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`March 4, 1999 Volume 83, Issue 5, Supplement 1, Pages 13–20
`
`Next Article >
`
`To read this article in full, please review your options for gaining access at the bottom of the page.
`
`Effects of sildenafil citrate on human hemodynamics
`
`Graham Jackson, MD
`
`Nigel Benjamin, MD Neville Jackson, MD Michael J Allen, MD
`,
`,
`,
`
`DOI: http://dx.doi.org/10.1016/S00029149(99)000430
`
`Article Info
`
`Abstract
`
`Full Text
`
`Images
`
`References
`
`Abstract
`Nitric oxide (NO) induces the formation of intracellular cyclic guanosine monophosphate (cGMP) by guanylate
`cyclase. Sildenafil, which selectively inhibits phosphodiesterase type 5 (PDE5) found predominantly in the
`corpora cavernosa of the penis, effectively blocks the degradation of cGMP and enhances erectile function in
`men with erectile dysfunction. The NO–cGMP pathway also plays an important role in mediating blood
`pressure. It is, therefore, possible that the therapeutic doses of sildenafil used to treat erectile dysfunction may
`have clinically significant effects on human hemodynamics. Three studies were undertaken to assess the
`effects of intravenously, intraarterially, and orally administered doses of sildenafil on blood pressure, heart
`rate, cardiac output, and forearm blood flow and venous compliance in healthy men. A fourth study evaluated
`the hemodynamic effects of intravenous sildenafil in men with stable ischemic heart disease. In healthy men,
`significant (p <0.01) decreases in supine systolic and diastolic blood pressures were observed with
`intravenous sildenafil (20, 40, and 80 mg) at the end of the infusion period when plasma levels of sildenafil
`were highest (mean decreases from baseline of 7.0/6.9 and 9.2/6.7 mm Hg, for the 40 and 80mg doses,
`respectively). These changes were transient and not dose related. Modest reductions in systemic vascular
`resistance also were observed (maximum decrease 16%), although heart rate was not affected by sildenafil
`administration when compared with placebo. Single oral doses of sildenafil (100, 150, and 200 mg) produced
`no significant changes in cardiac index from 1–12 hours postdose between placebo and sildenafiltreated
`subjects. The approved dosage strengths of sildenafil citrate are 25 mg, 50 mg, and 100 mg. The 80mg
`intravenous dose and the 200mg oral dose of sildenafil produced comparable plasma levels at twice the
`maximum therapeutic dose (recommended range, 25–100 mg). After brachial artery infusion of sildenafil (up to
`300 μg/min), there was a modest vasodilation of resistance arteries and a reversal of norepinephrineinduced
`preconstriction of forearm veins. These hemodynamic effects were similar to but smaller in magnitude than
`those of nitrates. In a small pilot study of men with ischemic heart disease, decreases from baseline in
`pulmonary arterial pressure (−27% at rest and −19% during exercise) and cardiac output (−7% at rest and
`−11% during exercise) were observed after 40mg intravenous doses of sildenafil. Sildenafil was well tolerated
`by subjects and patients in all studies, with headache and other symptoms of vasodilation the most commonly
`reported adverse effects of treatment. Modest, transient hemodynamic changes were observed in healthy men
`after single intravenous or oral doses of sildenafil even at supratherapeutic doses. In men with stable ischemic
`heart disease, sildenafil produced modest effects on hemodynamic parameters at rest and during exercise.
`
`To access this article, please choose from the options below
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`Related Articles
`
`Sildenafil citrate and bloodpressure–
`lowering drugs: results of drug
`interaction studies with an organic
`nitrate and a calcium antagonist
`American Journal of Cardiology, Vol. 83,
`Issue 5
`
`Efficacy and safety of sildenafil citrate
`in men with erectile dysfunction and
`stable coronary artery disease
`American Journal of Cardiology, Vol. 93,
`Issue 2
`
`Efficacy and safety of sildenafil citrate
`in men with erectile dysfunction and
`chronic heart failure
`American Journal of Cardiology, Vol. 95,
`Issue 1
`
`Efficacy and safety of sildenafil citrate
`in the treatment of erectile dysfunction
`in patients with ischemic heart
`disease
`American Journal of Cardiology, Vol. 83,
`Issue 5
`
`Cardiovascular effects of sildenafil
`citrate and recommendations for its
`use
`American Journal of Cardiology, Vol. 84,
`Issue 5
`
`View All
`
`ATI 1013-0001
`
`ATI v. ICOS
`IPR2018-01183
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`
`< Previous Article
`
`March 4, 1999 Volume 83, Issue 5, Supplement 1, Pages 13–20
`
`Next Article >
`
`To read this article in full, please review your options for gaining access at the bottom of the page.
`
`Effects of sildenafil citrate on human hemodynamics
`
`Graham Jackson, MD
`
`Nigel Benjamin, MD Neville Jackson, MD Michael J Allen, MD
`,
`,
`,
`
`DOI: http://dx.doi.org/10.1016/S00029149(99)000430
`
`Article Info
`
`Abstract
`
`Full Text
`
`Images
`
`References
`
`Abstract
`Nitric oxide (NO) induces the formation of intracellular cyclic guanosine monophosphate (cGMP) by guanylate
`cyclase. Sildenafil, which selectively inhibits phosphodiesterase type 5 (PDE5) found predominantly in the
`corpora cavernosa of the penis, effectively blocks the degradation of cGMP and enhances erectile function in
`men with erectile dysfunction. The NO–cGMP pathway also plays an important role in mediating blood
`pressure. It is, therefore, possible that the therapeutic doses of sildenafil used to treat erectile dysfunction may
`have clinically significant effects on human hemodynamics. Three studies were undertaken to assess the
`effects of intravenously, intraarterially, and orally administered doses of sildenafil on blood pressure, heart
`rate, cardiac output, and forearm blood flow and venous compliance in healthy men. A fourth study evaluated
`the hemodynamic effects of intravenous sildenafil in men with stable ischemic heart disease. In healthy men,
`significant (p <0.01) decreases in supine systolic and diastolic blood pressures were observed with
`intravenous sildenafil (20, 40, and 80 mg) at the end of the infusion period when plasma levels of sildenafil
`were highest (mean decreases from baseline of 7.0/6.9 and 9.2/6.7 mm Hg, for the 40 and 80mg doses,
`respectively). These changes were transient and not dose related. Modest reductions in systemic vascular
`resistance also were observed (maximum decrease 16%), although heart rate was not affected by sildenafil
`administration when compared with placebo. Single oral doses of sildenafil (100, 150, and 200 mg) produced
`no significant changes in cardiac index from 1–12 hours postdose between placebo and sildenafiltreated
`subjects. The approved dosage strengths of sildenafil citrate are 25 mg, 50 mg, and 100 mg. The 80mg
`intravenous dose and the 200mg oral dose of sildenafil produced comparable plasma levels at twice the
`maximum therapeutic dose (recommended range, 25–100 mg). After brachial artery infusion of sildenafil (up to
`300 μg/min), there was a modest vasodilation of resistance arteries and a reversal of norepinephrineinduced
`preconstriction of forearm veins. These hemodynamic effects were similar to but smaller in magnitude than
`those of nitrates. In a small pilot study of men with ischemic heart disease, decreases from baseline in
`pulmonary arterial pressure (−27% at rest and −19% during exercise) and cardiac output (−7% at rest and
`−11% during exercise) were observed after 40mg intravenous doses of sildenafil. Sildenafil was well tolerated
`by subjects and patients in all studies, with headache and other symptoms of vasodilation the most commonly
`reported adverse effects of treatment. Modest, transient hemodynamic changes were observed in healthy men
`after single intravenous or oral doses of sildenafil even at supratherapeutic doses. In men with stable ischemic
`heart disease, sildenafil produced modest effects on hemodynamic parameters at rest and during exercise.
`
`To access this article, please choose from the options below
`Log In
`Purchase access to this article
`$35.95 USD|PDF Download and 24 Hours
`Email/Username:
`Online Access
`Password:
`
`Claim Access
`
`Access this article on
`ScienceDirect
`
`Article Tools
`
`PDF (205 KB)
`Download Images(.ppt)
`About Images & Usage
`
`Email Article
`Add to My Reading List
`Export Citation
`Create Citation Alert
`Cited by in Scopus (304)
`
`Request Permissions
`Order Reprints
`(100 minimum order)
`
`Related Articles
`
`Sildenafil citrate and bloodpressure–
`lowering drugs: results of drug
`interaction studies with an organic
`nitrate and a calcium antagonist
`American Journal of Cardiology, Vol. 83,
`Issue 5
`
`Efficacy and safety of sildenafil citrate
`in men with erectile dysfunction and
`stable coronary artery disease
`American Journal of Cardiology, Vol. 93,
`Issue 2
`
`Efficacy and safety of sildenafil citrate
`in men with erectile dysfunction and
`chronic heart failure
`American Journal of Cardiology, Vol. 95,
`Issue 1
`
`Efficacy and safety of sildenafil citrate
`in the treatment of erectile dysfunction
`in patients with ischemic heart
`disease
`American Journal of Cardiology, Vol. 83,
`Issue 5
`
`Cardiovascular effects of sildenafil
`citrate and recommendations for its
`use
`American Journal of Cardiology, Vol. 84,
`Issue 5
`
`View All
`
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`© 1999 Excerpta Medica Inc. Published by Elsevier Inc. All rights reserved.
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`March 4, 1999 Volume 83, Issue 5, Supplement 1, Pages 13–20
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