N-Acetylcysteine (NAC) may potentiate the antihypertensive effect of ACE inhibitors via a nitric oxide-dependent mechanism (Suárez et al. 1995). NAC (1200 mg/day) potentiated the reduction in systolic and diastolic blood pressure induced by lisinopril (10 to 30 mg/day) in six patients with essential hypertension. In spontaneously hypertensive rats, NAC (300 mg/kg IV) potentiated the blood-pressure lowering effects of captopril and enalaprilat (Ruiz et al. 1994).

Treatment with NAC infusions (4 to 10 d/day) combined with prednisone (1 mg/kg) reversed cholestatic jaundice and pure red cell aplasia in a patient receiving gold sodium thiomalate (160 mg IM) for progressive psoriatic arthritis (Hansen et al. 1991). It is not known if these effects were attributable to NAC combined with prednisone or NAC therapy alone.

Adjunctive treatment with high dose NAC (600 mg po tid) in patients on maintenance immunosuppressive therapy for fibrosing alveolitis positively affected clinical course and pulmonary function (Behr et al. 1997). These findings may warrant further investigation in controlled clinical trials.

In one in vitro study, NAC (1 mM) significantly inhibited cisplatin-induced reactive oxygen species, an indicator of cytotoxicity, in bladder cancer cells (Miyajima et al. 1999). The reduction was attributed to the ability of NAC to enhance glutathione levels.

In vitro and in vivo studies have established that NAC protects against doxorubicin-induced cardiotoxicity (D'Agostini et al. 1998; Doroshow et al. 1981). NAC interacted synergistically with doxorubicin to prevent tumorigenicity, metastasis, and alopecia in mice (D'Agostini et al. 1998). In addition, NAC, alone and in combination with doxorubicin, enhanced survival in mice injected with melanoma cells (D'Agostini et al. 1998; De Flora et al. 1996). Clinical trials are needed to confirm these effects in humans.

In vitro, NAC potentiated the antiplatelet effects of nitroglycerin (Chirkov and Horowitz 1996).

Clinically, the combination of NAC (bolus dose of 2 g) and nitroglycerin (1.5 µg/kg/min) prolonged vasodilation and minimized the development of tolerance in patients with angina pectoris and normal left ventricular function (Pizzulli, et al. 1997). Positive results were also obtained in a double blind, placebo-controlled study of 200 patients with unstable angina taking transdermal nitroglycerin either alone or in combination with NAC; the combination of NAC and nitroglycerin resulted in fewer deaths and myocardial infarctions (Ardissino et al. 1997). In another randomized, double blind, placebo-controlled study, NAC (2400 mg bid) potentiated the effects of isosorbide-5-mononitrate (60 mg po) and increased exercise capacity in 10 patients with angina pectoris, both without nitrate tolerance (Svendsen et al. 1989). Although NAC may prevent nitrate tolerance, the high incidence of side effects, particularly intolerable headache, may preclude its clinical use (Ardissino et al. 1997; Iversen 1992).

In one study, topical application of NAC (15% w/v lotion) and oxiconazole prolonged the mean residence time of oxiconazole in the upper nail layers (51 to 100 mm) by as much as 73% (van Hoogdalem et al. 1997). NAC may increase binding of oxiconazole to nails.

Ardissino D, Merlini PA, Savonitto S, Demicheli G, et al. Effect of transdermal nitroglycerin or N-Acetylcysteine, or both, in the long-term treatment of unstable angina pectoris. J Am Coll Cardiol. 1997;29(5):941-947.

Behr J, Maier K, Degenkolb B, Krombach F, Vogelmeier C. Antioxidative and clinical effects of high-dose N-acetylcysteine in fibrosing alveolitis. Am J Respir Crit Care Med. 1997;156:1897-1901.

Chirkov YY, Horowitz JD. N-Acetylcysteine potentiates nitroglycerin-induced reversal of platelet aggregation. J Cardiovasc Pharmacol. 1996;28(3):375-380.

D'Agostini F, Bagnasco M, Giunciuglio D, Albini A, De Flora S. Inhibition by oral N-acetylcysteine of doxorubicin-induced clastogenicity and alopecia, and prevention of primary tumors and lung micrometastases in mice. Int J Oncol. 1998;13:217-224.

De Flora S, D'Agostini F, Masiello L, Giunciuglio D, Albini A. Synergism between N-Acetylcysteine and doxorubicin in the prevention of tumorigenicity and metastasis in murine models. Int J Cancer. 1996;67:842-848.

Doroshow JH, Locker GY, Ifrim I, Myers CE. Prevention of doxorubicin cardiac toxicity in the mouse by N-Acetylcysteine. J Clin Invest. 1981;68:1053-1064.

Hansen RM, Varma RR, Hanson GA. Gold induced hepatitis and pure red cell aplasia. Complete recovery after corticosteroid and N-Acetylcysteine therapy. J Rheumatol. 1991;18:1251-1253.

Iversen HK. N-Acetylcysteine enhances nitroglycerin-induced headache and cranial arterial responses. Clin Pharmacol Ther. 1992;52:125-133.

Miyajima A, Nakashima J, Tachibana M, Nakamura K, et al. N-Acetylcysteine modifies cis-Dichlorodiammineplatinum-induced effects in bladder cancer cells. Jpn J Cancer Res. 1999;90:565-570.

Pizzulli, L, Hagendorff A, Zirbes M, Jung W, Lüderitz B. N-Acetylcysteine attenuates nitroglycerin tolerance in patients with angina pectoris and normal left ventricular function. Am J Cardiol. 1997;79:28-33.

Ruiz FJ, Salom MG, Ingles AC, Quesada T, et al. N-acetyl-L-cysteine potentiates depressor response to captopril and enalaprilat in SHRs. Am J Physiol. 1994;267(36):R767-R772.

Suárez C, Del Arco C, Lahera V, Ruilope LM. N-Acetylcysteine potentiates the antihypertensive effect of angiotensin converting enzyme inhibitors [letter]. Am J Hypertens. 1995;8:859-861.

Svendsen JH, Klarlund K, Aldershvile J, Waldorff S. N-Acetylcysteine modifies the acute effects of isosorbide-5-mononitrate in angina pectoris patients evaluated by exercise testing. J Cardiovasc Pharmacol. 1989;13:320-323.

van Hoogdalem EJ, van den Hoven WE, Terpstra IJ, van Zijtveld J, Verschoor, JSC. Nail penetration of the antifungal agent oxiconazole after repeated topical application in healthy volunteers, and the effect of acetylcysteine. Eur J Pharm Sci. 1997;5:119-127.