HYDRALAZINE HYDROCHLORIDE-HYDROCHLOROTHIAZIDE-RESERPINE
Clinical safety rating: safe
MAOIs can cause excitability and hypertension Can cause depression and suicidal ideation.
Hydralazine directly relaxes arteriolar smooth muscle by unclear mechanism, possibly interfering with calcium movements; hydrochlorothiazide inhibits the Na+/Cl- cotransporter in distal convoluted tubules, reducing reabsorption of sodium and chloride; reserpine depletes catecholamines from adrenergic nerve endings by inhibiting vesicular monoamine transporter (VMAT), reducing sympathetic outflow.
| Metabolism | Hydralazine: N-acetylation (NAT2), hydrolysis; Hydrochlorothiazide: limited metabolism (<10%); Reserpine: extensive hepatic metabolism via CYP2D6 and other enzymes |
| Excretion | Hydralazine: 80% renal, 5% fecal; Hydrochlorothiazide: >95% renal; Reserpine: 60% renal, 40% fecal. |
| Half-life | Hydralazine: 3-7 h (slow acetylators) or 1-2 h (rapid acetylators); Hydrochlorothiazide: 6-15 h; Reserpine: 50-100 h (biphasic, terminal half-life). |
| Protein binding | Hydralazine: 87% bound to plasma proteins; Hydrochlorothiazide: 40-68% bound to albumin; Reserpine: 96% bound to plasma proteins. |
| Volume of Distribution | Hydralazine: 0.3-0.7 L/kg; Hydrochlorothiazide: 0.2-0.5 L/kg; Reserpine: 3-9 L/kg (large Vd due to tissue binding). |
| Bioavailability | Hydralazine: oral 30-50% (extensive first-pass metabolism); Hydrochlorothiazide: oral 70%; Reserpine: oral 50-60%. |
| Onset of Action | Hydralazine: oral 20-30 min, IV 5-20 min; Hydrochlorothiazide: oral 2 h; Reserpine: oral several days to weeks for full antihypertensive effect. |
| Duration of Action | Hydralazine: oral 2-6 h, IV 2-4 h; Hydrochlorothiazide: oral 6-12 h; Reserpine: oral 1-6 weeks (cumulative effect). |
1 tablet (25 mg hydralazine / 25 mg hydrochlorothiazide / 0.1 mg reserpine) orally once daily, increased to 2 tablets daily if needed.
| Dosage form | TABLET |
| Renal impairment | Contraindicated in severe renal impairment (CrCl <30 mL/min). For CrCl 30-50 mL/min: reduce dose by 50% or extend interval. For hydralazine: CrCl <30 mL/min: decrease dose to 25 mg/day. |
| Liver impairment | Contraindicated in Child-Pugh class B or C. Use with caution in mild hepatic impairment; reduce hydralazine dose by 50%. |
| Pediatric use | Not recommended for children under 12 years. For adolescents (≥12 years): initiate at 0.75 mg/kg/day hydralazine component orally in 2 divided doses, maximum 2.5 mg/kg/day or 200 mg/day. |
| Geriatric use | Initiate at lowest dose (1 tablet daily). Monitor for hypotension (especially orthostatic), electrolyte imbalance, and CNS depression. Avoid in patients with history of depression or parkinsonism. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
MAOIs can cause excitability and hypertension Can cause depression and suicidal ideation.
| FDA category | Animal |
| Breastfeeding | Hydralazine is excreted into breast milk in small amounts (M/P ratio ~1.0); hydrochlorothiazide concentrates in milk (M/P ratio ~1.5-2.0) and may reduce milk supply; reserpine is excreted and may cause adverse effects in infants (e.g., galactorrhea, drowsiness). Caution: Avoid combination if breastfeeding; use lowest doses and monitor infant for hypotension, electrolyte disturbances. |
| Teratogenic Risk |
■ FDA Black Box Warning
None
| Common Effects | Depression |
| Serious Effects |
Hydralazine: Hypersensitivity, mitral valve rheumatic heart disease; Hydrochlorothiazide: Anuria, hypersensitivity to sulfonamide-derived drugs; Reserpine: Hypersensitivity, active peptic ulcer, ulcerative colitis, mental depression, electroconvulsive therapy, pheochromocytoma
| Precautions | Hydralazine: Drug-induced lupus (especially slow acetylators), hypotension, myocardial infarction precipitation; Hydrochlorothiazide: Electrolyte disturbances, hyperuricemia, photosensitivity; Reserpine: Mental depression (active or history), peptic ulcer, paradoxical anxiety, extrapyramidal symptoms |
Loading safety data…
| First trimester: Hydralazine and hydrochlorothiazide are not associated with major malformations; reserpine has limited data but may cross placenta. Second/third trimester: Hydralazine may cause maternal hypotension and fetal distress; hydrochlorothiazide may cause fetal electrolyte disturbances, thrombocytopenia; reserpine may cause neonatal bradycardia, respiratory depression, hypothermia, and lethargy. Overall risk: FDA category C for hydralazine, D for hydrochlorothiazide (based on maternal benefit), and C for reserpine. |
| Fetal Monitoring | Monitor maternal blood pressure (avoid hypotension), serum electrolytes (especially potassium due to hydrochlorothiazide), and renal function. Fetal monitoring includes growth scans, amniotic fluid volume (hydrochlorothiazide risk of oligohydramnios), and neonatal monitoring for electrolyte imbalance, bradycardia, and respiratory depression. |
| Fertility Effects | Hydralazine may rarely cause reversible lupus-like syndrome affecting fertility; hydrochlorothiazide and reserpine have no established effects on fertility. However, reserpine can cause gynecomastia and menstrual irregularities. |