angiotensin II receptor antagonists
calcium channel blockers
- Treatment of hypertension; not indicated for initial therapy.
- May be used for add-on/switch therapy in patients not adequately controlled by two the following: angiotensin receptor blockers (ARBs), calcium-channel blockers or diuretics.
- Amlodipine– Inhibits the transport of calcium into myocardial and vascular smooth muscle cells, resulting in inhibition of excitation-contraction coupling and subsequent contraction.
- Hydrochlorothiazide– Increases excretion of sodium and water by inhibiting sodium reabsorption in the distal tubule.
- Promotes excretion of chloride, potassium, hydrogen, magnesium, phosphate, calcium and bicarbonate.
- May produce arteriolar dilation.
- Olmesartan– Blocks vasoconstrictor and aldosterone-secreting effects of angiotensin II at various receptor sites including vascular smooth muscle and the adrenal glands.
Lowering of BP.
Absorption: Amlodipine– Well absorbed after oral administration (64–90%); Hydrochlorothiazide– Rapidly absorbed after oral administration; Olmesartan medoxomil– converted to olmesartan (the active component); 26% bioavailability of olmesartan.
Distribution: Amlodipine– Probably crosses the placenta; Hydrochlorothiazide– Distributed into extracellular space; crosses the placenta and enters breast milk; Olmesartan– Crosses the placenta.
Protein Binding: Amlodipine– 95–98%; Olmesartan– 99%.
Metabolism and Excretion: Amlodipine– Mostly metabolized by the liver; Hydrochlorothiazide– Excreted mainly unchanged by the kidneys; Olmesartan– No further metabolism following conversion of pro-drug to active drug; 35–50% excreted unchanged in urine; remainder eliminated in feces via bile.
Half-life: Amlodipine– 30–50 hr (↑ in geriatric patients and patients with hepatic impairment); Hydrochlorothiazide– 6–15 hr; Olmesartan 13 hr.
TIME/ACTION PROFILE (antihypertensive effect)
|olmesartan PO||within 1 wk||2 wk||24 hr|
|amlodipine PO||unknown||6–9 hr||24 hr|
|hydrochlorothiazide PO||3–4 days||7–14 days||24 hr|
- Systolic BP <90 mm Hg.
Use Cautiously in:
- Severe hepatic impairment (dosage reduction recommended)
- Aortic stenosis
- History of HF
- OB: Lactation: Pedi: Safety not established
- Geri: Dose reduction recommended; ↑ risk of hypotension.
- Hypersensitivity (cross-sensitivity with other thiazides or sulfonamides may exist)
- Some products contain tartrazine and should be avoided in patients with known intolerance
Use Cautiously in:
- Renal or hepatic impairment
- OB: Jaundice or thrombocytopenia may be seen in the newborn.
- Bilateral renal artery stenosis
- OB: Can cause injury or death of fetus – if pregnancy occurs, discontinue immediately
- Lactation: Discontinue olmesartan or provide formula.
Use Cautiously in:
- Volume- or salt-depleted patients or patients receiving high doses of diuretics (correct deficits before initiating therapy or initiate at lower doses)
- Black patients (may not be as effective)
- Impaired renal function due to primary renal disease or HF (may worsen renal function)
- Patients with childbearing potential
- Pedi: Children <6 yr (safety not established).
Adverse Reactions/Side Effects
CNS: headache, dizziness, fatigue
CV: peripheral edema, angina, bradycardia, hypotension, palpitations
GI: gingival hyperplasia, nausea
CNS: dizziness, drowsiness, lethargy, weakness
GI: anorexia, cramping, hepatitis, nausea, vomiting
Derm: photosensitivity, rashes
F and E: hypokalemia, dehydration, hypercalcemia, hypochloremic alkalosis, hypomagnesemia, hyponatremia, hypophosphatemia, hypovolemia
Hemat: blood dyscrasias
Metabolic: hyperuricemia, hypercholesterolemia
MS: muscle cramps
F and E: hyperkalemia
GU: impaired renal function
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Additive hypotension may occur when used concurrently with fentanyl, other antihypertensives, nitrates, acute ingestion of alcohol, or quinidine.
- Antihypertensive effects may be ↓ by concurrent use of nonsteroidal anti-inflammatory agents.
- May ↑ risk of neurotoxicity with lithium.
Grapefruit juice ↑ serum levels and effect.
- Concurrent use with alcohol, barbiturates or opioids↑ risk of hypotension.
- Cholestyramine and colestipol ↓ absorption.
- Concurrent use of corticosteroids or adrenocorticotropin hormone (ACTH) ↑ risk of electrolyte depletion, including hypokalemia.
- ↑ lithium levels and the risk of toxicity; avoid concurrent use.
- NSAIDs may ↓ antihypertensive effectiveness.
- Additive hypotension with other antihypertensives .
- Excessive hypotension may occur with concurrent use of diuretics.
- Antihypertensive effect may be blunted by NSAIDs.
- ↑ risk of hyperkalemia with concurrent use of potassium supplements,potassium-containing salt substitutes,angiotensin-converting enzyme inhibitors, or potassium-sparing diuretics.
PO: (Adults) Initiate at equivalent doses of current single agents; may be increased every two weeks, increasing one component at a time to a maximum of olmesartan 40 mg/ amlodipine 10 mg/ hydrochlorothiazide 25 mg once daily.
Tablets: olmesartan 20 mg /amlodipine 5 mg/hydrochlorothiazide 12.5 mg, olmesartan 40 mg/ amlodipine 5 mg/hydrochlorothiazide 12.5 mg, olmesartan 40 mg/amlodipine 5 mg/hydrochlorothiazide 25 mg, olmesartan 40 mg/amlodipine 10 mg/hydrochlorothiazide 12.5 mg, olmesartan 40 mg/amlodipine 10 mg/hydrochlorothiazide 25 mg
- Assess BP (sitting, lying, standing) and pulse periodically during therapy.
- Monitor frequency of prescription refills to determine adherence to therapy.
- Assess patient for signs of angioedema (dyspnea, facial swelling). May rarely cause angioedema.
Lab Test Considerations: Monitor serum electrolytes and glucose periodically during therapy. May cause hypokalemia, hypomagnesemia, hyperglycemia, metabolic acidosis, dilutional hyponatremia, ↓ urinary calcium excretion, and hyperuricemia.Monitor renal function. May cause ↑ BUN and serum creatinine.May rarely cause slight ↓ in hemoglobin and hematocrit.
- May cause ↑ hepatic enzymes, cholesterol, and triglycerides.
- Correct volume depletion, if possible, before initiation of therapy.
- PO: Administer without regard to food.
- Emphasize the importance of continuing to take as directed, even if feeling well. Take missed doses as soon as remembered if not almost before next dose; do not double doses. Medication controls but does not cure hypertension. Instruct patient to take medication at the same time each day. Warn patient not to discontinue therapy unless directed by health care professional.
- Caution patient to avoid salt substitutes containing potassium or foods containing high levels of potassium or sodium unless directed by health care professional. See food sources for specific nutrients.
- Encourage patient to comply with additional interventions for hypertension (weight reduction, low-sodium diet, smoking cessation, moderation of alcohol consumption, regular exercise, and stress management). Medication controls but does not cure hypertension.
- Instruct patient and family on proper technique for monitoring BP. Advise them to check BP at least weekly and to report significant changes.
- May cause light-headedness, especially during first days of therapy. Advise patient to notify health care professional if light-headedness occurs; if syncope occurs discontinue until health care professional has been consulted. Caution patient to avoid sudden position changes to decrease orthostatic hypotension. Use of alcohol, standing for long periods, exercising, and hot weather may increase orthostatic hypotension.
- May cause dizziness. Caution patient to avoid driving and other activities requiring alertness until response to medication is known.
- Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to avoid concurrent use of Rx, OTC, and herbal products, especially NSAIDs and cough, cold, or allergy medications, without consulting health care professional.
- Instruct patient to notify health care professional of medication regimen before treatment or surgery.
- Instruct patient to notify health care professional if swelling of face, eyes, lips, or tongue, if difficulty swallowing or breathing, dry mouth, thirst, weakness, tiredness or sleepiness, restlessness, confusion, seizures, muscle pain or cramps, muscle tiredness, dizziness or fainting, low or no urine output, fast heartbeat, nausea or vomiting occur.
- Emphasize the importance of follow-up exams to evaluate effectiveness of medication.
- Advise women of childbearing age to use contraception and notify health care professional immediately if pregnancy is planned or suspected, or if breastfeeding.
↓ in BP without excessive side effects.
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