Usage
Papaverine is a vasodilator, primarily indicated for the treatment of various conditions involving spasms of smooth muscle. These include:
- Vascular spasm: Associated with conditions like acute myocardial infarction (coronary occlusion), angina pectoris, peripheral and pulmonary embolism, peripheral vascular disease with a vasospastic component, and certain cerebral angiospastic states.
- Visceral spasm: Such as ureteral, biliary, or gastrointestinal colic.
It has also been used off-label for erectile dysfunction (ED) through intracavernosal injection, but this is not an FDA-approved indication and carries risks.
Pharmacological Classification: Vasodilator, smooth muscle relaxant.
Mechanism of Action: Papaverine inhibits phosphodiesterase, leading to increased levels of cyclic AMP and cyclic GMP within smooth muscle cells. This results in smooth muscle relaxation and vasodilation, improving blood flow.
Alternate Names
Papaverine hydrochloride.
Numerous brand names exist internationally, varying by region.
How It Works
Pharmacodynamics: Papaverine relaxes smooth muscle, causing vasodilation and reducing spasms in blood vessels and visceral organs. This leads to improved blood flow and relief of ischemic symptoms. High doses can depress myocardial function.
Pharmacokinetics:
- Absorption: Oral absorption is approximately 54%.
- Metabolism: Primarily hepatic.
- Elimination: Renal excretion.
Mode of Action: Papaverine inhibits phosphodiesterase, leading to increased intracellular cyclic AMP and cyclic GMP. It is not related to nerve blockade or adrenergic receptor activity.
Elimination Pathways: Primarily hepatic metabolism followed by renal excretion.
Dosage
Standard Dosage
Adults:
- Oral (extended-release capsules): 150 mg every 12 hours, which can be increased to 150 mg every 8 hours or 300 mg every 12 hours.
- IV/IM: 30 to 120 mg every 3 hours as needed, administered slowly over 1-2 minutes.
Children:
Safety and efficacy not fully established. Dosages of 6 mg/kg/day divided into four IV or IM doses have been used.
Special Cases:
- Elderly Patients: May require lower doses due to age-related decline in organ function. Careful monitoring is recommended.
- Patients with Renal Impairment: Dosage adjustment may be necessary.
- Patients with Hepatic Dysfunction: Reduce dosage as needed due to impaired metabolism.
- Patients with Comorbid Conditions: Exercise caution in patients with heart conditions, glaucoma, or AV block.
Clinical Use Cases
Dosage guidelines for these clinical situations vary widely based on specific patient needs and the severity of the condition. Consult relevant guidelines and specialist literature for specific dosage recommendations.
Dosage Adjustments
Dosage modifications are crucial based on patient factors such as renal or hepatic dysfunction, and concomitant medications. Careful monitoring of vital signs and adverse effects is necessary to adjust the dose appropriately.
Side Effects
Common Side Effects
Nausea, abdominal distress, anorexia, constipation, malaise, drowsiness, vertigo, sweating, headache, diarrhea, skin rash, flushing, increased heart rate and respiratory rate, slight increase in blood pressure.
Rare but Serious Side Effects
Hepatic hypersensitivity (jaundice, eosinophilia, altered liver function tests), AV block, cardiac arrhythmias, severe hypotension, priapism (with intracavernosal injection), allergic reactions (hives, difficulty breathing, swelling).
Long-Term Effects
Priapism and penile fibrosis (with chronic intracavernosal use).
Adverse Drug Reactions (ADR)
Severe allergic reactions, severe cardiovascular effects (hypotension, arrhythmias), hepatotoxicity.
Contraindications
- Complete atrioventricular heart block.
- Hypersensitivity to papaverine.
- Intracorporeal injection for impotence is contraindicated due to the risk of priapism.
Drug Interactions
Papaverine interacts with numerous medications, including those affecting blood pressure, sedatives, anticoagulants, and some antidepressants. Consult a comprehensive drug interaction resource for detailed information.
- CYP450 Interactions: Limited data available.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C. Use with caution only if clearly needed.
- Breastfeeding: Excretion in breast milk is unknown. Exercise caution.
Drug Profile Summary
Refer to individual sections above.
Popular Combinations
Papaverine is sometimes used in combination with phentolamine and alprostadil for intracavernosal injection in treating ED, although this is not an FDA-approved indication.
Precautions
Use cautiously in patients with glaucoma, hepatic dysfunction, and cardiovascular disease. Monitor liver function tests in patients receiving prolonged therapy.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Papaverine?
A: Please refer to the Dosage section for detailed adult and pediatric dosing, along with adjustments based on renal/hepatic function and other patient-specific factors.
Q2: What are the primary uses of Papaverine?
A: Papaverine is primarily used for relieving vascular and visceral spasms associated with various conditions.
Q3: Is Papaverine safe to use during pregnancy?
A: Papaverine is a Pregnancy Category C drug. Use with caution only if the benefits outweigh the potential risks to the fetus.
Q4: What are the common side effects of Papaverine?
A: Common side effects include nausea, flushing, headache, dizziness, and changes in blood pressure and heart rate.
Q5: How is Papaverine administered?
A: Papaverine can be administered orally, intravenously, or intramuscularly. For certain specialized applications, like treating cerebral vasospasm, it might be given intra-arterially.
Q6: What are the contraindications for Papaverine use?
A: Papaverine is contraindicated in patients with complete atrioventricular heart block and hypersensitivity to the drug.
Q7: Does Papaverine interact with other medications?
A: Yes, Papaverine interacts with a wide range of drugs. Be sure to check for potential drug interactions before administering.
Q8: Are there any long-term effects associated with Papaverine use?
A: Long-term intracavernosal use can lead to priapism and penile fibrosis.
Q9: What should I monitor in patients taking Papaverine?
A: Monitor patients for blood pressure changes, heart rate irregularities, liver function, and allergic reactions.
Q10: Is Papaverine effective for all types of erectile dysfunction?
A: The effectiveness of Papaverine for ED is variable and depends on the underlying cause. It’s not FDA-approved for this use, and other treatment options are generally preferred.
