Tadalafil

Tadalafil (20 mg/ml)

Tadalafil may be advantageous to the following people in clinical settings:

• Men with erectile dysfunction (ED)
• Men with benign prostatic hyperplasia (BPH)
• Patients with pulmonary arterial hypertension
• Men seeking improved exercise capacity
• Individuals with combined ED and BPH symptoms

Tadalafil, which is a phosphodiesterase type 5 (PDE5) inhibitor, treats erectile dysfunction and benign prostatic hyperplasia. Doctors also prescribe it to treat pulmonary arterial hypertension because it helps widen blood vessels and supports better blood flow.

Tadalafil is FDA-approved and may be prescribed under its brand names, Cialis or Adcirca. 

Mechanism of Action

Tadalafil works through several mechanisms:

• Inhibition of PDE5 enzyme: Tadalafil selectively inhibits phosphodiesterase type 5 (PDE5), which is responsible for the degradation of cyclic guanosine monophosphate (cGMP). By preventing cGMP breakdown, tadalafil allows for increased levels of cGMP in smooth muscle cells, leading to smooth muscle relaxation and vasodilation.¹
• Enhancement of nitric oxide signalling: The increased cGMP levels amplify the effects of nitric oxide (NO) released during sexual stimulation, resulting in improved blood flow to the corpus cavernosum of the penis and facilitating erection.²
• Smooth muscle relaxation in the prostate and bladder: Tadalafil’s PDE5 inhibition also affects smooth muscle in the prostate and bladder neck. The bladder neck connects the bladder to the urethra, so relaxing these key muscles is a key mechanism for reducing urinary symptoms typically associated with an enlarged prostate.³
• Pulmonary vasodilation: In pulmonary arteries, PDE5 inhibition leads to vasodilation and reduced pulmonary arterial pressure, which is beneficial in treating pulmonary arterial hypertension.⁴

Therapeutic Potential

These mechanisms enable tadalafil to address multiple conditions related to smooth muscle function and blood flow:

• Erectile dysfunction: Tadalafil is highly effective for ED treatment. A meta-analysis of 22 randomised controlled trials involving 5,478 patients demonstrated that tadalafil significantly improved erectile function scores compared to a placebo, with efficacy rates ranging from 60-81% depending on dosage.⁵
• Benign prostatic hyperplasia: Tadalafil alleviates lower urinary tract symptoms associated with BPH by relaxing smooth muscle in the prostate and bladder. Clinical trials have shown significant improvements in International Prostate Symptom Scores (IPSS), with one study reporting an average reduction of 3.9 points after 12 weeks of 5 mg daily dosing.⁶
• Combined ED and BPH: For men experiencing both conditions, tadalafil provides dual benefits. A randomised trial of 606 men found that daily tadalafil improved both erectile function and BPH symptoms simultaneously, with 71% of patients reporting improved erectile function.⁷
• Pulmonary arterial hypertension: Tadalafil is approved for PAH treatment at higher doses (40 mg daily). A pivotal trial showed that tadalafil improved exercise capacity by an average of 33 meters in a six-minute walk test compared to placebo, along with improvements in PAH symptoms and haemodynamics.⁸
• Exercise performance: Some research suggests tadalafil may enhance exercise capacity in healthy individuals through improved blood flow and oxygen delivery, though results are mixed and more research is needed.₉

Safety

Tadalafil is generally well-tolerated, but certain side effects and contraindications should be noted:

Common side effects include:

• Headache (11-15% of users)
• Dyspepsia (10-12%)
• Back pain (6-12%)
• Myalgia (3-6%)
• Nasal congestion (3-4%)
• Flushing (2-3%)¹³

Serious considerations:

• Contraindicated in patients taking nitrates or nitric oxide donors due to risk of severe hypotension.¹⁰
• May cause sudden vision loss in rare cases (non-arteritic anterior ischaemic optic neuropathy)¹¹
• Can result in priapism (prolonged erection), requiring immediate medical attention.¹⁰
• Should be used cautiously in patients with cardiovascular disease.¹²
• May interact with alpha-blockers, causing symptomatic hypotension.^13,14

How It Compares to Other PDE5 Inhibitors

Tadalafil differs from sildenafil (Viagra) and vardenafil in several key ways:

• Duration of action: Tadalafil’s 17.5-hour half-life provides up to 36 hours of therapeutic effect, compared to 4-5 hours for sildenafil and vardenafil. This extended duration allows for greater spontaneity and the option for daily low-dose administration.¹⁵
• Food interactions: Unlike sildenafil, tadalafil absorption is minimally affected by food intake, providing more flexibility in administration timing.¹⁶
• Selectivity: While all PDE5 inhibitors are selective for PDE5, tadalafil also has some activity against PDE11, though the clinical significance of this is unclear.¹⁷
• BPH indication: Tadalafil is the only PDE5 inhibitor approved for the treatment of BPH, either alone or in combination with ED.¹⁸
• Onset of action: Sildenafil may have a slightly faster onset (30-60 minutes) compared to tadalafil (2 hours), though individual responses vary.¹⁹

Data Sheet

• CAS Number: 171596-29-5
• Molecular Formula: C₂₂H₁₉N₃O₄
• ChemSpider ID: 99301
• PubChem CID: 110635
• DrugBank ID: DB00820
• UNII: 742SXX0ICT

Conclusion

Tadalafil works as a strong and long-lasting PDE5 inhibitor. It helps in treating erectile dysfunction, benign prostatic hyperplasia, and pulmonary arterial hypertension. It is already FDA-approved and available via prescription. Its longer half-life sets it apart from other PDE5 inhibitors by providing relief for up to 36 hours, allowing it to be used either when needed or in small daily doses. 

We sell for research purposes only, and we encourage all individuals to consult with their doctor to determine if tadalafil is suitable for their specific circumstances. The information provided here does not constitute medical advice. 

References

1. Role of Nutraceuticals in Treating Erectile Dysfunction via Inhibition of Phosphodiesterase-5 Enzyme: A Mini Review – PubMed 
2. Chronic inhibition of phosphodiesterase 5 with tadalafil affords cardioprotection in a mouse model of metabolic syndrome: role of nitric oxide – PubMed 
3. In vitro effects of PDE5 inhibitors sildenafil, vardenafil and tadalafil on isolated human ureteral smooth muscle: a basic research approach – PubMed 
4. Tadalafil therapy for pulmonary arterial hypertension – PubMed 
5. Efficacy and safety of daily tadalafil in men with erectile dysfunction previously unresponsive to on-demand tadalafil – PubMed 
6. Tadalafil for the treatment of benign prostatic hyperplasia – PubMed 
7. Tadalafil – a therapeutic option in the management of BPH-LUTS – PubMed 
8. Tadalafil therapy for pulmonary arterial hypertension – PubMed 
9. The impact of PDE5 inhibitors on cardiovascular outcomes – PMC 
10. The efficacy and safety of PDE5 inhibitors – PubMed 
11. Vision disorders and phosphodiesterase type 5 inhibitors: a review of the evidence to date – PubMed 
12. Cardiovascular effects of tadalafil in patients on common antihypertensive therapies – PubMed 
13. Phosphodiesterase type 5 inhibitors for erectile dysfunction – PubMed 
14. Non-Arteritic Anterior Ischemic Optic Neuropathy Associated With the Use of Phosphodiesterase Type 5 Inhibitors: A Literature Review – PMC 
15. Patient preference and satisfaction in erectile dysfunction therapy: a comparison of the three phosphodiesterase-5 inhibitors sildenafil, vardenafil and tadalafil – PMC 
16. Efficacy and safety of tadalafil taken as needed for the treatment of erectile dysfunction in men: results of an integrated analysis – PMC 
17. Potency, selectivity, and consequences of nonselectivity of PDE inhibition – PubMed 
18. An open-label, multicentre, randomized, crossover study comparing sildenafil citrate and tadalafil for treating erectile dysfunction in men naïve to phosphodiesterase 5 inhibitor therapy – PubMed 
19. Tadalafil and vardenafil vs sildenafil: a review of patient-preference studies – PubMed