Enalapril/Hydrochlorothiazide

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Contents

[edit] BRAND NAMES

[edit] STRUCTURE

[edit] MECHANISM OF ACTION

Enalapril, an angiotensin-converting enzyme inhibitor (ACE inhibitor), is a prodrug which, when hydrolyzed to active enalaprilat, competes with angiotensin I for binding at the angiotensin-converting enzyme, blocking the conversion of angiotensin I to angiotensin II.

As angiotensin II is a vasoconstrictor which stimulates aldosterone secretion, the action of enalaprilat leads to diminished vasopressor activity and decreased aldosterone secretion.

Hydrochlorothiazide is a thiazide diuretic, it acts on the distal convoluted tubule by inhibiting the sodium-chloride symporter. thus, it reduces NaCl reabsorption, leading to a retention of water in the urine. This symporter reabsorbs about 5% of filtered sodium. Hydrochlorothiazide is less efficacious than loop diuretics in producing diuresis. Nevertheless, it is sufficiently powerful to satisfy most therapeutic needs requiring a diuretic, making it one of the mostly used diuretics. Hydrochlorothiazide enhance also Ca++ reabsorption in the distal convoluted tubule by inhibiting Na+ entry and thus enhancing the activity of Na+-Ca++ exchanger in the basolateral membrane of epithelial cells. After oral administration of hydrochlorothiazide, diuresis begins within 2 hours, peaks in about 4 hours and lasts about 6 to 12 hours

[edit] INDICATIONS

Treatment of hypertension. Lowering blood pressure lowers the risk of fatal and non-fatal cardiovascular events, primarily strokes and myocardial infarctions. ACE inhibitors have an effect on blood pressure that is less in black patients than in non-blacks

[edit] DOSAGE

A patient whose blood pressure is not adequately controlled with either Enalapril or Hydrochlorothiazide monotherapy may be switched to Enalapril/hydrochlorothiazide 20mg/6mg or Enalapril/hydrochlorothiazide 20mg/12.5mg. In hypertension, the usual dosage is one tablet (20mg/6mg or 20mg/12.5mg), administered once daily.

[edit] CONTRAINDICATIONS

  • Hypersensitivity to Enalapril, to Hydrochlorothiazide or to other sulfonamide-derived drugs.
  • Patients with a history of angioedema related to previous treatment with an angiotensin converting enzyme inhibitor and in patients with hereditary or idiopathic angioedema.
  • Coadministration of aliskiren in patients with diabetes.
  • Pregnancy and lactation
  • Anuria

[edit] PRECAUTIONS

[edit] INTERACTIONS

  • Patients on diuretics may experience an excessive reduction of blood pressure.
  • Caution is advised if non steroidal antiinflammatory drugs NSAIDs are prescribed with ACE inhibitors. (Concomitant use of NSAIDS may result in decreased ACE inhibitor effectiveness). In some patients with compromised renal function who are being treated with NSAIDS, the co-administration of ACE inhibitors may result in further deterioration of renal function. Cases of acute renal failure, usually reversible, have also been reported.
  • Potassium-sparing diuretics (e.g., spironolactone, eplerenone, triamterene, or amiloride), potassium supplements, or potassium-containing salt substitutes may have an additive effect on potassium retention, resulting in hyperkalemia.

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category D (US). ACE inhibitors can cause fetal and neonatal morbidity and mortality when administered to pregnant women (espacially in the second and third trimester of pregnancy). When pregnancy is detected, Enalapril/Hydrochlorothiazide should be discontinued as soon as possible.

[edit] SIDE EFFECTS

ACE inhibitors are usually well tolerated. Possible side effects include: Dry irritant cough attributable to accumulation of bradykinin, dizziness, fatigue, headache, blurred vision and weakness. GI disturbances include nausea, vomiting, diarrhea, constipation, and abnormal taste.

  • First dose hypotension (Rare in essential hypertension)
  • Risk of hyperkalemia due to potassium retention (rarely and especially in patients with renal dysfunction)
  • Angioedema (rare but potentially fatal; ACE inhibitors cause a higher rate of angioedema in black than in non-black patients). Notify physician if swelling of face, lips, tongue, or difficulty breathing occurs.
  • Skin rashes (very rare)

[edit] RELATED LINKS

[edit] REFERENCES

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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)