METHYLDOPA

(meth-ill-doe'pa)

Apo-Methyldopa

, Novomedopa

METHYLDOPATE HYDROCHLORIDE
(meth-ill-doe'pate)
Classifications: central-acting antihypertensive; alpha-adrenergic agonist;
Therapeutic:antihypertensive, central-acting
Pregnancy Category: B

Availability

125 mg, 250 mg, 500 mg tablets; 50 mg/mL injection

Action

Structurally related to catecholamines and their precursors. Has weak neurotransmitter properties; inhibits decarboxylation of dopa, thereby reducing concentration of dopamine, a precursor of norepinephrine. It also inhibits the precursor of serotonin. Reduces renal vascular resistance; maintains cardiac output without acceleration, but may slow heart rate; tends to support sodium and water retention.

Therapeutic Effect

Lowers standing and supine BP, and unlike adrenergic blockers, is not so prone to produce orthostatic hypotension, diurnal BP variations, or exercise hypertension.

Uses

Treatment of sustained moderate to severe hypertension, particularly in patients with kidney dysfunction. Also used in selected patients with carcinoid disease. Parenteral form has been used for treatment of hypertensive crises but is not preferred because of its slow onset of action.

Contraindications

Active liver disease (hepatitis, cirrhosis); pheochromocytoma; blood dyscrasias. Safety during pregnancy (category B) is not established.

Cautious Use

History of impaired liver or kidney function or disease; renal failure; autoimmune disease; cardiac disease; angina pectoris; history of mental depression; Parkinson's disease; young or older adult patients.

Route & Dosage

Hypertension
Adult: PO 250 mg b.i.d. or t.i.d., may be increased up to 3 g/d in divided doses, usual range 250–1000 mg total per day IV 250–500 mg q6h, may be increased up to 1 g q6h
Geriatric: PO 125 mg b.i.d. or t.i.d., may increase gradually (max: 3 g/d)
Child: PO 10 mg/kg/d in 2–4 divided doses (max: 3 g/d) IV 2–4 mg/kg/d in divided doses (max: 3 g/d)

Renal Impairment
Cl_cr >50 mL/min: dose q8h; 10–50 mL/min: dose q8–12h; <10 mL/min: dose q12–24h

Administration

Oral

Make dosage increases in evening to minimize daytime sedation. Some patients maintain adequate BP control with a single evening dose.

Intravenous

PREPARE: Intermittent: Dilute in 100–200 mL of D5W, as needed, to yield 10 mg/mL.

ADMINISTER: Intermittent: Give over 30–60 min.

INCOMPATIBILITIES Solution/additive: Amphotericin B, hydrocortisone, methohexital, tetracycline. Y-site: Fat emulsion.

Adverse Effects (≥1%)

Body as a Whole: Hypersensitivity (fever, skin eruptions, ulcerations of soles of feet, flu-like symptoms, lymphadenopathy, eosinophilia). CNS: Sedation, drowsiness, sluggishness, headache, weakness, fatigue, dizziness, vertigo, decrease in mental acuity, inability to concentrate, amnesia-like syndrome, parkinsonism, mild psychoses, depression, nightmares. CV: Orthostatic hypotension, syncope, bradycardia, myocarditis, edema, weight gain (sodium and water retention), paradoxic hypertensive reaction (especially with IV administration). GI: Diarrhea, constipation, abdominal distention, malabsorption syndrome, nausea, vomiting, dry mouth, sore or black tongue, sialadenitis, abnormal liver function tests, jaundice, hepatitis, hepatic necrosis (rare). Hematologic: Positive direct Coombs' test (common especially in African-Americans), granulocytopenia. Special Senses: Nasal stuffiness. Endocrine: Gynecomastia, lactation, decreased libido, impotence, hypothermia (large doses), positive tests for lupus and rheumatoid factors. Skin: Granulomatous skin lesions.

Diagnostic Test Interference

Methyldopa may interfere with serum creatinine measurements using alkaline picrate method, AST by colorimetric methods, and uric acid measurements by phosphotungstate method (with high methyldopa blood levels); it may produce false elevations of urinary catecholamines and increase in serum amylase in methyldopa-induced sialadenitis.

Interactions

Drug: amphetamines, tricyclic antidepressants, phenothiazines, barbituates may attenuate antihypertensive response; methyldopa may inhibit effectiveness of ephedrine; haloperidol may exacerbate psychiatric symptoms; with levodopa additive hypotension, increased CNS toxicity, especially psychosis; increases risk of lithium toxicity; methotrimeprazine causes excessive hypotension; mao inhibitors may cause hallucinations; phenoxybenzamine may cause urinary incontinence. Herbal: Licorice may affect electrolyte levels; ephedra, yohimbe, ginseng may decrease efficacy.

Pharmacokinetics

Absorption: About 50% absorbed from GI tract. Peak: 4–6 h. Duration: 24 h PO; 10–16 h IV. Distribution: Crosses placenta, distributed into breast milk. Metabolism: In liver and GI tract. Elimination: Primarily in urine. Half-Life: 1.7 h.

Nursing Implications

Assessment & Drug Effects

Check BP and pulse at least q30min until stabilized during IV infusion and observe for adequacy of urinary output.
Take BP at regular intervals in lying, sitting, and standing positions during period of dosage adjustment.
Supervision of ambulation in older adults and patients with impaired kidney function; both are particularly likely to manifest orthostatic hypotension with dizziness and light-headedness during period of dosage adjustment.
Monitor fluid and electrolyte balance and I&O. Report oliguria and changes in I&O ratio. Weigh patient daily, and check for edema because methyldopa favors sodium and water retention.
Lab tests: Schedule baseline and periodic blood counts and liver function tests especially during first 6–12 wk of therapy or if patient develops unexplained fever; periodic serum electrolytes.
Be alert to and report symptoms of mental depression (e.g., anorexia, insomnia, inattention to personal hygiene, withdrawal). Drug-induced depression may persist after drug is withdrawn.
Be alert that rising BP indicating tolerance to drug effect may occur during week 2 or 3 of therapy.

Patient & Family Education

Exercise caution with hot baths and showers, prolonged standing in one position, and strenuous exercise that may enhance orthostatic hypotension. Make position changes slowly, particularly from lying down to upright posture; dangle legs a few minutes before standing.
Be aware that transient sedation, drowsiness, mental depression, weakness, and headache commonly occur during first 24–72 h of therapy or whenever dosage is increased. Symptoms tend to disappear with continuation of therapy or dosage reduction.
Avoid potentially hazardous tasks such as driving until response to drug is known; drug may affect ability to perform activities requiring concentrated mental effort, especially during first few days of therapy or whenever dosage is increased.
Do not to take OTC medications unless approved by physician.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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