Usage
Alprostadil is prescribed for the treatment of erectile dysfunction (ED) in adult men. It is also used in newborns and infants to temporarily maintain the patency of the ductus arteriosus (PDA) until corrective surgery can be performed. Its pharmacological classifications include vasodilator and prostaglandin.
Alprostadil is a naturally occurring prostaglandin E1 analog. It functions as a vasodilator, primarily by relaxing smooth muscle in the vascular walls. For ED, this vasodilatory effect increases blood flow to the corpus cavernosum of the penis, facilitating erection. In neonates, it relaxes the smooth muscle in the ductus arteriosus walls, maintaining its opening and ensuring adequate blood flow to the lungs.
Alternate Names
Alprostadil is also known as prostaglandin E1 (PGE1). Brand names for alprostadil include Caverject, Caverject Impulse, Edex, Muse, and Prostin VR.
How It Works
Pharmacodynamics: Alprostadil exerts its vasodilatory effect by directly relaxing the smooth muscle in the walls of arteries and arterioles. This occurs through the activation of adenylate cyclase, which increases intracellular cyclic adenosine monophosphate (cAMP) levels. Elevated cAMP levels then lead to decreased intracellular calcium concentration, ultimately causing smooth muscle relaxation and vasodilation.
Pharmacokinetics:
- Absorption: Alprostadil is absorbed rapidly following intracavernosal or intraurethral administration. It has slower absorption with intravenous infusion.
- Metabolism: Alprostadil undergoes rapid metabolism, primarily in the lungs and liver. It is metabolized by oxidation and enzymatic conversion to inactive metabolites.
- Elimination: The metabolites of alprostadil are mainly excreted in the urine.
Mode of Action: Alprostadil binds to prostaglandin E (EP) receptors, specifically EP2 and EP4 subtypes, located on the smooth muscle cell membranes of the corpus cavernosum and the ductus arteriosus. Activation of these receptors stimulates adenylate cyclase, initiating the intracellular signaling cascade described above.
Receptor Binding, Enzyme Inhibition, or Neurotransmitter Modulation: Alprostadil primarily acts through receptor binding to EP2 and EP4 receptors. It does not significantly inhibit enzymes or modulate neurotransmitters.
Elimination Pathways: Alprostadil is primarily eliminated through hepatic metabolism, with renal excretion playing a minor role. It is metabolized in the lungs, by first-pass pulmonary uptake, and the liver.
Dosage
Standard Dosage
Adults (Erectile Dysfunction):
- Intracavernosal Injection: Initial dose of 2.5 mcg, titrated up to a maximum of 60 mcg depending on response. No more than 3 times per week, at least 24 hours apart.
- Intraurethral Suppository: 125-1000 mcg, no more than twice per day.
Children (Patent Ductus Arteriosus):
- Intravenous Infusion: 0.05-0.1 mcg/kg/min initially, titrated to maintain ductal patency.
Special Cases:
- Elderly Patients: Dose adjustments may be necessary based on renal function.
- Patients with Renal Impairment: Dosage modifications are necessary depending on the degree of impairment.
- Patients with Hepatic Dysfunction: Exercise caution, although specific dosage modifications are not well-established.
- Patients with Comorbid Conditions: Exercise caution in patients with cardiovascular diseases.
Clinical Use Cases
- Patent Ductus Arteriosus: Continuous intravenous infusion is used in neonates and infants with congenital heart defects to maintain the patency of the ductus arteriosus.
Dosage Adjustments
Dosage adjustments are necessary in patients with renal impairment, based on the degree of dysfunction. Adjustments for hepatic impairment are not well-established, but caution should be exercised. Elderly patients may require dose adjustments due to age-related decline in renal function.
Side Effects
Common Side Effects
- Intracavernosal Injection: Penile pain, prolonged erection, hematoma/bruising at injection site, fibrosis.
- Intraurethral Suppository: Urethral burning, pain, bleeding.
- Intravenous Infusion (Neonates): Apnea, bradycardia, fever, flushing, hypotension.
Rare but Serious Side Effects
- Priapism (prolonged erection lasting >4 hours)
- Penile fibrosis
- Urethral stricture
Long-Term Effects
- Penile fibrosis with repeated intracavernosal injections.
Adverse Drug Reactions (ADR)
Priapism is a significant ADR requiring immediate medical attention.
Contraindications
- Hypersensitivity to alprostadil.
- Predisposition to priapism (e.g., sickle cell anemia, multiple myeloma).
- Penile anatomical abnormalities (e.g., severe hypospadias, Peyronie’s disease).
Drug Interactions
- Vasodilators: Additive hypotensive effects.
- Anticoagulants: Increased risk of bleeding.
- Sympathomimetics: May decrease the effect of alprostadil.
- PDE5 inhibitors: Concomitant use is not recommended due to the risk of priapism.
Pregnancy and Breastfeeding
Alprostadil is not indicated for use in women. Male partners of pregnant women should use a condom during intercourse as it is unknown whether alprostadil in seminal fluid can cause harm to the fetus or induce early labor. Breastfeeding is not recommended as it is unknown if alprostadil is present in breast milk.
Drug Profile Summary
- Mechanism of Action: Vasodilator, relaxes smooth muscle.
- Side Effects: Penile pain, prolonged erection, priapism, urethral burning/bleeding, hypotension.
- Contraindications: Hypersensitivity, predisposition to priapism, penile anatomical abnormalities.
- Drug Interactions: Vasodilators, anticoagulants, sympathomimetics, PDE5 inhibitors.
- Pregnancy & Breastfeeding: Not indicated for use in women; men should use a condom with pregnant partners. Breastfeeding not recommended.
- Dosage: ED: 2.5-60 mcg intracavernosal, 125-1000 mcg intraurethral; PDA: 0.05-0.1 mcg/kg/min IV.
- Monitoring Parameters: Blood pressure, heart rate, respiratory rate (neonates), erection duration.
Popular Combinations
No commonly used drug combinations are recommended with alprostadil for ED or PDA.
Precautions
- Monitor for priapism and penile fibrosis.
- Train patients carefully in self-injection techniques.
- Use cautiously in patients with cardiovascular disease.
- Monitor respiratory function in neonates.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Alprostadil?
A: For erectile dysfunction, the intracavernosal injection dose starts at 2.5 mcg, titrated up to 60 mcg. The intraurethral dose is 125-1000 mcg. For PDA, the intravenous infusion dose is 0.05-0.1 mcg/kg/min.
Q2: What are the common side effects of Alprostadil?
A: Common side effects include penile pain, prolonged erection, urethral burning or bleeding, and hypotension.
Q3: What is Priapism, and what should be done if it occurs?
A: Priapism is a prolonged erection lasting more than 4 hours. It requires immediate medical intervention to prevent permanent damage to the penis.
Q4: Can Alprostadil be used with other ED medications?
A: Concomitant use with PDE5 inhibitors is not recommended due to the risk of priapism.
Q5: Is Alprostadil safe for patients with heart conditions?
A: Use with caution in patients with cardiovascular disease due to the risk of hypotension. Consult a cardiologist if necessary.
Q6: What are the contraindications to Alprostadil?
A: Contraindications include hypersensitivity to alprostadil, conditions predisposing to priapism, and penile anatomical abnormalities.
Q7: How should Alprostadil be administered for ED?
A: Alprostadil for ED can be administered via intracavernosal injection or intraurethral suppository.
Q8: How is Alprostadil used to treat Patent Ductus Arteriosus?
A: Alprostadil is given by continuous intravenous infusion in neonates to maintain ductal patency.
Q9: Are there any long-term side effects of using Alprostadil for ED?
A: Repeated intracavernosal injections may lead to penile fibrosis.
Q10: Can Alprostadil be used during pregnancy or breastfeeding?
A: Alprostadil is not indicated for use in women. Male partners of pregnant women should use a condom. Breastfeeding is not recommended.
