Vasodilators sildenafil

Erectile dysfunction is treated by local or systemic application of vasodilator drugs. The most effective is sildenafil, a phosphodiesterase-type 5 inhibitor. 

Vasodilators are a group of dtugs, which relax the smooth muscle cells of the blood vessels and lead to an increased local tissue blood flow, a reduced arterial pressure and a reduced central venous pressure. Vasodilators reduce the cardiac pre-load as well as after-load and thereby reduce cardiac work. They are used in a variety of conditions including hypertension, cardiac failure and treatment/prevention of angina pectoris. Major groups are Ca2+-channel blockers (e.g. dihydropyridines), NO-donators (e.g. organic nitrates), K+-channel openers (minoxidil), phosphodiesterase inhibitors (e.g. sildenafil), Rho-kinase inhibitors (e.g. Y27632) or substances with unknown mechanism of action (e.g. hydralazine). Inhibitors of the... 

A further characteristic of this principle is that, if the activity of phosphodiesterase is decreased, the concentration of cyclic GMP will increase to an extent dependent upon the extent of the decrease in activity. This characteristic has been made use of by the pharmaceutical industry. Cyclic GMP has a vasodilatory effect and this is the case for the arterioles that supply blood to the corpus cavemosum in the penis, which controls the erection of the penis. Drugs were developed (e.g. sildenafil) that inhibits cyclic GMP phosphodiesterase and hence increases the cyclic GMP level which resnlts in vasodilation of the arterioles and an increase in the snpply of blood to the spongy tissue of the corpus cavemosum, which expands resulting in erection. This dmg has been found to be effective in some patients snffering from erectile dysfunction. This can be a particular problem in diabetic patients and more elderly men (Chapter 19). 

Drugs that may interact with nitrates include alcohol, alteplase, aspirin, beta-blockers, calcium channel blockers, dihydroergotamine, heparin, nondepolarizing muscle relaxants, phenothiazines, phosphodiesterase inhibitors (eg, sildenafil, tadalafil, vardenafil), and vasodilators. 

Patients with the following underlying conditions can be particularly sensitive to the actions of vasodilators, including sildenafil, tadalafil, and vardenafil Those with left ventricular outflow obstruction (eg, aortic stenosis, idiopathic hypertrophic subaortic stenosis) and those with severely impaired autonomic control of blood pressure. 

Isosorbide Dinitrate Hydralazine (BiDil) [Antianginal, Antihypertensive/Vasodilator, Nitrate] Uses HF in African Amer-icans improve survival functional status, prolong time between hospitalizations Action Relaxes vascular smooth muscle peripheral vasodilator Dose Initially 1 tab tid PO (if not tol ated reduce to 1/2 tab tid), titrate >3-5 d as tolerated Max 2 tabs tid Caution [C, /-] recent MI, syncope, hypovolemia, hypotension, hep impair Contra For children, concomitant use w/ PDE5 inhibitors (sildenafil) Disp Tabs SE HA, dizziness, orthostatic hypotension, sinusitis, GI distress, tach, paresthesia, amblyopia Interactions t Risk of severe hypotension W/ antihypertensives, ASA, CCBs, MAOIs, phenothiazides, sildenafil, tadalafil, vardenafil, EtOH X pressor response Wf i -1- effects W7 NSAIDs EMS Use ASA, antihypertensives and CCBs w/ caution, may t hypotension concurrent Viagra-type drug use can lead to profound hypotension concurrent EtOH use can t effects OD May cause N/V, profound hypotension, skin flushing, HA from ICP, bradycardia, confusion, and circulatory collapse activated charcoal may be effective, epi use is contraindicated... 

The moderately selective PDE type V-inhibitor sildenafil (Viagra ) has been introduced in the treatment of erectile dysfunction. On the basis of cyclic GMP accumulation sildenafil is claimed to be a selective vasodilator in erectile tissues in the penis because of the high concentration of PDE type V in this region. Several of its adverse reactions (headache, flush, hypotension) reflect its vasodilator actions in other vascular beds than that of the penis. The drug will not be further discussed here. 

Sildenafil (Viagra, Revatio) [Vasodilator/PDE5 Inhibitor]... 

Sildenafil (citrate), a complicated piperazine-pyrazolopyrimidine structure, vasodilator and small muscle relaxant for erectile dysfunction [139755-83-2],... 

VASODILATOR ANTIHYPERTENSIVES-BOSENTAN SILDENAFIL 1 sildenafil levels Probable induction of metabolism Watch for poor response... 

Interactions. An important footnote to the use of nitrates (and NO-dilators generally) has been the marked potentiation of their vasodilator effects observed in patients taking the phosphodiesterase (PDE) inhibitor sildenafil (Viagra). This agent targets an isoform of PDE (PDE-5) expressed in the blood vessel wall. Other methylaxanthine PDE inhibitors, such as theophylline, do not cause a similar interaction because they are rather weak inhibitors of PDE-5, even at the doses effective in asthma. A... 

Schalcher C, Schad K, Brunner-La Rocca HP, et al. Interaction of sildenafil with cAMP-mediated vasodilation in vivo. Hypertension. 2003 40 763-767. 

To date, the actions of sildenafil in vascular disorders distinct from that of erectile dysfunction have yet to be studied adequately. For example, oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension (146a). 

Phosphodiesterase 5 (PDE5) is found in blood vessels supplying the corpora cavernosa. Sildenafil inhibits PDE 5 - T cGMP -> vasodilation - T blood flow ->T erectile response. If used concomitantly with nitrates or other potent vasodilators, the excessive fall in blood pressure may lead to death from cardiovascular causes, including myocardial infarct. 

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