sildenafil-citrate and Substance-Withdrawal-Syndrome

Systemic sclerosis (SSc) is a connective tissue disease frequently associated with Raynaud's Phenomenon (RP). Among possible pharmacological treatments, phosphodiesterase 5 inhibitors are considered in cases of severe non -responsive RP. We present the case of a male SSc patient wh presented with critical finger ischemia and concomitant appearance of myocardial fibrosis after sudden interruption of sildenafil treatment.

Topics: Antirheumatic Agents; Cardiomyopathies; Fingers; Humans; Ischemia; Male; Middle Aged; Myocardium; Raynaud Disease; Risk Factors; Scleroderma, Systemic; Sildenafil Citrate; Substance Withdrawal Syndrome; Time Factors

Chronic morphine exposure creates dependence and, upon cessation, withdrawal symptoms. Studies indicate the phosphodiesterase type 5 (PDE5) inhibitor sildenafil may provide centrally mediated benefits against withdrawal, and therefore, this study evaluated morphine withdrawal signs in dependent mice with and without sildenafil treatment.. Dependence was induced by repeated treatments with morphine over 5 consecutive days. The morphine-dependent mice received sildenafil (1, 5, 10, or 20 mg/kg, i.p.) 15 min prior to the precipitation of morphine withdrawal. On the last day, naloxone was injected 2 hours after the last morphine injection, and withdrawal signs were evaluated for 30 min after naloxone injection.. The administration of sildenafil reduced all of the morphine withdrawal symptoms.. The administration of sildenafil diminished morphine withdrawal signs in morphine-dependent mice. We hypothesize that the mechanism involves enhanced cyclic guanosine monophosphate (cGMP) activity, but further studies are recommended for a better understanding.

Topics: Animals; Male; Mice; Morphine; Phosphodiesterase 5 Inhibitors; Sildenafil Citrate; Substance Withdrawal Syndrome

Recent reports to the U.S. Food and Drug Administration Adverse Event Reporting System implicate sildenafil citrate in adverse emotional and aggressive behaviors. Sildenafil citrate (Viagra) is widely prescribed for erectile dysfunction and acts by inhibiting phosphodiesterase Type-5, resulting in accumulation of cyclic-guanosine monophosphate (cGMP). Cyclic-GMP is synthesized by guanylyl cyclase that is directly activated by the messenger molecule, nitric oxide (NO), formed throughout the CNS by the enzyme nitric oxide synthase (NOS). Elevated concentrations of cGMP have been associated with increased aggressive behavior. In addition, the potential effect of cGMP accumulation on NO-mediated behavioral and neuroendocrine function through possible feedback mechanisms remains unspecified; however, neuronal NOS (nNOS) inhibition by pharmacologic agents or ablation of the gene encoding nNOS increases aggressive behavior in male mice. We tested the hypothesis that sildenafil citrate may increase aggression via its actions on cGMP and potential feedback inhibition of NO concentrations. Male C57BL/6 mice were injected with saline vehicle (0), 2, 5, 8, or 10 mg/kg of sildenafil citrate thrice weekly for 4 weeks. Latency to display aggressive behavior, frequency, and duration of aggressive behavior were recorded during neutral-arena aggression tests. No change in agonistic behavior was observed in mice during treatment with sildenafil citrate. However, sildenafil-treated mice given the highest dose were generally more aggressive 1 week post-cessation of drug treatment as compared to vehicle-treated mice. Additional investigation into potential withdrawal effects or abuse doses seems warranted.

Topics: Aggression; Animals; Cyclic GMP; Least-Squares Analysis; Male; Mice; Mice, Inbred C57BL; Piperazines; Purines; Sildenafil Citrate; Substance Withdrawal Syndrome; Sulfones; Time Factors; Vasodilator Agents

Topics: Antihypertensive Agents; Bosentan; Extracorporeal Membrane Oxygenation; Female; Humans; Middle Aged; Nitric Oxide; Phosphodiesterase Inhibitors; Piperazines; Purines; Respiratory Distress Syndrome; Sildenafil Citrate; Substance Withdrawal Syndrome; Sulfonamides; Sulfones; Vasodilator Agents; Ventilator Weaning

Topics: Administration, Inhalation; Antihypertensive Agents; Epoprostenol; Humans; Hypertension, Pulmonary; Nitric Oxide; Phosphodiesterase Inhibitors; Piperazines; Purines; Recurrence; Sildenafil Citrate; Substance Withdrawal Syndrome; Sulfones; Vasodilator Agents

Topics: 3',5'-Cyclic-GMP Phosphodiesterases; Administration, Inhalation; Cyclic GMP; Female; Humans; Hypertension, Pulmonary; Infant; Infant, Newborn; Nitric Oxide; Phosphodiesterase Inhibitors; Piperazines; Purines; Sildenafil Citrate; Substance Withdrawal Syndrome; Sulfones