Lecture 12: Anti-Arrhythmic Drugs (Part II) Flashcards
What three drugs make up the Class 1A Anti-Arrythmic Class?
Quinidine, Procainamide, Disopyramide
How do Class 1A Anti-Arrythmics raise the threshold for AP and slow rate of depolarization in cardiac muscles?
(hint: what channels do they block?)
Block Na+ channels (preference for open channels)
How do Class 1A Anti-Arrythmics affect phase 0 upstroke? myocardial conduction velocity?
Class 1A Anti-Arrythmics
- Phase 0 upstroke: decrease
- Myocardial conduction velocity: decrease
True or False: Class 1A Anti-Arrythmics block Na and K channels
True
How do Class 1A Anti-Arrythmics affect outward K+ current, which is responsible for repolarization of membrane?
- Decrease outward K current
How do Class 1A Anti-Arrythmics affect ERP and AP duration?
Class 1A Anti-Arrythmics
- ERP: Increase
- AP duration: Increase
Quinidine, a Class 1A Anti-Arrythmic, increases conduction velocity in the nodes. Why is this?
Has a strong ANTI-CHOLINERGIC effect (in addition to Na+ blocking effect)
Contraindications for Quinidine?
Contraindications fro Disopyramide?
Quinidine: atrial flutter
Disopyramide: glaucoma, uropathy
DDI for Quinidine?
Quinidine and Digoxin (can lead to Digoxin toxicity)
True or False: Both quinidine and disopyramide have anti-cholinergic effects, but the latter is more severe
True
Of the three Class 1A Anti-Arrythmic drugs (Quinidine, Procainamide, Disopyramide) - which has the FEWEST anticholinergic effects and does NOT have a DDI with Digoxin?
Procainamide
All Class 1A agents are contraindicated in patients with _____ or with drugs that predispose patients to QT prolongation, leading to TdP
QT prolongation
True or False: Class 1B Anti-Arrythmics bind to both open and inactivated Na+ Channels
True
Binding perference for Class 1A Anti-Arrythmics vs. Class 1B Anti-Arrythmics?
Class 1A: Open
Class 1B: Inactive
How do Class 1B Anti-Arrythmics act on Na+ channels?
Block open and inactivated Na+ channels
What are the three drugs part of the Class 1B Anti-Arrythmics?
1) Lidocaine
2) Mexiletine
3) Phenytoin
Why can Class 1B Anti-Arrythmics lead to seizures or dizzyness?
Can cross BBB
True or False: Mexiletine is an analogue of lidocaine and has a negligible influence on QT interval compared to lidocaine, has less vagolytic affects
True
True or False: Phenytoin can be used as an anti-epileptic medication
True
Which class of anti-arrythmic drugs has the most potent Na+ channel blockers
Class 1C
How do Class 1B Anti-Arrythmics affect ERP and AP duration?
ERP: Decreased
AP Duration: Decreased
How do Class 1C Anti-Arrythmics affect phase 0 of ventricular cells?
Decrease phase 0 of ventricular cells
(as a result, suppresses pre-mature ventricular contraction)
Do Class 1C Anti-Arrythmics bind to open/active Na+ channel or closed/inactive Na+ channel?
Open/Active Na+ channel
What are the three Class 1C anti-arrythmics?
1) Flecainide
2) Encainide
3) Propafenone
True or False: Class 1B Anti-arrythmics can worsen a pre-existing arrythmia. Therefore: only approved for life-threatening situations, such as: paroxysmal supraventricular arrythmia
False - this is the case for class 1C anti-arrythima drugs
How do Class 1C Anti-arrythmics affect AP duration and ERP?
Normal - do not change
What two class 1C drugs can lead to developing cardiac arrest/mortality, as per NHLBI study?
Encainide
Flexainide
True or False: Propafenone can cause mortality
True
Order the anti-arrythmic drug class from strongest to weakest Na+ channel blocking ability
Na+ Blocking Ability
Class 1C > Class 1A > Class 1B
In the SA Node, the beta1 receptor triggers an increase in pacemaker activity via _____
Funny current/HCN
Typically, beta 1 receptors lead to increase SA nodal firing, which increases the phase ___ depolarization rate in pacemaker cells
phase 4
True or False: In the AV Node - beta 1 receptors increase calcium current, resulting in enhanced conduction velocity and decreased refractory period
True
Beta blockers belong to which class of anti-arrythmic drugs?
Class II anti-arrythmia drug
Beta 1 blockers act on both __ and ___ nodes to decrease phase ___ in pacemaker cells.
How does this effect ERP and rate of automaticity?
Beta 1 blockers act on: SA/AV Nodes to decrease phase 4 in pacemaker cells
- Prolongs ERP, decreases rate of automaticity
True or False: Non-specific beta blockers (propranolol, sotalol) come with warning of life threatening pro-arrythmia
True
What type of beta blockers are labetolol and carvediolol?
Atenolol and metoprolol?
Beta and alpha 1 receptor blockers
Specific beta 1 blockers
AE of non-specific beta blockers?
AE of beta blockers?
Bronchospasm (due to blocking B2)
Negative inotropic effect, bradycardia, block
What four drugs belong to the class III anti-arrythmic drug class?
1) Amiodarone
2) Dronedarone
3) Ibutilide
4) Dofetilide
____ channels play a major role in regulating plateau phase, specifically outward delayed rectifying K+ currents (K efflux)
K+ channels
Which class of Anti-Arrythmia drugs are K+ channel blockers?
Class III
How do K+ channel blockers (Class III) affect K+ efflux? Plateau phase, repolarization, and ERP?
K+ blockers prevent K+ efflux
- Longer plateau phase and re-polarization
- Increased ERP
____ shows K+ blocking activity and is considered to be a mixed class II and class III drug
Sotalol
AE associated with use of Class III drugs?
- Prolongation of plateau duration can give rise to EAD
- Can result in TdP
What is the metabolite of Amiodarone, a K+ channel blocker?
Des-ethyl Amiodarone
___ is a benzofuran compounds with 37% iodine that has HIGH affinity for thyroid cells and is toxic to thyroid follicular cells, ultimately leads to destruction of thyroid gland and hypothyroidism
Amiodarone
True or False: Amiodarone is known to inhibit 5-deiodinase activity, thereby decreasing conversion of T4 to T3; also known to be depositied in eyes, skin, and liver
True
True of False: Dronedarone is known to cause optic neuropathy, corneal deposits, and keratopathy with long-term use
False - Amiodarone
What anti-arrythmic drugs are associated with ocular toxicity?
Amiodarone
Quinidine and Disopyramide (Class 1A)
What drug and its metabolite are known to decrease dose of UV radiation known to cause erythema? Cause?
Amiodarone
- Induction of ROS and DNA damage by amiodarone and DEA (metabolite) by cutaneous tissue
What is a substitute for Amiodarone, with reduced toxic effects? Why is this substitute less toxic?
Dronedarone (or Ibutilide or Dofetilide)
- Sulfonamide moiety, results in less iodide toxicity and decreased 1/2 life
Calcium channel blockers belong to which type of anti-arrythmia drugs?
A. Class II
B. Class I
C. Class III
D. Class IV
D. Class IV
Calcium channel blockers primarily cat on which tissues?
SA and AV Nodal Tissues (these effects are more prominent than atrial and ventricular muscles)
How do Ca2+ blockers affect AP and conduction of impulses in nodal tissues?
Slows down AP and impulse conduction
True or False: The mechanism used by Ca channel blockers could be helpful in regulating AV Node mediated re-entry phenomenon
True
What two drugs belong to Class IV Anti-arrythmia drugs?
Verapamil and Diltiazem
Which class of Anti-Arrythmic drugs can cause AV nodal block?
Class IV
Class IV Anti-Arrythmia drugs - contraindications?
With beta-blockers, can precipitate HF
True or False: If Digoxin is co-admin with Verapamil or Diltiazem, could result in enhanced Digoxin toxicity
True
How does Ivabradine affect Na+ entry?
Inhibits Na entry and funny current through HCN in the SA Node
What can Ivabradine (Class 0) treat?
Arrythmias due to SA nodal origin
(e.g sinus tacchycardiacs)
What drug can treat A fib / Paroxysmal Supraventricular Tachy?
Digoxin
Which drug inhibits M3 receptors in SA and AV Nodes to normalize sinus rhythm and reverse AV Nodal block?
CI?
Atropine
- Glaucoma
True or False: Afib can lead to stroke
True
What drugs can be given as anti-coags to prevent stroke?
1) Dabigatran; Rivaroxaban; Apixaban - ban/tran
Treatment for A-fib induced stroke?
1) Heart rate controlling meds - Beta or Ca2+ blockers
2) Heart rhythm controlling meds - Na/K+ channel blockers
