Labetalol is a competitive antagonist of α1-, β1-, and β2-adrenergic receptors. The hemodynamic effects of the drug include reduced blood pressure, heart rate, and peripheral resistance, with little change in resting cardiac output or stroke volume. In open trials and controlled studies, labetalol was an effective antihypertensive. Labetalol compared favorably with β-blockers alone or in combination with vasodilators, for the treatment of hypertension. Reductions in heart rate are less pronounced with labetalol as compared with propranolol. Labetalol produces rapid reductions in blood pressure when administered intravenously for severe hypertension. The most frequent adverse reactions to the drug include fatigue, postural symptoms, headache, and gastrointestinal complaints. Labetalol may prove advantageous when vasodilation in addition to β-blockade is desired, or for selected patients experiencing adverse effects attributable to β-blockade. Until the clinical profile of labetalol is better defined, the use of the drug should be limited.
FarmerJBKennedyILevyGPMarshallRJ. Pharmacology of AH 5158; a drug which blocks both α- and β-adrenoceptors. Br J Pharmacol1972; 45: 660–75.
2.
SybertzEJSabinCSPulaKK. Alpha and beta adrenoceptor blocking properties of labetalol and its R,R-isomer, SCH 19927J Pharmacol Exp Ther1981; 218: 435–43.
3.
BrittainRTLevyGP. A review of the animal pharmacology of labetalol, a combined α- and β-adrenoceptor-blocking drug. Br J Clin Pharmacol1976; 3 (suppl): 681–94.
4.
MehtaJCohnJN. Hemodynamic effects of labetalol, an alpha and beta adrenergic blocking agent, in hypertensive subjects. Circulation1977; 55: 370–5.
5.
RichardsDATuckmanJPrichardBNC. Assessment of α-and β-adrenoceptor blocking actions of labetalol. Br J Clin Pharmacol1976; 3: 849–55.
6.
DrewGM. Pharmacologic characterization of the presynaptic α-adrenoceptors regulating cholinergic activity in the guinea pig ileum. Br J Pharmacol1978; 64: 293–300.
7.
AggerbeckMGuellaenGHanouneJBiochemical evidence for the dual action of labetalol on α- and β-adrenoceptors. Br J Pharmacol1978; 62: 543–8.
8.
CareyBWhalleyET. Labetalol possesses β-adrenoceptor agonist action on the rat isolated uterus. J Pharm Pharmacol1979; 31: 791–2.
9.
BreckenridgeAMMacneeCMOrmeNLERichardsDASterlinMJ. Rate of onset of hypotensive response with oral labetalol. Br J Clin Pharmacol1977; 4: 338P.
10.
DaviesABSubramanianVBGouldBRafteryEB. Rapid reduction of blood pressure with acute oral labetalol. Br J Clin Pharmacol1982; 13: 705–10.
11.
TrustPMRoseiEABrownJJ. Effect of blood pressure, angiotensin II and aldosterone concentrations during treatment of severe hypertension with intravenous labetalol: comparison with propranolol. Br J Clin Pharmacol1976; 3 (suppl): 799–803.
12.
RoseiEATrustPMBrownJJ. Effects of intravenous labetalol on blood pressure, angiotensin II and aldosterone in hypertension: comparison with propranolol. Clin Sci Mol Med1976; 51 (suppl): 497–9s.
13.
Ronne-RasmussenJOAndersenGSBowalJNAnderssonE. Acute effect of intravenous labetalol in the treatment of systemic arterial hypertension. Br J Clin Pharmacol1976; 3 (suppl): 805–8.
14.
PrichardBNCThompsonFOBoakesAJJoekesAM. Some haemodynamic effects of compound AH 5158 compared with propranolol, propranolol plus hydralazine, and diazoxide: the use of AH 5158 in the treatment of hypertension. Clin Sci Mol Med1975; 48 (suppl): 97–100s.
15.
GhoseRRSampsonA. Rapid onset of action of oral labetalol in severe hypertension. Curr Med Res Opin1977; 5: 147–51.
16.
GagnonRMMorissetteMPresantSSavardDLemireJ. Hemodynamic and coronary effects of intravenous labetalol in coronary artery disease. Am J Cardiol1982; 49: 1267–9.
17.
MaconochieJGWoodingsEPRichardsDA. Effects of labetalol and propranolol on histamine-induced bronchoconstriction in normal subjects. Br J Clin Pharmacol1977; 4: 157–62.
18.
SvendsenTLRasmussenSHartlingOJNielsenPETrap-JensenJ. Acute and long-term effects of labetalol on systemic and pulmonary haemodynamics in hypertensive patients. Eur J Clin Pharmacol1980; 17: 5–11.
19.
KochG. Haemodynamic effects of combined α- and β-adrenoceptor blockade after intravenous labetalol in hypertensive patients at rest and during exercise. Br J Clin Pharmacol1976; 3 (suppl): 725–8.
20.
KochG. Acute hemodynamic effects of an alpha- and beta-receptor blocking agent (AH 5158) on the systemic and pulmonary circulation at rest and during exercise in hypertensive patients. Am Heart J1977; 93: 585–91.
RasmussenSNielsenPE. Blood pressure, body fluid volumes and glomerular filtration rate during treatment with labetalol in essential hypertension. Br J Clin Pharmacol1981; 12: 349–53.
23.
KochG. Combined α- and β-adrenoceptor blockade with oral labetalol in hypertensive patients with reference to haemodynamic effects at rest and during exercise. Br J Clin Pharmacol1976; 3 (suppl): 729–32.
24.
KochG. Haemodynamic adaptation at rest and during exercise to long-term antihypertensive treatment with combined alpha-and beta-adrenoceptor blockade by labetalol. Br Heart J1979; 41: 192–8.
25.
FagardRAmeryAReybrouckTLijnenPBillietL. Response of the systemic and pulmonary circulation to alpha- and beta-receptor blockade (labetalol) at rest and during exercise in hypertensive patients. Circulation1979; 60: 1214–9.
26.
TaylorSHSilkeBNelsonGLCOkoliRCAhujaRC. Haemodynamic advantages of combined alpha-blockade and beta-blockade over beta-blockade alone in patients with coronary heart disease. Br Med J1982; 285: 325–7.
27.
Trap-JensenJClausenJPHartlingOJSvendsenTLKrogsgaardAR. Immediate effects of labetalol on central, splanchnic-hepatic and forearm haemodynamics during pleasant emotional stress in hypertensive patients. Postgrad Med J1980; 56 (suppl): 37–42.
28.
WeidmannPDeChatelRZieglerWHFlammerJReubiF. Alpha and beta adrenergic blockade with orally administered labetalol in hypertension: studies on blood volume, plasma renin, and aldosterone and catecholamine excretion. Am J Cardiol1978; 41: 570–6.
29.
HunyorSNBauerGERossMLarkinH. Labetalol and propranolol in mild hypertensives: comparison of blood pressure and plasma volume effects. Aust NZ J Med1980; 10: 162–6.
30.
SalvettiAPedrinelliRSassanoPArzilliF. Effect of increasing doses of labetalol on blood pressure, plasma renin activity and aldosterone in hypertensive patients. Clin Sci1979; 57: 401–4s.
31.
LammintaustaRKouluMAllonenH. Alpha- and beta-adrenoceptor blocking properties of labetalol in renin release. J Clin Pharmacol Biopharm1979; 17: 240–3.
32.
LijnenPJAmeryAKFagardRHReybrouckTMMoermanEJDeSchaepdryverAF. Effects of labetalol on plasma renin, aldosterone, and catecholamines in hypertensive patients. J Cardiovasc Pharmacol1979; 1: 625–32.
33.
ChristensenNJTrap-JensenJSvendsenTLRasmussenSNielsenPE. Effect of labetalol on plasma noradrenaline and adrenaline in hypertensive man. Eur J Clin Pharmacol1978; 14: 227–30.
34.
CarlsonJETrap-JensenJSvendsenTLNielsenPERasmussenSChristensenNJ. Effect of labetalol on plasma catecholamines at rest and during increased sympathetic activity. Postgrad Med J1980; 56 (suppl): 43–8.
35.
KeuschGWeidmannPZieglerWHDeChatelRReubiFC. Effects of chronic alpha and beta adrenoceptor blockade with labetalol on plasma catecholamines and renal function in hypertension. Klin Wochenschr1980; 58: 25–9.
36.
HamiltonCAJonesDHDargieHJReidJL. Does labetalol increase excretion of urinary catecholamines?. Br Med J1978; 2: 800.
37.
KobayashiKMiuraYTomiokaH. Falsely high urinary catecholamines induced by labetalol. Tohoku J Exp Med1979; 127: 63–9.
38.
MianoLKollochRDeQuattroV. Increased catecholamine excretion after labetalol therapy: a spurious effect of drug metabolites. Clin Chim Acta1979; 95: 211–7.
39.
PedersenEBLarsenJS. Effect of propranolol and labetalol on renal haemodynamics at rest and during exercise in essential hypertension. Postgrad Med J1980; 56 (suppl): 27–32.
40.
MaliniPLStrocchiENegroniSAmbrosioniEMagnaniB. Renal haemodynamics after chronic treatment with labetalol and propranolol. Br J Clin Pharmacol1982; 13 (suppl): 123–6s.
41.
NichollsDPHusainiMHBulpittCJStephensMDBButlerAG. Comparison of labetalol and propranolol in hypertension. Br J Clin Pharmacol1980; 9: 233–7.
42.
SkinnerCGaddieJPalmerKNV. Comparison of intravenous AH 5158 (Ibidomide) and propranolol in asthma. Br Med J1975; 1: 59–61.
43.
LarssonK. Influence of labetalol, propranolol and practolol in patients with asthma. Eur J Respir Dis1982; 63: 221–30.
44.
KantoJAllonenHKleimolaTMantylaR. Pharmacokinetics of labetalol in healthy volunteers. Int J Clin Pharmacol Ther Toxicol1981; 19: 41–4.
MantylaRAllonenHKantoJKleimolaTSellmanR. Effect of food on the bioavailability of labetalol. Br J Clin Pharmacol1980; 9: 435–7.
47.
DaneshmendTKRobertsCJC. The influence of food on the oral and intravenous pharmacokinetics of a high clearance drug: a study with labetalol. Br J Clin Pharmacol1982; 14: 73–8.
48.
LouisWJChristophidisNBrignellMVijayasekaranVMcNeilJVajdaFJE. Labetalol: bioavailability, drug plasma levels, plasma renin and catecholamines in acute and chronic treatment of resistant hypertension. Aust NZ J Med1978; 8: 602–9.
49.
MartinLEHopkinsRBlandR. Metabolism of labetalol by animals and man. Br J Clin Pharmacol1976; 3 (suppl): 695–710.
50.
KellyJGMcGarryKO'MalleyKO'BrienET. Bioavailability of labetalol increases with age. Br J Clin Pharmacol1982; 14: 304–5.
51.
HomeidaMJacksonLRobertsCJC. Decreased first-pass metabolism of labetalol in chronic liver disease. Br Med J1978; 2: 1048–50.
52.
RileyAJ. Clinical pharmacology of labetalol in pregnancy. J Cardiovasc Pharmacol1981; 3 (suppl): 53–9s.
53.
MichaelCA. Use of labetalol in the treatment of severe hypertension during pregnancy. Br J Clin Pharmacol1979; 8 (suppl): 211–5s.
54.
HopkinsRMartinLEOxfordJScullyN. Isolation and characterization of glucuronide conjugates of labetalol. In: AitioA, ed. Conjugation reactions in drug biotransformation. Amsterdam: Elsevier, 1978: 500.
55.
WoodAJFerryDGBaileyRR. Elimination kinetics of labetalol in severe renal failure. Br J Clin Pharmacol1982; 13 (suppl): 81–6s.
56.
BolliPWaal-ManningHJWoodAJSimpsonFO. Experience with labetalol in hypertension. Br J Clin Pharmacol1976; 3 (suppl): 765–71.
57.
BolliPWaal-ManningHJSimpsonFOSeemanHM. Treatment of hypertension with labetalol. NZ Med J1977; 86: 557–63.
58.
HarrisC. Labetalol in the difficult hypertensive patient in general practice. Curr Med Res Opin1978; 5: 618–24.
59.
GomezGPhillipsLA. Labetalol (‘Trandate’) in hypertension: a multicentre study in general practice. Curr Med Res Opin1980; 6: 677–84.
60.
MyersJMorganTWagaSHodgsonMAdamW. Long-term experiences with labetalol. Med J Aust1980; 1: 665–6.
61.
Waal-ManningHJSimpsonFO. Review of long-term treatment with labetalol. Br J Clin Pharmacol1982; 13 (suppl): 65–73s.
62.
BrogdenRNHeelRCSpeightTMAveryGS. Labetalol: a review of its pharmacology and therapeutic use in hypertension. Drugs1978; 15: 251–70.
63.
KaneJGreggIRichardsDA. A double-blind trial of labetalol. Br J Clin Pharmacol1976; 3 (suppl): 737–41.
64.
FrickMHPorstiP. Combined alpha- and beta-adrenoceptor blockade with labetalol in hypertension. Br Med J1976; 1: 1046–8.
65.
MilneBJLoganAG. Labetalol: potent antihypertensive agent that blocks both α- and β-adrenergic receptors. Can Med Assoc J1980; 22: 1013–6.
66.
HorvathJSCatersonRJCollettPDugginGGKellyDHTillerDJ. Labetalol and bendrofluazide: comparison of their antihypertensive effects. Med J Aust1979; 1: 626–8.
67.
DawsonAJohnsonBFSmithIKMunro-FaureAD. A comparison of the effects of labetalol, bendrofluazide and their combination in hypertension. Br J Clin Pharmacol1979; 8: 149–54.
68.
HarvaldB. Comparison of labetalol and propranolol in treatment of hypertension. Postgrad Med J1980; 56 (suppl): 65–8.
69.
PugsleyDArmstrongBNassimMBeilinLJ. Combined α-and β-adrenoceptor blockade in hypertension: a controlled trial of labetalol (AH 5158) compared with propranolol and placebo. Clin Sci Mol Med1976; 51 (suppl): 501–3s.
70.
PugsleyDJArmstrongBKNassimMABeilinLJ. Controlled comparison of labetalol and propranolol in the management of severe hypertension. Br J Clin Pharmacol1976; 3 (suppl): 777–82.
71.
KofodPKjaerKVejloSHvidtS. Labetalol and alprenolol. A comparative investigation of antihypertensive effect. Postgrad Med J1980; 56 (suppl): 69–74.
72.
RomoMHalttunenPSaarinenPSarnaS. Labetalol and pindolol in the treatment of hypertension: a comparative study. Ann Clin Res1979; 11: 249–52.
73.
McNeilJJLouisWJ. A double-blind crossover comparison of pindolol, metoprolol, atenolol and labetalol in mild to moderate hypertension. Br J Clin Pharmacol1979; 8 (suppl): 163–6s.
74.
Lund-JohansenP. Comparative haemodynamic effects of labetalol, timolol, prazosin and the combination of tolamolol and prazosin. Br J Clin Pharmacol1979; 8 (suppl): 107–11s.
75.
VanderVeurEten BergeBSDonkerAJMMayJFWesselingH. Comparison of labetalol, propranolol and hydralazine in hypertensive outpatients. Eur J Clin Pharmacol1982; 21: 457–60.
76.
BarnettAJKalowskiSGuestC. Labetalol compared with prindolol plus hydrallazine in the treatment of hypertension: a double-blind crossover study. Med J Aust1978; 1: 105–9.
77.
ThibonnierMLardouxMDCorvolP. Comparative trial of labetalol and acebutolol, alone or associated with dihydralazine, in treatment of essential hypertension. Br J Clin Pharmacol1980; 9: 561–7.
78.
JohnsonBFLaBrooyJMunro-FaureAD. The anti-hypertensive efficacy of combined α- and β-adrenoreceptor blockade with phentolamine-oxprenolol or with labetalol (AH 5158). Clin Sci Mol Med1976; 51: 505–7s.
LiljaMJounelaAJKarppanenH. Comparison of labetalol and Clonidine in hypertension. Eur J Clin Pharmacol1982; 21: 363–7.
81.
SternNTeicherARosenthalT. The treatment of hypertension by labetalol—a new alpha- and beta-adrenoreceptor blocking agent. Clin Cardiol1982; 5: 125–30.
82.
RosenthalTRabinowitzBBoichisHElazarEBraunerANeufeldHN. Use of labetalol in hypertensive patients during discontinuation of Clonidine therapy. Eur J Clin Pharmacol1981; 20: 237–40.
83.
RoseEABrownJJLeverAFRobertsonAS. Treatment of phaeochromocytoma and of Clonidine withdrawal hypertension with labetalol. Br J Clin Pharmacol1976; 3 (suppl): 809–15s.
84.
McGrathBPMatthewsPGWalterNMMaydomBWJohnstonCI. Emergency treatment of severe hypertension with intravenous labetalol. Med J Aust1978; 2: 410–1.
85.
LechiAPicottiGBCoveG. Intravenous labetalol in severe hypertension: effects on blood pressure, plasma renin activity and catecholamines. Arzneim-Forsch1981; 31: 524–6.
86.
CummingAMMBrownJJFraserR. Blood pressure reduction by incremental infusion of labetalol in patients with severe hypertension. Br J Clin Pharmacol1979; 8: 359–64.
87.
CummingAMMBrownJJLeverAFRobertsonJIS. Intravenous labetalol in the treatment of severe hypertension. Br J Clin Pharmacol1982; 13 (suppl): 93–6s.
88.
YeungCKThomasGWWhitworthJAKincaid-SmithP. Comparison of labetalol, Clonidine and diazoxide intravenously administered in severe hypertension. Med J Aust1979; 1: 499–500.
89.
MacCarthyEPForstGWStokesGS. Labetalol in hypertensive emergencies. Med J Aust1978; 1: 399–400.
90.
PapademetriousVNotargiacomoAVKhatriIMFreisED.Treatment of severe hypertension with intravenous labetalol. Clin Pharmacol Ther1982; 32: 431–5.
91.
PearsonRMGriffithDNWWoollardMJamesIMHavardGWH. Comparison of effects on cerebral blood flow on rapid reduction in systemic arterial pressure by diazoxide and labetalol in hypertensive patients: preliminary findings. Br J Clin Pharmacol1979; 8 (suppl): 195–8s.
92.
GhoseRRMathurYBUpadhyayMMorganWDKhanS. Treatment of hypertensive emergencies with oral labetalol. Br Med J1978; 2: 96.
93.
GhoseRR. Acute management of severe hypertension with oral labetalol. Br J Clin Pharmacol1979; 8 (suppl): 189–93s.
94.
LammingGDSymondsEM. Use of labetalol and methyldopa in pregnancy-induced hypertension. Br J Clin Pharmacol1979; 8 (suppl): 217–22s.
95.
MichaelCA. The evaluation of labetalol in the treatment of hypertension complicating pregnancy. Br J Clin Pharmacol1982; 13 (suppl): 127–31s.
96.
LammingGDPipkinF BroughtonSymondsEM. Comparison of the alpha- and beta-blocking drug, labetalol and methyldopa, in the treatment of moderate and severe pregnancy-induced hypertension. Clin Exp Hypertension1980; 2: 865–95.
97.
WalkerJJCrooksAErwinLCalderAA. Labetalol in pregnancy-induced hypertension: fetal and maternal effects. In: RileyASymondsEM, eds. The investigation of labetalol in the management of hypertension in pregnancy.Amsterdam: Excerpta Medica, 1982: 148–60.
98.
LunellNOHjemdahlPFredholmBB. Acute effects of labetalol on maternal metabolism and uteroplacental circulation in hypertension of pregnancy. In: RileyASymondsEM, eds. The investigation of labetalol in the management of hypertension in pregnancy. Amsterdam: Excerpta Medica, 1982: 34–45.
99.
TakedaTKanekoYOmaeT. The use of labetalol in Japan: results of multicentre clinical trials. Br J Clin Pharmacol1982; 13 (suppl): 49–57s.
100.
BriggsRSJBirtwellAJPholJEF. Hypertensive response to labetalol in phaeochromocytoma. Lancet1978; 1: 1045–6.
101.
MarxPGReidDS. Labetalol infusion in acute myocardial infarction with systemic hypertension. Br J Clin Pharmacol1979; 8 (suppl): 223–8s.
102.
TimmisADFowlerMBJaggaraoNSVChamberlainDA. Labetalol infusion for the treatment of hypertension in acute myocardial infarction. Eur Heart J1980; 1: 413–6.
103.
MeretojaOAAllonenHArolaMLaaksonenVO. Combined alpha- and beta-blockade with labetalol in post-open heart surgery hypertension: reversal of hemodynamic deterioration with glucagon. Chest1980; 78: 810–5.
104.
HalprinSFrishmanWKirschnerMStromJ. Clinical pharmacology of the new beta-adrenergic blocking drugs. Part II. Effects of oral labetalol in patients with both angina pectoris and hypertension: a preliminary experience. Am Heart J1980; 99: 388–96.
105.
FrishmanWHStromJAKirschnerM. Labetalol therapy in patients with systemic hypertension and angina pectoris: effects of combined alpha- and beta-adrenoceptor blockade. Am J Cardiol1981; 48: 917–28.
106.
CondorelliMBrevettiGChiarielloM. Effects of combined α- and β-blockade by labetalol in patients with coronary artery disease. Br J Clin Pharmacol1982; 13 (suppl): 101–10s.
107.
BoakesAJPrichardBNC. The effect of AH 5158, pindolol, propranolol, d-propranolol on acute exercise tolerance in angina pectoris (abstract). Br J Pharmacol1973; 47: 673–4P.
108.
MaxwellGM. Effects of alpha- and beta-adrenoceptor antagonist (AH 5158) upon general and coronary hemodynamics of intact dogs. Br J Pharmacol1973; 49: 370–2.
109.
LouisWJBrignellMJMcNeilJJChristophidisNVajdaFJE. Labetalol in hypertension. Lancet1978; 1: 452–3.
110.
HuaASPThomasGWKincaid-SmithP. Scalp tingling in patients on labetalol. Lancet1977; 2: 295.
111.
BaileyRR. Scalp tingling and difficulty in micturition in patients on labetalol. Lancet1977; 2: 720–1.
112.
FinlayAYWaddingtonE. Cutaneous reactions to labetalol. Br Med J1978; 1: 987.
113.
SavageRLLesnaMMucklowJCStevensonCJ. Cutaneous reactions to labetalol. Br Med J1978; 1: 987.
114.
GangeRWJonesEW. Bullous lichen planus caused by labetalol. Br Med J1978; 1: 816–7.
115.
FraisMABayleyTJ. Left ventricular failure with labetalol. Postgrad Med J1979; 55: 567–8.
116.
BaileyRR. Labetalol in the treatment of patients with hypertension and renal functional impairment. Br J Clin Pharmacol1979; 8 (suppl): 135–40s.
117.
CroftonMGabrielR. Pressor response after intravenous labetalol. Br Med J1977; 2: 737.
118.
WilsonJDBoothRJBullickJYCampbellDG. Antimitochondrial antibodies associated with labetalol. Lancet1980; 2: 312–3.
119.
GriffithsIDRichardsonJ. Lupus-type illness associated with labetalol. Br Med J1979; 2: 496–7.
120.
BrownRCCookeJLosowskyMS. SLE syndrome, probably induced by labetalol. Postgrad Med J1981; 57: 189–90.
121.
TeicherARosenthalTKissinESarovaI. Labetalol-induced toxic myopathy. Br Med J1981; 1: 1824–5.
122.
AnderssonOBerglundGHanssonL. Anti-hypertensive action, time of onset and effects on carbohydrate metabolism of labetalol. Br J Clin Pharmacol1976; 3 (suppl): 757–61.
123.
BarbieriCFerrariCCaldaraRCrossignaniRMBertazzoniA. Endocrine and metabolic effects of labetalol in man. J Cardiovasc Pharmacol1981; 3: 986–91.
124.
McGonigleRJSWilliamsLMurphyMJParsonsV. Labetalol and lipids. Lancet1981; 1: 163.
125.
SommersDKDeVilliersLSVanWykMSchoemanHS. The effects of labetalol and Oxprenolol on blood lipids. S Afr Med J1981; 60: 379–80.
126.
DaneshmendTKRobertsCJC. Cimetidine and bioavailability of labetalol. Lancet1981; 1: 565.
127.
HunterJM. Synergism between halothane and labetalol. Anaesthesia1979; 34: 257–9.
128.
ScottDBBuckleyFPDrummondGBLittlewoodDGMacraeWR. Cardiovascular effects of labetalol during halothane anaesthesia. Br J Clin Pharmacol1976; 3 (suppl): 817–21.
129.
New Zealand Hypertensive Study Group. A multicenter study of labetalol in hypertension. NZ Med J1981; 93: 215–8.
