ABSTRACT
BACKGROUND: The added benefits of angiotensin II type I receptor (AT(1)) blockers (ARBs) to ACE inhibition suggests that recommended doses of ACE inhibitors provide only partial inhibition of ACE in chronic heart failure (CHF). Accordingly, the level of ACE inhibition was assessed by the pressor response to angiotensin (Ang) I in patients who had been treated with recommended doses of ACE inhibitors. METHODS AND RESULTS: Forty-two patients with CHF receiving 40 mg/d of a long-acting ACE inhibitor or 150 mg of captopril were studied. Radial artery systolic pressure (RASP, mm Hg) was monitored noninvasively. The pressor response to ascending doses of Ang I was evaluated in all patients before and after administration of the ARB valsartan. The pressor response to Ang I before and after valsartan was also reevaluated in 11 patients after the dose of ACE inhibitor was doubled for 1 week. RASP increased linearly with significantly ascending doses of Ang I despite treatment with ACE inhibitors. The pressor response to Ang I was blunted significantly by valsartan. Ang I-induced increase in RASP did not correlate with duration of ACE inhibitor therapy. After the dose of ACE inhibitors was doubled, the pressor response to Ang I was no longer different from that noted after valsartan. CONCLUSIONS: Recommended doses of ACE inhibitors do not fully inhibit ACE in CHF. The level of ACE inhibition achieved is not related to duration of ACE inhibitor therapy. Greater ACE inhibition is also achieved at twice the recommended doses of ACE inhibitors.
Subject(s)
Angiotensin II/biosynthesis , Angiotensin I/pharmacology , Angiotensin Receptor Antagonists , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Antihypertensive Agents/therapeutic use , Blood Pressure/drug effects , Heart Failure/drug therapy , Peptidyl-Dipeptidase A/metabolism , Tetrazoles/therapeutic use , Valine/analogs & derivatives , Angiotensin I/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/pharmacology , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Antihypertensive Agents/administration & dosage , Antihypertensive Agents/pharmacology , Dose-Response Relationship, Drug , Drug Therapy, Combination , Enalapril/administration & dosage , Enalapril/therapeutic use , Female , Fosinopril/administration & dosage , Fosinopril/therapeutic use , Heart Failure/blood , Humans , Lisinopril/administration & dosage , Lisinopril/therapeutic use , Male , Receptor, Angiotensin, Type 1 , Receptor, Angiotensin, Type 2 , Receptors, Angiotensin/drug effects , Tetrazoles/administration & dosage , Tetrazoles/pharmacology , Treatment Failure , Valine/administration & dosage , Valine/pharmacology , Valine/therapeutic use , ValsartanABSTRACT
OBJECTIVE: To determine the safety and efficacy of 100 mg dapsone three times weekly for Pneumocystis carinii pneumonia (PCP) prophylaxis in HIV-infected, trimethoprim-sulfamethoxazole (TMP-SMX)-intolerant patients. DESIGN: Retrospective chart review of patients followed-up to 22 May 1992. SETTING: Infectious diseases outpatient clinic of a tertiary care center in suburban New York City. PATIENTS: Twenty-three HIV-infected patients requiring PCP prophylaxis with documented intolerance to TMP-SMX. MAIN OUTCOME MEASURES: Patients were followed clinically and with laboratory testing at approximately monthly intervals. RESULTS: Dapsone was discontinued in nine (39%) patients because of adverse reactions. All reactions occurred within the first 2 months of treatment. Two (14%) of the remaining 14 patients developed histologically proven PCP over 126 patient-months of follow-up. CONCLUSION: Approximately 40% of TMP-SMX-intolerant HIV-infected individuals are also intolerant of dapsone. Prophylaxis failures may be expected on a dose regimen of 100 mg dapsone three times weekly. More experience with other dose regimens and alternative agents is needed.
