RESERPINE AND HYDROFLUMETHIAZIDE
Clinical safety rating: safe
MAOIs can cause excitability and hypertension Can cause depression and suicidal ideation.
Reserpine irreversibly inhibits the vesicular monoamine transporter (VMAT2), depleting presynaptic stores of norepinephrine, dopamine, and serotonin in central and peripheral neurons, leading to reduced sympathetic outflow and decreased peripheral vascular resistance. Hydroflumethiazide is a thiazide diuretic that inhibits the sodium-chloride symporter (NCC) in the distal convoluted tubule, increasing excretion of sodium, chloride, and water, and reducing plasma volume and peripheral resistance.
| Metabolism | Reserpine is extensively metabolized in the liver by CYP2D6 and other enzymes; Hydroflumethiazide is not significantly metabolized, excreted unchanged in urine. |
| Excretion | Reserpine: renal (30% unchanged, 50% as metabolites), fecal (10%). Hydroflumethiazide: renal (>90% unchanged via organic anion transporter in proximal tubule), minimal biliary. |
| Half-life | Reserpine: 50-100 hours (terminal) due to prolonged neuronal binding, allowing once-daily dosing. Hydroflumethiazide: 6-15 hours (terminal), extended in renal impairment. |
| Protein binding | Reserpine: ~90-95% to albumin and α1-acid glycoprotein. Hydroflumethiazide: ~60-70% to albumin. |
| Volume of Distribution | Reserpine: 0.5-2 L/kg, extensive tissue binding (adrenergic neurons). Hydroflumethiazide: 1.2-3 L/kg, distributes to erythrocytes and tissues. |
| Bioavailability | Reserpine PO: 30-50% due to first-pass metabolism; consistent but variable. Hydroflumethiazide PO: ~65-75%. |
| Onset of Action | Reserpine PO: 3-6 days for full antihypertensive effect; initial effect within 1 week. Hydroflumethiazide PO: 2-3 hours for diuresis; 3-4 days for full antihypertensive effect. |
| Duration of Action | Reserpine: 1-6 weeks after discontinuation due to irreversible amine depletion. Hydroflumethiazide: 6-12 hours for diuresis; antihypertensive effect persists 12-24 hours. |
1 tablet (0.1 mg reserpine / 25 mg hydroflumethiazide) orally once daily. Dosage may be adjusted based on response; maximum reserpine 0.25 mg/day.
| Dosage form | TABLET |
| Renal impairment | GFR 30-60 mL/min: reduce dose by 50% of normal dose; GFR <30 mL/min: contraindicated (hydroflumethiazide ineffective, risk of azotemia). |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: reduce dose by 50%; Child-Pugh C: contraindicated due to risk of hepatic encephalopathy. |
| Pediatric use | Reserpine: 0.02 mg/kg/day orally in 1-2 divided doses (max 0.25 mg/day). Hydroflumethiazide: 1 mg/kg/day orally in 2 divided doses (max 2 mg/kg/day per dose). |
| Geriatric use | Start at half the standard dose (0.05 mg reserpine / 12.5 mg hydroflumethiazide) orally once daily; increase slowly based on BP response; monitor for orthostatic hypotension, electrolyte imbalances, and CNS depression. |
| 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; may cause infant respiratory depression, bradycardia, and nasal congestion. Hydroflumethiazide is excreted in breast milk; may suppress lactation and cause neonatal electrolyte disturbances. M/P ratio not available. Contraindicated during breastfeeding due to potential for serious adverse reactions in nursing infants. |
| Teratogenic Risk |
■ FDA Black Box Warning
None
| Common Effects | Depression |
| Serious Effects |
History of depression (especially with suicidal tendencies) or other major psychiatric illness; active peptic ulcer or ulcerative colitis; pheochromocytoma; concomitant electroconvulsive therapy (ECT); hypersensitivity to reserpine, hydroflumethiazide, or sulfonamide-derived drugs; anuria; severe renal impairment.
| Precautions | Risk of depression, suicide, or exacerbation of psychiatric disorders; bradycardia and orthostatic hypotension; electrolyte imbalances (hypokalemia, hyponatremia, hypomagnesemia, hypocalcemia) and volume depletion; increased serum uric acid and precipitation of gout; increased blood glucose and impaired glucose tolerance; systemic lupus erythematosus exacerbation; abrupt withdrawal may precipitate hypertensive crisis. |
Loading safety data…
| First trimester: Reserpine crosses placenta; association with congenital malformations not definitively established but risk cannot be excluded. Hydroflumethiazide: No adequate studies; thiazides may cause fetal or neonatal jaundice, thrombocytopenia, and electrolyte disturbances. Second and third trimesters: Reserpine may cause neonatal respiratory depression, bradycardia, hypothermia, and nasal congestion. Hydroflumethiazide may cause fetal or neonatal jaundice, thrombocytopenia, and electrolyte imbalances. Use only if benefit outweighs risk. |
| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and electrolytes (sodium, potassium). Monitor fetal growth and well-being via ultrasound and non-stress testing. Assess for signs of neonatal depression, bradycardia, hypothermia, and jaundice postpartum. Monitor infant for electrolyte imbalances and thrombocytopenia if exposed in utero. |
| Fertility Effects | Reserpine may cause decreased libido, impotence, and menstrual irregularities in women; may suppress reproductive function. Hydroflumethiazide has no direct effect on fertility but electrolyte disturbances may indirectly affect reproductive function. No evidence of permanent impairment. |