98 a
beneficial effect of this antibiotic. A controlled trial of this
drug in antibiotic-induced colitis is indicated. R. MODIGLIANI J. C. DELCHIER
Hôpital Saint-Lazare, 75010 Paris, France
MORTALITY ASSOCIATED WITH THE PILL
SIR,-The additional information about the Oxford/Family
Planning Association contraceptive study requested by Dr Hill’ is given in the following table: OXFORD/F.P.A. CONTRACEPTIVE STUDY: (i) woman-years of observation; (ii) observed number of deaths from circulatory disorders (LC.D. codes 390-458); (iii) expected numbers of deaths from circulatory disorders on basis of rates found in the Royal College of General Practitioners study. Method of contraception in
use at
entry:
4-31). After abdominal irradiation and anticancer chemotherapy, her physical status improved. The pleural effusion resolved, the abdominal mass got smaller, renal function became normal, but her hypertension remained. In an attempt to control her hypertension she was treated with oral propranolol, 10 mg every 8 h for three doses, and 15 mg every 8 h for five doses. Following the eighth dose (105 mg in 64 h) she became disoriented and agitated with perseveration. This was followed by a comatose state without localising signs. She had a generalised hyperflexia, bilaterally symmetrical Babinski signs, and sustained ankle and knee clonus. A lumbar tap revealed an opening pressure of 165 mm. Cerebrospinal-fluid glucose was 63 mg/dl and protein 19 mg/dl. Her electroencephalogram revealed a markedly slow and disorganised pattern with high voltage 1-2 Hz delta and 2-3.5Hz delta/theta waves arising from both hemispheres. A computerised tomographic scan of the head revealed a small, irregular low-density area in the right parietal region which did not change after contrast was injected. Her blood gas, electrolyte, and glucose levels were normal. Her serumcalcium was 7.6mg/dl, and her serum protein was 6 g/dl without any change in mental symptoms. At the onset of her disorientation, the propranolol was stopped. However, her symptoms progressed and did not begin to resolve until 80 h later when she rapidly became alert and oriented, but could recall little of the preceding 3 days’ events.
Repeated neurological examination revealed a complete disaphypereflexia and clonus. A repeat electrodays after the first was normal. Her hypertension continued end was eventually controlled with other
pearance of her encephalogram 6
The age-specific mortality-rates in our similar to those in the R.C.G.P. study.
investigation
are
very
agents.
Department of Social Medicine, University of Oxford, Oxford OX1 3QN
and
Community
M. P. VESSEY K. MCPHERSON
B. JOHNSON
SCALP TINGLING ON LABETALOL two lettersz3 describing unformication associated with the use of labetalol. In three cases the scalp was the only area to be affected. The Committee on Safety of Medicines has received a small number of similar reports. The affected region has usually been the scalp alone, though some describe widespread parsesthesise. In three cases formication is specifically described. The tendency to affect the scalp rather than other sites has not been apparent when paraesthesiae have been described as a possible adverse reaction to other drugs in this therapeutic
SIR,-In 1977 you published
pleasant parssthesix
or
group. The C.S.M. is especially interested in reports of suspected adverse reactions to the beta-adrenoceptor blocking agents. Committee
on Safety of Medicines, Finsbury Square House,
ERIC SCOWEN
London EC2A 1PP
ACUTE BRAIN SYNDROME AFTER PROPRANOLOL
SiR,—Dr Topliss and Dr Bonddescribed
an acute brain We have in an adult. after treatment propranolol syndrome seen a similar complication in a 12-year-old girl being treated for hypertension and lymphoma. After a 2-month history of weight loss, abdominal pain, and fever, a pelvic mass and pleural effusion were detected. Cytological examination of thoracentesis fluid revealed lymphoma cells. The patient was hypertensive (168/188 mm Hg), oliguric, and had a plasma-aldosterone of 187 mg/dl (normal
1. Hill, I. D. Lancet, 1977, ii, 1024. 2. Hua, A. S. P , Thomas, G. W., Kincaid-Smith, P. ibid. 3. Bailey, R. R. ibid. p. 720. 4. Topliss, D., Bond, R. ibid. p. 1133.
p. 295
the
half-life of
is reported be sustained over long periods of time. Central-nervous-system effects such as clouded sensorium have been reported in adults, but it is possible that more severe reactions may occur in children. Since the dose in children is not yet established (Physicians Desk Reference 1974) and dosages of 60 mg/day are suggested in the Harriet Lane Handbook (7th edition) we feel it important to report this observation. LAWRENCE HELSON Memorial Sloan-Kettering Cancer Center,
Although
to
be 2-3
biological
propranolol
h, the neurological effects appear
New York, N.Y. 10021, U.S.A.
to
LUZ DUQUE
VENTRICULAR TACHYCARDIA AFTER DISOPYRAMIDE
SiR,-In the correspondence (Dec. 3, p. 1185) following the by Dr Zainal and his colleagues (Oct. 29, p. 887) little
paper
made of the side-effects of disopyramide. Zainal et al. found that the incidence of urinary Although retention did not reach statistical significance, it was more common in the treated group, and in our experience has been a problem, particularly in the elderly. We report here the possibility of a more serious complication. A 57-year-old man had rheumatoid arthritis diagnosed in 1970 and treated with gold. In January, 1977, he was admitted with an acute, full-thickness, anteroseptal myocardial infarction from which he made a good recovery after 2 weeks in hospital. 10 days later he was admitted with a supraventricular tachycardia which was resistant to intravenous practolol and required direct-current shock to restore sinus rhythm. He was then treated with oral propranolol (40 mg twice daily) but as an outpatient continued to have palpitations. Oral disopyramide (100 mg three times daily) was started but the palpitation became worse and an electrocardiogram showed high nodal extrasystoles and supraventricular ectopic beats with aberrant conduction, neither of which had been previously noted. Both drugs were stopped and both his symptoms and
mention
was
the electrocardiogram improved. The patient was next admitted in September, 1977, with severe palpitation associated with hypotension which had ter-
99 minated spontaneously by the time of admission. He had a 1-week history of palpitation which he insisted had been made worse by disopyramide given by his general practitioner. 12 h after admission he had ventricular tachycardia which progressed to ventricular fibrillation despite intravenous lignocaine and practolol. Five high-energy direct-current shocks produced asystole, and sinus rhythm was restored by intracardiac adrenaline. This rhythm was complicated by multiple atrial and ventricular ectopic beats which persisted despite a lignocaine infusion. 10 h after the episode of ventricular fibrillation he was given intravenous disopyramide (100 mg) over a period of 5 min (he was unable to take oral medication at this time) and almost immediately he had ventricular tachycardia (about 240/min) associated with hypotension which required further direct-current shock. Electrolytes at this time were normal. Mexiletine was given but chaotic cardiac rhythm persisted (including five further episodes of ventricular fibrillation). An akinetic area of myocardium was excised surgically as an emergency and subsequently he has been in sinus
rhythm. Oral disopyramide was
associated with a worsening of palpitation on two occasions. When given intravenously it was associated with ventricular tachycardia. The myocardium was obviously very unstable at the time of intravenous injection and the ventricular tachycardia may have been purely coincidental. However the possibility of such a consequence, and the known side-effects of the drug, should be borne in mind before endorsing the recommendation of Zainal et al. that "oral disopyramide should be given for the first seven days after myocardial infarction to all patients not managed in coronary care
land et al. in their studies on 6 healthy subjects taking 1.6 g cimetidine daily for 6 days noted no consistent impairment of creatinine clearance but there was a wide range of variation. I have seen a 33-year-old man with duodenal ulcers who had a 28-day course of cimetidine (1 g daily). Pretreatment serumcreatinine was 116 fLmol;1. There was rapid improvement in his symptoms but by the 14th day of treatment his serum-creatinine had risen to 153 fLmol;1. 5 days after stopping cimetidine-creatinine was 180 µmo1/1 28 days after stopping it was 142 mol/1 with a creatinine clearance of 67-6 ml/min. 49 days after treatment creatinine clearance was 82 ml/min and after fluid deprivation urine osmolality was 1,096 mosm/kg. 17 weeks later the creatinine clearance was 122 ml/min. This patient’s transient deterioration in renal function with recovery was caused by the recommended dose of cimetidine. Portiuncula
Hospital,
Ballinasloe, Co. Galway,
MORGAN MCELLIGOTT
Ireland
PLASMA-PROLACTIN AND CIMETIDINE were reported in male treated with cimetidine for Zollinger-Ellison syndrome.3.. In a patient given cimetidine for 2 months a significant rise in plasma-prolactin was observed5 but Dr Petrillo and colleagues (Oct. 8, p. 761) were unable to confirm this finding.
SIR, -Breast pain and gynscomastia
patients
units".
PAUL SIKLOS T. M. CHALMERS D. W. EVANS
Addenbrooke’s Hospital, Cambridge CB2 2QC
CIMETIDINE OVERDOSE
SIR,-A middle-aged African man with
a
radiologically pro-
clinically active duodenal ulcer was prescribed a 2-month course of cimetidine. He was given three hundred 200 mg tablets and told to take one three times daily and two at night. When seen for review 1 month later it transpired that he had used all the tablets in the first week. Having obtained considerable pain relief with 1 day’s treatment at the recommended dose, he thought that taking more tablets would be of even greater benefit and proceeded to take approximately fifteen tablets four times daily (about 12 g per day) until the tablets were finished 5 days later. He noted no untoward effects and continued his job as an underground miner throughout the treatment. His dyspepsia disappeared and a repeat bariummeal examination 4 months after treatment showed no sign of ven
and
the ulcer. It would seem that high doses of cimetidine may be tolerated without adverse effects-indeed with excellent clinical results in this case. This information could be of use to casualty officers faced with accidental or deliberate overdose with cimetidine.
Nchanga Hospitals P.O. Box 63, Chingola,
Zambia
GEOFFREY V. GILL
IMPAIRED CREATININE CLEARANCE AFTER CIMETIDINE
and Hawkins’ summarising multicentre trials of cimetidine, note that serum-creatinine can rise early in treatment in patients on a higher dose. 3 patients stopped the drug while receiving 1.22 g daily; 2 had pre-existing renal disease and one had a pre-existing raised serum-creatinine. Bur-
Effect of cimetidine
plasma-prolactin (hPRL). injection; arrow indicates time of injection; *=values significantly different (p
beneficial effect of this antibiotic. A controlled trial of this
drug in antibiotic-induced colitis is indicated. R. MODIGLIANI J. C. DELCHIER
Hôpital Saint-Lazare, 75010 Paris, France
MORTALITY ASSOCIATED WITH THE PILL
SIR,-The additional information about the Oxford/Family
Planning Association contraceptive study requested by Dr Hill’ is given in the following table: OXFORD/F.P.A. CONTRACEPTIVE STUDY: (i) woman-years of observation; (ii) observed number of deaths from circulatory disorders (LC.D. codes 390-458); (iii) expected numbers of deaths from circulatory disorders on basis of rates found in the Royal College of General Practitioners study. Method of contraception in
use at
entry:
4-31). After abdominal irradiation and anticancer chemotherapy, her physical status improved. The pleural effusion resolved, the abdominal mass got smaller, renal function became normal, but her hypertension remained. In an attempt to control her hypertension she was treated with oral propranolol, 10 mg every 8 h for three doses, and 15 mg every 8 h for five doses. Following the eighth dose (105 mg in 64 h) she became disoriented and agitated with perseveration. This was followed by a comatose state without localising signs. She had a generalised hyperflexia, bilaterally symmetrical Babinski signs, and sustained ankle and knee clonus. A lumbar tap revealed an opening pressure of 165 mm. Cerebrospinal-fluid glucose was 63 mg/dl and protein 19 mg/dl. Her electroencephalogram revealed a markedly slow and disorganised pattern with high voltage 1-2 Hz delta and 2-3.5Hz delta/theta waves arising from both hemispheres. A computerised tomographic scan of the head revealed a small, irregular low-density area in the right parietal region which did not change after contrast was injected. Her blood gas, electrolyte, and glucose levels were normal. Her serumcalcium was 7.6mg/dl, and her serum protein was 6 g/dl without any change in mental symptoms. At the onset of her disorientation, the propranolol was stopped. However, her symptoms progressed and did not begin to resolve until 80 h later when she rapidly became alert and oriented, but could recall little of the preceding 3 days’ events.
Repeated neurological examination revealed a complete disaphypereflexia and clonus. A repeat electrodays after the first was normal. Her hypertension continued end was eventually controlled with other
pearance of her encephalogram 6
The age-specific mortality-rates in our similar to those in the R.C.G.P. study.
investigation
are
very
agents.
Department of Social Medicine, University of Oxford, Oxford OX1 3QN
and
Community
M. P. VESSEY K. MCPHERSON
B. JOHNSON
SCALP TINGLING ON LABETALOL two lettersz3 describing unformication associated with the use of labetalol. In three cases the scalp was the only area to be affected. The Committee on Safety of Medicines has received a small number of similar reports. The affected region has usually been the scalp alone, though some describe widespread parsesthesise. In three cases formication is specifically described. The tendency to affect the scalp rather than other sites has not been apparent when paraesthesiae have been described as a possible adverse reaction to other drugs in this therapeutic
SIR,-In 1977 you published
pleasant parssthesix
or
group. The C.S.M. is especially interested in reports of suspected adverse reactions to the beta-adrenoceptor blocking agents. Committee
on Safety of Medicines, Finsbury Square House,
ERIC SCOWEN
London EC2A 1PP
ACUTE BRAIN SYNDROME AFTER PROPRANOLOL
SiR,—Dr Topliss and Dr Bonddescribed
an acute brain We have in an adult. after treatment propranolol syndrome seen a similar complication in a 12-year-old girl being treated for hypertension and lymphoma. After a 2-month history of weight loss, abdominal pain, and fever, a pelvic mass and pleural effusion were detected. Cytological examination of thoracentesis fluid revealed lymphoma cells. The patient was hypertensive (168/188 mm Hg), oliguric, and had a plasma-aldosterone of 187 mg/dl (normal
1. Hill, I. D. Lancet, 1977, ii, 1024. 2. Hua, A. S. P , Thomas, G. W., Kincaid-Smith, P. ibid. 3. Bailey, R. R. ibid. p. 720. 4. Topliss, D., Bond, R. ibid. p. 1133.
p. 295
the
half-life of
is reported be sustained over long periods of time. Central-nervous-system effects such as clouded sensorium have been reported in adults, but it is possible that more severe reactions may occur in children. Since the dose in children is not yet established (Physicians Desk Reference 1974) and dosages of 60 mg/day are suggested in the Harriet Lane Handbook (7th edition) we feel it important to report this observation. LAWRENCE HELSON Memorial Sloan-Kettering Cancer Center,
Although
to
be 2-3
biological
propranolol
h, the neurological effects appear
New York, N.Y. 10021, U.S.A.
to
LUZ DUQUE
VENTRICULAR TACHYCARDIA AFTER DISOPYRAMIDE
SiR,-In the correspondence (Dec. 3, p. 1185) following the by Dr Zainal and his colleagues (Oct. 29, p. 887) little
paper
made of the side-effects of disopyramide. Zainal et al. found that the incidence of urinary Although retention did not reach statistical significance, it was more common in the treated group, and in our experience has been a problem, particularly in the elderly. We report here the possibility of a more serious complication. A 57-year-old man had rheumatoid arthritis diagnosed in 1970 and treated with gold. In January, 1977, he was admitted with an acute, full-thickness, anteroseptal myocardial infarction from which he made a good recovery after 2 weeks in hospital. 10 days later he was admitted with a supraventricular tachycardia which was resistant to intravenous practolol and required direct-current shock to restore sinus rhythm. He was then treated with oral propranolol (40 mg twice daily) but as an outpatient continued to have palpitations. Oral disopyramide (100 mg three times daily) was started but the palpitation became worse and an electrocardiogram showed high nodal extrasystoles and supraventricular ectopic beats with aberrant conduction, neither of which had been previously noted. Both drugs were stopped and both his symptoms and
mention
was
the electrocardiogram improved. The patient was next admitted in September, 1977, with severe palpitation associated with hypotension which had ter-
99 minated spontaneously by the time of admission. He had a 1-week history of palpitation which he insisted had been made worse by disopyramide given by his general practitioner. 12 h after admission he had ventricular tachycardia which progressed to ventricular fibrillation despite intravenous lignocaine and practolol. Five high-energy direct-current shocks produced asystole, and sinus rhythm was restored by intracardiac adrenaline. This rhythm was complicated by multiple atrial and ventricular ectopic beats which persisted despite a lignocaine infusion. 10 h after the episode of ventricular fibrillation he was given intravenous disopyramide (100 mg) over a period of 5 min (he was unable to take oral medication at this time) and almost immediately he had ventricular tachycardia (about 240/min) associated with hypotension which required further direct-current shock. Electrolytes at this time were normal. Mexiletine was given but chaotic cardiac rhythm persisted (including five further episodes of ventricular fibrillation). An akinetic area of myocardium was excised surgically as an emergency and subsequently he has been in sinus
rhythm. Oral disopyramide was
associated with a worsening of palpitation on two occasions. When given intravenously it was associated with ventricular tachycardia. The myocardium was obviously very unstable at the time of intravenous injection and the ventricular tachycardia may have been purely coincidental. However the possibility of such a consequence, and the known side-effects of the drug, should be borne in mind before endorsing the recommendation of Zainal et al. that "oral disopyramide should be given for the first seven days after myocardial infarction to all patients not managed in coronary care
land et al. in their studies on 6 healthy subjects taking 1.6 g cimetidine daily for 6 days noted no consistent impairment of creatinine clearance but there was a wide range of variation. I have seen a 33-year-old man with duodenal ulcers who had a 28-day course of cimetidine (1 g daily). Pretreatment serumcreatinine was 116 fLmol;1. There was rapid improvement in his symptoms but by the 14th day of treatment his serum-creatinine had risen to 153 fLmol;1. 5 days after stopping cimetidine-creatinine was 180 µmo1/1 28 days after stopping it was 142 mol/1 with a creatinine clearance of 67-6 ml/min. 49 days after treatment creatinine clearance was 82 ml/min and after fluid deprivation urine osmolality was 1,096 mosm/kg. 17 weeks later the creatinine clearance was 122 ml/min. This patient’s transient deterioration in renal function with recovery was caused by the recommended dose of cimetidine. Portiuncula
Hospital,
Ballinasloe, Co. Galway,
MORGAN MCELLIGOTT
Ireland
PLASMA-PROLACTIN AND CIMETIDINE were reported in male treated with cimetidine for Zollinger-Ellison syndrome.3.. In a patient given cimetidine for 2 months a significant rise in plasma-prolactin was observed5 but Dr Petrillo and colleagues (Oct. 8, p. 761) were unable to confirm this finding.
SIR, -Breast pain and gynscomastia
patients
units".
PAUL SIKLOS T. M. CHALMERS D. W. EVANS
Addenbrooke’s Hospital, Cambridge CB2 2QC
CIMETIDINE OVERDOSE
SIR,-A middle-aged African man with
a
radiologically pro-
clinically active duodenal ulcer was prescribed a 2-month course of cimetidine. He was given three hundred 200 mg tablets and told to take one three times daily and two at night. When seen for review 1 month later it transpired that he had used all the tablets in the first week. Having obtained considerable pain relief with 1 day’s treatment at the recommended dose, he thought that taking more tablets would be of even greater benefit and proceeded to take approximately fifteen tablets four times daily (about 12 g per day) until the tablets were finished 5 days later. He noted no untoward effects and continued his job as an underground miner throughout the treatment. His dyspepsia disappeared and a repeat bariummeal examination 4 months after treatment showed no sign of ven
and
the ulcer. It would seem that high doses of cimetidine may be tolerated without adverse effects-indeed with excellent clinical results in this case. This information could be of use to casualty officers faced with accidental or deliberate overdose with cimetidine.
Nchanga Hospitals P.O. Box 63, Chingola,
Zambia
GEOFFREY V. GILL
IMPAIRED CREATININE CLEARANCE AFTER CIMETIDINE
and Hawkins’ summarising multicentre trials of cimetidine, note that serum-creatinine can rise early in treatment in patients on a higher dose. 3 patients stopped the drug while receiving 1.22 g daily; 2 had pre-existing renal disease and one had a pre-existing raised serum-creatinine. Bur-
Effect of cimetidine
plasma-prolactin (hPRL). injection; arrow indicates time of injection; *=values significantly different (p
