Hydralazine Hydrochloride

Vasodilator Direct-acting arteriolar vasodilator (Phthalazine derivative)

Dosage & Administration Guidelines

Species Route Dose Frequency Duration & Clinical Notes
Dog PO 0.5-3 mg/kg q12h (every 12 hours) Duration: Variable; adjust based on blood pressure response and clinical status.
Notes: Start at low end and titrate upward. Monitor blood pressure and heart rate. For heart failure, use in combination with other therapies.
Cat PO 2.5-5 mg/cat (approximately 0.2-0.5 mg/kg) q12h Duration: Variable; adjust based on response.
Notes: Cats may be sensitive; start with low dose. Monitor for hypotension and tachycardia.
Horse PO 0.5-1.5 mg/kg q12h Duration: Variable; limited clinical data.
Notes: Use with caution; monitor cardiovascular parameters.
Rabbit PO 1-2 mg/kg q12h Duration: Variable; off-label use.
Notes: Limited data; use cautiously.

Clinical Indications & Species Uses

General Indications
  • Management of systemic hypertension
  • Adjunctive therapy for congestive heart failure (afterload reduction)
  • Pulmonary hypertension (off-label)
Dog (Canine)
  • Systemic hypertension (essential, renal, or secondary to hyperadrenocorticism)
  • Pulmonary hypertension (adjunctive therapy)
  • Heart failure (as an afterload reducer, especially in mitral regurgitation or dilated cardiomyopathy)
  • Hypertensive crisis (with careful monitoring)
Cat (Feline)
  • Systemic hypertension (especially associated with chronic kidney disease or hyperthyroidism)
  • Pulmonary hypertension (adjunctive therapy)
  • Heart failure (as an afterload reducer)
Horse (Equine)
  • Hypertension (rarely used; more common in research or specific clinical scenarios)
  • Pulmonary hypertension (experimental use)
Rabbit & Small Mammals
  • Hypertension (experimental or off-label use)
Exotic & Other Species
  • Hypertension in some exotic species (off-label use, limited data)

Pharmacology & Mechanism of Action

Drug Class: Vasodilator | Pharmacological Group: Direct-acting arteriolar vasodilator (Phthalazine derivative)

Mechanism of Action: Hydralazine directly relaxes arteriolar smooth muscle, leading to vasodilation and decreased peripheral vascular resistance. The exact mechanism is not fully understood, but it is thought to involve interference with calcium influx into smooth muscle cells, inhibition of inositol trisphosphate-induced calcium release, and possibly stimulation of nitric oxide release. This results in a reduction in afterload, increased cardiac output, and reflex sympathetic activation leading to tachycardia and increased renin release.

Pharmacodynamics: Hydralazine produces a rapid and sustained reduction in arterial blood pressure by dilating resistance arterioles. It has minimal effect on venous capacitance vessels. The decrease in afterload improves cardiac output in patients with heart failure. Reflex sympathetic stimulation can cause tachycardia, increased myocardial contractility, and increased renin-angiotensin-aldosterone system activity, which may lead to fluid retention and attenuation of the antihypertensive effect over time.

⚡ Pharmacokinetics Summary

Absorption: Hydralazine is well absorbed after oral administration, but its bioavailability is variable due to extensive first-pass metabolism in the liver and intestinal wall. In dogs, oral bioavailability is approximately 40-60%. Food may increase absorption.
Distribution: Hydralazine is widely distributed throughout the body, with high concentrations in the lungs, liver, and kidneys. It crosses the placenta and is excreted in milk. It is not highly protein-bound (approximately 87% in humans, but may vary in animals).
Metabolism: Hydralazine is extensively metabolized in the liver, primarily by acetylation (N-acetyltransferase) and hydroxylation. The rate of acetylation is genetically determined and can vary among species and individuals. In dogs, acetylation is the major pathway; in cats, it is also important. Metabolites are pharmacologically inactive.
Excretion: Metabolites and a small amount of unchanged drug are excreted primarily in the urine. The elimination half-life is short, but the pharmacodynamic effect may last longer than the plasma half-life due to persistent binding to vascular tissue.
Half-Life: Dog: approximately 1-2 hours; Cat: approximately 1-3 hours; Horse: approximately 1-2 hours (limited data).
Bioavailability: Oral: 40-60% in dogs; variable in other species due to first-pass metabolism.
Protein Binding: Approximately 87% in humans; may be similar in animals, but species-specific data are limited.

Available Formulations & Strengths

Oral Tablet 10 mg, 25 mg, 50 mg, 100 mg (PO)
Injectable Solution 20 mg/mL (1 mL ampule) (IV (for emergency use; not commonly used in veterinary practice))

Contraindications & Clinical Warnings

Contraindications:
  • Hypersensitivity to hydralazine or any component of the formulation
  • Severe hypotension or shock
  • Coronary artery disease or myocardial ischemia (due to reflex tachycardia)
  • Mitral valve stenosis (may worsen hemodynamics)
  • Dissecting aortic aneurysm (in humans; theoretical risk in animals)
Warnings & Clinical Precautions:
  • Use with caution in animals with renal or hepatic impairment.
  • May cause reflex tachycardia and increased myocardial oxygen demand; use cautiously in animals with pre-existing cardiac disease.
  • Can cause fluid retention; consider concurrent diuretic therapy in heart failure patients.
  • Monitor blood pressure regularly, especially during dose titration.
  • Abrupt discontinuation may cause rebound hypertension; taper dose if possible.
  • Use in pregnant or lactating animals only if clearly needed; safety not established.
  • In horses, use with caution due to limited data and potential for hypotension.

Adverse Effects & Reactions

Common:

  • Tachycardia
  • Hypotension
  • Anorexia
  • Vomiting
  • Diarrhea
  • Lethargy

Serious / Severe:

  • Severe hypotension
  • Cardiac arrhythmias (e.g., ventricular tachycardia)
  • Myocardial ischemia or infarction (rare)
  • Hepatotoxicity (rare, but reported in humans)
  • Lupus-like syndrome (rare, reported in humans; not well-documented in animals)

Rare:

  • Peripheral neuropathy
  • Blood dyscrasias (e.g., neutropenia, thrombocytopenia)
  • Drug-induced lupus erythematosus-like syndrome
  • Hypersensitivity reactions (rash, fever)

Key Drug Interactions

Interacting Drug / Class Clinical Effect & Mechanism Severity
Other antihypertensives (e.g., ACE inhibitors, beta-blockers, diuretics) Additive hypotensive effects; may require dose adjustment. Moderate
Beta-blockers May reduce reflex tachycardia but can also increase risk of excessive hypotension if combined. Moderate
Nitrates Additive vasodilation and hypotension. Moderate
Sympathomimetics (e.g., epinephrine, norepinephrine) May antagonize the hypotensive effect of hydralazine. Mild
NSAIDs May reduce the antihypertensive effect due to sodium and fluid retention. Mild

Overdose & Toxicity Management

Signs of Toxicity:

  • Severe hypotension
  • Tachycardia
  • Arrhythmias
  • Shock
  • Lethargy
  • Collapse

Emergency Treatment Protocol: Treatment is symptomatic and supportive. Induce emesis if recent oral ingestion and animal is conscious. Administer activated charcoal to reduce absorption. Provide intravenous fluids to support blood pressure. Use vasopressors (e.g., norepinephrine, phenylephrine) if severe hypotension persists. Monitor cardiac function and treat arrhythmias as needed. There is no specific antidote.

Food Animal Withdrawal Times

Not approved for food animals; no withdrawal times established. Do not use in food-producing animals.

Storage, Handling & Regulatory Information

Storage Temperature: Store at room temperature (20-25°C, 68-77°F). Protect from light and moisture.

Light Sensitivity: Light-sensitive — protect from direct exposure.

Handling & Special Conditions: Keep container tightly closed. Do not freeze injectable solution.

Dispensing Status: Prescription Required (Rx Only)

Approval Status: Not FDA-approved for veterinary use; used off-label in animals. Human-approved formulations are available.

Extra-Label (Off-Label) Use: In the US, extra-label use of hydralazine in animals is permitted under AMDUCA (Animal Medicinal Drug Use Clarification Act) provided there is a valid veterinarian-client-patient relationship, and no approved animal drug is available. However, it is not approved for use in food animals, and extra-label use in food animals is prohibited if it results in violative residues.

Clinical Pearls & Practice Notes

💡 Clinical Insights: Hydralazine is a direct-acting arteriolar vasodilator used primarily in dogs and cats for the management of systemic hypertension and as an adjunctive afterload reducer in heart failure. It is particularly useful in cases of hypertension secondary to renal disease or hyperadrenocorticism. Because it causes reflex tachycardia and fluid retention, it is often combined with a beta-blocker and a diuretic (e.g., in the classic 'triple therapy' for heart failure). Blood pressure and heart rate should be monitored closely during dose titration. The drug has a short half-life but a longer duration of action; twice-daily dosing is typical. In cats, dosing is often based on body weight or a fixed dose, but individual response varies. Use with caution in animals with pre-existing cardiac disease, and avoid in hypotensive or shock states. Due to lack of safety data, it should not be used in pregnant or lactating animals unless the benefits outweigh risks. For food animals, it is not recommended due to lack of withdrawal information.

References & Literature

  • 📚 Plumb's Veterinary Drug Handbook
  • 📚 Papich Veterinary Pharmacology and Therapeutics
  • 📚 Compendium of Veterinary Products (CVP)