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SCALP TINGLING IN PATIENTS ON LABETALOL
295 4 months after he stopped taking cimetidine he had a sore throat and mouth ulceration which was initially treated with paracetamol and penicillin V. A blood-count 5 days later showed Hb 12.9 g/dl, white blood-cells 2.2 x 109/1 (lymphocytes 98%, monocytes 1%, neutrophils 1%) and platelets 205x109/1. The ’Monospot’ test for glandular fever was negative and no abnormal cells were seen on the blood-film. The patient was admitted to hospital. On examination he looked ill, was pyrexial (38-5°C) and had hyperaemic gums and fauces, mouth ulcers, and marked cervical lymphadenopathy. There was epigastric tenderness but physical examination was otherwise normal. A bone-marrow biopsy on the day of admission was hypocellular showing a total absence of white-cell precursors but was normal in all other respects. He was reverse-barrier nursed and treated with prophylactic intravenous gentamicin, carbenicillin, and cephalothin plus oral metronidazole and nystatin. Subsequent marrow biopsies on the 4th, 7th, and 12th days of admission showed a gradual return of normal granulocyte precursors, and there was a corresponding improvement in his clinical condition. His peripheral-blood neutrophil-count had risen to 4 - 2 x 109/1 by the 14th day of admission. Serial blood, nasal, sputum, urine, and faecal specimens were sterile on culture, though a throat swab grew &bgr;-haemolytic streptococcus (not group A) which did not respond to intravenous chemotherapy but was subsequently treated with penicillin V for 7 days (with no adverse effects or neutropenia). Viral studies were unhelpful. Because of the long interval between the last dose of cimetidine and the onset of symptoms attributable to agranulocytosis, no causal relation between this drug and the marrow suppression can be established. Nevertheless this patient had not, to our knowledge, been exposed to any other drugs or agents known to cause agranulocytosis, and an association between the related compound metiamide and neutropenia is well established.’1 Kettering and District General Hospital, Kettering, Northamptonshire NN16 8UZ
the finding of this unusual side-effect in these indicates that it may be a genuine effect of the drug and warrant further investigation. ANDREW S. P. HUA University of Melbourne, GWYNNE W. THOMAS Royal Melbourne Hospital, PRISCILLA KINCAID-SMITH Melbourne, Victoria 3050, Australia
labetalol,’ and
patients
two
CHLORTHALIDONE AND SERUM CHOLESTEROL
SIR,-The observations of Ames and Hi112 on the effects of chlorthalidone on serum-cholesterol prompted us to examine data from a double-blind study of treatment in mild hypertension, in which chlorthalidone and reserpine were given to relatively young subjects with uncomplicated hypertension. The V.A.-N.H.B.L.I. Mild Hypertension Cooperative Study is supported jointly by the Veterans Administration Research Service and the Clinical Trials Section of the National Heart, Lung, and Blood Institute; it is a feasibility trial in four clinical centres and with central facilities. Cholesterol was measured by the total enzymatic method on the ’ABA 100’, standardised to meet W.H.O. criteria for lipid determinations in cardiovascular research. Data on cholesterol values before treatment (baseline), and after 1 year of follow-up, for a 21-50-year-old population with diastolic pressures of 85-105 mm Hg when not on treatment are available. 311 participants received active drug (50 or 100 mg chlorthalidone and, if needed, z 25 mg reserpine daily) and 325 received identical placebo tablets, neither participant nor physician knowing what the tablets were. The results, as mean (and s.E.) in mg/dl plasma, were:
ERIC R. CRAVEN
JOHN M. WHITTINGTON
SCALP TINGLING IN PATIENTS ON LABETALOL
SIR,-We have been conducting a clinical trial comparing the efficacy and side-effects of a combination therapy (diuretic, propranolol, and prazosin) with labetalol in moderately severe and severe hypertension. We have seen an unusual side-effect with labetalol which does not seem to have been previously reported with the oral form of this drug. A woman who works in the hospital kitchen complained, on the third day after active labetalol (100 mg twice daily) was substituted for placebo, of a most unpleasant sensation of insects crawling under her scalp; the sensation began about an hour after she had taken a labetalol tablet and lasted for several hours. This was thought to have been due to her working in the hot kitchen, and the patient was reassured and asked to continue taking the tablets. 2 days later, she insisted that she be taken off labetalol because the symptoms had persisted and her scalp had become tender to touch and combing. The symptoms subsided when the drug was withdrawn. A 35-year-old customs officer was symptom-free when labetalol was first given, but when the dose of labetalol was increased to 1600 mg a day he reported a tingling sensation in the scalp which started a couple of hours after taking his morning dose of labetalol and lasted for the rest of the day. He did not find the sensation distressing and was willing to continue taking the drug. We have now treated over thirty patients with labetalol and these were the only two who complained of this side-effect. Tingling of the scalp has been reported after intravenous
There was a statistically significant increase in the plasmacholesterol of the "active drug" group between the baseline and annual examinations (P<0001). The increase was most marked for those with the lowest baseline values: for 205 subjects with baseline values below 185 mg/dl the mean increase for the active drug group was 17.7 mg/dl whereas for the placebo drug group it was 2.2mg/dl. The increase was not related to reserpine exposure since the mean increase for the 159 participants who received chlorthalidone only was 11.6 mg/dl-i.e., approximately the same as the increase for all 311
on active drug(s). There
was a
J. A. H., Spence, 1975, i, 392.
R.
triglycerides-13-88
The difference
(after logarithmic transformation) was signifi(r<001). There was an associated loss in total bodyweight in the active-drug group of 1 -1 kg and a negligible increase in the placebo group of 0.2 kg. The active-drug group also had the expected changes in mean plasma potassium, uric acid, and, to a lesser extent, glucose. Although these lipid data are preliminary, they seem to corcant
roborate Ames and Hill’s observations. Birmingham, Iowa New
City,
Alabama
Iowa
Orleans, Louisiana
Minneapolis,
Minnesota
Veterans Administration Hospital. St. Louis, Missouri, 63106, U.S.A.
Minneapolis,
Minnesota
1. Collier, 1 Forrest,
concomitant increase in
mg/dl for the active-drug group and 4.3mg/dl for the controls.
2.
EDWARD FROHLICH
ANNE GOLDMAN H. MITCHELL Study Chairman
PERRY, JR
BERNARD STEELE
J. G., Dawnay, N. A. H., Nachev, C. H., Robinson, 1972, 44, 286. Ames, R., Hill, P. Lancet, 1976, i, 721. Pharmac.
Shearman, D. J. C., Celestin, L. R. Lancet,
HAROLD SCHNAPER
ANNETTE FITZ
B. F. Br.
J.
the finding of this unusual side-effect in these indicates that it may be a genuine effect of the drug and warrant further investigation. ANDREW S. P. HUA University of Melbourne, GWYNNE W. THOMAS Royal Melbourne Hospital, PRISCILLA KINCAID-SMITH Melbourne, Victoria 3050, Australia
labetalol,’ and
patients
two
CHLORTHALIDONE AND SERUM CHOLESTEROL
SIR,-The observations of Ames and Hi112 on the effects of chlorthalidone on serum-cholesterol prompted us to examine data from a double-blind study of treatment in mild hypertension, in which chlorthalidone and reserpine were given to relatively young subjects with uncomplicated hypertension. The V.A.-N.H.B.L.I. Mild Hypertension Cooperative Study is supported jointly by the Veterans Administration Research Service and the Clinical Trials Section of the National Heart, Lung, and Blood Institute; it is a feasibility trial in four clinical centres and with central facilities. Cholesterol was measured by the total enzymatic method on the ’ABA 100’, standardised to meet W.H.O. criteria for lipid determinations in cardiovascular research. Data on cholesterol values before treatment (baseline), and after 1 year of follow-up, for a 21-50-year-old population with diastolic pressures of 85-105 mm Hg when not on treatment are available. 311 participants received active drug (50 or 100 mg chlorthalidone and, if needed, z 25 mg reserpine daily) and 325 received identical placebo tablets, neither participant nor physician knowing what the tablets were. The results, as mean (and s.E.) in mg/dl plasma, were:
ERIC R. CRAVEN
JOHN M. WHITTINGTON
SCALP TINGLING IN PATIENTS ON LABETALOL
SIR,-We have been conducting a clinical trial comparing the efficacy and side-effects of a combination therapy (diuretic, propranolol, and prazosin) with labetalol in moderately severe and severe hypertension. We have seen an unusual side-effect with labetalol which does not seem to have been previously reported with the oral form of this drug. A woman who works in the hospital kitchen complained, on the third day after active labetalol (100 mg twice daily) was substituted for placebo, of a most unpleasant sensation of insects crawling under her scalp; the sensation began about an hour after she had taken a labetalol tablet and lasted for several hours. This was thought to have been due to her working in the hot kitchen, and the patient was reassured and asked to continue taking the tablets. 2 days later, she insisted that she be taken off labetalol because the symptoms had persisted and her scalp had become tender to touch and combing. The symptoms subsided when the drug was withdrawn. A 35-year-old customs officer was symptom-free when labetalol was first given, but when the dose of labetalol was increased to 1600 mg a day he reported a tingling sensation in the scalp which started a couple of hours after taking his morning dose of labetalol and lasted for the rest of the day. He did not find the sensation distressing and was willing to continue taking the drug. We have now treated over thirty patients with labetalol and these were the only two who complained of this side-effect. Tingling of the scalp has been reported after intravenous
There was a statistically significant increase in the plasmacholesterol of the "active drug" group between the baseline and annual examinations (P<0001). The increase was most marked for those with the lowest baseline values: for 205 subjects with baseline values below 185 mg/dl the mean increase for the active drug group was 17.7 mg/dl whereas for the placebo drug group it was 2.2mg/dl. The increase was not related to reserpine exposure since the mean increase for the 159 participants who received chlorthalidone only was 11.6 mg/dl-i.e., approximately the same as the increase for all 311
on active drug(s). There
was a
J. A. H., Spence, 1975, i, 392.
R.
triglycerides-13-88
The difference
(after logarithmic transformation) was signifi(r<001). There was an associated loss in total bodyweight in the active-drug group of 1 -1 kg and a negligible increase in the placebo group of 0.2 kg. The active-drug group also had the expected changes in mean plasma potassium, uric acid, and, to a lesser extent, glucose. Although these lipid data are preliminary, they seem to corcant
roborate Ames and Hill’s observations. Birmingham, Iowa New
City,
Alabama
Iowa
Orleans, Louisiana
Minneapolis,
Minnesota
Veterans Administration Hospital. St. Louis, Missouri, 63106, U.S.A.
Minneapolis,
Minnesota
1. Collier, 1 Forrest,
concomitant increase in
mg/dl for the active-drug group and 4.3mg/dl for the controls.
2.
EDWARD FROHLICH
ANNE GOLDMAN H. MITCHELL Study Chairman
PERRY, JR
BERNARD STEELE
J. G., Dawnay, N. A. H., Nachev, C. H., Robinson, 1972, 44, 286. Ames, R., Hill, P. Lancet, 1976, i, 721. Pharmac.
Shearman, D. J. C., Celestin, L. R. Lancet,
HAROLD SCHNAPER
ANNETTE FITZ
B. F. Br.
J.