Neurologic

In order to understand the success of the current oral therapy for ED, we first have to look at a brief overview of erectile physiology. Erections are initiated, maintained, and terminated due to a complex interaction between the neural and vascular components. Both central and peripheral factors are responsible for successful erections.

Vascular

The main event that seems to have the most influence on the maintenance of erections is the release of NO both from the autonomic nerve endings and the endothelial cells in the corpora cavernosum. The release of NO causes vasodilation of the smooth muscle cells (SMCs) and allows for tumescence to occur. NO facilitates vasodilation and relaxation by activating guanylate cyclase. This enzyme converts guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP), which is directly responsible for smooth muscle relaxation by its effect on intracellular calcium levels. Hyperpolarization occurs at the cell membrane, there is a decrease in cytoplasmic calcium, and the SMC relaxes. Levels of cGMP in the SMCs of the penis are regulated by the enzyme phosphodiesterase type 5 (PDE­5). Detumescence occurs with sympathetic nerve firing. Adrenergic nerves release norepinephrine (NE) that binds to a1 or a2 receptors on the SMC. This neurotransmitter is responsible for the activation of a G­protein and an influx of calcium into the SMC. As PDE­5 continues to breakdown cGMP to guanosine monophosphate (GMP), the SMCs and the endothelial cells con­ tract; this is the chronic state of the flaccid penis.

Oral Phosphodiesterase Inhibitors Viagra sales Australia

• PDE­5
• Pharmacokinetics and pharmacodynamics
• Side effects
• Safety
• Comparison

Phosphodiesterase, as mentioned in the previous section, is paramount to the breakdown of cGMP in the SMC. This enzyme is found in several different tissues throughout the body and has been categorized into 11 families. The family that is found in corpora cavernosum tissue as well as smooth muscle and vascular smooth muscle is PDE­5. As the role of PDE­5 was elucidated in the 1980s, drugs were targeted to inhibit this enzyme and increase the NO in SMCs. A result of this was an unexpected increase in NO in penile tissue and improvement in erectile function.

PDE­5 inhibitors were first marketed in 1998 with the dawn of sildenafil (Viagra®). This was followed closely in 2003 with vardenafil (Levitra®) and tadalafil Australia (Cialis®). As the market for these drugs has increased, it has been important to identify the safety, efficacy, and limitations of these drugs. When choosing a PDE­5 inhibitor for a patient, it is important to know the onset of action, efficacy, and duration. Studies usually will define the maximal plasma concentration (Cmax), time to reach this plasma concentration (Tmax), and the plasma half­life (t ½). How well these laboratory findings correlate to clinical findings is sometimes difficult to determine and the measuring tool most commonly used to evaluate efficacy is the International Index of Erectile Function (IIEF) domain score.