View source for Talk:Tadalafil

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'''Tadalafil''' is a phosphodiesterase type 5 (PDE5) inhibitor marketed under the trade name '''Cialis''' primarily used to treat erectile dysfunction (ED), benign prostatic hyperplasia (BPH) and Pulmonary Arterial Hypertension (PAH).<ref name="hahappbig">{{cite web | last=Fahmy | first=George | last2=Hess | first2=Jaclyn | title=Tadalafil | publisher=StatPearls Publishing | date=2024-03-20 | pmid=38753929 | url=https://www.ncbi.nlm.nih.gov/books/NBK603743/ | access-date=2024-10-09}}</ref> It is a post-synaptic [[agonist]] of the cGMP-specific phosphodiesterase type 5 (PDE5) enzyme, preventing cGMP breakdown and enhancing smooth muscle relaxation in the corpus cavernosum of the penis.<ref name="EMA">{{cite web|url=https://www.ema.europa.eu/en/documents/product-information/cialis-epar-product-information_en.pdf|title=Cialis: EPAR Product Information|publisher=European Medicines Agency (EMA)|access-date=January 24, 2023}}</ref>

[[File:Tadalafil_structure.png|thumb|Chemical Structure of Tadalafil]]

==Pharmacology==
Tadalafil is a selective PDE5 inhibitor, showing a [[selectivity]] of preference for PDE5 over other PDE isozymes including PDE1, PDE2, PDE3, PDE4, PDE6, PDE7, PDE8, PDE9, PDE10 and PDE11. PDE5 is found predominantly in the corpus cavernosum, prostate, liver and platelets.<ref>{{cite journal|last1=Ghofrani|first1=H. A.|last2=Barst|first2=R. J.|last3=Grimminger|first3=F.|last4=Humbert|first4=M.|last5=Wedzicha|first5=J. A.|last6=Wilkins|first6=M. R.|last7=Schermuly|first7=R. T.|title=Sildenafil for the treatment of lung fibrosis and pulmonary hypertension: from animal disease models to clinical trials|journal=Journal of the American College of Cardiology|volume=45|issue=10|pages=1699-706|year=2005|doi=10.1016/j.jacc.2005.02.054|pmid=15893196|issn=1552-0767}}</ref>

Tadalafil has an elimination half-life of 17.5 hours (range of 13-19 hours), longer than other PDE5 inhibitors: sildenafil (4-6 hours), vardenafil (4-5 hours) and avanafil (6-7 hours). Its relatively long half-life enables it to be prescribed for a frequency of once per day as needed.

Tadalafil's effects on phosphodiesterase 5 last approximately 36 hours after a single 20 mg dose. This allows improved sexual flexibility with spontaneously occurring moments of intimacy. However, the risk of side-effects also generally increases the higher the dosage. It exhibits a dose-response relationship, with higher doses producing stronger erections which are maintained for longer durations.

==Subjective effects==

The primary effects of tadalafil stem from inhibition of phosphodiesterase type 5 (PDE5) within the corpus cavernosum of the penis. This relaxes smooth muscle and widens blood vessels, allowing blood flow to increase. Consequently, the user may experience:

*- Enhanced capacity for sexual arousal and erection hardness when physically and psychologically stimulated
*- Prolonged erection duration
*- Erections more easily triggered but otherwise unchanged psychosexual response

[[File: Cialis Pills.jpg|thumbnail|250px|right|Common commercial formulation of tadalafil (Cialis).]]

Desired effects are mostly limited to improving physiological conditions for satisfactory sexual functioning. Enhancing or altering mental states is not the intended purpose of tadalafil use.

==Comedown==

As a PDE5 inhibitor, tadalafil has no meaningful "comedown" effects once it has cleared from the body and sexual stimulation has ceased. Any residual effects uniformly resolve within 24 hours after ingestion. However, some users report mild next-day fatigue or dizziness from its vasodilatory action.

==Tolerance and addiction potential==

Tadalafil is not considered addictive with a low abuse potential due to its mechanism of action. PDE5 inhibitors have an extremely low risk of abuse and tolerance.

With repeated high-dose tadalafil use, some degree of tolerance can develop within 7-10 days. Upon cessation, this tolerance returns to normal within a week. Limited reports suggest developing a psychological but not physiological dependence when taken daily for at least 6 months. However, compulsive redosing or dose escalation has not been documented with tadalafil outside its intended medical application.

==Toxicity and harm potential==

Tadalafil is generally well-tolerated in recommended medical dosages. It does not directly interact with brain chemistry in any way unlike classical psychedelics or stimulants. Overdoses are treated supportively in a clinical setting with a focus on symptom management.

Risk of physical harm from an overdose alone is very low due to tadalafil's high therapeutic index and natural ceiling effect, alongside lacking any toxicity at moderate to high dosages. Lethal overdoses are not expected unless combined with the simultaneous use of other depressants like alcohol or sedatives.

The main hazard associated with misuse is hypotension severe enough to cause loss of consciousness or cardiovascular issues. This predominantly occurs in those with pre-existing cardiovascular disease who take very high doses, especially when combined with nitrate medication or recreational drugs. However, medical interventions are usually sufficient if the individual is otherwise physically healthy.

===Interaction with stimulants===

While alone tadalafil presents no risk of physical harm, there are some dangers unique to the combination of PDE5 inhibitors and stimulants. Use with stimulants significantly increases the risk of [[hypertensive crisis]], a life-threatening medical emergency. This interaction works through synergistic vasoconstriction caused by both classes's inhibition of PDE isozymes like PDE1 and PDE3.

Specifically, citalopram should be avoided (overdose risk). Similarly, combination with cocaine or amphetamines poses a clear danger and is strongly discouraged due to the resulting severe magnification of their cardiovascular effects.

In comparison, combination with caffeine is relatively low risk provided overall caffeine intake remains in moderation. However, higher doses should still be avoided.

==Interactions==

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==Legal Status==

Tadalafil is legally available as a prescription medication in most jurisdictions for the treatment of erectile dysfunction and benign prostatic hyperplasia. However, recreational use is illegal without a valid prescription.

United States: It is a Schedule IV controlled substance.
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