Lecture 11 - Cardiac Glycosides Flashcards
List some cardiac glycosides
- digoxin
- digitoxin
- ouabain
What are cardiac glycosides indicated for?
- CHF
- atrial fibrillation
- atrial flutter
- PAT (paroxysmal atrial tachycardia)
Digoxin vs. Digitoxin:
What has higher BA?
digitoxin
Digoxin vs. Digitoxin:
What has larger Vd?
Digoxin
Digoxin vs. Digitoxin:
Which has more renal elimination?
Which has more hepatic metabolism?
Digoxin: 60-80% renal elimination
Digitoxin: 80% hepatic metabolism
Digoxin vs. Digitoxin:
Which has smaller half life?
Digoxin
Digoxin distributes into tissues such as the ______.
This is good for therapeutic effect but bad for toxic effect
myocardium
Cardiac glycosides interact with certain ______ and can cause a 2-fold serum increase in cardiac glycoside concentration - leading to potential toxicity
antibiotics
Mechanism of action of cardiac glycosides?
- inhibition of Na+
- K+-ATPase pump
Digoxin vs. Digitoxin:
Which has longer onset of action?
digitoxin
Digoxin vs. Digitoxin:
Which has longer time until maximum effect
digitoxin
What is the digitalis effect?
-scooping of the ST segment
What are the effects on the parasympathetic system?
-increased release of acetylcholine
What are the effects on the sympathetic system?
-increased efferent sympathetic discharge
What is the toxic dose of digoxin in a child?
1mg (few leaves of oleander or foxglove)
What is the toxic dose of digoxin in an adult?
3mg
What are digoxin toxic levels?
> 2ng/mL
What are risk factors for toxicity?
- Drug interactions
- Disease
What drug interactions increase risk for toxicity?
- Amiodarone (inhibits renal tubular secretion of digoxin)
- Antibiotics (decrease population of colonic bacteria)
- Quinidine
- Verapamil
What diseases increase risk for toxicity?
- renal failure
- MI
- electrolyte imbalances
- mortality is 3-25% higher in the elderly
What are signs and symptoms of ACUTE digoxin overdose?
- vomiting
- hyperkalemia
- sinus bradycardia
- sinoatrial arrest
- second or third degree AV block
- ventricular tachycardia/fibrillation
digoxin toxicity causes _____ myocardial hypercalcemia
intracellular
What are signs and symptoms of CHRONIC digoxin intoxication?
- visual disturbances
- weakness
- sinus bradycardia
- atrial fibrillation
- ventricular arrhythmias
- accelerated junctional tachycardia
- paroxysmal atrial tachycardia
- hypokalemia and hypomagnesemia (from use of diuretics)
How do we manage the intoxicated patient ?
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
Why would dialysis not really work for digoxin?
- 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
Why don’t you monitor digoxin levels after you give the antidote?
bc Dig levels will go WAY up because of digoxin-antibody complex
Digoxin-specific antibody fragments (Fab) are indicated for the management of patients with toxicity related to what drugs?
- digoxin
- digitoxin
- natural cardiac glycosides (oleander, toad venom)
Fab have high ____
specificity
Fab have sufficient cross-reactivity for other ____ _____
cardiac glycosides
Describe dose and administration of DigiFab
- 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’)
What do DigiFab antibodies bind to?
intravascular free digoxin
*the binding affinity of DigiFab for digoxin»_space; than the affinity of digoxin for the ATPase
DigiFab diffuses into the ____ space (3-fold larger Vd)
interstitial
DigiFab:
-time to onset of response ?
19 min (0-60 min)
DigiFab:
-time to complete response?
88 min (30-360min)
Each vial of DigiFab binds ____ mg of digoxin
0.5
How do you determine the # vials you need if you know the digoxin serum concentration?
of vials = digoxin serum conc (ng/mL) x patient weight (kg) / 100
How do you determine the # of vials you need if you know the amount ingested?
of vials = amount ingested (mg) / 0.5 (mg/vial)
Roughly how many vials for an acute ingestion?
10-20 vials (both adult and child)
Roughly how many vials for a chronic toxicity in adults?
3-6 vials
Roughly how many vials for a chronic toxicity in children?
1-2 vials
What should DigiFab be used for?
- 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
in cardiac toxicity, you do not see metabolic ______
acidosis
What is the Chinese medication made of toad venom also known as “love stone”
Chan su
*contains bufadienolide (cardiac glycoside - toxicity similar to that of digoxin)
if potassium is not high, you know it’s ____ toxicity
chronic
