Positive INOTROPIC Agents Flashcards
Inotropic Agents main action?
Increases contractility
Digoxin is a ______. 2 other ones are _______and ________
Cardiac glycosides; Digitoxin OUABAIN
Digoxin extracted from which plant?
Fox glove plant
Digoxin (—tropic effects)
Effects are due to
Positive inotropic
Negative chronotropic
Negative dromotrophic
Combination of several mechanisms of action.
Digoxin : MECHANISM OF ACTION selectively and reversibly bind to the
- alpha subunit of the sodium potassium pump and inhibits its action in the sarcolemma of cardiac cells.
- This leads to a decrease in the outward Na+ movement and an INCREASE in intracellular Na+ concentration.
- The high cellular Na+ concentration reduces the inward Na+ movement via the Na+/Ca2+ EXCHANGER
- This in turn DECREASE the outward movement of calcium via the Na+/Ca2+ exchanger and results in INCREASE INTRACELLULAR CA2+ concentration.
- Ca2+ is then accumulated in higher concentration in the SR.
Digoxin NET EFFECT
Increase force of contraction (enhances myocardial contractility)
Digoxin has an indirect effect______ AKA
Enhances parasympathetic effect at the heart.
Neurohormonal effect of digoxin
Digoxin on heart: EKG and conduction
Prolong refractory period - Prolonged PR Interval
Decreases conduction velocity through the AV node.
Digoxin does what to baroreceptors
resulting in? ___________ and reduced activity of _______and _________
Sensitizes the baroreceptors
Results in increased afferent inhibitory activity and reduced activity of the SNS and Renin-angiotensin system pressure.
Overactive Sympathetic system and RAAS System happens in ______and digoxin leads to a
Heart failure; decrease in the degrees of activation of the SNS and Renin angiotensin system.
Effects of digoxin in HF
Increase CO Lower PA pressure Lower PCWP Lower LVEF Decrease systolic and End diastolic dimensions
Pharmokinetics of digoxin
Absorption : don’t need to know
Bioavailability : depending on dosage from
70-100%
IV onset of action of digoxin
5-30 minutes
Distribution of digoxin (what muscles)
HUGE VOLUME OF DISTRIBUTION
Distribute to CARDIAC and SKELETAL MUSCLE
Heart concentration of digoxin ______ than plasma
> 15-30 Times than plasma
Does digoxin distribute into adipose tissue
NO
Protein binding of digoxin
20-30%
Loading dose and maintenance dose of digoxin based on
Lean body weight
Metabolism of digoxin where ? how much?
Small percentage in the liver
Metabolism of digoxin: is it dependent on Cytochrome p450?
NO
Elimination (met+ excretion)
2/3 unchanged in the urine
What is the Half life of digoxin? Increases with _______
Anuric patients
36hours ; renal failure
up to 5 days
Digoxin is not removed by
exchanged transfusions or peritoneal dialysis or hemodialysis
Not all drugs excreted by kidneys
can be removed by hemodialysis
Digoxin Clearance REDUCED/DECREASED in _____, _____, ______ which leads to ______IN digoxin concentrations
CHF
Hypothyroidism
Renal dysfunction
increased
Digoxin Clearance INCREASED in_______ which leads to _______In digoxin concentrations.
HYPERthyroidism; decreased
Therapeutic index of Digoxin is
narrow margin of safety (TI)
Therapeutic dose of digoxin for adults
0.5-2 ng/mL
Therapeutic dose of digoxin for INFANTS and CHILDREN
2.3-3.5 ng/mL
CHF therapeutic range
0.5-0.9 ng/mL
The therapeutic range for digoxin is ________ for patients w. HF
Lower
Obtain digoxin levels at least ______after the dose due to __________
6-8 hours; Long distribution phase of the drug.
Warning precautions for Digoxin : 3 electrolytes to monitor
Other precautions/warnings : C-MEESSIAH
HYPOKALEMIA
HYPOMAGNESEMIA
HYPERCALCEMIA
Constrictive Cardiomyopathies Myxedema coma End stage Renal Disease Elderly Sick sinus syndrome Severe pulmonary disease Incomplete AV block Acute MI Hypoxia
Not used in ______why?
acute decreased LV contractiliy ; there are better drugs with less toxicity
Cardioversion of digoxin patients Y/N why/not?
NEVER –> may lead to Vfib
Drugs INCREASE serum digoxin levels by DECREASING digoxin clearance:
What do you do? VEQDAD
What do you do to the dose of digoxin if patients are already taking those meds?
Diltiazem Verapamil Quinidine Amiodarone Dronedarone Erythromycin
Decrease dose by 50%
Drugs DECREASE serum digoxin levels by INCREASING digoxin clearance:
PRAMP
Antacids Rifampin Phenobarbital Phenytoin Metoclopramide.
Avoid pre-operatively
Cimetidine, Omeprazole, Indomethacin, Ibuprofen
Avoid pre-operatively, may increase digoxin levels.
Omeprazole, ….
Enhances pharmacodynamic effect of digoxin
Sympathomimetic
Halothane and digozin
Halogenated carbon antagonize digoxin effects; decrease digoxin effect
Drug to drug interactions of digoxin;
Co-administration of dig with betablockers and non-dihydropyridine CCB increases the risk of bradycardia and AV block
Thiazide and loop diuretics or any drug
that facilitated renal loss of potassium and magnesium can cause hypokalemia and hypomagnesemia and thus increase the risk of digoxin toxicity.
Digoxin in high concentrations can cause
Toxicity
inhibition of sodium ATP ase transport system, which leads to TOO Much accumulation of Ca2+ ion s in the Sarcoplasmic recticulum …Can AcTIVIATE the SNS
The increased in intracellular _______ loading and ________ ________ACtivity contribute to the generation of both atrial and ventricular arrhythmia
Calcium; increased sympathetic
What rule of digoxin toxicity
Plasma concentration of less < 0.5 ng/mL
**Digoxin responses are
**dose dependent
Digoxin toxicity: explain heart
The slope of phase 4 depolarization of the cardiac action potential is enhanced by digoxin. (increased rate of automaticity) especially if the patient is hypokalemic, which can produces various cardiac arrhythmia.
Digoxin toxicity
CRF
Most frequent causes of digoxin toxicity
Renal failure.
During anesthesia
hyperventilation can decrease serum K+ concentration an averatge of 0.5 mEq/L for every 10 mmHg decrease in PaCo2 which could cause hypokalemia
Older patients most at risk for developing toxicity due to
Decreased renal function
Decreased muscle mass
Drug-drug interactions
Cardiac manifestations of Digoxin Toxicity?
Predisposes patient to cardiac manifestation of dig toxicity?
Hypokalemia
Hypomagnesemia
Hypercalcemia
***Non-cardiac Signs and symptoms of digoxin toxicity (MOST COMMON)
Nausea Vomiting Diarrhea (NVD)
Other signs of non-cardiac
Visual Halos
Drowsiness and fativue. TRIGEMINAL NEURALGIA.
Cardiac Signs and symptoms of digoxin toxicity ?
Most reported ?
ANY (atrial or ventricular arrhythmias)
MOSt common reported. PAT with AV block
Digoxin and ATPase
compete with Potassium at the binding site of the Na+/K+ ATPase
Treatment of Digoxin toxicity
Correct predisposing causes (hypokalemia, hypomagnesemia, arterial hypoxemia)
****Treatment of Digoxin toxicity: Digoxin induced ventricular arrythmia
***Lidocaine IV or Phenytoin IV
Antidote of digoxin ?
Acute overdose?
DIGIBIND
activated charcoal
Antidote of digoxin
(digoxin immune fab) DIGIBIND
Life threatening or potentially life threatening digoxin toxicity treated with
Digoxin immune fab
Digibind is an _____ -______ agent
Digibind mechanism of action
antigen biding agent
the Fab fragments bind molecules of free digoxin making them UNavailable at their sit of action on cells in the body
Digoxin immune fab has greater affinity for digoxin than digoxin does for its receptor binding site on the Na-KPase pump.
The Fab fragment-digoxin accumulates in the blood and the complex is then excreted by the kidneys.
Name 2 Selective Phosphodiesterase III Inhibitors?
Milrinone
Imamrinone
Name 2 NON-Selective Phosphodiesterase III Inhibitors?
Theophylline
Aminophylline
Name five NON-catecholamines and non glycosides INOTROPIC agents
Selective PDIII Inhibitors
Non-selective PDIII inhibitors
Calcium
Glucagon
Principal CV effect of digoxin is ______and 5 main effects
Dose dependent Increased SV and CO Decreased heart size Decreased LVEDP / wall tension Decreased Oxygen consumption Frank Starling curse shifted to the LEFT
EKG effects of digoxin
Prolongs P-R interval due to delayed conduction of cardiac impulses through AV node
Short QTI
When digitalis is discontinued , the changes in the ECG disappear when ? _______why?
After several weeks
long half life
***Clinical uses of digoxin (main and others)
MANAGEMENT OF CHRONIC CHF
Enhancing vagal tone
Digoxin control ventricular respons rate,
added to BBlockers and CCB for additional ventricular rate control.
What are the benefits of digoxin in chronic CHF ? Has it been shown to reduce mortality in HF patients?
Neurohormonal modulating effects and positive inotropic effects.
No
Use of digoxin is WPW? why/not?
Do not use also in
no –> lead to very rapid ventricular response or VFib
Constrictive pericarditis
Idiopathic hypertrophic sub aortic stenosis
3 meds that protect against digitalis enhanced cardiac automaticity
Fentanyl
Enflurane
isoflurane
This dose of plasma concentration definitely toxic
> 3ng/ml
The most common cause of digoxin Toxicity in the ABSENCE OF RENAL DYSFUNCTION
Concurrent administration diuretics that cause k+ depletion.
What does HYPERKALEMIC state does to digoxin cardiac effects?
Decreases digoxin cardiac effects.
What does HYPOKALEMIC state does to digoxin cardiac effects?
Increases/potentiates digoxin cardiac effects
What does both MAG and CALCIUM do ?
Increases digoxin cardiac effects
What is the most frequent cause of death from digoxin toxicity
Vtach/Vfib
Severe acute digoxin intoxication may lead to which electrolyte imbalance?
HYPERKALEMIA
Digoxin contraindicated in 3 conditions
Wolf Parkinson White syndrome –>VFib
Cardioversion –> risk for Vfib increased
Acute Left ventricular failure or HIGH CARDIAC OUTPUT
Increases cardiac effects of digoxin_____(electrolyte abrnormality)
Hypokalemia
Hypomagnesemia
HYPERCALCEMIA
Decreases cardiac effects of digoxin_____(electrolyte abrnormality)
HYPERKALEMIA