Kohagra

Sildenafil citrate, an oral therapy for erectile dysfunction, is the citrate salt of sildenafil, a selective inhibitor of cyclic guanosine monophosphate (cGMP)-specific phosphodiesterase type 5 (PDE5). Sildenafil citrate is designated chemically as 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo [4,3-d] pyrimidin-5,yl)-4-ethoxyphenyl[sulfonyl]-4-methylpiperazone citrate. Sildenafil citrate is a white to off-white crystalline powder with a solubility of 3.5 mg/mL in water and a molecular weight of 666.7.
Each film-coated tablet contains: Sildenafil (as Citrate) 25 mg/50 mg/100 mg.

Phosphodiesterase-5 (PDE5) inhibitor.
Pharmacology: Pharmacodynamics: Sildenafil is a selective inhibitor of phosphodiesterases (PDEs). It has greatest selectivity for PDE type 5 (PDE5), an isoenzyme that inactivates cyclic guanosine monophosphate (cGMP). PDE5 is the predominant type in the corpus cavernosum of the penis and is involved in the breakdown (hydrolysis) of cGMP to GMP. Nitric oxide (NO) released in the corpus cavernosum during sexual stimulation is most likely the major neurotransmitter mediating physiologic penile erection. Nitric Oxide mediates relaxation of the vascular smooth muscle of the corpus cavernosum by activating soluble guanylate cyclase thereby increasing cGMP production. cGMP is a second messenger for G-protein-coupled receptor protein kinases involved in regulating the vascular tone of the arterioles of the corpus cavernosum. Sildenafil enhances penile erection by augmenting NO-mediated, cGMP-dependent vascular smooth muscle relaxation pathways. Upon NO release during sexual stimulation (resulting in increased cGMP production), Sildenafil (by inhibiting cGMP breakdown thus increasing cGMP levels in the corpus cavernosum) produces smooth muscle relaxation of the corpus cavernosum. Vascular smooth muscle relaxation in the corpus cavernosum leads to increased penile blood flow. Sildenafil has no effect on penile erection in the absence of sexual arousal.
Pharmacokinetics: Sildenafil is rapidly absorbed after an oral dose, with a bioavailability of about 40% Peak plasma concentrations occur within 30 to 120 minutes; the rate of absorption is reduced when sildenafil is given with food. Sildenafil is widely distributed into tissues and is about 96% bound to plasma proteins. It is metabolized in the liver mainly by cytochrome P-450 isoenzyme CYP3A4 (the major route) and CYP2C9. The major metabolite, N-desmethyl sildenafil (UK-103320) also has some activity. The terminal half-lives of sildenafil and the N-desmethyl metabolite are about 4 hours. Sildenafil is excreted as metabolites, mainly in the faeces, and to a lesser extent the urine clearance may be reduces in elderly and in patients with hepatic or severe renal impairment.

It is used in the management of erectile dysfunction and pulmonary arterial hypertension.

Adults: The recommended dose is 50 mg, taken as needed approximately 1 hour before sexual activity. Based on efficacy and toleration, the dose may be increased to 100 mg or decreased to 25 mg. The maximum recommended dose is 100 mg. The maximum recommended dosing frequency is once per day.

Adverse events were similar to those seen at lower doses. In cases of overdose, supportive measures should be adopted as required. Renal dialysis is not expected to accelerate clearance as Sildenafil is highly bound to plasma proteins and not eliminated in the urine.

Sildenafil citrate is not indicated for use in women. Use of sildenafil citrate is contraindicated in patients with a known hypersensitivity to any component of the tablet Consistent with its known effect on the nitric oxide/cGMP pathway, Sildenafil citrate was shown to potentiate the hypotensive effects of nitrates, and its co-administration with nitric oxide donors or nitrates in any form is therefore contraindicated.

There is a potential for cardiac risk for sexual activity in patients with pre-existing cardiovascular disease.
Therefore, treatments for erectile dysfunction, including sildenafil citrate, should not be generally used in men: For whom sexual activity is advisable because of their underlying cardiovascular status; Patients who have suffered a myocardial infarction, stroke or life-threatening arrhythmia within the last months; Patients with resting hypotension (BP <90/50) or hypertension (BP >170/110); patients with cardiac failure or coronary artery disease causing unstable angina; patients with retinitis pigmentosa (a minority of these patients have genetic disorders of retinal phosphodiesterases).

Caution is required in patients with hepatic or severe renal impairment, and dosage reduction of sildenafil may be necessary. Care is also needed in patients with anatomical deformation of the penis or haematological disorders that may predispose them to priapism. Patients who experience dizziness or visual disturbances should not drive or operate machine.

Headache, flushing, and dyspepsia. Visual disturbances such as blurred vision, photophobia, chromatopsia, cyanopsia, eye irritation, pain and redness of the eyes. Dizziness insomnia, anxiety, vertigo, epistaxis, nasal congestion, pyrexia, and gastrointestinal disturbances such as diarrhea and vomiting. Priapism can occur. Skin rashes, erythema, alopecia limb and/or back pain, myalgia, facial oedema, fluid retention, paraesthenia, and urinary-tract infection. Dyspnoea, cough, rhinitis sinusitis, bronchitis, and cellulitis can occur.

Sildenafil or other phosphodiesterase type-5 inhibitors may potentiate the hypotensive effects of organic nitrates, and are therefore contraindicated in patients receiving such drugs. Sildenafil may also enhance the hypotensive effect of nicorandil and use of the two drugs together should be avoided. Symptomatic hypotension may also occur when phosphodiesterase type-5 inhibitors are given with alpha blockers. Drugs that inhibit cytochrome P450 isoenzyme CYP3A4, such as cimetidine, delavirdine, erythromycin, Itraconazole, and ketoconazole, may reduce the clearance of phosphodiesterase type-5 inhibitors, necessitating a reduction in dosage. Plasma concentrations of phosphodiesterase type-5 inhibitors are significantly increased by HIV-protease inhibitors, and particularly so by ritonavir-booster regimens. Grape fruit should be avoided with sildenafil or other phosphodiesterase type-5 inhibitors as it may increase their plasma concentrations. Inducers of CYP3A4, such as rifampicin, are likely to decrease plasma concentrations of phosphodiesterase type-5 inhibitors.

Store at temperatures not exceeding 30°C and protect from direct sunlight.

Drugs for Erectile Dysfunction & Ejaculatory Disorders

G04BE03 - sildenafil ; Belongs to the class of drugs used in erectile dysfunction.

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