Summary
Tramadol is a centrally acting analgesic that has been shown to be effective in a variety of acute and chronic pain states. Unlike other centrally acting analgesics, it exerts a dual action by binding to the opioid receptor site in the central nervous system and by weakly inhibiting the reuptake of biogenic amines. Tramadol is rapidly and almost completely absorbed, with an onset of action occurring within 1 hour of oral administration. The recommended dosage is 50 to 100mg every 4 to 6 hours; however, regular administration is an alternative, particularly for chronic pain states such as osteoarthritis, where the use of the recently developed sustained release formulation may represent an important advantage. Published studies specifically evaluating the use of tramadol in this disease support its effectiveness. Nausea, drowsiness, constipation, dizziness, and sweating have been reported in association with tramadol use. Nausea occurs early in the course of administration, and may be reduced by slowly titrating the dose of tramadol against response. Tramadol would appear to be particularly useful in the elderly population affected by osteoarthritis because, unlike nonsteroidal anti-inflammatory drugs, it does not aggravate hypertension or congestive heart failure, nor does it have the potential to cause peptic ulcer disease. Compared with narcotics, tramadol does not induce significant respiratory depression, constipation, or have significant abuse potential.
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References
Moskowtiz RW. Osteoarthritis. In: Katz WA, editor. Diagnosis and management of rheumatic diseases. Philadelphia: JB Lippincott, 1988: 569–81.
National Pain Survey, Lewis Harris and Associates, Inc., 1994
Bradley JD, Brandt KD, Katz BP, et al. Comparison of an anti- inflammatory dose of ibuprofen, analgesic dose of ibuprofen and acetaminophen in the treatment of osteoarthritis of the knee. N Engl J Med 1991; 325: 87–91.
Simon L. Toxicities of nonsteroidal anti-inflammatory drugs. Curr Opin Rheumatol 1992; 4: 301–8.
Friderichs E, Felgenhuer F, Jongschaap P, et al. Pharmakologische Untersuchungen zur Analgesie, Abhängigkeits und Toleranzentwicklung von Tramadol, einem stark wirkenden Analgetikum. Arzneimittelforschung/Drug Res 1978; 28: 122.
Barth H, Durra S, Giertz H, et al. Long-term administration of the centrally acting analgesic tramadol did not induce dependence or tolerance [abstract 439]. Pain 1987; Suppl. 4: S231
Keup W. Missbrauchsmuster bei Abhangigkeit von Alkohol, Medikamenten und Drogen: Frühwarnsystem-daten für die Bundesrepublik Deutschland 1976–1990. Lambertus, Freiberg im Breisgau, 1993
Collart L, Luthy C, Dayer P. Multimodal analgesic effect of tramadol [abstract]. Clin Pharmacol Ther 1993; 53: 223.
Raffa RB, Nayak RK, Liao S, et al. Mechanism(s) of action and pharmacokinetics of tramadol hydrochloride. Rev Contemp Pharmacother 1995; 6: 485–97.
Grond S, Meuser T, Zech D, et al. Analgesic efficacy and safety of tramadol enantiomers in comparison with the racemate: a randomised, double-blind study with gynaecological patients using intravenous patient-controlled analgesia. Pain 1995; 62: 313–20.
Liao S, Hill JF, Nayak RK. Pharmacokinetics of tramadol following single and multiple oral doses in man [abstract]. Pharm Res 1992; 9 Suppl. 10: S308.
Lintz W, Barth H, Osterloh G, et al. Bioavailability of enterai tramadol formulations. 1st communication: capsules. Arzneimittelforschung/Drug Res 1986; 36: 1278–83.
Paar WD, Frankus P, Dengler HJ. The metabolism of tramadol by human liver microsomes. Clin Invest 1992; 70: 708–10.
Lintz W, Erlacin S, Frankus E, et al. Biotransformation of tramadol in man and animal. Arzneimittelforschung/Drug Res 1981; 31: 1932–43.
Suvonnakote T, Thitadilok W, Atisook R, et al. Pain relief during labour. J Med Assoc Thai 1986; 69: 575–80.
ULTRAM® (tramadol HCl) prescribing information. Raritan, NJ: McNeil Pharmaceutical, 1995
Grünenthal, data on file. Report no. FO-PK 163/1
Budd K. Chronic pain: challenge and response. Drugs 1994; 47 Suppl. 1: 33–8.
Grünenthal, data on file. Report no. FO-PK 240
Grünenthal, data on file. Report no. FO-PK 241
Hennies HH, Friderichs E, Schneider J. Receptor binding, analgesic and antitussive potency of tramadol and other selected opioids. Arzneimittelforschung/Drug Res 1988; 38: 877–80.
TRAMAL® (Tramadol Hcl). Prescribing information. Grünenthal GmbH, Stolberg, Germany
RW Johnson Pharmaceutical Research Institute, data on file
Sunshine A, Alaska E, Slafta J. A comparison of the analgesic effects of tramadol (Upjohn U-26, 225A and propoxyphene HC1). Bulletin. Problems of drug dependence, National Academy of Sciences, National Research Counsel, Washington, DC, 1970, 6901–4
Sunshine A, Olson NZ, Zighelboim I, et al. Analgesic oral efficacy of tramadol hydrochloride in post-operative pain. Clin Pharmacol Ther 1992; 51: 740–6.
Sunshine A. New clinical experience with tramadol. Drugs 1994; 47 Suppl. 1: 8–18.
Gobel H, Stadler Th. Treatment of pain due to postherpetic neuralgia with tramadol. Results of an open, parallel pilot study versus clomipramine with or without levomepromazine. Clin Drug Invest 1995; 10: 208–14.
Rauck RL, Ruoff GE, McMillen JI. Comparison of tramadol and acetaminophen with codeine for long-term pain management in elderly patients. Curr Ther Res 1994; 55: 1417–31.
Roth SH. Safety and efficacy of tramadol HC1 in breakthrough osteoarthritis pain. Rheumatol Eur 1995; 24 Suppl. 12: 310.
Bird HA, Hill J, Stratford GC, et al. A double-blind cross-over study comparing the analgesic efficacy of tramadol with pentazocine in patients with osteoarthritis. J Drug Dev Clin Pract 1995; 7: 181–8.
Rousi T, Pohjola R, Martio J. Tramadol in the treatment of osteoarthritic pain: a double-blind, crossover study versus dextropropoxyphene. XIIth European Congress on Rheumatology: Jun 30–Jul 6: Budapest, Hungary: 1991
Pavelka K. Functional outcome and joint pain is improved in osteoarthritis patients receiving an NSAID or a centrally acting analgesic. Ann Rheum Dis. In press
Cossmann M, Wilsmann KM. Parenteral administration of tramadol (Tramai®): an open clinical trial to assess the effect and side effects after single parenteral application. Münch Med Wochenschr 1988; 130: 633–6.
Cossmann M, Wilsmann KM. Treatment of prolonged pain: assessment of the efficacy and safety of repeated administration of tramadol (Tramai®). Münch Med Wochenschr 1987; 129: 851–4.
Cossmann M, Wilsmann KM. Effect and side effect of tramadol: an open phase IV study with 7198 patients. Therapiewoche 1987; 37: 3475–85.
Lee CR, McTavish D, Sorkin EM. Tramadol: a preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in acute and chronic pain states. Drugs 1993; 46: 313–40.
Riedel F, von Stockhausen HB. Severe cerebral depression after intoxication with tramadol in a 6-month old infant. Eur J Clin Pharmacol 1984: 26: 631–2
Cossmann M, Kohnen C. General tolerability and adverse event profile of tramadol hydrochloride. Rev Contemp Pharmacother 1995; 6: 513–31.
Dalgin PH. Use of tramadol in chronic pain. Clin Geriatr 1995; 3: 17–30.
Kayser V, Besson JM, Guilbaud G. Effects of the analgesic agent tramadol in normal and arthritic rats; comparison with the effects of different opioids, including tolerance and cross tolerance to morphine. Eur J Pharmacol 1991; 195: 37–45.
Preston KL, Jasinski DR, Testa M. Abuse potential and pharmacologic comparison of tramadol and morphine. Drug Alcohol Depend 1991; 27: 7–17.
Richter W, Barth H, Flohe L, et al. Clinical investigation of the development of dependence during oral therapy with tramadol. Arzneimittelforschung/Drug Res 1985; 35: 1742–4.
Baum C, Kennedy DL, Forbes MB. Utilization of nonsteroidal antiinflammatory drugs. Arthritis Rheum 1985; 28: 686–92.
Brandt KD. Should osteoarthritis be treated with nonsteroidal antiinflammatory drugs? Rheum Dis Clin 1993; 19: 697–712
Todd PA, Clissold SP. Naproxen. A reappraisal of its pharmacology and therapeutic use in rheumatic diseases in pain states. Drugs 1990; 40: 91–137.
Myers SL, Brandt KD, Ehrlich JW, et al. Synovial inflammation in patients with early osteoarthritis of the knee. J Rheumatol 1990; 17: 1662–9.
Jones AC, Berman P, Doherty M. Nonsteroidal anti-inflammatory drug usage and requirement in elderly acute hospital admissions. Br J Rheumatol 1992; 31: 45–8
Hochberg MC, Altman RD, Brandt KD, et al. Guidelines for the medical management of osteoarthritis. Part I. Osteoarthritis of the hip. Arthritis Rheum 1995; 38: 1335–40.
Hochberg MC, Altman RD, Brandt KD, et al. Guidelines for the medical management of osteoarthritis. Part II. Osteoarthritis of the knee. Arthritis Rheum 1995; 38: 1341–6.
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Katz, W.A. Pharmacology and Clinical Experience with Tramadol in Osteoarthritis. Drugs 52 (Suppl 3), 39–47 (1996). https://doi.org/10.2165/00003495-199600523-00007
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DOI: https://doi.org/10.2165/00003495-199600523-00007