Aliskiren

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Contents

[edit] BRAND NAMES

[edit] STRUCTURE

Aliskiren.jpg

[edit] MECHANISM OF ACTION

Renin is secreted by the kidney in response to decreases in blood volume and renal perfusion. Renin cleaves angiotensinogen to form the inactive decapeptide angiotensin I. Angiotensin I is converted to the active octapeptide angiotensin II by angiotensin-converting enzyme (ACE) and non-ACE pathways.

Angiotensin II is a powerful vasoconstrictor and promotes aldosterone release which normally acts to retain sodium and water. Together, these effects increase blood pressure.

Aliskiren, is a renin inhibitor. By inhibiting the enzyme renin, aliskiren inhibits the Renin Angiotensin Aldosterone System (RAAS) at the point of activation, blocking the conversion of angiotensinogen to angiotensin I and decreasing levels of angiotensin I and angiotensin II. This causes vasodilation, so that the blood pressure drops. This may reduce the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.

Whereas other agents that inhibit the RAAS (ACEI and angiotensin II receptor blockers (ARB)) cause a compensatory rise in plasma renin activity (PRA), treatment with aliskiren decreases PRA in hypertensive patients by approximately 50 to 80%.

[edit] INDICATIONS

Treatment of hypertension, to lower blood pressure. Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions.

[edit] DOSAGE

The recommended dose is 150 mg once a day, with a light meal. The dose may be increased to 300 mg once a day in patients whose blood pressure is not adequately controlled. The antihypertensive effect of a given dose is substantially attained (85-90%) by 2 weeks.

Aliskiren may be taken alone or in combination with other medicines for hypertension, with the exception of Angiotensin Converting Enzyme (ACE) Inhibitors(Benazepril, Captopril, Cilazapril, Delapril, Enalapril, Fosinopril, Lisinopril,Moexipril, Perindopril, Quinapril, Ramipril, Trandolapril, Zofenopril) or Angiotensin II receptor antagonists (Azilsartan, Candesartan, Eprosartan, Irbesartan, Losartan, Olmesartan, Telmisartan, Valsartan) in patients with diabetes, or moderate or severe kidney impairment.

[edit] DOSAGE FORMS AND STRENGTHS

Tablets: 150 mg, 300 mg

[edit] CONTRAINDICATIONS

[edit] WARNINGS AND PRECAUTIONS

  • Avoid concomitant use with Angiotensin II receptor antagonists or ACE inhibitors in patients with renal impairment (GFR<60 mL/min)
  • Anaphylactic Reactions and Head and Neck Angioedema: Discontinue use of Tekturna and monitor until signs and symptoms resolve.
  • Hypotension in volume and/or salt depleted patients: Correct imbalances before initiating therapy.
  • Impaired renal function: Monitor serum creatinine periodically.
  • Hyperkalemia: Monitor potassium levels periodically

[edit] INTERACTIONS

  • Cyclosporine: Avoid concomitant use
  • Itraconazole: Avoid concomitant use
  • NSAIDs use may lead to increased risk of renal impairment and loss of antihypertensive effect

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category D (US). Use of drugs that act on the renin-angiotensin system during the second and third trimesters of pregnancy reduces fetal renal function and increases fetal and neonatal morbidity and death. Resulting oligohydramnios can be associated with fetal lung hypoplasia and skeletal deformations. Potential neonatal adverse effects include skull hypoplasia, anuria, hypotension, renal failure, and death. When pregnancy is detected, discontinue Aliskiren as soon as possible.
  • Nursing Mothers: It is not known whether aliskiren is excreted in human breast milk. Aliskiren was secreted in the milk of lactating rats. Because of the potential for adverse effects on the nursing infant, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother.

[edit] SIDE EFFECTS

Most common adverse reaction: diarrhea (incidence 2.3%)

[edit] RELATED LINKS

[edit] BIBLIOGRAPHY

[edit] REFERENCES

Antihypertensives
ACE inhibitors Benazepril (Lotensin)   Captopril (Capoten)   Cilazapril   Delapril   Enalapril (Renitec, Vasotec)   Fosinopril (Monopril)  Lisinopril (Prinivil, Zestril)   Moexipril (Univasc)  Perindopril (Aceon)  Quinapril (Accupril)  Ramipril (Altace, Triatec)   Trandolapril (Mavik)  Zofenopril (Bifril, Zopranol)
Angiotensin II receptor antagonist Azilsartan (Edarbi)   Candesartan (Atacand)   Eprosartan (Teveten)   Irbesartan (Aprovel, Avapro, Karvea)   Losartan (Cozaar)   Olmesartan (Benicar, Olmetec)   Telmisartan (Micadis)   Valsartan (Diovan, Tareg)
Renin inhibitors Aliskiren (Rasilez, Tekturna)
Alpha-1 blockers Doxazosin (Cardura)   Prazosin (Minipress)   Terazosin (Hytrin)
Alpha-2 agonists (centrally acting) Clonidine (Oral route)   Clonidine (Transdermal) (Catapresan)   Guanfacine (Tenex)   Methyldopa (Aldomet)
Calcium channel blockers Dihydropyridines‎ Amlodipine (Norvasc)   Barnidipine (Vasexten)   Felodipine (Plendil)   Isradipine (Dynacirc)   Lacidipine (Lacipil, Motens)   Lercanidipine (Zanidip)   Manidipine   Nicardipine   Nifedipine (Adalat)   Nisoldipine   Nitrendipine
Benzothiazepine‎ Diltiazem (Cardizem, Taztia XT, Tiazac, Tildiem)
Phenylalkylamine‎ Gallopamil   Verapamil (Calan)
Beta blockers Beta1 selective (cardioselective) Acebutolol (Sectral)   Atenolol (Tenormin)   Betaxolol (Kerlon)   Bisoprolol (Concor)   Celiprolol (Cordiax)   Metoprolol (Betaloc, Lopressor, Toprol-XL)   Nebivolol (Bystolic, Lobivon, Nebilox)
Nonselective (Beta1 and Beta2 blockers) Oxprenolol (Trasitensin)   Propranolol (Inderal)   Timolol (Blocadren)
Nonselective (Beta1, Beta2 and Alpha1 blockers) Carvedilol (Dilatrend)   Labetalol (Trandate)
Beta blocker with intrinsic sympathomimetic activity (ISA) Acebutolol (Sectral)   Celiprolol (Cordiax)
Lipophilic Beta blockers Propranolol (Inderal)   Metoprolol (Betaloc, Lopressor, Toprol-XL)   Oxprenolol (Trasitensin)
Diuretics Carbonic anhydrase inhibitors Acetazolamide (Diamox)
Loop diuretics Bumetanide   Etacrynic acid   Furosemide (Lasix)   Piretanide   Torasemide (Demadex)
Thiazide diuretics Chlorothiazide (Diuril)   Hydrochlorothiazide (Esidrex)
Thiazide-like diuretics Chlortalidone (Hygroton)   Indapamide (Lozol, Lozide)   Metolazone
Potassium-sparing diuretics Epithelial sodium channel blockers: Amiloride (Midamor)   Triamterene (Dyrenium)
Aldosterone receptor antagonists: Potassium canrenoate   Eplerenone (Inspra)   Spironolactone (Aldactone)
Osmotic diuretics Mannitol
Combination therapy Amiloride/Hydrochlorothiazide (Moduretic)   Spironolactone/Hydrochlorothiazide (Aldactazide)