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SRNAPharmacology I > Positive INOTROPIC Agents > Flashcards

Positive INOTROPIC Agents Flashcards

1
Q

Inotropic Agents main action?

A

Increases contractility

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2
Q

Digoxin is a ______. 2 other ones are _______and ________

A

Cardiac glycosides; Digitoxin OUABAIN

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3
Q

Digoxin extracted from which plant?

A

Fox glove plant

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4
Q

Digoxin (—tropic effects)

Effects are due to

A

Positive inotropic
Negative chronotropic
Negative dromotrophic

Combination of several mechanisms of action.

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5
Q

Digoxin : MECHANISM OF ACTION selectively and reversibly bind to the

A
  1. alpha subunit of the sodium potassium pump and inhibits its action in the sarcolemma of cardiac cells.
  2. This leads to a decrease in the outward Na+ movement and an INCREASE in intracellular Na+ concentration.
  3. The high cellular Na+ concentration reduces the inward Na+ movement via the Na+/Ca2+ EXCHANGER
  4. This in turn DECREASE the outward movement of calcium via the Na+/Ca2+ exchanger and results in INCREASE INTRACELLULAR CA2+ concentration.
  5. Ca2+ is then accumulated in higher concentration in the SR.
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6
Q

Digoxin NET EFFECT

A

Increase force of contraction (enhances myocardial contractility)

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7
Q

Digoxin has an indirect effect______ AKA

A

Enhances parasympathetic effect at the heart.

Neurohormonal effect of digoxin

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8
Q

Digoxin on heart: EKG and conduction

A

Prolong refractory period - Prolonged PR Interval

Decreases conduction velocity through the AV node.

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9
Q

Digoxin does what to baroreceptors

resulting in? ___________ and reduced activity of _______and _________

A

Sensitizes the baroreceptors

Results in increased afferent inhibitory activity and reduced activity of the SNS and Renin-angiotensin system pressure.

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10
Q

Overactive Sympathetic system and RAAS System happens in ______and digoxin leads to a

A

Heart failure; decrease in the degrees of activation of the SNS and Renin angiotensin system.

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11
Q

Effects of digoxin in HF

A 
Increase CO 
Lower PA pressure
Lower PCWP
Lower LVEF
Decrease systolic and End diastolic dimensions
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12
Q

Pharmokinetics of digoxin

A

Absorption : don’t need to know
Bioavailability : depending on dosage from
70-100%

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13
Q

IV onset of action of digoxin

A

5-30 minutes

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14
Q

Distribution of digoxin (what muscles)

A

HUGE VOLUME OF DISTRIBUTION

Distribute to CARDIAC and SKELETAL MUSCLE

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15
Q

Heart concentration of digoxin ______ than plasma

A

> 15-30 Times than plasma

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16
Q

Does digoxin distribute into adipose tissue

A

NO

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17
Q

Protein binding of digoxin

A

20-30%

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18
Q

Loading dose and maintenance dose of digoxin based on

A

Lean body weight

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19
Q

Metabolism of digoxin where ? how much?

A

Small percentage in the liver

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20
Q

Metabolism of digoxin: is it dependent on Cytochrome p450?

A

NO

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21
Q

Elimination (met+ excretion)

A

2/3 unchanged in the urine

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22
Q

What is the Half life of digoxin? Increases with _______

Anuric patients

A

36hours ; renal failure

up to 5 days

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23
Q

Digoxin is not removed by

A

exchanged transfusions or peritoneal dialysis or hemodialysis

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24
Q

Not all drugs excreted by kidneys

A

can be removed by hemodialysis

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25
Q

Digoxin Clearance REDUCED/DECREASED in _____, _____, ______ which leads to ______IN digoxin concentrations

A

CHF
Hypothyroidism
Renal dysfunction
increased

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26
Q

Digoxin Clearance INCREASED in_______ which leads to _______In digoxin concentrations.

A

HYPERthyroidism; decreased

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27
Q

Therapeutic index of Digoxin is

A

narrow margin of safety (TI)

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28
Q

Therapeutic dose of digoxin for adults

A

0.5-2 ng/mL

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29
Q

Therapeutic dose of digoxin for INFANTS and CHILDREN

A

2.3-3.5 ng/mL

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30
Q

CHF therapeutic range

A

0.5-0.9 ng/mL

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31
Q

The therapeutic range for digoxin is ________ for patients w. HF

A

Lower

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32
Q

Obtain digoxin levels at least ______after the dose due to __________

A

6-8 hours; Long distribution phase of the drug.

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33
Q

Warning precautions for Digoxin : 3 electrolytes to monitor

Other precautions/warnings : C-MEESSIAH

A

HYPOKALEMIA
HYPOMAGNESEMIA
HYPERCALCEMIA

Constrictive Cardiomyopathies
Myxedema coma
End stage Renal Disease
Elderly
Sick sinus syndrome
Severe pulmonary disease
Incomplete AV block
Acute MI
Hypoxia
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34
Q

Not used in ______why?

A

acute decreased LV contractiliy ; there are better drugs with less toxicity

35
Q

Cardioversion of digoxin patients Y/N why/not?

A

NEVER –> may lead to Vfib

36
Q

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?

A 
Diltiazem
Verapamil
Quinidine
Amiodarone
Dronedarone
Erythromycin

Decrease dose by 50%

37
Q

Drugs DECREASE serum digoxin levels by INCREASING digoxin clearance:
PRAMP

A 
Antacids
Rifampin
Phenobarbital
Phenytoin
Metoclopramide.
38
Q

Avoid pre-operatively

A

Cimetidine, Omeprazole, Indomethacin, Ibuprofen

39
Q

Avoid pre-operatively, may increase digoxin levels.

A

Omeprazole, ….

40
Q

Enhances pharmacodynamic effect of digoxin

A

Sympathomimetic

41
Q

Halothane and digozin

A

Halogenated carbon antagonize digoxin effects; decrease digoxin effect

42
Q

Drug to drug interactions of digoxin;

A

Co-administration of dig with betablockers and non-dihydropyridine CCB increases the risk of bradycardia and AV block

43
Q

Thiazide and loop diuretics or any drug

A

that facilitated renal loss of potassium and magnesium can cause hypokalemia and hypomagnesemia and thus increase the risk of digoxin toxicity.

44
Q

Digoxin in high concentrations can cause

A

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

45
Q

The increased in intracellular _______ loading and ________ ________ACtivity contribute to the generation of both atrial and ventricular arrhythmia

A

Calcium; increased sympathetic

46
Q

What rule of digoxin toxicity

A

Plasma concentration of less < 0.5 ng/mL

47
Q

**Digoxin responses are

A

**dose dependent

48
Q

Digoxin toxicity: explain heart

A

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.

49
Q

Digoxin toxicity

A

CRF

50
Q

Most frequent causes of digoxin toxicity

A

Renal failure.

51
Q

During anesthesia

A

hyperventilation can decrease serum K+ concentration an averatge of 0.5 mEq/L for every 10 mmHg decrease in PaCo2 which could cause hypokalemia

52
Q

Older patients most at risk for developing toxicity due to

A

Decreased renal function
Decreased muscle mass
Drug-drug interactions

53
Q

Cardiac manifestations of Digoxin Toxicity?

Predisposes patient to cardiac manifestation of dig toxicity?

A

Hypokalemia
Hypomagnesemia
Hypercalcemia

54
Q

***Non-cardiac Signs and symptoms of digoxin toxicity (MOST COMMON)

A

Nausea Vomiting Diarrhea (NVD)

55
Q

Other signs of non-cardiac

A

Visual Halos

Drowsiness and fativue. TRIGEMINAL NEURALGIA.

56
Q

Cardiac Signs and symptoms of digoxin toxicity ?

Most reported ?

A

ANY (atrial or ventricular arrhythmias)

MOSt common reported. PAT with AV block

57
Q

Digoxin and ATPase

A

compete with Potassium at the binding site of the Na+/K+ ATPase

58
Q

Treatment of Digoxin toxicity

A

Correct predisposing causes (hypokalemia, hypomagnesemia, arterial hypoxemia)

59
Q

****Treatment of Digoxin toxicity: Digoxin induced ventricular arrythmia

A

***Lidocaine IV or Phenytoin IV

60
Q

Antidote of digoxin ?

Acute overdose?

A

DIGIBIND

activated charcoal

61
Q

Antidote of digoxin

A

(digoxin immune fab) DIGIBIND

62
Q

Life threatening or potentially life threatening digoxin toxicity treated with

A

Digoxin immune fab

63
Q

Digibind is an _____ -______ agent

Digibind mechanism of action

A

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.

64
Q

Name 2 Selective Phosphodiesterase III Inhibitors?

A

Milrinone

Imamrinone

65
Q

Name 2 NON-Selective Phosphodiesterase III Inhibitors?

A

Theophylline

Aminophylline

66
Q

Name five NON-catecholamines and non glycosides INOTROPIC agents

A

Selective PDIII Inhibitors
Non-selective PDIII inhibitors
Calcium
Glucagon

67
Q

Principal CV effect of digoxin is ______and 5 main effects

A 
Dose dependent
Increased SV and CO
Decreased heart size
Decreased LVEDP / wall tension
Decreased Oxygen consumption
Frank Starling curse shifted to the LEFT
68
Q

EKG effects of digoxin

A

Prolongs P-R interval due to delayed conduction of cardiac impulses through AV node
Short QTI

69
Q

When digitalis is discontinued , the changes in the ECG disappear when ? _______why?

A

After several weeks

long half life

70
Q

***Clinical uses of digoxin (main and others)

A

MANAGEMENT OF CHRONIC CHF
Enhancing vagal tone
Digoxin control ventricular respons rate,
added to BBlockers and CCB for additional ventricular rate control.

71
Q

What are the benefits of digoxin in chronic CHF ? Has it been shown to reduce mortality in HF patients?

A

Neurohormonal modulating effects and positive inotropic effects.
No

72
Q

Use of digoxin is WPW? why/not?

Do not use also in

A

no –> lead to very rapid ventricular response or VFib
Constrictive pericarditis
Idiopathic hypertrophic sub aortic stenosis

73
Q

3 meds that protect against digitalis enhanced cardiac automaticity

A

Fentanyl
Enflurane
isoflurane

74
Q

This dose of plasma concentration definitely toxic

A

> 3ng/ml

75
Q

The most common cause of digoxin Toxicity in the ABSENCE OF RENAL DYSFUNCTION

A

Concurrent administration diuretics that cause k+ depletion.

76
Q

What does HYPERKALEMIC state does to digoxin cardiac effects?

A

Decreases digoxin cardiac effects.

77
Q

What does HYPOKALEMIC state does to digoxin cardiac effects?

A

Increases/potentiates digoxin cardiac effects

78
Q

What does both MAG and CALCIUM do ?

A

Increases digoxin cardiac effects

79
Q

What is the most frequent cause of death from digoxin toxicity

A

Vtach/Vfib

80
Q

Severe acute digoxin intoxication may lead to which electrolyte imbalance?

A

HYPERKALEMIA

81
Q

Digoxin contraindicated in 3 conditions

A

Wolf Parkinson White syndrome –>VFib
Cardioversion –> risk for Vfib increased
Acute Left ventricular failure or HIGH CARDIAC OUTPUT

82
Q

Increases cardiac effects of digoxin_____(electrolyte abrnormality)

A

Hypokalemia
Hypomagnesemia
HYPERCALCEMIA

83
Q

Decreases cardiac effects of digoxin_____(electrolyte abrnormality)

A

HYPERKALEMIA

SRNAPharmacology I (29 decks)

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