Prepared and Presented by Clinical pharmacist Dr. Alan R. Mohammed Pharmacy Practice Experience I Drugs Used In Cardiovascular Diseases Part Two For 4th Year Students/College of Pharmacy Prepared and Presented by Clinical pharmacist Dr. Alan R. Mohammed

Contents Angiotensin Converting Enzyme Inhibitors: 1- Lisinopril 2- Ramipril 3- Benzepril Angiotensin II receptor blocker: 1- Valsartan 2- Irbesartan

Learning Outcomes Understand the indications, dosage forms, doses, cautions, contraindications, and side effects of commonly used drugs in cardiovascular disease. Demonstrate effective patient counseling abilities. Understand the mechanisms of action of Angiotensin Converting Enzyme Inhibitors and angiotensin receptor blockers.

Angiotensin Converting Enzyme Inhibitors 1- Inhibits the enzyme ACE, thereby decreases the plasma concentration of angiotensin II. 2- Funcions of Angiotensin II are: - potent vasoconstrictor (both arterioles and venules) - degrade bradykinin - enhance aldosterone secretion 3- Therapeutic effects include: - decrease peripheral arterial resistance. - decrease blood pressure.

Angiotensin Converting Enzyme Inhibitors - decrease after and pre-load - decrease pulmonary vascular resistance. - increase cardiac output (in HF) - increase exercise tolerance - decrease cardiac and vascular remodeling 4- Except for captopril and lisinopril, the other ACE-I are prodrugs.

Lisinopril Brand name: Zestril Generic name: Lisinopril Dosage forms: Tablets (2.5, 5, 10, 20, 30, 40 mg), Oral solution (1 mg/ml). Indications & Doses: 1- Acute myocardial infarction: 2.5-10 mg/day 2- Hypertension: 5-40 mg/day, max. 80 mg/d 3- Heart Failure: 5-40 mg/day 4- Diabetic nephropathy: 5-40 mg/day

Lisinopril (Cont.) Cautions: Renal impairment, DM, potassium sparing diuretics, severe aortic stenosis, collagen vascular disease, hypertrophic cardiomyopathy. Contraindication: Hypersensitivity, Angioedema (hereditary, idiopathic, drug induced), concomitant use with sacubitril/valsartan, concomitant use with aliskiren in patients with DM, renal impairment., pregnancy. Side Effects: Dizziness, cough, hyperkalemia, angioedema, headache diarrhea, etc. Drug Interaction: NSAIDs (↓effects), pregabalin (↑toxicity), Insulin (↑effect), tadalafil (↑effect), etc.

Lisinopril (Cont.) Patient Counseling and other information: 1- In case of MI if the systolic BP<90 mm Hg for more than 1 h, discontinue. 2- In case of Hypertension and the patient on diuretic, either stop diuretic for 2-3 days before initiating the ACE-I or use reduced dose with close monitoring. 3- Use without regard to meal. 4- Tablets can be crushed, or compounding in oral suspention. 5- Go to emergency hospital if you suffer from swelling in face, lips, tongue, or throat.

Ramipril Brand name: Altace,Tritace Generic name: Ramipril Dosage forms: Capsules (1.25, 2.5, 5, 10 mg) Indications & Doses: 1- Stroke/MI prevention: 2.5-10 mg/day 2- Hypertension: 1.25-20 mg/12-24 hours 3- Heart Failure (post MI): 1.25-5 mg/12 hours 4- Diabetic nephropathy: 1.25-20 mg/day

Ramipril (Cont.) Cautions: Hypovolemia, hyponatremia, renal artery stenosis, renal impairement, DM, etc. Contraindication: Hypersensitivity, concomitant use with sacubitril/valsartan, concomitant use with aliskiren in patients with DM, renal impairment., pregnancy. Side Effects: Cough, Hypotension, nausea, vertigo, angioedema, headache diarrhea, etc. Drug Interaction: NSAIDs (↓effects), pregabalin (↑toxicity), Insulin (↑effect), tadalafil (↑effect), etc.

Ramipril (Cont.) Patient Counseling and other information: 1- Needs weeks before full effects. 2- If once daily dosing does not control the BP until the end of the day, either increase the dose or give it every 12 hours. 3- Abrupt discontinuance not associated with rapid increase in BP. 4- Capsules can be opened and sprinkled on applesauce or mixed with water or apple juice. 5- Pregnancy category D 6- Take without regard to food

Benazepril Brand name: Lotensin Generic name: Benazepril Dosage forms: Tablets (5, 10, 20, 40 mg) Indications & Doses: 1- Hypertension: 5-40 mg/12-24 hours 2- Nephropathy (nondiabetic): 10-20 mg/d

Benazepril (Cont.) Cautions: Hypovolemia, hyponatremia, renal artery stenosis, renal impairement, DM, etc. Contraindication: Hypersensitivity, concomitant use with sacubitril/valsartan, concomitant use with aliskiren in patients with DM, renal impairment., pregnancy, Angioedema (hereditary, idiopathic) Side Effects: Cough, , headache, dizziness, fatigue, nausea, angioedema, etc. Drug Interaction: NSAIDs (↓effects), pregabalin (↑toxicity), Insulin (↑effect), tadalafil (↑effect), etc.

Benazepril (Cont.) Patient Counseling and other information: 1- No sexual dysfunction side effect. 2- Good choice in hyperlipidaemia patients. 3- Need weeks before full effects. 4- Abrupt discontinuance not associated with rapid increase in BP. 5- Pregnancy category D 6- take without regard to food

Valsartan Brand name: Diovan Generic name: Valsartan Dosage forms: Tablets (40, 80, 160, 320 mg) Indications & Doses: 1- Hypertension: 80-320 mg/d 2- Heart failure: 40-160 mg/12h 3- Post MI therapy in left ventricular Dysfunction: 20-160 mg/12 hours

Valsartan (Cont.) Cautions: Hereditary angioedema, volume depletion, severe congestive heart failure, surgery, anesthesia, etc. Contraindication: Hypersensitivity, concomitant use with aliskiren in patients with DM. Side Effects: Dizziness, , ↑ BUN, hyperkalemia, fatigue, viral infection, etc. Drug Interaction: NSAIDs (↓effects), ACE-I (↑effects), Insulin (↑effect), sildenafil (↑effect), etc.

Valsartan (Cont.) Patient Counseling and other information: 1- Maximum blood pressure reduction after 4 weeks. 2- Pregnancy category D

Irbesartan Brand name: Avapro Generic name: Irbesartan Dosage forms: Tablets (75, 150, 300 mg) Indications & Doses: 1- Hypertension: 75-300 mg/d 2- Nephropathy in type 2 DM: 75-300 mg/d

Irbesartan (Cont.) Cautions: Renal impairment, hepatic impairment, volume depletion, severe congestive heart failure, angioedema, etc. Contraindication: Hypersensitivity, concomitant use with aliskiren in patients with DM. Side Effects: Dizziness, , Upper respiratory tract infection, hyperkalemia, orthostatic hypotension, diarrhea, etc. Drug Interaction: NSAIDs (↓effects), ACE-I (↑effects), Insulin (↑effect), tadalafil (↑effect), etc.

Irbesartan (Cont.) Patient Counseling and other information: 1- Take irbesartan without regard to meal. 2- Do not need dosage adjustment in mild to severe renal impairment (unless hypovolumic).

Questions

References Mancano MA, Gallagher JC. Frequently Prescribed Medications; Drugs You Need to Know. 2012. Jones & Bartlett Learning (ISBN: 978-0-7637-8177-0) www.medscape.com Hochadel M. Mosby’s drug reference for health professions. 4th edition, 2014. Elsevier, USA. (ISBN: 978-0-323-07737-8) British National Formulary (BNF). Trevor AJ, Katzung BG, Hall MK. Pharmacology: examination and board review. 11th edition, 2015. Mc Graw Hill Education Lange, USA.

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