J Am Board Fam Pract: first published as 10.3122/jabfm.5.3.319 on 1 May 1992. Downloaded from Neutralization Of The Effects Of Captopril By The Use Of Ibuprofen In An Elderly Woman

David V. Espino, M.D., and Malcolm C. Lancaster, M.D.

The use of converting (ACE) ministration of methyldopa. Captopril was pre­ inhibitors has become more widespread because scribed at 12.5 mg three times a day. Three of their favorable results in lowering blood pres­ days later her blood pressure while sitting was sure, as well as their favorable side-effect profile. 90/60 mmHg, with no orthostatic symptoms or Many elderly patients have multiple medication changes. The methyldopa dosage was sub­ changes for chronic diseases, however, and the sequently discontinued. Because her blood pres­ potential for adverse drug interactions between sure measurements continued to be about 160/90 ACE inhibitors and other medications is always mmHg, her captopril dosage was increased to present. 25 mg three times a day. During the subsequent The following case report demonstrates that 6 weeks the patient's blood pressure measure­ the hypotensive effect of captopril can be neutral­ ments ranged from 120170 to 180/100 mmHg. ized by concomitant use of ibuprofen, a com­ Three months after the original visit, the monly used nonsteroidal anti-inflammatory patient's ibuprofen dosage was increased to 800 agent. mg three times a day. Concomitantly her blood pressure measurements became consistently case Report higher than 150/90 mmHg. Her captopril dosage A 70-year-old white woman had a history of was increased first to 37.5 mg three times a day that was controlled by methyldopa, and then to 50 mg three times a day, with no 250 mg four times a day, and trichlormethiazide, significant beneficial response in blood pressure 2 mg once a day. Her average blood pressure control. , 12.5 mg daily, was reading while receiving these medications was therefore added. 130/80 mmHg. For the next 3 months, during which time the In an attempt to institute monotherapy for the patient took ibuprofen intermittently, her blood http://www.jabfm.org/ patient's blood pressure, trichlormethiazide was pressure values continued to be erratic, but lower, discontinued; no elevation in blood pressure was ranging from 120170 to 156/100 mmHg. recorded on close reevaluation. Two weeks later During periods in which the patient was not she was referred to a physiatrist for evaluation of taking ibuprofen, her blood pressure readings osteoarthritis of the hip. She was prescribed ranged from 122178 to 137185 mmHg, contrast­ ibuprofen therapy, 400 mg four times daily, and ingwith the blood pressure readings ranging from had initial pain relief. Her home-monitored 160/95 to 165/100 mmHg while she was taking on 26 September 2021 by guest. Protected copyright. blood pressure measurements, however, appeared 400 mg of ibuprofen three times a day. Ibuprofen to rise with the addition ofibuprofen to her treat­ was discontinued, and the patient was prescribed ment regimen. sulindac, 150 mg twice a day. The patient's blood Two weeks later the patient reported that her pressure dropped within 2 days to consistent home blood pressure reading was 170/110 values of about 130/80 mmHg with no further mmHg. In the office her blood pressure was re­ change in her captopril or hydrochlorothiazide corded as 180/125 mmHg despite continued ad- dosage. The hydrochlorothiazide was sub­ sequently discontinued, and the patient's blood pressure continues to be well controlled on Submitted, revised, 13 August 1991. From the Division of Geriatrics, Department of Family Prac­ captopril alone, which she has been taking for a tice, University of TeDS Health Science Center at San Antonio. total of 8 weeks. Her pain caused by osteoarthritis Address reprint requests to David Espino, M.D., Division of has also been well controlled on sulindac. During Geriatrics, Department of Family Practice, University ofTeDS Health Science Center at San Antonio, 7703 Floyd Curl Drive, the time the changes in medication regimens San Antonio, TX 78284-7795. were occurring, the patient was taking no other

Effects of Captopril and Ibuprofen 319 J Am Board Fam Pract: first published as 10.3122/jabfm.5.3.319 on 1 May 1992. Downloaded from

medication, and there had been no other changes competitive inhibition of the effects of captopril in the patient's medication regimen, lifestyle, on this system. This inhibition, in turn, leads to a or health status. Furthermore, the patient's decrease in the hypotensive effects of captopril renal function, as measured by serum creatinine when ibuprofen is jointly administered, even in (mean =70 jJ.mollL [0.8 mg/dL]) and blood urea over-the-counter dosages. IS nitrogen (mean =8.6 mmollL [24 mgldL)), was The exact pathways by which ibuprofen in­ normal and unchanged during this period. hibits the hypotensive effects of captopril in pa­ tients with low remain unknown, because Discussion current effects cannot definitely be ascribed to the This case report shows that ibuprofen in an eld­ changes in tissue hormone production previously erly patient can interfere with the antihyperten­ described.16,17 It is possible that could be sive effects of captopril. a better alternative in the aged because it has been Anti-inflammatory agents are capable of in­ shown to be resistant to the effects of indometha­ hibiting antihypertensive effects of certain medi­ cin. IS Until· these mechanisms are determined, cations. That different nonsteroidal anti-inflam­ however, extreme care should be exercised when matory agents interfere with the J3-blocker and prescribing captopril and ibuprofen in concert. In classes of antihypertensive medications addition, if it is necessary to use the two medica­ has been well documented. 1-4 The blunting of the tions together, the patient's blood pressure should antihypertensive action of ACE inhibitors by in­ be closely monitored. domethacin has also been described.s,6 It is also important to mention that sulindac The ability of captopril to reduce blood pres­ could be a better alternative if concomitant treat­ sure is believed to be related, in part, to inhibition ment with an antihypertensive medication is con­ of the conversion of angiotensin I to angiotensin sidered. Sulindac has had negligible interactions II7,s (Figure 1). In addition, the administration of when used with other antihypertensive agentsl9 captopril potentiates the release of and certainly should be considered. Sulindac with its concomitant effects on renal vasodilata­ also does not appear to inhibit bradykinin to the tion.9 This effect appears to be mediated by a extent that other nonsteroidal anti-inflammatory prostacyclin-like substance that can be inhibited agents do.20 by the administration of indomethacin, ibupro­ Finally, although the 150 mgld dosage of fen, and possibly other nonsteroidal anti-inflam­ captopril is sometimes necessary for adequate http://www.jabfm.org/ matory agents. 10,11 antihypertensive control,21 it is a large dosage for With low renin concentrations or in a sodium­ an elderly person, even for one who has normal restricted state, such as that found in the aged, the renal function, and, as such, warrants close moni­ potentiation of bradykinin and the toring of the patient. system appears to supervene the effects of the renin-angiotensin system as the hypotensive ac­ Summary on 26 September 2021 by guest. Protected copyright. tion of captopril.l2-14 Consequently, the effects of This case report demonstrates that the antihyper­ ibuprofen on the prostaglandin system can lead to tensive effects of captopril were neutralized by the concomitant administration of ibuprofen. Angiolensfnogen If elderly patients on ACE inhibitors show evi­ RenIn ----+! AIdosIitrOne dence of a "noncompliant" worsening of their hypertension, a thorough review of all the -, j~r;:::-">-=--= patient's medications, including the use of over­ the-counter ibuprofen, should be undertaken. ~~ @ Enzyme

_ --:----+" Sradytdnin _v_ References 1. Salvetti A, Arzilli F, Pedrinelli R, Beggi P, Motolese M. Interaction between oxprenolol and indometha­ r~=='''''kWl"?1 cin on blood pressure in. essential hypertensive pa­ ProoIOc:yC:tln-lllo w.._ tients. Eur j Clin Pharmaco11982; 22:197-201. Fipre 1. Proposed mechanisms oldie antihypertensive 2. Watkins j, Abbott EC, Hensby CN, Webster j, eft'eds of captoprU. Dollery CT. Attenuation of hypotensive effect of

320 JABFP May-june 1992 Vol. 5 No.3 J Am Board Fam Pract: first published as 10.3122/jabfm.5.3.319 on 1 May 1992. Downloaded from propranolol and thiazide by indomethacin. sive mechanism of captopril in low re~ hyperten­ Br MedJ 1980; 281:702-5. sion. Clin Sci 1980; 59(SuppI6): 1415-144S. 3. Salvetti A, Petrinelli R, Alberici P, Magagna A, 13. Moore 'I}, Crantz FR, Hollenberg NK, Kiletsky RJ, Abdel-Haq B. The influence of indomethacin and Leboff MS, Swartz SL, et al. Contribution of prosta­ sulindac on some pharmacologic actions of atenolol glandins to the antihypertensive action of captopril in hypertensive patients. Br J Clin Pharmacol 1984; in essential hypertension. Hypertension 1981; 3: 17(Suppl):108S-111S. 168-73. 4. Steiness E, Waldorff S. Different interactions of in­ 14. Miller LG, PrichardJG. Selecting nonsteroidal anti­ domethacin and sulindac with thiazides in hyperten­ inflammatory drugs: pharmacologic and clinical sion. Br MedJ 1982; 285:1702-3. considerations. J Am Board Fam Pract 1989; 2: 5. Flower RJ, Moncada S, Vane JR. Analgesic-anti­ 257-71. pyretics and anti-inflammatory agents; drugs em­ 15. Radack KL, Deck CC, Bloomfield SS.lbuprofen in­ ployed in the treatment of gout. In: Gilman AG, terferes with the efficacy of antihypertensive drugs. Goodman LS, Rail Tw, Murad F, editors. Good­ A randomized, double-blind, placebo-controlled man and Gilman's the pharmacological basis of ther­ trial of ibuprofen compared with acetaminophen. apeutics. 7th ed. New York: Macmillan, 1985: Ann IntemMed 1987; 107:628-35. 674-715. 16. Williams GH. Converting-enzyme inhibitors in the 6. Salvetti A, Abdul-Haq B, Magagna A, Pedrinelli R. treatment of hypertension. N Engl J Med 1988; Indomethacin reduces the antihypertensive action 319:1517-25. ofenalapri1. ClinExpHypertens 1987; 9:559-67. 17. Seto S, Aoi W, Iwami K, Yamaguchi T, Ashizawa N, 7. Ram Cv. Captopril. Arch Intern Med 1982; Kusano S, et al. Effect of propranolol and indo­ 142:914-6. methacin on the depressive action of captopril in 8. Schaefer RM, Heidland A. Captopril - indications patients with essential hypertension. am Exp and clinical problems. Contrib Nephrol 1984; Hypertens 1987; 9:623-7. 43:182-203. 18. Shaw W, Shapiro D, Antonello J, Cressman M, 9. Swartz SL, Williams GH, Hollenberg NK, Levine V1asses P, 0pariI S. Indomethacin does not blunt the L, Dlohy RG, Moore 'I}. Captopril-induced antihypertensive effect oflisinopril. Clin Pharmacol changes in prostaglandin production: relationship Ther 1987; 41 :219. Abstract. to vascular responses in nonnal man. J Clin Invest 19. Schuna AA, Vejraska BD, HiattJG, Kochar M, Day 1980; 65:1257-64. R, Goodfriend TL. Lack of interaction between 10. Ogihara T, Maruyama A, Hata T, Mikami II, sulindac or naproxen and propranolol in hy­ Nakamaru M, Nab T, et al. Honnonal responses to pertensive patients. J Clin Pharmacol 1989; 29: long-tenn converting enzyme inhibition in hyperten­ 524-8. sive patients. ClinPharmacol Ther 1981; 30:328-35. 20. Puddey IB, Berlin LJ, Vandongen R, Banks R, Rouse 11. Fujita T, Yamashita N, Yamashita K. Effect of indo­ I. Differential effects of sulindac and indomethacin http://www.jabfm.org/ methacin on antihypertensive action of captopril in on blood pressure in treated essential hypertensive hypertensive patients. Clin Exp Hypertens 1981; subjects. Clin Sci 1985; 69:327-36. 3:939-52. 21. Jenkins AC, Knill JR, Dreslinski GR. Captopril in 12. Abe K, Ito T, Sato M, Haruyama T, Sato K, Ornata the treattnent of the elderly hypertensive patient. K, et a1. Role of prostaglandin in the antihyperten- Arch IntemMed 1985; 145:2029-31. on 26 September 2021 by guest. Protected copyright.

Effects ofCaptopril and Ibuprofen 321