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
16
Q
Vasoactive Medications - properties
A
Vasopressors – ↑ BP by vasoconstriction (↑SVR)
Inotropy – ↑ myocardial contractility & CO (↑SV)
Chronotropy – ↑ heart rate
Dromotropy – ↑ in conduction of impulse
Lusitropy – ↑ diastolic relaxation
17
Q
Vasoactive drugs - Receptor Activity
A
- Agonist – promotes receptor activity
- Direct – bind to the receptors
- Indirect – increase endogenous activity
- Antagonist – inhibits receptor activity
- Exogenous – synthetic medications
- i.e. dobutamine
- Endogenous – naturally occurring substances
- i.e. dopamine
18
Q
Fundamental Principles
A
- MAP = SVR * CO
- SVR: how well arteries can squeeze
- CO: volume of blood pumped by each ventricle per minutes.
- CO = HR * SV
- HR: how well heart is pumping
- SV:howfullR&Lsidesare
- HR: beats per minutes
- SV: volume of blood pumped per beat or stroke
- Consists of Preload, Contractility and Afterload
- Intrinsic control: extent of venous return
- Extrinsic control: extent of sympathetic stimulation of the heart
- BOTH controls increase SV by increasing the strength of contraction of the heart
19
Q
What happens in Shock?
A
Septic shock (Warm)
- Dilated arteries and decrease volume “the tank is dry”
- Heart compensates - pumping harder and faster
- High HR, high SV, high CO, low SVR
Hypovolemic shock (Cold)
- Increase HR to compensate for loss of circulating volume and arteries are constricted to maintain BP
- High HR, low SV, low CO, high SVR
Cardiogenic shock
- Low CO (bad heart) with a high wedge pressure since left ventricle can’t empty and pressure backs up
- Low SV, low CO, High SVR (body constricts arterial bed to keep BP high)
20
Q
alpha, beta, and dopamine (DA) receptor activity
A
- alpha1 (arteries, GI/GU, liver, ventricle) – vasoconstriction, contractility, lowers insulin secretion
- alpha2 (arteries, CNS) – vasoconstriction, sedation
- beta1 (heart) – ^^ HR, contractility, conduction
- beta2 (lungs, GI/GU, skel musc, liver) – smooth musc relaxation, bronchodilation lowers K, ^ insulin secretion
- DA (heart, renal, pulm artery) – ^^ contractility, +diuresis, vasodilates
21
Q
Vasoactive Medications
A
- Catecholamines (Sympathomimetics)
- Act on receptors of the sympathetic nervous system and mimic the sympathetic nervous system
- i.e. Epinephrine, Norepinephrine
- Act on receptors of the sympathetic nervous system and mimic the sympathetic nervous system
- Vasopressin Analogs
- Phosphodiesterase Inhibitors
- Vasodilators
22
Q
Catecholamines
A
Catecholamines
-
Alpha Adrenergic Agonists
- Norepinephrine
- Phenylephrine
-
Beta Adrenergic Agonists
- Epinephrine
- Dopamine
- Dobutamine
- Isoproterenol
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
Epinephrine
* 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
Dopamine
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
Dobutamine
* 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
28
Isoproterenol
* Non-selective beta agonists, all beta
* *Blood pressure effects are based on cardiac output x total peripheral vascular resistance*
Indication
* Hypotension associated w/bradycardia or heart block
* Post heart transplant to ↑HR
Benefits
* Helps maintain heart rate
* Bronchodilation and pulmonary vasodilation
Negative Effect
* Tachyarrhythmias
* Increased myocardial oxygen demand
29
Catecholamines Adverse Effects
Dose related effects
* Central nervous system stimulation
* Tremors, restlessness
* Confusion, psychosis
Hyperglycemia
* Glycolysis and glyconeogenesis
↓ Serum potassium levels
* Beta agonists (Dobutamine, Isoproterenol)
Excessive vasoconstriction
* ↓ blood flow to vital organs – kidneys & GI tract
* GI tract ischemia or necrosis
* Epinephrine & Norepinephrine
Dysrhythmias
* Higher risk with beta 1 agonists
Extravasation
* All vasoconstrictors can cause severe tissue necrosis
* Alpha agonists -- norepi, phenylephrine, dopamine
* Reverse effects with phentolamine SQ (alpha antagonist)
30
VASOPRESSIN ANALOGS
Vasopressin
* Antidiuretic hormone
* Interaction with V1 V2 V3 receptors
* V1 receptors in vascular smooth muscle
* Produces vasoconstriction
* Low concentrations in pulmonary vessels cause NO release and vasodilation → hypotension
* Indication – Dosing varies greatly!
* Primary treatment of DI or GI bleeding
* Treatment of catecholamine refractory shock
* Vasopressin deficient state in shock and sepsis
* Low dose improves MAP and decreases catecholamine needs
* Recovers SVR
* Increases BP
* Negative Effects
* Hyponatremia
* Pulmonary vasoconstriction
* Mesenteric ischemia with high doses
31
PHOSPHODIESTERASE INHIBITORS: Milrinone
* 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
32
Nitroglycerin
* Organic nitrate
* Nitric oxide-mediated smooth muscle vasodilation
* Direct vasodilator with less effect on arterioles
Indication
* Improve myocardial perfusion post cardiac surgery
* Coronary vasodilation improves myocardial regional blood flow and myocardial oxygen demand
* Faster recovery from perioperative myocardial ischemia
Benefits
* Reduces:
* Right and left filling pressures
* Systemic & pulmonary vascular resistance
* Systemic blood pressure
* Increases cardiac output
* Provides afterload reduction
Negative Effects
* Hypotension, tachycardia, paradoxical bradycardia
* Methemoglobinemia
* Risk with all forms of nitrates
* Continuous infusions \> 24 hrs produce a nitrate tolerance or tachyphylaxis
33
Vasoactive drugs: Combination of Effects
* Low dose epinephrine
* ↑ inotropy (contractility), ↑ chronotropy (HR), ↓ SVR
* ↑ CO with mild vasodilation
* Dopamine
* ↑ inotropy (contractility)
* ↑CO
* Milrinone
* ↑ inotropy (contractility)
* lusitropy (↑ diastolic relaxation)
* ↓ preload and SVR
* Vasodilation
34
Neonatal Considerations
* Neonatal myocardium is not the same
* Decreased myocardial contractility
* Less sympathetic innervation than mature heart
* Decreased availability of endogenous norepinephrine
* Underdeveloped calcium regulatory mechanisms
