Tadalafil, (6R-trans)-6-(1,3-benzodioxol-5-yl)-2,3,6,7,12,12a-hexahydro-2-methyl-pyrazino[1＇, 2＇ :1,6]pyrido[3,4-b]indole-1,4-dione (Clialis), is a kind of PDE5 inhibitor and an orally administered drug. 

It is a b-carboline derivative and it is structurally distinct from vardenafil (Levitraw) and sildenafil (Viagraw), both of which are PDE5 inhibitors based on a fused pyrimidine core structure. Powder Tadalafil (CAS 171596-29-5) increase the blood flow into the corpus cavernosum by relaxing the blood vessels muscles, and this enables a man to achieve an erection.

Tadalafil powder was approved by the United States (U.S.) Food and Drug Administration (FDA) in 2003 for the treatment of dysfunction (ED), and marketed worldwide under the brand name Cialis.

It is also used to treat pulmonary arterial hypertension and benign prostatic hyperplasia, a condition in which the prostate gland becomes enlarged, causing problems with urination.

Tadalafil’s distinguishing pharmacologic feature is its longer half-life (17.5 hours) compared with Viagra and Levitra (4-5 hours).

This longer half-life results in a longer duration of action and is, in part, responsible for the Cialis nickname of the “weekend pill.”

This longer half-life also is the basis of current investigation for tadalafil’s use in pulmonary arterial hypertension as a once-daily therapy.

Mechanism of Action

Penile erection during sexual stimulation is achieved by the relaxation of penile arteries and corpus cavernosal smooth muscles, leading to increased blood flow to the organ.

This relaxation allows for increased blood flow through the penile arteries, while this blood fills two chambers inside the penis called the corpora cavernosa.

As the chambers fill with blood, the penis grows rigid. Erection ends when the muscles contract and the accumulated blood can flow out through the penile veins.

This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells and then controls the dilation and contraction of the blood vessels that carry blood to and from the penis.

Cyclic GMP causes smooth muscle relaxation and increased blood flow into the corpus cavernosum, and is degraded by the cGMP specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum located around the penis.

Tadalafil inhibits PDE5 and thereby enhances by increasing the amount of cGMP available. Tadalafil stops PDE5 from destroying cGMP and then increases the available cGMP to achieve  function and causes the erection to last for longer.

However, as the half-life of Tadalafil is relatively short, its effect wears off in the course of 2 days making PDE5 come back and sex health decreases. 

With continued use it will take longer to achieve the effect such as low-strength Cialis 4-5 days for 4-5 days.

Application

• Erectile dysfunction (ED)
• Pulmonary arterial hypertension
• Benign prostatic hyperplasia
• Analgesic
• Norepinephrine uptake blocker
• Mu-opiod receptor agonist

Recommended Tadalafil powder Dosage

Cialis comes in yellow, film-coated and almond-shaped tablets in 5, 10 and 20 milligram (mg) doses. The recommended starting dose of Cialis powder for use as needed in most patients is 10 mg, taken prior to anticipated sexual activity.

A first dose is 10 milligrams (mg) at least 30 minutes before sexual activity. The dose can increase to 20 mg or decreased to 5 mg, based on individual efficacy and tolerability. But, the maximum is 20 mg as a single dose.

The maximum recommended dosing frequency is once per day in most patients. it should not should take no more than one dose in 24 hours. Patients who expect to be sexually active at least twice a week can take a daily dose of 5 mg, and this may be reduced to 2.5 mg once daily, depending on the individual reaction.

Cialis powder for use as needed was shown to improve function compared to placebo up to 36 hours following dosing.

Therefore, when advising patients on optimal use of Cialis powder, this should be taken into consideration.

It is worth noting that an erection will not occur just by taking a pill. And do not take Cialis for dysfunction if you are taking Adcirca for pulmonary arterial hypertension.

Beside, Tadalafil for dysfunction is only for use by adults aged 18 years and above.

Benefits

♦ Tadalafil powder may help relax the muscle in your prostate and bladder. This could help improve your BPH symptoms.

♦ To improve ED symptoms, tadalafil powder helps increase blood flow to the penis. This can help you get and keep an erection.

For tadalafil powder to help you have an erection, you need to be sexually aroused.

♦ For PAH, tadalafil powder works to improve ability to exercise by relaxing blood vessels in your lungs. This increases blood flow.

Side effects

Along with its needed effects, a medicine may cause some unwanted effects.

Although not all of these side effects may occur, if they do occur they may need medical attention.

Please check the following side effects of Raw Powder tadalafil powder:

Common side effects

▪ headache

▪ upset stomach

▪ back pain

▪ muscle aches

▪ flushing (reddish skin)

▪ stuffy or runny nose

▪ diarrhea

Rare but serious side effects 

A prolonged erection that can lead to damage to the penis, vision problems, and hearing loss.

Contradictions

▲Heart rhythm problems, angina, or any kind of heart disease

▲High or low blood pressure

▲Congestive heart failure or stroke within the last 6 months, or myocardial infarction within the last 3 months

▲Sickle cell anemia, multiple myeloma, hemophilia, leukemia, or another blood disorder

▲Liver or kidney disease

▲Stomach ulcer

▲Retinitis pigmentosa

▲Structural deformity of the penis, such as Peyronie’s disease

▲Any health condition that is advised not to have sexual intercourse

Tadalafil interaction

Tadalafil has a modest synergistic effect on the nitrate-induced reduction in blood pressure. Tadalafil can cause a serious drop in your blood pressure when used with nitrates, which can lead to dizziness, fainting, and rarely heart attack or stroke. 

In clinical studies, significant rates of response were reported up to 36 h following drug ingestion.

Tadalafil is predominantly metabolized in the liver by CYP3A4 to entities that are not active against PDE5 and excreted mainly as metabolites in the feces and the urine.

The pharmacokinetics of tadalafil are unaffected by factors such as intake of food and alcohol, age, the presence of diabetes, and mild or moderate hepatic insufficiency.

The most common drug-related adverse events are headache, back pain, dyspepsia, and myalgia.

At 10 and 20 mg doses, Tadalafil does not have a significant effect on blood pressure and heart rate and does not result in increased instances of myocardial infarction.

Rare reports of prolonged erections greater than 4 h and priapism have been noted with the use of tadalafil. Priapism, if not treated properly, can result in irreversible damage to the tissue.

Further information

Tadalafil powder, sildenafil powder, and vardenafil powder all act by inhibiting the PDE5 enzyme, but these drugs also inhibit PDE enzymes 6, 1, and 11 in varying degrees.  For example, Sildenafil and vardenafil inhibit PDE6, an enzyme found in the eye, more than tadalafil. Some sildenafil users see a bluish tinge and have a heightened sensitivity to light because of PDE6 inhibition. Besides, Sildenafil and vardenafil also inhibit PDE1 more than tadalafil. PDE1 is found in the brain, heart, and vascular smooth muscle. It is thought that the inhibition of PDE1 by sildenafil and vardenafil leads to vasodilation, flushing, and tachycardia.

Compared to the performance in PDE6 and PDE1, tadalafil performed more prominently on PDE11. PDE11 is expressed in skeletal muscle, the prostate, the liver, the kidney, the pituitary gland, and the testes. However, the effects on the body of inhibiting PDE11 are not known.