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Think of:

Think of:. 1. Antihypertensives. 2. Antiarrhythmics. 3. Antianginal drugs. 4. Drugs used in Myocardial infarction. 5. Drugs used in Heart failure. 6. Antihyperlipidemic drugs. ANTIHYPERTENSIVES. 1. Diuretics. 2. ACEI (Angiotensin Converting Enzyme Inhibitors).

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  1. Think of: 1. Antihypertensives 2. Antiarrhythmics 3. Antianginal drugs 4. Drugs used in Myocardial infarction 5. Drugs used in Heart failure 6. Antihyperlipidemic drugs

  2. ANTIHYPERTENSIVES 1. Diuretics 2. ACEI (Angiotensin Converting Enzyme Inhibitors) 3. ARB (Angiotensin Receptors Blockers) 4. BB (Beta Blockers) 5. CCB (Calcium Channels Blockers) 6. Alpha 2 agonist 7. Adrenergic Neuronal Blocking Drugs 8. Alpha Blockers 9. Direct Acting Vasodilators

  3. Which classes of Antihypertensive drugs have proven to decrease mortalilty from Heart diseases? Buzz word: 1. Beta Blockers 2. ACE inhibitors 3. Thiazides Diuretics

  4. What's Hypertension? Elevated systolic, diastolic blood pressure or both. What's Normal blood pressure? 120 Systolic = 80 Diastolic

  5. When Antihypertensives are indicated? Stage I Hypertension: 140-159 Systolic = 90-99 Diastolic Recommended: Thiazide diuretic Consider: ACEI, ARB, BB, or CCB

  6. Stage II hypertension: >160 Systolic = >100 Diastolic Recommended: Two-drug Combination Thiazide diuretics + ACEI or Thiazide diuretics + ARB + BB + CCB

  7. How about Prehypertension? 120-139 Systolic = 80-89 Diastolic Recommended: Life style modification Weight reduction Moderate alcohol intake Regular physical activity Reduction of sodium intake Smoking cessation

  8. How about if the patient presents with: Hypertension + Medical condition = Hypertension + (Compelling indications) 1. Hypertension in patient with Angina Pectoris Buzz word: BB, CCB 2. Hypertension in patient with BPH: Buzz word: alpha blocker 3. Hypertension in a diabetic patient: Buzz word: ACE inhibitors, ARB

  9. 4. Hypertension in a patient with Heart failure: Buzz word: ACE inhibitors, ARB, BB 5. Hypertension in patient after having an MI: Buzz word: BB 6. Hypertension in a patient with Hyperlipidemia: Buzz word: Alpha blocker, CCB

  10. Resistant or Difficult to control Hypertension (2006) Hypertension that is not responding to combination therapy For a Patient with refractory hypertension, which combination of classes will reduce the systolic BP the most? A. Adding an alpha blocker to a beta blocker B. Adding an ARB to an ACE inhibitor C. Adding spironolactone to a thiazide diuretic D. Adding a dihydropyridine CCB to a nonhydropyridine CCB

  11. Which one of the following activities can have the greatest effect on a blood-pressure reading? A. The consumption of three alcoholic drinks 12 h before the measurement B. The drinking of a cup of coffee 1h before the measurement C. The smoking of a cigarette 15 minutes before the measurement D. The use of a cuff that is one size too small for the patient

  12. Mechanism affecting Blood Pressure BP = CO X TPR CO = SV X HR BP = SV X HR X TPR 1. Increase SV: edema, increase renin-angiotensin activity Rx Buzz word: Diuretics, ACE inhibitors 2. Increase HR: due to decrease vagal tone and increase sympathetic tone Rx Buzz word: BB 3. Increase peripheral resistance: Increase sympathetic tone Rx Buzz word: alpha 2 agonist alpha blockers CCB Direct acting vasodilators

  13. 1. Diuretics Types of Diuretics 1. Thiazides diuretics 2. Loop diuretics 3. Osmotic diuretics 4. Carbonic anhydrase inhibitors 5. Potassium-Sparing diuretics

  14. Nephron Anatomy Site of action of diuretics Secretion Reabsorption Filtration CA inhibitors Thiazides Osmotic K+ sparing Loop Urine (Henle) Excretion

  15. 1. Thiazides Diuretics Buzz word: Chlorothiazide Hydrochlorothiazide Chlorthalidone Indapamide Metolazone MOA: Inhibit Na/Cl cotransport Increase excretion: Na+, K+, Cl-, Mg++, HCO3 decrease excretion: Ca++, uric acid Side effects: Hyponatremia, hypokalemia, hypomagnesia, Metabolic Alkalosis Hypercalcemia, hyperuricemia Increase plasma cholesterol and TGs (except indapamide)

  16. 2. Loop Diuretics Buzz word: Furosemide Bumetanide Torsemide Ethacrynic acid MOA: Inhibit the Na+/K+ dichloride cotransport system Increase excretion: Na+, K+, Mg++, Cl, HCO3, Ca++ Side effects: Hyponatremia, hypokalemia, hypomagnesia Metabolic alkalosis, Hypocalcemia Buzz word: Ototoxicity Drug Interactions: loop diuretic + Antibiotic (aminoglycosides) Increased risk for Ototoxicity

  17. 3. Osmotic Diuretics Buzz word: Mannitol Urea MOA: Increase the osmotic pressure in the proximal tubule inhibition of reabsorption of water and electrolytes Indications Buzz word: Increase intracranial and intraocular pressure Acute renal failure

  18. 4. Carbonic anhydraze inhibitors Buzz word: Acetazolamide Dorzolamide MOA: increase excretion of Na+, K+, and HCO3 Side effects: Hyperchloremic metabolic acidosis, hypokalemia Indications Buzz word: Rx of Glaucoma Rx of overdose of acidic drugs Why?

  19. 5. K+ Sparing Diuretics Buzz word: Spironolactone (Aldosterone Antagonist) Amiloride Block Na+ reabsorption They spare K+ Triamterene Side Effects: Hyperkalemia, metabolic acidosis Nephrolithiasis (triamterene) decrease libido (spironolactone) Indications Buzz word: Spironolactone + ACE inhibitors increased survival in heart failure Spironolactone antiandrogenic effect: Rx of Hirsutism Amiloride used for Rx of Nephrogenic DI caused by lithium What drug is used for Rx of Nephrogenic DI in general?

  20. 2. ACE inhibitors Angiotensin Converting Enzyme Inhibitors Buzz word: Drugs ending with "Pril" Captopril Enalapril IV for hypertensive emergency Lisinopril Fosinopril no dose adjustment in renal failure

  21. Mechanism of action: Inhibit angiotensin converting enzyme inhibit Angiotensin I Angiotensin II ACE (Potent vasoconstrictor) inhibit Bradykinin Inactivate compound ACE side effects: vasodilation via EDRF dry cough

  22. Buzz word: ACE inhibitors are the best for Hypertension in DM: Why? Diabetic patients tend to get nephropathy ACE inhibitors slow down renal damage Buzz word: ACE inhibitors may produce hyperkalemia and acute renal failure (proteinuria) as adverse effects Buzz word(2006): ACE inhibitors and Pregnancy ACE inhibitors are contraindicated in 2nd and 3rd trimester Fetopathy Oligohydramnios, IUGR, hypocalvaria, Renal failure.

  23. Buzz word (2006) Congenital malformation of which systems are the most frequent among children exposed to ACE inhibitors during first trimester? A. Cardiac and CNS B. Hematological C.Musculoskeletal D. Pulmonary

  24. 3. ARB (Angiotensin II Receptors Blockers) Buzz word: Drugs ending in "sartan" Losartan Valsartan Buzz word: No dry cough Candesartan Irbesartan They block angiotensin II (type 1) reduce vasoconstriction AT-1 receptors Adverse reactions: Acute renal failure Contraindicated in Pregnancy

  25. 4. BB (Beta blockers) Buzz word: drugs ending in "olol" Propranolol Atenolol Pindolol Labetalol Carvedilol Buzz word: White respond better than African American Safe in pregnancy

  26. Indications: 1. Coronary artery disease 2. Tachyarrhythmia 3. Migraine headaches 4. Anxiety Contraindications: Asthma, heart block Adverse effects: Bronchospasm, fatigue, glucose intolerance Cautions: 1. Mask signs of hypoglycemia 2. Abrupt withdrawal can cause hypotension Upregulation of # of receptors

  27. 5. CCB (Calcium Channel Blockers) Buzz word: Drugs ending in "dipine" Amlodipine the most commonly prescribed Nifedipine Isradipine Buzz word: Dihydropyridines (vascular tissues) Exception: Diltiazem Verapamil Buzz word: Nonhydropyridines (heart)

  28. MOA: block the L-type Ca++ channels Dihydropyridines Buzz word: Reflex tachycardia flushing, ankle edema Nondihydropyridines Buzz word: decrease cardiac contractility possible AV block Indications: Angina pectoris, peripheral vascular disease, tachyarrhythmia. Buzz word: Nimodipine is approved for acute subarachnoid hemorrahge prevents post hgic vasospasm African American and elderly respond well

  29. 6. Alpha 2 agonist Buzz word: Clonidine Mild to moderate Hypertension (patches cause less side effects) Side effects: Edema, rebound hypertension after sudden withdrawal Buzz word: alpha methyl dopa Mild to moderate hypertension side effects: +ve Coombs test: hemolytic anemia Safe in pregnancy and renal dysfunction

  30. 7. Adrenergic Neurononal Blocking Drugs Buzz word: Guanethidine Binds to storage vesicles and inhibit release of NE Side effects: Fluid retention Contraindicated with Antidepressants Buzz word: Reserpine Binds to storage vesicles and destroys them It causes depletion of NE, DA and serotonin Side effect Buzz word: Psychotic depression and suicide

  31. 8. Alpha blockers Buzz word: Prazocin - Doxazocin - Terazocin Lower blood pressure and used for BPH Side effects: First dose "Syncope", orthostatic hypotension Buzz word: Incontinence in women when coughing, sneezing or trying to lift a weight Why? alpha blockade effect on the bladder and sphincter

  32. 9. Direct acting Vasodilators Buzz word: Hydralazine Relaxes arteriolar smooth muscle Side effects: Reflex tachycardia, palpitations (use a BB) Buzz word: SLE like syndrome and hemolytic anemia Buzz word: Sodium Nitroprusside Dilate both resistance and capacitance vessels Long term side effects: accumulation of cyanide and thiocyanate Buzz word: Drug of choice for Rx of hypertensive crisis (IV)

  33. Buzz word: Minoxidil A prodrug which after sulfation appears to activate K+ channels Side effects: Hypertrichosis buzz word: Rogaine (Topically) for baldness Buzz word: Diazoxide Activates K+ channels causing relaxation of smooth muscle Side effects: Hyperglycemia (decrease insulin release from B cells) Hypertrichosis IV Rx of hypertensive emergencies Used to Rx insulinoma Buzz word: Sulfonylureas (oral hypoglycemic) work on the same type of K+ channel but close them

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