries showing occlusion of the second and third fingers.
tabolized by the liver, including macrolides which are contraindicated in association with ergotamine tartrate, other drugs can lead to hypersensitization to the vasoconstrictor effects of ergotamine tartrate as shown by the present case involving ampicillin. REFERENCES 1. Ancalmo N, Ochsner JL. Peripheral ischemia secondary to ergotamine intoxication. Arch Surg 1974;109:832-834. 2. Merhoff GC, Porter JM. Ergot intoxication: historical review and description of unusual clinical manifestations. Ann Surg 1974;180:773-779. 3. Maples M, Mulherin JL, Harris J. Arterial complications of ergotism. Ann Surg 1981;47:224-227. 4. Kempczinski RF, Buckley CJ, Darling RC. Vascular insults secondary to ergotism. Surgery 1976;79:597-600. 5. Neveux E, Lesgourgues B, Luton JP, et al. Ergotisme aigu par association proprionate d’e´rythromycine-dihydroergotamine. Nouv Press Med 1981;10:2830. 6. Boacharlat J, Franco A, Carpentier P, et al. Ergotisme en milieu psychiatrique par association DHE—proprionate d’e´rythromycine: a` propos d’une observation. Ann Me´d Psychol 1980;138:292-296. 7. Leroy F, Asseman P, Pruvost P, et al. Dihydroergotamineerythromycininduced ergotism. Ann Int Med 1988;109:249.
Annals of Vascular Surgery
8. Ghali R, De Lean J, Douville Y, et al. Erythromycinassociated ergotamine intoxication: arteriographic and electrophysiologic analysis of a rare cause of severe ischemia of the lower extremities and associated ischemic neuropathy. Ann Vasc Surg 1993;7:291-296. 9. Gilman AG, Goodman LS, Gilman A (eds). The Pharmacological Basis of Therapeutics, 6 ed. New York: MacMillan, 1980, pp 939-947. 10. Turnbull AC. Obstetrics-traditional uses of ergot compounds. Postgrad Med J 1976;52:15-16. 11. Tanner JR. St Anthony’s fire then and now: a case report and historical review. Can J Surg 1987;30:291-293. 12. Schmidt R, Erasmi H, Walter M, et al. Ergotisme et ischémie des membres. Ann Cardiol Angeiol 1992;41:489-495. 13. Richter AM, Banker VP. Carotid ergotism, a complication of migraine therapy. Radiology 1973;106:339-340. 14. Goldfisher J. Acute myocardial infarction secondary to ergot therapy. N Engl J Med 1960;262:860-863. 15. Fedotin MC, Hartmann C. Ergotamin poisoning producing renal arterial spasm. N Engl J Med 1970;283:518-520. 16. Greene FL, Ariyan S, Stansel HC Jr. Mesenteric and peripheral vascular ischemia secondary to ergotism. Surgery 1977; 81:176-179. 17. Henry LG, Blackwood JS, Conley JE, Bernhard VM. Ergotism. Arch Surg 1975;110:929-932. 18. Porter JM, Friedman EI, Mills JL. Occlusive and vasospastic diseases involving distal upper extremity arteries-Raynaud’s syndrome. In Rutherford RB, ed. Vascular Surgery. Philadelphia: WB Saunders, 1994, pp 961-976. 19. Babgy RS, Cooper RV. Angiography in ergotism. AJR 1972; 116:179-186. 20. Larcan A, Lambert H. Les intoxications par les de´rive´s de l’ergot de seigle. Paris, Masson, 1977. 21. Hemingway DL. Ergot poisoning with multisystem involvement. Milit Med 1965;10:257-260. 22. Fagerberg S, Jorulf H, Sanderg CG. Ergotism, arteriospastic disease and recovery, studied angiographically. Acta Med Scand 1967;182:769-772. 23. Venter CP, Joubert Ph, Buys AC. Severe peripheral ischemia during concomitant use of beta-blockers and ergot alcaloids. Br Med J 1984;289:288-289. 24. Scheife RT, Neu HC. Bacampicillin hydrochloride: chemistry, pharmacology and clinical use. Pharmacotherapy 1982; 2:313-321. 25. Wells Ke, Steed DL, Zajko AB, Webster MW. Recognition and treatment of arterial insufficiency from cafergot. J Vasc Surg 1986;4:8-15. 26. Magee R. Saint Anthony’s fire revisited. Vascular problems associated with migraine medication. Med J Aust 1991;154: 145-149. 27. Bongard O, Bounameaux H. Severe iatrogenic ergotism: incidence and clinical importance. Vasa 1991;20:153-156. 28. Lewis PJ, Noseworthy TW, Fitzegerald AA, et al. Rapid reversal of ergotamine-induced vasospasm. Can J Neurol Sci 1986;13:72-74. 29. Carliner NH, Denune DP, Finchs CS, et al. Sodium nitroprusside treatment of ergotamine-induced peripheral ischemia. JAMA 1974;227:308-309. 30. Andersen PK, Christensen KN, Hole P, et al. Sodium nitroprusside and epidural blockade in the treatment of ergotism. N Engl J Med 1977;296:1271-1273. 31. Edwards RJ, Fulde GW, Mcgrath MA. Successful limb salvage with prostaglandin infusion: a review of ergotamine toxicity. Med J Aust 1991;155:825-827.
Individual hypersensitivity to the vasoconstrictor effects of ergotamine tartrate has been observed even at doses within recommended limits. Hypersensitivity can be induced by concomitant use with other drugs. The best-documented example of drug-induced hypersensitivity to ergotamine tartrate involves antibiotics of the macrolides class. The mechanism underlying this interaction appears to be interference with metabolism of ergotamine tartrate by the liver. In the present report we describe a case of upper extremity ischemia during concomitant use of ergotamine tartrate and ampicillin. The fact that the effect was not dose-dependent, disappeared when administration of ampicillin was discontinued, and reappeared when administration of ampicillin was resumed suggests that the underlying mechanism in our patient was immunologic. Since immunologic hypersensitivity to the vasoconstrictor effects of ergotamine tartrate is unpredictable, great caution and close surveillance is advisable when ergotamine tartrate is used in association with other drugs. (Ann Vasc Surg 1997;11:420-424.)
Preparations containing ergotamine tartrate are used mainly for treatment of migraine. Even at normal therapeutic doses ergotamine tartrate can induce vascular spasm and lead to ischemic manifestations.1–4 Concomitant use of ergotamine tartrate with some drugs, especially antibiotics of the macrolides class, can induce ischemic manifestations even when ergotamine tartrate is administered at doses within the recommended limits. 5–7 The mechanism underlying this drug interaction has not been firmly established, but interference with metabolism of ergotamine tartrate by the liver is the most widespread hypothesis.8 In the present report we describe a case of upper extremity ischemia during concomitant use of ergotamine tartrate and an antibiotic from another class, i.e., ampicillin. The From the Service de Chirurgie Vasculaire, Hoˆpital Ambroise Pare´, Boulogne, France. Correspondence to: O. Goe¨au-Brissonnie`re, MD, PhD, Service de Chirurgie Vasculaire, Hôpital Ambroise Paré, 9, avenue du Ge´ne´ral de Gaulle, 92104 Boulogne Cedex, France. 420
mechanism underlying this reaction was not related to metabolism by the liver.
CASE REPORT A 54-year-old woman was hospitalized for subacute right upper extremity ischemia of 3 weeks duration. The patient was a chronic migraine sufferer and during attacks regularly took 3 to 4 tablets of Migwelt (ergotamine tartrate 2 mg, caffeine 91.5 mg, cyclizine chlorhydrate 50 mg). She did not smoke and had never experienced Raynaud’s syndrome. Three weeks before hospitalization the patient had taken two tablets of Bacampicinet (bacampicillin 400 mg) for sore throat. She experienced palpations, coldness, and pallor of the right upper extremity which disappeared spontaneously. Several days later the patient took the antibiotic again and re-experienced the same symptoms. Sensing a connection between intake of the antibiotic and the symptoms, the patient discontinued Bacampicinet but continued to take Migwelt. However subacute right upper extremity ischemia persisted and the patient was hospitalized. Upon admission examination revealed bilateral loss of humeral, radial, and cubital pulses. Axillary pulse was
Vol. 11, No. 4, 1997
present. On the right the hand was pale and cold with paresthesia and pain in digits but without motor deficit. On the left there was loss of pulses but no ischemic manifestations. Pulses were present in the lower extremities and all other clinical findings were normal. Arteriography of the upper extremities was performed. The right subclavian and axillary arteries were normal (Figs. 1A and 2A) but there were several short stenoses in the circumflex artery and a long tight stenosis in the brachial artery. The deep brachial artery was not opacified. Findings on the left (Figs. 3A and 4A) were the same as those on the right. Diagnosis was ergotamine intoxication in association with concomitant use of ampicillin. Migwel* was discontinued and heparin was administered intravenously with vasodilators (buflomedil 50 mg and pentoxifylline 300 mg, twice a day). The patient improved rapidly. Pain disappeared, warmth returned to the hand, and radial and cubital pulses reappeared in both extremities. The patient was discharged from the hospital after 11 days. Control arteriography was performed three weeks later. Findings (Figs. 1B, 2B, 3B, and 4B) were normal in all upper extremity arteries except the digital arteries of the second and third right fingers which showed occlusion (Fig. 5).
DISCUSSION Vascular complications due to ergotamine intoxication have been recognized since the Middle Ages when they were referred to as Saint Anthony’s fire.9 Ischemia of the extremities is due to vascular spasm and can lead to gangrene. The offending agent which has been isolated from rye ergot and identified as the sclerotium of the fungus Claviceps purpurea is found in poor quality bread. Currently derivatives of rye ergot (ergotamine tartrate) are used pharmacologically as ocytocics10 and antimigraine agents.11 Ergotamine tartrate contains an amino acid alkaloid radical that induces vasoconstriction by acting as an antagonist and partial agonist of adrenergic and tryptaminergic receptors.9,12 Ischemic manifestations can occur anywhere including the carotid,13 coronary,14 renal,15 and mesenteric16 arteries but the most frequent sites are in the extremities, especially the lower extremities.17 Involvement of the upper extremities is more uncommon.18 Vascular side-effects of ergotamine tartrate have been observed during long-term administration within recommended dose limits, overdosage, and acute administration in hypersensitive subjects.19 Ischemic complications have usually occurred during chronic administration.20 Several predisposing factors have been implicated in ergotamine tartrate intoxication including severe infection, coronary heart disease, hepatic disease, kidney insufficiency, thyrotoxicosis, arterial hypertension, pregnancy,
Case reports
421
and chronic occlusive arterial disease.21 Druginduced hypersensitivity has been reported not only with antibiotics of the macrolides class but also with oral contraceptives22 and beta-blockers.23 The exact mechanism underlying these drug interactions is unclear, but the most widespread hypothesis is interference with liver metabolism. Adverse effects during concomitant use of macrolides seems to be due to inhibition of metabolism of ergotamine tartrate by the liver. As a result, caution has been advised when prescribing drugs metabolized by the liver in association with ergotamine tartrate.8 To our knowledge, this is the first report of hypersensitivity to ergotamine tartrate during concomitant use of ampicillin. Bacampicillin is a prodrug of ampicillin that is rapidly and completely hydrolyzed in ampicillin. The only difference with ampicillin is bioavailability.24 Interference with liver metabolism is a less likely hypothesis than with macrolides since the major organ of excretion of ampicillin is the kidney, biliary excretion accounting for only 20% of the total clearance. This suggests the possibility that an immunologic mechanism may be involved in the induction of hypersensitization to the vasoconstrictor effects of ergotamine tartrate by ampicillin. This hypothesis is supported by the fact that the effect was not dosedependent, disappeared when ampicillin was discontinued, and immediately reappeared when ampicillin was resumed. Regardless of the underlying mechanism, the present case underlines the unpredictability of vascular complications and thus the need for close surveillance when prescribing another drug in association with ergotamine tartrate. Treatment depends mainly on discontinuing ergotamine tartrate.25,26 However, vasoconstrictor effects can persist for several days due to accumulation of the drug in the smooth muscle of arteries.27 Some authors have proposed administration of heparin alone or in combination with a vasodilator, the most effective being sodium nitroprusside.28–30 In the present report, heparin was effective. Heparin diminishes intraarterial thrombus which can persist even after spasm has disappeared as demonstrated in our patient by the absence of opacification of digital arteries. Prostacyclin has also been successfully used by some authors.31
CONCLUSIONS Prescription of preparations containing ergotamine tartrate require close surveillance due to the danger of ischemic manifestations. Concomitant use of other drugs increases the need for caution due to possible drug interactions. In addition to drugs me-
422
Case reports
Annals of Vascular Surgery
Fig. 1. Arteriograms showing A upper right arm before treatment, B upper right arm after treatment. Fig. 2. Arteriograms showing A lower right arm before treatment, B lower right arm after treatment.
Fig. 3. Arteriograms showing A upper left arm before treatment, B upper left arm after treatment. Fig. 4. Arteriograms showing A lower left arm before treatment, B lower left arm after treatment.
424
Case reports
Fig. 5. Arteriogram of digital arteries showing occlusion of the second and third fingers.
tabolized by the liver, including macrolides which are contraindicated in association with ergotamine tartrate, other drugs can lead to hypersensitization to the vasoconstrictor effects of ergotamine tartrate as shown by the present case involving ampicillin. REFERENCES 1. Ancalmo N, Ochsner JL. Peripheral ischemia secondary to ergotamine intoxication. Arch Surg 1974;109:832-834. 2. Merhoff GC, Porter JM. Ergot intoxication: historical review and description of unusual clinical manifestations. Ann Surg 1974;180:773-779. 3. Maples M, Mulherin JL, Harris J. Arterial complications of ergotism. Ann Surg 1981;47:224-227. 4. Kempczinski RF, Buckley CJ, Darling RC. Vascular insults secondary to ergotism. Surgery 1976;79:597-600. 5. Neveux E, Lesgourgues B, Luton JP, et al. Ergotisme aigu par association proprionate d’e´rythromycine-dihydroergotamine. Nouv Press Med 1981;10:2830. 6. Boacharlat J, Franco A, Carpentier P, et al. Ergotisme en milieu psychiatrique par association DHE—proprionate d’e´rythromycine: a` propos d’une observation. Ann Me´d Psychol 1980;138:292-296. 7. Leroy F, Asseman P, Pruvost P, et al. Dihydroergotamineerythromycininduced ergotism. Ann Int Med 1988;109:249.
Annals of Vascular Surgery
8. Ghali R, De Lean J, Douville Y, et al. Erythromycinassociated ergotamine intoxication: arteriographic and electrophysiologic analysis of a rare cause of severe ischemia of the lower extremities and associated ischemic neuropathy. Ann Vasc Surg 1993;7:291-296. 9. Gilman AG, Goodman LS, Gilman A (eds). The Pharmacological Basis of Therapeutics, 6 ed. New York: MacMillan, 1980, pp 939-947. 10. Turnbull AC. Obstetrics-traditional uses of ergot compounds. Postgrad Med J 1976;52:15-16. 11. Tanner JR. St Anthony’s fire then and now: a case report and historical review. Can J Surg 1987;30:291-293. 12. Schmidt R, Erasmi H, Walter M, et al. Ergotisme et ischémie des membres. Ann Cardiol Angeiol 1992;41:489-495. 13. Richter AM, Banker VP. Carotid ergotism, a complication of migraine therapy. Radiology 1973;106:339-340. 14. Goldfisher J. Acute myocardial infarction secondary to ergot therapy. N Engl J Med 1960;262:860-863. 15. Fedotin MC, Hartmann C. Ergotamin poisoning producing renal arterial spasm. N Engl J Med 1970;283:518-520. 16. Greene FL, Ariyan S, Stansel HC Jr. Mesenteric and peripheral vascular ischemia secondary to ergotism. Surgery 1977; 81:176-179. 17. Henry LG, Blackwood JS, Conley JE, Bernhard VM. Ergotism. Arch Surg 1975;110:929-932. 18. Porter JM, Friedman EI, Mills JL. Occlusive and vasospastic diseases involving distal upper extremity arteries-Raynaud’s syndrome. In Rutherford RB, ed. Vascular Surgery. Philadelphia: WB Saunders, 1994, pp 961-976. 19. Babgy RS, Cooper RV. Angiography in ergotism. AJR 1972; 116:179-186. 20. Larcan A, Lambert H. Les intoxications par les de´rive´s de l’ergot de seigle. Paris, Masson, 1977. 21. Hemingway DL. Ergot poisoning with multisystem involvement. Milit Med 1965;10:257-260. 22. Fagerberg S, Jorulf H, Sanderg CG. Ergotism, arteriospastic disease and recovery, studied angiographically. Acta Med Scand 1967;182:769-772. 23. Venter CP, Joubert Ph, Buys AC. Severe peripheral ischemia during concomitant use of beta-blockers and ergot alcaloids. Br Med J 1984;289:288-289. 24. Scheife RT, Neu HC. Bacampicillin hydrochloride: chemistry, pharmacology and clinical use. Pharmacotherapy 1982; 2:313-321. 25. Wells Ke, Steed DL, Zajko AB, Webster MW. Recognition and treatment of arterial insufficiency from cafergot. J Vasc Surg 1986;4:8-15. 26. Magee R. Saint Anthony’s fire revisited. Vascular problems associated with migraine medication. Med J Aust 1991;154: 145-149. 27. Bongard O, Bounameaux H. Severe iatrogenic ergotism: incidence and clinical importance. Vasa 1991;20:153-156. 28. Lewis PJ, Noseworthy TW, Fitzegerald AA, et al. Rapid reversal of ergotamine-induced vasospasm. Can J Neurol Sci 1986;13:72-74. 29. Carliner NH, Denune DP, Finchs CS, et al. Sodium nitroprusside treatment of ergotamine-induced peripheral ischemia. JAMA 1974;227:308-309. 30. Andersen PK, Christensen KN, Hole P, et al. Sodium nitroprusside and epidural blockade in the treatment of ergotism. N Engl J Med 1977;296:1271-1273. 31. Edwards RJ, Fulde GW, Mcgrath MA. Successful limb salvage with prostaglandin infusion: a review of ergotamine toxicity. Med J Aust 1991;155:825-827.