NUR521 Module 4: Cardiovascular Hemodynamics

Hemodynamics and Diuretics

• Review of the circulatory system and cardiac output regulation
• Diuretics:
  • Sites of action:
    • PCT (proximal convoluted tubule): reabsorbs 65% of filtered sodium and chloride, and all of the bicarbonate and potassium in the filtrate
    • Loop of Henle: decreases the volume of the tubular urine and causes the urine to become concentrated
    • Early segment of distal convoluted tubule: reabsorbs 10% of filtered sodium and chloride
    • Distal nephron: site of sodium-potassium exchange and regulation of final urine concentration
• Triamterene/Dyrenium:
  • Non-aldosterone antagonist, potassium-sparing diuretic
  • Disrupts Na-K exchange in the distal nephron, decreasing Na reabsorption and reducing K secretion
  • Minimal diuresis
• Indications and uses of diuretics:
  • Furosemide: rapid or massive mobilization of fluid, pulmonary edema, heart failure, hypertension
  • Thiazide: hypertension, edema, CHF, hepatic or renal disease
  • Spironolactone: hypertension, edema, CHF, counteracts K-wasting diuretics, off-label uses
  • Triamterene: hypertension, edema, combination with furosemide to counteract K-wasting effects
• Factors to consider when choosing a diuretic:
  • Renal function
  • Indications and contraindications
  • Potential side effects
• Adverse effects of diuretics:
  • Furosemide: K wasting, hyponatremia, hypochloremia, dehydration, hypotension
  • Thiazide: hyponatremia, hypochloremia, dehydration, hypotension, hyperglycemia, hyperuricemia
  • Spironolactone: shown to cause tumors in rats, avoid unnecessary use

Vasodilators

• Hydralazine:
  • MOA: dilates arterioles, decreases peripheral resistance, and lowers arterial BP
  • Uses: hypertension crisis, heart failure, reduces afterload for a short time in CHF
  • Can be used in infants 1 month
  • Requires combination with beta blockers to prevent reflex tachycardia
  • Contraindicated in CAD, high risk for falls in older adults

Heart Failure

• Review of pathophysiology and stages of HF:
  • Ventricular dysfunction, reduced CO, insufficient tissue perfusion, fluid accumulation
  • Tx: diuretics, RAAS inhibitors, beta blockers, digoxin
• Stages of HF:
  • Systolic HF (HFrEF): LV dysfunction, reduced EF
  • Diastolic HF (HFpEF): LV can't relax, muscle is stiff
• Left and right heart failure:
  • Left: LV pumps inefficiently, blood backs up into the lungs, pulmonary edema
  • Right: RV pumps inefficiently, blood backs up into the venous system, liver congestion, ascites, edema in legs

Digoxin

• MOA: (+) inotropic action, increases myocardial contraction force, increases CO, alters electric activity of the heart
• Uses: treats CHF and dysrhythmias, 2nd line agent
• Adverse effects and contraindications:
  • Digoxin-induced dysrhythmias, narrow therapeutic window, hypokalemia
• Dosing and administration:
  • Hold for HR 100 despite max statins

Lifestyle Changes

• Eat better, move more, stop smoking, healthy BMI, manage stress

Statins

• Who needs to take a statin?
• Teach patients about statins:

Type 2 Diabetes

• Pharmacologic approach:
  • Guided by person-centered tx factors (comorbidities, tx goals, social determinants of health, lifestyle)
  • ACE inhibitor or ARB to reduce risk of diabetic nephropathy and manage diabetic hypertension
  • Metformin or combination therapy
  • Early intro of insulin if necessary
  • Glucagon-like peptide 1 receptor agonist preferred to insulin when possible
• A1C target goal for older adults: individualized, beware of overtreatment and polypharmacy
• Older adults at risk for:
  • Overtreatment and polypharmacy
  • Hypoglycemia
  • Management should be personalized to reduce hypoglycemia risk

Sodium-Potassium Exchange

• Aldosterone, the principal mineralocorticoid of the adrenal cortex, stimulates reabsorption of sodium from the distal nephron and causes potassium to be secreted.
• This can be viewed as an exchange mechanism, promoting sodium-potassium exchange by stimulating cells of the distal nephron to synthesize more pumps responsible for sodium and potassium transport.

Diuretics

Furosemide (Loop Diuretic)

• Acts in the thick segment of the ascending limb of the loop of Henle, blocking reabsorption of Na and Cl, preventing reabsorption of water, which equals profound diuresis even when renal blood flow and GFR are low.
• Can be combined with a thiazide diuretic (no use in combining with any other loop diuretic).
• Indicated for use when rapid or massive mobilization of fluid is required, such as pulmonary edema associated with CHF, edema from heart, liver, or kidney that haven’t responded to other drugs, and/or HTN.

Hydrochlorothiazide/Microzide (Thiazide Diuretic)

• Promotes urine production by blocking reabsorption of Na and Cl in the early segment of the distal convoluted tubule, resulting in water retention in the nephron and increased flow of urine.
• Indicated for use in HTN, edema in CHF, hepatic, or renal disease.

Spironolactone/Aldactone (Aldosterone Antagonist, Potassium-Sparing Diuretic)

• Blocks the action of aldosterone in the distal nephron, resulting in retention of K and excretion of Na.
• Diuresis is scanty because most Na has already been reabsorbed before reaching the distal tubule.
• Indicated for use in HTN, edema, CHF (blocking aldosterone creates protective effects), counteracts K-wasting diuretics, off-label: acne, hair loss, hirsutism, hormone therapy for transgender females.

Triamterene/Dyrenium (Non-Aldosterone Antagonist, Potassium-Sparing Diuretic)

• Disrupts Na-K exchange in the distal nephron by direct inhibition, resulting in decreased Na reabsorption and reduced K secretion, and increased Na excretion and K conservation.
• Minimal diuresis.
• Indicated for use in HTN, edema, combo drug can augment Lasix and counteract K-wasting effects.

Factors to Consider When Choosing a Diuretic

• Renal function: Furosemide can cause more loss of fluid and electrolytes than any other diuretic, K wasting, do not give if K is low.
• Thiazide: MUST have an adequate kidney function to work (minimum 20-30mL/min), CI with digoxin, lithium, and other HTN meds.
• Patient age: Furosemide use in caution in pts over 65 who are at higher risk for hyponatremia.

Adverse Effects of Diuretics

• ALL diuretics can cause profound diuresis with fluid and electrolyte depletion.
• Loop & thiazide AE: hyponatremia, hypochloremia, dehydration, hypotension, hypokalemia, ototoxicity (loop), hyperglycemia, hyperuricemia, reduced HDL, increased LDL.
• Spironolactone BBW: shown to cause tumors in rats, avoid unnecessary use.

Two-Drug Combinations for BP Control

• ACEI plus a thiazide diuretic, an ACEI plus a CCB, or a β blocker plus a thiazide.
• Review comorbid conditions that influence a prescriber’s choice of antihypertensive medication.

Comorbid Conditions and Antihypertensive Medication

• HTN & CKD: ACE inhibitor + loop diuretic (avoid thiazide and potassium-sparing drugs; ineffective), if intolerant to ACE, do ARB.
• HTN & DM: ACE inhibitors, ARBs, Ca Channel blockers (CCBs) are preferred.
• ACEIs & ARBs can slow progression of renal damage and reduce albuminuria.
• β blockers can mask sings of hypoglycemia.
• Thiazide & loop diuretics can cause hyperglycemia.

RAAS Drugs

ACEIs

• Blocks the conversion of angiotensin I to II, resulting in vasodilation, decreased blood volume, and cardiac remodeling, potassium retention, and fetal injury can occur.
• Increase levels of bradykinin through the inhibition of Kinase II, which also results in vasodilation, COUGH, and rarely angioedema.

ARBs

• Compare and contrast ACE-I and ARB: differences in MOA, similarities, and when to prescribe one over the other.
• MOA: blocks the effects of angiotensin II on BP, but does not affect kinin metabolism or bradykinin levels.

Direct Renin Inhibitor

• Eplerenone (Inspra): Potassium-sparing aldosterone antagonist (25 & 50 mg).
• MOA: selective blockage of aldosterone receptors without blocking receptors for other steroid hormones; promotes retention of potassium and increased secretion of Na and water, resulting in reduced blood volume and BP.
• USE: HTN & HF after tx with ACEI and BBs.
• AE: has less AE than spironolactone because it’s more selective, hyperkalemia.

CCB

• MOA: prevents calcium ions from entering cells, resulting in vasodilation and decreased heart contractility and rate.
• USE: Tx HTN, angina pectoris, cardiac arrhythmias.
• CI: hypotension, sick sinus syndrome, 2nd or 3rd degree HB, grapefruit juice, can intensify effects of beta blockers.
• AE: eczematous rash in older adults, dizziness, flushing, HA, edema of ankles & feet, worsening of HB.

Vasodilators

Hydralazine

• MOA: dilates arterioles, resulting in decreased peripheral resistance and lowered arterial BP.
• USE: HTN crisis, HF (reduces afterload for a short time in CHF).
• Can be used in infants 1 month.
• CI: CAD → angina attacks.
• High risk for falls in older adults (polypharmacy & orthostatic hypotension).

Cardiovascular I: Hemodynamics and Diuretics

• The circulatory system and cardiac output regulation are reviewed
• Diuretics work in the kidney, with different sites of action:
  • PCT (Proximal Convoluting Tubule): High resorptive capacity, reabsorbs 65% of filtered sodium and chloride, and all bicarbonate and potassium
  • Loop of Henle: Descending limb is freely permeable to water, decreases tubular urine volume and increases tonicity
  • Early segment of distal convoluted tubule: Reabsorbs 10% of filtered sodium and chloride, with water following passively
  • Distal nephron: Site of sodium-potassium exchange (under aldosterone influence) and final urine concentration (regulated by ADH)

Eplerenone (Inspra)

• MOA: Selective blockage of aldosterone receptors, promoting potassium retention and increased sodium and water secretion
• USE: Hypertension and Heart Failure, especially in patients already on ACEI and BBs
• AE: Hyperkalemia, with symptoms including dizziness, confusion, abnormal HR, numbness, and tingling
• CI: Potassium supplements, impaired renal function, and DM II with microalbuminuria

Calcium Channel Blockers (CCB)

• MOA: Prevent calcium ions from entering cells, leading to vasodilation and reduced heart contractile force
• USE: Hypertension, angina pectoris, and cardiac arrhythmias
• CI: Hypotension, sick sinus syndrome, 2nd or 3rd degree heart block, and grapefruit juice (which can intensify effects of beta blockers)
• AE: Eczematous rash in older adults, dizziness, flushing, headache, and edema of ankles and feet

Dihydropyridines (Nifedipine)

• MOA: Similar to CCB, but with more selective action on vascular smooth muscle
• USE: Hypertension and angina pectoris
• AE: Reflex tachycardia, especially with immediate-release formulation
• CI: CAD, as it can exacerbate angina attacks
• Pt education: Record anginal episodes, BP, and AE

Vasodilators (Hydralazine)

• MOA: Dilates arterioles, decreasing peripheral resistance and lowering arterial BP
• USE: Hypertension crisis and Heart Failure (reduces afterload for a short time in CHF)
• CI: CAD, as it can exacerbate angina attacks
• AE: High risk for falls in older adults due to polypharmacy and orthostatic hypotension
• Requires combination with beta blockers to prevent reflex tachycardia

Heart Failure (HF)

• Pathophysiology: Ventricular dysfunction, reduced CO, and insufficient tissue perfusion, leading to fluid accumulation
• Stages of HF:
  • Systolic HF (HFrEF): LV can't contract properly
  • Diastolic HF (HFpEF): LV can't relax, muscle is stiff
• Tx: Diuretics, RAAS inhibitors, beta blockers, and digoxin
• Left HF: Blood backs up into the lungs, leading to pulmonary edema and RHF
• Right HF: Blood backs up into the venous system, leading to liver congestion, ascites, and edema in legs

Digoxin

• MOA: (+) Inotropic action, increasing myocardial contraction force, and altering eclectic activity of the heart
• USE: CHF and dysrhythmias, but not a first-line agent
• AE/CI: Digoxin-induced dysrhythmias, narrow therapeutic window, hypokalemia, and many interactions
• S/S of toxicity: Nausea, vomiting, and ECG changes
• Antidote: Digoxin immune fab (Digibind)

Lifestyle Changes for HF Management

• Eat better
• Move more
• Stop smoking
• Healthy BMI
• Manage stress