Usage
Phenylpropanolamine is primarily prescribed for the control of urinary incontinence in dogs due to urethral sphincter hypotonus. It was previously used in humans as a nasal decongestant for the common cold and as an appetite suppressant for weight loss, but these uses have been discontinued due to an increased risk of hemorrhagic stroke. Its pharmacological classification is sympathomimetic agent. Phenylpropanolamine acts by stimulating alpha-adrenergic receptors in the urethral sphincter, causing the muscle to contract and increasing its tone, thereby reducing urine leakage.
Alternate Names
Phenylpropanolamine is also known as PPA. Brand names for veterinary use include Proin and Proin ER. Numerous brand names were previously used for human formulations.
How It Works
Pharmacodynamics: Phenylpropanolamine is an indirectly acting sympathomimetic amine. It acts primarily as a norepinephrine-releasing agent, stimulating alpha-adrenergic receptors in the smooth muscle of the urethra. This stimulation leads to contraction of the urethral sphincter, increasing resistance to urine flow and reducing incontinence. Systemic effects may include elevated heart rate and blood pressure.
Pharmacokinetics: Phenylpropanolamine is well-absorbed orally. It is metabolized in the liver and excreted primarily by the kidneys. Extended-release formulations provide sustained drug levels over a 24-hour period. Concomitant administration with food slows the absorption of extended-release formulations but does not affect overall bioavailability.
Mode of Action: Phenylpropanolamine indirectly activates adrenergic receptors by increasing the release of norepinephrine from presynaptic nerve terminals. This increased norepinephrine concentration in the synaptic cleft leads to stimulation of postsynaptic alpha-adrenergic receptors in the urethral sphincter.
Elimination Pathways: Primarily renal excretion, with some hepatic metabolism.
Dosage
Standard Dosage
Adults (Canine):
- Proin Chewable Tablets: 2 mg/kg body weight orally twice daily.
- Proin ER Extended-Release Tablets: 2-4 mg/kg body weight orally once daily, administered with food. Do not split or crush tablets. Dogs weighing less than 10 lbs cannot be safely dosed with Proin ER.
Children (Canine): Pediatric dosing should be based on weight, following the guidelines for adult dogs.
Special Cases (Canine):
- Elderly Patients: Use with caution and monitor blood pressure closely.
- Patients with Renal Impairment: Reduce dosage and monitor closely for signs of toxicity.
- Patients with Hepatic Dysfunction: Use with caution.
- Patients with Comorbid Conditions: Use with caution in patients with hypertension, heart disease, diabetes mellitus, glaucoma, hyperthyroidism, or other conditions that may predispose to hypertension or be exacerbated by sympathomimetic effects.
Clinical Use Cases
Phenylpropanolamine is not indicated for use in clinical scenarios such as intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations in human medicine. Its primary clinical use is for the management of urinary incontinence in dogs.
Dosage Adjustments
Dose adjustments may be necessary based on patient response and the presence of comorbidities. Regular blood pressure monitoring is essential, especially for patients with pre-existing cardiovascular conditions or those receiving concurrent medications that may interact with phenylpropanolamine.
Side Effects
Common Side Effects:
Restlessness, increased thirst, loss of appetite, irritability, vomiting, diarrhea, difficulty urinating.
Rare but Serious Side Effects:
Seizures, hypertension, stroke-like symptoms (e.g., ataxia, paresis), cardiac arrhythmias, collapse.
Long-Term Effects:
Chronic hypertension may develop with prolonged use.
Adverse Drug Reactions (ADR):
Hypertensive crisis, hemorrhagic stroke (rare but serious).
Contraindications
- Hypersensitivity to phenylpropanolamine.
- Pregnancy.
- Concurrent use or within 14 days of monoamine oxidase inhibitors (MAOIs).
- Pre-existing conditions such as glaucoma, severe heart disease, uncontrolled hypertension, or diabetes mellitus (unless under close veterinary supervision).
Drug Interactions
- MAOIs: May cause severe hypertension or hypertensive crisis.
- Tricyclic antidepressants (TCAs): Increased risk of hypertension.
- Nonsteroidal anti-inflammatory drugs (NSAIDs): Increased risk of hypertension.
- Other sympathomimetics: Additive effects on heart rate and blood pressure.
- Reserpine: May antagonize the effects of phenylpropanolamine.
- L-Deprenyl (Selegiline): May cause unpredictable blood pressure fluctuations.
Pregnancy and Breastfeeding
Phenylpropanolamine is contraindicated in pregnancy. Its safety during breastfeeding has not been established.
Drug Profile Summary
- Mechanism of Action: Indirect-acting sympathomimetic, norepinephrine-releasing agent.
- Side Effects: Restlessness, increased thirst, loss of appetite, irritability, hypertension, seizures (rare).
- Contraindications: Hypersensitivity, pregnancy, concurrent MAOI use.
- Drug Interactions: MAOIs, TCAs, NSAIDs, sympathomimetics.
- Pregnancy & Breastfeeding: Contraindicated in pregnancy, use with caution during breastfeeding.
- Dosage: Varies depending on formulation and patient, typically 2-4 mg/kg once or twice daily for dogs.
- Monitoring Parameters: Blood pressure, heart rate, urinary function.
Popular Combinations
In veterinary medicine, phenylpropanolamine may be used in combination with estrogens (e.g., diethylstilbestrol, estriol) for the treatment of urinary incontinence in spayed female dogs.
Precautions
- Monitor blood pressure regularly, especially in patients at risk for hypertension.
- Ensure adequate water intake.
- Use with caution in patients with pre-existing cardiovascular disease, renal or hepatic dysfunction, diabetes, or glaucoma.
- Monitor for adverse reactions.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Phenylpropanolamine in dogs?
A: The dosage depends on the formulation and the individual dog’s weight and condition. Proin chewable tablets are typically given at 2 mg/kg twice daily, whereas Proin ER extended-release tablets are given at 2-4 mg/kg once daily. Always consult with a veterinarian for appropriate dosing recommendations.
Q2: How does Phenylpropanolamine work to control urinary incontinence?
A: Phenylpropanolamine stimulates alpha-adrenergic receptors in the urethral sphincter, causing the muscle to contract and increasing its tone, which helps to prevent urine leakage.
Q3: What are the most common side effects of Phenylpropanolamine?
A: The most common side effects include restlessness, increased thirst, loss of appetite, irritability, vomiting, and diarrhea.
Q4: Are there any serious side effects I should be aware of?
A: While rare, serious side effects such as seizures, hypertension, stroke-like symptoms, and cardiac arrhythmias have been reported. Contact a veterinarian immediately if these occur.
Q5: Can Phenylpropanolamine be used in pregnant or breastfeeding dogs?
A: Phenylpropanolamine is contraindicated during pregnancy and should be used with caution during breastfeeding. Consult with a veterinarian regarding its use in these situations.
Q6: What are the contraindications for Phenylpropanolamine use?
A: Contraindications include hypersensitivity to phenylpropanolamine, concurrent use or recent use of MAOIs, and certain pre-existing medical conditions such as glaucoma, severe heart disease, uncontrolled hypertension, or diabetes mellitus (unless closely monitored).
Q7: What other medications interact with Phenylpropanolamine?
A: Phenylpropanolamine can interact with MAOIs, tricyclic antidepressants (TCAs), NSAIDs, other sympathomimetics, reserpine, and L-Deprenyl. It’s crucial to inform the veterinarian of all medications the patient is currently taking.
Q8: How should Phenylpropanolamine be stored?
A: Phenylpropanolamine should be stored at room temperature, away from light and moisture, and out of reach of children and pets.
Q9: How long does it take for Phenylpropanolamine to start working?
A: While effects may be seen within 1-2 hours, it may take several days of consistent dosing to fully assess the medication’s effectiveness.
Q10: Should I be concerned about my pet’s blood pressure while on this medication?
A: Blood pressure should be monitored regularly, particularly when starting therapy and then at least twice yearly during ongoing treatment. More frequent monitoring may be necessary in patients with pre-existing conditions that predispose them to hypertension.
