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Author Topic: Health risks of Erectile dysfunction

April 07, 2021, 07:54:35 AM
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jessica231


Cardiovascular safety Clinical trial results of the four PDE5Is and post-marketing data of sildenafil, tadalafil, and vardenafil have demonstrated no increase in myocardial infarction rates in patients receiving PDE5Is, as part of either RCTs or open-label studies, or compared to expected rates in age-matched male populations.

None of the PDE5Is harmed total exercise time or time-to-ischemia during exercise testing in men with stable angina. Chronic or on-demand use is well tolerated with a similar safety profile. All PDE5Is are contraindicated in:

i) patients who have suffered from a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months;
ii) patients with resting hypotension (blood pressure < 90/50 mmHg) or hypertension (blood pressure > 170/100 mmHg);
iii) patients with unstable angina, angina with sexual intercourse, or congestive heart failure.

What is Vidalista 60 mg?
 
A viagra containing the important Sildenafil Citrate is liable for assisting with ED and hypertension. Both these issues are associated with unpredictable bloodstream in the vessels. 
 
Vidalista 60 mg widens the veins, which brings about a better bloodstream, an interaction known as vasodilation. Legitimate progression of blood likewise implies a lower possibility of getting a coronary illness or a stroke. Vidalista helps in keeping an erection for as long as 4 hours.
 
The patient should take the pill with a glass of water 1 hour earlier.
Try not to surpass the dose past one pill in 24 hours.
Stay away from high-fat dinners.
Stay away from liquor.


Nitrates are contraindicated with PDE5 inhibitors Absolute contraindication to PDE5Is is represented by patients who are using any form of organic nitrate (e.g. nitroglycerine, isosorbide mononitrate, and isosorbide dinitrate) or nitric oxide (NO) donors (e.g. other nitrate preparations used to treat angina, as well as amyl nitrite or amyl nitrate (“poppers” used for recreation).

They result in cGMP accumulation and unpredictable falls in blood pressure and symptoms of hypotension. The duration of interaction between organic nitrates and PDE5Is depends upon the PDE5I and nitrate used.

If a PDE5I is taken and the patient develops chest pain, nitroglycerine must be withheld for at least 24 h if sildenafil (and probably also vardenafil) is used (half-life, 4 h), or at least 48 h if tadalafil is used (half-life, 17.5 h), and for no less than 12 h if avanafil is used (half-life, 6-17 h).

Antihypertensive drugs Co-administration of PDE5Is with antihypertensive agents (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, calcium blockers, β-blockers, and diuretics) may result in small additive decreases in blood pressure, which are usually minor.

In general, the adverse event profile of a PDE5I is not made worse by a background of antihypertensive medication, even when the patient is taking several antihypertensive agents.

α-Blocker interactions All PDE5Is show some interaction with α-blockers, which under some conditions may result in orthostatic hypotension. Sildenafil labeling advises that 50 or 100 mg sildenafil should be used with caution in patients taking an α-blocker (especially doxazosin).

Hypotension is more likely to occur within 4 h following treatment with an α-blocker. A starting dose of 25 mg is recommended.
• Concomitant treatment with vardenafil should only be initiated if the patient has been stabilized on his α-blocker therapy. Co-administration of vardenafil with tamsulosin is not associated with clinically significant hypotension.

•Tadalafil is not recommended in patients taking doxazosin, but this is not the case for tamsulosin.
• Avanafil labeling currently reports that patients should be stable on α-blocker therapy before initiating avanafil. In these patients, avanafil should be initiated at the lowest dose of 50 mg. Conversely, in those patients already taking an optimized dose of avanafil, α-blocker therapy should be initiated at the lowest dose.

Dosage adjustment Drugs that inhibit the CYP34A pathway will inhibit the metabolic breakdown of PDE5Is, thus increasing PDE5Is blood levels (among them, ketoconazole, ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, and telithromycin).

Therefore, lower doses of PDE5Is are necessary. However, other agents, such as rifampin, phenobarbital, phenytoin, and carbamazepine, may induce and enhance the breakdown of PDE5Is, so that higher doses of PDE5Is are required. Severe kidney or hepatic dysfunction may require dose adjustments or warnings.

Management of non-responders to PDE5 inhibitors The two main reasons why patients fail to respond to a PDE5I are either incorrect drug use or lack of efficacy of the drug. Data suggest that an adequate trial involves at least six attempts with a particular drug [119]. The management of non-responders depends upon identifying the underlying cause.

Check that the patient has been using a licensed medication There is a large black market in PDE5Is. The amount of active drugs in these medications varies enormously and it is important to check how and from which source the patient has obtained his medication.

Check that the medication has been properly prescribed and correctly used The main reason why patients fail to use their medication correctly is inadequate counseling from their physician. The main ways in which a drug may be incorrectly used are:

i) failure to use adequate sexual stimulation;
ii) failure to use an adequate dose; and,
iii) failure to wait an adequate amount of time between taking the medication and attempting sexual intercourse.

Lack of adequate sexual stimulation:
PDE5I action is dependent on the release of NO by the parasympathetic nerve endings in the erectile tissue of the penis. The usual stimulus for NO release is sexual stimulation, and without adequate sexual stimulation (and NO release), the drugs cannot work. Oral PDE5Is take different times to reach maximal plasma concentrations.

Although pharmacological activity is achieved at plasma levels well below the maximal plasma concentration, there will be a period following oral ingestion of the medication during which the drug is ineffective. Even though all four drugs have an onset of action in some patients within 15-30 min of oral ingestion, most patients require a longer delay between taking the medication.

Absorption of sildenafil can be delayed by a meal, and absorption of vardenafil can be delayed by a fatty meal. Absorption of tadalafil is less affected provided there is enough delay between oral ingestion and an attempt at sexual intercourse. When avanafil is taken with a high-fat meal, the rate of absorption is reduced with a mean delay in Tmax of 1.25 h and a mean reduction in Cmax of 39% (200 mg).

There is no effect on the extent of exposure (AUC). The small changes in avanafil Cmax are considered to be of minimal clinical significance. It is possible to wait too long after taking medication before attempting sexual intercourse.

The half-life of sildenafil and vardenafil is about 4 h, suggesting that the normal window of efficacy is 6-8 h following drug ingestion, although responses following this time are well recognized. The half-life of avanafil is 6-17 h. Tadalafil has a longer half-life of ~17.5 h, so the window of efficacy is much longer at ~36 h.

Data from uncontrolled studies suggest patient education can help salvage apparent non-responders to a PDE5I. After emphasizing the importance of dose, timing, and sexual stimulation to the patient, EF can be effectively restored following re-administration of the relevant PDE5I.

Avanafil is a highly-selective PDE5I that recently became commercially available. Avanafil has a high ratio of inhibiting PDE5 as compared with other PDE subtypes allowing for the drug to be used for ED while minimizing adverse effects.

Fifty, 100, and 200 mg doses have been approved for on-demand treatment of ED. The recommended starting dose is 100 mg taken orally as needed approximately 30 min before sexual activity and should be adapted according to efficacy and tolerability.

In the general population with ED, the mean percentage of attempts resulting in successful intercourse was approximately 47%, 58%, and 59% for the 50 mg, 100 mg, and 200 mg avanafil groups, respectively, as compared with approximately 28% for placebo.

Data from sexual attempts made within 15 minutes of dosing showed successful attempts in 64%, 67%, and 71% cases, with avanafil 50, 100, and 200 mg, respectively. The maximum recommended dosing frequency is once per day. Dosage adjustments are not warranted based on renal function, hepatic function, age, or gender.

Pairwise meta-analytic data from available studies suggested that avanafil significantly improved patient scores for IIEF, SEP2, SEP3, and GAQ, with an evident dose-response relationship.

Administration with food may delay the onset of effect compared with administration in the fasted state but avanafil can be taken with or without food. The efficacy of avanafil in any subgroup of patients with ED, including difficult-to-treat subgroups (e.g diabetes mellitus), has been successfully established.
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April 08, 2021, 06:12:34 AM
Reply #1
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DELEPE


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