Conclusion
Pharmacokinetics is a branch of pharmacology concerned with the effect of the organism on drugs and is one of the factors which determine the magnitude of the drug effect. In normals considerable variation is seen in the pharmacokinetics of drugs. Changes in the pharmacokinetics of anaesthetics have been documented under many circumstances including in the elderly, in patients in shock, and in patients on other drug therapy such as cimetidine. These alterations should be considered during the practice of anaesthesia in order to avoid predictable toxicity due to excessive drug concentrations or reduced elimination.
Over the past 20 years much information has been reported concerning both the pharmacokinetics and pharmacodynamics of drugs, but these determinations have frequently been made independently of each other. In future research, the combination of pharmacokinetics with a pharmacodynamic endpoint will provide a more comprehensive approach to the pharmacology of drugs and permit more rational drug therapy.
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References
Butler TC. Some historical reflections on drug metabolism. Ann NY Acad Sci 1971; 179: 502–7.
FromWagner JG. Fundamentals of clinical pharmacokinetics. Drug Intelligence Publications Inc., Hamilton, Illinois, 1975.
Nelson E. Kinetics of drug absorption, distribution, metabolism and excretion. J Pharm Sci 1961; 50: 181–92.
Greenblatt DJ, Koch-Weser J. Clinical Pharmacokinetics. N Engl J Med 1975; 293: 702-5, 964–70.
Gibaldi M, Perrier D. Pharmacokinetics. Marcel Dekker Inc. New York, 1975.
van Rossum JM (ed). Kinetics of Drug Action Handb. Exp. Pharm. 47 1977.
Stanski DR, Watkins WD. Drug disposition in Anesthesia. Grune & Stratton, New York, 1982.
Boreus LO. Pharmacokinetics and clinical response. Eur J Clin Pharmacol 1980; 18: 51–3.
Dollery CT. Pharmacokinetics - master or servant. Eur J Clin Pharmacol 1973; 6: 1–2.
Turner P. Blood level or pharmacological response. Br J Clin Pharmacol 1974; I: 11.
Schmucker DL. Age-related changes in drug distribution. Pharmacological Reviews 1979; 30: 445–56.
Ritschel WA. Drug action and interaction in the geriatric patient. Sonderdruck Scientia Pharmaceutica 1977; 45: 304–10.
Schumacher GE, Using pharmacokinetics in drug therapy VII. Pharmacokinetic factors influencing drug therapy in the aged. Am J Hosp Pharm 1980; 37; 559–62.
Kato R, Vassanelli P, Frontino G, Chiesera E. Variation in the activity of liver microsomal drug metabolizing enzymes in rat in relation to the age. Biochem Pharmacol 1964; 13: 1037–51.
Irvine RE, Grove J, Toseland PA, Trounce JR. The effect of age on the hydroxylation of amylobarbitone sodium in man. Br J Clin Pharmacol 1974; 1: 41–3.
Ritschel WA. Age-dependent disposition of amobarbital: Analog computer evaluation. J Am Ger Soc 1978; 26: 540–3.
Cltan K, Kendall MJ, Mitchard M, Wells WDE. Effect of ageing on plasma pethidine concentrations. Br J Clin Pharmacol 1975; 2: 297–302.
Mather LE, Meffin PJ. Clinical pharmacokinetics pethedine. Clin Pharmacokinetics 1978; 3: 352–68.
Greenblatt DJ, Allen MD, Harmatz JS, Shader RI. Diazepam disposition determinants. Clin Pharmacol Ther 1980; 27: 301–12.
Duvaldestin P, Berger JL, Saada J, Desmonts MD. Pancuronium: pharmacokinetics and pharmacodynamics in the elderly. Anesthesiology 1980;53:S284.
Chmietewski AT, Pybus DA, Loach AB, Goat VA. Recovery from neuromuscular blockade: a comparison between old and young patients. Anaesthesia 1978; 33: 539–42.
Jung D, Mayersohn M, Perrier D, Calkes SJ, Sounders R. Thiopental disposition as a function of age in female patients undergoing surgery. Anesthesiology 1982; 56: 263–8.
Harrison’s Principles of Internal Medicine 9th edition. Editors: Isselbacher KJ, Adams RD, Braunwald E, Petersdorf RG, Wilson JD. McGraw-Hill Book Company, New York 1980.
Halford RJ. A critique of intravenous anaesthesia in war surgery. Anesthesiology 1943; 4: 67–9.
Becker KE. Gas chromatographic assay for free and total plasma levels of thiopental. Anesthesiology 1976; 45: 656–60.
Ghoneim MM, Van Hamme MJ. Pharmacokinetics of thiopentone: Effects of enflurane and nitrous oxide anaesthesia and surgery. Br J Anaesthesia 1978; 50: 1237–41.
Pardy BJ, Dudley HAF. Sequential patterns of hemodynamic and metabolic changes in experimental hypovolemic shock. 1. Response to acute hemorrhage. Br J Surg 1979; 66: 84–8.
Birgens HS, Henrikson J, Matzen P, Poulsen H. The shock liver. Acta Med Scand 1978; 204: 417–21.
Duvaldestin P. Pharmacokinetics in intravenous anaesthetic practice. Clin Pharmacokinet 1981; 6: 61–82.
Nxumalo JL, Teranaka M, Schenk WG. Sensitivity of indocyanine green half-life changes relative to circulatory shock state. J Surg Res 1977; 23:400–4.
Benowitz NL, Meister W. Pharmacokinetics in patients with cardiac failure. Clin Pharmacokinet 1976; 1:389–405.
Cullen BF, Miller, MG. Drug interactions and anesthesia: A Review. Anesth Analg 1979; 58: 413–23.
Manchikanti L, Kraus JW, Edds SP. Cimetidine and related drugs in anesthesia. Anesth Analg 1982; 61: 595–608.
Somogyi A, Gugler R. Drug interaction with cimetidine. Clin Pharmacokinet 1982; 7: 23–41.
Bauman JH, Kimelblatt BJ. Cimetidine as an inhibition of drug metabolism: Therapeutic implications and review of the literature. Drug Intell Clin Pharm 1982; 16: 380–6.
Feely J, Wilkinson GR, Wood AJJ. Reduction of liver blood flow and propranolol metabolism by cimetidine. N Engl J Med 1981; 304: 692–5.
Klotz V, Reiman I. Delayed clearance of diazepam due to cimetidine. N Engl J Med 1980; 302: 1012–4.
McGowan WAW, Dundee JW. The effect of intravenous cimetidine on the absorption of orally administered diazepam and lorazepam. Br J Clin Pharmacol 1982; 14: 207–11.
Fine A, Churchill DN. Potentially lethal interaction of cimetidine and morphine. Can Med Assoc J 1981; 124: 1434–6.
Campbell MA, Plachetka JR, Jackson JE, Moon JF, Finley PN. Cimetidine decreases theophylline clearance. Ann Intern Med 1981; 95: 68–9.
DiFazio CA, Moscicki JC, DiFazio CJ. Cimetidine inhibits lidocaine plasma clearance. Anesthesiology 1982; 57: A188.
Feely J, Wilkinson GR, McAllister CB, Wood AJJ. Increased toxicity and reduced clearance of lidocaine by cimetidine. Ann Intern Med 1982; 96: 592–4.
Lidocaine-cimetidine interaction can be toxic. JAMA 1982; 247: 174-5.
Bauman JH, Kimelblatt BJ, Wible DA, Kucich JM. Cimetidine and drug metabolism. Can Med Assoc J 1982; 127: 199.
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This work was supported in part by a grant from Associated Medical Services.
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Moffat, J.A., Milne, B. Pharmacokinetics in anaesthesia. Can Anaesth Soc J 30, 300–307 (1983). https://doi.org/10.1007/BF03013813
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DOI: https://doi.org/10.1007/BF03013813