Anti-arrhythmics (edited) Flashcards
What’s heart rate (u)
HR describes the frequency of depolarization of the ventricles
What’s the normal resting HR (normal sinus rhythm - NSR)?
60-100 beats per minute
Can Arrythmias be silent?
Yes-a small percentage are silent (asymptomatic)
In most pts that experience sx, what do they experience?
- Palpitations (feeling like there’s fluttering or racing)
- feeling like heart is skipping a beat
- Dizziness
- Lightheadedness
- SOB
- Chest pain
- Fatigue
In severe cases, what sx may one experience?
Syncope
Heart failure
Death
What’s the most common etiology of arrhythmias?
Myocardial ischemia
OR
Infarction secondary to coronary artery dx
List the non-cardiac conditions that may trigger arrhythmias.
Electrolyte imbalances especially those involving potassium, magnesium, sodium and calcium
Elevated sympathetic states such as hyperthyroidism and infection
drugs- including illicit and antiarrythmics
List the electrolytes that may trigger arrhythmias when they are out of balance
Potassium
Magnesium
Sodium
Calcium
What’s QT prolongation?
Drug- induced slowing of the rate of ventricular depolarization and repolarization (from beginning of QRS complex-end of T wave) , which can result in a particularly dangerous ventricular tachyarrhythmia called Torsade de Pointes (TdP)-can cause sudden cardiac death
What’s the resting value?
-90 mV
What happens in phase 0 of action potential?
Depolarization (determines conduction velocity)
Na channels OPEN (entering cell)
Class 1a, 1b, 1c antiarrythmthmias target the open Na channel
What determines conduction velocity?
Depolarization
What’s the value of phase 1 of action potential?
+ 10mV
What happens in phase 1 of action potential?
PEAK
Na channels CLOSE
What happens in phase 2 (plateau)?
PLATEAU
Ca channels OPEN (entering cell)
K channels OPEN (EXITING cell)
What happens in phase 3?
Repolarization
Ca2+ channels CLOSE
K channel stays open (continue exiting cells) -class III antiarrythmics target the open K channel Na may enter cell (late inward Na current)
What happens in phase 4?
Automaticity
Slow increase in potential
When is refractory period of action potential?
Phase 1 to end of phase 3
How’s arrhythmias classified?
Based on their location of origin into:
Supraventricular
OR
Ventricular
What’s Supraventricular arrhythmias?
Arrhythmias originating ABOVE atrioventricular node
What’s ventricular arrhythmias?
Originating BELOW the atrioventricular node
What’s the most common Supraventricular arrhythmias? (U)
Atrial fibrillation (AFib)
What’s AFib?
Results from multiple waves of electrical impulses in the atria, resulting in an irregular and usually RAPID VENTRICULAR RESPONSE
Why does the mgt of AFib involve anticoagulation?
Due to disorganized depolarization of the atria, coordinated atrial contraction is impaired, blood becomes stagnant in atria increasing risk of clot formation, which increases the risk of thromboembolism and stroke
What type of ventricular tachycardia is a medical emergency?
Ventricular tachycardia without a pulse
What’s a risk factor for Torsade De Pointes (TdP)? (U)
Prolongation of the QT prolongation
What’s Torsade de Pointes (TdP)? What can it result in?
TdP is a particularly lethal ventricular tachyarrhythmia which is most commonly ass. with drugs and can result in SUDDEN CARDIAC DEATH
How is QT interval measured? What’s the measured space define?
From beginning of the QRS complex to the end of the T wave
Reflect ventricular depolarization and repolarization
What pre-existing condition may cause additive QT prolongation?
Any pre-existing cardiac condition
What class of antiarrhythmics also result in additive QT prolongation? (U)
Class I especially Ia (Disopyramide, Quinidine, Procainamide) double quarter pounder
and Class III (Amiodarone, Ibutilide, Dofetilide, Dronedarone, Sotalol) AIDDS
Name main antibiotics that may cause additive QT prolongation. (U)
Quinolones (Ciprofloxacin, Levo, Moxi, Nor, Ofloxacin, Gemi, Spar)
Macrolides (Azithromycin, Erythromycin, Clarithromycin, Telithromycin)
Which Azole antifungal is most responsible for causing additive QT prolongation? (U)
Voriconazole
Which anticancer is most responsible for causing additive QT prolongation? (U)
Nilotinib
Which SSRI is most responsible for causing additive QT prolongation? (U)
Citalopram (Celexa), escitalopram
What’s the max dose of citalopram to prevent additive QT prolongation?
40mg/d
When is 20mg citalopram the max dose to prevent additive QT prolongation?
60+ years Liver impairment HF S/P MI 2C19 poor metabolizer Pt on 2C19 inhibitors Taking QT prolonging drugs
Whats the max dose in for Escitalopram (Lexapro) to prevent additive QT prolongation?
In the elderly?
20mg/d
Don’t exceed 10mg/d
What’s the preferred antidepressant in cardiac pts to prevent QT prolongation?
Sertraline (Zoloft)
What antidepressant should be avoided if pt has cardiac risk?
Citalopram
Which antiemetic agent is most responsible for causing additive QT prolongation? (U)
5-HT3-receptor antagonists (Dolasetron, Ondansetron, Granisetron, Palonosetron)
Which antipsychotic is most responsible for causing additive QT prolongation? (U)
Thioridazine
Which other agent is most responsible for causing additive QT prolongation? (U)
Methadone
What’s the 2 main reasons antiarrhythmic drugs are used?
Rhythm
Class I and III (used to terminate arrhythmias and restore and maintain normal sinus rhythm)
Rate
Class II and IV and Digoxin (used to slow ventricular rate during a Supraventricular arrhythmias)
What class of antiarrhythmic drugs is used to terminate arrhythmias and restore and maintain normal sinus rhythm? Cardioversion
Class I and III
Disopyramide, Quinidine, Procainamide,
Lidocaine, Mexiletine
Flecainide, Propafenone,
Amiodarone, Ibutilide, Dofetilide, Dronedarone, Sotalol (AIDDS)
What class of antiarrhythmic agent is used to slow ventricular rate during a Supraventricular arrhythmias?
Class II
Beta-blockers
Class IV
Verapamil, Diltiazem
Digoxin
What must be done prior to starting any medication for NON-LIFE-THREATENING arrhythmia? (U)
Check pts electrolytes
AND
Run a toxicology screen
What’s the Vaughan Williams classification of antiarrhythmics?
Class I a, b, c
Class II
Class III
Class IV
List drugs that are listed as class Ia.
Double Quarter Pounder
Disopyramide
Quinidine
Procainamide
List drugs that are listed as class Ib
Lettuce, Mayo
Lidocaine
Mexiletine
List drugs that are listed as class Ic
Fries Please
Flecainide
Propafenone
List drugs that are listed as class II
Beta-blockers
List drugs that are listed as class III
DDSIA
Dieting During Stress Is Awful
Dofetilide
Dronedarone
Sotalol
Ibutilide
Amiodarone
List drugs that are listed as class IV
Verapamil
Diltiazem
How are class I antiarrhythmics sub-classified?
They are Na channel blockers. Proarrhythmic (increase arrhythmia risk). -Inotrope (decrease force of heart contraction)
They are divided based on the DURATION of time they bind to Na channel
Ia - Intermediate Na channel blockers and they also block K channel
Ib - Fast Na channel blockers
Ic - Long Na channel blockers
Define class Ia antiarrhythmics
INTERMEDIATE Na + K channel blockers
Double Quarter Pounder
Disopyramide
Quinidine
Procainamide
Define class Ib antiarrhythmics
FAST Na channel blockers
Lettuce, Mayo
Lidocaine
Mexiletine
Define class Ic antiarrhythmics
LONG Na channel blocker
Fries Please
Flecainide
Propafenone
MOA of class Ia antiarrhythmics?
REDUCE conduction velocity and automaticity
INCREASE refractory period
What’s the black box warning associated with Quinidine (class Ia)?
Control AV conduction BEFORE initiating-may increase mortality in AFib or flutter
Warning: DILE- avoid G6PD deficient-can cause positive Coombs test
SE of quinidine (class Ia)? (U)
Diarrhea (35%)
Stomach cramping (22%)
QT prolongation
Hepatotoxicity
Nausea/vomiting
Lightheadedness
Cinchonism (tinnitus, hearing loss, blurred vision, headache, delirium)
Are the different salts of quinidine interchangeable
No!
267mg of gluconate = 200mg of sulfate form
What’s unique about Procainamide injection?
Has a active metabolite - N-acetyl Procainamide (NAPA)
NAPA is really cleared
What’s the black box warning associated with Procainamide injection?
Fatal blood dyscrasias e.g. Agranulocytosis
Long-term use -> Positive antibody (ANA) in 50% of pts which may result in DILE
SEs of Procainamide injection?(u)
Hypotension
Rash
DILE
QT prolongation
Agranulocytosis
What’s the SE of Disopyramide?
Anticholinergics effect (xerostomia, constipation, urinary constipation)
Can cause HF, BPH, urinary retention, narrow angle glaucoma, and myasthenia gravis (due to anticholinergic effects
Effect of class Ia agents (double quarter pounder) on QT prolongation?
ALL class Ia can have additive QT prolongation with other agents that also prolong the QT interval
What are class Ib agents (Mayo, Lettuce) ONLY used for?
Ventricular arrhythmias (no efficacy for Supraventricular arrhythmias such as AFib)
When are class Ic agents absolutely contraindicated?
Structural Heart issues:
Patients with heart failure (HF)
OR
myocardial infarction (MI)
MOA of class II antiarrhythmics?
Block beta-blockers (block the sympathetic activity that may be causing the arrhythmia)
AND
Indirectly block Ca channels= decrease in ion conduction speed
slows the rate
What are class II antiarrhythmics used for?
To slow the ventricular rate in Supraventricular tachyarrhythmia (eg. AFib)
MOA of class III agents? (AIDDS)
Blocks K channels -> significant increase in refractory period
What’s the exception to the MOA of class III agents?
Ibutilide - works by activating the late inward Na current which also results in increased refractory period
In addition to blocking K channel, what other channels/receptors do Amiodarone and Dronedarone act on?
They also block
Alpha & beta adrenergic receptors
Ca channels
Na channels
In addition to blocking K channel, what other channels/receptors do Soltalol act on?
Significant B-adnerergic receptor blocker
What’s the class of amiodarone? And brand name?
Class III
Pacerone
Nexterone
What’s the black box warning of amiodarone?
Pulmonary toxicity, hepatotoxicity, proarrhythmic- use ONLY for life-threatening arrhythmias. Pts should be hospitalized when LOADING DOSE is given
SE of amiodarone (cordarone/pacerone)
WARNING: hyper/HYPO thyroidism (inhibits T3->T4) ----chemical structure contains iodine(like thyroid hormone) Optic neuropathy photosensitivity- SLATE BLUE SKIN neurotoxicity-(peripheral neuropathy) SJS/TEN
Hypotension Bradycardia Corneal microdeposits Dizziness Ataxia GI upset N/V Constipation Tremor Photosensitivity DILE
Hypo/hyperthyroidism (more hypo than hyper)
Bradycardia
What considerations are taken when amiodarone (cardarone, pacerone, nexterone) will be infused over 2 hrs?
Should be admin in a non-polyvinyl chloride (non-PVC) container such as polyolefin or glass
Recommended to be added to D5W
What’s the advantage of premixed IV bag? (U)
Comes in GALAXY container (nonPVC, nonDEHP)
Longer stability-24 months at room temp
PVC bag not an issue
Comes in commonly used concentrations
What’s the half- life of amiodarone?
40-60 days
When’s amiodarone recommended?
Commonly used antiarrhythmic despite all it’s side effects
Antiarrhythmic drug of choice in pts with heart failure
Which is the class III agent has to be given with meals?
Dronedarone - 400mg PO BID with meals
What’s the black box warning of Dronedarone?
Increased risk of death, stroke, or HF in pts with decompensated HF (class IV or any class with a recent hospitalization) or permanent AFib
SE of Dronedarone? (U)
Warning: hepatic failure, pulmonary disease (including fibrosis and pneumonitis)
QT prolongation Bradycardia Increased SCr (and possibly BUN) N/V/D ab pain Hypokalemia Hypomagnesemia
note: no iodine in structure so little/no thyroid effects
What’s the pregnancy cat. of Dronedarone?
X
When’s Dronedarone used?
Only in pts who can be converted to normal sinus rhythm
What’s the monitoring parameters for Tikosyn (Dofetilide)?
Box: continuous ECG monitoring
and CrCl monitoring for a minimum of 3 days after initiation or re-initiation
What’s the effect of ALL class III agents on QT prolongation?
Can have additive QT prolongation with other agents that also prolong the QT interval
What should be considered wrt to electrolytes and ALL anti-arrhythmic?
Electrolyte abnormalities (k, Na, Ca, Mg) should be corrected before any antiarrhythmics is initiated
What’s the consequence of not correcting electrolyte before initiating antiarrhythmics?
Risk of arrhythmia is increased
What should be avoided with use of class III antiarrhythmics?
Grapefruit juice/pdts
Ephedra
St. John’s wort (P-glycoprotein inducer)
What meds should be reduced when starting amiodarone? By how much?
Digoxin (reduce by 50%) and Warfarin (reduce by 30%-50%)
What class of drugs should use lower doses with amiodarone?
Simvastatin, Lovastatin, Atorvastatin
T/F? Monitor INR after initiating Dronedarone in pts with Warfarin
True
MOA of class IV agents?
They block L-type Ca channels, slowing SA and AV nodal conduction velocity
Uses of class IV agents?
Used to slow ventricular rate in Supraventricular tachyarrhythmia
List agents under class IV antiarrhythmics?
Diltiazem (Cardizem)
Verapamil (Calan/ Verelan/ Covera HS)
What type of CCBs are used in antiarrhythmics?
Only non-dihydropyridine CCBs are used
When is CCB is preferred over b-blocker in pts with arrhythmias?
If co- existing asthma/COPD in pts
Other antiarrhythmics not included in Vaughan Williams classification?
Adenosine (Adenocard)
Digoxin (Lanoxin)
MOA of adenosine?
Slows conduction through the AV node via activation of adenosine-1 receptors
Uses of adenosine in arrhythmias?
Used to restore normal sinus rhythm in Supraventricular re-entrant tachyarrhythmia
Effects of digoxin?(u)
Digoxin enhances vagal tone, resulting in decrease ventricular rate in atrial tachyarrhythmia
What’s the brand name of digoxin? (U)
Lanoxin, Digitek, Digox
What’s the therapeutic range of digoxin (lanoxin) for AFib?
0.8-2 ng/mL
What’s the antidote for Digoxin (lanoxin)?
DigiFab
Whats the first signs of digoxin (lanoxin) toxicity? (U)
Nausea/vomiting
Loss of appetite
Bradycardia
Other signs of digoxin (lanoxin) toxicity? SEVERE
Blurred/ double vision
Altered color perception
Greenish-yellow halos around lights or objects
Abdominal pain
Confusion
Delirium
Arrhythmia (prolonged PR interval, accelerated junctional rhythm, bidirectional ventricular tachycardia)
Is digoxin (lanoxin) used alone?
Not usually
Used in combo with b-blockers or CCB
Since digoxin is mostly renally cleared, whats the concern with digoxin (lanoxin) use here?
In decreased renal fxn -> reduce digoxin dose
In acute renal failure -> hold digoxin
What increases risk of digoxin (lanoxin) toxicity?
Hypokalemia (K < 3.5 mEq/L)
Hypomagnesemia
Hypercalcemia
Role of medication guide in amiodarone dosing?
Dispense medication guide with amiodarone
Should amiodarone be taken with food?
Amiodarone can be taken with/ without food.
BUT, if you should stick to which ever method you use e.g. If you start taking amiodarone with food, then you need to continue taking it with food, while on the med
What body organs need to be monitored while in amiodarone?
ECG BP HR
electrolytes
pulmonary function (chest x-ray)
Thyroid- baseline q 3-6 mo
LFTs- baseline and q 6 mo
eye exams
Photosensitivity and amiodarone?
Amiodarone may cause your skin to be more sensitive to the sun.
Stay out of the sun
Can cause skin to turn blue-gray (not harmful & goes away months after drug is stopped)-infrequent
What’s the brand name for Dronedarone?
Multaq
What’s the potassium safe range for pt on digoxin?
3.5-5 mEq/L
What’s arrhythmias?
Caused by abnormalities in the formation and/or conduction of these electrical impulses
Amiodarone unique injection info
Incompatible with heparin-use saline flush
Use 0.22 micron filter
adenosine brand?
Adenocard
t 1/2 less than 10 seconds
used in paroxysmal supra ventricular tachycardia (PSVT)-activates adenosine receptors=decrease AV node conduction
dofetilide brand?
Tikosyn
Ibutilide brand?
Corvert
Sotalol brand?
Betapace, Sotylize, Sørine
Non-selective beta blocker
Box: adjust dosing interval based on CrCl (QT prolongation directly related to stall concentration)
Propafenone brand
Rythmol
Note: can cause metallic taste disturbance
lidocaine brand
Xylocaine
used for refractory VT/ cardiac arrest
disopyramide brand
Norpace
non-DHP CCB side effects
edema, HA, dizzy, hypotension, arrhythmia, HF, constipation (more with verapamil), gingival hyperplasia
Amiodarone inhibits
2C9, 2D6, 3A4, P-gp
Amiodarone is a substrate of
3A4, 2C8, and p-gP
Avoid strong inducers/inhibitors
amiodarone + digoxin
when starting amiodarone decrease Digoxin by 50%
amiodarone+ warfarin
when starting amiodarone decrease warfarin by 30-50%
amiodarone + statin
simvastatin max 20mg/d
lovastatin max 40 mg/d
Do NOT use amiodarone with
sofosbuvir (Sovaldi) used for Hep C
it enhances the bradycardia effect of amiodarone
statins that are not 3A4 metabolized
prava, rosuva, pitava
typical digoxin dose
0.125-0.25 mg PO daily
when CrCl<50 decrease dose or decrease dose frequency
oral to IV
decrease oral 20-25% when going to IV
digoxin use
to help heart beat at more regular RATE
Na-K-ATPase blocker: blocking that pump= Increase force (+inotrope) Decrease HR (-chronotrope)