Sildenafil

BRAND NAMES:

Liqrev -  Liqrev is an oral suspension consisting of sildenafil as the active ingredient that helps in treating pulmonary arterial hypertension.

Revatio – Revatio contains sildenafil as the active ingredient which is available in the market as Revatio sildenafil 20mg tablets.

Viagra – Viagra is available as tablets which is a composition of sildenafil.

MECHANISM OF ACTION:

Nitric oxide is created in the corpus cavernosum during sexual stimulation, which is what causes penile erections. Nitric oxide activates guanylate cyclase, which relaxes the smooth muscle of the corpus cavernosum, allowing blood to flow and increasing the concentration of cyclic guanosine monophosphate. It does not directly relax the isolated human corpus cavernosum, but by inhibiting phosphodiesterase type 5, which degrades cyclic guanosine monophosphate in the corpus cavernosum, it enhances the effects of nitric oxide. During sexual stimulation, nitric oxide is created locally; sildenafil inhibits phosphodiesterase type 5 in the corpus cavernosum, increasing cyclic guanosine monophosphate levels and causing smooth muscle relaxation and blood flow.

PHARMACOKINETICS:

Absorption: When taken orally, it takes 30 to 120 minutes to reach peak plasma concentrations. It is less noticeable when consumed alongside a high-fat meal.

Distribution: The volume of distribution of sildenafil is approximately 105L.

Metabolism: Sildenafil undergoes hepatic metabolism. It is mainly metabolized through the CYP3A4  major and CYP2C9 minor route hepatic microsomal isoenzymes. The major circulating metabolites result from N- desmethylation of sildenafil.

Excretion: Sildenafil is excreted as metabolites majority in the feces up to 0% of the administered oral dose and 3% through the urine of the administered oral dose.

PHARMACODYNAMICS:

In placebo-controlled crossover investigations of patients with organic or psychogenic erectile dysfunction, sexual stimulation improved erections. The efficacy of sildenafil will increase after 6 minutes of ingestion. 

Sitting blood pressure in healthy individuals decreased after a single dosage of sildenafil. Sitting blood pressure decreased significantly within 1-2 hours of treatment.

 DOSAGE AND ADMINISTRATION:

Sildenafil is available in oral tablets, suspension, and injections with different strengths.

• For erectile dysfunction, sildenafil is available as oral tablets 25 mg, 50 mg, and 100 mg. 50 mg of oral sildenafil is prescribed mostly in patients one hour before sexual activity. The dose can be decreased to 25 mg or can be increased to 100 mg depending on the individuals.

• For pulmonary arterial hypertension, the recommended dosage for tablet and oral suspension is 5 mg or 20 mg three times daily. 2.5 mg or 10 mg dosed injections are prescribed three times a day intravenously. Injections are prescribed when the patient is unable to take medicine orally.

CONTRAINDICATIONS:

Sildenafil is contraindicated with nitrates, and hypersensitivity to any of its components.

DRUG INTERACTIONS:

Drug interactions may change the efficacy of the drug or can cause some adverse effects.

Some medications that interact with sildenafil are

• Alpha-blockers – Doxazosin, tamsulosin
• Angina – nitrates such as nitroglycerin, isosorbide
• Antifungals – Itraconazole, ketoconazole
• Antibiotics – Clarithromycin, erythromycin 
• Erectile dysfunction or Pulmonary hypertension – Tadalafil, vardenafil
• Rifampin
• Ritonavir
• Mifepristone

FOOD INTERACTIONS:

Avoid grapefruit and grape juices, alcohol, and high-fat meals along with the sildenafil.

ADVERSE EFFECTS:

• Decrease of hearing
• Nasal congestion
• Myalgia
• Headache
• Flushing
• Dyspepsia
• Nausea
• Dizziness
• Back pain
• Tinnitus

TOXICITY:

Overdose of sildenafil may cause some toxic effects

• Visual disturbance
• Change in blood pressure