Amlodipine [MC*]
Brand Names Norvasc®
Therapeutic Class 24:28 Calcium Channel Blocking Agents 
Use Treatment of hypertension and angina
Off-label use includes management of hypertension in renal and bone marrow transplant patients.
Warnings May increase frequency, duration, and severity of angina or precipitate acute MI during initiation of therapy or dosage increase (particularly in patients with severe obstructive coronary artery disease)
Precautions Use with caution in patients with CHF or severe aortic stenosis; use with caution and reduce the dose in patients with severe hepatic impairment; acute hypotension may rarely occur
Adverse Reactions
Cardiovascular system: Peripheral edema, flushing, palpitations; rarely: hypotension, arrhythmia, chest pain, syncope, peripheral ischemia, vasculitis; MI (rare)
Central nervous system: Headache, dizziness, somnolence, fatigue; less common: vertigo, insomnia, abnormal dreams, nervousness, depression, anxiety
Dermatologic: Rash, pruritus, erythema multiforme, angioedema 
Endocrine & Metabolic: Sexual dysfunction, gynecomastia, hyperglycemia, weight gain, weight loss
Gastrointestinal: Nausea, abdominal pain, dyspepsia, anorexia, constipation, diarrhea, dysphagia, pancreatitis, vomiting, xerostomia; gingival hyperplasia (may be less than with nifedipine)
Hematologic: Thrombocytopenia, leukopenia, purpura
Hepatic: Jaundice, elevated liver enzymes
Neuromuscular & skeletal: Muscle cramps, asthenia, arthralgia, myalgia, paresthesia, peripheral neuropathy, hypoesthesia, tremor
Ocular: Diplopia, abnormal vision, eye pain, conjunctivitis
Otic: Tinnitus
Respiratory: Dyspnea, epistaxis
Miscellaneous: Diaphoresis, hypersensitivity reactions, thirst
Drug Interactions Cytochrome P450 isoenzyme CYP3A4 substrate 
Azole antifungal agents may inhibit the metabolism of amlodipine and result in an increase in amlodipine serum concentrations or effect; calcium may decrease the pharmacologic effect of calcium channel blockers; rifampin may decrease amlodipine serum concentrations; amlodipine may (or may not) increase cyclosporine serum concentrations (conflicting studies exist)
Usual Dosage Oral:
Hypertension: Children:
<50 kg: 0.05-0.3 mg/kg once daily; maximum initial dose: 5 mg/day 
6-17 years: 2.5-5 mg once daily; maximum dose: 10 mg/day
Adults: Hypertension: Initial: 2.5-5 mg once daily; use initial dose of 2.5 mg once daily in patients who are small, fragile, or elderly, and when adding amlodipine to other antihypertensive therapy; in general, titrate dose over 7-14 days to fully assess effects; usual dose: 5 mg once daily; maximum dose: 10 mg once daily; usual dosage range (JNC 7): 2.5-10 mg once daily
Dosing adjustment in renal impairment: Not needed; patients may receive the usual initial dose
Dosing adjustment in hepatic impairment: Adults: Initial: 2.5 mg once daily
Administration Oral: May be administered without regard to food; use caution if administered with grapefruit juice (grapefruit juice may increase amlodipine peak serum concentrations by 15%)
Dosage Forms
Suspension, oral: 1 mg/mL, extemporaneously prepared by pharmacy 
Tablet: 2.5 mg, 5 mg, 10 mg

Atenolol [MC]
Brand Names Tenormin®
Therapeutic Class 24:04 Cardiac Drugs
Use Treatment of hypertension, alone or in combination with other agents; management of angina pectoris, postmyocardial infarction patients 
Contraindications Hypersensitivity to beta-blocking agents, pulmonary edema, cardiogenic shock, bradycardia, heart block without a pacemaker, uncompensated congestive heart failure, sinus node dysfunction, A-V conduction abnormalities, diabetes mellitus
Warnings Safety and efficacy in children have not been established; administer with caution to patients (especially the elderly) with bronchospastic disease, CHF, renal dysfunction, severe peripheral vascular disease, myasthenia gravis, diabetes mellitus, hyperthyroidism. Abrupt withdrawal of the drug should be avoided, drug should be discontinued over 1-2 weeks; may potentiate hypoglycemia in a diabetic patient and mask signs and symptoms; modify dosage in patients with renal impairment.
Adverse Reactions
Cardiovascular: Bradycardia, hypotension, second or third degree A-V block
Central nervous system: Dizziness, fatigue, lethargy, headache, nightmares
Gastrointestinal: Constipation, nausea, diarrhea
Respiratory: Wheezing and dyspnea have occurred with higher doses (eg, >100 mg/day in adults)
Drug Interactions Additive effect with other hypotensive agents; atenolol (especially at higher doses) may reverse the therapeutic effects of theophylline
Usual Dosage Oral:
Children: 1-2 mg/kg/dose given once daily
Adults:
Hypertension: 50 mg once daily, may increase to 100 mg/day; doses >100 mg are unlikely to produce any further benefit
Angina pectoris: 50 mg once daily, may increase to 100 mg/day; some patients may require 200 mg/day

Dosing interval in renal impairment:
Clcr, 15-35 mL/minute: Administer 50 mg/day maximum
Clcr, <15 mL/minute: Administer 50 mg every other day maximum 
Moderately dialyzable (20% to 50%)
Administration Oral: May be administered without regard to food 
Monitoring Parameters Monitor blood pressure, apical and radial pulses, fluid I & 0, daily weight, respirations, and circulation in extremities before and during therapy
Patient Information Abrupt withdrawal of the drug should be avoided 
Additional Information In diabetic patients, atenolol may potentiate hypoglycemia and mask signs and symptoms of hypoglycemia.
Dosage Forms Tablet: 25 mg, 50 mg, 100 mg

Bumetanide
Brand Names Bumex® 
Therapeutic Class 40:28 Diuretics 
Use Management of edema secondary to congestive heart failure or hepatic or renal disease including nephrotic syndrome; may also be used alone or in combination with antihypertensives in the treatment of hypertension 
Contraindications In anuria or increasing azotemia
Warnings Loop diuretics are potent diuretics; excess amounts can lead to profound diuresis with fluid and electrolyte loss; close medical supervision and dose evaluation is required; use caution in patients with known hypersensitivity to sulfonamides or thiazides (due to possible cross-sensitivity; avoid in history of severe reactions)
Precautions Use with caution in patients with cirrhosis
Adverse Reactions
Cardiovascular: Hypotension, chest pain
Central nervous system: Dizziness, headache, encephalopathy, vertigo 
Endocrine & metabolic: Hyperglycemia, hypokalemia, hypochloremia, hyponatremia
Gastrointestinal: Cramps, nausea, vomiting, diarrhea
Hepatic: Alteration of liver function test results
Neuromuscular & skeletal: Weakness, muscle cramps, arthritic pain 
Otic: Potential ototoxicity
Renal: Decreased uric acid excretion, increased serum creatinine
Drug Interactions Indomethacin and probenecid may decrease bumetanide's effect; additive hypotension with other antihypertensive agents 
Usual Dosage Oral, I.M., IV.:
Neonates: 0.01-0.05 mg/kg/dose every 24-48 hours
Infants and Children: 0.015-0.1 mg/kg/dose every 6-24 hours (maximum: 10 mg/day)

Adults:
Oral: 0.5-2 mg/dose (10 mg/day maximum) 1-2 times/day
I.M., IV.: 0.5-1 mg/dose (10 mg/day maximum)
Administration Give I.V. slowly, over 1-2 minutes; maximum concentration: 0.25 mg/mL (undiluted)
Additional Information Cross-sensitivity with furosemide is rare; ratio of bumetanide to furosemide is 1:40; patients with impaired hepatic function must be monitored carefully, often requiring reduced doses; larger doses may be necessary in patients with impaired renal function to obtain the same therapeutic response
Dosage Forms
Injection: 0.25 mg/mL (2 mL, 10 mL)
Tablet: 0.5 mg, 1 mg

Clonidine Hydrochloride [MC*]
Brand Names Catapres®
Therapeutic Class 24:08 Hypotensive Agents
Use Management of hypertension; aid in the diagnosis of pheochromocytoma and growth hormone deficiency; alternate agent for the treatment of attention-deficit/hyperactivity disorder (ADHD); adjunct in the treatment of neuropathic pain; epidural form is used in combination with opiates for relief of severe pain in cancer patients whose pain was not relieved by opiates alone
Warnings Do not abruptly discontinue as rapid increase in blood pressure and symptoms of sympathetic overactivity (such as increased heart rate, tremor, agitation, anxiety, insomnia, sweating, palpitations) may occur; if need to discontinue, taper dose gradually over more than 1 week
Precautions Dosage modification may be required in patients with renal impairment; use with caution in cerebrovascular disease, coronary insufficiency, sinus node dysfunction
Adverse Reactions
Cardiovascular: Raynaud's phenomenon, hypotension, bradycardia, palpitations, tachycardia, congestive heart failure, rebound hypertension if discontinued abruptly
Central nervous system: Drowsiness, headache, dizziness, fatigue, insomnia, anxiety
Dermatologic: Rash, local skin reactions with patch
Endocrine & metabolic: Sodium and water retention
Gastrointestinal: Constipation, anorexia, dry mouth
Miscellaneous: Parotid pain
Drug Interactions Use with methylphenidate may potentially increase ECG effects. Tricyclic antidepressants antagonize hypotensive effects of clonidine; beta-blockers may potentiate bradycardia in patients receiving clonidine and may increase the rebound hypertension seen with clonidine withdrawal; discontinue beta-blocker several days before clonidine is tapered off.
Usual Dosage
Children: Oral:
Initial: 5-25 mcg/kg/day in divided doses every 6-12 hours; allow 5-7 days between dose adjustments; maximum: 0.9 mg/day
Clonidine tolerance test (test of growth hormone release from the pituitary): 0.15 mg/m2 or 4 mcg/kg as a single dose
ADHD: Initial: 0.05 mg/day, increase every 3-7 days by 0.05 mg/day to 3-5 mcg/kg/day given in divided doses 3-4 times/day; maximum dose: 0.3-0.4 mg/day
Analgesia: Epidural (continuous infusion): Reserved for cancer patients with severe intractable pain, unresponsive to other analgesics or epidural or spinal opiates: Initial: 0.5 mcg/kg/hour; adjust with caution, based on clinical effect; usual range: 0.5-2 mcg/kg/hour; do not exceed adult doses
Neuropathic pain: Oral: Some centers use the following doses (see Galloway, 2000): Initial: 2 mcg/kg/dose every 4-6 hours; increase incrementally over several days; range: 2-4 mcg/kg/dose every 4-6 hours; may also be given as transdermal (see Transdermal)
Transdermal: Children may be switched to the transdermal delivery system after oral therapy is titrated to an optimal and stable dose; a transdermal dose approximately equivalent to the total oral daily dose may be used (see Hunt, 1990; see Administration)

Adults:
Oral: Initial dose: 0.1 mg twice daily, usual maintenance dose: 0.2-1.2 mg/day in 2-4 divided doses; maximum recommended dose: 2.4 mg/day
Transdermal: Applied once weekly as transdermal delivery system; initial therapy with 0.1 mg/24 hours applied once every 7 days; adjust dosage based on response; hypotensive action may not begin until 2-3 days after initial application
Diagnosis of pheochromocytoma: 0.3 mg as a single dose after baseline catecholamine levels drawn
Analgesia: Epidural (continuous infusion): Initial: 30 mcg/hour; titrate to clinical effect; usual maximum dose: 40 mcg/hour
Administration Patches should be applied weekly at bedtime to a clean, hairless area of the upper outer arm or chest; rotate patch sites weekly Note: Transdermal patch is a membrane-controlled system; do not cut the patch to deliver partial doses; rate of drug delivery, reservoir contents, and adhesion may be affected if cut; if partial dose is needed, surface area of patch can be blocked proportionally using adhesive bandage
Dosage Forms
Injection, epidural solution, as hydrochloride [preservative free] (Duraclon™): 100 mcg/mL (10 mL)
Patch, transdermal: 1, 2, and 3 (0.1, 0.2, 0.3 mg/day for 7 days duration) Suspension, oral: 100 mcg/mL, extemporaneously prepared by pharmacy
Tablet: 0.1 mg, 0.2 mg

Chlorothiazide
Brand Names Diuril®
Therapeutic Class 40:28 Diuretics
Use Management of mild to moderate hypertension; edema associated with congestive heart failure, pregnancy, or nephrotic syndrome 
Contraindications Cross-sensitivity with other thiazides or sulfonamides; do not use in anuric patients; avoid extravasation
Adverse Reactions
Cardiovascular: Hypotension
Central nervous system: Dizziness, vertigo, paresthesias
Dermatologic: Rash, photosensitivity
Endocrine & metabolic: Hypokalemia, hypochloremic alkalosis, hyperglycemia, hyperlipidemia, hyperuricemia
Gastrointestinal: Anorexia, nausea, vomiting, cramping, diarrhea, pancreatitis, constipation
Hematologic: Rarely blood dyscrasias
Hepatic: Intrahepatic cholestasis
Neuromuscular & skeletal: Muscle weakness
Renal: Prerenal azotemia, hematuria
Drug Interactions Nonsteroidal anti-inflammatory drug (NSAID) + chlorothiazide may decrease antihypertensive effect; additive potassium losses with steroids, loop diuretics and amphotericin B; decreased lithium clearance; increased hypersensitivity reactions to allopurinol; increased hyperglycemia with diazoxide; decreased absorption of chlorothiazide when administered with cholestyramine
Usual Dosage I.V. dosage in infants and children has not been well established. The following I.V. dosages in infants and children have been extrapolated from oral absorption data (10% to 20%) and have been used successfully.

Infants <6 months:
Oral: 20-40 mg/kg/day in 2 divided doses (maximum: 375 mg/day)
I.V.: 2-8 mg/kg/day in 2 divided doses (doses up to 20 mg/kg/day have been used)
Infants >6 months and Children:
Oral: 20 mg/kg/day in 2 divided doses (maximum: 1 g/day)
IV.: 4 mg/kg/day (doses up to 20 mg/kg/day have been used)
Adults:
Hypertension: Oral: 125-500 mg once daily 
Edema:
Oral: 500 mg to 2 g/day divided in 1-2 doses 
I.V.:100-500 mg/day divided in 1-2 doses 
Administration
Oral: Administer with food
Parenteral: Dilute 500 mg vial with 18 mL sterile water  
Do not administer I.M. or SubQ; administer by direct I.V. infusion over 3-5 minutes or I.V. infusion over 30 minutes in dextrose or normal saline; avoid extravasation of parenteral solution since it is extremely irritating to tissues
Additional Information Experience with I.V. administration in infants and children has been limited; this route is generally not recommended 
Dosage Forms
Injection: 500 mg (20 mL)
Suspension: 250 mg/5 mL (237 mL)
Tablet: 500 mg
Enalapril [MC*]
Brand Names Vasotec®
Therapeutic Class 24:04 Cardiac Drugs
Use Management of mild to severe hypertension and congestive heart failure
Contraindications Hypersensitivity to ACE inhibitors
Precautions Use with caution and modify dosage in patients with renal impairment (especially renal artery stenosis), hyponatremia, hypovolemia, severe congestive heart failure or with coadministered diuretic therapy; experience in children is limited; use with caution in neonates; injectable product contains benzyl alcohol 9 mg/mL
Adverse Reactions
Cardiovascular: Hypotension, syncope
Central nervous system: Fatigue, vertigo, insomnia, dizziness, headache
Dermatologic: Rash, angioedema
Endocrine & metabolic: Hypoglycemia, hyperkalemia
Gastrointestinal: Nausea, diarrhea, loss of taste perception
Hematologic: Agranulocytosis, neutropenia, anemia
Neuromuscular & skeletal: Muscle cramps
Renal: Deterioration in renal function
Respiratory: Cough
Drug Interactions Use with potassium-sparing diuretics may result in an additive hyperkalemic effect; diuretics or other antihypertensive agents may increase hypotensive effect; indomethacin may decrease hypotensive effect; enalapril may increase lithium levels
Pharmacodynamics
Onset of action:
Oral: Within 1 hour
I.V.: Within 15 minutes
Maximum effect:
Oral: Within 4-8 hours
I.V.: Within 1-4 hour
Pharmacokinetics
Metabolism: Enalapril is a prodrug and undergoes biotransformation to enalaprilat in the liver
Elimination: Primarily renal
Usual Dosage Use lower listed initial dose in patients with hyponatremia, hypovolemia, severe congestive heart failure, decreased renal function, or in those receiving diuretics

Neonates:
Oral: Enalapril: Initial: 0.1 mg/kg/day given every 24 hours; increase dose and interval as required every few days
I.V.: Enalaprilat: 5-10 mcg/kg/dose administered every 8-24 hours (as determined by blood pressure readings) has been used for the treatment of neonatal hypertension; monitor patients carefully; select patients may require higher doses
Infants and Children:
Oral: Enalapril: Initial: 0.1 mg/kg/day in 1-2 divided doses; increase as required over 2 weeks to maximum of 0.5 mg/kg/day; mean dose required for CHF improvement in 39 children (9 days to 17 years of age) was 0.36 mg/kg/day; investigationally, select individuals have been treated with doses up to 0.94 mg/kg/day (Leversha, 1994)
I.V.: Enalaprilat: 5-10 mcg/kg/dose administered every 8-24 hours (as determined by blood pressure readings); monitor patients carefully; select patients may require higher doses
Adults:
Oral: Enalapril: 2.5-5 mg/day then increase as required, usually 10-40 mg/day in 1-2 divided doses
I.V.: Enalaprilat: 0.625-1.25 mg/dose, every 6 hours
Dosing adjustment in renal impairment:
Clcr 10-50 mL/minute: Administer 75% to 100% of the usual dose 
Clcr <10 mL/minute: Administer 50% of the usual dose
Administration I.V.: May be administered undiluted or diluted in dextrose or normal saline and given over 5 minutes
Dosage Forms
Injection, as enalaprilat: 1.25 mg/mL (2 mL)
Suspension, oral: 1 mg/mL, extemporaneously prepared by pharmacy 
Tablet: 2.5 mg, 5 mg, 10 mg, 20 mg

Furosemide [MC*]
Brand Names Lasix®
Therapeutic Class 40:28 Diuretics
Use Management of edema associated with congestive heart failure and hepatic or renal disease; used alone or in combination with antihypertensives in treatment of hypertension
Contraindications Anuria
Warnings Loop diuretics are potent diuretics; excess amounts can lead to profound diuresis with fluid and electrolyte loss; use caution in patients with known hypersensitivity to sulfonamides or thiazides (due to possible cross-sensitivity; avoid in history of severe reactions)
Precautions Hepatic cirrhosis (rapid alterations in fluid/electrolytes may precipitate coma)
Adverse Reactions
Cardiovascular: Orthostatic hypotension
Central nervous system: Dizziness, vertigo, headache
Dermatologic: Urticaria, photosensitivity
Endocrine & metabolic: Hypokalemia, hyponatremia, hypochloremia, alkalosis, dehydration, hyperuricemia
Gastrointestinal: Pancreatitis, nausea, anorexia, vomiting, constipation, abdominal cramping; oral solutions may cause diarrhea due to sorbitol content
Hematologic: Agranulocytosis, anemia, thrombocytopenia
Hepatic: Ischemic hepatitis, jaundice
Otic: Potential ototoxicity
Renal: Nephrocalcinosis, prerenal azotemia, interstitial nephritis, hypercalciuria
Drug Interactions Drugs affected by potassium depletion (eg, digoxin); decreased furosemide diuretic effect in the presence of salicylates and NSAIDs; antidiabetic agents decrease glucose tolerance; aminoglycosides increase ototoxicity; increased oral anticoagulant activity of warfarin
Stability Protect from light
Pharmacokinetics 50% of oral dose or 80% of I.V. dose is excreted in the urine within 24 hours; the remainder is eliminated by other nonrenal pathways including liver metabolism and excretion of unchanged drug in the feces
Usual Dosage
Premature neonates:
I.M., I.V.: 1-2 mg/kg/dose given every 12-24 hours
Oral: Bioavailability is poor by this route. Doses of 1-4 mg/kg/dose 1-2 times/day have been used.
Children: 
Oral, I.M., I.V.: 1-2 mg/kg/dose up to 6 mg/kg/day in divided doses every 6-12 hours
Continuous infusion: 0.05-0.4 mg/kg/hour; titrate dosage to clinical effect 
Adults:
Oral: Initial: 20-80 mg/dose; increase in increments of 20-40 mg/dose at intervals of 6-8 hours; usual maintenance dose interval is twice daily or every day; may be titrated up to 600 mg/day with severe edematous states
I.M., I.V.: 20-40 mg/dose; repeat in 1-2 hours as needed and increase by 20 mg/dose until the desired effect has been obtained; usual dosing interval: 6-12 hours
Continuous I.V. infusion: Initial I.V. bolus dose of 0.1 mg/kg followed by continuous I.V. infusion doses of 0.1 mg/kg/hour doubled every 2 hours to a maximum of 0.4 mg/kg/hour
Administration For I.V. push, may be administered undiluted over 1-2 minutes; maximum rate: 0.5 mg/kg/minute for doses <120 mg and 4 mg/ minute for doses >120 mg. For I.V. infusion, dilute to 1-2 mg/mL or 10 mg/ mL at a rate of 0.1-0.4 mg/kg/hour
Dosage Forms <pj Injection: 10 mg/mL (2 mL, 4 mL, 10 mL)
Solution, oral: 10 mg/mL (2 mg/mL, extemporaneously prepared by pharmacy)
Tablet: 20 mg, 40 mg, 80 mg
HydrALAZINE Hydrochloride [MC]
Medication Safety Issues
Sound-alike/look-alike issues:
HydrALAZINE may be confused with hydrOXYzine
Brand Names Apresoline®
Therapeutic Class 24:08 Hypotensive Agents
Use Management of moderate to severe hypertension, congestive heart failure, hypertension secondary to pre-eclampsia/eclampsia 
Contraindications Dissecting aortic aneurysm, mitral valve rheumatic heart disease, known or suspected coronary artery disease 
Precautions Discontinue hydralazine in patients who develop SLE-like syndrome or positive ANA. Use with caution in patients with severe renal disease or cerebral vascular accidents.
Adverse Reactions
Cardiovascular: Palpitations, flushing, tachycardia, edema, orthostatic hypotension (rarely)
Central nervous system: Malaise, peripheral neuritis, headache, dizziness, fever
Gastrointestinal: Anorexia, nausea, vomiting, diarrhea
Hematologic: Blood dyscrasias
Neuromuscular & skeletal: Weakness
Miscellaneous: Lupus-like syndrome
Drug Interactions MAO inhibitors may cause a significant decrease in blood pressure; sympathomimetics may induce tachycardia and angina; NSAIDs may decrease hypotensive effects
Usual Dosage
Infants and Children:
Oral: Initial: 0.75-1.0 mg/kg/day in 2-4 divided doses, not to exceed 25 mg/dose; increase over 3-4 weeks to maximum of 5 mg/kg/day in infants and 7.5 mg/kg/day in children; maximum daily dose: 200 mg/ day
I.M., I.V.: 0.1-0.2 mg/kg/dose (initial dose not to exceed 20 mg) every 4-6 hours as needed

Adults:
Oral: Initial: 10 mg 4 times/day, increase by 10-25 mg/dose every 2-5 days to maximum of 300 mg/day 
I.M., I.V.:
Hypertensive reaction: Initial: 10-20 mg/dose every 4-6 hours as needed, may increase to 40 mg/dose
Pre-eclampsia/eclampsia: 5 mg/dose then 5-10 mg every 20-30 minutes as needed
Dosing interval in renal impairment:
Clcr 10-50 mL/minute: Administer every 8 hours
Clcr <10 mL/minute: Administer every 8-12 hours in fast acetylators and every 12-24 hours in slow acetylators
Administration For I.V. push, may administer undiluted over 3-5 minutes; maximum rate: 0.2 mg/kg/minute
Additional Information Slow acetylators, patients with decreased renal function and patients receiving >200 mg/day (chronically) are at higher risk for SLE.
Dosage Forms
Injection: 20 mg/mL (1 mL)
Tablet: 10 mg, 25 mg, 50 mg

Hydrochlorothiazide [MC]
Therapeutic Class 40:28 Diuretics
Use Management of mild to moderate hypertension; treatment of edema in congestive heart failure and nephrotic syndrome
Contraindications Cross-sensitivity with other thiazides or sulfonamides 
Precautions Use with caution in patients with severe renal disease (Clcr, <10 mL/minute), impaired hepatic function, gout, lupus erythematosus, and diabetes mellitus
Adverse Reactions
Cardiovascular: Hypotension
Endocrine & metabolic: Dehydration, hypokalemia, hyperglycemia, hypochloremic metabolic alkalosis, hyperuricemia, hyperlipidemia 
Gastrointestinal: Nausea, vomiting, anorexia, diarrhea, cramping, pancreatitis
Hematologic: Aplastic anemia, hemolytic anemia, leukopenia, agranulocytosis, thrombocytopenia
Hepatic: Hepatitis, intrahepatic cholestasis
Renal: Prerenal azotemia
Drug Interactions Diuretic-induced hypokalemia and hypomagnesemia may precipitate digitalis-induced arrhythmias; may precipitate hyperglycemia with diazoxide; additive potassium losses with steroids and amphotericin B; NSAIDs decrease natriuretic response and antihypertensive effects; ↑ NSAIDs nephrotoxicity; hydrochlorothiazide decreases effectiveness of antidiabetic agents in blood sugar control
Usual Dosage Oral:
Children (daily dosages should be decreased if used with other antihypertensives):
<6 months: 2-3 mg/kg/day in 2 divided doses; maximum: 37.5 mg/day 
>6 months: 2 mg/kg/day in 2 divided doses; maximum: 200 mg/day
Adults: 12.5-100 mg/day in 1-2 doses; maximum: 200 mg/day 
Dosage Forms Tablet: 25 mg, 50 mg

Hydrochlorothiazide and Spironolactone [MC*]
Brand Names Aldactazide®
Therapeutic Class 40:28 Diuretics; 40:28.10 Potassium-Sparing Diuretics
Use Management of mild to moderate hypertension; treatment of edema in congestive heart failure and nephrotic syndrome
Contraindications Anuria, hyperkalemia, renal or hepatic failure, hypersensitivity to hydrochlorothiazide, spironolactone, or any component; patients receiving triamterene or amiloride
Adverse Reactions
Central nervous system: Lethargy, headache
Dermatologic: Rash
Endocrine & metabolic: Hyperkalemia, gynecomastia, hyperchloremic metabolic acidosis, dehydration, hyponatremia
Gastrointestinal: Anorexia, nausea, vomiting, diarrhea
Drug Interactions See individual components
Usual Dosage Oral:
Children: 1.5-3.0 mg/kg/day (of spironolactone) in 2-4 divided doses 
Adults: 12.5-200 mg in 1-2 divided doses
Dosage Forms
Suspension, oral: Hydrochlorothiazide 25 mg and spironolactone 25 mg per 5 mL, extemporaneously prepared by pharmacy
Tablet: Hydrochlorothiazide 25 mg and spironolactone 25 mg

Isradipine [MC]
Brand Names DynaCirc®
Therapeutic Class 24:08 Hypotensive Agents
Use Treatment of hypertension, congestive heart failure, migraine prophylaxis
Contraindications Sinus bradycardia, advanced heart block, ventricular tachycardia, cardiogenic shock, hypotension, congestive heart failure; hypersensitivity to isradipine or any component, hypersensitivity to calcium channel blockers and adenosine; atrial fibrillation or flutter associated with accessory conduction pathways; not to be given within a few hours of I.V. beta-blocking agents
Warnings Avoid use in hypotension, congestive heart failure, cardiac conduction defects, PVCs, idiopathic hypertrophic subaortic stenosis; may cause platelet inhibition; do not abruptly withdraw; may cause hepatic dysfunction or increased angina; increased intracranial pressure with cranial tumors
Adverse Reactions
Cardiovascular: Arrhythmia, bradycardia, hypotension, palpitations Central nervous system: Dizziness, headache
Dermatologic: Rash
Gastrointestinal: Nausea, diarrhea, abdominal discomfort
Hepatic: Mild to marked elevations in liver function tests
Respiratory: Shortness of breath
Drug Interactions
Increased toxicity/effect/levels:
Isradipine and beta-blockers may increase cardiovascular adverse effects; with fentanyl, isradipine therapy may cause severe hypotension
Isradipine and cyclosporine may minimally increase cyclosporine levels 
Azole antifungals may inhibit the calcium channel blocker's metabolism; avoid this combination. Try an antifungal like terbinafine (if appropriate) or monitor closely for altered effect of the calcium channel blocker.
Rifampin increases the metabolism of the calcium channel blocker; adjust the dose of the calcium channel blocker to maintain efficacy. 
Sildenafil, tadalafil, vardenafil: Blood pressure-lowering effects may be additive; use caution.
Usual Dosage
Children: Oral: Hypertension: 0.05-0.15 mg/kg/dose every 8 hours; max: 20 mg/day

Adults: 2.5 mg twice daily; antihypertensive response seen in 2-3 hours; maximal response in 2-4 weeks; increase dose at 2- to 4-week intervals at 2.5-5 mg increments; usual dose range: 5-20 mg/day. Note: Most patients show no improvement with doses >10 mg/day but adverse reaction rate increases
Dosage Forms
Capsule, immediate release: 2.5 mg, 5 mg
Suspension, oral: 1 mg/mL, extemporaneously prepared by pharmacy 
Tablet, controlled release: 5 mg, 10 mg

Lisinopril [MC*]
Brand Names Prinivil®; Zestril®
Therapeutic Class 24:32.04 Angiotensin Converting Enzyme Inhibitors 
Use Management of hypertension
Off-label uses include treatment of essential and renal vascular hypertension in the pediatric population, and the management of proteinuria in familial focal segmental glomerulosclerosis (FSGS) and Alport's syndrome.
Contraindications Hypersensitivity to lisinopril, any component, or other ACE inhibitors; patients with idiopathic or hereditary angioedema or a history of angioedema with previous ACE inhibitor use
Warnings Serious adverse effects including angioedema, anaphylactoid reactions, neutropenia, agranulocytosis, hypotension, and hepatic failure may occur (see Adverse Reactions); angioedema may occur in the head, neck, extremities, or intestines; angioedema of the larynx, glottis, or tongue may cause airway obstruction [appropriate treatment (eg, establishing patent airway and/or SubQ epinephrine) should be readily available]; risk of neutropenia may be increased in patients with renal dysfunction, especially if the patients have collagen vascular diseases
Precautions Use with caution and modify dosage in patients with renal impairment, especially renal artery stenosis; elevated BUN and Scr may occur in these patients; discontinuation of concomitant diuretic or lisinopril may be needed; use with caution and modify dosage in patients with hyponatremia, hypovolemia, severe CHF, left ventricular outflow tract obstruction, or with coadministered diuretic therapy. Severe hypotension may occur in patients who are sodium and/or volume depleted; initiate lower doses and monitor closely when starting therapy in these patients.
Adverse Reactions Note: No relevant differences in adverse reactions between pediatric and adult patients has been identified.
Cardiovascular: Hypotension, chest discomfort, orthostatic hypotension, syncope
Central nervous system: Dizziness, headache, fatigue
Dermatologic: Rash, angioedema. Note: The relative risk of angioedema with ACE inhibitors is higher within the first 30 days of use (compared to >1 year of use), for Black Americans (compared to Whites), for lisinopril or enalapril (compared to captopril), and for patients previously hospitalized within 30 days (Brown, 1996).
Endocrine & metabolic: Hyperkalemia
Gastrointestinal: Diarrhea, nausea, vomiting, ageusia, intestinal angioedema (rare)
Hematologic: Neutropenia, agranulocytosis
Hepatic: Cholestatic jaundice, fulminant hepatic necrosis (rare, but potentially fatal)
Renal: Elevated BUN, elevated serum creatinine, proteinuria
Respiratory: Cough, dyspnea, eosinophilic pneumonitis; Note: An isolated dry cough lasting >3 weeks was reported in 7 of 42 pediatric patients (17%) receiving ACE inhibitors
Neuromuscular & skeletal: Weakness
Miscellaneous: Anaphylactoid reactions
Drug Interactions Use with potassium-sparing diuretics may result in an additive hyperkalemic effect; diuretics and other antihypertensive agents may increase hypotensive effect; indomethacin or NSAIDs may decrease hypotensive effect; lisinopril may increase lithium levels; use with NSAIDs in patients with renal impairment may further decrease renal function (usually reversible)
Mechanism of Action Competitive inhibitor of angiotensin-converting enzyme (ACE); prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor; results in lower levels of angiotensin II which causes an increase in plasma renin activity and a reduction in aldosterone secretion
Usual Dosage Oral: Dosage must be titrated according to patient's response; use lower doses (-1/2 of those listed) for patients with hyponatremia, hypovolemia, severe CHF, decreased renal function, or in those receiving diuretics:
Hypertension (Note: If possible, discontinue diuretics 2-3 days prior to initiating lisinopril; restart diuretic, if needed, after blood pressure is stable):
Children <6 years: 0.07-0.15 mg/kg once daily; maximum dose: 2.5 mg/day*
Children .6 years: Initial: 0.07 mg/kg once daily; maximum initial dose: 5 mg once daily; increase dose at 1- to 2-week intervals; doses >0.61 mg/kg or >40 mg have not been evaluated
Adults: Initial: 10 mg/day given once daily: increase dose by 5-10 mg/ day at 1- to 2-week intervals; usual dose: 20-40 mg/day given once daily; doses up to 80 mg/day have been used, but do not appear to have a greater effect; usual dosage range (JNC 7): 10-40 mg once daily
CHF: Adults: Initial: 5 mg once daily (with diuretics and digitalis); increase dose by 10 mg/day at .2 week intervals based on clinical response; usual dose: 5-20 mg/day given once daily; maximum dose: 40 mg/day
Dosing adjustment in renal impairment:
Children: Clcr <30 mL/minute/1.73 m2: Use is not recommended Adults: Modify initial dose and cautiously titrate dose based on clinical response
Clcr 10-30 mL/minute: Administer 50% of normal dose
Clcr <10 mL/minute: Administer 25% of normal dose
*Shaw W, Hogg R, Delucchi A, Sakihara G, et al, "Lisinopril Pharmacokinetics in Hypertensive Children and Infants," Am J Hypertens 15(4, Part 2):4bA, April 2002 (in Soc. Proc.)
Nursing Implications Discontinue if angioedema occurs; observe closely for hypotension after the first dose or initiation of a new higher dose (keep in mind that maximum effect on blood pressure occurs at 6-8 hours) 
Dosage Forms
Suspension, oral: 1 mg/mL, extemporaneously prepared by pharmacy 
Tablet: 2.5 mg, 5 mg, 40 mg

Metolazone [MC*]
Brand Names Zaroxolyn®
Therapeutic Class 40:28 Diuretics
Use Management of mild to moderate hypertension; treatment of edema in congestive heart failure and nephrotic syndrome; impaired renal function Contraindications Hypersensitivity to thiazide diuretics or sulfonamide-derived drugs; patients with hepatic coma
Precautions Use with caution in patients with severe renal disease, impaired hepatic function, gout, lupus erythematosus, diabetes mellitus, moderate-high cholesterol concentrations, and/or high triglycerides
Adverse Reactions
Cardiovascular: Palpitations, chest pain, orthostatic hypotension 
Central nervous system: Vertigo, headache, chills
Dermatologic: Rash
Endocrine & metabolic: Hypokalemia, hyponatremia, hypochloremia, metabolic alkalosis, hyperglycemia, hyperuricemia, hypomagnesemia 
Gastrointestinal: Abdominal bloating, GI irritation
Hematologic: Blood dyscrasias, aplastic anemia, hemolytic anemia, leukopenia, agranulocytosis, thrombocytopenia
Hepatic: Hepatitis
Neuromuscular & skeletal: Joint pain, back pain
Ocular: Eye itching
Otic: Tinnitus
Renal: Polyuria, prerenal azotemia, uremia
Respiratory: Cough, sinus congestion, epistaxis
Drug Interactions Increased digoxin toxicity, increased lithium toxicity; additive potassium losses with amphotericin B and steroids; salicylates and NSAIDs decrease antihypertensive effects
Usual Dosage Oral:
Children: 0.2-0.4 mg/kg/day divided every 12-24 hours

Adults:
Edema: Initiate at 5 mg once daily, may increase to a maximum of 20 mg/24 hours based on patient response
Hypertension: 2.5-5 mg/dose every 24 hours
Dosage Forms
Suspension, oral: 1 mg/mL, extemporaneously prepared by pharmacy 
Tablet: 2.5 mg, 5 mg

Metoprolol
Brand Names Lopressor®; Toprol XL®
Therapeutic Class 24:24 Beta-Adrenergic Blocking Agents
Use Management of hypertension, angina pectoris, and arrhythmias (such as multifocal atrial tachycardia); prevention of MI and migraine headaches; extended release tablets are also indicated to reduce mortality and hospitalization in adults with CHF (stable NYHA Class II or III) who are receiving ACE inhibitors, diuretics, and/or digoxin
Restrictions Non-Formulary status
Contraindications Hypersensitivity to metoprolol or any component; sinus bradycardia; heart block greater then first degree; sick sinus syndrome (except in patients with a functioning artificial pacemaker); cardiogenic shock; uncompensated CHF
Warnings May depress myocardial activity and precipitate CHF, use with caution and monitor closely, especially in patients with compensated heart failure. In patients with coronary artery disease, exacerbation of angina and, in some cases, MI may occur following abrupt discontinuation of therapy. Beta-blockers should generally be avoided in patients with bronchospastic disease; metoprolol, with relative beta1 selectivity, should be used with caution and closely monitored in patients with bronchospastic disease; beta2 stimulants and the lowest possible dose of metoprolol should be used in these patients. Metoprolol may block hypoglycemia-induced tachycardia and blood pressure changes; use with caution in patients with diabetes mellitus. Metoprolol decreases the ability of the heart to respond to reflex adrenergic stimuli and may increase the risk of general anesthesia and surgical procedures. May mask clinical signs of hyperthyroidism (exacerbation of symptoms of hyperthyroidism, including thyroid storm, may occur following abrupt discontinuation). Use with caution with verapamil, diltiazem, or anesthetic agents that decrease myocardial function (bradycardia or heart block may occur).
Precautions Use with caution in patients with hepatic dysfunction and in patients with peripheral vascular disease (beta-blockers may aggravate arterial insufficiency). Patients who have a history of severe anaphylactic hypersensitivity reactions to various substances may be more reactive while receiving beta-blockers; these patients may not be responsive to the normal doses of epinephrine used to treat hypersensitivity reactions. Use with caution in patients with pheochromocytoma; these patients should receive an alpha-blocking agent before receipt of any beta-blocking agent. 
Adverse Reactions
Cardiovascular: Bradycardia, reduced peripheral circulation, palpitations, CHF, hypotension, peripheral edema, worsening of AV conduction disturbances, heart block (second and third degree)
Central nervous system: Dizziness, tiredness, depression, mental confusion, insomnia
Dermatologic: Rash, pruritus, worsening of psoriasis
Gastrointestinal: Diarrhea, nausea, abdominal pain, xerostomia, constipation, vomiting
Hematologic (potential): Agranulocytosis, thrombocytopenia
Hepatic: Hepatitis, hepatic dysfunction, jaundice; rare: elevated transaminase, alkaline phosphatase, LDH
Respiratory: Bronchospasm, wheezing, dyspnea
Drug Interactions Cytochrome P450 isoenzyme CYP2D6 substrate 
Catecholamine-depleting drugs, such as reserpine or MAO inhibitors, may have additive effects (hypotension, bradycardia); hypotensive agents, diuretics, cardiac glycosides, amiodarone, calcium channel blockers, agents that slow AV conduction, and myocardial depressant general anesthetics may have additive effects with beta-blockers; verapamil may significantly increase the oral bioavailability of metoprolol (avoid concomitant use or reduce metoprolol dose and monitor closely); cimetidine, ciprofloxacin, fluoxetine, hydralazine, oral contraceptives, propoxyphene, and quinidine may increase metoprolol serum concentrations and effects. Abrupt withdrawal of clonidine while receiving beta-blockers may result in an exaggerated hypertensive crisis; NSAIDs may decrease the antihypertensive effects of beta-blockers; barbiturates and rifampin may increase the metabolism of metoprolol and decrease metoprolol serum concentrations; metoprolol may increase lidocaine serum concentrations
Usual Dosage (See Additional Information)
Oral: Hypertension:
Children: No pediatric studies are available
Adolescents: Limited information is available. Sixteen hypertensive adolescents (>=13 years of age) were treated with an initial dose of 50 mg twice daily; patients were seen every 4-6 weeks and doses were increased to 100 mg twice daily if blood pressure was not controlled 
Adults:
Tablets (nonsustained release): Initial: 100 mg/day in single or divided doses, increase at weekly intervals to desired effect; usual dosage range: 100-450 mg/day; doses >450 mg/day have not been studied; usual dosage range (JNC 7): 50-100 mg/day in 1-2 divided doses
Note: Lower once-daily dosing (especially 100 mg/day) may not control blood pressure for 24 hours; larger or more frequent dosing may be needed. Patients with bronchospastic diseases should receive the lowest possible daily dose; dose should initially be divided into 3 doses per day (to avoid high plasma concentrations).
Extended release tablets: Initial: 50-100 mg/day as a single dose; increase at weekly intervals to desired effect; doses >400 mg/day have not been studied; usual dosage range (JNC 7): 50-100 mg once daily
Oral: Congestive heart failure: Adults: Extended release tablets: Initial: NYHA Class II heart failure: 25 mg once daily; more severe heart failure: 12.5 mg once daily; may double the dose every 2 weeks as tolerated; maximum: 200 mg/day
Additional Information Do not abruptly discontinue therapy, taper dosage gradually over 1-2 weeks. Beta-blockers without intrinsic sympathomimetic activity (such as metoprolol) have been shown to decrease morbidity and mortality when initiated in the acute treatment of MI and continued long term; metoprolol injection is used for early treatment of definitive or suspected MI; consult adult reference for further information.

Limited pediatric dosing information is available in the literature; in one case report, oral metoprolol (2 mg/kg/day in 3 divided doses) helped control paroxysmal supraventricular tachycardia in a 6 month old infant receiving digoxin (see Hepner, 1983). Low dose oral metoprolol (initial: 0.1 mg/kg/dose given twice daily, then increased slowly as needed to a maximum of 0.9 ± 0.7 mg/kg/day) was used to treat severe CHF that failed conventional therapy in 4 children (mean age: 7.8 years) with cardiomyopathy who were under consideration for heart transplantation (see Shaddy, 1998). A follow-up report in 15 children, 2.5-15 years of age (mean: 8.6 ± 1.3 years), used low dose oral metoprolol [Initial: 0.1-0.2 mg/kg/dose given twice daily, then increased slowly as needed to a maximum of 1.1 ± 0.1 mg/kg/day (range: 0.5-2.3 mg/kg/day)] to treat dilated cardiomyopathy and CHF; all patients received ACE inhibitors, digoxin, and diuretics before starting metoprolol (see Shaddy, 1999). Two studies (Muller, 1993; O'Marcaigh, 1994) assessed metoprolol for unexplained syncope in children at I.V. doses of 0.1 to 0.2 mg/kg for tilt table testing; in both studies, oral metoprolol was given after tilt table testing to select patients; initial oral doses of 0.8-2.8 mg/kg/day were used in 15 patients (8-20 years of age), but treatment was discontinued in 3 patients receiving 1.8-2.8 mg/kg/day due to adverse effects (Muller, 1993); oral doses of 1 to 2 mg/kg/day, rounded to the nearest 25 mg/day and divided into 2 doses daily were used in 19 patients (7-18 years of age) with unexplained syncope; the mean effective dose was 1.5 mg/kg/day (O'Marcaigh, 1994). High-dose beta-blocker therapy has been recommended to treat childhood hypertrophic cardiomyopathy (see Ostman-Smith 1999). Further pediatric studies are required before these doses can be recommended.
Dosage Forms
Injection: 1 mg/mL
Suspension, oral: 10 mg/mL, extemporaneously prepared by pharmacy 
Tablet 50 mg, 100 mg
Tablet, extended release (Toprol XL®): 25 mg, 50 mg

Minoxidil
Brand Names Loniten® Oral
Therapeutic Class 24:08 Hypotensive Agents; 84:36 Skin and Mucous Membrane Agents, Miscellaneous
Use Management of severe hypertension
Contraindications Pheochromocytoma
Precautions Use with caution in patients with coronary artery disease or with recent myocardial infarction, pulmonary hypertension, significant renal dysfunction, congestive heart failure
Adverse Reactions
Cardiovascular: Edema, congestive heart failure, tachycardia, angina, pericardial effusion and tamponade, ECG changes
Central nervous system: Dizziness, fatigue, headache
Dermatologic: Hypertrichosis (commonly occurs within 1-2 months of therapy), coarsening facial features, dermatologic reactions, rash, Stevens-Johnson syndrome, sunburn
Endocrine & metabolic: Sodium and water retention
Gastrointestinal: Weight gain
Respiratory: Pulmonary hypertension/edema
Drug Interactions Concurrent administration with guanethidine may cause profound orthostatic hypotensive effects; additive hypotensive effects with other hypotensive agents or diuretics
Usual Dosage Oral:
Children <12 years: Hypertension: Initial: 0.1-0.2 mg/kg once daily; maximum: 5 mg/day; increase gradually every 3 days; usual dosage: 0.25-1 mg/kg/day in 1-2 divided doses; maximum: 50 mg/day
Children >12 years and Adults: Hypertension: Initial: 5 mg once daily, increase gradually every 3 days; usual dose: 10-40 mg/day in 1-2 divided doses; maximum: 100 mg/day
Additional Information Usually used with a beta-blocker (to treat minoxidil-induced tachycardia) and a diuretic (for treatment of water retention/ edema); may take 1-6 months for hypertrichosis to totally reverse after minoxidil therapy is discontinued
Dosage Forms
Suspension, oral: 2 mg/mL, extemporaneously prepared by pharmacy
Tablet: 2.5 mg, 10 mg

NiCARdipine Hydrochloride
Medication Safety Issues 
Sound-alike/look-alike issues:
NiCARdipine may be confused with NIFEdipine or NIMOdipine
Brand Names Cardene®
Therapeutic Class 24:04 Cardiac Drugs
Use Treatment of chronic stable angina; management of essential hypertension, migraine prophylaxis
Unlabeled Use: Congestive heart failure
Contraindications Contraindicated in severe hypotension or second and third degree heart block, sinus bradycardia, advanced heart block, ventricular tachycardia, cardiogenic shock, atrial fibrillation or flutter associated with accessory conduction pathways, CHF; hypersensitivity to calcium channel blockers and adenosine; not to be given within a few hours of I.V. beta-blocking agents
Warnings Use with caution in titrating dosages for impaired renal or hepatic function patients; may increase frequency, severity, and duration of angina during initiation of therapy; do not abruptly withdraw
Adverse Reactions
Cardiovascular: Flushing, hypotension, tachycardia, palpitation, syncope, peripheral edema
Central nervous system: Headache, dizziness
Dermatologic: Dermatitis, urticaria
Gastrointestinal: Nausea, vomiting
Respiratory: Shortness of breath
Miscellaneous: Sweating, polyuria, injection site reaction and pain 
Drug Interactions
Azole antifungals may inhibit the calcium channel blocker's metabolism; avoid this combination.
Calcium may reduce the calcium channel blocker's effects, particularly hypotension.
Cyclosporine's serum concentrations are increased by nicardipine; avoid this combination. Tacrolimus may be affected similarly.
CYP2C8/9 substrates: Nicardipine may increase the levels/effects of CYP2C8/9 substrates. Example substrates include amiodarone, fluoxetine, glimepiride, glipizide, nateglinide, phenytoin, pioglitazone, rosiglitazone, sertraline, and warfarin.
CYP2C19 substrates: Nicardipine may increase the levels/effects of CYP2C19 substrates. Example substrates include citalopram, diazepam, methsuximide, phenytoin, propranolol, and sertraline.
CYP2D6 substrates: Nicardipine may increase the levels/effects of CYP2D6 substrates. Example substrates include amphetamines, selected beta-blockers, dextromethorphan, fluoxetine, lidocaine, mirtazapine, nefazodone, paroxetine, risperidone, ritonavir, thioridazine, tricyclic antidepressants, and venlafaxine.
CYP2D6 prodrug substrates: Nicardipine may decrease the levels/effects of CYP2D6 prodrug substrates. Example prodrug substrates include codeine, hydrocodone, oxycodone, and tramadol.
CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of nicardipine. Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine, phenobarbital, phenytoin, and rifamycins.
CYP3A4 inhibitors: May increase the levels/effects of nicardipine. Example inhibitors include azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin, imatinib, isoniazid, nefazodone, propofol, protease inhibitors, quinidine, and verapamil.
CYP3A4 substrates: Nicardipine may increase the levels/effects of CYP3A4 substrates. Example substrates include benzodiazepines, calcium channel blockers, mirtazapine, nateglinide, nefazodone, tacrolimus, and venlafaxine. Selected benzodiazepines (midazolam and triazolam), cisapride, ergot alkaloids, selected HMG-CoA reductase inhibitors (lovastatin and simvastatin), and pimozide are generally contraindicated with strong CYP3A4 inhibitors.
Metoprolol: Concentration of metoprolol is increased by 25% with concurrent use.
Nafcillin decreases plasma concentration of nicardipine; avoid this combination.
Propranolol: May decrease the metabolism of nicardipine.
Rifampin increases the metabolism of the calcium channel blocker; adjust the dose of the calcium channel blocker to maintain efficacy. Sildenafil, tadalafil, vardenafil: Blood pressure-lowering effects may be additive; use caution.
Vecuronium: Clearance of vecuronium is decreased by 25% with use of I.V. nicardipine; reduce dose of muscle relaxant. 
Pharmacodynamics Onset of action: Oral: 20 minutes; I.V.: 1-5 minutes Usual Dosage
Children: IV.: Initial dose: 1 mcg/kg/minute, may increase to 5 mcg/kg/ minute
Adults: I.V.: Initial: 5 mg/hour increased by 2.5 mg/hour every 15 minutes to a maximum of 15 mg/hour or 1-5 mcg/kg/minute
Monitoring Parameters Monitor closely for orthostasis; heart rate, signs and symptoms of CHF; monitor blood pressure 1, 2, and 8 hours after dosing
Nursing Implications To assess adequacy of blood pressure response, measure blood pressure 8 hours after dosing
Additional Information I.V. ampuls must be diluted; dilute to 0.1 mg/mL for a peripheral line (caution: thrombophlebitis with peripheral infusion) and 0.5 mg/mL for a central line; stable in glass or PVC bags for 24 hours; infusion site should be changed every 12 hours if administered via peripheral vein, I.V. tubing should contain in-line filter
Dosage Forms Injection: 2.5 mg/mL (10 mL)

NIFEdipine [MC]
Medication Safety Issues
Sound-alike/look-alike issues:
NIFEdipine may be confused with niCARdipine or NIMOdipine 
Brand Names Adalat® CC; Procardia®; Procardia XL®
Therapeutic Class 24:04 Cardiac Drugs
Use Angina, hypertrophic cardiomyopathy, hypertension
Warnings Excessive hypotension may occur, especially during initiation of therapy or dosage increase (more common with concurrent beta-blocker therapy; monitor blood pressure closely); profound hypotension, MI, and death have been reported in adults when immediate release nifedipine has been used (orally or sublingually) for acute reduction of blood pressure (manufacturer does not recommended use of capsules for acute reduction of blood pressure)
Precautions May increase frequency, duration, and severity of angina during initiation of therapy; use with caution in patients with congestive heart failure or aortic stenosis (especially with concomitant beta-blocker) 
Adverse Reactions
Cardiovascular: Flushing, hypotension, tachycardia, palpitations, syncope, peripheral edema
Central nervous system: Dizziness, fever, headache, chills
Dermatologic: Dermatitis, urticaria, purpura
Endocrine & metabolic: Sweating
Gastrointestinal: Nausea, diarrhea, constipation, gingival hyperplasia 
Hematologic: Thrombocytopenia, leukopenia, anemia
Neuromuscular & skeletal: Joint stiffness, arthritis with increased ANA 
Ocular: Blurred vision, transient blindness
Respiratory: Shortness of breath
Drug Interactions Beta-blockers may increase cardiovascular adverse effects; anesthetic doses of fentanyl may lead to hypotension; cimetidine may increase nifedipine serum concentration; nifedipine may increase phenytoin, cyclosporine, and possibly digoxin serum concentrations; nifedipine may increase quinidine levels and has an antiplatelet action that may increase bleeding time
Pharmacodynamics
Onset of action:
S.L. or "bite and swallow": Within 1-5 minutes
Oral:
Immediate release: Within 20-30 minutes 
Extended release: 2-2.5 hours
Duration:
Immediate release: 4-8 hours
Extended release: 24 hours
Usual Dosage
Children: Oral, S.L.:
Hypertensive emergencies: 0.25-0.5 mg/kg/dose; maximum: 10 mg/ dose; may repeat if needed every 4-6 hours; monitor carefully; maximum 1-2 mg/kg/day
Hypertrophic cardiomyopathy: 0.6-0.9 mg/kg/24 hours in 3-4 divided doses
Adults: Initial: 10 mg 3 times/day as capsules or 30-60 mg once daily as sustained release tablet; maintenance: 10-30 mg 3-4 times/day (capsules); maximum: 180 mg/24 hours (capsules) or 120 mg/day (sustained release)
Administration When measuring smaller doses from the liquid-filled capsules, consider the following concentrations (for Adalat® and Procardia®) 10 mg capsule = 10 mg/0.34 mL; 20 mg capsule = 20 mg/0.45 mL
Nursing Implications Do not crush or break sustained release tablets
Dosage Forms
Capsule, liquid-filled: 10 mg, 20 mg 
Tablet, sustained release: 30 mg, 60 mg

Nitroprusside Sodium
Brand Names Nipride®
Therapeutic Class 24:08 Hypotensive Agents
Use Management of hypertensive crises; congestive heart failure; used for controlled hypotension to reduce bleeding during surgery
Contraindications Decreased cerebral perfusion; arteriovenous shunt or coarctation of the aorta (ie, compensatory hypertension)
Warnings Excessive amounts of nitroprusside can cause cyanide toxicity (usually in patients with decreased liver function) or thiocyanate toxicity (usually in patients with decreased renal function or in patients with normal renal function but prolonged nitroprusside use)
Precautions Use with caution in patients with increased intracranial pressure (head trauma, cerebral hemorrhage), severe renal impairment, hepatic failure, hypothyroidism, hyponatremia
Adverse Reactions
Cardiovascular: Excessive hypotensive response, palpitations, substernal distress
Central nervous system: Restlessness, weakness, disorientation, psychosis, headache, increased intracranial pressure
Endocrine & metabolic: Sweating, thyroid suppression, thiocyanate toxicity, cyanide toxicity
Gastrointestinal: Nausea, vomiting
Stability Promptly wrap in aluminum foil or other opaque material to protect from light. It is not necessary to wrap administration set or I.V. tubing. 
Pharmacokinetics
Half-life: <10 minutes
Thiocyanate: 2.7-7 days
Metabolism: Converted to cyanide by erythrocyte and tissue sulfhydryl group interactions; cyanide is converted in the liver by rhodanese to thiocyanate
Elimination: Thiocyanate is excreted in the urine
Usual Dosage Children and Adults: I.V.: Continuous infusion: Start 0.5 mcg/kg/minute, titrate to effect; usual dose: 3 mcg/kg/minute, rarely need >5 mcg/kg/minute; maximum: 10 mcg/kg/minute
Administration Parenteral: I.V. continuous infusion only via controlled infusion device; not for direct injection; solution should be protected from light but not necessary to wrap administration set or I.V. tubing; in fluid restricted patients a final maximum concentration of 1 mg/mL has been used
Additional Information May add sodium thiosulfate (at a concentration of 10:1 / thiosulfate:nitroprusside) to decrease risk of cyanide toxicity 
Dosage Forms Injection, solution, as sodium: 25 mg/mL (2 mL)

Spironolactone [MC*]
Brand Names Aldactone®
Therapeutic Class 40:28.10 Potassium-Sparing Diuretics
Use Management of edema associated with excessive aldosterone excretion; hypertension; primary hyperaldosteronism; hypokalemia 
Contraindications Renal failure, anuria, hyperkalemia
Precautions Use with caution in patients with dehydration, hyponatremia, impaired renal clearance (CIcr <50 mL/minute) or hepatic dysfunction; patients receiving other potassium-sparing diuretics or potassium supplements
Adverse Reactions
Central nervous system: Lethargy, headache, mental confusion, ataxia, fever
Dermatologic: Rash
Endocrine & metabolic: Hyperkalemia, dehydration, hyponatremia, hyperchloremic metabolic acidosis, amenorrhea, gynecomastia (in males) 
Gastrointestinal: Anorexia, nausea, vomiting, diarrhea, gastritis 
Hematologic: Agranulocytosis
Renal: Increased BUN
Drug Interactions Potassium, other potassium-sparing diuretics, and angiotensin-converting enzyme inhibitors (eg, captopril) may additively increase the serum potassium; may decrease digoxin clearance and attenuate its inotropic effect; decreased hypoprothrombinemic effect of oral anticoagulants
Pharmacokinetics
Metabolism: Hepatic
Elimination: Urinary and biliary
Usual Dosage Oral:
Children: 1-3.3 mg/kg/day in divided doses every 6-24 hours
Diagnosis of primary aldosteronism: 100-400 mg/m2/day in 1-2 divided doses

Adults:
Edema, hypertension, hypokalemia: 25-200 mg/day in 1-2 divided doses
Diagnosis of primary aldosteronism: 100-400 mg/day in 1-2 divided doses

Dosing interval in renal impairment:
Clcr 10-50 mL/minute: Administer every 12-24 hours
CIcr <10 mL/minute: Avoid use
Dosage Forms
Suspension, oral: 2 mg/mL, extemporaneously prepared by pharmacy
Tablet: 25 mg, 100 mg