Phosphodiesterase type inhibitors

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

Phosphodiesterase type 5 inhibitors are commonly prescribed for erectile dysfunction and include sildenafil, vardenafil,... 

Viagra (sildenafil) Phosphodiesterase type 5 inhibitor Mort and Brigitte Harris Foundation Phase I... 

Drugs that affect all phosphodiesterase type 5 inhibitors include the following alcohol, amlodipine, angiotensin II receptor blockers, antacids, bendroflumethiazide, beta blockers, cimetidine, diuretics, enalaphl, metoprolol, nifedipine, rifampin, tacrolimus. 

Drugs that may be affected by itraconazole include alfentanil, almotriptan, alprazolam, amphotericin B, aripiprazole, benzodiazepines, buspirone, busulfan, calcium blockers, carbamazepine, cilostazol, cisapride, corticosteroids, cyclosporine, digoxin, disopyramide, docetaxel, dofetilide, eletriptan, epierenone, ergot alkaloids, haloperidol, HMG-CoA reductase inhibitors, hydantoins (phenytoin), hypoglycemic agents, oral midazolam, phosphodiesterase type 5 inhibitors, pimozide, polyenes, protease inhibitors, quinidine, rifamycins, sirolimus, tacrolimus, tolterodine, triazolam, trimetrexate, vinca alkaloids, warfarin, and zolpidem. 

Drugs that may be affected by indinavir include antiarrhythmics, clarithromycin, dihydropyridine calcium channel blockers, HMG-CoA reductase inhibitors, immunosuppressant agents, phosphodiesterase type 5 inhibitors, pimozide, saquinavir, trazodone, cisapride, amiodarone, benzodiazepines, ergot alkaloids, fentanyl, rifamycins, ritonavir. 

Antunes, J.E., Freitas, M.P., da Cunha, E.F.F., Ramalho, T.C., Rittner, R. In silico prediction of novel phosphodiesterase type-5 inhibitors derived from sildenafil, vardenafil and tadalafil. Bioorg. Med. Chem. 2008, 16, 7599-606. 

Venodilators Releases nitric oxide (NO) activates guanylyl cyclase (see Chapter 12) Venodilation reduces preload and ventricular stretch Acute and chronic heart failure angina Oral 4-6 h duration Toxicity Postural hypotension, tachycardia, headache Interactions Additive with other vasodilators and synergistic with phosphodiesterase type 5 inhibitors... 

Snow KJ. Erectile dysfunction in patients with diabetes mellitus advances in treatment with phosphodiesterase Type 5 inhibitors. BrJ Diab Vase Dis 2002 2 282-287. 

Porst H, Rosen R, Padma-Nathan H, et al. Efficacy and tolerability of vardenafil, a new selective phosphodiesterase type 5 inhibitor, in patients with erectile dysfunction the first at home clinical trial. IntJ Impot Res 2001 13 192-199. 

Jackson G, Martin E, McGing E, etal. Successful withdrawal of oral long-acting nitrates to facilitate phosphodiesterase Type 5 Inhibitor use in stable coronary disease patients with erectile dysfunction. J Sex Med 2005 2 513-516. 

ANTIHYPERTENSIVES AND HEART FAILURE DRUGS PHOSPHODIESTERASE TYPE 5 INHIBITORS ... 

CALCIUM CHANNEL BLOCKERS PHOSPHODIESTERASE TYPE 5 INHIBITORS t hypotensive action particularly with sildenafil and vardenafil Additive effect phosphodiesterase type S inhibitors cause vasodilatation Warn patients of the small risk of postural 1 BP... 

CALCIUM CHANNEL BLOCKERS POTASSIUM CHANNEL ACTIVATORS t hypotensive effect Additive effect Avoid co-administration of nicorandil with phosphodiesterase type 5 inhibitors. With other drugs, monitor BP closely... 

MACROUDES PHOSPHODIESTERASE TYPE 5 INHIBITORS t phosphodiesterase type 5 inhibitor levels with erythromycin, and possibly clarithromycin and telithromycin Inhibition of metabolism 1 dose of these phosphodiesterase inhibitors (e.g. start vardenafil at 5 mg)... 

PROTEASE INHIBITORS PHOSPHODIESTERASE TYPE 5 INHIBITORS-SILDENAFIL, TADALAFIL, VARDENAFIL t sildenafil, tadalafil and vardenafil levels Inhibition of CYP3A4- and possibly CYP2C9-mediated metabolism of sildenafil Use with caution monitor BP closely. UK manufacturers recommend avoiding co-administration of vardenafil with protease inhibitors in patients >75 years. US manufacturers recommend using with caution, starting with a daily dose of 2.5 mg... 

CIMETIDINE PHOSPHODIESTERASE TYPE 5 INHIBITORS -SILDENAFIL t efficacy and adverse effects of sildenafil Inhibition of metabolism via CYP3A4 Consider a starting dose of 25 mg of sildenafil... 

UROLOGICAL DRUGS ERECTILE DYSFUNCTION Phosphodiesterase type 5 inhibitors... 

PHOSPHODIESTERASE TYPE 5 INHIBITORS -SILDENAFIL ANTICANCER AND IMMUNOMODULATING DRUGS-CICLOSPORIN T plasma concentrations of cidosporin, with risk of adverse effects Competitive inhibition of CYP3A4-mediated metabolism of cidosporin Be aware. Sildenafil is taken intermittently and is unlikely to be of clinical significance unless concomitant therapy is long term... 

PHOSPHODIESTERASE TYPE 5 INHIBITORS ANTIFUNGALS-AZOLES T sildenafil, tadalafil and vardenafil levels Inhibition of metabolism l dose of these phosphodiesterase type 5 inhibitors... 

PHOSPHODIESTERASE TYPE 5 INHIBITORS (e.g. sildenafil, tadalafil, vardenafil) GRAPEFRUIT JUICE Possibly t efficacy and t adverse effects, e.g. hypotension Small t in bioavailability, t variability in pharmacokinetics, i.e. interindividual variations in metabolism Safest to advise against intake of grapefruit juice for at least 48 hours prior to intending to take any of these preparations. When necessaiy, the starting dose of sildenafil should not exceed 25-50 mg and that of tadalafil 10 mg. Avoid co-administration with vardenafil... 

PHOSPHODIESTERASE TYPE 5 INHIBITORS NICORANDIL Risk of severe 1 BP Additive effect Avoid co-administration... 

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