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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
Digoxin Clearance REDUCED/DECREASED in _____, _____, ______ which leads to ______IN digoxin concentrations
CHF Hypothyroidism Renal dysfunction increased
26
Digoxin Clearance INCREASED in_______ which leads to _______In digoxin concentrations.
HYPERthyroidism; decreased
27
Therapeutic index of Digoxin is
narrow margin of safety (TI)
28
Therapeutic dose of digoxin for adults
0.5-2 ng/mL
29
Therapeutic dose of digoxin for INFANTS and CHILDREN
2.3-3.5 ng/mL
30
CHF therapeutic range
0.5-0.9 ng/mL
31
The therapeutic range for digoxin is ________ for patients w. HF
Lower
32
Obtain digoxin levels at least ______after the dose due to __________
6-8 hours; Long distribution phase of the drug.
33
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 ```
34
Not used in ______why?
acute decreased LV contractiliy ; there are better drugs with less toxicity
35
Cardioversion of digoxin patients Y/N why/not?
NEVER --> may lead to Vfib
36
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%
37
Drugs DECREASE serum digoxin levels by INCREASING digoxin clearance: PRAMP
``` Antacids Rifampin Phenobarbital Phenytoin Metoclopramide. ```
38
Avoid pre-operatively
Cimetidine, Omeprazole, Indomethacin, Ibuprofen
39
Avoid pre-operatively, may increase digoxin levels.
Omeprazole, ....
40
Enhances pharmacodynamic effect of digoxin
Sympathomimetic
41
Halothane and digozin
Halogenated carbon antagonize digoxin effects; decrease digoxin effect
42
Drug to drug interactions of digoxin;
Co-administration of dig with betablockers and non-dihydropyridine CCB increases the risk of bradycardia and AV block
43
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.
44
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
45
The increased in intracellular _______ loading and ________ ________ACtivity contribute to the generation of both atrial and ventricular arrhythmia
Calcium; increased sympathetic
46
What rule of digoxin toxicity
Plasma concentration of less < 0.5 ng/mL
47
****Digoxin responses are
****dose dependent
48
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.
49
Digoxin toxicity
CRF
50
Most frequent causes of digoxin toxicity
Renal failure.
51
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
52
Older patients most at risk for developing toxicity due to
Decreased renal function Decreased muscle mass Drug-drug interactions
53
Cardiac manifestations of Digoxin Toxicity? | Predisposes patient to cardiac manifestation of dig toxicity?
Hypokalemia Hypomagnesemia Hypercalcemia
54
***Non-cardiac Signs and symptoms of digoxin toxicity (MOST COMMON)
Nausea Vomiting Diarrhea (NVD)
55
Other signs of non-cardiac
Visual Halos | Drowsiness and fativue. TRIGEMINAL NEURALGIA.
56
Cardiac Signs and symptoms of digoxin toxicity ? | Most reported ?
ANY (atrial or ventricular arrhythmias) | MOSt common reported. PAT with AV block
57
Digoxin and ATPase
compete with Potassium at the binding site of the Na+/K+ ATPase
58
Treatment of Digoxin toxicity
Correct predisposing causes (hypokalemia, hypomagnesemia, arterial hypoxemia)
59
******Treatment of Digoxin toxicity: Digoxin induced ventricular arrythmia
***Lidocaine IV or Phenytoin IV
60
Antidote of digoxin ? | Acute overdose?
DIGIBIND | activated charcoal
61
Antidote of digoxin
(digoxin immune fab) DIGIBIND
62
Life threatening or potentially life threatening digoxin toxicity treated with
Digoxin immune fab
63
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.
64
Name 2 Selective Phosphodiesterase III Inhibitors?
Milrinone | Imamrinone
65
Name 2 NON-Selective Phosphodiesterase III Inhibitors?
Theophylline | Aminophylline
66
Name five NON-catecholamines and non glycosides INOTROPIC agents
Selective PDIII Inhibitors Non-selective PDIII inhibitors Calcium Glucagon
67
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 ```
68
EKG effects of digoxin
Prolongs P-R interval due to delayed conduction of cardiac impulses through AV node Short QTI
69
When digitalis is discontinued , the changes in the ECG disappear when ? _______why?
After several weeks | long half life
70
***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.
71
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
72
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
73
3 meds that protect against digitalis enhanced cardiac automaticity
Fentanyl Enflurane isoflurane
74
This dose of plasma concentration definitely toxic
>3ng/ml
75
The most common cause of digoxin Toxicity in the ABSENCE OF RENAL DYSFUNCTION
Concurrent administration diuretics that cause k+ depletion.
76
What does HYPERKALEMIC state does to digoxin cardiac effects?
Decreases digoxin cardiac effects.
77
What does HYPOKALEMIC state does to digoxin cardiac effects?
Increases/potentiates digoxin cardiac effects
78
What does both MAG and CALCIUM do ?
Increases digoxin cardiac effects
79
What is the most frequent cause of death from digoxin toxicity
Vtach/Vfib
80
Severe acute digoxin intoxication may lead to which electrolyte imbalance?
HYPERKALEMIA
81
Digoxin contraindicated in 3 conditions
Wolf Parkinson White syndrome -->VFib Cardioversion --> risk for Vfib increased Acute Left ventricular failure or HIGH CARDIAC OUTPUT
82
Increases cardiac effects of digoxin_____(electrolyte abrnormality)
Hypokalemia Hypomagnesemia HYPERCALCEMIA
83
Decreases cardiac effects of digoxin_____(electrolyte abrnormality)
HYPERKALEMIA

SRNAPharmacology I (29 decks)

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