Lisinopril

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Contents

[edit] BRAND NAMES

[edit] STRUCTURE

Lisinopril.jpg

[edit] MECHANISM OF ACTION

Lisinopril is an ACE inhibitor. (Angiotensin Converting Enzyme Inhibitor) ACE inhibitors acts by:

  • Inhibiting the formation of angiotensin II from the inactive angiotensin I. Angiotensin II is a potent vasoconstrictor that leads to increased blood pressure.
  • ACE catalyses the breakdown of bradykinin (a powerful vasodilator). Therefore, ACE inhibitors, by inhibiting bradykinin metabolism, increase bradykinin levels, which can contribute to the vasodilator activity
  • Angiotensin II promotes aldosterone release which normally acts to retain sodium and water, therefore ACE inhibitors promote renal excretion of sodium and water (natriuretic and diuretic effects) by blocking angiotensin II stimulation of aldosterone secretion.

Upon multiple dosing, lisinopril exhibits an effective half-life of accumulation of 12 hours

[edit] INDICATIONS

  • Treatment of hypertension, alone or in combination with other antihypertensive agents, especially thiazide-like diuretics. (ACE inhibitors have an effect on blood pressure that is less in black patients than in non-blacks)
  • Adjunctive therapy in the management of heart failure in patients who are not responding adequately to diuretics and digitalis.
  • Treatment of hemodynamically stable patients within 24 hours of acute myocardial infarction, to improve survival.

[edit] DOSAGE

  • Hypertension: The recommended initial dose in patients not on diuretics is 10 mg once a day. Dosage should be adjusted according to blood pressure response. The usual dosage range is 20-40 mg/day administered in a single dose. in some patients, the antihypertensive effect may diminish toward the end of the dosing interval. In such patients, an increase in dosage should be considered.
  • Heart failure: The recommended initial dose is 5 mg once a day. Maintenance dose is 5-20 mg once a day. Dosage should be increased, over a several week period.
  • Acute Myocardial Infarction: In hemodynamically stable patients within 24 hours of the onset of symptoms of acute myocardial infarction, the first dose of Lisinopril is 5 mg given orally, followed by 5 mg after 24 hours, 10 mg after 48 hours and then 10 mg once daily. Dosing should continue for six weeks. Patients should receive, as appropriate, the standard recommended treatments such as thrombolytics, aspirin and betablockers. Patients with a low systolic blood pressure (less than or equal to 120 mmHg) when treatment is started or during the first 3 days after the infarct should be given a lower 2.5 mg oral dose of Lisinopril. If hypotension occurs (systolic blood pressure less than or equal to 100 mmHg) a daily maintenance dose of 5 mg may be given with temporary reductions to 2.5 mg if needed. If prolonged hypotension occurs (systolic blood pressure less than 90 mmHg for more than 1 hour) Lisinopril should be withdrawn.

Lisinopril absorption is not influenced by the presence of food in the gastrointestinal tract

[edit] CONTRAINDICATIONS

  • Hypersensitivity to Lisinopril
  • 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

[edit] PRECAUTIONS

[edit] INTERACTIONS

  • Patients on diuretics may experience an excessive reduction of blood pressure.
  • Concomitant administration of ACE inhibitors and antidiabetic medicines (insulins, oral hypoglycemic agents) may cause an increased blood glucose-lowering effect with risk of hypoglycemia.
  • 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 may have an additive effect on potassium retention, resulting in hyperkalemia.
  • Aliskiren: Dual blockade of the renin-angiotensin-aldosterone system like taking an ACE inhibitor plus a direct renin inhibitors (Aliskiren) is associated with increased risks of hypotension, syncope, hyperkalemia, and changes in renal function (including acute renal failure) compared to monotherapy.
  • Lithium toxicity has been reported when used in combination with ACE inhibitors.

[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, Lisinopril 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, hypotension, fatigue, upper respiratory infection, headache and weakness. GI disturbances include nausea, vomiting, and diarrhea.

  • Risk of hyperkalaemia due to potassium retention (rarely and especially in patients with renal dysfunction)
  • Angioedema (rare but potentially fatal).
  • Skin rashes (very rare)

[edit] RELATED LINKS

ACE INHIBITORS: Mechanism of Action, Indications and Side Effects

[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)