Abstract
In the drug therapy of cardiac emergencies, it is necessary to rapidly achieve therapeutic drug concentrations and adjust drug dose as the patient’s clinical status changes. Cardiac dysfunction is often present and may alter drug pharmacokinetics. Circulatory failure causes sympathetically mediated vasoconstriction in most tissues, with relative sparing of the brain and heart due to autoregulation. Blood flow to vasoconstricted tissues is reduced, and the available cardiac output is redistributed so that the heart and brain receive a greater fraction. Drug distribution to tissues is therefore slowed, and the initial concentration of drug in blood is higher when circulatory failure is present than when it is absent. This higher blood concentration is reflected by higher concentrations of drug in the brain and heart, which are relatively well perfused. Initial doses of many drugs need to be reduced in patients with circulatory failure to prevent cardiac or central nervous system toxicity.
Cardiac output is markedly diminished during cardiopulmonary resuscitation (CPR), but blood flow distribution is qualitatively similar to that of circulatory failure with spontaneous circulation. Pneumatic trousers increase lower extremity vascular resistance and may produce a similar redistribution of blood flow. Drug distribution during the use of CPR or pneumatic trousers should be similar to that of circulatory failure with spontaneous circulation, but few data are available to guide drug dosing during the use of these interventions. Animal data suggest that the central volume of distribution of some drugs during CPR may be as small as one-tenth of normal.
Drug metabolism in circulatory failure may be impaired by reduced hepatic blood flow resulting in decreased clearance of highly extracted drugs, or by hepatocellular dysfunction resulting in decreased clearance of poorly extracted drugs. Drug excretion may be impaired by reduced renal blood flow resulting in decreased filtration or secretion and increased reabsorption. The maintenance dose of many drugs must therefore be reduced in the presence of circulatory failure.
Intravenous drug administration is preferred in patients with circulatory failure. The central intravenous route is often convenient but must be used cautiously when administering potentially cardiotoxic drugs. Intratracheal administration appears to be a promising alternative for some drugs, such as adrenaline (epinephrine). Intracardiac injections are hazardous and offer no demonstrated advantage over other routes.
Interpretation of drug concentrations in blood during cardiac emergencies must take account of the degree of protein binding of drug. Increases in the acute phase reactant α1-acid glycoprotein may decrease the unbound concentration of highly extracted drugs or increase the total concentration of poorly extracted drugs. Heparin can displace drugs from albumin by increasing free fatty acid concentrations, but this appears to be an in vitro artefact. The site of drug sampling may also be important: arterial concentrations of drug may greatly exceed venous concentrations during the distribution phase due to tissue uptake of drug.
Most antiarrhylhmic drugs have half-lives of at least several hours and require many hours to reach a steady-state blood concentration when administered as a constant rate intravenous infusion. Therapeutic blood concentrations of such drugs can be achieved more rapidlv by administering a loading dose consisting of I or more intravenous bolus doses or rapid infusions. Catecholamines have half-lives of several minutes, so a loading dose is not required. The application of pharmacokinetic and pharmacodynamic considerations to drug dosing in cardiac emergencies is illustrated by considering the use of several anti-arrhythmic agents [lignocaine (lidocaine), procainamide, verapamil, propranolol, bretylium], inotropic and vasopressor agents [noradrenaline (norepinephrine), adrenaline, dopamine, dobutamine, isoprenaline (isoproterenol)], and atropine.
Similar content being viewed by others
References
Anderson, J.L.; Patterson, E.; Conlon, M.; Pasyk, S.; Pitt, B. and Lucchesi, B.R.: Kinetics of antifibrillatory effects of bretylium: Correlation with myocardial drug concentrations. American Journal of Cardiology 46: 583–592 (1980a).
Anderson, J.L.; Patterson, E.; Wagner, J.G.; Johnson, T.A.; Lucchesi, B.R. and Bertram, P.: Clinical pharmacokinetics of intravenous and oral bretylium tosylate in survivors of ventricular tachycardia or fibrillation: Clinical application of a new assay for bretylium. Journal of Cardiovascular Pharmacology 3: 485–599 (1981).
Anderson, J.L.; Patterson, E.; Wagner, J.G.; Stewart, J.R.; Behm, H.L. and Lucchesi, B.R.: Oral and intravenous bretylium disposition. Clinical Pharmacology and Therapeutics 28: 468–478 (1980b).
Anderson, P.; Bondesson, U. and Sylven, C.: Clinical pharmacokinetics of verapamil in patients with atrial fibrillation. European Journal of Clinical Pharmacology 23: 49–57 (1982).
Aronow, W.S.; Landa, D.; Plasencia, G.; Wong, R.; Karlsberg, R.P. and Ferlinz, J.: Verapamil in atrial fibrillation and atrial flutter. Clinical Pharmacology and Therapeutics 26: 578–583 (1979).
Barchowsky, A.; Shand, D.G.; Stargel, W.W.; Wagner, G.S. and Routledge, P.A.: On the role of alpha-1-acid glycoprotein in lignocaine accumulation following myocardial infarction. British Journal of Clinical Pharmacology 13: 411–415 (1982).
Bauer, L.A.; Brown, T.; Gibaldi, M.; Hudson, L.; Nelson, S.; Raisys, V. and Shea, J.P.: Influence of long-term infusions on lidocaine kinetics. Clinical Pharmacology and Therapeutics 31: 433–437 (1982).
Bax, N.D.S.; Tucker, G.T. and Woods, H.F.: Lignocaine and in-docyaninc green kinetics in patients following myocardial infarction. British Journal of Clinical Pharmacology 10: 353–361 (1980).
Bellet, S.; Roman, L.; Kistis, J.B. and Fleischmann, D.: Intramuscular lidocaine in the therapy of ventricular arrhythmias. American Journal of Cardiology 27: 291–293 (1971).
Benowitz, N.: Effect of cardiac disease on pharmacokinetics: Pathophysiologic considerations; in Benet et al. (Eds) The Pharmacokinetic Basis of Drug Treatment (In press, 1984).
Benowitz, N.; Forsyth, R.P.; Melmon, K.L. and Rowland, M.: Lidocaine disposition kinetics in monkey and man. II. Effects of hemorrhage and sympathomimetic drug administration. Clinical Pharmacology and Therapeutics 16: 99–109 (1974a).
Benowitz, N.; Forsyth, R.P.; Melmon, K.L. and Rowland, M.: Lidocaine disposition kinetics in monkey and man. I. Prediction by a perfusion model. Clinical Pharmacology and Therapeutics 16: 87–98 (1974b).
Benowitz, N.L. and Meister, W.: Pharmacokinetics in patients with cardiac failure. Clinical Pharmacokinetics 1: 389–405 (1976).
Benowitz, N.L. and Meister, W.: Clinical pharmacokinetics of lidocaine. Clinical Pharmacokinetics 3: 177–201 (1978).
Beregovich, J.; Reicher-Reiss, H. and Grishman, A.: Haemodynamic effects of isoprenaline in acute myocardial infarction. British Heart Journal 34: 705–710 (1972).
Beregovich, J.; Reicher-Reiss, H.; Kunstadt, D. and Grishman, A.: Hemodynamic effects of isoproterenol in cardiac surgery. Journal of Thoracic and Cardiovascular Surgery 62: 957–964 (1971).
Bishopm, R.L. and Weisfeldt, M.L.: Sodium bicarbonate administration during cardiac arrest. Journal of the American Medical Association 235: 506–509 (1976).
Bivins, H.G.; Knopp, R.; Tiernan, C; dos Santos, P.A.L. and Kallsen, G.: Blood volume displacement with inflation of antishock trousers. Annals of Emergency Medicine 409: 37–40 (1982).
Brown, J.E.; Kitchell, B.B.; Bjornsson, T.D. and Shand, D.G.: The artifactual nature of heparin-induced drug protein-binding alterations. Clinical Pharmacology and Therapeutics 30: 636–643 (1981).
Brown, J.E. and Shand, D.G.: Therapeutic drug monitoring of antiarrhythmic agents. Clinical Pharmacokinetics 7: 125–148 (1982).
Camarata, S.J.; Weill, M.H.; Hanashiro, P.K. and Shubin, H.: Cardiac arrest in the critically ill. I. A study of predisposing causes in 132 patients. Circulation 44: 688–695 (1971).
Chadda, K.D.: Lichstein, E.; Gupta, P.K. and Choy, R.: Bradycardia hypotension syndrome in acute myocardial infarction. American Journal of Medicine 59: 158–164 (1975).
Chadda, K.D.; Lichstein, E.; Gupta, P.K. and Kourtesis, P.: Effects of atropine in patients with bradyarrhythmia complicating myocardial infarction. American Journal of Medicine 63: 503–510 (1977).
Chamberlain, D.A., Turner, P. and Sneddon, J.M.: Effects of atropine on heart-rate in healthy man. Lancet 2: 12–15 (1967).
Chandra, N.; Snyder, L.D. and Weisfeldt, J.L.: Abdominal binding during cardiopulmonary resuscitation in man. Journal of the American Medical Association 246: 351–353 (1981).
Chiou, W.L.; Lam, G.; Chen, M.L. and Lee, M.G.: Arterial-venous plasma concentration differences of six drugs in the dog and rabbit after intravenous administration. Research Communications in Chemistry, Pathology, and Pharmacology 32: 27–39 (1981).
Chou, R.C. and Levy, G.: Effect of heparin or salicylate infusion on serum protein binding and on concentrations of phenytoin in serum, brain and cerebrospinal fluid of rats. Journal of Pharmacology and Experimental Therapeutics 219: 42–48 (1981).
Chow, M.S.S.; Ronfeldt, R.A.; Hamilton, R.A.; Helmink, A. and Fieldman, A.: Effect of external cardiopulmonary resuscitation on lidocaine pharmacokinetics in dogs. Journal of Pharmacology and Experimental Therapeutics 244: 531–537 (1983).
Chow, M.S.S.; Ronfeldt, R.A.; Ruffet, D. and Fieldman, A.: Lidocaine pharmacokinetics during cardiac arrest and external cardiopulmonary resuscitation. American Heart Journal 102: 799–801 (1981).
Clutter, W.E.; Bier, D.M.; Shah, S.D. and Cryer, P.E.: Epinephrine plasma metabolic clearance rates and physiologic thresholds for metabolic and hemodynamic actions in man. Journal of Clinical Investigation 66: 94–101 (1980).
Cohen, H.C.; Gozo Jr, E.G.; Langendorf, R.; Kaplan, B.M.; Chan, A.; Pick, A. and Glick, G.: Response of resistant ventricular tachycardia to bretylium. Relation to site of ectopic focus and location of myocardial disease. Circulation 47: 331–340 (1973).
Cohen, L.S.; Rosenthal, J.E.; Homer Jr, D.W.; Atkins, J.M.; Mathews, O.A. and Sarnoff, S.J.: Plasma levels of lidocaine after intramuscular administration. American Journal of Cardiology 29: 520–523 (1972).
Cohn, J.N.; Tristani, F.E. and Khatri, I.M.: Cardiac and peripheral vascular effects of digitalis in clinical cardiogenic shock. American Heart Journal 78: 318–330 (1969).
Coltart, D.J. and Shand, D.G.: Plasma propranolol levels in the quantitative assessment of β-adrenergic blockade in man. British Medical Journal 3: 731–734 (1970).
Cooper, M.J. and Abinader, E.G.: Atropine-induced ventricular fibrillation: Case report and review of the literature. American Heart Journal 92: 225–227 (1979).
Crawford, M.H.; Ludden, T.M.; Kennedy, G.T.; Sodums, M.T.; O’Rourke, R.A. and Amon, K.W.: Hemodynamic effects of N-acetylprocainamide in heart disease. Clinical Pharmacology and Therapeutics 31: 459–465 (1982).
Dauchot, P. and Gravenstein, J.S.: Bradycardia after myocardial ischemia and its treatment with atropine. Anesthesiology 44: 501–518 (1976).
Davison, R.; Barresi, V.; Parker, M.; Meyers, S.N. and Talano, J.V.: Intracardiac injections during cardiopulmonary resuscitation. Journal of the American Medical Association 244: 1110–1111 (1980).
Davison, R.; Parker, M. and Atkinson Jr, A.J.: Excessive serum lidocaine levels during maintenance infusions: Mechanisms and prevention. American Heart Journal 104: 203–208 (1982).
DeMots, H.; Rahimtoola, S.H.; McAnulty, J.H. and Porter, G.A.: Effects of ouabain on coronary and systemic vascular resistance and myocardial oxygen consumption in patients without heart failure. American Journal of Cardiology 41: 88–93 (1978).
Dhurandhar, R.W.; Teasdale, S.J. and Manon, W.A.: Bretylium tosylate in the management of refractory ventricular fibrillation. Canada Medical Association Journal 105: 161–173 (1971).
Doherty, J.E. and Perkins, W.H.: Studies with tritiated digoxin in human subjects after intravenous administration. American Heart Journal 63: 528–536 (1962).
Dominic, J.; McAllister Jr, R.G.; Kuo, C.S.; Reddy, C.P. and Surawicz, B.: Verapamil plasma levels and ventricular rate response in patients with atrial fibrillation and flutter. Clinical Pharmacology and Therapeutics 26: 710–714 (1979).
Dominic, J.A.; Bourne, D.W.A.; Tan, T.G.; Kirsten, E.B. and McAllister Jr, R.G.: The pharmacology of verapamil. III. Pharmacokinetics in normal subjects after intravenous drug administration. Journal of Cardiovascular Pharmacology 3: 25–38 (1981).
Duchin, K.L. and Schrier, R.W.: Interrelationship between renal haemodynamics, drug kinetics and drug action. Clinical Pharmacokinetics 3: 58–71 (1978).
Eichelbaum, M.; Somogyi, A.; von Unruh, G.E. and Dengler, H.J.: Simultaneous determination of the intravenous and oral pharmacokinetic parameters of D,L-verapamil using stable isotope-labelled verapamil. European Journal of Clinical Pharmacology 19: 133–137 (1981).
Elam, J.O.: The intrapulmonary route for CPR drugs; in Safar (Ed.) Advances in Cardiopulmonary Resuscitation, pp. 132–140 (Springer, New York 1977).
Esler, M.; Jackman, G.; Leonard, P.; Skews, H.; Bobik, A. and Korner, P.: Effect of norepinephrine uptake blockers on nor-epinephrine kinetics. Clinical Pharmacology and Therapeutics 29: 12–20 (1981).
Estes, J.W.: Clinical pharmacokinetics of heparin. Clinical Pharmacokinetics 5: 204–220 (1980).
Feely, J.; Wade, D.: McAllister, C.B.; Wilkinson, G.R. and Robertson, D.: Effect of hypotension on liver blood flow and lidocaine disposition. New England Journal of Medicine 307: 866–869 (1982a).
Feely, J.; Wilkinson, G.R.; McAllister, C.B. and Wood, J.J.: Increased toxicity and reduced clearance of lidocaine by cimetidine. Annals of Internal Medicine 96: 592–594 (1982b).
FitzGerald, G.A.: Barnes, P.; Hamilton, C.A. and Dollery, C.T.: Circulating adrenaline and blood pressure: The metabolic effects and kinetics of infused adrenaline in man. European Journal of Clinical Investigation 10: 401–406 (1980).
FitzGerald, G.A.; Hossman, V.; Hamilton, C.A.; Reid, J.L.; Davies, D.S. and Dollery, C.T.: Interindividual variation in kinetics of infused norepinephrine. Clinical Pharmacology and Therapeutics 26: 669–675 (1979).
Gadzinski, D.S.; White, B.C.; Hoehner, P.J.; Hoehner, T.; Krome, C and White, J.D.: Canine cerebral cortical blood flow and vascular resistance post cardiac arrest. Annals of Emergency Medicine 11: 58–63 (1982).
Gaffney, F.A.; Thal, E.R.; Taylor, W.F.; Bastian, B.C.; Weigelt, J.A.; Atkins, J.M. and Blomqvist, C.G.: Hemodynamic effects of medical anti-shock trousers (MAST garment). Journal of Trauma 21: 931–937 (1981).
Galeazzi, R.L.; Benet, L.Z. and Sheiner, L.B.: Relationship between the pharmacokinetics and pharmacodynamics of procainamide. Clinical Pharmacology and Therapeutics 20: 278–289 (1976).
Galster, A.D.; Clutter, W.E.; Cryer, P.E.; Collins, J.A. and Bier, D.M.: Epinephrine plasma thresholds for lipolytic effects in man. Journal of Clinical Investigation 67: 1729–1738 (1981).
Garret, E.R.; Green Jr, J.R. and Bailer, M.: Bretylium pharmacokinetics and bioavailabilities in man with various doses and modes of administration. Biopharmaceutics and Drug Disposition 3: 129–164 (1982).
George, C.F.; Conolly, M.E.; Fenyvesi, T.; Briant, R. and Dollery, C.T.: Intravenously administered isoproterenol sulfate doseresponse curves in man. Archives of Internal Medicine 130: 361–364 (1972).
Giacomini, K.M.; Swezey, S.E.; Giacomi, J.C and Blaschke, T.F.: Administration of heparin causes in vitro release of non-esterified fatty acids in human plasma. Life Science 27: 771–780 (1980).
Giardina, E.G.V.; Heissenbuttel, R.H. and Bigger, J.T.: Intermittent intravenous procaine amide to treat ventricular arrhythmias. Correlation of plasma concentration with effect on arrhythmia, electrocardiogram, and blood pressure. Annals of Internal Medicine 78: 183–193 (1973).
Gillespie, T.A.; Ambos, H.D.; Sobel, B.E. and Roberts, R.: Effects of dobutamine in patients with acute myocardial infarction. American Journal of Cardiology 39: 588–594 (1977).
Goldberg, A.H.: Cardiopulmonary arrest. New England Journal of Medicine 290: 381–385 (1974).
Goldberg, L.I.; Hsieh, Y.Y. and Resnekov, L.: Newer catechol-amines for treatment of heart failure and shock: An update on dopamine and first look at dobutamine. Progress in Cardiovascular Disease 19: 327–340 (1977).
Gomeni, R.; Bianchetti, G.; Sega, R. and Morselli, P.L.: Pharmacokinetics of propranolol in normal healthy volunteers. Journal of Pharmacokinetics and Biopharmacology 5: 183–192 (1977).
Gonzales, R. and Scheinman, M.M.: Treatment of supraventricular arrhythmias with intravenous and oral verapamil. Chest 80: 465–470 (1981).
Gravenstein, J.S.; Andersen, T.W. and De Padua, C.B.: Effects of atropine and scopolamine on the cardiovascular system in man. Anesthesiology 25: 123–130 (1964).
Greenberg, M.I.; Mayede, D.V.; Chrzanowski, R.; Brumwell, D.; Baskin, S.I. and Roberts, J.R.: Endotracheal administration of atropine sulfate. Annals of Emergency Medicine 11: 546–548 (1982).
Greenberg, M.I.; Roberts, J.R. and Baskin, S.I.: Endotracheal naloxone reversal of morphine-induced respiratory depression in rabbits. Annals of Emergency Medicine 9: 289–291 (1980).
Greenberg, M.I.; Roberts, J.R.; Krusz, J.C. and Baskin, S.I.: Endotracheal epinephrine in a canine anaphylactic shock model. Journal of the American College of Emergency Physicians 8: 500–503 (1979).
Greenspan, A.M.; Horowitz, L.N.; Spielman, S.R. and Josephson, M.E.: Large dose procainamide therapy for ventricular tachyarrhythmia. American Journal of Cardiology 46: 453–462 (1980).
Halkin, H.; Meffin, P.; Melmon, K.L. and Rowland, M.: Influence of congestive heart failure on blood levels of lidocaine and its active monodeethylated metabolite. Clinical Pharmacology and Therapeutics 17: 669–676 (1975).
Harrison, D.C.: Practical guidelines for the use of lidocaine. Prevention and treatment of cardiac arrhythmias. Journal of the American Medical Association 233: 1202–1204 (1975).
Hepner, G.W.; Vesell, E.S. and Tantum, K.R.: Reduced drug elimination in congestive heart failure. Studies using aminopyrine as a model drug. American Journal of Medicine 65: 271–276 (1978).
Higgins, C.B.; Vatner, S.F.; Franklin, D. and Braunwald, E.: Effects of experimentally produced heart failure on the peripheral vascular response to severe exercise in conscious dogs. Circulation Research 31: 186–194 (1972a).
Higgins, C.B.; Vatner, S.F.; Millard, R.W.; Franklin, D. and Braunwald, E.: Alterations in regional hemodynamics in experimental heart failure in conscious dogs. Transactions of the Association of American Physicians 85: 267–275 (1972b).
Hoffman, J.R.: External counterpressure and the MAST suit: Current and future roles. Annals of Emergency Medicine 9: 419–421 (1980).
Holloway, E.L.; Polumbo, R.A. and Harrison, D.C.: Acute circulatory effects of dopamine in patients with pulmonary hypertension. British Heart Journal 37: 482–485 (1975).
Holzer, J.; Karliner, J.S.; O’Rourke, R.A.; Pitt, W. and Ross Jr, J.: Effectiveness of dopamine in patients with cardiogenic shock. American Journal of Cardiology 32: 79–84 (1973).
Jarnberg, P.O.; Bengtsson, L.; Ekstrand, J. and Hamberger, B.: Dopamine infusion in man, plasma calecholamine levels and pharmacokinetics. Acta Anaesthesiologica Scandinavica 25: 328–331 (1981).
Jose, A.D. and Taylor, R.R.: Autonomic blockade by propranolol and atropine to study intrinsic myocardial function in man. Journal of Clinical Investigation 48: 2019–2031 (1969).
Jugdutt, B.I. and Lee, S.J.K.: Intravenous therapy with propranolol in acute myocardial infarction. Effects on changes in the S-T segment and hemodynamics. Chest 74: 514–521 (1978).
Kaplan, B.M. and Knott Jr, A.P.: Closed-chest cardiac massage for circulatory arrest. Archives of Internal Medicine 114: 5–12 (1964).
Kates, R.E.; Keefe, D.L.D.; Schwartz, J.; Harapat, S.; Kirsten, E.B. and Harrison, D.C: Verapamil disposition kinetics in chronic atrial fibrillation. Clinical Pharmacology and Therapeutics 30: 44–51 (1981).
Koch-Weser, J.: Bretylium. New England Journal of Medicine 300: 473–477 (1979).
Koch-Weser, J. and Klein, S.W.: Procainamide dosage schedules, plasma concentrations, and clinical effects. Journal of the American Medical Association 215: 1454–1460 (1971).
Kornhauser, D.M.; Wood, A.J.J.; Vestal, R.E.; Wilkinson, G.R.; Branch, R.A. and Shand, D.G.: Biological determinants of propranolol disposition in man. Clinical Pharmacology and Therapeutics 23: 165–174 (1978).
Koup, J.R.; Greenblatt, D.J.; Jusko, W.J.; Smith, T.W. and Koch-Weser, J.: Pharmacokinetics of digoxin in normal subjects after intravenous bolus and infusion doses. Journal of Pharmacokinetics and Biopharmacology 3: 181–192 (1975).
Kuhn, G.J.; White, B.C.; Sweetnam, R.E.; Mumey, J.F.; Rydesky, M.F.; Tintinalli, J.E.; Krome, R.L. and Hoehner, P.J.: Peripheral vs central circulation times during CPR: A pilot study. Annals of Emergency Medicine 10: 417–419 (1981).
Lam, G. and Chiou, W.L.: Arterial and venous blood sampling in pharmacokinetic studies: Propranolol in rabbits and dogs. Research Communications in Chemistry, Pathology and Pharmacology 33: 33–47 (1981).
Leier, C.V.; Heban, P.T.; Huss, P.; Bush, C.A. and Lewis, R.P.: Comparative systemic and regional hemodynamic effects of dopamine and dobutamine in patients with cardiomyopathic heart failure. Circulation 58: 466–475 (1978).
Leier, C.V.; Unverferth, D.V. and Kates, R.E.: The relationship between plasma dobutamine concentrations and cardiovascular responses in cardiac failure. American Journal of Medicine 66: 238–242 (1979).
Lelorier, J.; Grenon, D. and Latour, Y.: Pharmacokinetics of lidocaine after prolonged intravenous infusions in uncomplicated myocardial infarction. Annals of Internal Medicine 87: 700–702 (1977).
Lepeschkin, E.; Mrachett, H.; Schroeder, G.; Wagner, R.; dePaula e Silva, P. and Raab, W.: Effect of epinephrine and norepinephrine on the electrocardiogram of 100 normal subjects. American Journal of Cardiology 5: 594–603 (1960).
Lie, K.I.; Wellens, H.J. and Van Capelle, F.J.: Lidocaine in the prevention of primary ventricular fibrillation. New England Journal of Medicine 291: 1324–1326 (1974).
Lima, J.J.; Conti, D.R.; Goldfarb, A.L.; Golden, L.H. and Jusko, W.J.: Pharmacokinetic approach to intravenous procainamide therapy. European Journal of Clinical Pharmacology 13: 303–308 (1978).
Lima, J.J.; Goldfarb, A.L.; Conti, D.R.; Golden, L.H.; Bascomb, B.L.; Benedetti, G.M. and Jusko, W.J.: Safety and efficacy of procainamide infusions. American Journal of Cardiology 43: 98–105 (1979).
Mandel, W.; Hazukawa, H.; Danzing, R. and Marcus, H.S.: Evaluation of sinoatrial node function in man by overdrive suppression. Circulation 44: 59–64 (1971).
Mangiardi, L.M.; Hariman, R.J.; McAllister Jr, R.G.; Bhargava, V.; Surawicz, B. and Shabelai, R.: Electrophysiologic and hemodynamic effects of verapamil. Circulation 57: 366–372 (1978).
Marcus, F.I.: Use of digitalis in acute myocardial infarction. Circulation 62: 17–19 (1980).
Massumi, R.A.; Mason, D.T. and Amsterdam, E.A.: Ventricular fibrillation and tachycardia after intravenous atropine for treatment of bradycardias. New England Journal of Medicine 287: 336–338 (1972).
McAllister Jr, R.G.; Bourne, D.W.A. and Dittert, L.W.: The pharmacology of verapamil. I. Elimination kinetics in dogs and correlation of plasma levels with effect on the electrocardiogram. Journal of Pharmacological and Experimental Therapeutics 202: 38–44 (1977).
McDevitt, D.G. and Shand, D.G.: Plasma concentrations and the time-course of beta blockade due to propranolol. Clinical Pharmacology and Therapeutics 18: 708–713 (1975).
McDonald, J.L.: Systolic and mean arterial pressures during manual and mechanical CPR in humans. Critical Care Medicine 9: 382–383 (1981).
Mclnlyre, K.M.: Cardiovascular pharmacology: Part II; in Mc-Intyre and Lewis (Eds) Textbook of Advanced Cardiac Life Support, pp. IX-6 (American Heart Association, 1981).
Morton, H.J.V. and Thomas, E.T.: Effect of atropine on the heartrate. Lancet 2: 1313–1315 (1958).
Mueller, H.S.; Evans, R. and Ayres, S.M.: Effect of dopamine on hemodynamics and myocardial metabolism in shock following acute myocardial infarction in man. Circulation 57: 361–365 (1978).
Narang, P.K.; Adir, J.; Josselson, J.; Yacobi, A. and Sadler, J.: Pharmacokinetics of bretylium in man after intravenous administration. Journal of Pharmacokinetics and Biopharmacology 8: 363–372 (1980).
Noneman, J.W. and Rogers, J.F.: Lidocaine prophylaxis in acute myocardial infarction. Medicine 57: 501–515 (1978).
Ochs, H.R., Carstens, G. and Greenblatt, D.J.: Reduction in lidocaine clearance during continuous infusion and by coadministration of propranolol. New England Journal of Medicine 303: 373–377 (1980).
Paterson, J.W.: Human pharmacology: Comparison of intravenous isoprenalinc and salbutamol in asthmatic patients. Postgraduate Medical Journal 47(Suppl): 38–39 (1971).
Patwardhan, R.V.; Desmond, P.V.; Johnson, R.F.; Dunn, G.D.; Robertson, D.H.; Hoyumpa, A.M. and Schenker, S.: Effects of caffeine on plasma free fatty acids, urinary catecholamines, and drug binding. Clinical Pharmacology and Therapeutics 28: 398–403 (1980).
Pine, M.; Favrot, L; Smith, S.; McDonald, K. and Chidsey, C.A.: Correlation of plasma propranolol concentration with therapeutic response in patients with angina pectoris. Circulation 52: 886–893 (1975).
Prescott, L.F.; Adjepon-Yamoah, K.K. and Talbot, R.G.: Impaired lignocaine metabolism in patients with myocardial infarction and cardiac failure. British Medical Journal 1: 939–941 (1976).
Redding, J.S.; Asuncion, J.S. and Pearson, J.W.: Effective routes of drug administration during cardiac arrest. Anesthesiology and Analgesics 46: 253–258 (1967).
Reiter, M.J.; Shand, D.G.; Aanonsen, L.M.; Wagoner, R.; McCarthy, E. and Pritchett, E.L.C.: Pharmacokinetics of verapamil: Experience with a sustained intravenous infusion regimen. American Journal of Cardiology 50: 716–721 (1982a).
Reiter, M.J.; Shand, D.G. and Pritchett, E.L.C.: Comparison of intravenous and oral verapamil dosing. Clinical Pharmacology and Therapeutics 32: 711–720 (1982b).
Reuning, R.H.; Sams, R.A. and Notari, R.E.: Role of pharmacokinetics in drug dosage adjustment. I. Pharmacologic effect kinetics and apparent volume of distribution of digoxin. Journal of Clinical Pharmacology 13: 127–141 (1973).
Roberts, J.R.; Greenberg, M.I. and Baskin, S.I.: Endotracheal epinephrine in cardiorespiratory collapse. Journal of the American College of Emergency Physicians 8: 515–519 (1979a).
Roberts, J.R.; Greenerg, M.I.; Knaub, M.A.; Kendrick, Z.V. and Baskin, S.I.: Blood levels following intravenous and endotracheal epinephrine administration. Journal of the American College of Emergency Physicians 8: 53–56 (1979b).
Romhilt, D.W.; Bloomfield, S.S.; Lipicky, R.J.; Welch, R.M. and Fowler, N.O.: Evaluation of bretylium tosylate for the treatment of premature ventricular contractions. Circulation 45: 800–807 (1972).
Rosenblum, R. and Frieden, J.: Intravenous dopamine in the treatment of myocardiac dysfunction after open-heart surgery. American Heart Journal 83: 743–748 (1972).
Routledge, P.A.; Shand, D.G.; Barchowsky, A.; Wagner, G. and Stargel, W.W.: Relationship between alpha one-acid glycoprotein and lidocaine disposition in myocardial infarction. Clinical Pharmacology and Therapeutics 30: 154–157 (1981).
Routledge, P.A.; Stargel, W.W.; Wanger, G.S. and Shand, D.G.; Increased alpha-1-acid glycoprotein and lidocaine disposition in myocardial infarction. Annals of Internal Medicine 93: 701–704 (1980).
Rowland, M. and Tozer, T.N.: Clinical Pharmacokinetics: Concepts and Applications, p. 138 (Lea and Febiger, Philadelphia 1980).
Salzer, L.B.; Weinrib, A.B.; Marina, R.J. and Lima, J.J.: A comparison of methods of lidocaine administration in patients. Clinical Pharmacology and Therapeutics 29: 617–624 (1981).
Scheinman, M.M.; Thorburn, D. and Abbott, J.A.: Use of atropine in patients with acute myocardial infarction and sinus bradycardia. Circulation 52: 627–633 (1975).
Schinz, A.; Schnelle, K.; Klein, G. and Blomer, H.: Time sequence of direct vascular and inotropic effects following intravenous administration of digoxin in normal man. International Journal of Clinical Pharmacology 15: 189–193 (1977).
Schomerus, M.; Spiegelhaider, B.; Stieren, B. and Eichelbaum, M.: Physiological disposition of verapamil in man. Cardiovascular Research 10: 605–612 (1976).
Shand, D.G.; Nuckolls, E.M. and Oates, J.A.: Plasma propranolol levels in adults with observations in four children. Clinical Pharmacology and Therapeutics 11: 112–120 (1969).
Shapiro, W.; Narahara, K. and Taubert, K.: Relationship of plasma digitoxin and digoxin to cardiac response following intravenous digitalization in man. Circulation 42: 1065–1072 (1970).
Silverberg, A.B.; Shah, S.D.; Haymond, M.W. and Cryer, P.E.: Norepinephrine: Hormone and neurotransmitter in man. American Journal of Physiology 234: 252–256 (1978).
Singh, B.N.; Ellrodt, G. and Peter, C.T.: Verapamil: A review of its pharmacological properties and therapeutic use. Drugs 15: 169–197 (1978).
Singh, J.B. and Kocot, S.L.: A controlled trial of intramuscular lidocaine in the prevention of premature ventricular contractions associated with acute myocardial infarction. American Heart Journal 91: 430–436 (1976).
Smith, T.W.: Drug therapy. Digitalis glycosides. New England Journal of Medicine 288: 719–724 (1973).
Smulyan, H.; Weinberg, S.E. and Howanitz, P.J.: Continuous propranolol infusion following abdominal surgery. Journal of the American Medical Association 247: 2539–2542 (1982).
Sonnenblick, E.H; Frishman, W.H. and LeJemtel, T.H.: Dobutamine: A new synthetic cardioactive sympathetic amine. New England Journal of Medicine 300: 17–22 (1979).
Stenson, R.E.; Constantino, R.T. and Harrison, D.C.: Interrelationships of hepatic blood flow, cardiac output, and blood levels of lidocaine in man. Circulation 43: 205–211 (1971).
Stone, P.H.; Amman, E.M.; Muller, J.E. and Braunwald, E.: Calcium channel blocking agents in the treatment of cardiovascular disorders. Part II: Hemodynamic effects and clinical applications. Annals of Internal Medicine 93: 886–904 (1980).
Sullivan, T.J.: Cardiac disorders in penicillin-induced anaphylaxis. Journal of the American Medical Association 248: 2161–2162 (1982).
Tern, G.; Vellani, C.W.; Higgins, M.R. and Doig, A.: Bretylium tosylate in treatment of refractory ventricular arrhythmias complicating myocardial infarction. British Heart Journal 32: 21–25 (1970).
Thomson, P.D.; Melmon, K.L.: Richardson, J.A.; Cohn, K.; Steinbrunn, W.; Cudihee, R. and Rowland, M.: Lidocaine pharmacokinetics in advanced heart failure, liver disease, and renal failure in humans. Annals of Internal Medicine 78: 499–508 (1973).
Valentine, P.A.; Frew, J.L.; Mashford, M.L. and Sloman, J.G.: Lidocaine in the prevention of sudden death in the pre-hospital phase of acute infarction. A double-blind study. New England Journal of Medicine 291: 1327–1331 (1974).
Voorhees, W.D.; Babbs, C.F. and Tacker, W.A.: Regional blood flow during cardiopulmonary resuscitation in dogs. Critical Care Medicine 8: 134–136 (1980).
Waller, E.S.: Pharmacoktnetic principles of lidocaine dosing in relation to disease state. Journal of Clinical Pharmacology 21: 181–194 (1981).
Webb, S.W.; Adgey, A.A.J. and Pantridge, J.F.: Autonomic disturbance at onset of acute myocardial infarction. British Medical Journal 2: 89–92 (1972).
Wilkinson, G.R. and Shand, D.G.: A physiologic approach to hepatic drug clearance. Clinical Pharmacology and Therapeutics 18: 377–390 (1975).
Woosley, R.L.; Shand, D.; Kornhauser, D.; Nies, A.S. and Oates, J.A.: Relation of plasma concentration and dose of propranolol to its effect on resistant ventricular arrhythmias. (Abstract.) Clinical Research 25: 262A (1977).
Wyman, M.G.; Goldreyer, B.N.; Cannom, D.S.; Ludden, T.M. and Lalka, D.: Factors influencing procainamide total body clearance in the immediate postmyocardial infarction period. Journal of Clinical Pharmacology 21: 20–25 (1981).
Wyman, M.G.; Lalka, D.; Hammersmith, L.; Cannom, D.S. and Goldreyer, B.N.: Multiple bolus technique for lidocaine administration during the first hours of an acute myocardial infarction. American Journal of Cardiology 41: 313–317 (1978).
Zelis, R. and Mason, D.T.: Compensatory mechanisms in congestive heart failure — the role of the peripheral resistance vessels. New England Journal of Medicine 282: 962–964 (1970).
Zelis, R.; Mason, D.T. and Braunwald, E.: Partition of blood flow to the cutaneous and muscular beds of the forearm at rest and during leg exercise in normal subjects and in patients with heart failure. Circulation Research 24: 799–805 (1969).
Zener, J.C.; Kerber, R.E.; Spivack, A.P. and Harrison, D.C.: Blood lidocaine levels and kinetics following high-dose intramuscular administration. Circulation 47: 984–988 (1973).
Zito, R.A. and Reid, P.R.: Lidocaine kinetics predicted by in-docyanine green clearance. New England Journal of Medicine 298: 1160–1163 (1978).
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Pentel, P., Benowitz, N. Pharmacokinetic and Pharmacodynamic Considerations in Drug Therapy of Cardiac Emergencies. Clin Pharmacokinet 9, 273–308 (1984). https://doi.org/10.2165/00003088-198409040-00001
Published:
Issue Date:
DOI: https://doi.org/10.2165/00003088-198409040-00001