RESERPINE, HYDRALAZINE HYDROCHLORIDE AND HYDROCHLOROTHIAZIDE
Clinical safety rating: safe
MAOIs can cause excitability and hypertension Can cause depression and suicidal ideation.
Reserpine depletes catecholamines from adrenergic nerve endings by irreversibly inhibiting vesicular monoamine transporter 2 (VMAT2), reducing sympathetic outflow. Hydralazine directly relaxes arteriolar smooth muscle via unclear mechanism, possibly involving nitric oxide. Hydrochlorothiazide increases renal excretion of sodium and water by inhibiting Na+/Cl- symporter in distal convoluted tubule.
| Metabolism | Reserpine: hepatic metabolism (CYP3A4); Hydralazine: hepatic acetylation (N-acetyltransferase); Hydrochlorothiazide: not metabolized, excreted renally. |
| Excretion | Reserpine: renal (30% unchanged, remainder as metabolites); hydralazine: renal (80-90% as metabolites, <10% unchanged); hydrochlorothiazide: renal (95% unchanged via organic anion transporters). |
| Half-life | Reserpine: 33-50 hours (prolonged in renal impairment); hydralazine: 2-4 hours (rapid acetylators) to 4-8 hours (slow acetylators); hydrochlorothiazide: 6-15 hours (increased in renal impairment). |
| Protein binding | Reserpine: 96% (mainly to alpha1-acid glycoprotein and albumin); hydralazine: 87% (albumin); hydrochlorothiazide: 40-68% (albumin). |
| Volume of Distribution | Reserpine: 10-20 L/kg (extensive tissue binding); hydralazine: 1-2 L/kg; hydrochlorothiazide: 3.6-8.5 L/kg. |
| Bioavailability | Reserpine oral: 50%; hydralazine oral: 26-55% (influenced by acetylator status); hydrochlorothiazide oral: 65-75% (reduced with food). |
| Onset of Action | Reserpine oral: 3-6 days; hydralazine oral: 20-30 minutes; hydrochlorothiazide oral: 2 hours. |
| Duration of Action | Reserpine: 1-6 weeks (prolonged due to storage in adrenergic neurons); hydralazine: 6-12 hours; hydrochlorothiazide: 6-12 hours. |
Oral: 1 tablet (0.1 mg reserpine, 25 mg hydralazine, 15 mg hydrochlorothiazide) 1 to 4 times daily. Maximum: 2 tablets per dose (200 mg hydralazine equivalent) and 200 mg hydralazine/day.
| Dosage form | TABLET |
| Renal impairment | CrCl 30-50 mL/min: Reduce dose to 1 tablet daily or every other day. CrCl 15-29 mL/min: Use every other day or discontinue if not responding. CrCl <15 mL/min: Avoid use due to thiazide ineffectiveness and risk of azotemia. |
| Liver impairment | Child-Pugh Class A: No adjustment. Class B: Reduce dose by 50% (e.g., 1 tablet every other day). Class C: Avoid use due to accumulation of reserpine and hydralazine. |
| Pediatric use | Not recommended for children under 12 years. For adolescents >12 years: Same as adult dose adjusted for weight (0.1 mg reserpine, 25 mg hydralazine, 15 mg hydrochlorothiazide per tablet) starting at 0.5 to 1 tablet daily, titrate up to 2 tablets twice daily. |
| Geriatric use | Start at 0.5 tablet (0.05 mg reserpine, 12.5 mg hydralazine, 7.5 mg hydrochlorothiazide) once daily. Titrate slowly to 0.5 tablet twice daily. Maximum: 1 tablet twice daily. Monitor for orthostatic hypotension, electrolyte imbalance, and renal function. |
| 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 | Reserpine is excreted in breast milk (M/P ratio not established); may cause extrapyramidal disorders in infant. Hydralazine is minimally excreted; safe with monitoring. HCTZ is excreted in small amounts; may suppress lactation. Due to reserpine, breastfeeding is contraindicated. |
| Teratogenic Risk | First trimester: Reserpine crosses placenta; animal studies show increased fetal abnormalities; human data limited. Hydralazine: no major teratogenic risk. HCTZ: risk of fetal/neonatal jaundice; use only if clearly needed. Second and third trimesters: HCTZ may cause electrolyte imbalance, thrombocytopenia; hydralazine and reserpine may cause neonatal hypotension, bradycardia, and respiratory depression. Avoid use for pregnancy-induced hypertension due to risk of decreased placental perfusion. |
■ FDA Black Box Warning
None
| Common Effects | Depression |
| Serious Effects |
["History of depression","Active peptic ulcer","Ulcerative colitis","Pheochromocytoma","Hypersensitivity to any component","Anuria"]
| Precautions | ["Depression, suicidal ideation (reserpine)","Lupus-like syndrome (hydralazine, especially in slow acetylators)","Electrolyte disturbances, hypotension (hydrochlorothiazide)","May cause acute angle-closure glaucoma","Avoid abrupt withdrawal (reserpine may cause severe hypertension)"] |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and electrolyte levels (especially potassium with HCTZ). Assess fetal growth and amniotic fluid volume via ultrasound. Neonatal monitoring for bradycardia, hypotension, extrapyramidal symptoms (reserpine), and thrombocytopenia (HCTZ). |
| Fertility Effects | Reserpine may decrease libido and cause gynecomastia in males; hydralazine and HCTZ have minimal reported effects on fertility. No significant impact on female fertility documented. |