Tadalafil-5

Mechanism of action:

• Penile erection during sexual arousal is caused by an increase in penile flow as a result of penile arteries relaxation and smooth muscle of the corpus cavernosum. This reaction is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cyclic guanosine monophosphate (commonly known as cyclic GMP or cGMP) in smooth muscle cells. cGMP relaxes smooth muscle and increases blood flow to the corpus covarnosum.
• Inhibition of phosphodiesterase type 5 (PDE5) enhances erectile function by increasing the amount of cGMP. Tadalafil (and sildenafil and vardenafil) inhibits PDE5. However, because local penile release of nitric oxide requires sexual stimulation, tadafil’s inhibition of PDA5 would have no effect without sexual stimulation.

Pharmacokinetics:

• Absorption – After single oral-dose administration, the maximum observed plasma concentration (Cmax) of tadalafil is achieved between 30 minutes and 6 hours (median time between 2 hours). The absolute bioavailability of tadalafil after oral dosing has not been determined. The rate and extent of absorption of tadalafil is not affected by food; thus this tablet can be taken with or without food.
• Distribution – The average apparent volume of distribution after oral administration is approximately 63 L, indicating that tadalafil is distributed in tissues. At therapeutic concentrations, 94% of tadalafil in plasma is bound to protein. Less than 0.0005% of the administered dose appeared in the semen of healthy subjects.
• Metabolism – Tadlafil is metabolized primarily by CYP3A4 to a catechol metabolite. The catechol metabolite undergoes extensive methylation and glucuronidation to form methylcatechol and methylcatechol glucuronide conjugates, respectively. The major circulating metabolite is methylcatechol glucononide. Methylcatechol concentrations are less than 10% of glucoronide concentrations. In vitro data suggest that metabolites are not expected to be pharmacologically active at concentrated metabolite concentrations. Elimination – The average oral clearance for tadalafil is 2.5 L / hr and the average terminal half-life in healthy life is 17.5 hours. Tadalafil is excreted mainly in the form of feces (about 61% of the dose) and to some extent in the urine (about 36% of the dose).

Pharmacodynamics:

• Tadalafil is used to treat male erectile dysfunction (impotence) and pulmonary arterial hypertension (PAH). Part of the physiological process of erectile dysfunction involves the release of nitric oxide (NO) in the corpus cavernosum. This enzyme then activates the gynylate cyclase resulting in increased levels of cyclic guanosine monophosphate (cGMP), which relaxes smooth muscle in the corpus cavernosum, resulting in increased blood growth and an erection. Tadalafil is a potent and selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) responsible for the degradation of cGMP in the corpus cavernosum. This means that, with tadalafil on board, normal sexual arousal leads to an increase in the level of the corpus that occurs in the corpus cavernum which leads to better erections. Without sexual stimulation and activation of the NO / cGMP system, tadalafil should not cause erection.

Precautions:

• Before taking tadalafil, tell your doctor or pharmacist if you are allergic to it; Or if you have any other allergies. This product may contain inactive ingredients, which may cause allergies or other problems. Talk to your pharmacist for more details.
• Before using this medicine, tell your doctor or pharmacist your medical history, specifically: heart problems (such as heart attack or life-threatening irregular heartbeat in the past 6 months, chest pain / angina , Heart failure), stroke months in the past 6, kidney disease, liver disease, high or low blood pressure, severe loss of body water (dehydration), penis status (Such as angulation, fibrosis / scarring, pyroneic disease), history of painful / prolonged erections (keratism), conditions that may increase the risk of keratosis (eg sickle cell anemia, leukemia, multiple myeloma), eye conditions. Problems (eg retinitis) pigmentosa, sudden loss of vision, NAION), bleeding disorders, active stomach ulcers.

Side effects:

• To reduce the risk of dizziness and lighthouse, rise slowly when getting up from a sitting or lying position.
• Remember that your doctor has prescribed this medicine because he or she has decided that the benefit to you outweighs the risk of side effects. Many people using this medicine do not have serious side effects.
• Sexual activity can put extra pressure on your heart, especially if you have heart problems. If you have a heart problem and experience any of these serious side effects while having sex, stop immediately and seek medical help: severe dizziness, fainting, chest / jaw / arm pain, nausea.
• Rarely, there may be a sudden loss of vision, including permanent blindness in one or both eyes (NAION). If this is a serious problem, stop taking Tadalafil and seek medical attention immediately. If you have heart disease, diabetes, high cholesterol, some other eye problems (“congested disc”), high blood pressure, if you are over 50, or if you smoke, you are slightly more likely to develop NAION.

Dosage:

• The recommended starting dose of this tablet in most patients is 10 mg, taken prior to anticipated sexual activity. Depending on individual efficacy and tolerability, the dose may be increased to 20 mg or reduced to 5 mg. The frequency of the maximum recommended dose is once per day in most patients.

Over dosage:

• Healthy subjects have been given a single dose of up to 500 mg, and patients have been given multiple daily doses of up to 100 mg. Adverse events were similar to those observed at low doses. In cases of overdose, standard supportive measures should be adopted as required. Hemodialysis carelessly contributes to tadalafil elimination.

Warning:

• General – Physicians should consider their patients’ heart conditions, as there is a degree of cardiovascular risk related to sexual activity. Therefore, treatment for erectile dysfunction, including this tablet, should not be used in men for whom sexual activity occurs inadvisably as a result of their underlying heart condition. Left ventricular outflow obstruction – Patients with left ventricular outflow obstruction, (eg, aortic stenosis and idiopathic hypertrophic subaortic stenosis) may be sensitive to the action of vasodilators, including PDE5 inhibitors.

Duration of action:

• Although sildenafil, vardenafil, and tadalafil all work by inhibiting PDE5, pharmacological distortion of tadalafil has a longer half-life (17.5 hours) than sildenafil and vardenafil, both of which are 4–5 hours. This translates to a longer duration of the verb, which is partly responsible for the nickname “The Weekend Pill”. In addition, prolonged half-life is the basis for the daily therapeutic use of tadalafil for the treatment of pulmonary arterial hypertension.

Drug- drug interation:

• Tadalafil can cause a severe drop in your blood pressure when used with nitrate, causing dizziness, fainting, and rarely a heart attack or stroke. Do not use tadalafil with any of the following: Some medications used to treat chest pain / angina (nitrates such as nitroglycerin, isosorbide), recreational drugs called “poppers” containing amyl or butyl nitrite. Are included.
• If you are taking an alpha blocker drug (such as doxazosin, tamsulosin) to treat an enlarged prostate / BPH or high blood pressure, your blood pressure may be very low leading to dizziness or fainting. Your doctor may begin treatment with a low dose of tadalafil or adjust your alpha blocker medication to reduce your risk of low blood pressure.
• Other medications may affect the removal of tadalafil from your body, which may affect how tadalafil works. Examples include azole antifungals (such as itraconazole, ketoconazole), macrolide antibiotics (eg clarithromycin, erythromycin), HIV protease inhibitors (eg fosamenevir, ritonavir), hepatitis C virus protease inhibitors (such as bosepirvir telomeres, telavir).

Adverse reactions:

• These may include headaches, back pain, muscle aches, pain in your arms and legs, facial redness, stuffy nose, and indigestion. Do not take Tadalafil if you also take medicines called nitrates (often prescribed for chest pains).

Pregnancy:

• This brand of medicine is not commonly used in women. During pregnancy, tadalafil should be used only when clearly needed. Discuss the risks and benefits with your doctor.

Fertility:

• There have been no studies evaluating the effect of tadalafil on fertility in men.

Containdication:

• Nitrates – Administration of this tablet to patients who are using any type of organic nitrate regularly and / or intermittently is contraindicated. In clinical pharmacology studies, tadalafil was shown to enforcing hypothetical effects of nitrate. It is thought to result from the combined effects of nitrates and tadalafil on the nitric oxide / cGMP pathway. Hypersensitivity – this tablet is known to patients with tadalafil or any component of the tablet.

Storage:

• Do not store tadalafil for 2.5 mg, 10 mg and 20 mg – above 30 ° C.

Breastfeeding:

• Pregnancy and breastfeeding women can be treated with pulmonary hypertension. If you have pulmonary hypertension, tadalafil is not recommended in pregnancy or while breastfeeding.