1. Treatment Goals for BP
    • Patient Population
    • Target Blood Pressure

    • Most patients
    • < 140/90 mmHg

    • Diabetes mellitus
    • < 130/80 mmHg

    • Chronic kidney disease
    • <130/80 mmHg
  2. Aggressive BP lowering for high risk patients
    • Most patients for general prevention
    • <140/90 mmHg

    • Patients with diabetes (CAD risk equivalent), significant CKD, known CAD (MI, stable angina, unstable angina), noncoronary atherosclerotic vascular disease (ischemic stroke, TIA, PAD, abdominal aortic aneurism [CAD risk equivalents]), Framingham risk score > 10%
    • <130/80 mmHg

    • Patients with left ventricular dysfunction (HF)
    • <120/80 mmHg
    Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)
  4. During ALLHAT trial what remains unsurpasseed for reducing CV morbidity and mortality?
    Thiazide type diuretics
    Primary Endpoints
    fatal CHD

    nonfatal MI
    Secondary endpoints
    other hypertension-related complications

  7. What is JNC7 Recommendations for 1st line therapy to treat HTN?
    Thiazide-like diuretic

    based on clinical trials showing morbidity & mortality reductions
    Avoiding Cardiovascular Events through COMbination Therapy in Patients LIving with Systolic Hypertension
  9. In a clincical controversy which combination was found to be superior for reducing CV events in high risk patients?

    A. benazepril + amlodipine

    B. benazepril + HCTZ
    A. benazepril + amlodipine
  10. Compelling Indications of HTN
    • Heart Failure
    • Post Myocardial Infarction
    • High Coronary Disease Risk
    • Diabetes Mellitus
    • Chronic Kidney Disease
    • Recurrent Stroke Prevention
  11. Medication for No Compelling Indications
    Stage 1 Hypertension
    (SBP 140-159 or DBP 90-99)
    Thiazide-type diuretics

    ACE inhibitor, ARB, CCB, or combination
  12. Medication for No Compelling Indications

    Stage 2 Hypertension
    (SBP> 160 or DBP> 100)
    Two-drug combination for most

    Usually a thiazide-type diuretic with an ACE inhibitor, or ARB, or CCB
  13. Compelling Indications Pharmacotherapy
    Left Ventricular Function:
    • Standard: Diuretic with ACE inhibitor
    • then add Beta-Blocker

    Add-on: ARB or aldosterone anatagonist
  14. Compelling Indications Pharmacotherapy
    Postmyocardial Infarction:
    Standard: Beta-Blocker than add ACE inhibitor or ARB

    Add-on: Aldosterone antagonist
  15. Compelling Indications Pharmacotherapy
    Coronary Disease:
    Standard: Beta-Blocker then add ACE inhibitor or ARB

    Add-on: CCB, diuretic
  16. Compelling Indications Pharmacotherapy
    Diabetes Mellitus:
    Stanard: Ace inhibitor or ARB

    Add-on: diuretic

    2nd add-on: Beta-blocker, CCB
  17. Compelling Indications Pharmacotherapy
    Chronic Kidney Disease:
    Standard: ACE inhibitor or ARB
  18. Compelling Indications Pharmacotherapy
    Recurrent Stroke Prevention:
    Standard: Diuretic with ACE inhibitor or ARB
  19. Trial of Preventing Hypertension (TROPHY) showed treating prehypertension with which drug decreased progression to stage 1 hypertension?
    candesartan - ARB
  20. Signs and symptoms of preeclampsia
    BP>140/90 mmHg after 20 weeks’ gestation with proteinuria
  21. Drug of choice for treating HTN in pregnancy:
    Methyldopa-(Central Sympatholytics)

    While Labetolol -(Alpha/Beta-Blocker) has increasingly been preferred over methyldopa because of fewer side effects
  22. Intial BP drop with diuretics caused by:
  23. Types of Diuretics:
    • Thiazide - chlorthalidone, hydrochlorothiazide (HCTZ), indapamide, metolazone
    • Loop - bumetanide, furosemide, torsemide
    • Potassium-sparing - amiloride, triamterene
    • Aldosterone antagonists - eplerenone, spironolactone
  24. Thiazide Diuretics
    Dosing and Adverse effects
    • Dose in morning to avoid nocturnal diuresis
    • —Adverse effects: hypokalemia, hypomagnesemia, hypercalcemia, hyperuricemia, hyperuricemia, hyperglycemia, hyperlipidemia, sexual dysfunction
    • —lithium toxicity with concurrent administration
  25. Loop Diuretics
    Dosing and Adverse effects
    • Dose in AM or afternoon to avoid nocturnal diuresis
    • Higher doses may be needed for patients with severely decreased glomerular filtration rate or heart failure
    • Used in patients with kidney dysfunction (SCr > 2.5)
    • Adverse effects: hypokalemia, hypomagnesemia, hypocalcemia, hyperuricemia, hyperuricemia
  26. Potassium-sparing Diuretics
    Dosing and Adverse effects
    • Dose in AM or afternoon to avoid nocturnal diuresis
    • Generally reserved for diuretic-induced hypokalemia patients
    • Weak diuretics, generally used in combination with thiazide diuretics to minimize hypokalemia
    • Adverse effects: may cause hyperkalemia especially in combination with an ACE inhibitor, angiotensin-receptor blocker or potassium supplements
    • avoid in patients with CKD or diabetes
  27. Aldosterone Antagonists
    Dosing and Adverse effects
    Dose in AM or afternoon to avoid nocturnal diuresis

    Due to increased risk of hyperkalemia, eplerenone contraindicated in CrCl < 50 mL/min & patients with type 2 diabetes & proteinuria

    • Adverse effects:
    • may cause hyperkalemia especially in combination with ACE inhibitor, angiotensin-receptor blocker or potassium supplements

    avoid in CKD or DM patients

    Gynecomastia: up to 10% of patients taking spironolactone
  28. What is a 2nd line diuretic for most patients?
    ACE Inhibitors
  29. Function and Effect of ACE inhibitors:
    • Block bradykinin degradation; stimulate synthesis of other vasodilating substances such as prostaglandin E2 & prostacyclin
    • Prevent or regress left ventricular hypertrophy by reducing angiotensin II myocardial stimulation
  30. What must be monitored when patient is prescribed ACE inhibitors?
    Monitor serum K+ & SCr within 4 weeks of initiation or dose increase
  31. ACE Inhibitors
    Adverse effects:
    • Adverse effects:
    • cough - up to 20% of patients due to increased bradykinin
    • angioedema
    • hyperkalemia: particularly in patients with CKD or DM
    • neutropenia, agranulocytosis, proteinuria, glomerulonephritis, acute renal failure
  32. ARBs
    Adverse effects
    • Adverse effects:
    • orthostatic hypotension
    • renal insufficiency
    • hyperkalemia
  33. True or False
    ARBs do not block bradykinin breakdown
    • True
    • Do not block bradykinin breakdown
    • less cough than ACE Inhibitors
  34. Should ACE inhibitors or ARBs be used in treating HTN during preganancy?
    • NO
    • Pregnancy category C in 1st trimester
    • Pregnancy category D in 2nd & 3rd trimester
  35. Renin Inhibitor
    Action and Adverse effects
    • Inhibits angiotensinogen to angiotensin I conversion
    • Does not block bradykinin breakdown
    • less cough than ACE Inhibitors
    • Adverse effects: orthostatic hypotension, hyperkalemia
  36. Action of Beta-Blockers
    • Inhibit renin release
    • weak association with antihypertensive effect
    • Negative chronotropic & inotropic cardiac effects reduce CO
  37. Action of Beta-Blockers with intrinsic sympathomimetic activity (ISA)
    • do not reduce CO
    • lower BP
    • decrease peripheral resistance
  38. Beta-Blockers
    Adverse effects:
    • bradycardia
    • atrioventricular conduction abnormalities
    • acute heart failure
    • abrupt discontinuation may cause rebound hypertension or unstable angina, myocardial infarction, & death in patients with high coronary disease risk
    • bronchospastic pulmonary disease exacerbation
    • may aggravate intermittent claudication, Raynaud’s phenomenon
  39. Beta1 Receptors:
    • heart, kidney
    • stimulation increases HR, contractility, renin release
  40. Beta2 Receptors:
    • lungs, liver, pancreas, arteriolar smooth muscle
    • stimulation causes bronchodilation & vasodilation
    • mediate insulin secretion & glycogenolysis
  41. Types of Beta-Blockers:
    • Cardioselective - atenolol, betaxolol, bisoprolol, metoprolol, nebivolol
    • Nonselective - nadolol, propranolol, timolol
    • Intrinsic sympathomimetic activity -acebutolol, carteolol, penbutolol, pindolol
    • Mixed α- and β-blockers - carvedilol, labetolol
  42. Which types of Beta-Blockers are generally preferred for treating HTN?
    • Cardioselective Beta-Blockers
    • (Beta1)
  43. Which type of Beta-Blocker is safer to use in patients with bronchospastic disease?
    • Cardioselective Beta-Blockers
    • (Beta1)
    • Safer in patients with bronchospastic disease, peripheral arterial disease, diabetes
    • may exacerbate bronchospastic disease when selectivity lost at high doses
    • dose where selectivity lost varies from patient to patient
  44. Nonselective Beta-Blockers
    Additional benefits in:
    • essential tremor
    • migraine headache
    • thyrotoxicosis
  45. Mixed α- & β-blockers
    Adverse effects:
    additional blockade produces more orthostatic hypotension
  46. CCBs
    • Inhibit influx of Ca2+ across cardiac & smooth muscle cell membranes
    • muscle contraction requires increased free intracellular Ca2+ concentration
    • CCBs block high-voltage (L-type) Ca2+ channels resulting in coronary & peripheral vasodilation
  47. Types of CCBs:
    • Dihydropyridines: amlodipine, felodipine, isradipine, nicardipine, nifedipine, nisoldipine, clevidipine
    • Non-dihydropyridines: diltiazem, verapamil
  48. Adverse effects of non-dihydropyridines:
    • bradycardia
    • atrioventricular block
    • systolic HF
  49. Alpha1-Blockers
    Adverse effects:
    • orthostatic hypotension
    • 1st dose phenomenon: transient dizziness, faintness, palpitations, syncope within 1 to 3 hours of 1st dose
    • lassitude, vivid dreams, depression
    • priapism
    • Na+/H2O retention
  50. Alpha1-Blockers
    Dosing and Usage
    • 1st dose at bedtime
    • Used with diuretics to minimize edema Caution in elderly patients
    • Reduce benign prostatic hypertrophy symptoms
    • block postsynaptic α1-adrenergic receptors on the prostate
    • relaxation
    • decreased urinary outflow resistance
  51. Central Alpha2-Agonists
    Adverse effects:
    • Adverse effects: sodium/water retention
    • abrupt discontinuation may cause rebound HTN
    • depression
    • orthostatic hypotension
    • dizziness
    • Clonidine: anticholinergic side effects
    • Methyldopa: can cause hepatitis, hemolytic anemia (rare)
  52. Suffix(es) of Beta-Blockers
  53. Suffix(es) of CCBs Dihydropyridines
  54. Suffix(es) of ACE inhibitors
  55. Suffix(es) of ARBs
    • -tan
    • -tin
  56. Suffix(es) of Alpha-Blockers
    • -sin
    • -mine
  57. Direct Arterial Vasodilators
    Adverse Effects:
    • sodium/water retention
    • angina
    • Hydralazine can cause lupus-like syndrome
    • Minoxidil can cause hypertrichosis
  58. Action of Reserpine (Central Sympatholytic)
    • Peripheral adrenergic antagonist
    • depletes norephinephrine from sympathetic nerve endings; blocks norephinephrine transport into storage granules
    • reduces norephinephrine release into synapse following nerve stimulation
    • reduced sympathetic tone
    • peripheral vascular resistance reduction
    • decreased BP
    • depletes catecholamines from brain & myocardium
  59. Reserpine (Central Sympatholytic)
    Adverse Effects:
    • sedation
    • depression
    • decreased CO
    • sodium/water retention
    • increased gastric acid secretion
    • diarrhea
    • bradycardia
    • Use with diuretic (preferably thiazide) to avoid fluid retention
  60. Orthostatic Hypotension:
    Decrease in SBP > 20 mmHg or DBP > 10 mmHg when changing from supine to standing position
  61. Hypertensive Crisis
    • BP > 180/120 mmHg
    • reduce gradually
  62. Hypertensive urgency:
    • elevated BP
    • no acute or progressing target-organ injury
  63. Hypertensive emergency
    • acute or progressing target-organ damage
    • encephalopathy, intracranial hemorrhage, acute left ventricular failure with pulmonary edema, dissecting aortic aneurysm, unstable angina, eclampsia
  64. Sodium nitroprusside
    Adverse Effects:
    Nausea, vomiting, muscle twitching, sweating, thiocyanate and cyanide intoxication
  65. Sodium nitroprusside
    Special Indications:
    Most hypertensive emergencies; caution with high intracranial pressure, azotemia, or in chronic kidney disease
  66. Nicardipine hydrochloride
    Adverse Effects:
    Tachycardia, headache, flushing, local phlebitis
  67. Nicardipine hydrochloride
    Special Indications:
    Most hypertensive emergencies except acute heart failure; caution with coronary ischemia
  68. Clevidipine butyrate
    Adverse Effects:
    Headache, syncope, dyspnea, nausea, vomiting
  69. Clevidipine butyrate
    Special Indications:
    Most hypertensive emergencies except severe aortic stenosis; caution with heart failure
  70. Fenoldopam mesylate
    Adverse Effects:
    Tachycardia, headache, nausea, flushing
  71. Fenoldopam mesylate
    Special Indications:
    Most hypertensive emergencies; caution with glaucoma
  72. Nitroglycerin
    Adverse Effects:
    Headache, vomiting, methemoglobinemia, tolerance with prolonged use
  73. Nitroglycerin
    Special Indications:
    Coronary ischemia
  74. Hydralazine hydrochloride
    Adverse Effects:
    Tachycardia, flushing, headache vomiting, aggravation of angina
  75. Hydralazine hydrochloride
    Special Indications:
    Eclampsia (In Hypertensive Emergency)
  76. Labetalol hydrochloride
    Adverse Effects:
    Vomiting, scalp tingling, bronchoconstriction, dizziness, nausea, heart block, orthostatic hypotension
  77. Labetalol hydrochloride
    Special Indications:
    Most hypertensive emergencies except acute heart failure
  78. Esmolol hydrochloride
    Adverse Effects:
    Hypotension, nausea, asthma, first-degree heart block, heart failure
  79. Esmolol hydrochloride
    Special Indications:
    Aortic dissection; perioperative
  80. Monitoring Diuretics:
    • Parameters:
    • blood pressure
    • BUN/serum creatinine
    • serum electrolytes (K+, Mg2+, Na+)
    • uric acid (for thiazides)
  81. Monitoring Beta-Blockers:
    • Parameters:
    • blood pressure
    • heart rate
  82. Monitoring:
    Aldosterone antagonists
    ACE inhibitors
    Angiotensin II receptor blockers
    Direct Renin inhibitors
    • Parameters:
    • blood pressure
    • BUN/serum creatinine
    • serum potassium
  83. Monitoring CCBs:
    • Parameters:
    • blood pressure
    • heart rate
  84. Resistant Hypertension:
    failure to achieve BP goal on full doses of 3 drug regimen including a diuretic
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