How does tadalafil differ from the other two PDE5 inhibitors sildenafil and vardenafil?

Tadalafil differs from these two other PDE5  inhibitors in several ways. First, the tadalafil  molecule belongs to a distinct chemical class  and is structurally different from the other  PDE5 inhibitors. Second, tadalafil has a plasma  half-life of 17.5 hrs, resulting in an ability to  improve erectile function for up to 36 hours  [22–24]. The plasma half-life of sildenafil  citrate is about 4 hours and the plasma halflife  of vardenafil HCl is about 4.5 hours [25,26].  The duration of action of sildenafil citrate has  been shown in one study to be up to 4 hours  [27].

Does tadalafil have an erectogenic effect in the absence of sexual stimulation?

No. Sexual stimulation (tactile, visual, etc.) is  required to release nitric oxide to initiate its  activation of cGMP. Tadalafil does not augment  nitric oxide release and only works by inhibiting  phosphodiesterase 5. 

What is the pharmacokinetic profile of tadalafil?

 Pharmacokinetics (PK) simply stated is ‘‘what  the body does to the drug’’ (ie, how the drug  is absorbed, eliminated and metabolized). Pharmacodynamics  or PD is ‘‘what the drug does to  the body.’’  Absorption: After single oral-dose administration  of tadalafil, the maximum observed  plasma concentration (Cmax) is achieved  between 30 minutes and 6 hours (median time  of 2 hours), although an erectogenic effect is  not predicated on the need to reach Cmax. The  time to reach Cmax is referred to as Tmax.  Neither the rate nor the extent of absorption of  tadalafil is influenced by food. Thus tadalafil  may be taken with or without food.  Metabolism: Tadalafil is predominantly metabolized  by CYP3A4 to a methyl catechol glucuronide  metabolite. In vitro data suggest  that metabolites are not expected to be pharmacologically  active following a dose of  tadalafil.  Elimination: The mean elimination half-life  (also sometimes referred to as ‘‘terminal halflife’’)  for tadalafil is 17.5 hours in healthy  subjects. The half-life is the time it takes for  the plasma concentration of drug in the body  to be reduced by 50%. Tadalafil is excreted  predominately as inactive metabolites, mainly  in the feces and to a lesser extent, urine. 
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What is the clinical significance of inhibiting PDE6 and PDE11?

PDE6 is located in the retina, and is an essential  component of visual transduction. Inhibition  of PDE6 can result in transient vision  changes such as blue halos and increased sensitivity  to light [16]. Buy viagra online pharmacy has no significant  effect on PDE6. Sildenafil and vardenafil inhibit  PDE6 at concentrations within the therapeutic  range.  The localization of PDE11 has not been fully  characterized. PDE11 protein and/or messenger  RNA have been reported in a number of human  tissues, including prostate, pituitary, skeletal  muscle, and testes [17,18]. However, the function  of PDE11 is unknown. No clinical consequences  of PDE11 inhibition have been  identified, including no adverse effects on spermatogenesis  or serum reproductive hormones  [19]. Neither sildenafil nor vardenafil inhibit  PDE11 at therapeutic concentrations. Tadalafil  inhibits PDE11 at high plasma concentrations  within the therapeutic range [20,21]. 

Are there other PDE enzymes? Does tadalafil inhibit other PDEs?

The term phosphodiesterase refers to a ‘‘superfamily’’  of enzymes consisting in humans of 11  families (isozymes or isoenzymes). Classification  of the PDEs is based on their structure and  whether they regulate the substrate cAMP,  cGMP, or both. The PDEs are variously distributed  throughout the body.  Different drugs have different selectivity for  inhibiting the various PDE families. For example,  a number of older compounds such as  theophylline and papaverine inhibit many or  all of the PDE isozymes including PDE5 [12–14].  In contrast, the three PDE5 inhibitors are more  selective for inhibiting PDE5 relative to the  other PDE isoenzymes. None of the PDE5 inhibitors  has any significant effect against PDEs  1–4 and 7–10, but sildenafil citrate and vardenafil  HCl do have some activity against PDE6  and tadalafil has some activity against PDE 11  [15]. 

What is tadalafil and how does it work?

Tadalafil is currently approved in at least 90  countries as an oral treatment for erectile  dysfunction (ED). It is marketed throughout  the world as Cialis1 (pronounced ‘‘See-AL-is’’).  In Saudi Arabia, tadalafil is marketed as both  Cialis1 and Snafi1.  Tadalafil is an inhibitor of PDE5. After entering  smooth muscle cells in arteries within the  corpus cavernosum of the penis, tadalafil competitively  inhibits PDE5, and prevents the inactivation  of the intracellular messenger cGMP.  Consequently, by inhibiting PDE5 in the corpus  cavernosum, tadalafil prolongs the action  of cGMP, facilitating the erectile response to  sexual stimulation. 

What is phosphodiesterase 5 (PDE5)?

Phosphodiesterase 5 (PDE5) is an enzyme that terminates the activity of cGMP by converting it to an inactive form [10,11]. In the penis, the inactivation of cGMP by PDE5 blocks the cascade of events supporting erection, resulting in detumescence.

What is the physiological mechanism of an erection? - Tadalafil and Erectile Dysfunction Basics

An erection is a neuro-vascular event in which  the degree of erection depends upon the balance  between arterial inflow and venous outflow  (Figure 1) [2]. Psychological or physical  sexual stimulation initiates the release of nitric  oxide—the ‘‘first messenger’’—from neurons  and endothelial cells in the penis. Nitric oxide  leads to increased generation of cyclic guanosine  monophosphate (cGMP). The cGMP,  which is an intracellular second messenger,  in turn activates protein kinase G. Protein  kinase G decreases calcium in the cytosol,  which ultimately leads to the relaxation of  the smooth muscle of the corpus cavernosum.  Arterial inflow increases and the venules  are compressed, impeding the outflow of  blood, which causes an erection by increased  blood trapping. 
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How is ED diagnosed? - Tadalafil and Erectile Dysfunction Basics

ED is defined as the inability to achieve an erection that is adequate for intercourse. Supplement Keywords Erectile dysfunction Tadalafil  2005 WPMH GmbH. Published by Elsevier Ireland Ltd. Vol. 2, No. 1, pp. 141–157, March 2005 143 ED is generally a patient-driven diagnosis, determined by taking a careful medical history. There are no specific laboratory tests that clinically diagnose the presence or absence of ED.

How should men with ED be evaluated prior to therapy?

Except in rare circumstances, the initial evaluation  of men does not impact what will be  offered for treatment. Rather, screening aims  to identify comorbid cardiovascular disease,  diabetes, hyperlipidemia, hypertension, hypogonadism,  and depression, all of which merit  intervention in their own right.  Because most men with ED have a disproportionate  burden of comorbidities, it is considered  appropriate to measure lipids and glucose  after an overnight fast, and to record blood  pressure to screen for treatable conditions.  SinceEDmay bemedication-induced, screening  for concomitant administration of possible causative  medicines (eg., thiazide diuretics, beta  blockers, serotonin-selective reuptake inhibitors  (SSRIs), alpha-reductase inhibitors, and  aldosterone antagonists) is important [3–8].  Hypogonadism is an uncommon cause of ED  (causative in less than 5% of ED cases). Testosterone  testing is of utility in men with low  libido. In such men initial screening with a  morning total testosterone is reasonable, to be  followed with a repeat morning total testosterone  and free testosterone if the initial screen is  below normal or in the low normal range. The  practice of measuring testosterone in men  with intact libido has been reported to not  be cost-effective .