Reserpine

Usage

• Reserpine is prescribed primarily for the management of hypertension (high blood pressure). Historically, it was also used to treat psychiatric disorders, particularly severe agitation in individuals with mental disorders, but safer and more effective alternatives are now preferred.
• Pharmacological Classification: Antihypertensive, Rauwolfia alkaloid. It can also be categorized as a sympatholytic or adrenergic blocking agent.
• Mechanism of Action: Reserpine depletes catecholamines (norepinephrine, dopamine, and serotonin) from presynaptic storage vesicles in central and peripheral neurons. This depletion reduces sympathetic activity, leading to vasodilation, decreased heart rate, and a consequent reduction in blood pressure.

Alternate Names

• International Nonproprietary Name (INN): Reserpine.
• Brand Names: Serpasil (Note: Reserpine is no longer readily available in many countries, including the United States, in its brand-name formulation. It may be available in bulk form or compounded formulations).

How It Works

• Pharmacodynamics: Reserpine exerts its antihypertensive effect by depleting catecholamines from peripheral sympathetic nerve endings. This results in decreased peripheral vascular resistance, decreased cardiac output, and reduced blood pressure. It also has central nervous system (CNS) effects, causing sedation and tranquility due to depletion of central catecholamines and serotonin.
• Pharmacokinetics: Reserpine is well absorbed orally. It is highly lipophilic and extensively distributed throughout the body, including the CNS. It is metabolized in the liver via CYP enzymes and eliminated primarily through hepatic routes. Some excretion occurs via the kidneys. The half-life is prolonged, with a terminal half-life of approximately 33 hours.
• Mode of Action: Reserpine binds to the vesicular monoamine transporter (VMAT), inhibiting the transport of catecholamines and serotonin into storage vesicles within the presynaptic nerve terminal. This leads to depletion of these neurotransmitters in the synaptic cleft. The depletion of norepinephrine reduces sympathetic tone.
• Receptor Binding, Enzyme Inhibition or Neurotransmitter Modulation: Reserpine’s primary mechanism is the inhibition of VMAT, which results in neurotransmitter depletion. It does not directly interact with adrenergic receptors or inhibit enzymes involved in catecholamine synthesis.
• Elimination Pathways: Primarily hepatic metabolism and biliary excretion. Some renal excretion occurs.

Dosage

Standard Dosage

Adults:

• Hypertension: Initial dose: 0.05-0.1 mg orally once daily, titrated cautiously based on response. Maintenance dose: 0.1-0.25 mg orally once daily. Historically, higher initial doses (0.5 mg daily) were used, but these are associated with an increased risk of adverse effects. It’s important to start low and go slow, especially in elderly patients.

Children:

• Reserpine is generally not recommended for use in children due to the lack of robust safety and efficacy data in pediatric populations. If used, the dose should be carefully titrated based on weight and clinical response, starting at a very low dose.

Special Cases:

• Elderly Patients: Start with a low initial dose (0.05 mg daily) and titrate very cautiously due to increased sensitivity to adverse effects, particularly CNS effects.
• Patients with Renal Impairment: Caution is advised. Close monitoring is necessary, as reserpine may accumulate in patients with significant renal dysfunction.
• Patients with Hepatic Dysfunction: Caution is advised, and dosage adjustments may be necessary due to altered metabolism.
• Patients with Comorbid Conditions: Caution is warranted in patients with a history of peptic ulcer disease, ulcerative colitis, depression, asthma, or cardiac conduction abnormalities.

Clinical Use Cases

Reserpine is not typically recommended for acute or emergency situations like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations due to its slow onset of action and potential for side effects. Other agents are preferred in these settings.

Dosage Adjustments

Dose adjustments should be made cautiously based on the patient’s clinical response and tolerability. Patients with renal or hepatic impairment may require lower doses. Concurrent use with other antihypertensive medications may necessitate dose reductions.

Side Effects

Common Side Effects:

• Nasal congestion, stuffy nose
• Drowsiness, dizziness, fatigue
• Depression, nightmares
• Gastrointestinal upset (nausea, vomiting, diarrhea)
• Bradycardia (slow heart rate)
• Weight gain

Rare but Serious Side Effects:

• Severe depression with suicidal ideation
• Parkinsonism (tremor, rigidity, bradykinesia)
• Galactorrhea (breast milk production)
• Gynecomastia (breast enlargement in males)

Long-Term Effects:

• Long-term use of reserpine may increase the risk of depression.
• Some studies have suggested a potential association between long-term reserpine use and breast cancer, but the evidence is inconclusive.

Adverse Drug Reactions (ADR):

• Severe hypotension
• Bradycardia with syncope
• Worsening of asthma
• Extrapyramidal symptoms (e.g., tardive dyskinesia)

Contraindications

• Hypersensitivity to reserpine
• History of depression, especially with suicidal tendencies
• Active peptic ulcer disease or ulcerative colitis
• Parkinson’s disease
• Pheochromocytoma
• Concurrent use of MAO inhibitors

Drug Interactions

• MAO inhibitors: Avoid concurrent use.
• Tricyclic antidepressants: May decrease the antihypertensive effect of reserpine.
• Sympathomimetics: May have altered effects with reserpine.
• Digitalis glycosides and antiarrhythmic agents: Use with caution.
• Other antihypertensive medications: Additive effects may occur.
• Alcohol: May potentiate the sedative effects of reserpine.

Pregnancy and Breastfeeding

• Pregnancy Safety Category: C (According to some sources, it is equivalent to category D).
• Fetal Risks: Reserpine can cross the placenta and has been shown to cause adverse effects in animal studies. Limited human data suggest a potential increased risk of nasal congestion, lethargy, and anorexia in newborns exposed near term. Avoiding use during pregnancy, especially the first trimester, is generally recommended.
• Breastfeeding: Reserpine is excreted in breast milk. While no definitive adverse effects have been reported in nursing infants, it is generally advisable to avoid reserpine during breastfeeding or to choose an alternative antihypertensive agent.

Drug Profile Summary

• Mechanism of Action: Depletes catecholamines from presynaptic nerve terminals, leading to decreased sympathetic activity.
• Side Effects: Nasal congestion, drowsiness, depression, gastrointestinal upset, bradycardia.
• Contraindications: Depression, peptic ulcer disease, ulcerative colitis, Parkinson’s disease, pheochromocytoma.
• Drug Interactions: MAO inhibitors, tricyclic antidepressants, sympathomimetics, digitalis.
• Pregnancy & Breastfeeding: Generally avoid due to potential fetal risks and excretion in breast milk.
• Dosage: Hypertension (adults): 0.05-0.25 mg orally once daily.
• Monitoring Parameters: Blood pressure, heart rate, mood changes, and signs of depression.

Popular Combinations

Historically, reserpine was often used in combination with thiazide diuretics (e.g., hydrochlorothiazide) or hydralazine to enhance antihypertensive effects. However, due to the availability of safer and more effective alternatives, these combinations are less frequently used now.

Precautions

• General Precautions: Monitor blood pressure, heart rate, and mental status regularly.
• Specific Populations: Use with extreme caution in elderly patients and those with renal or hepatic impairment. Avoid in pregnancy and breastfeeding.
• Lifestyle Considerations: Limit alcohol intake. Advise patients about potential sedative effects and caution against driving or operating machinery.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Reserpine in hypertension?

A: The initial dose is typically 0.05-0.1 mg orally once daily, titrated cautiously to a maintenance dose of 0.1-0.25 mg/day.

Q2: What are the common side effects of Reserpine?

A: Nasal congestion, drowsiness, dizziness, depression, gastrointestinal upset, and bradycardia are common side effects.

Q3: Is Reserpine safe in pregnancy?

A: No. Reserpine is generally contraindicated during pregnancy due to potential fetal risks.

Q4: Can Reserpine be used in patients with a history of depression?

A: No. Reserpine is contraindicated in patients with a history of depression due to the risk of exacerbating or precipitating depression.

Q5: How does Reserpine work to lower blood pressure?

A: It depletes catecholamines from sympathetic nerve endings, reducing peripheral vascular resistance and cardiac output.

Q6: What are the significant drug interactions with Reserpine?

A: MAO inhibitors, tricyclic antidepressants, sympathomimetics, and digitalis have significant interactions with Reserpine.

Q7: Are there any specific monitoring parameters for patients taking Reserpine?

A: Monitor blood pressure, heart rate, and mental status regularly. Be vigilant for signs of depression.

Q8: Is Reserpine still commonly used for hypertension?

A: No. While effective, Reserpine is now less commonly used for hypertension due to the availability of newer, safer, and better-tolerated antihypertensive agents.

Q9: Can Reserpine be used in patients with peptic ulcers?

A: No. Reserpine is contraindicated in patients with active peptic ulcer disease because it can increase gastric acid secretion and worsen ulcer symptoms.