Usage
Dihydralazine + Reserpine is primarily prescribed for the management of essential hypertension (high blood pressure). It is a fixed-dose combination product containing two antihypertensive agents. It falls under the pharmacological classification of antihypertensives.
Dihydralazine acts as a direct-acting vasodilator, primarily affecting arterioles, leading to a decrease in peripheral vascular resistance and lowering blood pressure. Reserpine is a centrally-acting antihypertensive that depletes catecholamines (norepinephrine, dopamine, and serotonin) from central and peripheral sympathetic nerve endings, resulting in decreased sympathetic tone and vasodilation.
Alternate Names
While there isn’t a universally recognized international non-proprietary name distinct from “dihydralazine + reserpine”, regional variations may exist. Brand names for this combination include Ser-Ap-Es.
How It Works
Pharmacodynamics: Dihydralazine lowers blood pressure by directly relaxing arterial smooth muscle. The precise mechanism of this vasodilation is not fully elucidated but may involve interference with calcium influx into vascular smooth muscle cells. Reserpine, through catecholamine depletion, decreases sympathetic nervous system activity, leading to reduced vascular tone and cardiac output. The combined effect results in a more pronounced antihypertensive response.
Pharmacokinetics: Dihydralazine is well-absorbed orally, undergoes extensive first-pass metabolism in the liver, and is primarily excreted in the urine as metabolites. Reserpine is also well-absorbed orally, extensively metabolized in the liver, and eliminated slowly with a long half-life. It binds strongly to tissues, resulting in prolonged antihypertensive effects.
Mode of Action: At the cellular level, dihydralazine likely inhibits vascular smooth muscle contraction through mechanisms involving intracellular calcium regulation. Reserpine irreversibly binds to and blocks the vesicular monoamine transporter (VMAT), which is responsible for transporting catecholamines into storage vesicles within nerve terminals. This blockade leads to depletion of these neurotransmitters in both central and peripheral nervous systems.
Elimination Pathways: Dihydralazine is mainly excreted as metabolites in the urine with a small amount eliminated in the feces. Reserpine is primarily metabolized in the liver, with some renal excretion.
Dosage
Standard Dosage
Adults:
The typical initial dose is one tablet daily. This may be increased gradually to a maintenance dose of one to two tablets per day administered in one or two divided doses. The maximum recommended daily dose of reserpine is 0.25mg.
Children:
Use in children is generally not recommended due to limited safety and efficacy data. Dosage must be carefully determined by a physician if deemed absolutely necessary.
Special Cases:
- Elderly Patients: Start with a lower dose (e.g., half the standard adult dose) and titrate cautiously according to response and tolerability.
- Patients with Renal Impairment: Use with caution in patients with severe renal dysfunction, as both dihydralazine and reserpine require dose adjustments.
- Patients with Hepatic Dysfunction: Use with caution in patients with impaired liver function due to potential alterations in drug metabolism.
- Patients with Comorbid Conditions: Close monitoring and dose adjustments may be needed in patients with heart failure, diabetes, or other cardiovascular conditions.
Clinical Use Cases
This combination is not typically used in the contexts of intubation, surgical procedures, mechanical ventilation, ICU care, or emergency situations. Its use is primarily focused on long-term management of chronic hypertension.
Dosage Adjustments
Individualized dose titration is essential based on patient-specific factors, including renal function, hepatic function, and response to therapy.
Side Effects
Common Side Effects
- Dizziness
- Headache
- Nasal congestion
- Drowsiness
- Nausea
- Vomiting
- Diarrhea
- Palpitations
- Angina pectoris
Rare but Serious Side Effects
- Depression
- Bradycardia
- Orthostatic hypotension
- Drug-induced lupus-like syndrome
Long-Term Effects
- Weight gain
- Fluid retention
- Electrolyte imbalances
Adverse Drug Reactions (ADR)
- Severe hypotension
- Myocardial ischemia
- Heart failure exacerbations
Contraindications
- Hypersensitivity to either dihydralazine or reserpine
- History of depression
- Active peptic ulcer disease
- Pheochromocytoma
Drug Interactions
- MAO inhibitors
- Tricyclic antidepressants
- Other antihypertensives
- Digoxin
- Certain diabetes medications
Pregnancy and Breastfeeding
This combination is generally avoided during pregnancy, especially in the first trimester. Reserpine is potentially harmful to the fetus. The safety of this combination during breastfeeding is not fully established. Use with caution or consider alternative antihypertensive therapies.
Drug Profile Summary
- Mechanism of Action: Dihydralazine is a direct vasodilator; reserpine depletes catecholamines, reducing sympathetic activity.
- Side Effects: Common: dizziness, headache, nasal congestion; Serious: depression, bradycardia, orthostatic hypotension.
- Contraindications: Depression, peptic ulcer disease, pheochromocytoma.
- Drug Interactions: MAO inhibitors, tricyclic antidepressants, other antihypertensives.
- Pregnancy & Breastfeeding: Generally avoided in pregnancy. Use with caution during breastfeeding.
- Dosage: Initial: 1 tablet daily; Maintenance: 1-2 tablets daily.
- Monitoring Parameters: Blood pressure, heart rate, weight, signs of depression.
Popular Combinations
Dihydralazine and reserpine are sometimes combined with a thiazide diuretic for enhanced antihypertensive effects.
Precautions
Close monitoring of blood pressure and heart rate is essential. Pre-existing cardiovascular, renal, and hepatic conditions warrant careful assessment and dose adjustments. Caution is advised for elderly patients and those with a history of depression.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Dihydralazine + Reserpine?
A: The usual initial dose is one tablet daily, adjusted based on individual response to a maximum of two tablets daily (with reserpine’s dose not to exceed 0.25mg/day).
Q2: What are the most common side effects?
A: Dizziness, headache, nasal congestion, drowsiness, nausea, and palpitations.
Q3: What are the serious side effects to be aware of?
A: Depression, bradycardia, orthostatic hypotension, and lupus-like syndrome.
Q4: Is this drug safe during pregnancy?
A: No, it is generally avoided during pregnancy, especially in the first trimester, due to potential fetal harm from reserpine.
Q5: Can this drug be used in patients with renal impairment?
A: Use with extreme caution and dose adjustments in patients with impaired renal function.
Q6: What are the key drug interactions?
A: MAO inhibitors, tricyclic antidepressants, other antihypertensives can interact significantly.
Q7: What should I monitor in patients taking this medication?
A: Monitor blood pressure, heart rate, weight, and watch for signs of depression.
Q8: What are the contraindications for this medication?
A: Contraindicated in patients with a history of depression, active peptic ulcer disease, and pheochromocytoma.
Q9: How does this drug work to lower blood pressure?
A: Dihydralazine is a direct vasodilator, and reserpine depletes catecholamines, reducing sympathetic nervous system activity, both lowering blood pressure through different mechanisms.
Q10: Are there any dietary restrictions while taking this medication?
A: While specific dietary restrictions aren’t typically associated with this medication, a low-sodium diet is generally recommended for hypertension management. Alcohol may potentiate the hypotensive effects of the medication and should be used with caution.
