Cards Flashcards
1
Q
Digoxin
A
Increases force of myocardial contraction and creates a positive inotropic effect in heart failures results in:
- Slowing of cardiac rate
- Disappearance of gallop rhythm
- Improved tissue perfusion
- Diuresis and relief of edema
- Decreased venous pressure
MOA:
- Inhibits Na+, K+ exchange pump and Na+, K+-ATPase
- Enhances contraction by increasing influx of Ca++
- SVT – Slows rate of sinus node through vagal nerve; increases refractory period
2
Q
Digoxin ADME
A
- Oral Bioavailability ~75%
- Bioavailability is affected by intestinal flora
- P-glycoprotein, present in intestinal cells, pumps digoxin back into intestinal lumen, limits its absorption
- Medications that inhibits P-glycoprotein can increase digoxin bioavailability (e.g., macrolides)
- Higher Vd in infants and children than adults
- Renal excretion
- Adjust for renal impairment
3
Q
Digoxin Dosing
A
- Digitalizing dose may be administered over first 24 hours
- 50% of dose x 1, then 2 doses at 25% 6-8 hour intervals
- Oral therapy is initiated 12 hours after last loading dose
- Higher risk of digoxin toxicity in infants with loading doses
- Without loading dose
- Full therapeutic effect takes 4 to 7 days
- Commercially available as:
- Solution, 0.125 mcg and 0.25 mcg tablets, IV formulation
- Monitor for drug interactions – increase risk of toxicity
4
Q
Digoxin AE and Monitoring
A
AE:
- Cardiac – bradycardia, A-V block, vtach, vfib
- GI – N/V/D, anorexia
- CNS – dizziness, headache, malaise,
- Vision – Visual disturbances (Blurred or yellow vision)
Monitoring Parameters
- Heart rate and rhythm, ECG
- Serum potassium, magnesium, calcium (especially with co- administration of diuretics)
- Hypokalemia: Increases digoxin distribution to heart and muscles
- Renal function
- Serum digoxin concentrations
5
Q
Digoxin Concentration Levels
A
Therapeutic Range
- Obtain levels 8-12 hours post dose
- 0.5 to 2 ng/mL; (debate regarding benefits of levels > 1 ng/mL)
- Sweet spot: 0.5-0.9 – increasingly toxic >1
Increased risk of toxicity
- With levels >2 ng/mL
- Electrolyte abnormalities – hypokalemia, hypomagnesemia, hypercalcemia,
Endogenous Digoxin-Like Substances (EDLS)/ Digoxin-like immunoreactive Substance (DLIS)
- Seen in serum of newborn infants, pregnant women, and patients with hypertension or renal and hepatic disease
- May interfere clinical interpretation of serum concentrations during digoxin therapy
- more labs cannot differentiate, most concern in NBs due to low CrCl
6
Q
Digoxin Heart Failure Dosing
A
7
Q
ACE-Inhibitors
A
- Indicated for moderate or severe degrees of LV dysfunction, regardless of symptoms (ARB if ACE-I not tolerated)
MOA
- Block angiotensin II and aldosterone formation
- Potentiate effects of diuretics
- Diminish sympathetic activity
- Cause both arterial and venous dilation and consequently increase cardiac output and decrease right and left filling pressures and end-diastolic volumes
- Most commonly utilized agents in pediatrics
- Captopril
- Enalapril (prodrug for enalaprilat) IV/PO – dosing very different
8
Q
ACE-I AE and Monitoring
A
AE:
- Neonates and infants more sensitive
- Especially hypotension and nephrotoxicity
- Dry, hacking cough (esp captopril)
- CNS – confusion, drowsiness
- CV – syncope, orthostatic hypotension
- Rash, hyperkalemia, hyponatremia, nephrotic syndrome
Monitoring Parameters
- BP; serum potassium;
- Renal function, BUN, SCr
- Angioedema and anaphylactic reactions (try ARB is angioedema with ACE-I)
9
Q
Enalapril Dosing
A
Formulations
- Oral solution (Epaned); tablets
PO Dosing (Enalapril)
- 0.1 mg/kg/day initially up to 0.5 mg/kg/day in two divided doses
IV Dosing (Enalaprilat)
- 5 - 10 mcg/kg/dose (0.005 to 0.01 mg/kg/dose) q8-24 h (maximum dose 1.25 mg/dose)
10
Q
ARBs
A
- No effect on bradykinin metabolism
- More selective blockers of angiotensin effects than ACE inhibitors
AE – similar to ACE inhibitors
- Cough and angioedema can occur but are uncommon
- Commonly used: Irbesartan, losartan – both oral tablets
- **Both ACE-I and ARBs are contraindicated in Pregnancy
11
Q
Diuretics
A
Loop Diuretics – most potent
- Furosemide (40 mg PO)
- Oral bioavailability ~50%
- Torsemide (20 mg PO)
- Longer t1/2 than furosemide
- Bumetanide (1 mg PO)
Thiazide Diuretics
- Hydrochlorothiazide
- Chlorothiazide
- Metolazone**(thiazide-like)
12
Q
Loop Diuretics
A
- Most potent Diuretic
- Inhibit NaCl reabsorption in think ascending limb of loop of Henle
- Increase Ca++ and Mg++ excretion
- Significantly increase K+ excretion
- Multiple Indications
- Remain active in advanced renal failure • Edematous state
- Nephrotic syndrome
- CLD/RDS
- Hypercalcemic states
- Better controlled diuresis with continuous infusion
13
Q
Thiazide Diuretics
A
- Thiazide Diuretics
- Decrease NaCl reabsorption in distal convoluted tubule
- Stimulate Ca++ reabsorption in distal tubule
- Thiazides (except metolazone) are ineffective at GFRs < 30mL/min/1.73 m2
- Multiple Indications
- Edematous state
- Hypertension
- Proximal Tubular Renal Acidosis (increase bicarbonate concentrations)
- Nephrogenic Diabetes Insipidus
14
Q
Other Diuretics
A
Carbonic Anhydrase Inhibitors – weak diuretics
- Acetazolamide
- MOA: Inhibition of carbonic anhydrase, present in tubular cells and proximal tubular cells, results in urinary excretion of HCO3-, Na+, K+ – promoting alkaline diuresis
K+ Sparing/Aldosterone Receptor Antagonists
- Spironolactone
- MOA: Competitively inhibits binding of aldosterone to mineralocorticoid receptor, decreasing synthesis of aldosterone- induced proteins; Results in NaCl & water excretion while conserving K+ and H+ ions
- Often used in combination with other diuretics to increase K+
15
Q
Diuretics Adverse Effects
A
Loop diuretics
- Ototoxicity (usually reversible), hyperuricemia, hyperglycemia, hyperlipidemia, hypersensitivity
- Caution with drug interaction with nephrotoxic medications
Thiazide diuretics
- Hyperglycemia, insulin resistance, hyperlipidemia, hypersensitivity (fever, rash, purpura, anaphylaxis, interstitial nephritis), hyperuricemia
K+ Sparing/Aldosterone Receptor Antagonists
- Gynecomastia, hirsutism, impotence, and menstrual irregularities
23
Q
Norepinephrine
A
- Primary neurotransmitter in sympathetic system
- Potent vasoconstriction
- Elevation of SVR with improved perfusion – compromise organ blood flow
Indications:
- Spinal shock
- Warm shock with hypotension
- Low SVR states
Benefits:
- Increase venous return
- Improves cardiac preload
- Increases SVR and afterload
Negative Effects:
- Increased myocardial oxygen demand
- Organ ischemia due to vasoconstriction
- Severe extremity ischemia w/high dose
**Remember to fill the tank before you constrict the vessels
24
Q
Phenylephrine (pure alpha)
A
- Pure alpha-adrenergic agonist
- Vasoconstriction
- **Beneficial for severe hypotension without beta effects –Tachycardia or Tachyarrhythmia; warm shock
Indication
- Hypotension caused by tachydysrthythmias
- Hypercyanotic spells in TOF
- ↑ SVR needed to ↑ pulmonary blood flow
- Warm shock with hypotension
Benefits
- Systemic arterial vasoconstriction without beta effects on the heart
- ↓ arrhythmia potential
Negative Effects
- Reflex bradycardia secondary to ↑BP
- Vasoconstriction
- Decreased renal and splanchnic perfusion
25
Q
Epinephrine
A
- Low dose = +vasodilation
- High dose = +vasoconstriction (>0.2 lose beta effects)
Indication
- Shock, especially if dopamine refractory
- Low dose for severe systolic dysfunction after surgery
Benefits
- Low dose - increased contractility
- High dose – increased afterload
- Increase blood pressure
- Mid dose – increased SVR but is balance by increased contractility
- High dose – increased afterload may impair myocardial function and end-organ perfusion
Negative Effects
- Arrhythmias (anything that effects B1 has this risk)
- Increased myocardial oxygen demand
- More splanchnic vasoconstriction
- Abdominal ischemia with impaired blood flow (hold trophic feeds unless v low dose)
- Extravasation
- Severe vasospasm and tissue injury
- ↓ Serum potassium and phosphorus
- Hyperglycemia
26
Q
Dopamine
A
Dose-dependent hemodynamic effects
- Renal dose (low dose) controversial
- Direct & indirect adrenergic activity
Indications
- Shock and Hypotension
- Low cardiac states or myocardial dysfunction
Benefits
- β1 effects increases contractility
- Improves HR and BP
- Increases amount of Norepinephrine active in the body (secondary effect)
- At higher doses, DA stimulates release of NE which then stimulates alpha1 receptors to cause vasoconstriction and ↑SVR
Negative Effects
- Arrhythmias
- Increased myocardial oxygen demand
- Vasoconstriction with high dose
- Extravasation –> tissue necrosis
- May develop tolerance over time
27
Q
Dobutamine
A
- Used in adults > NICU > pediatrics*
- Milrinone used more often than dobutamine due dobutamine tolerance development*
Indications
- Cardiogenic shock
- Low-output shock with acceptable BP (↑ SVR)
Benefits
- ↑ myocardial contractility
- ↑ cardiac output (vasodilation)
- Reduction in cardiac filling pressures
Negative Effects
- Arrhythmias
- Increased myocardial oxygen demand
- May lower blood pressure
- Tachycardia with high dose
- Long term use associated with decreased survival
- Tolerance develops quicker at 48-72 hours
31
Q
PHOSPHODIESTERASE INHIBITORS: Milrinone
A
- PDE type III enzyme inhibitor
- Inhibits breakdown of cAMP and ↑cAMP in the myocardium, ↑Ca to the heart, ↑Contractility
- Vasodilator
- Longer half-life 2 to 4 hrs
- Adjust doses in renal failure
Indication
- Cardiogenic shock
- Heart failure
Benefits
- ↑ heart rate and contractility
- Enhances diastolic myocardial relaxation
- Vascular smooth muscle relaxation
- Decrease preload
- Beneficial effects on RV function
- Greater effect on decreasing SVR
- Does not increase heart’s oxygen demand (preferred over other inotropes in patients with ischemic cardiomyopathy)
Negative Effects
- Hypotension with rapid administration
- Ventricular arrhythmias (rare in kids)
- Headache
