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ACE - Inhibitors
Angiotensin-converting enzyme (ACE) inhibitors are key medications for managing hypertension, heart failure, diabetic nephropathy, and myocardial infarction, primarily by reducing levels of angiotensin II and increasing bradykinin levels. They can have adverse effects like hypotension, hyperkalemia, cough, and renal impairment, necessitating caution in certain patients, such as those pregnant or with kidney issues. ACE inhibitors are generally well-tolerated and require careful monitoring, especially during initiation of therapy.
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ACE - Inhibitors
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- 2. Angiotensin – ConvertingEnzyme (ACE) Inhibitors • The ACE inhibitors are important drugs for treating Hypertension, Heart Failure Diabetic Nephropathy & Myocardial Infarction (MI) • Beneficial effects results largely from suppressing formation of Angiotensin-II
- 3. Mechanism of Action 1)Reducing levels of Angiotensin-II(through inhibition of ACE) ACE inhibitors can dilate Blood Vessels (Primarily Arterioles & to lesser extent the veins) Reduce Blood Volume (Through effects on the Kidney) Prevent or reverse Angiotensin II-mediated pathologic changes in the Heart & Blood Vessels
- 4. 2) Increasing levelsof Bradykinin (through Inhibition of Kinase II ) Elevation of Bradykinin levels promotes Vasodilation Bradykinin promotes Vasodilation by stimulating production of Prostaglandins and Nitirc Oxide)
- 5. Adverse Effects • Likebeneficial effects, certain Adverse effects result from inhibiting ACE/KINASE II. • Inhibition of ACE can cause : Hypotension Hyperkalemia Renal Failure Fetal Injury • Inhibition of KINASE II, with resultant accumulation of Bradykinin, can cause Cough & Angioedema.
- 6. Pharmacokinetics • All ACEinhibitors are administered orally , except Enalapril which is given IV • Except Captopril & Moexipril, all oral ACE inhibitors can be administered with food. • Except Captopril, all ACE inhibitors have prolonged half-lives,& can be administered just once or twice a day. • Captopril is administered 2 or 3 times a day. • All ACE inhibitors are excreted by the KIDNEYS.As a result, nearly all can accumulate to dangerous levels in patients with Kidney disease, & hence dosages must be reduced in these patients.
- 7. Generic Name BENAZEPRIL CAPTOPRIL ENALAPRIL FOSINOPRIL ENALAPRILAT Trade Name Lotensin Capoten Vasotec Monopril VasotecI.V Indications Hypertension Hypertension Heart Failure LVD after MI Diabetic Nephropathy Hypertension Heart Failure Asymptomatic LVD Hypertension Heart failure Hypertension Starting Dose 10 mg once/day 25 mg bid or tid 2.5 mg tid 12.5 mg tid 25 mg tid 5 mg once/day 2.5 mg bid 2.5 mg bid 10 mg once/day 10 mg once /day 1.25 mg every 6hr Maintenance Dose 20-40 mg/day 25-50 mg bid,tid 50-100 mg tid 50 mg tid 25 mg tid 10-40 mg/day 10-20 mg bid 10mg bid 20-40mg/day 20-40mg/day
- 8. LISINOPRIL MOEXIPRIL QUINAPRIL RAMIPRIL TRANDOPRIL Prinivil, Zestril Univasc Accupril Altace Mavik Hypertension Heart Failure AcuteMI Hypertension Hypertension Heart Failure Hypertension Heart failure Prevention of MI, stroke,& death in people at high risk for CVD Hypertension Heart Failure after MI LVD after MI 10 mg once/day 5 mg once/day 5 mg once/day 7.5mg once/day 10-20mg/day 5mg bid 2.5 mg once/day 2.5 mg bid 2.5 mg/day for 1 week 1 mg once/day 1 mg once/day 1 mg once/day 20-40mgonce/d 20-40mgonce/d 10mgonce/day 7.5-30 mg/day in 1 or 2 doses. 20-80mg/day 20-40mg bid 2.5-20mg/day 5mg bid 5mg once/day for 3 weeks. 2-4mg once/day 4mg once/day 4mg once/day
- 9. THERAPEUTIC USES ACE inhibitorsproduce Therapeutic effects in: HYPERTENSION HEART FAILURE MYOCARDIAL INFARCTION DIABETIC & NONDABETIC NEPHROPATHY PREVENTION OF MI DEATH IN HIGH CARDIOVASCULAR RISK PATIENTS
- 10. ADVERSE EFFECTS • ACEinhibitors are generally well tolerated. • Some adverse effects (e.g., First Dose Hypotension, Hyperkalemia) are due to reduction in Angiotensin II • Whereas others (Cough, Angioedema) are due to elevation of Bradykinin.
- 11. • First-Dose Hypotension •Cough • Hyperkalemia • Renal failure • Fetal Injury • Angioedema • Dysgeusia & Rash • Neutropenia
- 12. Nursing Implications ACE INHIBITORS Benazepril Captopril Enalapril Enalaprilat Fosinopril Lisinopril Moexipril Perindopril Quinapril
- 13. • Therapeutic goal Reduction of Blood Pressure in patients with Hypertension (all ACE inhibitors) Hemodynamic improvement in patients with Heartfailure (Captopril,Enalapril,Fosinopril,Lisinopril,Moexipril,Quinapril) Slowed progression of Diabetic Nephropathy (Captopril) Reduction of Mortality following acute MI (Lisnopril) Treatment of Heart Failure After MI (Ramipril, Transdolapril) Reduction of risk of MI,Stroke or Death from Cardiovascular causes in patients at high risk (Ramipril)
- 14. BASELINE DATA DetermineBlood Pressure & obtain a White Blood Cell Count & differential. IDENTIFYING HIGH-RISK PATIENTS ACE inhibitors are contraindicated during the Second & Third trimesters of pregnancy Patients with Bilateral Renal Artery Stenosis OR history of Hypersensitivity reactions (especially Angioedema) to ACE inhibitors. Exercise Caution in patients with salt or volume depletion, Renal Impairment or Collagen disease, those taking Potassium supplements, potasium-sparing diuretics or Lithium
- 15. ROUTES Oral : AllACE inhibitors (except enalarilat) Intravenous : Enalaprilat. Dosage & Administration Begin therapy with low doses & then gradually increase the dosage. Instruct patients to administer captopril & Moexipril at least 1 hour before Meals. All the other oral ACE inhibitors can be administered with food.
- 16. Monitor Therapeutic Effects Monitor Blood Pressure closely for 2 hours after the first dose and periodically thereafter. Obtain a White Blood Cell count & Differential count eevery 2 weeks for the first 3 months of therapy & periodically thereafter. HYPERTENSION - Monitor for reduced Blood Pressure 140/90mm Hg. HEART FAILURE - monitor for lessening f signs & symptoms (e.g., Dyspnea, Cyanosis, jugular vein distension, Edema),Diabetic Nephropathy- monitor for Proteinuria.
- 17. MINIMIZING ADVERSE EFFECTS First-DoseHypotension – Severe Hypotension occur with the first dose. Minimize Hypotension by 1) Withdrawing Diuretics 1 week before initiating ACE inhibitors 2) Using low initial doses 3) Monitor Blood pressure for 2 hours following the first dose. 4) Instruct patients to lie down if Hypotension develops. 5) Infuse Normal saline to restore Pressure.
- 18. COUGH Warn patientsabout the possibility of Persistent, dry, irritating, Non productive cough. It ma be necessary to discontinue the ACE inhibitor. HYPERKALEMIA ACE inhibitors may increase potassium levels. Instruct patients to avoid Potassium supplements and Potassium-containing salt substitutes unless prescribed by physician. Potassium – sparing diuretics must also be avoided.
- 19. Fetal Injury Warnpregnant women that ACE inhibiotrs taken during the Second & Third trimesters of pregnancy can cause fetal injury (Hypotension, Hyperkalemia, Skull Hypoplasia, Anuria, Reversible & Irreversible renal failure, Death) If the patient becomes pregnant, withdraw ACE inhibitors as soon as possible, reassure women ACE inhibitors do not represent the risk during first trimester. Closely monitor infants who have been exposed to ACE inhibitors during the second or third trimester for Hypotension, Oliguria & Hyperkalemia.
- 20. Angioedema This rare& potentially fatal reaction is characterized by giant wheals edema of the tongue, glottis & Pharynx. If Angioedema occurs, discontinue the ACE inhibitor and never use it again. Treat severe reactions with subcutaneous epinephrine. Renal Failure Renal failure is a risk for patients with bilateral renal artery stenosis or stenosis in the artery of a single kidney.ACE inhibitors are contraindicated to this people
- 21. Neutropenia (Mainly withCaptopril) Neutropenia poses a high risk of infection. Inform patient about daily signs of infection(Fever, Sore throat, Mouth sores) & instruct them to notify physicians if these occur. Obtain WBC & Differential count every 2 weeks during the first 3 months of therapy & periodically thereafter If neutropenia develops withdraw the drug immediately –(It should get normalized approximately of 2 weeks). Neutropenia is most likely in patients with renal impairment & collagen vascular disease.
- 22. Rash & Dysgeusia( Mainly with Captopril) Minimize these reactions by avoiding high doses. Instruct patients to notify the physician if rash or dysgeusia persist. If dysgeusia results in Anorexia & Weight loss,withdraw the drug. Rash & Dysgeusia resolve with cessation of treatment.
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