Neurologic, Psychological, and Aggressive Disturbances with Sildenafil

Milman, Harry A.; Arnold, Suzanne B

doi:10.1345/aph.1a402

Cited by 82 publications

(46 citation statements)

References 37 publications

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“…Some authors have established combinations as sildenafil-inhaled NO (38), sildenafil surfactant (35), or sildenafil bosentan (30), with effective pulmonary results. Although sildenafil is a very good drug for pulmonary hypertension treatment, it is necessary to evaluate the side effects such as systemic hypotension, gastric alterations (39), retinal vascular damage (40,41), neurologic, and psychological disturbances (42,43).…”

Section: Discussionmentioning

confidence: 99%

Sildenafil Reverses Hypoxic Pulmonary Hypertension in Highland and Lowland Newborn Sheep

et al. 2008

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Perinatal exposure to chronic hypoxia induces sustained hypertension and structural and functional changes in the pulmonary vascular bed. We hypothesized that highland newborn lambs (HLNB, 3600 m) have a higher pulmonary arterial pressure (PAP) due in part to a higher activity/expression of phosphodiesterase 5 (PDE5). We administered sildenafil, a PDE5 inhibitor, during basal and hypoxic conditions in the pulmonary hypertensive HLNB and compared them to lowland newborn lambs (LLNB, 580 m). Additionally, we compared the vasodilator responses to sildenafil in isolated small pulmonary arteries and the PDE5 mRNA expression and evaluated the vascular remodeling by histomorphometric analysis in these newborn lambs. Under basal conditions, HLNB had a higher PAP and cardiac output compared with LLNB. Sildenafil decreased the PAP during basal conditions and completely prevented the PAP increase during hypoxia in both groups. HLNB showed a greater contractile capacity and a higher maximal dilation to sildenafil. PDE5 mRNA expression did not show significant differences between HLNB and LLNB. The distal pulmonary arteries showed an increased wall thickness in HLNB. Our results showed that HLNB are more sensitive to sildenafil and therefore could be useful for treatment of pulmonary hypertension in high-altitude neonates. E xposure of lowland species to high altitude produces pulmonary vasoconstriction and remodeling resulting in pulmonary hypertension. Previously, we have shown that newborn lambs gestated and born at high altitude have an increased pulmonary arterial pressure (PAP) and vascular reactivity compared with those born at sea level (1). Appropriate increases in pulmonary vascular resistance (PVR) are adaptive, matching pulmonary perfusion to the reduced oxygenation. However, excessive increases in PVR, if maintained over time, lead to structural changes of the pulmonary vasculature, such as an increase in vascular muscle cells and fibrosis in the adventitia of the vessel (2-4). In newborns, either at altitude or sea level, this pulmonary arterial hypertension is ultimately due to a failure in the regulation of the PVR at birth by mechanisms not fully understood, which implies an imbalance in vasoconstrictors and vasodilators, leading to hypoxemia and sustained pulmonary hypertension. Indeed, one of the major causes of persistent pulmonary hypertension in the newborn is chronic hypoxia in utero (5) and is characterized by hypoxemia that is frequently refractory to conventional management, with a mortality rate near 10% (6). The incidence of this syndrome may be higher at high altitudes (7), an important issue considering that more than 140 million people worldwide live at more than 2500 m (8). Moreover, it has been suggested that during chronic hypoxia, production of vasoconstrictors is enhanced, while synthesis of vasodilators is reduced in the lung (9,10). A mechanism that favors this high vascular tone is the hydrolysis of cyclic guanosine monophosphate (cGMP) by phosphodiesterases (PDEs). The major ...

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Section: Discussionmentioning

confidence: 99%

Sildenafil Reverses Hypoxic Pulmonary Hypertension in Highland and Lowland Newborn Sheep

et al. 2008

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“…It is the citrate salt of sildenafil, which is a selective inhibitor of phosphodiesterase type 5 (PDE-5), an enzyme found in the corpus cavernosum (1,2). Its pharmacologic mechanism of action is associated with nitric oxide (NO).…”

Section: Discussionmentioning

confidence: 99%

“…Some published studies identified that Viagra® can cross blood-brain barrier (BBB). In 1989, studies proved that NO is also formed in the CNS by NO synthase (NOS), and possibly has a role in CNS transduction and function (2,8). It is likely that Viagra® modulates the brain function by increasing the NO-cGMP cascade.…”

Section: Discussionmentioning

confidence: 99%

“…But these studies have described the relationship between aggressive behavior and hippocampal lesions, not white matter toxicity. Whether this will induce CNS adverse effect like toxic encephalopathy is unclear (2).…”

Section: Discussionmentioning

confidence: 99%

“…Most commonly reported adverse effects include headache (16%), facial flushing (10%), dyspepsia (7%), nasal congestion (4%), and visual disturbances (3%) (1). Sildenafil may also cause central nervous system (CNS) adverse effects such as dizziness, depression, insomnia, abnormal dreams, somnolence, and nervousness, but these are very rarely identified (1,2). Here we present a case of toxic encephalopathy induced by sildenafil since there were no reported cases about neuroradiologic findings of Viagra induced toxic encephalopathy.…”

Section: Introductionmentioning

confidence: 96%

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A Rare Case of Viagra Induced Toxic Encephalopathy

Jeong

Jeon

Kim

et al. 2016

Investig Magn Reson Imaging

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Viagra has been prescribed worldwide to treat men with erectile dysfunction. Clinical trials have shown that Viagra may cause various kinds of adverse effects include some central nervous system (CNS) adverse effects. Although extremely rare, toxic encephalopathy also can be one of those effects. This report presents a case of encephalopathy caused by Viagra in correlation with its radiologic findings. Its pharmacologic mechanism and potential effects on the biochemistry of the CNS are reviewed.

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Differential effect of the PDE5 inhibitors, sildenafil and zaprinast, in aging‐ and lipopolysaccharide‐induced cognitive dysfunction in mice

Patil

Jain

Singh

et al. 2004

Drug Development Research

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In the present study, we have investigated the effects of exogenously administered cyclic GMP-specific PDE5 inhibitors, sildenafil and zaprinast, on cognitive performance in aged-and lipopolysaccharide (LPS)-treated mice using passive avoidance and plus-maze tasks. Aged and LPStreated mice showed poor retention of memory in step-through passive avoidance and plus-maze task. Administration of PDE5 inhibitors reversed the age-induced retention deficits in both of the test paradigms. Also, PDE5 inhibitors on acute administration in young mice showed improvement in memory retention when tested in both of the paradigms. However, the effect of two PDE5 inhibitors was more pronounced in aged animals than that in young mice. PDE5 inhibitors enhanced the retention deficits in LPS-treated animals, which might be due to elevation of cGMP levels caused by sildenafil and zaprinast. In conclusion, these results indicated that differential effects of PDE5 inhibitors in aging and LPS-treated mice, but its prudential effect in aged mice may suggest new therapeutic use of these compounds. Drug Dev.

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Neurologic, Psychological, and Aggressive Disturbances with Sildenafil

Abstract: It is recommended that, before prescribing sildenafil for erectile dysfunction, clinicians should caution their patients and their partners on the possibility of neurologic, emotional, or psychological disturbances; amnesia or loss of consciousness; or aggressive behavior.

Cited by 82 publications

References 37 publications

Sildenafil Reverses Hypoxic Pulmonary Hypertension in Highland and Lowland Newborn Sheep

Sildenafil Reverses Hypoxic Pulmonary Hypertension in Highland and Lowland Newborn Sheep

A Rare Case of Viagra Induced Toxic Encephalopathy

Differential effect of the PDE5 inhibitors, sildenafil and zaprinast, in aging‐ and lipopolysaccharide‐induced cognitive dysfunction in mice

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