Current Medical Research and Opinion
ISSN: 0300-7995 (Print) 1473-4877 (Online) Journal homepage: http://www.tandfonline.com/loi/icmo20
Poor hypotensive response and tachyphylaxis following intravenous labetalol C. C. Anderson & Roger Gabriel To cite this article: C. C. Anderson & Roger Gabriel (1978) Poor hypotensive response and tachyphylaxis following intravenous labetalol, Current Medical Research and Opinion, 5:5, 424-426, DOI: 10.1185/03007997809111909 To link to this article: http://dx.doi.org/10.1185/03007997809111909
Published online: 11 Aug 2008.
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Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=icmo20 Download by: [University of Otago]
Date: 12 November 2015, At: 20:03
Current Medical Research and Opinion
Vol. 5, No. 5 , 1978
Poor hypotensive response and tachyphylaxis following intravenous labetalol
and
C. C. Anderson, M.B., Ch.B., Roger Gabriel, M.Sc., M.R.C.P. St. Mary’s Hospital, London, England
Downloaded by [University of Otago] at 20:03 12 November 2015
Curr. Med. Res. Opin., (1978), 5,424.
Received: 17th February 1978
Summary Three renal patients with transplant kidneys and uncontrolled hypertension were treated with intravenous doses of labetalol. Only minor depressor effects were noted and tachyphylaxis developed in 1 patient. Other parenteral hypotensive agents reduced blood pressure satisfactorily, Key words: Labetalol - antihypertensive agents - hypertension - tachyphylaxis
Introduction Labetalol (‘Trandate’t) is a new hypotensive agent which is recommended for intravenous use in the control of severe hypertension. To date, there have been reports’-8 of the successful control of hypertension in just over 100 such patients. The present short report gives details of our use of labetalol intravenously in 3 patients, in 2 of whom there was an inadequate hypotensive response and in the third tachyphylaxis developed.
Case reports Case 1. A 46-year old male Indian had received a transplant kidney 4 years previously. He was admitted to hospital because of hypertension and renal failure (creatinine clearance 5 ml/minute). Blood pressure was between 170 to 205/120 to 145 mmHg, despite 640 mg propranolol, 20 mg debrisoquine and 120 mg frusemide daily. When the blood pressure was 190/138 mmHg and pulse 84 beats/minute, 25 mg labetalol(O.54 mg/kg body weight) was given as an intravenous bolus. The diastolic pressure was reduced by only 8 mmHg and the pulse by 10 beats/minute for 30 minutes. At this stage, 50 mg labetalol (1.1 rng/kg body weight) produced no change in blood pressure or pulse. Subsequently, the blood pressure fell to 120/90 mmHg following 20 mg hydrallazine intravenously. Case 2. A 19-yearold male Englishman who had received a transplant kidney 2 months previously was admitted because of hypertension. Creatinine clearance was 78 ml/minute and the plasma renin activity was 3023 pg/ml plasma/hour (upper limit for age about 2000 pg/ml plasma/hour). He was receiving only 10 rng prednisolone and 75 mg azathioprine daily. An intravenous bolus of 100 mg labetalol(l.3 mg/kg body weight) was given when the blood pressure was 195/130 mmHg and this changed the pressure to 190/130 mmHg in 5 minutes. Twenty minutes later the blood pressure had
ttrade mark, Allen and Hanburys 424
C. C. Anderson and Roger Gabriel
Downloaded by [University of Otago] at 20:03 12 November 2015
increased again to 196/140 mmHg. A further bolus of 50 mg labetalol(O.69 mg/kg body weight) was given but there was no change in blood pressure. The hypertension fell to 170/96 mmHg after 20 mg hydrallazine intravenously. Case 3. A 35-year old male Englishman, weight 64 kg, was admitted because of failing transplant kidney function and hypertension. Creatinine clearance was 1 ml/minute, plasma renin activity was 27850 pg/ml plasrna/hour, and plasma aldosterone was 1240 pmol/l (47.8 ng/100 ml), normal values being less than 330 pmol/l(12.0 ng/100 ml). The patient had been receiving 960 mg propran0101, 2 g alpha methyldopa, 20 mg debrisoquine, 80 mg frusemide, 15 mg prednisolone, and 100 mg azathioprine daily. These drugs, however, had not been taken for 24 hours because of vomiting. As there was a fresh haemorhage in one fundus, a parenteral hypotensive agent was used. A labetalol infusion was set up and separate intravenous doses were also given (Figure 1). Again only minor depressor effects were noted and a tachyphylactic response was evident throughout the whole period of treatment, especially after the intravenous bolus doses of the drug. The total dose of labetalol used in this case was 700 mg. Blood pressure was finally brought under control with sodium nitroprusside. Figure 1. Change in blood pressure, pulse rate (beatslmin), and mean arterial pressure (MAP) during labetalol infusion and separate 50 mg (0.78 mg/kg body weight) and 100 mg (1.56 mg,kg body weight) intravenous doses of labetalol: Patient No. 3
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Discussion We are unable to explain our lack of success in these 3 patients; the features they had in common were severe hypertension, transplant kidneys, and immunosuppressive drugs. Patients 2 and 3 had very raised plasma renin concentrations. It could be argued that the first patient was treated with insufficiently large doses of labetalol 425
Poor hypotensive response and tachyphylaxis following intravenous Iabetalol
Downloaded by [University of Otago] at 20:03 12 November 2015
but, as he was in mild congestive heart failure, an increase in dose seemed unwise. While it is not reasonable to expect therapeutic success in every patient, the minor depressor effects in the first 2 patients and the tachyphylactic response in the third patient should be emphasized to contrast with the successful use of parenteral labetalol previously reported. An inadequate hypotensive response following intravenous labetalol has been briefly recorded previously.8 It appears from our experience that if 2 adequate parenteral doses of labetalol are unsuccessful a longer established hypotensive drug should then be used in preference to increasing doses of labetalol.
References 1. -Brown, J. J., Lever, A. F., Cumming, A. M. M., and Robertson, J. I. S., (1977). Labetalol in hypertension. Lancet, 1,1147. 2. Joekes, A. M., and Thompson, F. D., (1976). Acute haemodynamiceffects of labetalol and its subsequent use as an oral hypotensive agent. Br. J. Clin. Pharmacol., 3, Suppl. 3,789. 3. Pearson, R. M., and Harvard, C. W. H., (1976). Intravenous labetalol in hypertensive patients treated with @-adrenoceptor-blockingdrugs. Br. J. Clin. Pharmcol., 3, Suppl. 3,795. 4. Prichard, B. N. C., Thompson, F. D., Boakes, A. J., and Joekes, A. M., (1975). Some haemodynamic effects of compound AH 5158 compared with propranolol, propranolol plus hydrallazine and diazoxide. Clin.Sci. Molec. Med., 48, Suppl. 2,97. 5. Ronne-Rasmussen, J. O., Anderson, G. S., Bowal-Jensen, N., and Anderson, E., (1976). Acute effect of intravenous labetalol in the treatment of systemic arterial hypertension. Br. J. Clin. Pharmacol., 3, Suppl. 3,805. 6. Rosei, E. A., Brown, J. J., Lever, A. F., Robertson, A. S.,Robertson, J. I. S., and Trust, P. M., (1976). Treatment of phaeochromocytoma and clonidine withdrawal hypertension with labetalol. Br. J. Clin.Pharmacol., 3, Suppl. 3,809. 7. Scott, D. B., Buckley, F. P., Drummond, G. B., Littlewood, D. G., and Macrae, W. R., (1976). Cardiovascular effects of labetalol during halothane anaesthesia. Br. J. Clin.Pharmacol., 3, Suppl. 3, 817. 8. Trust, P. M., Rosei, E. A., Brown, J. J., Fraser, R., Lever, A. F., Morton, J. J., and Robertson, J. I. S., (1976). Effect of blood pressure, angiotensin I1 and aldosterone concentrations during
treatment of severe hypertension with intravenous labetalol: comparison with propranolol. Br. J. Clin.Pharmacol., 3, Suppl. 3,799.
426
ISSN: 0300-7995 (Print) 1473-4877 (Online) Journal homepage: http://www.tandfonline.com/loi/icmo20
Poor hypotensive response and tachyphylaxis following intravenous labetalol C. C. Anderson & Roger Gabriel To cite this article: C. C. Anderson & Roger Gabriel (1978) Poor hypotensive response and tachyphylaxis following intravenous labetalol, Current Medical Research and Opinion, 5:5, 424-426, DOI: 10.1185/03007997809111909 To link to this article: http://dx.doi.org/10.1185/03007997809111909
Published online: 11 Aug 2008.
Submit your article to this journal
Article views: 6
View related articles
Full Terms & Conditions of access and use can be found at http://www.tandfonline.com/action/journalInformation?journalCode=icmo20 Download by: [University of Otago]
Date: 12 November 2015, At: 20:03
Current Medical Research and Opinion
Vol. 5, No. 5 , 1978
Poor hypotensive response and tachyphylaxis following intravenous labetalol
and
C. C. Anderson, M.B., Ch.B., Roger Gabriel, M.Sc., M.R.C.P. St. Mary’s Hospital, London, England
Downloaded by [University of Otago] at 20:03 12 November 2015
Curr. Med. Res. Opin., (1978), 5,424.
Received: 17th February 1978
Summary Three renal patients with transplant kidneys and uncontrolled hypertension were treated with intravenous doses of labetalol. Only minor depressor effects were noted and tachyphylaxis developed in 1 patient. Other parenteral hypotensive agents reduced blood pressure satisfactorily, Key words: Labetalol - antihypertensive agents - hypertension - tachyphylaxis
Introduction Labetalol (‘Trandate’t) is a new hypotensive agent which is recommended for intravenous use in the control of severe hypertension. To date, there have been reports’-8 of the successful control of hypertension in just over 100 such patients. The present short report gives details of our use of labetalol intravenously in 3 patients, in 2 of whom there was an inadequate hypotensive response and in the third tachyphylaxis developed.
Case reports Case 1. A 46-year old male Indian had received a transplant kidney 4 years previously. He was admitted to hospital because of hypertension and renal failure (creatinine clearance 5 ml/minute). Blood pressure was between 170 to 205/120 to 145 mmHg, despite 640 mg propranolol, 20 mg debrisoquine and 120 mg frusemide daily. When the blood pressure was 190/138 mmHg and pulse 84 beats/minute, 25 mg labetalol(O.54 mg/kg body weight) was given as an intravenous bolus. The diastolic pressure was reduced by only 8 mmHg and the pulse by 10 beats/minute for 30 minutes. At this stage, 50 mg labetalol (1.1 rng/kg body weight) produced no change in blood pressure or pulse. Subsequently, the blood pressure fell to 120/90 mmHg following 20 mg hydrallazine intravenously. Case 2. A 19-yearold male Englishman who had received a transplant kidney 2 months previously was admitted because of hypertension. Creatinine clearance was 78 ml/minute and the plasma renin activity was 3023 pg/ml plasma/hour (upper limit for age about 2000 pg/ml plasma/hour). He was receiving only 10 rng prednisolone and 75 mg azathioprine daily. An intravenous bolus of 100 mg labetalol(l.3 mg/kg body weight) was given when the blood pressure was 195/130 mmHg and this changed the pressure to 190/130 mmHg in 5 minutes. Twenty minutes later the blood pressure had
ttrade mark, Allen and Hanburys 424
C. C. Anderson and Roger Gabriel
Downloaded by [University of Otago] at 20:03 12 November 2015
increased again to 196/140 mmHg. A further bolus of 50 mg labetalol(O.69 mg/kg body weight) was given but there was no change in blood pressure. The hypertension fell to 170/96 mmHg after 20 mg hydrallazine intravenously. Case 3. A 35-year old male Englishman, weight 64 kg, was admitted because of failing transplant kidney function and hypertension. Creatinine clearance was 1 ml/minute, plasma renin activity was 27850 pg/ml plasrna/hour, and plasma aldosterone was 1240 pmol/l (47.8 ng/100 ml), normal values being less than 330 pmol/l(12.0 ng/100 ml). The patient had been receiving 960 mg propran0101, 2 g alpha methyldopa, 20 mg debrisoquine, 80 mg frusemide, 15 mg prednisolone, and 100 mg azathioprine daily. These drugs, however, had not been taken for 24 hours because of vomiting. As there was a fresh haemorhage in one fundus, a parenteral hypotensive agent was used. A labetalol infusion was set up and separate intravenous doses were also given (Figure 1). Again only minor depressor effects were noted and a tachyphylactic response was evident throughout the whole period of treatment, especially after the intravenous bolus doses of the drug. The total dose of labetalol used in this case was 700 mg. Blood pressure was finally brought under control with sodium nitroprusside. Figure 1. Change in blood pressure, pulse rate (beatslmin), and mean arterial pressure (MAP) during labetalol infusion and separate 50 mg (0.78 mg/kg body weight) and 100 mg (1.56 mg,kg body weight) intravenous doses of labetalol: Patient No. 3
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=--
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0
I
I
I
I
-
I
I
3
3
I
1
4
I
1
5
Hours Note: all measurements were made in the lying position and the diastolic end point was taken at the 4th Korotkoff phase
Discussion We are unable to explain our lack of success in these 3 patients; the features they had in common were severe hypertension, transplant kidneys, and immunosuppressive drugs. Patients 2 and 3 had very raised plasma renin concentrations. It could be argued that the first patient was treated with insufficiently large doses of labetalol 425
Poor hypotensive response and tachyphylaxis following intravenous Iabetalol
Downloaded by [University of Otago] at 20:03 12 November 2015
but, as he was in mild congestive heart failure, an increase in dose seemed unwise. While it is not reasonable to expect therapeutic success in every patient, the minor depressor effects in the first 2 patients and the tachyphylactic response in the third patient should be emphasized to contrast with the successful use of parenteral labetalol previously reported. An inadequate hypotensive response following intravenous labetalol has been briefly recorded previously.8 It appears from our experience that if 2 adequate parenteral doses of labetalol are unsuccessful a longer established hypotensive drug should then be used in preference to increasing doses of labetalol.
References 1. -Brown, J. J., Lever, A. F., Cumming, A. M. M., and Robertson, J. I. S., (1977). Labetalol in hypertension. Lancet, 1,1147. 2. Joekes, A. M., and Thompson, F. D., (1976). Acute haemodynamiceffects of labetalol and its subsequent use as an oral hypotensive agent. Br. J. Clin. Pharmacol., 3, Suppl. 3,789. 3. Pearson, R. M., and Harvard, C. W. H., (1976). Intravenous labetalol in hypertensive patients treated with @-adrenoceptor-blockingdrugs. Br. J. Clin. Pharmcol., 3, Suppl. 3,795. 4. Prichard, B. N. C., Thompson, F. D., Boakes, A. J., and Joekes, A. M., (1975). Some haemodynamic effects of compound AH 5158 compared with propranolol, propranolol plus hydrallazine and diazoxide. Clin.Sci. Molec. Med., 48, Suppl. 2,97. 5. Ronne-Rasmussen, J. O., Anderson, G. S., Bowal-Jensen, N., and Anderson, E., (1976). Acute effect of intravenous labetalol in the treatment of systemic arterial hypertension. Br. J. Clin. Pharmacol., 3, Suppl. 3,805. 6. Rosei, E. A., Brown, J. J., Lever, A. F., Robertson, A. S.,Robertson, J. I. S., and Trust, P. M., (1976). Treatment of phaeochromocytoma and clonidine withdrawal hypertension with labetalol. Br. J. Clin.Pharmacol., 3, Suppl. 3,809. 7. Scott, D. B., Buckley, F. P., Drummond, G. B., Littlewood, D. G., and Macrae, W. R., (1976). Cardiovascular effects of labetalol during halothane anaesthesia. Br. J. Clin.Pharmacol., 3, Suppl. 3, 817. 8. Trust, P. M., Rosei, E. A., Brown, J. J., Fraser, R., Lever, A. F., Morton, J. J., and Robertson, J. I. S., (1976). Effect of blood pressure, angiotensin I1 and aldosterone concentrations during
treatment of severe hypertension with intravenous labetalol: comparison with propranolol. Br. J. Clin.Pharmacol., 3, Suppl. 3,799.
426
