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Simple Analgesics

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Summary

A number of drugs are available that act fairly specifically as ‘mild’ analgesics, although this description by no means implies that their clinical effectiveness is limited to the relief of slight painand trivial disability. They are effective by mouth and their action is mediated peripherally. Among the possible mechanisms of action, the inhibition of prostaglandin synthesis is currently regarded as most likely to be relevant. Some centrally acting drugs of the narcotic analgesic type, such as codeine and dextropropoxyphene are effective orally; they are usable in the same way as other mild analgesics and may be preferable for some types of pain.

Many problems arise in the assessment and comparison of mild analgesics, both experimentally and clinically. Subjective assessments may be made on a pain scale by the patient himself, or by a trained observer. Individual variations are all-important, and the limitations of controlled trials need to be remembered.

Alternative drugs and mixtures have little advantage over aspirin, but specific drug tolerance, in the long term, varies from patient to patient. Gastric irritation is most likely to occur with aspirin in the presence of chronic dyspepsia or acute precipitating causes such as alcoholic gastritis. Allergy also occurs in some susceptible individuals. The risk of renal damage with phenacetin is increasingly appreciated, and the possibility of hepatic damage from paracetamol is now recognised. Other side-effects and interactions are summarised in the review, and some notes are given on therapeutic and non-therapeutic use.

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References

  • Avery, G.S.: Check list to potentially clinically important interactions. Drugs 5: 187–211 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Beaver, W.T.; Wallenstein, S.L.; Houde, R.W. and Rogers, A.: A comparison of the analgesic effects of parenteral methadone and morphine, and of oral and parenteral methadone, in patients with cancer. Clinical Pharmacology and Therapeutics 8: 415–426(1967).

    PubMed  CAS  Google Scholar 

  • Beecher, H.K.: Pain in men wounded in battle. Annals of Surgery 123: 96–105 (1946).

    Article  PubMed  CAS  Google Scholar 

  • Beecher, H.K.: in The Measurement of Subjective Responses (Oxford University Press, London 1959).

    Google Scholar 

  • Beecher, H.K.: in Clinical Evaluation of Analgesic Drugs. Acta Anaesthesiologica Scandinavica, Supplement 25: 323–324(1966).

    Google Scholar 

  • Bellville, J.W.; Forrest, W.H. and Brown, B.W.: Clinical and statistical methodology for co-operative clinical assays of analgesics. Clinical Pharmacology and Therapeutics 9: 290–302 (1968a).

    PubMed  CAS  Google Scholar 

  • Bellville, J.W.; Forrest, W.H.; Elashoff, Janet and Laska, E.: Evaluating side-effects of analgesics in a co-operative clinical study. Clinical Pharmacology and Therapeutics 9: 303–313 (1968b).

    PubMed  CAS  Google Scholar 

  • Benson, R.E. and Boleyn, T.: Paracetamol overdosage: A plan of management. Anaesthesia and Intensive Care 4: 334–339 (1974).

    Google Scholar 

  • Brody, T.M.: Action of sodium salicylate and related compounds in tissue metabolism in vitro. Journal of Pharmacology and Experimental Therapeutics 117: 39–51(1956).

    PubMed  CAS  Google Scholar 

  • Chafee, F.H. and Settipane, G.A.: Aspirin intolerance. I. Frequency in an allergic population. Journal of Allergy and Clinical Immunology 53: 193–199 (1974).

    Google Scholar 

  • Clouet, D.H.: in Narcotic drugs: Biochemical Pharmacology (Plenum Press, New York 1971).

    Google Scholar 

  • Collier, H.O.J.: in Dixon et al. (Eds) Salicylates: An International Symposium (Churchill, London 1963).

  • Collier, H.O.J.: A pharmacological analysis of aspirin. Advances in Pharmacology and Chemotherapy 7: 333–405 (1969).

    Article  PubMed  CAS  Google Scholar 

  • Collier, H.O.J.; Dinneen, L.C.; Johnson, C.A. and Schneider, C: The abdominal constriction response and its suppression by analgesic drugs in the mouse. British Journal of Pharmacology 32: 295–310 (1968).

    CAS  Google Scholar 

  • Collier, H.O.J.; Hammond, A.R.; Horwood-Barrett, S. and Schneider, C: Rapid induction by acetylcholine, bradykinin and potassium of a nociceptive response in mice and its selective antagonism by aspirin. Nature 204: 1316–1318(1964).

    Article  PubMed  CAS  Google Scholar 

  • Collier, H.O.J. and Shorley, P.G.: Analgesic antipyretic drugs as antagonists of bradykinin. British Journal of Pharmacology 15: 601–610(1960).

    CAS  Google Scholar 

  • Conney, A.H.; Sansur, M.; Soroko, F.; Koster, R. and Burns, J.J.: Enzyme induction and inhibition in studies on the pharmacological actions of aceto-phenetidin. Journal of Pharmacology and Experimental Therapeutics 151: 133–138 (1966).

    PubMed  CAS  Google Scholar 

  • Dordoni, B.; Willson, R.A.; Thompson, R.P.H. and Williams, R.: Reduction of absorption of paracetamol by activated charcoal and cholestyramine: A possible therapeutic measure. British Medical Journal 3: 86–87 (1973).

    Article  PubMed  CAS  Google Scholar 

  • Dreser, H.: Pharmakologisches über aspirin (acetylsali-cylsäure). Pflugers Archives ges. Physiology 76: 306–318(1899).

    Article  CAS  Google Scholar 

  • Editorial: Aspirin and what else? British Medical Journal 3: 5–6 (1974).

  • Eichenholz, A.; Mulhausen, R.O. and Redleaf, P.S.: Nature of acid-base disturbance in salicylate intoxication. Metabolism 12: 164–175 (1963).

    CAS  Google Scholar 

  • Ellis, E.S.: in Ancient Anodynes (Heinemann, London 1946).

    Google Scholar 

  • Ferreira, S.H.; Mancada, S. and Vane, J.R.: Indomethacin and aspirin abolishes prostaglandin release from the spleen. Nature 231: 237–239 (1971).

    Article  CAS  Google Scholar 

  • Finck, A.D. and Katz, R.L.: Prevention of cholera-induced intestinal secretion in the cat by aspirin. Nature 238: 273–274 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Flower, R.J. and Vane J.R.: Inhibition of prostaglandin synthetase in brain explains the antipyretic activity of paracetamol (40-acetamidophenol). Nature 240: 410–411 (1972).

    Article  PubMed  CAS  Google Scholar 

  • Forrest, J.A.H.; Roscoe, P.; Prescott, L.F. and Stevenson, I.H.: Abnormal drug metabolism after barbiturate and paracetamol overdose. British Medical Journal 4: 499–502 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Gilman, A.: Analgesic nephrotoxicity. A pharmacological analysis. American Journal of Medicine 36: 167–173(1964).

    CAS  Google Scholar 

  • Gross, M. and Greenberg, L.A.: in The Salicylates. A critical bibliographic review (Hillhouse Press, New Haven 1948).

    Google Scholar 

  • Guzman, F.; Braun, C. and Lim, R.K.S.: Visceral pain and the pseudaffective response to intra-arterial injection of bradykinin and other algesics agents. Archives International Pharmacodynamics 136: 353–384(1962).

    CAS  Google Scholar 

  • Guzman, F.; Braun, C.; Lim, R.K.S.; Potter, G.D. and Rodgers, D.W.: Narcotic and non-narcotic analgesics which block visceral pain evoked by intra-arterial injection of bradykinin and other algesic agents. Archives International Pharmacodyanmics 149: 571–588(1964).

    CAS  Google Scholar 

  • Hart, F.D. (Ed.): in The Treatment of Chronic Pain (Medical and Technical Publishing Co., Lancaster 1974).

    Google Scholar 

  • Havill, J.H.: Malignant hyperthermia caused by salicylate overdosage associated with phenelzine therapy — a case report. Anaesthesia and Intensive Care 4: 380–383 (1974).

    Google Scholar 

  • Head, H.: On disturbances of sensation with especial reference to the pain of visceral disease. Brain 16: 1–130(1893).

    Article  Google Scholar 

  • Houde, R.W.: Assessment of analgesic activity; in Way (Ed.) New Concepts in Pain and its Clinical Management (F.A. Davis and Co., Philadelphia 1967).

    Google Scholar 

  • Huskisson, E.C.: Simple analgesics for arthritis. British Medical Journal 4: 196–200 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Jollow, D.J.; Mitchell, J.R.; Potter, W.Z.; Davis, D.C.; Gillette, J.R. and Brodie, B.B.: Acetaminophen-induced hepatic necrosis. II. Role of covalent binding in vivo. Journal of Pharmacology and Experimental Therapeutics 187: 195–202 (1973).

    CAS  Google Scholar 

  • Keele, K.D.: The pain chart. Lancet 2: 6–8 (1948).

    Article  PubMed  CAS  Google Scholar 

  • Lester, D.; Lolli, G. and Greenberg, L.A.: The fate of acetylsalicylic acid. Journal of Pharmacology 87: 329–342 (1946).

    CAS  Google Scholar 

  • Levy, G.: Comparison of dissolution and absorption rates of different commercial aspirin tablets. Journal of Pharmaceutical Sciences 50: 388–392 (1961).

    Article  PubMed  CAS  Google Scholar 

  • Levy, G.: Effect of certain tablet formulation factors on dissolution rate of the active ingredient. I. Importance of using appropriate agitation intensities for in vitro dissolution rate measurements to reflect in vivo conditions. Journal of Pharmaceutical Sciences 52: 1039–1046 (1963).

    CAS  Google Scholar 

  • Levy, G.; Antkowiak, J.M.; Procknal, J.A. and White, D.C.: Effect of certain tablet formulation factors on dissolution rate of the active ingredient. II. Granule size, starch concentration, and compression pressure. Journal of Pharmaceutical Sciences 52: 1047–1051 (1963).

    CAS  Google Scholar 

  • Levy, G. and Gumtow, R.H.: Effect of certain tablet formulation factors on dissolution rate of the active ingredient. III. Tablet lubricants. Journal of Pharmaceutical Sciences 52: 1139–1144 (1963).

    CAS  Google Scholar 

  • Levy, G. and Hollister, L.E.: Failure of U.S.P. disintegration test to assess physiologic availability of enteric coated tablets. New York State Journal of Medicine 64: 3002–3005 (1964).

    CAS  Google Scholar 

  • Lewis, J.W.; Bentley, K.W. and Cowan, A.: Narcotic analgesics and antagonists. Annual Review of Pharmacology 11: 241–270(1971).

    Article  PubMed  CAS  Google Scholar 

  • Lim, R.K.S.; Guzman, F.; Rodgers, D.W.; Goto, K.; Braun, C; Dickerson, G.D. and Engle, R.J.: Site of action of narcotic and non-narcotic analgesics determined by blocking bradykinin-evoked visceral pain. Archives International Pharmacodynamics 152: 25–58(1964).

    CAS  Google Scholar 

  • Livingston, W.K.: in Pain Mechanisms (Macmillan, New York 1947).

    Google Scholar 

  • Loan, W.B. and Morrison, J.D.: Strong analgesics: Pharmacological and therapeutic aspects. Drugs 5: 108–143 (1973).

    Article  CAS  Google Scholar 

  • McCleave, D.J. and Havill, J.: A review of acute salicylate poisoning. Anaesthesia and Intensive Care 4: 340–344 (1974).

    Google Scholar 

  • Mackenzie, J.: Some points bearing on the association of sensory disorders and visceral disease. Brain 16: 321–354(1893).

    Article  Google Scholar 

  • MacLagan, T.: The treatment of acute rheumatism by salicin. Lancet 1: 342–343 and 383–385 (1876).

    Article  Google Scholar 

  • Macklon, A.F.; Craft, A.W.; Thompson, M. and Kerr, D.N.S.: Aspirin and analgesic nephropathy, British Medical Journal 1: 597–600 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Major, C.T. and Pleuvry, B.J.: Effects of a-methyl-p-tyrosine, p-chloro-phenylalanine, L-β(3,4-dihydroxyphenyl) alanine, 5-hydroxy-tryptophan and diethyldithiocarbamate on the analgesic activity of morphine and methylamphetamine in the mouse. British Journal of Pharmacology 42: 512–521 (1971).

    Article  PubMed  CAS  Google Scholar 

  • Mehta, M.: in Intractable Pain (Saunders, London 1973).

    Google Scholar 

  • Melzack, R. and Wall, P.D.: Pain mechanisms: A new theory. Science 150: 971–978 (1965).

    Article  PubMed  CAS  Google Scholar 

  • Mills, D.G.; Borda, LT.; Philp, R.B. and Eldridge, C: Effects of in vitro aspirin on blood platelets of gastrointestinal bleeders. Clinical Pharmacology and Therapeutics 15: 187–192(1974).

    PubMed  CAS  Google Scholar 

  • Mitchell, J.R.; Jollow, DJ.; Potter, W.Z.; Davis, D.C.; Gillette, J.R. and Brodie, B.B.: Acetaminophen-induced hepatic necrosis I. Role of drug metabolism. Journal of Pharmacology and Experimental Therapeutics 187: 185–194(1973).

    CAS  Google Scholar 

  • Murray, R.M.: Analgesic nephropathy: Removal of phenacetin from proprietary analgesics. British Medical Journal 4: 131–132(1972).

    Article  PubMed  CAS  Google Scholar 

  • Murray, R.M.; Lawson, D.H. and Linton, A.L.: Analgesic nephropathy: Clinical syndrome and prognosis. British Medical Journal 1: 479–482 (1971).

    Article  PubMed  CAS  Google Scholar 

  • New Zealand Rheumatism Association Study: Aspirin and the kidney. British Medical Journal 1: 593–596 (1974).

    Google Scholar 

  • O’Reilly, R.A.; Sahud, M.A. and Aggeler, P.M.: Impact of aspirin and chlorthalidone on the pharmacodynamics of oral anticoagulant drugs in man. Annals of the New York Academy of Sciences 179: 173–186(1971).

    Article  PubMed  Google Scholar 

  • Papper, E.M.; Brodie, B.B. and Rovenstine, E.A.: Postoperative pain: Its use in the comparative evaluation of analgesics. Surgery 32: 107–109 (1952).

    PubMed  CAS  Google Scholar 

  • Parkhouse, J.: Recording and analysis of clinical data. British Journal of Anaesthesia 39: 35–37 (1967).

    Article  PubMed  CAS  Google Scholar 

  • Parkhouse, J.; Collie, J.A. and Wood, V.: A study of aspirin and nepenthe. British Journal of Anaesthesia 39: 38–49(1967).

    Article  PubMed  CAS  Google Scholar 

  • Parkhouse, J. and Hallinon, P.: A comparison of aspirin and paracetamol. British Journal of Anaesthesia 39: 146–154(1967).

    Article  PubMed  CAS  Google Scholar 

  • Parkhouse, J.; Heppenstall, C; Smith, E. and Wright, V.: An attempt to evaluate a rapidly acting oral analgesic. Canadian Medical Association Journal 100: 1057–1058(1969).

    PubMed  CAS  Google Scholar 

  • Parkhouse, J.; Lambrechts, W. and Simpson, B.R.J.: The incidence of postoperative pain. British Journal of Anaesthesia 33: 345–353 (1961).

    Article  PubMed  CAS  Google Scholar 

  • Parkhouse, J.; Rees-Lewis, M.; Skolnik, M. and Peters, H.: The clinical dose response to aspirin. British Journal of Anaesthesia 40: 433–441 (1968).

    Article  PubMed  CAS  Google Scholar 

  • Prescott, L.F.: Effects of acetylsalicylic acid, phenacetin, paracetamol and caffeine on renal tubular epithelium. Lancet 2: 91–96 (1965).

    Article  Google Scholar 

  • Prescott, L.F.: Clinically important drug interactions. Drugs 5: 161–186(1973).

    Article  PubMed  CAS  Google Scholar 

  • Prescott, L.F.; Newton, R.W.; Swainson, C.P.; Wright, N.; Forrest, A.R.W. and Matthew, H.: Successful treatment of severe paracetamol overdosage with cysteamine. Lancet 1: 588–592 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Prescott, L.F. and Wright, N.: The effects of hepatic and renal damage on paracetamol metabolism and excretion following overdosage. A pharmacokinetic study. British Journal of Pharmacology 49: 602–613 (1973).

    CAS  Google Scholar 

  • Proudfoot, A.T. and Wright, N.: Acute paracetamol poisoning. British Medical Journal 4: 557–558 (1970).

    Article  Google Scholar 

  • Rees, G.J.; Stead, A.L. and Bush, G.H.: Salicylate poisoning. British Medical Journal 2: 1454 (1960).

    Article  Google Scholar 

  • Rogers, A.: Pain and the cancer patient. Nursing Clinics of North America 2: 671–682 (1967).

    Google Scholar 

  • Schreiner, G.E.: The nephrotoxicity of analgesic abuse. Annals of Internal Medicine 57: 1047–1052 (1962).

    PubMed  CAS  Google Scholar 

  • Segar, W.E. and Holliday, M.A.: Physiologic abnormalities of salicylate intoxication. New England Journal of Medicine 259: 1191–1198(1958).

    Article  PubMed  CAS  Google Scholar 

  • Settipane, G.A.; Chafee, F.H. and Klein, D.E.: Aspirin intolerance. II A prospective study in an atopic and normal population. Journal of Allergy and Clinical Immunology 53: 200–204 (1974).

    Article  PubMed  CAS  Google Scholar 

  • Singer, R.B.: The acid-base disturbance in salicylate intoxication. Medicine 33: 1–13 (1954).

    Article  PubMed  CAS  Google Scholar 

  • Smith, G.M.; Egbert, L.D. and Beecher, H.K.: The submaximal effort tourniquet method of producing experimental pain in man: Sensitivity to 5mg of morphine and 0.6gr of aspirin. Federation Proceedings (Abstract) 25: 501, No. 2 part 1 (1966).

    Google Scholar 

  • Smith, J.B. and Willis, A.L.: Aspirin selectively inhibits prostaglandin production in human platelets. Nature 231: 235–237 (1971).

    CAS  Google Scholar 

  • Smith, M.J.H. and Smith, P.K. (Eds): in The Salicylates: A critical bibliographic review (Interscience Publishers, New York 1966).

    Google Scholar 

  • Smith, P.K.; Gleason, H.L.; Stoll, C.B. and Orgorzalek, S.: Studies on the pharmacology of salicylates. Journal of Pharmacology 87: 237–255 (1946).

    CAS  Google Scholar 

  • Starr, M.S. and West, G.B.: Bradykinin and oedema formation in heated paws. British Journal of Pharmacology 31: 178–187 (1967).

    CAS  Google Scholar 

  • Sunshine, A.; Laska, E.; Meisner, M. and Morgan, S.: Analgesic studies of indomethacin as analysed by computer techniques. Clinical Pharmacology and Therapeutics 5: 699–707 (1964).

    PubMed  CAS  Google Scholar 

  • Swerdlow, M. (Ed): in Relief of Intractable Pain (Excerpta Medica, Amsterdam 1974).

    Google Scholar 

  • Türker, K. and Kiran, B.K.: The antagonistic effect of noramidopyrine methanesulfonate on some pharmacological actions of the synthetic bradykinin. Arzneimittel-Forschung 14: 1318–1319(1964).

    Google Scholar 

  • Vane, J.R.: Inhibition of prostaglandin synthesis as a mechanism of action of aspirin-like drugs. Nature 231: 232–235(1971).

    CAS  Google Scholar 

  • Vane, J.R.: Prostaglandins and the aspirin-like drugs. Hospital Practice 7: 61–67 (1972).

    Google Scholar 

  • Winter, CA.: in Garattini and Dukes (Eds) Non-Steroidal Anti-inflammatory Drugs. (Excerpta Medica, Amsterdam 1965).

    Google Scholar 

  • Winters, R.W.; White, J.S.; Hughes, M.C. and Ordway, N.K.: Disturbances of acid-base equilibrium in salicylate intoxication. Pediatrics 23: 260–285 (1959).

    PubMed  CAS  Google Scholar 

  • Woodbury, D.M.: Analgesics and antipyretics; in Goodman and Gilman (Eds) The Pharmacological Basis of Therapeutics 3rd edition (Macmillan, New York 1968).

    Google Scholar 

  • Wright, N. and Prescott, L.F.: Paracetamol overdosage: Potentiation of hepatotoxicity by previous drug therapy. Scottish Medical Journal 18: 56–59 (1973).

    CAS  Google Scholar 

  • Yu, T.F. and Gutman, A.B.: Study of the paradoxical effects of salicylate in low, intermediate and high dosage on the renal mechanisms of excretion of urate in man. Journal of Clinical Investigation 38: 1298–1315(1959).

    Article  PubMed  CAS  Google Scholar 

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Parkhouse, J. Simple Analgesics. Drugs 10, 366–393 (1975). https://doi.org/10.2165/00003495-197510050-00007

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