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Year 4 - Toxicology > Lecture 11 - Cardiac Glycosides > Flashcards

Lecture 11 - Cardiac Glycosides Flashcards

1
Q

List some cardiac glycosides

A
  • digoxin
  • digitoxin
  • ouabain
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2
Q

What are cardiac glycosides indicated for?

A
  • CHF
  • atrial fibrillation
  • atrial flutter
  • PAT (paroxysmal atrial tachycardia)
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3
Q

Digoxin vs. Digitoxin:

What has higher BA?

A

digitoxin

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4
Q

Digoxin vs. Digitoxin:

What has larger Vd?

A

Digoxin

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5
Q

Digoxin vs. Digitoxin:

Which has more renal elimination?
Which has more hepatic metabolism?

A

Digoxin: 60-80% renal elimination

Digitoxin: 80% hepatic metabolism

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6
Q

Digoxin vs. Digitoxin:

Which has smaller half life?

A

Digoxin

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7
Q

Digoxin distributes into tissues such as the ______.

This is good for therapeutic effect but bad for toxic effect

A

myocardium

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8
Q

Cardiac glycosides interact with certain ______ and can cause a 2-fold serum increase in cardiac glycoside concentration - leading to potential toxicity

A

antibiotics

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9
Q

Mechanism of action of cardiac glycosides?

A
  • inhibition of Na+

- K+-ATPase pump

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10
Q

Digoxin vs. Digitoxin:

Which has longer onset of action?

A

digitoxin

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11
Q

Digoxin vs. Digitoxin:

Which has longer time until maximum effect

A

digitoxin

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12
Q

What is the digitalis effect?

A

-scooping of the ST segment

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13
Q

What are the effects on the parasympathetic system?

A

-increased release of acetylcholine

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14
Q

What are the effects on the sympathetic system?

A

-increased efferent sympathetic discharge

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15
Q

What is the toxic dose of digoxin in a child?

A

1mg (few leaves of oleander or foxglove)

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16
Q

What is the toxic dose of digoxin in an adult?

A

3mg

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17
Q

What are digoxin toxic levels?

A

> 2ng/mL

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18
Q

What are risk factors for toxicity?

A
  • Drug interactions

- Disease

19
Q

What drug interactions increase risk for toxicity?

A
  • Amiodarone (inhibits renal tubular secretion of digoxin)
  • Antibiotics (decrease population of colonic bacteria)
  • Quinidine
  • Verapamil
20
Q

What diseases increase risk for toxicity?

A
  • renal failure
  • MI
  • electrolyte imbalances
  • mortality is 3-25% higher in the elderly
21
Q

What are signs and symptoms of ACUTE digoxin overdose?

A
  • vomiting
  • hyperkalemia
  • sinus bradycardia
  • sinoatrial arrest
  • second or third degree AV block
  • ventricular tachycardia/fibrillation
22
Q

digoxin toxicity causes _____ myocardial hypercalcemia

A

intracellular

23
Q

What are signs and symptoms of CHRONIC digoxin intoxication?

A
  • visual disturbances
  • weakness
  • sinus bradycardia
  • atrial fibrillation
  • ventricular arrhythmias
  • accelerated junctional tachycardia
  • paroxysmal atrial tachycardia
  • hypokalemia and hypomagnesemia (from use of diuretics)
24
Q

How do we manage the intoxicated patient ?

A

Emergency and supportive measures:

  • protect airways, assist ventilation
  • treat hyperkalemia (insulin
  • treat bradycardia or heart block (use atropine - if unresponsive then use antibodies to digoxin)
  • treat ventricular tachyarrhythmias
  • decontamination (gastric emptying or activated charcoal)
  • enhanced elimination (MDAC)
  • Antidotes - digoxin-specific antibody fragments (Fab) DigiFab
  • Monitoring of digoxin levels
25
Q

Why would dialysis not really work for digoxin?

A
  • it has high Vd so it is not really in the plasma
  • could still be useful if you can lower the plasma levels just a little bit when you’re dealing with life-threatening concentrations of Digoxin overdose
26
Q

Why don’t you monitor digoxin levels after you give the antidote?

A

bc Dig levels will go WAY up because of digoxin-antibody complex

27
Q

Digoxin-specific antibody fragments (Fab) are indicated for the management of patients with toxicity related to what drugs?

A
  • digoxin
  • digitoxin
  • natural cardiac glycosides (oleander, toad venom)
28
Q

Fab have high ____

A

specificity

29
Q

Fab have sufficient cross-reactivity for other ____ _____

A

cardiac glycosides

30
Q

Describe dose and administration of DigiFab

A
  • vials contain 40mg of purified, lyophilized, ovine digoxin-specific Fab to be reconstituted with 4 mL water for IV
  • administration: infusion over 15’ to 2 hours (at least 30’)
31
Q

What do DigiFab antibodies bind to?

A

intravascular free digoxin

*the binding affinity of DigiFab for digoxin&raquo_space; than the affinity of digoxin for the ATPase

32
Q

DigiFab diffuses into the ____ space (3-fold larger Vd)

A

interstitial

33
Q

DigiFab:

-time to onset of response ?

A

19 min (0-60 min)

34
Q

DigiFab:

-time to complete response?

A

88 min (30-360min)

35
Q

Each vial of DigiFab binds ____ mg of digoxin

A

0.5

36
Q

How do you determine the # vials you need if you know the digoxin serum concentration?

A

of vials = digoxin serum conc (ng/mL) x patient weight (kg) / 100

37
Q

How do you determine the # of vials you need if you know the amount ingested?

A

of vials = amount ingested (mg) / 0.5 (mg/vial)

38
Q

Roughly how many vials for an acute ingestion?

A

10-20 vials (both adult and child)

39
Q

Roughly how many vials for a chronic toxicity in adults?

A

3-6 vials

40
Q

Roughly how many vials for a chronic toxicity in children?

A

1-2 vials

41
Q

What should DigiFab be used for?

A
  • life-threatening cardiac glycosides
  • patients with progressive bradydysrhythmias (severe sinus bradycardia or second or third degree heart block unresponsive to atropine
  • patients with severe ventricular dysrhythmias (VT or VF)
  • patients with potassium > 5.5 mEq/mL
  • Acute ingestions
    • > 4mg in healthy child (>0.1mg/kg)
    • > 10mg in healthy adult
  • Serum concentrations in > 10ng/mL (lower in the elderly)
  • rapid progression of clinical signs and symptoms (cardiac and GI effects) and rising potassium levels
42
Q

in cardiac toxicity, you do not see metabolic ______

A

acidosis

43
Q

What is the Chinese medication made of toad venom also known as “love stone”

A

Chan su

*contains bufadienolide (cardiac glycoside - toxicity similar to that of digoxin)

44
Q

if potassium is not high, you know it’s ____ toxicity

A

chronic

Year 4 - Toxicology (24 decks)

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