Clinical Pharmacology

How Viagra works?
The penis gets erect during sexual stimulation when increased blood flows to the penis resulting from relaxation of penile arteries and corpus cavernosal smooth muscle. This is due to the release of nitric oxide ( NO) from nerve terminals and endothelial cells which in turn leads to the synthesis of cGMP in smooth muscle cells.

Cyclic GMP (cGMP) causes muscle in the penis to relax so that more blood can flow in. Cialis is a selective inhibitor of PDE5. It enhances the effect of nitric oxide ( NO) by inhibiting the action of phosphodiesterase type 5 (PDE5) found in Corpus cavernosum smooth muscles in the penis. It is more effective, almost > 4000-fold more potent for PDE5 than for other phosphodiesterases. Inhibition of PDE5 leads to an increases in the amount of cGMP.

Viagra Drug Interaction

Absorption and Distribution:
Sildenafil citrate, the active ingredient in Viagra , is rapidly absorbed after oral administration . After single oral-dose administration, Sildenafil citrate achieves the maximum observed plasma concentration (C max ) 30 to 120 minutes (median 60 minutes) . When sildenafil citrate is taken with a high fat meal, the rate of absorption is reduced, with a mean delay in Tmax of 60 minutes and a mean reduction in Cmax of 29%. The mean steady state volume of distribution (Vss) for sildenafil is 105 L, indicating distribution into the tissues.

Metabolism
Sildenafil gets metabolised by the cytochrome CYP3A4 (major route) and CYP2C9 (minor route) hepatic microsomal isoenzymes. The major circulating metabolite results from N-desmethylation of sildenafil, and is itself further metabolized. This metabolite the metabolite accounts for about 20% of sildenafil's pharmacologic effects.

Elimination
Sildenafil gets eliminated from the body mainly in the form of faeces (80%) and urine ( 13%).

Pharmacodynamics

Effects of Sildenafil Citrate on Erectile Response :
In clinical trials, the administration of sildenafil citrate improved erectile response as assessed by an objective measurement of hardness and duration of erections (RigiScan). Most studies assessed the efficacy of sildenafil citrate approximately 60 minutes post dose. The time course of effect was examined in one study, showing an effect for up to 4 hours but the response was diminished compared to 2 hours.

Effects of Sildenafil Citrate on Blood Pressure :
Administration of Sildenafil Citrate to healthy volunteers produced decreases in supine blood pressure (mean maximum decrease of 8.4/5.5 mmHg). Larger effects were recorded among patients receiving concomitant nitrates

Effects of Sildenafil Citrate on Vision:
Sildenafil Citrate can lead to transient dose-related impairment of color discrimination (blue/green).

Viagra dosage and administration
Viagra tablets are taken orally once a day.

Dosage for healthy adult men
For most patients, the recommended dose is 50 mg taken, as needed, approximately 1 hour before sexual activity. The maximum recommended Viagra dosing frequency is once per day. It may be taken without food and alcohol constraints.

Dosage for older men
If you are older than age 65, or have serious liver or kidney problems, your doctor may start you at the lowest dose (25 mg) of Viagra.

Dosage for men taking certain medicines
If you are taking protease inhibitors, such as for the treatment of HIV, your doctor may recommend a 25 mg dose and may limit you to a maximum single dose of 25 mg of VIAGRA in a 48 hour period . If you are taking alpha-blocker therapy, you should not take more than 25 mg of Viagra at the same time (within 4 hours) as your dose of alpha-blocker.