12 Questions
What is the primary mechanism by which tadalafil improves erectile function?
By increasing blood flow to the penis in response to sexual stimulation
What is the effect of tadalafil on PDE5 compared to PDE6?
It is approximately 700-fold more potent for PDE5
What is the time at which the mean maximum observed plasma concentration (Cmax) of tadalafil is achieved?
2 hours after dosing
Which of the following statements about tadalafil is FALSE?
It directly stimulates smooth muscle relaxation in the penile tissues
What is the effect of tadalafil on other phosphodiesterases compared to PDE5?
It is > 10 000-fold more potent for PDE5 than for PDE7 through PDE10
In which tissue is PDE5 primarily found?
Corpus cavernosum smooth muscle
What percentage of tadalafil in plasma is bound to proteins at therapeutic concentrations?
94 %
Which cytochrome P450 isoform is primarily responsible for tadalafil's metabolism?
CYP3A4
What is the approximate volume of distribution for tadalafil?
63 L
How do elderly patients (65 years or over) respond to tadalafil compared to healthy subjects aged 19 to 45 years?
They have higher exposure to tadalafil.
What is the primary route of excretion for tadalafil and its metabolites?
Faeces
How does tadalafil's pharmacokinetics change in patients with diabetes compared to healthy subjects?
The AUC value is approximately 19 % lower.
Study Notes
Mechanism of Action
- Tadalafil improves erectile function by increasing blood flow to the penis in response to sexual stimulation.
- It does so by inhibiting phosphodiesterase type 5 (PDE5), leading to increased levels of cyclic guanosine monophosphate (cGMP) in the corpus cavernosum.
- This results in smooth muscle relaxation and increased blood flow into the penile tissues, producing an erection.
Pharmacodynamic Effects
- Tadalafil is a selective inhibitor of PDE5, which is found in corpus cavernosum smooth muscle, vascular and visceral smooth muscle, skeletal muscle, platelets, kidney, lung, and cerebellum.
- It is approximately 700-fold more potent for PDE5 than for PDE6, and >10,000-fold more potent for PDE5 than for PDE7 through PDE10.
Pharmacokinetic Properties
- Tadalafil is well absorbed after oral administration, with a median time to maximum observed plasma concentration (Cmax) of 2 hours after dosing.
- Food and time of dosing do not affect the rate and extent of absorption.
- The mean volume of distribution is approximately 63 L, and 94% of tadalafil in plasma is bound to proteins.
Biotransformation and Elimination
- Tadalafil is metabolized by cytochrome P450 CYP3A4, with the major circulating metabolite being the methylcatechol glucuronide.
- The metabolite is at least 13,000-fold less potent than tadalafil for PDE5.
- The mean half-life is 17.5 hours in healthy subjects, and tadalafil is excreted predominantly as metabolites, mainly in the feces (61% of the dose) and to a lesser extent in the urine (36% of the dose).
Special Populations
- Elderly patients (65 years or over) have a lower oral clearance of tadalafil, resulting in 25% higher exposure (AUC) relative to healthy subjects aged 19 to 45 years.
- Patients with mild or moderate renal impairment have higher tadalafil exposure (AUC) than healthy subjects.
- Patients with mild and moderate hepatic impairment (Child-Pugh Class A and B) have comparable exposure to healthy subjects, and no dose adjustment is required.
- Patients with diabetes have approximately 19% lower tadalafil exposure (AUC) than healthy subjects, but this difference does not warrant a dose adjustment.
Learn how Tadalafil works to improve erectile function by increasing blood flow to the penis. Understand its role in inhibiting PDE5 and increasing cGMP levels.
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