Pharmacokinetic–Hemodynamic Interactions Between Vasopressin and Nitroglycerin: Comparison Between Intravenous and Cutaneous Routes of Nitrate Delivery

Blei, Andrés T.; Friedman, Steve; Gottstein, Jeanne; Robertson, Gary; Fung, Ho‐Leung

doi:10.1002/hep.1840050219

Cited by 16 publications

(3 citation statements)

References 27 publications

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“…It is, of course very difficult to administer a drug sublingually when the patient is unable to cooperate. Perhaps nitroglycerin can be administered transdermally for this purpose (18). Our trial, however, clearly demonstrates that nitroglycerin can prevent some of the complications of vasopressin.…”

Section: Previous Controlled Trials Have Shown That the Efficacy Of Imentioning

confidence: 72%

Controlled trial of vasopressin plus nitroglycerin vs. vasopressin alone in the treatment of bleeding esophageal varices

et al. 1986

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Thirty-nine patients admitted during a 16-month period for acute bleeding from varices confirmed by emergency endoscopy were randomized to receive either continuous intravenous infusions of vasopressin alone (0.66 units per min) (Group I: 19 patients) or vasopressin plus sublingual nitroglycerin (0.6 mg every 30 min for 6 hr) (Group II: 20 patients). The two groups of patients were similar in the type and severity of their cirrhosis. Bleeding was controlled initially in 47% (9/19) of the patients in Group I and 55% (11/20) of the patients in Group II after 6 hr of infusion (not statistically significant). Complete control of bleeding during 24 hr of infusion was achieved in only 4 of 19 patients in Group I (21%) but in 9 of 20 in Group II (45%). This difference is not statistically significant. The total number of patients with complications during infusions were significantly different statistically in the vasopressin and vasopressin-nitroglycerin groups, respectively (17/19 vs. 7/20, p less than 0.001). Major complications requiring immediate cessation of infusions were observed in 6 of 19 of the patients in Group I (32%) and in 2 of 20 in Group II (10%) (p less than 0.05). Mortality (58% in Group I, 55% in Group II) and transfusion requirements were similar in the two groups. This study shows that the addition of sublingual nitroglycerin to intravenous vasopressin does not alter the efficacy of vasopressin alone in controlling hemorrhage from esophageal varices, but it does significantly reduce the complications.

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Section: Previous Controlled Trials Have Shown That the Efficacy Of Imentioning

confidence: 72%

Controlled trial of vasopressin plus nitroglycerin vs. vasopressin alone in the treatment of bleeding esophageal varices

et al. 1986

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“…In this regard, the PPVL rat model has proven adequate for the assessment of the beneficial effects of new pharmacological agents used in the treatment of portal hypertension, such as ␤-blockers, [33][34][35] nitrates, 36 and spironolactone. 37 Therefore, the results of the present study strongly support the conclusion that F-180 has significant therapeutic potential and may represent a new pharmacological alternative in the medical treatment of portal hypertension.…”

Section: Discussionmentioning

confidence: 99%

Effects of F-180, a new selective vasoconstrictor peptide, compared with terlipressin and vasopressin on systemic and splanchnic hemodynamics in a rat model of portal hypertension

Bernadich

Bandi

Melin³

et al. 1998

Hepatology

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The present study is aimed at characterizing the portal, splanchnic, and systemic circulatory effects of F-180, a new long-acting analog of vasopressin (VP) with selective effect on the vascular (V 1 ) receptor, both in normal rats and in portal-hypertensive animals. In preliminary vasopressor tests, F-180 was 18 times more potent than terlipressin (TP) (164 ؎ 10 IU ؋ mmol ؊1 vs. 9.2 ؎ 1.2 IU ؋ mmol ؊1 ) and four times less potent than arginine VP (614 ؎ 25 IU ؋ mmol ؊1 ). F-180 had negligible antidiuretic potency, resulting in vascular selectivity (V 1 /V 2 ) of 858 compared with 1.0 for VP and 2.2 for TP. In portal-hypertensive rats with partial portal vein ligation (PPVL), the vasopressor effect of F-180 was 19 times that of TP on a molar basis (ED 50 F-180: 0.54 vs. TP: 10.02 nmol ؋ kg ؊1 ). At low doses (0.405 nmol ؋ kg ؊1 ), F-180 significantly reduced portal pressure (PP) (؊13.8% ؎ 6.7%) and superior mesenteric artery blood flow (SMABF) (؊25.6% ؎ 4.5%), whereas TP at 8.10 nmol ؋ kg ؊1 was required to achieve comparable splanchnic effects; however, this dose caused a significantly greater increase in mean arterial pressure (MAP) than F-180 at 0.405 nmol ؋ kg ؊1 (28.2% ؎ 2.7% vs. 8.9% ؎ 2.7% at 20 minutes; P F .05). F-180 at 0.405 nmol ؋ kg ؊1 had effects on PP and SMABF similar to a 30-minute intravenous infusion of VP at 10 mU ؋ kg ؊1 in PPVL rats, but VP caused a significantly greater elevation in systemic vascular resistance (SVR) and MAP, and more pronounced reduction in cardiac index (P F .05). (HEPATOLOGY 1998;27:351-356.)

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“…Only two of the eleven randomized trials investigating vasopressin have been placebo controlled, and there remains considerable doubt about vasopressin's real effectiveness [13]. The combination of vasopressin wih nitroglycerin may be more effective [3,17,19,57]. It is the current recommended therapy in Cape Town, where the nitroglycerin is administered sublingually.…”

Section: Immediate Managementmentioning

confidence: 96%

The use of sclerotherapy for the management of oesophageal varices in portal hypertension

Terblanche

1988

Surg Endosc

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Although sclerotherapy is currently the most widely used treatment for the management of both acute variceal bleeding and the long-term management of patients with varices, its definitive role in the treatment of these patients has yet to be finally proven. Sclerotherapy appears to be the most effective treatment for the majority of patients with acute variceal bleeding. Failures require either a shunt or a transection and/or devascularisation procedure. Current evidence favours simple staple gun transection or a shunt (either a portacaval shunt or a side-to-side narrow diameter polytetrafluoroethylene graft between the portal vein and vena cava). In long-term management of patients after a variceal bleed the currently favoured treatment is repeated sclerotherapy. However, failures should be identified early. We define failures as patients who present with varices that are either difficult to eradicate by sclerotherapy or who have repeated life-threatening variceal bleeds during the course of repeated injection sclerotherapy. Such patients should have either a portal-to-systemic shunt or a transection and devascularisation operation. Further controlled trials are required to define the specific indications for the individual forms of therapy. Prophylactic treatment for varices that have not yet bled is unjustified at present.

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Pharmacokinetic–Hemodynamic Interactions Between Vasopressin and Nitroglycerin: Comparison Between Intravenous and Cutaneous Routes of Nitrate Delivery

Cited by 16 publications

References 27 publications

Controlled trial of vasopressin plus nitroglycerin vs. vasopressin alone in the treatment of bleeding esophageal varices

Controlled trial of vasopressin plus nitroglycerin vs. vasopressin alone in the treatment of bleeding esophageal varices

Effects of F-180, a new selective vasoconstrictor peptide, compared with terlipressin and vasopressin on systemic and splanchnic hemodynamics in a rat model of portal hypertension

The use of sclerotherapy for the management of oesophageal varices in portal hypertension

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