Cialis super force review

The 4,000-times lower selectivity for PDE3 (involved in myocardial contractility) is important because the inhibitors of this isoenzyme (milrinone, vesnarinone, and enoximone) used for treating heart failure cause cardiac arrhythmia and have other noxious effects 8,10 .

The peak of plasma concentration of sildenafil occurs 30 to 120 minutes (mean of 60 minutes) after oral ingestion, during fasting. In the liver, sildenafil is partially converted into a metabolite that accounts for approximately 20% of its pharmacological action, and both circulate almost completely bound to plasma cialis super force review proteins (96%).

The major hepatic metabolic pathways are the cytochrome P450 3A4 (main) and P450 2C9 (secondary) 8,11 .

Excretion is predominantly fecal (80%); only 13% are urinary. For a given oral dose of sildenafil, plasma concentrations of the drug may be 40% higher in individuals above 65 years of age, 80% higher in individuals with hepatic failure, and 100% higher in individuals with severe renal failure (creatinine clearance 11 (table I). Effect on penile tumescence ? Sildenafil is effective in erectile dysfunction of various causes, such as vascular (diabetes), neuroreflexogenic (spinal cord damage), and psychogenic, which has been confirmed in cialis super force review 21 multicenter double-blind randomized trials controlled with placebo 11,12 .

Cardiovascular effects ? 1) Sildenafil does not interfere with myocardial contractility in healthy volunteers.

However, studies in patients with heart failure are still lacking; 2) Sildenafil causes a mild and transient drop in systolic (8 to 10 mmHg) and diastolic (4 to 6 mmHg) blood pressures, with a peak one hour after the oral dose, ingested during fasting, returning to the baseline in 4 hours. This effect results from the peripheral arterial and venous vasodilating action of sildenafil, and it is not dose- (25 to 100 mg) or age-dependent, and seldom causes orthostatic hypotension; 3) sildenafil does not have a significant effect on heart rate 11, 12.

Effect on platelets ? Bleeding episodes and increase in the bleeding and prothrombin times have not been observed, even in patients using acetylsalicylic acid or warfarin. However, assessment

with

Effect on vision - Increase in light sensitivity and a blue-greenish or blurred vision due to the inhibiting action of sildenafil on 6 phosphodiesterase present in the retinal photoreceptors

may

Sildenafil should be carefully used in the presence of retinitis pigmentosa 11, 12 .

Adverse effects ? 1) Vasodilating effects: headache (16%), flushing (10%), and rhinitis (4%). Dizziness (2%), hypotension and postural hypotension (2% each) occurred with equal frequency in the sildenafil and placebo groups; 2) Gastrointestinal effects: dyspepsia due to reflux (7%); 3) Visual effects: increase in light sensitivity or blue-greenish or blurred vision (3%), mainly with doses of 100mg; 4) Musculoskeletal effects: muscle pains, especially with multiple doses, without alterations in the concentration of creatinine phosphokinase and in the electromyogram; 5) Priapism: occasionally reported 11,12 .

Nitrates ? Sildenafil increases the vasodilating action of nitrates and may cause potentially fatal severe hypotension. Based on the pharmacokinetic profile of sildenafil, nitrates should not be used within the 24 hours following the use of sildenafil.

This period should be expanded in those situations prolonging the action of sildenafil (see pharmacokinetics and metabolism).

On the other hand, the use of sildenafil is contraindicated if the nitrate was used in the preceding 24 hours, even sublingual nitrate. In the case of oral route, this precaution is justified because the potential effect of residual traces of nitrate in the organism has not yet been well clarified.

In the case of the sublingual witrate, duration of the action is short, but its use may suggest the need for repeating the dose during or after the intercourse facilitated by sildenafil. Table II shows the medications based on organic nitrates available in the Brazilian market. The anesthetic agent nitrous oxide does not interact with sildenafil 11 . Antihypertensive medications ? Adverse hypotensive effects have not been observed with the antagonists of cialis super force review the calcium channels, angiotensin-converting enzyme inhibitors, thiazides, loop diuretics, potassium sparing diuretics, and alpha- and beta-blockers. In a specific study with amlodipine, the response to sildenafil was not different from the response to placebo. However, one should be cautious when the therapeutical scheme comprises a drug that uses or inhibits the cytochrome P450 3A4 (table I) 6,11 .

Other medications ? Sildenafil does not interact with aspirin and warfarin, and no data regarding antiaggregating agents such as ticlopidine, clopidogrel and dipyridamole are available. In regard to cimetidine and erythromycin, both inhibitors of the cytochrome P450 3A4, it is advisable to begin with low doses of sildenafil (25 mg). Other medications are also metabolized through thisroute; therefore, a competitive inhibition may occur, but the effects of their interaction with sildenafil have not yet been adequately tested 11 (table I).

Other associated conditions ? 1) renal failure: mild (80 to 50 mL/min) and moderate (49 to 30 mL/min) reductions in the creatinine clearance do not significantly affect the metabolism of sildenafil.

In cases of severe renal failure (creatinine clearance 11 ; 2) elderly patients: similar caution should be observed with elderly patients, in whom the plasma concentration of creatinine in the presence of reduction in the muscle mass overestimates the value of creatinine clearance; 3) hepatic failure: the same caution with renal failure should be observed in this situation. Sildenafil in the patient with cardiovascular disease. Circulatory effects in sexual intercourse ? a) in healthy individuals : cardiac overload and metabolic consumption are variable.

In the laboratory, healthy men with their usual female partners reach a heart rate of approximately 110 bpm with female-on-top-coitus and of approximately 127 bpm with male-on-top coitus, corresponding to an exercise of 2.5 to 3.3 METs 11 ; b) in patients with coronary arterial disease : in NYHA functional classes I and II patients without antianginal medication, ischemia occurred during sexual intercourse in 1/3 of the patients, and it was silent 2/3 of the time.

All these patients had ischemia on treadmill stress testing. The mean heart rate varied around 118 bpm, but in some patients it reached 185 bpm at orgasm. In a study with 19 patients, angina during sexual intercourse did not occur with the use of beta-blockers, in parallel with reduction in the mean maximum heart rate from 125 bpm to 82 bpm. Other small studies showed that coitus may cause ventricular extrasystoles not triggered by other stimuli 12 ; c) death of patients with coronary artery disease during sexual intercourse: death during sexual intercourse is rare (0.6% of

the

Even though coitus may trigger an acute myocardial infarction, the relative risk in the 2 hours following sexual activity is low (2.5, CI 95%, 1.7 to 3.7).

And even in this case, direct contribution of coitus to acute myocardial infarction seems to have occurred only 0.9% of the time. Regular physical exercise seems to reduce the risk of acute myocardial infarction during coitus 12 .

It is important to emphasize that these encouraging data do not apply to patients, who, using or not using sildenafil, increase their circulatory and metabolic overload beyond their usual limits, as may happen in extramarital coitus or in coitus after excessive ingestion of food and alcoholic beverages; d) risk assessment : the treadmill stress test may assess the potential risk of a normal coitus in a patient with coronary artery disease.