What is TADALAFIL / CIALIS?
Tadalafil, sold under the brand name Cialis among others, is a medication used to treat erectile dysfunction (ED), benign prostatic hyperplasia (BPH), and pulmonary arterial hypertension. It is a tablet taken by mouth. Onset is typically within half an hour and the duration is up to 36 hours.
Common side effects include headache, muscle pain, flushed skin, and nausea. Caution is advised in those with cardiovascular disease. Rare but serious side effects include a prolonged erection that can lead to damage to the penis, vision problems, and hearing loss. Tadalafil is not recommended in people taking nitrovasodilators such as nitroglycerin, as this may result in a serious drop in blood pressure. Tadalafil is a PDE5 inhibitor which increases blood flow to the penis with sexual arousal. It also dilates blood vessels in the lungs, which lowers the pulmonary artery pressure.
Tadalafil was approved for medical use in the United States in 2003. It is available as a generic medication in the United States and United Kingdom. In the UK it costs the NHS about 80p per dose as of 2019. In the United States the wholesale cost of this amount is about US$1.91. In 2017, it was the 282nd most commonly prescribed medication in the United States, with more than one million prescriptions.
Tadalafil is used to treat erectile dysfunction (ED), benign prostatic hyperplasia (BPH), and pulmonary arterial hypertension.
Erectile dysfunction
Tadalafil once-daily is FDA-approved for ED, for sale in 2.5, 5, 10, and 20 mg strengths. The price of the 5 mg and 2.5 mg are often similar, so some people score and split the pill.
Benign prostatic hypertrophy
A meta‐analysis found that tadalafil 5 mg once‐daily is an effective treatment for lower urinary tract symptoms due to prostatic hyperplasia and that such treatment had a low rate of adverse effects. Tadalafil 10 mg is FDA-approved for men as a once-daily therapy to treat and prevent symptoms of benign prostatic hypertrophy (BPH), such as urinary urgency, hesitancy, weak stream, dribbling, and incontinence.
Pulmonary arterial hypertension
Tadalafil 40 mg is approved in the United States, Canada, and Japan as a once-daily therapy to improve exercise ability in patients with pulmonary arterial hypertension (PAH).
The pulmonary vascular lumen is decreased in PAH as a result of vasoconstriction and vascular remodeling, resulting in increased pulmonary artery pressure and pulmonary vascular resistance. Tadalafil causes pulmonary artery vasodilation, and inhibits vascular remodeling, thus lowering pulmonary arterial pressure and resistance. Right heart failure is the principal consequence of severe pulmonary arterial hypertension.
The most common potential side effects when using tadalafil are headache, stomach discomfort or pain, indigestion, burping, acid reflux, back pain, muscle aches, flushing, and stuffy and runny nose. These side effects reflect the ability of PDE5 inhibition to cause vasodilation (cause blood vessels to widen), and usually resolve after a few hours. Back pain and muscle aches can occur 12 to 24 hours after taking the drug, and these symptoms usually resolve within 48 hours of onset.
Vision
In May 2005, the U.S. Food and Drug Administration found that tadalafil (along with other PDE5 inhibitors) was associated with vision impairment related to NAION (non-arteritic anterior ischemic optic neuropathy). Most, but not all, of these patients had underlying anatomic or vascular risk factors for development of NAION, unrelated to PDE5 use. The FDA concluded that they were not able to draw a cause and effect relationship, only an association; the label of all three PDE5 inhibitors was changed to alert clinicians to that fact. A 2019 meta-analysis found that tadalafil exposure was not associated with NAION.
Hearing
In October 2007, the FDA announced that the labeling for all PDE5 inhibitors, including tadalafil, requires a more prominent warning of the potential risk of sudden hearing loss as the result of postmarketing reports of temporary deafness associated with use of PDE5 inhibitors.
Tadalafil is metabolized predominantly by the hepatic CYP3A4 enzyme system. The presence of other drugs which induce this system can shorten tadalafil half-life and reduce serum levels, and hence efficacy, of the drug.
Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and the smooth muscle of the corpus cavernosum. This response is mediated by the release of nitric oxide (NO) from nerve terminals and endothelial cells, which stimulates the synthesis of cyclic guanosine monophosphate (more commonly known as cyclic GMP or cGMP) in smooth muscle cells. cGMP relaxes smooth muscle and increases blood flow to the corpus cavernosum.
The inhibition of phosphodiesterase type 5 (PDE5) enhances erectile function by increasing the amount of cGMP. Tadalafil (and sildenafil and vardenafil) inhibits PDE5. However, because sexual stimulation is required to initiate the local penile release of nitric oxide, tadalafil's inhibition of PDE5 will have no effect without direct sexual stimulation of the penis.
Duration of action
Although sildenafil, vardenafil, and tadalafil all work by inhibiting PDE5, tadalafil's pharmacologic distinction is its longer half-life (17.5 hours), compared to sildenafil and vardenafil, which are both 4–5 hours. This translates to a longer duration of action, which is partly responsible for "The Weekend Pill" nickname. Furthermore, the longer half-life is the basis for tadalafil's daily therapeutic use in treating pulmonary arterial hypertension.
Comparison with actions of other PDE5 inhibitors
Tadalafil, sildenafil, and vardenafil all act by inhibiting the PDE5 enzyme, but these drugs also inhibit PDE enzymes 6, 1, and 11 in varying degrees.
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.
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.
Tadalafil inhibits PDE11 more than sildenafil or vardenafil. PDE11 is expressed in skeletal muscle, the prostate, the liver, the kidney, the pituitary gland, and the testes. The effects on the body of inhibiting PDE11 are not known.
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