HYLAZIN

Indications

• Hypertension
• Severe hypertension
• Hypertensive emergencies

Dosage

Children: Refer to the BNF for Children for appropriate dosing in paediatric patients.

Adults: The usual starting dose is 10 mg orally four times a day, increased as necessary to a maximum of 300 mg per day.

Mechanism of action

Hydralazine may interfere with calcium transport in vascular smooth muscle by an unknown mechanism to relax arteriolar smooth muscle and lower blood pressure. The interference with calcium transport may be by preventing influx of calcium into cells, preventing calcium release from intracellular compartments, directly acting on actin and myosin, or a combination of these actions. Additionally, hydralazine competes with protocollagen prolyl hydroxylase for free iron, inhibiting the hydroxylation of HIF-1α, thus preventing its degradation. This results in the induction of HIF-1α and VEGF, promoting endothelial cell proliferation and angiogenesis.

Pharmacodynamics

Hydralazine primarily relaxes arteriolar smooth muscle, resulting in a decrease in vascular resistance and lowering blood pressure. The drug has a short duration of action of 2-6 hours and a wide therapeutic window, with patients tolerating doses up to 300 mg. Caution is advised regarding the potential development of systemic lupus erythematosus syndrome in certain patients.

Pharmacokinetics

Hydralazine is absorbed rapidly from the gastrointestinal tract, but its bioavailability can vary significantly due to first-pass metabolism. The drug undergoes extensive hepatic metabolism and is excreted primarily in the urine. Its half-life is approximately 3-7 hours, and it is important to monitor blood pressure and adjust dosages accordingly.

Contra-indications

• Hypersensitivity to hydralazine or any excipients
• History of systemic lupus erythematosus
• Mitral valve rheumatic heart disease
• Severe hypotension

Adverse effects

• Headache
• Tachycardia
• Palpitations
• Nausea
• Vomiting
• Diarrhea
• Anorexia
• Dizziness
• Flushing
• Rash
• Arthralgia
• Lupus-like syndrome

Interactions

• Concurrent use with other antihypertensives may enhance hypotensive effects
• Non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the antihypertensive effect
• Hydralazine may increase the effects of certain cardiac glycosides

Precautions

• Use with caution in patients with renal impairment
• Monitor blood pressure regularly during treatment
• Use with caution in patients with coronary artery disease
• Caution in patients with a history of myocardial infarction

Pregnancy

Hydralazine is classified as category C. It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Hydralazine is excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

Store in a cool, dry place away from light. Keep out of reach of children.

Formulations

• Tablets: 25 mg, 50 mg, 100 mg
• Injection: 20 mg/2 mL

Indications

• Hypertension
• Severe hypertension (adjunct therapy)
• Resistant hypertension

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidelines.

Adults: Initially, 10 mg orally 4 times daily, increased as necessary, up to a maximum of 300 mg daily in divided doses.

Mechanism of action

Hydralazine hydrochloride acts primarily as a direct arterial vasodilator. It induces vasodilation by interfering with calcium ion movement in vascular smooth muscle, ultimately leading to relaxation of the blood vessels. This effect is mediated through the release of nitric oxide, which stimulates guanylate cyclase, resulting in increased levels of cyclic GMP and relaxation of smooth muscle.

Pharmacodynamics

The pharmacodynamics of hydralazine involve a decrease in peripheral vascular resistance, which effectively lowers blood pressure. The onset of action occurs within 15 to 30 minutes when administered orally, with peak effects typically observed around 1 to 2 hours post-administration. The drug is known to elicit reflex tachycardia and increased cardiac output due to the drop in systemic vascular resistance.

Pharmacokinetics

Hydralazine is well-absorbed from the gastrointestinal tract, with an oral bioavailability of approximately 25% to 50%. It is metabolized in the liver primarily through acetylation and has a half-life of about 3 to 7 hours. The drug is predominantly excreted in urine as metabolites. Renal impairment may necessitate dosage adjustments due to the risk of accumulation.

Contra-indications

• Hypersensitivity to hydralazine or any of its components
• History of systemic lupus erythematosus
• Severe renal impairment
• Coronary artery disease

Adverse effects

• Fluid retention
• Joint disorders
• Tachycardia
• Hypotension
• Headache
• Nausea
• Palpitations
• Lupus-like syndrome
• Skin reactions
• Angina pectoris
• Oedema
• Pericardial disorders
• Myalgia
• Leukopenia
• Thrombocytopenia
• Eosinophilia
• Acute kidney injury
• Stevens-Johnson syndrome

Interactions

• Minoxidil
• Other antihypertensives may have additive effects leading to hypotension
• Nonsteroidal anti-inflammatory drugs (NSAIDs) may reduce the antihypertensive effect

Precautions

• Monitor blood pressure regularly during treatment
• Use with caution in patients with hepatic impairment
• Patients with a history of cardiovascular disease should be monitored closely
• Adjust dose in renal impairment or if creatinine clearance is less than 30 mL/min

Pregnancy

Avoid during pregnancy due to potential toxicity including reduced placental perfusion and neonatal thrombocytopenia.

Breast-feeding

Present in breast milk, but the effects on the infant are not known.

Storage

Store in a cool, dry place away from light.

Formulations

• Hydralazine hydrochloride 25 mg tablets
• Hydralazine hydrochloride 50 mg tablets
• Hydralazine hydrochloride 100 mg tablets

Mechanism of action

Hydralazine may interfere with calcium transport in vascular smooth muscle by an unknown mechanism to relax arteriolar smooth muscle and lower blood pressure. The interference with calcium transport may be by preventing influx of calcium into cells, preventing calcium release from intracellular compartments, directly acting on actin and myosin, or a combination of these actions. This decrease in vascular resistance leads to increased heart rate, stroke volume, and cardiac output. Hydralazine also competes with protocollagen prolyl hydroxylase (CPH) for free iron. This competition inhibits CPH mediated hydroxylation of HIF-1α, preventing the degradation of HIF-1α. Induction of HIF-1α and VEGF promote proliferation of endothelial cells and angiogenesis.

Pharmacodynamics

Hydralazine interferes with calcium transport to relax arteriolar smooth muscle and lower blood pressure. Hydralazine has a short duration of action of 2-6h. This drug has a wide therapeutic window, as patients can tolerate doses of up to 300mg. Patients should be cautioned regarding the risk of developing systemic lupus erythematosus syndrome.