Madeline Gervase

1

Cardiovascular Medications
and Hypertension

• Madeline Gervase
• RN,MSN,CCRN,FNP
• Advanced Practice Nurse

2
Introduction

• Pharmacology versus Therapeutics
• Diseases

• HTN
• CAD
• AMI

• CHF
• Arrhythmias
• Thromboembolic

3
Goals and Objectives

• To provide general information about
  cardiovascular medications
• Learn pharmacologic properties including
  mechanism of action, adverse effects, and
  clinical use of the following medications

• Diuretics
• ACE inhibitors
• ARBs
• Beta blockers

• CCBs
• Vasodilators
• Nitrates
• Digoxin

4
Hypertension

• BPCO X SVR
• CO
• Myocardial contractility, heart rate, venous
  return
• Venous return
• Total blood volume
• Kidney
• Percentage of blood volume circulating centrally
• Venous tone
• SVR
• Arteriolar smooth muscle tone

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Hypertension

• Kidney
• Production of renin
• Regulation of blood volume
• Sympathetic nervous system
• Regulation of cardiac output and peripheral
  resistance
• Renin-angiotensin-aldosterone
• Vasoconstriction (angiotensin II)
• Increased cardiac output secondary to sodium
  retention (aldosterone)

6
Hypertension Medications

• Diuretics
• Reduce blood volume
• Inhibitors of angiotensin
• Reduce SVR and blood volume
• Sympatholytic agents
• Reduce SVR and CO
• Direct vasodilators
• Reduce SVR

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Diuretics

• General mechanism of action
• Decrease blood volume
• Long-term effects from decreased PVR
• Specific mechanisms
• Effect transport proteins of tubular cells
• Prevent water reabsorption
• Inhibit enzymes
• Interfere with hormone receptors

8
Diuretics
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Carbonic Anhydrase Inhibitors

• Acetazolamide, methazolamide
• CA leads to reabsorption of bicarbonate
• Inhibition leads to a sodium bicarbonate diuresis
  and reduction in bicarbonate stores
• Not used for hypertension
• Glaucoma, urinary alkalination (uric acid
  elimination, ASA), acute altitude sickness

10
Osmotic

• Mannitol, glycerin
• Large, non absorbed molecule passing through
  highly water permeable proximal tubule and
  descending limb of Loop decreases reabsorption of
  water
• Not used for hypertension
• Reduce intraocular, intracranial pressure

11
Loop

• Furosemide, bumetanide, ethacrynic acid,
  torsemide
• Inhibition of Na/K/Cl transport in the ascending
  limb of the Loop of Henle, increases excretion of
  Na and water.
• CV uses primarily in CHF, also edema, renal
  failure

12
Thiazide

• Hydrochlorothiazide, chlorthalidone, indapamide,
  metolazone
• Inhibits NaCl cotransporter in epithelial cells
  of distal convoluted tubule

13
Potassium Sparing

• Spironolactone competitive antagonist binds to
  aldosterone receptors, increases Na excretion
• Amiloride, triamterene acts on the collecting
  tubule to inhibit sodium transport through ion
  channels

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Diuretics
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Clinical Uses

• Hypertension
• Thiazide, thiazide with potassium sparing
• CHF
• Loop
• Spironolactone
• Edema
• Loop

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Adverse Effects

• Thiazide
• Hypokalemic metabolic alkalosis
• Hyperuricemia
• Impaired carbohydrate tolerance
• Hyperlipidemia
• Hyponatremia
• Loop
• Hypokalemic metabolic alkalosis
• Ototoxicity
• Hyperuricemia
• Hypomagnesemia

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Adverse Effects

• Potassium Sparing
• Hyperkalemia
• Hyperchloremic metabolic acidosis
• Gynecomastia
• Acute renal failure
• Kidney stones

18
Diuretic Mechanisms

• Effect transport proteins of tubular cells
• Loop, thiazide, amiloride, triamterene
• Prevent water reabsorption
• Osmotic
• Inhibit enzymes
• Acetazolamide
• Interfere with hormone receptors
• Spironolactone

19
ACE Inhibitors
20
Angiotensin Receptor Blockers
21
Angiotensinogen
Kininogen
Kalikrein
Increased prostaglandin synthesis
Angiotensin I
Bradykinin
Converting Enzyme
1
1
Angiotensin II
Inactive
2
2
Vasoconstriction
Aldosterone secretion
Vasodilation
Increased sodium and water retention
Decreased peripheral vascular resistance
Increased peripheral vascular resistance
Increased blood pressure
Decreased blood pressure
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Clinical Uses

• HTN
• CHF
• Diabetic Nephropathy
• Post-MI

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Adverse Effects

• Hypotension
• Acute renal failure
• Hyperkalemia
• Dry cough
• Angioedema
• CI in 2nd and 3rd trimester

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Beta Blockers

• Competitively antagonize the effects of
  catecholamines at B-adrenergic receptors.
• Decrease heart rate, stroke volume and cardiac
  output
• Initial increase in peripheral resistance from
  blockade of B-receptors in vessels that promote
  vasodilation, leaving unopposed alpha
  vasoconstriction

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Beta Blockers

• Cardioselective
• ISA
• MSA
• Mixed
• First pass
• Renal
• Half life

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Beta Blockers

• Clinical Uses
• Adverse Effects

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Calcium Channel Blockers

• Inhibition of calcium influx into arterial smooth
  muscle cells
• Nifedipine and other dihydropiridine agents are
  more selective as vasodilators, with less cardiac
  depressant effects than diltiazem and verapamil

28
CCB

• Smooth muscle long lasting relaxation
• Cardiac muscle reduction in contractility
  throught the heart and decrease in sinus node
  pacemaker rate and AV node conduction velocity

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CCB

• Dihydropyridine
• Amlodipine
• Felodipine
• Isradipine
• Nicardipine
• Nimodipine
• Nisoldipine
• Nitrendipine

• Miscellaneous
• Bepridil
• Diltiazem
• Verapamil

30
CCB

• Clinical Uses
• Adverse Effects

31
Central Alpha2-Receptor Agonists

• Clonidine, guanabenz, guanfacine, and methyldopa
• Decrease sympathetic outflow from the vasomotor
  center in the brain and increase in vagal tone.
• Peripheral activity plays a lesser role
• Stimulation of presynaptic a2-receptors decreases
  sympathetic tone

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Central Alpha2-Receptor Agonists

• Effects
• Decreased heart rate
• Decreased peripheral resistance
• Decreased renin activity
• Blunted baroreceptor reflexes

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Central Alpha2-Receptor Agonists

• Sedation and dry mouth
• Depression
• Rebound hypertension

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Methyldopa

• Catecholamine type molecule
• Stimulates central inhibitory alpha-adrenergic
  receptors
• Decreases peripheral vascular resistance,
  decreases systolic and diastolic BP, decreases
  heart rate

35
Methyldopa

• Sodium and fluid accumulation lead to tolerance
  of hypotensive effect, therefore diuretic use is
  needed
• Rare hepatitis and hemolytic anemia
• Coombs' positive (20)
• Coombs' positive HA (1)

36
Clonidine

• Reduces sympathetic outflow from the brain
  secondary to direct stimulation of
  alpha-receptors in the medulla
• Increased vagal tone leads to decreases in
  peripheral vascular resistance and heart rate
• Baroreceptors are blunted, leading to orthostatic
  hypotension and tachycardia

37
Clonidine

• Weekly patch for improved compliance and fewer
  side effects
• Disadvantages cost, skin irritation, 2-3 day
  delay of effect

38
Clonidine

• Uses
• Hypertensive urgency
• Adjunctive pain therapy
• Withdrawal alcohol, BZD, nicotine, opiate
• Adjunct to prolong anesthesia
• Migraine prophylaxis
• Menopausal symptoms
• Anxiety-related disorders

39
Alpha1 Blockers

• Prazosin, terazosin, doxazosin
• Selective alpha-1 blockade decreases total
  peripheral resistance and venous return.
• Inhibition of alpha-1 receptors in the periphery
  prevents vasoconstriction from adrenergic
  stimulation, allowing vasodilation without
  affecting heart rate or cardiac index.

40
Alpha1 Blockers

• Benign Prostatic Hypertrophy
• Prevent stimulation of alpha-1 receptors and
  subsequent smooth muscle contraction in the
  bladder neck and prostatic urethra
• Significantly increase urinary flow rates and
  decrease outflow obstruction and irritation
  symptoms

41
Alpha1 Blockers

• CNS side effects lassitude, vivid dreams,
  depression
• First dose phenomenon dizziness, faintness,
  palpitations, syncope
• ALLHAT

42
Vasodilators

• Hydralazine, minoxidil
• Relax arteriolar smooth muscle by increasing the
  intracellular concentration of cyclic GMP
• Decrease peripheral vascular resistance
• Activate baroreceptor reflexes, increasing
  sympathetic outflow
• Activate RAA system

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Vasodilator

• Hypotensive effect diminishes over time without
  concomitant use of a diuretic and sympathetic
  inhibitor.
• Angina can be exacerbated if vasodilators are
  used without sympathetic inhibitor (B blocker)

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Vasodilator

• Hydralazine lupus-like syndrome, dermatitis,
  drug fever, peripheral neuropathy, hepatitis,
  vascular headache
• Minoxidil greater compensatory effects (HR, CO,
  renin, sodium retention), hypertrichosis

45
Vasodilators

• Nitroprusside
• IV used for hypertensive emergency
• Decreases PVR without increasing CO, unless there
  is left ventricular failure
• Continuous IV infusion, effect is immediate and
  lasts 2-5 minutes
• Thiocyanate levels should be measured if infusion
  lasts longer than 72 hours

46
Vasodilators

• Diazoxide
• Direct acting arteriolar vasodilator decreases
  PVR, increases cardiac output, and maintains or
  increases renal plasma flow
• IV use for HTN emergency
• SE nausea, vomiting, tachycardia, hyperglycemia
• Use with diuretic

47
Cardiac Glycosides - Digoxin

• Positive inotropic effect
• Inhibits active transmembrane transport of sodium
  and potassium
• Binds to membrane-bound sodium-potassium ATPase
  enzyme, disabling the pump
• Increase of intracellular sodium activates
  sodium-calcium pump, increasing intracellular
  calcium

48
Digoxin

• Increased calcium improves myocardial
  contractility
• Indirect effect of vagal stimulation on SA and AB
  nodes, decreases sinus rate

49
Digoxin

• Loading dose 10 mcg/kg IV or PO
• 75 oral bioavailability
• Oral maintenance dose 0.125 to 0.5 mg
• Renal function, baseline cardiac function, size,
  age affect dosing
• Monitor drug levels

50
Digoxin

• Used in heart failure with supraventricular
  tachyarrhythmias
• Early in therapy to control ventricular response
• Used in HF with NSR
• No survival benefit
• Reduces symptoms and improves quality of life

51
Digoxin

• Adverse effects
• GI- N/V, abdominal pain, anorexia
• CNS- headache, hallucination, delirium,
• Vision changes
• Gynecomastia
• Arrhythmias
• Hypokalemia
• Hypercalcemia
• Hypomagnesemia

52
Nitrates

• Used in ischemic heart disease
• Reduces myocardial oxygen demand secondary to
  venodilation and arterial dilation, causing a
  reduction in wall stress from reduced ventricular
  volume and pressure
• Direct dilation of coronary arteries

53
Nitrates

• Mechanism
• Smooth muscle relaxation
• Nitric oxide stimulates guanylyl cyclase which
  increases cGMP leading to relaxation
• Preload and afterload are reduced
• Cardiac output and blood pressure are reduced
• Oxygen requirement is reduced

54
Nitrates

• Pharmacokinetics
• Large first-pass effect
• Short half lives (except isosorbide mononitrate)
• Large interindividual variations in blood
  concentrations

55
Nitrates

• Short, intermediate, long
• Acute attack v. prophylaxis
• IV, sublingual, PO, transdermal
• Half life 1-5 minutes
• Isosorbide dinitrate is well absorbed and has
  half-life of 5 hours

56
Nitrates

• Tolerance
• Adverse effects postural hypotension,
  headaches, flushing, nausea