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  • 1. Cardiovascular DrugsCardiovascular Drugs Dra. Hena W. Alcantara
  • 2. The Cardiovascular SystemThe Cardiovascular System • Heart • Blood • Blood Vessels –Arteries –Veins –Capillaries
  • 3. The HeartThe Heart
  • 4. BloodBlood
  • 5. Blood VesselsBlood Vessels
  • 6. CirculationCirculation
  • 7. In simple terms…In simple terms… • The heart is a pump. • It pumps blood through a system of blood vessels that has a limited volume capacity. • An electric conduction system maintains regular rate and rhythm. • Myocardial cells require oxygen.
  • 8. MalfunctionsMalfunctions when the heart can no longer pump enough blood to meet the metabolic demands of the body HEART FAILURE when blood volume is great compared to the space available inside blood vessels HYPERTENSION
  • 9. MalfunctionsMalfunctions when the electrical conduction pathways malfunction ARRHYTHMIA the heart’s way of signaling that some of the cells are not getting enough oxygen ANGINA
  • 10. MalfunctionsMalfunctions when oxygen- starved areas of the heart begin dying MYOCARDIAL INFARCTION when you broke with someone…
  • 11. Cardiovascular DrugsCardiovascular Drugs
  • 12. Cardiovascular DrugsCardiovascular Drugs • Anti-hypertensives • Drugs for Heart Failure • Anti-anginal and Drugs for MI • Anti-arrhythmic Agents
  • 13. Anti-Hypertensive DrugsAnti-Hypertensive Drugs
  • 14. Physiology of BP RegulationPhysiology of BP Regulation • Hydraulic Equation: BP = CO x TPR
  • 15. Blood Pressure Heart Rate Low Blood Pressure Low Blood Volume Na+ depletion Angiotensin I Sympathetic AdrenergicSympathetic Adrenergic SystemSystem Pituitary Gland Na+ & H2O Reabsorption Aldosterone Blood Volume Rises Venous Return x Stroke Volumex Renin –Renin – AngiotensinAngiotensin SystemSystem Angiotensin II ACE vasoconstriction = Factors that alter the Blood Pressure EquationFactors that alter the Blood Pressure Equation Kidney Renin Cardiac Output Total Peripheral Arterial Resistance
  • 16. Determinants of BloodDeterminants of Blood PressurePressure • Cardiac Output (CO) –volume of blood pumped out by the heart in 1 minute –approximately 2.2 – 3.5 L / min / m2 BSA –determined by Stroke Volume (SV) and Heart Rate (HR)
  • 17. • Stroke Volume (SV) –volume of blood pumped out by the heart in every contraction –determined by: • Inotropic activity –strength of cardiac contraction • Venous return – cardiac preload; amount of blood delivered to the heart from the veins; affected by the tone of the veins Determinants of BloodDeterminants of Blood PressurePressure
  • 18. • Heart Rate (HR) –speed of heart contraction –chronotropism • Fluid Content of the Blood • Total Peripheral Resistance (TPR) – resistance or pressure encountered by the heart as it pumps out blood into the peripheral circulation (cardiac afterload) –determined by the arterioles Determinants of BloodDeterminants of Blood PressurePressure
  • 19. Mechanisms of BPMechanisms of BP RegulationRegulation • Baroreceptor Reflex Arch Mechanism –aka: Postural Reflex Mechanism –moment-to-moment BP regulation • Baroreceptor – a type of sensory nerve ending found in the walls of the atria of the heart, the vena cava, the aortic arch, and the carotid sinus that is stimulated by changes in pressure • Renin Angiotensin Aldosterone
  • 20. Angiotensinogen (from the liver) Renin Angiotensin I (inactive) Angiotensin Converting Enzyme (ACE) or Peptidyl dipeptidase (majority found in the lungs) Angiotensin II (active) -direct vasoconstriction -stimulates synthesis & release of Epi & NE -stimulates the synthesis & release of aldosterone Renin Angiotensin AldosteroneRenin Angiotensin Aldosterone System (RAAS)System (RAAS)
  • 21. HypertensionHypertension
  • 22. HypertensionHypertension • persistent or recurrent elevation of BP defined as having a: –Systolic reading > 140 mmHg –Diastolic reading > 90 mmHg –BP > 140/90 • most common cardiovascular disorder
  • 23. HypertensionHypertension • Systole –the period during which the ventricles are contracting • Diastole –the period during which the ventricles are relaxed and filling with blood
  • 24. HypertensionHypertension • Essential (Primary, Idiopathic) – hypertension with no identifiable cause – accounts for > 90% of HTNsive cases • Secondary – resulting from identifiable causes • kidney diseases • adrenal cortical disorders • pheochromocytoma (adrenal medulla tumor) • coarctation of the aorta • drugs such as steroids, sympathomimetics, contraceptives – treat the underlying cause – accounts for ~ 10% of HTNsive cases
  • 25. Classification of BP based on the 7Classification of BP based on the 7thth Report of theReport of the Joint National Committee on Detection, EvaluationJoint National Committee on Detection, Evaluation and Treatment of High Blood Pressure (JNC VII)and Treatment of High Blood Pressure (JNC VII) Classification of Blood Pressure (JNC VII) Systolic BP, mm Hg Diastolic BP, mm Hg Normal <120 and <80 Prehypertension 120-139 or 80-89 Stage 1 hypertension 140-159 or 90-99 Stage 2 hypertension >160 or >100 Adapted from JNC VII
  • 26. Hypertensive EmergencyHypertensive Emergency • aka: Hypertensive Crisis • rare, but life-threatening situation • systolic pressure > 210 mm Hg • diastolic pressure > 150 mm Hg
  • 27. Risk FactorsRisk Factors • Family history • Patient history • Racial predisposition – More common in blacks • Obesity • Smoking • Stress • High dietary intake – Saturated fats and sodium • Sedentary lifestyle • DM • Hyperlipidemia • Gender – males • Age > 60 • Postmenopausal women
  • 28. Treatment GoalsTreatment Goals • Rule out uncommon secondary causes of hypertension • Determine the presence and extent of target organ damage • Determine the presence of other CV risk factors • To lower BP with minimal side effects
  • 29. ComplicationsComplications • Cardiac effects – Increased oxygen requirements  angina pectoris; because of atherosclerosis  angina, MI, sudden death • Renal effects – Increased blood volume; renal parenchymal damage due to atherosclerosis • Cerebral effects – Transient ischemic attacks, cerebral thromboses, aneurysms with hemorrhage • Retinal effects – Visual defects (blurred vision, spots, blindness)
  • 30. TreatmentTreatment • First line: diuretics (thiazides) and beta blockers • Alternatives: ACE inhibitors, ARBs, alpha blockers, calcium- channel blockers  for px who cannot tolerate first line agents • Monitor: – blood pressure routinely – observe adverse effects • Patient Counseling: – Importance of compliance  make px realize seriousness of noncompliance
  • 31. Anti-hypertensivesAnti-hypertensives • Diuretics • Sympathoplegics • Vasodilators • Calcium Channel Blockers (CCBs) • ACE Inhibitors • Angiotensin II Receptor Blockers (ARBs)
  • 32. DiureticsDiuretics • agents that cause urinary loss of Na+ and H2O • Gen MOA: act on their specific sites in the renal tubule
  • 33. Five major classesFive major classes 1. Thiazides and thiazide-like 2. Loop diuretics 3. Potassium-sparing 4. Carbonic anhydrase inhibitors 5. Osmotic diuretics
  • 34. Renal TubuleRenal Tubule
  • 35. Carbonic AnhydraseCarbonic Anhydrase InhibitorsInhibitors • MOA: inhibit carbonic anhydrase (the enzyme that catalyzes the reaction of CO2 and H2O leading to H+ and HCO3 - ) that can lead to the spillage of Na+ causing diuresis. • act on the proximal convoluted tubule (PCT)
  • 36. Carbonic AnhydraseCarbonic Anhydrase InhibitorsInhibitors • Acetazolamide • Brinzolamide • Dorzolamide
  • 37. Carbonic AnhydraseCarbonic Anhydrase InhibitorsInhibitors • limited diuretic effect (2 to 3 days) • SE: metabolic acidosis, bone marrow depression (sulfonamide-like toxicity), allergic reactions (Stevens-Johnson’s Syndrome)
  • 38. Loop DiureticsLoop Diuretics • aka: High Ceiling Diuretics • high ceiling (most efficacious) as compared with other diuretics • act on the thick ascending Loop of Henle
  • 39. Loop DiureticsLoop Diuretics • MOA: inhibit the Cl-Na-K- cotransporter at the thick ascending LOH • Furosemide • Bumetanide • Torsemide • Ethacrynic acid
  • 40. Loop DiureticsLoop Diuretics • for px who cannot tolerate thiazides, have renal impairment, or ineffectiveness of thiazides • SE: hypovolemia, ototoxicity, increase serum creatinine • DI: their efficacy can be reduced by NSAIDs
  • 41. Loop DiureticsLoop Diuretics • Side-effects –Hypokalemia –Bicarbonate is lost in the urine –INCREASED calcium excretion Hypocalcemia –Ototoxicity • due to the electrolyte imbalances
  • 42. Thiazide DiureticsThiazide Diuretics • MOA: inhibit Na-Cl-cotransporter at the distal convoluted tubule • Chlorothiazide • Hydrochlorothiazide • Chlorthalidone • Indapamide
  • 43. Thiazide DiureticsThiazide Diuretics • first-line drug for uncomplicated hypertension as recommended by JNC 7 • effective initial therapy together with beta-blockers • also used for Nephrogenic Diabetes
  • 44. Thiazide DiureticsThiazide Diuretics • SE: hypokalemia, hyponatremia, hyperuricemia, hyperglycemia, hyperlipidemia • DI: their efficacy can be reduced by NSAIDs
  • 45. ThiazideThiazide • Side effects –Hypokalemia –DECREASED calcium excretion hypercalcemia –DECREASED uric acid secretion hyperuricemia –Hyperglycemia
  • 46. Potassium-Sparing DiureticsPotassium-Sparing Diuretics • MOA: act in the collecting tubule by inhibiting Na+ reabsorption, K+ secretion and H+ secretion • Spironolactone • Eprenolone • Amiloride • Triamterene
  • 47. Potassium-Sparing DiureticsPotassium-Sparing Diuretics • for patients where potassium loss is significant and supplementation is not feasible • often combined with thiazides  potentiation –Amiloride, Spirinolactone, Triamterene • precautions –Avoid in px with acute renal failure; use with caution  px with impaired renal function
  • 48. Potassium Rich FoodsPotassium Rich Foods TOPP PNBB’S
  • 49. • T- Tomatoes • O-Oranges • P- Peaches • P-potatoes • P-Prunes • N-Nuts • B-Banana • B-Broccoli • S-Spinatch
  • 50. Potassium-Sparing DiureticsPotassium-Sparing Diuretics • not associated with hypokalemia • can be given with other diuretics to lessen the risk of hypokalemia • SE: hyperkalemia, gynecomastia, impotence, sterility
  • 51. Osmotic DiureticsOsmotic Diuretics • MOA: increase the osmotic pressure at the proximal convoluted tubule and Loop of Henle preventing water reabsorption • Mannitol • Sorbitol • Urea
  • 52. Osmotic DiureticsOsmotic Diuretics • used to induce forced diuresis • mostly used to reduce intracranial pressure • SE: hypernatremia, hypovolemia
  • 53. Diuretics ComparisonDiuretics Comparison Diuretic class Major site of action Special Side effect (s) 1. Carbonic anhydrase inhibitor Proximal tubule Acidosis 2. Thiazide and thiazide like Distal tubule Hyperuricemia Hypokalemia 3. Loop diuretics L p of Henle Hypokalemia Ototoxicity 4. Potassium sparing Distal tubule Hyperkalemia 5. Osmotic diuretic Glomerulus Hypovolemia & hypotension
  • 54. Diuretics ComparisonDiuretics ComparisonDiuretic class Special Uses 1. Carbonic anhydrase inhibitor Mountain sickness Meniere’s disease 2. Thiazide and thiazide like Nephrolithiasis due to calcium stones Hypocalcemia 3. Loop diuretics Hypercalcemia 4. Potassium sparing CHF taking digoxin 5. Osmotic diuretic Increased ICP LITHIUM TOXICITY
  • 55. SympathoplegicsSympathoplegics
  • 56. SympathoplegicsSympathoplegics • Centrally-acting • Peripherally-acting • Alpha-1 blockers • Beta blockers
  • 57. Centrally-ActingCentrally-Acting SympathoplegicsSympathoplegics
  • 58. Centrally-ActingCentrally-Acting SympathoplegicsSympathoplegics • MOA: act primarily within the CNS on alpha-2 receptors to decrease sympathetic outflow to the CVS • Clonidine • Methyldopa • Guanfacine • Guanabenz
  • 59. ClonidineClonidine • MOA: agonist at alpha-2 receptors (leading to vasodilation) • effective in patients with renal impairment • SE: transient increase in BP, sedation/depression, rebound
  • 60. MethyldopaMethyldopa • reduce TPR with little effect on CO and blood flow to vital organs (such as kidneys) • effective for patients with renal impairment • used in the management of HTN in
  • 61. MethyldopaMethyldopa • SE: sedation, depression, hepatotoxicity (at doses >2g / day), (+) Coomb,s Test* * Coomb’s Test – indicator of a possible immune-mediated hemolytic anemia
  • 62. Guanfacine, GuanabenzGuanfacine, Guanabenz • adjunctive therapy to other anti- HTNsive drugs • avoided unless necessary to treat severe refractory HTN that is unresponsive to other meds
  • 63. Peripherally-ActingPeripherally-Acting SympathoplegicsSympathoplegics
  • 64. Peripherally-ActingPeripherally-Acting SympathoplegicsSympathoplegics • Trimethaphan • Reserpine • Guanethidine • Guanadrel
  • 65. TrimethaphanTrimethaphan • ganglionic receptor blocker • given via IV infusion • used in hypertensive emergencies caused by pulmonary edema or aortic aneurism when other agents cannot be used
  • 66. ReserpineReserpine • plant alkaloid • inhibits catecholamine (NE, Epi, Dopamine, Serotonin) storage • impairs sympathetic function because of decreased release of Norepinephrine (NE)
  • 67. Guanethidine, GuanadrelGuanethidine, Guanadrel • inhibit the response of the adrenergic nerve to stimulation or to indirectly- acting sympathetic amines • blocks the release of stored Norepinephrine • SE: orthostatic hypotension, impaired male sexual function
  • 68. Alpha-1 BlockersAlpha-1 Blockers
  • 69. Alpha-1 BlockersAlpha-1 Blockers • MOA: inhibit the alpha-1 receptors, resulting to vasodilation of arteries and veins • Prazosin • Doxazosin • Alfazosin • Terazosin
  • 70. Alpha-1 BlockersAlpha-1 Blockers • alternative drugs for the management of HTN esp among patients with BPH • First-Dose Phenomenon: –orthostatic hypotension –syncope –remedy: take the drug at bedtime, slow increase in dose
  • 71. Beta BlockersBeta Blockers
  • 72. Beta BlockersBeta Blockers • used for the initial therapy of HTN; effective for patients with rapid resting HR or concomitant IHD • MOA –Block stimulation of renin secretion –Decrease contractility  decrease CO –Decrease sympathetic output centrally –Reduction in HR  reduced CO –Combination of all
  • 73. Beta BlockersBeta Blockers • SE/Precautions/Contraindications: –can mask hypoglycemia –CI to patients with bronchospastic disease: COPD, Bronchial Asthma –rebound tachycardia and HTN –easy fatigability –severe bradycardia and heartblock (seen esp with concomitant use of verapamil and diltiazem)
  • 74. Beta BlockersBeta Blockers • Selective B – Betaxolol B – Bisoprolol E – Esmolol A – Acebutolol A – Atenolol M – Metoprolol • Membrane Stabilizing Activity – Anesthetic-like effect – Cannot be given as ophthalmic drops P – Propranolol P – Pindolol A – Acebutolol L – Labetalol M – Metoprolol
  • 75. Beta BlockersBeta Blockers • Mixed alpha and beta blocking effect L – Labetalol C – Carvedilol • Intrinsic sympathomimetic activity – partial agonist effect – not usually associated with rebound hypertension A – Acebutolol B – Bisoprolol C – Carteolol P – Pindolol P - Penbutolol
  • 76. Nematodes (Roundworms)Nematodes (Roundworms)
  • 77. Nematodes (Roundworms)Nematodes (Roundworms)
  • 78. VasodilatorsVasodilators
  • 79. VasodilatorsVasodilators • second-line agents • directly relax the peripheral vascular smooth muscles • not used alone  inc in plasma renin activity, CO, HR
  • 80. VasodilatorsVasodilators • common SE: reflex tachycardia, peripheral edema • common CI: as single agents, should be avoided in patients with Ischemic Heart Disease (IHD)
  • 81. VasodilatorsVasodilators • Hydralazine • Diazoxide • Minoxidil • Sodium Nitroprusside
  • 82. HydralazineHydralazine • used in the management of HTN in pregnancy • SE: Lupus-like side effect (drug- induced SLE or Systemic Lupus Erythematosus)
  • 83. DiazoxideDiazoxide • used in the emergency treatment of hypertensive crisis
  • 84. MinoxidilMinoxidil • most effective arteriolar vasodilator • SE: hypertrichosis, hirsutism
  • 85. Sodium NitroprussideSodium Nitroprusside • metabolized in the body into nitric oxide (NO) also called EDRF or Endothelium-Derived Relaxing Factor • 1st line drug for almost all types of HTNsive emergencies
  • 86. Sodium NitroprussideSodium Nitroprusside • Caution: use freshly prepared solutions or admixtures • protect from light • SE: thiocyanate or cyanide toxicity, acute psychosis, severe hypotension, coma, death
  • 87. Calcium Channel BlockersCalcium Channel Blockers
  • 88. Calcium Channel BlockersCalcium Channel Blockers (CCBs)(CCBs) • alternative for the mgt of HTN • MOA –Inhibit influx of Ca through the slow channels in vascular smooth muscle and cause relaxation
  • 89. • Dihydropyridine (DHP) – block Ca channels in the blood vessels – Nifedipine, Nicardipine, Felodipine, Amlodipine • Non-dihydropyridine (Non-DHP) – block Ca channels both in the heart and blood vessels – Verapamil – heart > blood vessels – Diltiazem – heart = blood vessels ClassificationClassification
  • 90. Calcium Channel BlockersCalcium Channel Blockers (CCBs)(CCBs) • SE: –peripheral edema –reflex tachycardia (DHP) –bradycardia (Non-DHP) –heart block (Non-DHP + Beta Blocker)
  • 91. ACE InhibitorsACE Inhibitors
  • 92. Angiotensin Converting EnzymeAngiotensin Converting Enzyme InhibitorsInhibitors • MOA: inhibit ACE, thereby preventing the conversion of angiotensin I into the active form angiotensin II • Short-acting – Captopril • Long-acting – Enalapril – Lisinopril – Perindopril Generally, long acting ACE Inhibitors are prodrugs: Enalapril Enalaprilat (prodrug) (active)
  • 93. • SE: –idiosyncratic dry cough ACE Bradykinin inactive fragments (causes cough) –angioedema –hyperkalemia Angiotensin Converting EnzymeAngiotensin Converting Enzyme InhibitorsInhibitors
  • 94. Angiotensin II ReceptorAngiotensin II Receptor BlockersBlockers
  • 95. Angiotensin II ReceptorAngiotensin II Receptor Blockers (ARBs)Blockers (ARBs) • direct inhibitors of angiotensin II receptors • Losartan, Valdesartan, Candesartan • clinical use: same as ACE Inhibitors • Advantage over ACE inhibitors: less associated with dry cough
  • 96. 1. A friend has very severe hypertension and asks1. A friend has very severe hypertension and asks about a drugabout a drug her doctor wishes to prescribe. Herher doctor wishes to prescribe. Her physician has explained that this drug isphysician has explained that this drug is associated with tachycardia and fluid retention (w/cassociated with tachycardia and fluid retention (w/c may be marked) and increased hair growth. Whichmay be marked) and increased hair growth. Which of the following is most likely to produce the effectsof the following is most likely to produce the effects that your friend has described?that your friend has described? A. Captopril B. Guanethidine C. Minoxidil D. Prazosin E. Propanolol
  • 97. 2. A patient is admitted to the emergency2. A patient is admitted to the emergency department with severe bradycardia following adepartment with severe bradycardia following a drug overdose. His family reports that he has beendrug overdose. His family reports that he has been depressed about his hypertension. Each of thedepressed about his hypertension. Each of the following can slow the heart rate EXCEPTfollowing can slow the heart rate EXCEPT A. Clonidine B. Guanethidine C. Hydralazine D. Propanolol E. Reserpine
  • 98. 2. A patient is admitted to the emergency2. A patient is admitted to the emergency department with severe bradycardia following adepartment with severe bradycardia following a drug overdose. His family reports that he has beendrug overdose. His family reports that he has been depressed about his hypertension. Each of thedepressed about his hypertension. Each of the following can slow the heart rate EXCEPTfollowing can slow the heart rate EXCEPT A. Clonidine B. Guanethidine C. Hydralazine D. Propanolol E. Reserpine
  • 99. 2. A patient is admitted to the emergency2. A patient is admitted to the emergency department with severe bradycardia following adepartment with severe bradycardia following a drug overdose. His family reports that he has beendrug overdose. His family reports that he has been depressed about his hypertension. Each of thedepressed about his hypertension. Each of the following can slow the heart rate EXCEPTfollowing can slow the heart rate EXCEPT A. Clonidine B. Guanethidine C. Hydralazine D. Propanolol E. Reserpine
  • 100. 3. Which one of the following is characteristic of3. Which one of the following is characteristic of enalapril treatment in patients with essentialenalapril treatment in patients with essential hypertension?hypertension? A. Competitively blocks angiotensin II at its receptor B. Decreases angiotensin II concentration in the blood C. Decreases renin concentration in the blood D. Increases sodium and decreases potassium in the blood E. Decreases sodium and increases potassium in the urine
  • 101. 4. A pregnant patient is admitted to the4. A pregnant patient is admitted to the hematology service with moderately severehematology service with moderately severe hemolytic anemia. After a thorough workup, thehemolytic anemia. After a thorough workup, the only positive finding is a history of treatment withonly positive finding is a history of treatment with an antihypertensive drug since 2 months afteran antihypertensive drug since 2 months after beginning the pregnancy. The most likely cause ofbeginning the pregnancy. The most likely cause of the patient’s blood disorder isthe patient’s blood disorder is A. Atenolol B. Captopril C. Hydralazine D. Methyldopa E. Minoxidil
  • 102. 5. Postural hypotension is a common5. Postural hypotension is a common adverse effect of which one of theadverse effect of which one of the following types of drugs?following types of drugs? A. ACE inhibitors B. Alpha receptor blockers C. Arteriolar dilators D. Beta-selective receptor blockers E. Nonselective B-blockers
  • 103. 5. Postural hypotension is a common5. Postural hypotension is a common adverse effect of which one of theadverse effect of which one of the following types of drugs?following types of drugs? A. ACE inhibitors B. Alpha receptor blockers C. Arteriolar dilators D. Beta-selective receptor blockers E. Nonselective B-blockers
  • 104. 5. Postural hypotension is a common5. Postural hypotension is a common adverse effect of which one of theadverse effect of which one of the following types of drugs?following types of drugs? A. ACE inhibitors B. Alpha receptor blockers C. Arteriolar dilators D. Beta-selective receptor blockers E. Nonselective B-blockers
  • 105. Congestive Heart FailureCongestive Heart Failure
  • 106. Heart FailureHeart Failure • is the failure of the heart as a pump • inability of the heart to pump sufficient amount of blood to the body
  • 107. Congestive Heart FailureCongestive Heart Failure • pumping ability of the heart becomes impaired • accompanied by congestion of body tissues • etiology –acute MI, HPN, cardiomyopathies –excessive work demands on the heart
  • 108. Forms of CHFForms of CHF • High-output – uncommon – caused by excessive need for cardiac output – high metabolic demands • Low-output – caused by disorders that impair the pumping ability of the heart (IHD) – normal metabolic demands, heart unable to meet them
  • 109. Forms of CHFForms of CHF • Right sided – fatigue – jugular vein distension – liver engorgement – anorexia, GI distress – cyanosis – elevation in peripheral venous pressure – peripheral edema • Left-sided – exertional dyspnea – paroxysmal nocturnal dyspnea – cough – blood-tinged sputum – cyanosis – pulmonary edema
  • 110. Treatment GoalsTreatment Goals • To remove or mitigate the underlying cause • To relieve the symptoms and improve pump function by: – Reducing metabolic demands (rest, relaxation, pharm’l controls) – Reduce fluid volume excess (food intake, meds) – Administer digitalis and other inotropic agents – Promote px compliance and self-regulation through education
  • 111. Compensatory MechanismCompensatory Mechanism • Myocardial Hypertrophy –long-term compensatory mechanism –increase in the number of contractile elements in myocardial cells as a means of increasing their myocardial performance –ventricular remodeling
  • 112. Compensatory MechanismCompensatory Mechanism • Frank-Starling Mechanism –is the intrinsic ability of the heart to adapt to changing volumes of inflowing blood –the greater the heart muscle is stretched during filling, the greater the force of contraction and the greater the quantity of blood pumped into the aorta –within physiologic limits, the heart pumps all the blood that comes to it without allowing excessive damming of
  • 113. Drugs for CHFDrugs for CHF
  • 114. Drugs for CHFDrugs for CHF • Inotropic Agents –Cardiac glycosides –Beta Agonists –Phosphodiesterase Inhibitors • Unloaders –ACE Inhibitors & ARBs –Beta Blockers –Diuretics –Vasodilators
  • 115. TREATING CONGESTIVE HEART FAILURE U N L O A D UPRIGHT POSITION NITRATES (LOW DOSE) LASIX OXYGEN AMINOPHYLLINE DIGOXIN F A S T FLUIDS (DECREASE) AFTERLOAD (DECREASE) SODIUM RESTRICTION TEST (Dig Level, ABGs, Potassium Level)
  • 116. Cardiac GlycosidesCardiac Glycosides • from Digitalis species • Digoxin, Digitoxin • MOA: inhibit the Na-K-ATPase pump leading to an increase in intracellular calcium
  • 117. Cardiac GlycosidesCardiac Glycosides • Digoxin – ~75% Bioavailable – half-life: 36-40 hours – 20-40% protein bound – excreted in the urine • Digitoxin – >90% Bioavailable – half-life: 168 hours – >90% protein bound – excreted in the bile
  • 118. Cardiac GlycosidesCardiac Glycosides - have low therapeutic indices - toxicity can be enhanced by: - hypokalemia - hypomagnesemia - hypercalcemia
  • 119. ToxicityToxicity • Cardiac Manifestations –arrhythmias (ventricular tachycardia) –cardiac death • Extra-cardiac Manifestations –GI disturbances (nausea & vomiting) –visual disturbances (blurred vision, alteration of color perception, haloes on dark objects)
  • 120. Management of ToxicityManagement of Toxicity • give potassium supplement • give digitalis antibodies (FAB fragments) • for arrhythmias, give lidocaine or amiodarone
  • 121. Nematodes (Roundworms)Nematodes (Roundworms)
  • 122. Beta-1 AgonistsBeta-1 Agonists • Dopamine • Dobutamine • MOA: increase intracellular cAMP, which results in the activation of protein kinase, that leads to an increase in intracellular calcium
  • 123. DobutamineDobutamine • given as an IV infusion • primarily used in the management of acute heart failure in the hospital setting
  • 124. Phosphodiesterase InhibitorsPhosphodiesterase Inhibitors • MOA: inhibits the enzyme phosphodiesterase which hydrolyses cAMP , thereby prolonging the action of protein kinase • Amrinone • Milrinone
  • 125. UnloadersUnloaders • ACE Inhibitors & ARBs – preload and afterload unloaders – vasodilating effect – Captopril, Enalapril • Beta Blockers – vasodilating effect – Metoprolol, Misoprolol, Carvedilol • Diuretics – preload unloaders – Spironolactone • Vasodilators
  • 126. 1. Drugs that have been found to be useful in one1. Drugs that have been found to be useful in one or more types of heart failure include all of theor more types of heart failure include all of the following EXCEPTfollowing EXCEPT A. Na+/K+ ATPase inhibitors B. Alpha-adrenoceptor agonists C. Beta-adrenoceptor agonists D. ACE inhibitors
  • 127. 2. The mechanism of action of digitalis is2. The mechanism of action of digitalis is associated withassociated with A. A decrease in calcium uptake by the sarcoplasmic reticulum B. An increase in ATP synthesis C. A modification of the actin molecule D. An increase in systolic intracellular calcium levels E. A block of cardiac B adrenoceptors
  • 128. 4. A 65-year old woman has been admitted to the4. A 65-year old woman has been admitted to the coronary care unit with a left ventricular myocardialcoronary care unit with a left ventricular myocardial infarction. If this patient develops acute severeinfarction. If this patient develops acute severe heart failure with mark pulmonary edema, whichheart failure with mark pulmonary edema, which one of the following would be most useful?one of the following would be most useful? A. Digoxin B. Furosemide C. Minoxidil D. Propanolol E. Spironolactone
  • 129. 6. Drugs associated with clinically useful or6. Drugs associated with clinically useful or physiologically important positive inotropic effectsphysiologically important positive inotropic effects include all of the following EXCEPTinclude all of the following EXCEPT A. Amrinone B. Captopril C. Digoxin D. Dobutamine E. Norepinphrine
  • 130. 7. Successful therapy of heart failure with digoxin7. Successful therapy of heart failure with digoxin will result in which one of the following?will result in which one of the following? A. Decreased heart rate B. Increased afterload C. Increased aldosterone D. Increased renin secretion E. Increased sympathetic outflow to the heart
  • 131. 8. Which of the following has been shown to8. Which of the following has been shown to prolong life in patients with chronic congestiveprolong life in patients with chronic congestive failure but has a negative inotropic effect onfailure but has a negative inotropic effect on cardiac contractility?cardiac contractility? A. Carvedilol B. Digoxin C. Dobutamine D. Enalapril E. Furosemide
  • 132. 10. Which of the following is the drug of choice in10. Which of the following is the drug of choice in treating suicidal overdose of digitoxin?treating suicidal overdose of digitoxin? A. Digoxin antibodies B. Lidocaine C. Magnesium D. Phenytoin E. Potassium
  • 133. Coronary Artery DiseasesCoronary Artery Diseases (CAD)(CAD) oror Ischemic Heart DiseasesIschemic Heart Diseases (IHD)(IHD)
  • 134. Coronary Artery DiseasesCoronary Artery Diseases
  • 135. Coronary Artery DiseasesCoronary Artery Diseases • occur when the coronary arteries become so narrowed by atherosclerosis that they are unable to deliver sufficient blood to the heart muscle – Localized areas of thickened tunica intima associated with accumulation of
  • 136. Coronary Artery DiseasesCoronary Artery Diseases • Angina Pectoris – episodic, reversible oxygen insufficiency – severe chest pains generally radiating to the left shoulder and down the inner side of the arm – usually precipitated by physical exertion or emotional stress • Myocardial Ischemia – deprivation of oxygen to a portion of the myocardium (reversible) • Myocardial Infarction – severe, prolonged deprivation of oxygen to a portion
  • 137. Risks FactorsRisks Factors • Smoking • Hypertension • Diabetes Mellitus • Males >45 yo; Females >55 yo • Dyslipidemia • Obesity • Family history of CAD • Others: – sedentary lifestyle, hx of chronic inflammation
  • 138. EtiologyEtiology • Decreased blood flow – Atherosclerosis – most common cause – Coronary artery spasm – sustained contraction of 1 or more coronary arteries  Prinzmetal’s angina or MI – Traumatic injury – that interferes with blood flow in the heart – Embolic events – can abruptly restrict oxygen supply • Increased oxygen demand – Exertion and emotional stress  sympathetic stimulation  increase HR • Reduced blood oxygenation
  • 139. Angina PectorisAngina Pectoris • chest pain • a symptom of myocardial ischemia in the absence of an infaction
  • 140. Angina PectorisAngina Pectoris • Types: – Stable Angina • aka: Classical Angina • develops on exertion and lasts for < 5 min • relieved with rest or drugs • mechanism: imbalance oxygen supply – Unstable Angina • can be experienced at rest, or with increasing severity for the last 1-2 months or a new chest pain for < 1 month
  • 141. Angina PectorisAngina Pectoris • Types: –Angina Decubitus • nocturnal angina • occurs in recumbent position –Prinzmetal Angina • aka: Variant Angina • precipitated by coronary artery spasm
  • 142. Drugs for Angina PectorisDrugs for Angina Pectoris • Nitrates • Beta Blockers • Calcium Channel Blockers
  • 143. NitratesNitrates • MOA: metabolized into NO in the body, leading to peripheral vasodilation • examples –amyl nitrite –nitroglycerin –isosorbide dinitrate (ISDN) –isosorbide mononitrate (ISMN) • SE:
  • 144. Beta BlockersBeta Blockers • drug of choice for stable angina • MOA: decreases HR & contractility  reduce oxygen demand (rest and during exertion)  reduce arterial BP
  • 145. CCBsCCBs • MOA – inhibits calcium influx into vascular smooth muscle & heart muscles  increased blood flow  enhance oxygen supply  prevent and reverse coronary spasm – dilates peripheral arterioles & reduce contractility  reduce total peripheral vascular resistance  reduced oxygen demand • Indications – Stable angina not controlled by nitrates & beta blockers; px who could not take beta blockers – Prinzmetal’s angina (with or without nitrates)
  • 146. Other AgentsOther Agents • Morphine –Unstable angina with no CI; IV doses given after 3 sublingual nitroglycerin tabs have failed to relieve pain • Aspirin –Indefinite in px with stable or unstable angina • Heparin, Enoxaparin, Dalteparin –Together with aspirin  hospitalized px with unstable angina until resolved
  • 147. Myocardial InfarctionMyocardial Infarction
  • 148. Myocardial Infarction (MI)Myocardial Infarction (MI) –Results from prolonged myocardial ischemia, precipitated in most cases by an occlusive coronary thrombus at the site of a pre-existing atherosclerotic plaque Cellular ischemia Tissue injury Tissue necrosis Note: Damage on myocardial tissue is not reversible  myocardial tissue dies
  • 149. Myocardial Infarction (MI)Myocardial Infarction (MI)
  • 150. Myocardial Infarction (MI)Myocardial Infarction (MI) • persistent, severe chest pain or pressure  “crushing”, “squeezing” or heavy “an elephant sitting on the chest”
  • 151. Signs and Symptoms of MISigns and Symptoms of MI • Compared to angina – Pain persists longer – Not relieved by rest or nitroglycerin – Sense of impending doom, sweating, nausea, vomiting, difficulty in breathing; some px  fainting and sudden death – Extreme anxiety, restlessness, ashen pallor • Some px: – Mild or indigestion-like pain, manifest in worsening CHF, loss of consciousness, acute confusion, dyspnea, sudden drop in BP, lethal arrhythmia
  • 152. Drugs for MIDrugs for MI
  • 153. IMMEDIATE TREATMENT FOR MYOCARDIAL INFARCTION M O N MORPHINE OXYGEN NITROGLYCERINE ASA
  • 154. Drugs for MIDrugs for MI • Nitrates • Oxygen • Morphine • Thrombolytic Agents
  • 155. NitratesNitrates • MOA – Decrease oxygen demand and facilitate coronary blood flow – converted to nitric oxide intracellularly which activates guanylate cyclase  increase cGMP  dephosphorylation of myosin light chain  relaxation of vascular smooth muscle  vasodilation • Important SE – HEADACHE – most common side effect – Tolerance (“Nitrate-free interval”) – Postural hypotension, facial flushing, reflex
  • 156. OxygenOxygen • for patients who have chest pain and who may be ischemic • improve oxygenation of myocardium
  • 157. MorphineMorphine • MOA – causes venous pooling and reduces preload, cardiac workload, and oxygen consumption – IV until pain is relieved • Indication – DOC for MI pain and anxiety • Precautions – can produce orthostatic hypotension and fainting – monitor for hypotension & signs of resp depression
  • 158. Thrombolytic AgentsThrombolytic Agents • MOA: – Lysis of thrombus clot • The following are given IV within 12 h to restore normal blood flow in an acute MI: – Recombinant t-PA (recombinant tissue-type plasminogen activator alteplase) – Streptokinase – Anisoylated plasminogen streptokinase activator complex (APSAC) – Reteplase – Tenecteplase
  • 159. Post thrombolysis adjunctivePost thrombolysis adjunctive therapytherapy • Aspirin – prevents platelet aggregation; shown to reduce post-infarct mortality – also: dipyridamole, ticlopidine, clopidogrel • Heparin – prevent re-occlusion once a coronary artery has been opened – not used with streptokinase  increased risk of hemorrhage • Warfarin – reduce mortality, prevent recurrent MI
  • 160. Post thrombolysis adjunctivePost thrombolysis adjunctive therapytherapy • Beta Blockers – if administered early  reduce ischemia, reduce potential zone of infarction, decrease oxygen demands, preserve left ventricular function, decrease cardiac workload • ACE Inhibitors – improve exercise capacity and reduce mortality in px with CHF; aid in the prevention of progressive ventricular remodelling • “Statins” – reduced mortality due to MI when used by px to aggressively lower cholesterol
  • 161. Post thrombolysis adjunctivePost thrombolysis adjunctive therapytherapy • Lidocaine –used for px who develop ventricular arrhythmia • Calcium Channel Blockers –decrease incidence of reinfarction in px with non-Q-wave infarcts; not for acute mgt.
  • 162. Items 1-3. Mr. Green, 60 years old, hasItems 1-3. Mr. Green, 60 years old, has severe chest pain when he attempts to carrysevere chest pain when he attempts to carry parcels upstairs to his apartment. The painparcels upstairs to his apartment. The pain rapidly disappears when he rest. A decisionrapidly disappears when he rest. A decision is made to treat him with nitroglycerin.is made to treat him with nitroglycerin.
  • 163. 2. In advising Mr. Green about the adverse effects2. In advising Mr. Green about the adverse effects he may notice, you point out that nitroglycerin inhe may notice, you point out that nitroglycerin in moderate doses often produces certain symptoms.moderate doses often produces certain symptoms. These toxicities result from all of the followingThese toxicities result from all of the following EXCEPTEXCEPT A. Meningeal vasodilation B. Reflex tachycardia C. Hypotension D. Methemoglobinemia
  • 164. 3. 2 years later, Mr. Green returns complaining3. 2 years later, Mr. Green returns complaining that his nitroglycerin works well when he takes itthat his nitroglycerin works well when he takes it for an acute attack but that he is having frequentfor an acute attack but that he is having frequent attacks now and would like something to preventattacks now and would like something to prevent them. Useful drugs for the prophylaxis of angina ofthem. Useful drugs for the prophylaxis of angina of effort include which one of the following?effort include which one of the following? A. Amyl nitrite B. Diltiazem C. Sublingual isosorbide dinitrate D. Sublingual nitroglycerin
  • 165. 4. The antianginal effect of propanolol may be4. The antianginal effect of propanolol may be attributed to which one of the following?attributed to which one of the following? A. Block of exercise-induced tachycardia B. Decreased end-diastolic ventricular volume C. Dilation of constricted coronary vessels D. Increased cardiac force E. Decreases heart rate
  • 166. 5. The major common determinant of myocardial5. The major common determinant of myocardial oxygen consumption isoxygen consumption is A. Blood volume B. Cardiac output C. Diastolic blood pressure D. Heart rate E. Myocardial fiber tension
  • 167. 6. You are considering therapeutic options for a6. You are considering therapeutic options for a new patient who presents with hypertension andnew patient who presents with hypertension and angina. In considering adverse effects, you noteangina. In considering adverse effects, you note that an adverse effect which nitroglycerin,that an adverse effect which nitroglycerin, prazosin, and ganglion blockers have in commonprazosin, and ganglion blockers have in common isis A. Bradycardia B. Impaired sexual function C. Lupus erythematosus syndrome D. Orthostatic hypotension E. Throbbing headache
  • 168. 7. A patient is admitted to the emergency7. A patient is admitted to the emergency department following a drug overdose. He is noteddepartment following a drug overdose. He is noted to have severe tachycardia. He has been receivingto have severe tachycardia. He has been receiving therapy for hypertension and angina. A drug thattherapy for hypertension and angina. A drug that often causes tachycardia isoften causes tachycardia is A. Diltiazem B. Guanethidine C. Isosorbide dinitrate D. Propanolol E. Verapamil
  • 169. ArrhythmiasArrhythmias
  • 170. ArrhythmiasArrhythmias • deviations from normal heartbeat pattern –abnormalities in impulse formation –conduction disturbances
  • 171. ArrhythmiasArrhythmias • The heart is endowed with a specialized electrogenic system for: –Generating rhythmical impulses to cause rhythmical contraction of the heart muscle –Conducting these impulses rapidly throughout the heart
  • 172. Cardiac Conduction SystemCardiac Conduction System • Sinoatrial node – Pacemaker of the heart – 60 – 100 beats/min – Location: posterior wall of the right atrium near the entrance of the superior vena cava • Atrioventricular node – Location: posterior septal wall of the right atrium immediately behind the tricuspid valve – Connects the atrial and ventricular conduction systems
  • 173. Cardiac Conduction SystemCardiac Conduction System • Bundle of His (AV bundle) –Delayed transmission • Delays in transmission provide mechanical advantage  atria complete ejection of blood before initiating ventricular contraction• Purkinje system – Supplies the ventricles – Has large fibers that allow for rapid conduction and almost simultaneous excitation of the entire left and right ventricles – Rapid rate of ejection is necessary for the swift and efficient ejection of blood from the heart
  • 174. Cardiac Conduction SystemCardiac Conduction System
  • 175. Myocardial Action PotentialMyocardial Action Potential • electric current generated by nerve and muscle cells • involve movement or flow of electrically charged ions at the level of the cell membrane
  • 176. Myocardial Action PotentialMyocardial Action Potential
  • 177. Resting Membrane PotentialResting Membrane Potential • membrane is relatively permeable to K+ • charges of opposite polarity become aligned along the membrane (+)  outside (-)  inside
  • 178. DepolarizationDepolarization • cell membrane suddenly becomes selectively permeable to current-carrying ions such as Na+ • Na+ enters cell  sharp rise of intracellular potential to positivity while K+ migrate outside
  • 179. RepolarizationRepolarization • re-establishment of the resting potential • slower process; increased permeability to K+  K+ ions move outward  removes (+) charges inside the cell – The Na-K pump helps to preserve the intracellular negativity by moving 3
  • 180. Myocardial Action PotentialMyocardial Action Potential • Five Phases: Phase 0: Rapid Depolarization Phase 1: Early Rapid Repolarization Phase 2: Plateau Phase of Repolarization Phase 3: Final Rapid Repolarization Phase 4: Slow Depolarization
  • 181. Myocardial Action PotentialMyocardial Action Potential
  • 182. Myocardial Action PotentialMyocardial Action Potential
  • 183. Electrocardiography (ECG)Electrocardiography (ECG) • A recording of the electrical activity of the heart during depolarization- repolarization –P wave • SA node and atrial depolarization –QRS complex • Ventricular depolarization –T wave • Ventricular repolarization
  • 184. Electrocardiography (ECG)Electrocardiography (ECG) –Isoelectric line between P wave & Q wave • Depolarization of the AV node, bundle branches, Purkinje system –ST segment • Absolute refractory period; part of ventricular repolarization –Atrial repolarization occurs during ventricular depolarization and is hidden in the QRS complex.
  • 185. Cardiac arrhythmia mayCardiac arrhythmia may cause the heart tocause the heart to • To beat too slowly • To beat too rapidly • To respond to impulses originating from sites other than the SA node • To respond to impulses travelling along extra pathways
  • 186. CAUSES OF ARRHYTHMIACAUSES OF ARRHYTHMIA • Abnormal automaticity • Effect of drug • Abnormalities in impulse conduction
  • 187. Electrocardiography (ECG)Electrocardiography (ECG)
  • 188. Action Potential & ECGAction Potential & ECG
  • 189. Classification of ArrhythmiasClassification of Arrhythmias • By origin –Supraventricular arrhythmia • Stem from enhanced automaticity of the SA node or from re-entry conduction –Ventricular arrhythmia • Occur when an ectopic pacemaker triggers a ventricular contraction before the SA node fires
  • 190. Normal ECG PatternNormal ECG Pattern
  • 191. ECG Patterns of ArrhythmiasECG Patterns of Arrhythmias
  • 192. Anti-arrhythmic AgentsAnti-arrhythmic Agents
  • 193. AntiarrhythmicsAntiarrhythmics Sodium Channel Blockers Class IA Class IB Class IC •Quinidine •Procainamide •Disopyramide •Lidocaine •Tocainide •Mexiletine •Phenytoin •Flecainide •Propafenone •Moricizine Beta Adrenergic Blockers Class II •Propranolol •Esmolol •Acebutolol Potassium Channel Blockers Class III •Amiodarone •Sotalol •Bretylium Calcium Channel Blockers Class IV •Verapamil •Diltiazem
  • 194. CLASS 1ACLASS 1A • Slows phase 0 depolarization • Prolong action potential • Slow conduction
  • 195. CLASS 1BCLASS 1B • Shortens phase 3 repolarization • Decrease duration of action potential
  • 196. CLASS 1CCLASS 1C • Markedly slow phase 0 depolarization
  • 197. CLASS IICLASS II • Suppresses phase 4 depolarization
  • 198. CLASS IIICLASS III • Prolongs phase 3 repolarization
  • 199. CLASS IVCLASS IV • Slows phase 4 spontaneous depolarization • Shorten action potential
  • 200. Miscellaneous AgentsMiscellaneous Agents • Adenosine • MgSO4
  • 201. TYPE OF ARRHYTHMIATYPE OF ARRHYTHMIA AND DRUGSAND DRUGS • Atrial flutter • Class 1 – quinidine • Class II - propranolol • Class IV – verapamil • Others - digoxin
  • 202. • Atrial fibrillation • 1- quinidine • 2- propranolol • 3- amniodarone • 4 – anticoagulant
  • 203. • AV –NODAL REENTRY • PROPRANOLOL • VERAPAMIL • DIGOXIN
  • 204. • ACUTE SUPRAVENTRICULAR TACHYCARDIA • Verapamil • adenosine
  • 205. • ACUTE VENTRICULAR TACHYCARDIA • Lidocaine • Sotalol • Amniodarone
  • 206. • VENTRICULAR FIBBRILLATION • Lidocaine • Bretylium • Amnidarone • epinephrine
  • 207. ProcainamideProcainamide • can cause SLE (Systemic Lupus Erythematosus)
  • 208. QuinidineQuinidine • drug interaction with digoxin • can increase serum levels of digoxin by at least 2x
  • 209. LidocaineLidocaine • anesthetic • DOC for digitalis-induced arrhythmias
  • 210. PropafenonePropafenone • for acute atrial fibrillation
  • 211. AmiodaroneAmiodarone • iodine-containing molecule • first-line treatment for almost all types of Ventricular Tachycardia and Atrial Fibrillation
  • 212. VerapamilVerapamil • alternative for acute SVT (Supraventricular Tachycardia)
  • 213. AdenosineAdenosine • first-line drug for acute SVT
  • 214. Drugs for CoagulationDrugs for Coagulation DisordersDisorders
  • 215. Clotting MechanismClotting Mechanism • inciting event: epithelial vascular injury • followed by: – migration of platelets to the site of injury – platelet aggregation • aka: primary hemostasis • white thrombus • platelet plug • unstable clot – deposition of fibrin over the plug – attachment of other blood cells • aka: secondary hemostasis • red thrombus • stable clot
  • 216. Clotting MechanismClotting Mechanism • thrombus –clot that adheres to a blood vessel wall • embolus –detached thrombus
  • 217. Clotting MechanismClotting Mechanism • the coagulation process that generates thrombin that is essential in the formation of fibrin used in clot formation involves coagulation cascade
  • 218. Coagulation CascadeCoagulation Cascade
  • 219. Drugs for CoagulationDrugs for Coagulation DisordersDisorders Anticoagulants Anti-Platelet Drugs Fibrinolytic Agents Pro-coagulant Drugs
  • 220. AnticoagulantsAnticoagulants
  • 221. AnticoagulantsAnticoagulants • Site of action – synthesis of or directly against clotting factors (II, IIa) • Types: – Parenteral • Hirudin, Heparin – Oral • Dicumarol, Warfarin
  • 222. Parenteral AnticoagulantsParenteral Anticoagulants
  • 223. HirudinHirudin • obtained from medicinal leeches (Hirudo medicinalis) • used in the management of HIT (Heparin-Induced Thrombocytopenia) • Lepirudin – produced by recombinant DNA technology
  • 224. HeparinHeparin • heterogeneous mixture of sulfated mucopolysaccharides –Regular or Unfractionated heparin • activates antithrombin III which in turn inactivates thrombin (IIa); Ixa, Xa, Xia • SQ/IV –Low MW Heparin • Inactivates IIa and Xa • Enoxaparin,fraxiparin,dalteparin • SQ
  • 225. HeparinHeparin • Clinical use –initiation of anticoagulant therapy –mgt of MI or unstable angina –tx & prevention of pulmonary embolism & DVT –anticoagulation in pregnancy (APAS) • SE: –hemorrhage (monitor aPTT – activated partial thromboplastin time) 2-2.5x or delay of 50 – 80 secs except SQ –Thrombocytopenia
  • 226. CONTRAINDICATIONSCONTRAINDICATIONS • Hypersensitivity • Active bleeding • Thrombocytopenia • Severe HPN • Active TB
  • 227. Oral AnticoagulantsOral Anticoagulants
  • 228. • DICUMAROL • aka: bis-hydroxycoumarin • high incidence of GI side-effects • PHENPROCOUMON • INDANEDIONES ex: anisindione,phenindione • WARFARIN
  • 229. • MOA: blocks carboxylation of X, IX,VII,II • ONSET: 8 – 12 hrs maximum after 1 to 3days
  • 230. • delay in the anticoagulant effect • Clinical use – Chronic anticoagulation (DVT prophylaxis, cardiac thrombus, prosthetic heart valves) • SE: – Hemorrhage • Monitor PT (Prothrombin Time) and INR (International Normalized Ratio) • Goal for INR = 2-3 • <2  insufficient dose • >3  x’sive dose • With prosthetic heart valves INR goal = 3-4
  • 231. SE:SE: • Hemorrhagic dse of the newborn • Teratogenic: abnormal bone formation • Cutaneous necrosis • Purple toe syndrome • Alopecia, urticaria,dermatitis
  • 232. Anti-Platelet DrugsAnti-Platelet Drugs
  • 233. Anti-Platelet DrugsAnti-Platelet Drugs • Thromboxane Synthesis Inhibitors • Phosphodiesterase Inhibitors • ADP Inhibitors • Glycoprotein IIb/IIIa Inhibitors
  • 234. Thromboxane SynthesisThromboxane Synthesis InhibitorsInhibitors • Irreversibly acetylates COX- inhibition of TXA2 synthesis, lasts for 8 – 10 days • Aspirin –primary prophylaxis for MI –secondary prophylaxis for MI and stroke
  • 235. Phosphodiesterase InhibitorsPhosphodiesterase Inhibitors • Dypiridamole –given together with antiplatelet; ineffective when alone –Inc CAMP –SE: coronary steal phenomenon
  • 236. ADP Inhibitors -ADP Inhibitors - ThienopyridinesThienopyridines • Ticlopidine –SE: thrombocytopenia purpura,neutropenia, –n/v,diarrhea • Clopidogrel –safer than ticlopidine
  • 237. Glycoprotein InhibitorsGlycoprotein Inhibitors • Abciximab • Eptifibatide • Tirofiban
  • 238. Fibrinolytic AgentsFibrinolytic Agents
  • 239. Fibrinolytic Agents /Fibrinolytic Agents / ThrombolyticsThrombolytics • MOA – catalyse activation of plasminogen to plasmin(serine protease) • Use – mgt of severe pulmonary embolism – heart attack, acute MI,DVT • Ex – Streptokinase – destroy fibrin that is either bound to clots or is in the unbound form – Tissue plasminogen activator – binds to fibrin bound to a clot – Anistreplase (APSAC)
  • 240. Pro-coagulant DrugsPro-coagulant Drugs
  • 241. Pro-coagulant DrugsPro-coagulant Drugs • Mgt of bleeding disorders –Vitamin K • K1 – phytonadione (in plants, useful clinically) • K2 – menaquinone (intestinal bacteria) • K3 – menadione (synthetic) • used for Vit. K deficiency; hemorrhagic disorders in newborns –Aminocaproic Acid • prevents activation of plasminogen – Tranexamic Acid (analogue)
  • 242. Drugs for DyslipidemiaDrugs for Dyslipidemia
  • 243. DyslipidemiaDyslipidemia • Hypercholesterolemia (inc LDL, dec HDL) • Hypertriglyceridemia (inc TG, ~ inc VLDL, chylomicrons) • Liver –Only organ in the body that efficiently uses cholesterol • Converts it to bile salts
  • 244. Cholesterol SynthesisCholesterol Synthesis HMG-CoA Mevalonat e Cholesterol HMG-CoA Reductase Cholesterol Source –Diet (exogenous) –Endogenous hydroxymethylglutaryl- Coenzyme A (HMG-CoA)
  • 245. AtherosclerosisAtherosclerosis Condition associated with cholesterol deposition in vascular smooth muscles (arthroma) with consequent narrowing of the lumen of the
  • 246. AtherosclerosisAtherosclerosis • Could lead to… –CAD –Cerebrovascular disease –Aortic disease –Renal artery disease
  • 247. AtherosclerosisAtherosclerosis • Major Risk factors – Age (males: > 45; females: > 55) – Smoking – DM – HPN – Dyslipidemia – Obesity – Family history of premature heart • Minor Risk Factors – Chronic infection – Sedentary lifestyle • Modifiable Risk Factors – By therapy – By lifestyle change
  • 248. Drugs for DyslipidemiaDrugs for Dyslipidemia • HMG-CoA Reductase Inhibitors • Nicotinic Acid • Bile Acid Sequesterants • Fibric Acid Derivatives • Probucol
  • 249. HMG-CoA ReductaseHMG-CoA Reductase InhibitorsInhibitors • “-statins” • MOA: inhibit the enzyme HMG-CoA Reductase, thereby inhibiting the first step (rate-limiting step) in cholesterol synthesis • first-line drugs for dyslipidemia
  • 250. • Diurnal Pattern of Cholesterol Synthesis –means that the biosynthesis of cholesterol in the body occurs at night –thus most statins are given at bedtime (esp the short-acting ones) HMG-CoA ReductaseHMG-CoA Reductase InhibitorsInhibitors
  • 251. HMG-CoA ReductaseHMG-CoA Reductase InhibitorsInhibitors • Short-acting – simvastatin – lovastatin – fluvastatin • Long-acting – atorvastatin – rosuvastatin Long-acting statins can be given any time of the day.
  • 252. • SE: –hepatotoxicity –myositis –rhabdomyolysis (muscle wasting) HMG-CoA ReductaseHMG-CoA Reductase InhibitorsInhibitors
  • 253. Nicotinic AcidNicotinic Acid • unknown MOA • used in the management of hypertriglyceridemia • SE: flushing (due to percutaneous vasodilation), myositis
  • 254. Bile Acid SequesterantsBile Acid Sequesterants • aka: Bile Acid – Binding Resins • MOA: Inhibit reabsorption of bile acid • since liver must maintain a certain amount of bile, it will synthesize bile from endogenous cholesterol when bile levels go low
  • 255. Bile Acid SequesterantsBile Acid Sequesterants • Cholestyramine • Colestipol • SE: –constipation –impaired absorption of certain drugs –may increase incidence / risk of biliary stone formation
  • 256. Fibric Acid DerivativesFibric Acid Derivatives • MOA: stimulate lipoprotein lipase which decreases triglycerides • first-line drug in hypertriglyceridemia • Gemfibrozil • Fenofibrate • Clofibrate (withdrawn)
  • 257. Fibric Acid DerivativesFibric Acid Derivatives • SE: –myositis –rhabdomyolysis –increase risk of bile stone formation –hepatobiliary cancer (Clofibrate)
  • 258. ProbucolProbucol • MOA: anti-oxidant • SE: –increase risk of arrhythmia –produces fetid odor
  • 259. Ok, before we end ourOk, before we end our lecture, quiz muna tayo…lecture, quiz muna tayo… 
  • 260. Question 1:Question 1: • Which enzyme is responsible for the conversion of Angiotensin I into the active form Angiotensin II? A. Renin B. ACE C. HMG-CoA D. Streptokinase B
  • 261. Question 2:Question 2: • A 55 y/o male patient was diagnosed to have uncomplicated HTN. Which of the following drugs would most likely be given to him? A. Thiazide diuretic + Beta Blocker B. ACE Inhibitor C. CCB + ACE Inhibitor D. ACEi + ARB A
  • 262. Question 3:Question 3: • From the list of anti-hypertensive drugs below, select the one most likely to lower blood sugar: A. Prazosin B. Nifedipine C. Propranolol D. Hydralazine E. Labetalol C
  • 263. Question 4:Question 4: • Which of the following conditions predisposes a patient taking digitalis into arrhythmia? A. hypocalcemia B. decreased heart rate C. hyponatremia D. hypokalemia D
  • 264. Question 5:Question 5: • All of the following mechanisms of action correctly match a drug, EXCEPT: A. Quinidine: blocks Na+ channels B. Bretylium: blocks K+ channels C. Propranolol: blocks β-receptors D. Procainamide: blocks K+ channelsD
  • 265. Question 6:Question 6: • Which of the following adverse effects is associated with nitrates? A. nausea B. throbbing headache C. sexual dysfunction D. anemia B
  • 266. Question 7:Question 7: • A patient experienced orthostatic hypotension after taking the first dose of her drug. She most likely took: A. Labetalol B. Valdesartan C. Prazosin D. Digoxin C
  • 267. Question 8:Question 8: • Mrs. G. R. is a hypertensive patient under therapy. After some time, she developed Lupus-like symptoms. Which of the ff drugs may have cause this? A. Hydralazine B. Losartan C. Furosemide A
  • 268. Question 9:Question 9: • Which of the following antagonizes the co-factor functions of Vitamin K? A. Tranexamic acid B. Heparin C. Warfarin D. Hirudin C
  • 269. Question 10:Question 10: • The following drugs for dyslipidemia can cause rhabdomyolysis, EXCEPT: A. simvastatin B. atorvastatin C. colestipol D. fenofibrate C
  • 270. ““The only thing greater than the powerThe only thing greater than the power of the mind is the courage of theof the mind is the courage of the heart.”heart.” - from the movie,- from the movie, A Beautiful MindA Beautiful Mind