Skip to main content
SpringerLink
Log in

The Pharmacokinetics of Lignocaine and β-Adrenoceptor Antagonists in Patients with Acute Myocardial Infarction

  • Review Article
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

Lignocaine (lidocaine) and β-adrenoceptor antagonists are widely used after acute myocardial infarction. The therapeutic value of these agents depends on the achievement and maintenance of safe and effective plasma concentrations. Lignocaine pharmacokinetics after acute myocardial infarction (MI) are controlled by a number of variables. The single most important is left ventricular function, which affects both volume of distribution and plasma clearance. Other major factors include bodyweight, age, hepatic function, the presence of obesity, and concomitant drug therapy. Lignocaine is extensively bound to α1-acid glycoprotein, a plasma protein which is also an acute phase reactant. Increases in α1-acid glycoprotein concentration occur after an acute MI, decreasing the free fraction of lignocaine in the plasma and consequently decreasing total plasma lignocaine clearance without altering the clearance of non-protein-bound lignocaine. Complex changes in lignocaine disposition occur with long term infusions, and therefore early discontinuation of lignocaine infusions (within 24 hours) should be undertaken whenever possible. Because the risk of ventricular tachyarrhythmia declines rapidly after the onset of an acute MI, lignocaine therapy can be rationally discontinued within 24 hours in most patients.

Lignocaine has a narrow toxic/therapeutic index, so that pharmacokinetic factors are critical in dose selection. In contrast, β-adrenoceptor antagonists’ adverse effects are more related to the presence of predisposing conditions (such as asthma, heart failure, brady-arrhythmias, etc.) than to plasma concentration. The pharmacokinetics of β-adrenoceptor antagonists are important to help assure therapeutic efficacy, to provide information about the anticipated time course of drug action, and to predict the possible role of ancillary drug effects (such as direct membrane action) and loss of cardioselectivity. Lipid solubility is the main determinant of the pharmacokinetic properties of a β-adrenoceptor antagonist. Lipid-soluble agents like propranolol and metoprolol are well absorbed orally, and undergo rapid hepatic metabolism, with important presystemic clearance and a short plasma half-life. Water-soluble drugs like sotalol, atenolol, and nadolol are less well absorbed, and are eliminated more slowly by renal excretion. Clinical assessment of β-adrenoceptor antagonism is more valuable than plasma concentration determinations in evaluating the adequacy of the dose of a particular β-adrenoceptor antagonist.

This review considers the factors that determine the pharmacodynamic and pharmacokinetic properties of lignocaine and β-adrenoceptor antagonists after acute MI. These factors are then related to the principles of rational dose selection for these agents.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Abernethy DR, Greenblatt DJ. Impairment of lidocaine clearance in elderly male subjects. Journal of Cardiovascular Pharmacology 5: 1093–1096, 1983

    PubMed  CAS  Google Scholar 

  • Abernethy DR, Greenblatt DJ. Lidocaine disposition in obesity. American Journal of Cardiology 53: 1183–1186, 1984

    PubMed  CAS  Google Scholar 

  • Adgey AAJ, Allen JD, Geddes JS, et al. Acute phase of myocardial infarction. Lancet 2: 501–504, 1971

    PubMed  CAS  Google Scholar 

  • Al-Asady AH, Bax NDS, Lennard MS, et al. Selectivity of inhibition of lignocaine metabolism by adrenoceptor antagonists. British Journal of Pharmacology 77: 48P, 1982

    Google Scholar 

  • Alderman EL, Kerber RE, Harrison DC. Evaluation of lidocaine resistance in man using intermittent large-dose infusion techniques. American Journal of Cardiology 34: 342–349, 1974

    PubMed  CAS  Google Scholar 

  • Aps C, Bell JA, Jenkins BS, et al. Logical approach to lignocaine therapy. British Medical Journal 1: 13–15, 1975

    Google Scholar 

  • Barchowsky A, Shand DG, Stargel WW, et al. On the role of α1-acid glycoprotein in lignocaine accumulation following myocardial infarction. British Journal of Clinical Pharmacology 13: 411–415, 1982

    PubMed  CAS  Google Scholar 

  • Bauer LA, Brown T, Gibaldi M, et al. Influence of long-term infusions on lidocaine kinetics. Clinical Pharmacology and Therapeutics 31: 433–437, 1982

    PubMed  CAS  Google Scholar 

  • Bax NDS, Lennard MS, Tucker GT. Inhibition of antipyrine metabolism by β-adrenoceptor antagonists. British Journal of Clinical Pharmacology 12: 779–784, 1981

    PubMed  CAS  Google Scholar 

  • Bax NDS, Tucker GT, Woods HF. Lignocaine and indocyanine green kinetics in patients following myocardial infarction. British Journal of Clinical Pharmacology 10: 353–361, 1980

    PubMed  CAS  Google Scholar 

  • Bellet S, Roman L, Kostis JB, et al. Intramuscular lidocaine in the therapy of ventricular arrhythmias. American Journal of Cardiology 27: 291–293, 1971

    PubMed  CAS  Google Scholar 

  • Benfield P, Clissold SP, Brogden RN. Metoprolol: an updated review of its pharmacodynamic and pharmacokinetic properties, and therapeutic efficacy, in hypertension, ischaemic heart disease and related cardiovascular disorders. Drugs 31: 376–429, 1986

    PubMed  CAS  Google Scholar 

  • Bennett MA, Wilner JM, Pentecost BI. Controlled trial of lignocaine in prophylaxis of ventricular arrhythmias complicating myocardial infarction. Lancet 2: 909–911, 1970

    PubMed  CAS  Google Scholar 

  • Benowitz N, Forsyth RP, Melmon KL, et al. Lidocaine disposition kinetics in monkey and man. Clinical Pharmacology and Therapeutics 16: 99–109, 1974

    PubMed  CAS  Google Scholar 

  • Bernstein V, Bernstein M, Griffiths J, et al. Lidocaine intramuscularly in acute myocardial infarction. Journal of the American Medical Association 8: 1027–1031, 1972

    Google Scholar 

  • Bleifield W, Merx W, Heinrich KW, et al. Controlled trial of prophylactic treatment with lidocaine in acute myocardial infarction. European Journal of Clinical Pharmacology 6: 119–127, 1973

    Google Scholar 

  • Blumer J, Strong JM, Atkinson Jr JA. The convulsant potency of lidocaine and its N-dealkylated metabolites. Journal of Pharmacology and Experimental Therapeutics 1: 31–36, 1973

    Google Scholar 

  • Bobik A, Jennings GL, Ashley P, et al. Timolol pharmacokinetics and effects on heart rate and blood pressure after acute and chronic administration. European Journal of Clinical Pharmacology 16: 243–249, 1979

    CAS  Google Scholar 

  • Boudoulas H, Beaver BM, Kates RE, et al. Pharmacodynamics of intropic and chronotropic responses to oral therapy with propranolol. Chest 73: 146–153, 1978

    PubMed  CAS  Google Scholar 

  • Boudoulas H, Lewis RP, Kates RE, et al. Hypersensitivity to adrenergic stimulation after propranolol withdrawal in normal subjects. Annals of Internal Medicine 87: 433–436, 1977b

    PubMed  CAS  Google Scholar 

  • Boudoulas H, Schaal SF, Lewis RP, et al. Negative inotropic effect of lidocaine in patients with coronary artery disease and normal subjects. Chest 71: 170–175, 1977a

    PubMed  CAS  Google Scholar 

  • Boyes RN, Scott DB, Jebson PJ, et al. Pharmacokinetics of lidocaine in man. Clinical Pharmacology and Therapeutics 12: 105–115, 1971

    PubMed  CAS  Google Scholar 

  • Branch RA, Shand DG, Wilkinson GR, et al. The reduction of lidocaine clearance by dipropranolol: an example of hemodynamic drug interaction. Journal of Pharmacology and Experimental Therapeutics 184: 515–519, 1973

    PubMed  CAS  Google Scholar 

  • Bromage PR, Robson JG. Concentrations of lignocaine in the blood after intravenous, intramuscular epidural and endotracheal administration. Anaesthesia 16: 461–478, 1961

    PubMed  CAS  Google Scholar 

  • Buckman K, Claiborne K, deGuzman M, et al. Lidocaine efficacy and toxicity assessed by a new, rapid method. Clinical Pharmacology and Therapeutics 28: 177–181, 1980

    PubMed  CAS  Google Scholar 

  • Burney RG, DiFazio CA, Peach MJ, et al. Anti-arrhythmic effects of lidocaine metabolites. American Heart Journal 88: 765–769, 1974

    PubMed  CAS  Google Scholar 

  • Chopra MP, Thadani U, Portal RW, et al. Lignocaine therapy for ventricular ectopic activity after acute myocardial infarction: a double-blind trial. British Medical Journal 3: 668–670, 1971

    PubMed  CAS  Google Scholar 

  • Chow MSS, Ronfeld RA, Ruffett D, et al. Lidocaine pharmacokinetics during cardiac arrest and external cardiopulmonary resuscitation. American Heart Journal 102: 799–801, 1981

    PubMed  CAS  Google Scholar 

  • Church G, Biern R. Prophylactic lidocaine in acute myocardial infarction. Abstract. Circulation 45, 46 (Suppl. 2): 11–139, 1972

    Google Scholar 

  • Cohen LS, Rosenthal JE, Horner DW, et al. Plasma levels of lidocaine after intramuscular administration. American Journal of Cardiology 29: 520–523, 1972

    PubMed  CAS  Google Scholar 

  • Collinsworth KA, Kaiman SM, Harrison DC. The clinical pharmacology of lidocaine as an antiarrhythmic drug. Circulation 50: 1217–1231, 1974

    PubMed  CAS  Google Scholar 

  • Collinsworth KA, Strong JM, Atkinson Jr JA, et al. Pharmacokinetics and metabolism of lidocaine in patients with renal failure. Clinical Pharmacology and Therapeutics 18: 59–64, 1975

    PubMed  CAS  Google Scholar 

  • Conrad KA, Byers JM, Finley PR, et al. Lidocaine elimination: effects of metoprolol and propranolol. Clinical Pharmacology and Therapeutics 33: 133–138, 1983

    PubMed  CAS  Google Scholar 

  • Conway FJ, Fitzgerald JD, McAinsh J, et al. Human pharmacokinetic and pharmacodynamic studies on atenolol (ICI 66,082), a new cardioselective β-adrenoceptor blocking drug. British Journal of Clinical Pharmacology 3: 267–272, 1976

    PubMed  CAS  Google Scholar 

  • Cusson J, Nattel S, Matthews C, et al. Age-dependent lidocaine disposition in patients with acute myocardial infarction. Clinical Pharmacology and Therapeutics 37: 381–386, 1985

    PubMed  CAS  Google Scholar 

  • Danahy DT, Aronow WS. Lidocaine-induced cardiac rate changes in atrial fibrillation and atrial flutter. American Heart Journal 95: 474–482, 1978

    PubMed  CAS  Google Scholar 

  • Darby S, Bennett MA, Cruickshank JC, et al. Trial of combined intramuscular and intravenous lignocaine in prophylaxis of ventricular tachyarrhythmias. Lancet 1: 817–819, 1972

    PubMed  CAS  Google Scholar 

  • Davison R, Parker M, Atkinson Jr JA. Excessive serum lidocaine levels during maintenance infusions: mechanisms and prevention. American Heart Journal 104: 203–208, 1982

    PubMed  CAS  Google Scholar 

  • deBoer AG, Breimer DD, Mattie H, et al. Rectal bioavailability of lidocaine in man: partial avoidance of ‘first-pass’ metabolism. Clinical Pharmacology and Therapeutics 26: 701–709, 1979

    CAS  Google Scholar 

  • Deglin SM, Deglin JM, Wurtzbacher J, et al. Rapid serum lidocaine determination in the coronary care unit. Journal of the American Medical Association 244: 571–573, 1980

    PubMed  CAS  Google Scholar 

  • Dhingra RC, Prakash C, Cummings JM, et al. Electrophysiologic effects of lidocaine on sinus node and atrium in patients with and without sinoatrial dysfunction. Circulation 57: 448–454, 1978

    PubMed  CAS  Google Scholar 

  • Drayer DE, Lorenzo B, Werns S, et al. Plasma levels, protein binding and elimination data of lidocaine and active metabolites in cardiac patients of various ages. Clinical Pharmacology and Therapeutics 34: 14–22, 1983

    PubMed  CAS  Google Scholar 

  • Duff JH, Roden DM, Brorson L, et al. Electrophysiologic actions of high plasma concentrations of propranolol in human subjects. Journal of the American College of Cardiology 2: 1134–1140, 1983

    PubMed  CAS  Google Scholar 

  • Euler DE, Nattel S, Spear JF, et al. Effect of sympathetic tone on ventricular arrhythmias during circumflex coronary occlusion. American Journal of Physiology 249: H1045–H1050, 1985

    PubMed  CAS  Google Scholar 

  • Feely J, Guy E. Lack of effect of ranitidine on the disposition of lignocaine. British Journal of Clinical Pharmacology 15: 378–379, 1983

    PubMed  CAS  Google Scholar 

  • Feely J, Wilkinson GR, McAllister B, et al. Increased toxicity and reduced clearance of lidocaine by cimetidine. Annals of Internal Medicine 96: 592–594, 1982

    PubMed  CAS  Google Scholar 

  • Fehmers MCO, Dunning AJ. Intramuscularly and orally administered lidocaine in the treatment of ventricular arrhythmias in acute myocardial infarction. American Journal of Cardiology 29: 514–519, 1972

    PubMed  CAS  Google Scholar 

  • Foldes FF, Molloy R, McNall PG, et al. Comparison of toxicity of intravenously given local anesthetic agents in man. Journal of the American Medical Association 172: 1493–1498, 1960

    PubMed  CAS  Google Scholar 

  • Fredrick DS, Boersma RB. Lidocaine infusions: effect of duration and method of discontinuation on recurrence of arrhythmias and pharmacokinetic variables. American Journal of Hospital Pharmacy 36: 778–781, 1979

    PubMed  CAS  Google Scholar 

  • Freestone S, Silas JH, Lennard MS, et al. Comparison of two long-acting preparations of metoprolol with conventional metoprolol and atenolol in healthy men during chronic dosing. British Journal of Clinical Pharmacology 14: 713–718, 1982

    PubMed  CAS  Google Scholar 

  • Frishman W, Silverman R, Strom J, et al. Clinical pharmacology of the new beta-adrenergic blocking drugs: Part 4: adverse effects: choosing a β-adrenoreceptor blocker. American Heart Journal 98: 256–263, 1979

    PubMed  CAS  Google Scholar 

  • Galeazzi RL, Gugger M, Weidmann P. Beta blockade with pindolol: differential cardiac and renal effects despite similar plasma kinetics in normal and uremic man. Kidney International 15: 661–668, 1979

    PubMed  CAS  Google Scholar 

  • Gengo FM, Green JA. Beta-blockers. In Evans et al. (Eds) Applied pharmacokinetics: principles of therapeutic drug monitoring, pp. 735–781, Applied Therapeutics, Inc., Spokane, 1986

    Google Scholar 

  • Gengo FM, Huntoon L, McHugh WB. Lipid-soluble and water-soluble β-blockers: comparison of the CNS depressant effect. Archives of Internal Medicine 147: 39–43, 1987

    PubMed  CAS  Google Scholar 

  • Gianelly R, von der Groeben JO, Spivack AP, et al. Effect of lidocaine on ventricular arrhythmias in patients with coronary heart disease. New England Journal of Medicine 277: 1215–1219, 1967

    PubMed  CAS  Google Scholar 

  • Gillis AM, Kates R. Influence of protein binding on the myocardial uptake and pharmacodynamics of propafenone. Journal of Cardiovascular Pharmacology 8: 1163–1167, 1986

    PubMed  CAS  Google Scholar 

  • Goldman L, Batsford WP. Risk-benefit stratification as a guide to lidocaine prophylaxis of primary ventricular fibrillation in acute myocardial infarction: an analytic review. Yale Journal of Biology and Medicine 52: 455–466, 1979

    PubMed  CAS  Google Scholar 

  • Greenblatt DJ, Franke K, Huffman DH. Impariment of antipyrine clearance in humans by propranolol. Circulation 57: 1161–1164, 1978

    PubMed  CAS  Google Scholar 

  • Gupta PK, Lichstein E, Chadda KD. Lidocaine-induced heart block in patients with bundle branch block. American Journal of Cardiology 33: 487–492, 1974

    PubMed  CAS  Google Scholar 

  • Halkin H, Meffin P, Melmon KL, et al. Influence of congestive heart failure on blood levels of lidocaine and its active monodeethylated metabolite. Clinical Pharmacology and Therapeutics 17: 669–676, 1975

    PubMed  CAS  Google Scholar 

  • Herlitz J. The Miami trial: development of myocardial infarction. Drugs 29 (Suppl. 1): 3, 1985

    Google Scholar 

  • Herlitz J, Hjalmarson A, Waagstein F. Beta blockade and chest pain in acute myocardial infarction. American Heart Journal 112: 1120–1126, 1986

    PubMed  CAS  Google Scholar 

  • Huang JD, Øie S: Effect of altered disopyramide binding on its pharmacologic response in rabbits. Journal of Pharmacology and Experimental Therapeutics 223: 469–471, 1982

    PubMed  CAS  Google Scholar 

  • Huet PM, LeLorier J, Pomier G, et al. Bioavailability of lidocaine in normal volunteers and cirrhotic patients. Abstract. Gastroenterology 75: 969, 1978

    Google Scholar 

  • Ishizaki T, Tawara K, Oyama Y, et al. Clinical pharmacologic observations on timolol. I. Disposition and effect in relation to plasma level in normal individuals. Journal of Clinical Pharmacology 18: 511–518, 1978

    PubMed  CAS  Google Scholar 

  • ISIS-1 Collaborative Group: Randomised trial of intravenous atenolol among 16,027 cases of suspected acute myocardial infarction. Lancet 2: 57–66, 1986

    Google Scholar 

  • Jewitt DE, Kishon Y, Thomas M. Lignocaine in the management of arrhythmias after acute myocardial infarction. Lancet 1: 266–270, 1968

    Google Scholar 

  • Joel SE, Bryson SM, Small M, et al. Kinetic predictive techniques applied to lignocaine therapeutic drug monitoring. Therapeutic Drug Monitoring 5: 271–277, 1983

    PubMed  CAS  Google Scholar 

  • Johnsson G, Regårdh CG. Clinical pharmacokinetics of β-adrenoceptor blocking drugs. Clinical Pharmacokinetics 1: 233–263, 1976

    PubMed  CAS  Google Scholar 

  • Jordo L, Attman PO, Aurell M, et al. Pharmacokinetic and pharmacodynamic properties of metoprolol in patients with impaired renal function. Clinical Pharmacokinetics 5: 169–180, 1980

    PubMed  CAS  Google Scholar 

  • Jordo L, Johnsson G, Lundborg P, et al. Pharmacokinetics of lidocaine in healthy individuals pretreated with multiple doses of metoprolol. International Journal of Clinical Pharmacology, Therapy, and Toxicology 22: 312–315, 1984

    PubMed  CAS  Google Scholar 

  • Keenaghan JB, Boyes RN. The tissue distribution, metabolism and excretion of lidocaine in rats, guinea pigs, dogs and man. Journal of Pharmacology and Experimental Therapeutics 180: 454–463, 1972

    PubMed  CAS  Google Scholar 

  • Kirch W, Schafer-Korting M, et al. Clinical experience with atenolol in patients with chronic liver disease. Journal of Clinical Pharmacology 23: 171–177, 1983

    PubMed  CAS  Google Scholar 

  • Knapp AB, Maguire W, Keren G, et al. The cimetidine-lidocaine interaction. Annals of Internal Medicine 98: 174–177, 1983

    PubMed  CAS  Google Scholar 

  • Koster RW, Dunning AJ. Intra-muscular lidocaine for prevention of lethal arrhythmias in the prehospitalization phase of acute myocardial infarction. New England Journal of Medicine 313: 1105–1110, 1985

    PubMed  CAS  Google Scholar 

  • Krüger-Thiemer E. Continuous intravenous infusion and multicompartment accumulation. European Journal of Pharmacology 4: 317–324, 1968

    PubMed  Google Scholar 

  • LeLorier J, Grenon D, Latour Y, et al. Pharmacokinetics of lidocaine after prolonged intravenous infusions in uncomplicated myocardial infarction. Annals of Internal Medicine 87: 700–702, 1977a

    PubMed  CAS  Google Scholar 

  • LeLorier J, Moisan R, Gagné J, et al. Effect of the duration of infusion on the disposition of lidocaine in dogs. Journal of Pharmacology and Experimental Therapeutics 203: 507–511, 1977b

    PubMed  CAS  Google Scholar 

  • Levy R, Charuzi Y, Mandel W. Lignocaine: a new technique for intravenous administration. British Heart Journal 39: 1026–1028, 1977

    PubMed  CAS  Google Scholar 

  • Lewis RV, McDevitt DG. Adverse reactions and interactions with β-adrenoceptor blocking drugs. Medical Toxicology 1: 343–361, 1986

    PubMed  CAS  Google Scholar 

  • Lie KI, Welleng HJ, vanCapelle FJ, Durrer D. Lidocaine in the prevention of primary ventricular fibrillation. New England Journal of Medicine 291: 1324–1326, 1974

    PubMed  CAS  Google Scholar 

  • Likoff W. Cardiac arrhythmias complicating surgery. American Journal of Cardiology 3: 427–429, 1959

    PubMed  CAS  Google Scholar 

  • Lown B, Fakhro A, Hood WB, et al. The coronary care unit: new perspectives and directions. Journal of the American Medical Association 199: 188–198, 1967

    PubMed  CAS  Google Scholar 

  • Mather LE, Thomas J. Metabolism of lidocaine in man. Life Science 11: 915–919, 1972

    CAS  Google Scholar 

  • Marriott HJL, Bieza CF. Alarming ventricular acceleration after lidocaine administration. Chest 61: 682–683, 1972

    PubMed  CAS  Google Scholar 

  • McDevitt DG, Frisk-Holmberg M, Hollifield JW, et al. Plasma binding and the affinity of propranolol for a beta receptor in man. Clinical Pharmacology and Therapeutics 20: 152–157, 1976

    PubMed  CAS  Google Scholar 

  • McNamara PJ, Slaughter RL, Pieper JA, et al. Factors influencing serum protein binding of lidocaine in humans. Anesthesia and Analgesia 60: 395–400, 1981

    PubMed  CAS  Google Scholar 

  • Meier J. Pharmacokinetic comparison of pindolol with other beta-adrenoceptor-blocking agents. American Heart Journal 104: 364–373, 1982

    PubMed  CAS  Google Scholar 

  • Melander A, Danielson K, Schersten B, et al. Enhancement of the bioavailability of propranolol and metoprolol by food. Clinical Pharmacology and Therapeutics 22: 108–113, 1977

    PubMed  CAS  Google Scholar 

  • Miller RR, Olson HG, Amsterdam EA, et al. Propranolol-withdrawal rebound phenomenon: exacerbations of coronary events after abrupt cessation of antianginal therapy. New England Journal of Medicine 293: 416–418, 1975

    PubMed  CAS  Google Scholar 

  • Miners JO, Wing LMH, Lillywhite KJ, et al. Failure of ‘therapeutic’ doses of β-adrenoceptor antagonists to alter the disposition of tolbutamide and lignocaine. British Journal of Clinical Pharmacology 18: 853–860, 1984

    PubMed  CAS  Google Scholar 

  • Mogensen L. Ventricular tachyarrhythmias and lignocaine prophylaxis in acute myocardial infarction. Acta Medica Scandinavica (Suppl.) 513: 1–80, 1970

    CAS  Google Scholar 

  • Morris KG, Higginbotham B, Coleman RE, et al. Comparison of high dose and medium-dose propranolol in the relief of exercise-induced myocardial ischemia. American Journal of Cardiology 52: 7–13, 1983

    PubMed  CAS  Google Scholar 

  • Mullane JF, Kaufman J, Dvornik D, et al. Propranolol dosage, plasma concentration, and beta-blockade. Clinical Pharmacology and Therapeutics 32: 692–700, 1982

    PubMed  CAS  Google Scholar 

  • Nation RL, Triggs EJ, Selig M. Lignocaine kinetics in cardiac patients and aged subjects. British Journal of Clinical Pharmacology 4: 439–448, 1977

    PubMed  CAS  Google Scholar 

  • Nattel S, Pedersen DH, Zipes DP. Alterations in regional myocardial distribution and arrhythmogenic effects of aprinidine produced by coronary artery occlusion in the dog. Cardiovascular Research 15: 80–85, 1981

    PubMed  CAS  Google Scholar 

  • Nattel S, Rangno RE, Van Loon G. Mechanism of propranolol withdrawal phenomena. Circulation 59: 1158–1164, 1979b

    PubMed  CAS  Google Scholar 

  • Nattel S, Rikenberger R, Lehrman LL, et al. Therapeutic blood lidocaine concentrations after local anesthesia for cardiac electrophysiologic studies. New England Journal of Medicine 301: 418–420, 1979a

    PubMed  CAS  Google Scholar 

  • Nattel S, Shanks J, Rangno RE. Propranolol withdrawal. Annals of Internal Medicine 89: 288, 1978

    PubMed  CAS  Google Scholar 

  • Nelson SD, Garland WA, Breck GD, et al. Quantification of lidocaine and several metabolites utilizing chemical-ionization mass spectrometry and stable isotope labeling. Journal of Pharmaceutical Sciences 66: 1180–1190, 1977

    PubMed  CAS  Google Scholar 

  • Norris RM. β-Adrenoceptor blockers: an update on their role in acute myocardial infarction. Drugs 29: 97–104, 1985

    PubMed  CAS  Google Scholar 

  • Norris RM, Barnaby PF, Brown MA, et al. Prevention of ventricular fibrillation during acute myocardial infarction by intravenous propranolol. Lancet 2: 883–886, 1984

    PubMed  CAS  Google Scholar 

  • Ochs HR, Carstens G, Greenblatt DJ. Reduction in lidocaine clearance during continuous infusion and by coadministration of propranolol. New England Journal of Medicine 303: 373–377, 1980

    PubMed  CAS  Google Scholar 

  • Ochs HR, Skanderra D, Abernethy DR, et al. Effect of penbutolol on lidocaine kinetics. Arzneimittel-Forschung 33: 1680–1681, 1983

    PubMed  CAS  Google Scholar 

  • Ohnhaus EE, Münch U, Meier J. Elimination of pindolol in liver disease. European Journal of Clinical Pharmacology 22: 247–251, 1982

    PubMed  CAS  Google Scholar 

  • Ohnhaus EE, Nuesch E, Meier J, et al. Pharmacokinetics of unlabelled and 14C-labelled pindolol in uraemia. European Journal of Clinical Pharmacology 7: 25–29, 1974

    PubMed  CAS  Google Scholar 

  • Øie S, Levy G. Relationship between renal function and elimination kinetics of pindolol in man. European Journal of Clinical Pharmacology 9: 115–116, 1975

    PubMed  Google Scholar 

  • Oltmanns D, Lübben C, Pentz R, et al. Plasma levels of lidocaine after intramuscular injection and subsequent infusion in patients with acute myocardial infarction. International Journal of Clinical Pharmacology, Therapy, and Toxicology 20: 582–584, 1982

    PubMed  CAS  Google Scholar 

  • Perucca E, Richens A. Reduction of oral bioavailability of lignocaine by induction of first pass metabolism in epileptic patients. British Journal of Clinical Pharmacology 8: 21–31, 1979

    PubMed  CAS  Google Scholar 

  • Pessayre D, Lebrec D, Descatoire V, et al. Mechanism for reduced drug clearance in patients with cirrhosis. Gastroenterology 74: 566–571, 1978

    PubMed  CAS  Google Scholar 

  • Pfeifer JH, Greenblatt DJ, Koch-Weser J. Clinical use and toxicity of intravenous lidocaine. Amerian Heart Journal 92: 168–173, 1976

    CAS  Google Scholar 

  • Piafsky KM, Borgõ O, Odar-Cederlöf I, et al. Increased plasma protein binding of propranolol and chlorpromazine mediated by disease-induced elevations of plasma α1 acid glycoprotein. New England Journal of Medicine 299: 1435–1439, 1978

    PubMed  CAS  Google Scholar 

  • Piafsky KM, Knoppert D. Binding of local anesthetics to α1 acid glycoprotein. Clinical Research 36: 836a, 1978

    Google Scholar 

  • Pieper JA, Rodman JH. Lidocaine. In Evans et al. (Eds) Applied pharmacokinetics: principles of therapeutic drug monitoring, 2nd ed., Applied Therapeutics Inc., Spokane, 1986

    Google Scholar 

  • Pieper JA, Wyman MG, Goldreyer BN, et al. Lidocaine toxicity: effects of total versus free lidocaine concentrations. Abstract. Circulation 62 (part ii): III–181, 1980

    Google Scholar 

  • Pine M, Favrot L, Smith S, et al. Correlation of plasma propranolol concentration with therapeutic response in patients with angina pectoris. Circulation 52: 886–893, 1975

    PubMed  CAS  Google Scholar 

  • Pitt A, Lipp H, Anderson ST. Lignocaine given prophylactically to patients with acute myocardial infarction. Lancet 1: 612–616, 1971

    PubMed  CAS  Google Scholar 

  • Prescott F, Adjepon-Yamoah KK, Talbot RG. Impaired lignocaine metabolism in patients with myocardial infarction and cardiac failure. British Medical Journal 1: 939–941, 1976

    PubMed  CAS  Google Scholar 

  • Rangno RE, Langlois S, Lutterodt A: Metoprolol withdrawal phenomena: mechanism and prevention. Clinical Pharmacology and Therapeutics 31: 8–15, 1982a

    PubMed  CAS  Google Scholar 

  • Rango RE, Nattel S, Lutterodt A. Prevention of propranolol withdrawal mechanism by prolonged small dose propranolol schedule. American Journal of Cardiology 49: 828–833, 1982b

    Google Scholar 

  • Regårdh CG, Jordo L, Ervik M, et al. Pharmacokinetics of metoprolol in patients with hepatic cirrhosis. Clinical Pharmacokinetics of β-adrenoceptor antagonists: an update. Clinical Pharmacokinetics 6: 375–388, 1981

    PubMed  Google Scholar 

  • Riddell JG, McAllister CB, Wilkinson GR, et al. A new method for constant plasma drug concentrations application to lidocaine. Annals of Internal Medicine 100: 25–28, 1984

    PubMed  CAS  Google Scholar 

  • Riddell JG, Harron DWG, Shanks RG. Clinical pharmacokinetics of β-adrenoceptor antagonists: an update. Clinical Pharmacokinetics 12: 305–320, 1987

    PubMed  CAS  Google Scholar 

  • Rodman JH, Jelliffe RW, Kolb E, et al. Clinical studies with computer assisted initial lidocaine therapy. Archives of Internal Medicine 144: 703–709, 1984

    PubMed  CAS  Google Scholar 

  • Routledge PA, Barchowsky BS, Bjornsson TD, et al. Lidocaine plasma protein binding. Clinical Pharmacology and Therapeutics 27: 347–351, 1980a

    PubMed  CAS  Google Scholar 

  • Routledge PA, Shand DG. Clinical pharmacokinetics of propranolol. Clinical Pharmacokinetics 4: 73–90, 1979

    PubMed  CAS  Google Scholar 

  • Routledge PA, Shand DG, Barchowsky BS, et al. Relationship between α1-acid glycoprotein and lidocaine disposition in myocardial infarction. Clinical Pharmacology and Therapeutics 30: 154–157, 1981

    PubMed  CAS  Google Scholar 

  • Routledge PA, Stargel WW, Barchowsky BS, et al. Control of lidocaine therapy: new perspectives. Therapeutic Drug Monitoring 4: 265–270, 1982

    PubMed  CAS  Google Scholar 

  • Routledge PA, Stargel WW, Wagener GS, et al. Increased alpha1-acid glycoprotein and lidocaine disposition in myocardial infarction. Annals of Internal Medicine 93: 701–704, 1980b

    PubMed  CAS  Google Scholar 

  • Rowland M, Thomson PD, Guichard A, et al. Disposition kinetics of lidocaine in normal subjects. Annals of the New York Academy of Sciences 179: 383–398, 1971

    PubMed  CAS  Google Scholar 

  • Rydén L, Ariniego R, Arnman K, et al. A double-blind trial of metoprolol in acute myocardial infarction. New England Journal of Medicine 308: 614–618, 1983

    PubMed  Google Scholar 

  • Rydén L, Waldenström A, Ehn L, et al. Comparison between effectiveness of intramuscular and intravenous lignocaine on ventricular arrhythmia complicating acute myocardial infarction. British Heart Journal 35: 1124–1131, 1973

    PubMed  Google Scholar 

  • Salem SA, McDevitt DG. Central effects of beta-adrenoceptor antagonists. Clinical Pharmacology and Therapeutics 33: 52–57, 1983

    PubMed  CAS  Google Scholar 

  • Sawyer DR, Ludden TM, Crawford MH. Continuous infusion of lidocaine in patients with cardiac arrhythmias-unpredictability of plasma concentrations. Archives of Internal Medicine 141: 43–45, 1981

    PubMed  CAS  Google Scholar 

  • Schneck DW, Luderer JR, Davis D, et al. Effects of nadolol and propranolol on plasma lidocaine clearance. Clinical Pharmacology and Therapeutics 36: 584–587, 1984

    PubMed  CAS  Google Scholar 

  • Schwartz ML, Meyer MB, Covino BG, et al. Antiarrhythmic effectiveness of intramuscular lidocaine: influence of different injection sites. Journal of Clinical Pharmacology 14: 77–83, 1974

    PubMed  CAS  Google Scholar 

  • Scott DB, Jebson PJ, Godman MJ, et al. Oral lignocaine. Lancet 1: 93, 1970

    PubMed  CAS  Google Scholar 

  • Sebaldt RJ, Nattel S, Kreeft JH, et al. Lidocaine therapy with an exponentially declining infusion. Annals of Internal Medicine 101: 632–634, 1984

    PubMed  CAS  Google Scholar 

  • Seiler KU, Schuster KJ, Meyer GJ, et al. The pharmacokinetics of metoprolol and its metabolites in dialysis patients. Clinical Pharmacokinetics 5: 192–198, 1980

    PubMed  CAS  Google Scholar 

  • Shand DG, Kornhauser DM, Wilkinson GR. Effects of route of administration and blood flow on hepatic drug elimination. Journal of Pharmacology and Experimental Therapeutics 195: 424–432, 1975

    PubMed  CAS  Google Scholar 

  • Sheridan DJ, Crawford L, Rawlins MD, et al. Antiarrhythmic action of lignocaine in early myocardial infarction. Lancet 1: 824–825, 1977

    PubMed  CAS  Google Scholar 

  • Singh JB, Kocot L. A controlled trial of intramuscular lidocaine in the prevention of premature ventricular contractions associated with acute myocardial infarction. Amerian Heart Journal 91: 430–436, 1976

    CAS  Google Scholar 

  • Southworth JL, McKusick VA, Pierce EC, et al. Ventricular fibrillation precipitated by cardiac catheterization. Journal of the American Medical Association 143: 717–720, 1950

    PubMed  CAS  Google Scholar 

  • Stargel WW, Shand DG, Routledge PA, et al. Clinical comparison of rapid infusion and multiple injection methods for lidocaine loading. American Heart Journal 102: 872–875, 1981

    PubMed  CAS  Google Scholar 

  • Stenson RE, Constantino RT, Harrison DC. Interrelationships of hepatic blood flow, cardiac output, and blood levels of lidocaine in man. Circulation 43: 205–211, 1971

    PubMed  CAS  Google Scholar 

  • Strong JM, Mayfield DE, Atkinson Jr JA, et al. Pharmacological activity, metabolism, and pharmacokinetics of glycinexylidide. Clinical Pharmacology and Therapeutics 17: 184–194, 1975

    PubMed  CAS  Google Scholar 

  • Suzuki T, Fujita S, Kawai R. Precursor-metabolite interaction in the metabolism of lidocaine. Journal of Pharmacological Sciences 73: 136–138, 1984

    CAS  Google Scholar 

  • Svendsen TL, Tango M, Waldorf S, et al. Effects of propranolol and pindolol on plasma lignocaine clearance in man. British Journal of Clinical Pharmacology 13: 223S–226S, 1982

    PubMed  CAS  Google Scholar 

  • Taylor EA, Jefferson D, Carroll JD, et al. Cerebrospinal fluid concentrations of propranolol, pindolol and atenolol in man: evidence for central actions of β-adrenoceptor antagonists. British Journal of Clinical Pharmacology 12: 549–559, 1981

    PubMed  CAS  Google Scholar 

  • Thadani U, Parker JO. Propranolol in the treatment of angina pectoris. Circulation 59: 571–579, 1979

    PubMed  CAS  Google Scholar 

  • The Miami Trial Research Group: metoprolol in acute myocardial infarction (Miami): a randomised placebo-controlled international trial. European Heart Journal 6: 199–226, 1985

    Google Scholar 

  • Thomson PD, Melmon KL, Richardson JA, et al. Lidocaine pharmacokinetics in advanced heart failure, liver disease and renal failure in humans. Annals of Internal Medicine 78: 499–508, 1973

    PubMed  CAS  Google Scholar 

  • Valentine PA, Frew JL, Mashford ML, et al. Lidocaine in the prevention of sudden death in the pre-hospital phase of acute infarction. New England Journal of Medicine 291: 1327–1331, 1974

    PubMed  CAS  Google Scholar 

  • Vedin JA, Kristianson JK, Wilhemsson CE. Pharmacokinetics of intravenous timolol in patients with acute myocardial infarction and in healthy volunteers. European Journal of Clinical Pharmacology 23: 43–47, 1982

    PubMed  CAS  Google Scholar 

  • Vestal RE. Drug use in the elderly: a review of problems and special considerations. Drugs 16: 358–382, 1978

    PubMed  CAS  Google Scholar 

  • Vozeh S, Berger M, Wenk M, et al. Rapid prediction of individual dosage requirements for lignocaine. Clinical Pharmacokinetics 9: 354–363, 1984

    PubMed  CAS  Google Scholar 

  • Vozeh S, Hillman R, Wandell M, et al. Computer-assisted drug assay interpretation based on bayesian estimation of individual pharmacokinetics: application to lidocaine. Therapeutic Drug Monitoring 7: 66–73, 1985

    PubMed  CAS  Google Scholar 

  • Vu VT, Chen CP. Effects of dl-propranolol on lidocaine disposition in the perfused rat liver. Drug Metabolism and Disposition 10: 350–355, 1982

    PubMed  CAS  Google Scholar 

  • Waagstein F (for the Miami Trial Research Group). The Miami trial: treatment of chest pain. Drugs 29 (Suppl. 1): 3–4, 1985

    Google Scholar 

  • Waiden RJ, Bhattacharjee P, Tomlinson B, et al. The effect of intrinsic sympathomimetic activity on β-receptor responsiveness after β-adrenoceptor blockade withdrawal. British Journal of Clinical Pharmacology 13: 259S–364S, 1982

    Google Scholar 

  • Wang T, Bergstrand RH, Thompson KA, et al. Concentration-dependent pharmacologic properties of sotalol. American Journal of Cardiology 57: 1160–1165, 1986

    PubMed  CAS  Google Scholar 

  • Weiss WA. Intravenous use of lidocaine for ventricular arrhythmias. Anesthesia and Analgesia 39: 369–381, 1960

    PubMed  CAS  Google Scholar 

  • Wilhelmsson C (for the Miami Trial Research Group). The Miami Trial: methodology and patient population. Drugs 29 (Suppl. 1): 2–6, 1985

    Google Scholar 

  • Wilkinson GR, Shand DG. A physiological approach to hepatic drug clearance. Clinical Pharmacology and Therapeutics 18: 377–390, 1975

    PubMed  CAS  Google Scholar 

  • Wilkinson R. β-Blockers and renal function. Drugs 23: 195–206, 1982

    PubMed  CAS  Google Scholar 

  • Williams RL, Blaschike TF, Meffin PJ, et al. Influence of viral hepatitis on the disposition of two compounds with high hepatic clearance: lidocaine and indocyanine green. Clinical Pharmacology and Therapeutics 20: 290–299, 1976

    PubMed  CAS  Google Scholar 

  • Wing LMH, Miners JO, Birkett DJ, et al. Lidocaine disposition: sex differences and effects of cimetidine. Clinical Pharmacology and Therapeutics 35: 695–701, 1984

    PubMed  CAS  Google Scholar 

  • Wong BYS, Hurwitz A. Simple method for maintaining serum lidocaine levels in the therapeutic range. Archives of Internal Medicine 145: 1588–1591, 1985

    PubMed  CAS  Google Scholar 

  • Wood AJJ, Kornhauser DM, Wilkinson GR, et al. The influence of cirrhosis on steady-state blood concentrations of unbound propranolol after oral administration. Clinical Pharmacokinetics 3: 478–487, 1978

    PubMed  CAS  Google Scholar 

  • Wyman MG, Lalka D, Hammersmith L, et al. Multiple bolus technique for lidocaine administration during the first hours of an acute myocardial infarction. American Journal of Cardiology 41: 313–317, 1978

    PubMed  CAS  Google Scholar 

  • Wyman MG, Slaughter RL, Faroino DA, et al. Multiple bolus technique for lidocaine in acute ischemic heart disease. II. Treatment of refractory ventricular arrythmias and the pharmacokinetic significance of severe left ventricular failure. Journal of the American College of Cardiology 2: 764–769, 1983

    PubMed  CAS  Google Scholar 

  • Wyse DG, Kellen J, Tarn Y, et al. Increased efficacy and toxicity of lidocaine in patients on beta blockers. Abstract. Circulation 74: 11–43, 1986

    Google Scholar 

  • Zener JC, Kerber RE, Spivack AP, et al. Blood lidocaine levels and kinetics following high-dose intramuscular administration. Circulation 47: 984–988, 1973

    PubMed  CAS  Google Scholar 

  • Zito RA, Reid PR. Lidocaine kinetics predicted by indocyanine green clearance. New England Journal of Medicine 298: 1160–1163, 1978

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pharmacology and Therapeutics and Medicine, McGill University, Canada

    Stanley Nattel, Guy Gagne & Marie Pineau

  2. Department of Medicine and Pharmacy, Montreal General Hospital, Canada

    Stanley Nattel, Guy Gagne & Marie Pineau

  3. Department of Medicine and Research Institute, Montreal Heart Institute, Montreal, Canada

    Stanley Nattel, Guy Gagne & Marie Pineau

Authors
  1. Stanley Nattel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Guy Gagne
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Marie Pineau
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nattel, S., Gagne, G. & Pineau, M. The Pharmacokinetics of Lignocaine and β-Adrenoceptor Antagonists in Patients with Acute Myocardial Infarction. Clin-Pharmacokinet 13, 293–316 (1987). https://doi.org/10.2165/00003088-198713050-00002

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-198713050-00002

Keywords

Search

Navigation