Antiarrhythmic Drugs Flashcards
Strategy when thinking of tachycardias?
Divide into:
ventricular
supraventricular tachycardias
What would be a target of ventricular tachycardias?
Na+ channels to block ventricular depolarization
Na+ channel blockers have what effects on ECG?
prolong the QRS interval
Class I drugs have what major action?
block Na+ channels
K+ channel blockers have what effect on ECG?
They prolong QT intervals
Class 1 drugs have what major MOA?
They block Na+ channels
What are the different classes of Class I antiarrythmics based on? Explain
their ability to dissociate from Na+ channels?
1a intermediate
1b least effect on phase 0
1c greatest phase 0 depression; therefore prolongs QRS the most
What causes phase 1 of fast response fibers?
Na+ channels inactivated
Some His Purkinje cells transient outward K+ currents with inward Cl- currents contribute to notch and overshoot
What are the causes of phase 2 in fast response fibers?
plateau phase in which a slow influx of Ca2+ (Ica-L) is balanced by late appearing outward K+ current (the delayed rectifier current Ik)
Are there any major antiarrythmic effects of drugs on phase 1 or 2 of fast response fibers?
no
What ion channels are responsible for phase 3 in fast response fibers?
repolarization phase in which the delayed rectifier K+ current rapidly increases as the Ca2+ current dies out because of time-dependent channel inactivation
Which class of anti-arrhythmic drugs slows the re-polarization phase?
class III
What are the phase 4 resting potential of the fast muscle fibers maintained by?
activity of the Na+/K+ ATPase
Capacity of a fast muscle fiber to depolarize is associated with what?
number of Na+ channels in ready state
The more negative the RMP in fast muscle fibers the faster or slower the response?
faster the response
What are the 3 major determinant of conduction velocity?
- Rate of phase 0 depolarization - as Vmax decreases, conduction velocity decreases and vice versa.
- Threshold potential- the less negative, the slower the conduction velocity
- The resting potential - the more negative the RP, the faster the conduction
What types of drugs are good for SVTs?
Those that target the slow response fibers
What is spontaneous depolarization phase 4 is caused by what? (slow responnse fibers)
not completely understood
composite of inward Na+ (If) and Ca2+ (Ica-t) currents and outward K+ currents (Ik)
Depolarization of slow fibers depends on what channels?
on activation of Ca2+ channels (Ica-L and Ica-t)
Which class of antiarrhythmics can slow or block phase 0 in slow response fibers?
class IV
During repolarization of slow response fibers Ca2+ currents are opposed and overcome by what?
delayed rectifier K+ current
phase 3
Which class of anti-arrythmics can slow down phases 4 in pacemaker fibers?
Class II and IV
What are class II antiarrhythmics?
B blockers
What are class IV anti-arrythmics?
CCBs
What is refractoriness?
the inability to respond to stimulus
What is ERP?
ERP effective refractory period
when no stimulus can elicit a response
How long does ERP last?
lasts into late stage 3 of AP because Na+ channels are effectively inactivated and not into the ready state
How do K+ channel blocker affect ERP?
they prolong ERP
What are RRPs? What is the purpose?
relative refractory period
when a strong stimulus can elicit a response but the timing will be out of sync with rest of heart and arrhythmias may occur
Ratio of ERP to APD is a measure of what?
refractoriness
What may decreases in ERP cause?
formation and propagation of premature impulses
At what V does M gate typically close?
-50 mV
At approx. what voltage does h gate open?
-85mV
Do K+ blockers prolong APD?
yes
What are the 3 conformations of sodium channels?
resting or ready state, M gate closed h open
open active state M gate open h open
inactive or refractory state M gate open h closed
Why is rate of recovery slower in ischemic tissue?
because cells partly depolarized at rest
What is the MOA of Class 1A anti-arrythmics?
Na+ channel blocker (tend to target open state more than inactivated state sodium channels)
Block K+ channels
What are the effects of APD and ERP in Class 1A drugs?
increases APD and ERP
What are the prototype Class 1A drugs?
Quinidine
Procainamide
Dysopyramide
What are the prototype Class 1B drugs?
lidocaine
What are the prototype Class 1C drugs?
Flecainide
Propafenone
What is the mnemonic to remember Class 1A, 1B, 1C drugs?
Double Quarter Pounder with Lettuce and Fries Please
dysopyridine
quinidine
procainamide
lidocaine
flecainide
propafenone
What are some properties of the drug quinidine that could give rise to specific S/E of the drug?
causes muscarinic receptor block: increases HR and AV conduction
causes Alpha block: causes vasodilation and reflex tachycardia
Because Quinidine is a weak base what are some drugs you can take that would increase it’s absorption in the body?
increased absorption with antacids
What are the A/E of quinidine?
- cinchonism (GI, tinnitus, ocular dysfunction, CNS excitation)
- hypotension
- prolongation of QRS and QT interval associated with syncope (torsade)
What drugs can cause torsade from classes of anti-arrythmics?
K+ channel blockers
Compared to quinidine, does procainamide have more or less autonomic side effects?
has fewer
Why is it important to remember metabolization of procainamide?
because it can cause SLE in slow acetylators
Special MOA of procainamide to remember.
The parent drug procainamide blocks the Na+ channels while the metabolite NAPA N acetyl procainamide blocks K+ channels
A/E of Procainamide?
drug induced SLE
hematotoxicity (thrombocytopenia, agranulocytosis)
CV effects (torsade)
Class 1B anti-arrythmics MOA.
target inactivated Na+ channels
How do Class 1B anti-arrythmics affect APD?
decrease APD due to block of sodium window currents
Main benefit of Class 1B drugs?
they increase diastole and extend time for recovery
basically takes longer to reach the next AP prolonging phase 4 RMP
Indications for lidocaine?
acute treatment not prophylactic because has short half-life
post MI, open-heart surgery, digoxin toxicity-ventricular arrhythmias only
Indications for Mexiletine?
can take it orally and has higher bioavailability than lidocaine so can use for more chronic management
Why must lidocaine be given via IV?
because of first pass metabolism giving it short half life.
Describe effect of Class 1C drugs on APD?
no effect on APD
Do Class 1C drugs affect the ANS?
no
What is the MOA of Class 1C drugs?
block fast Na+ channels (Ina) especially in His Purkinje
What is the major drug to remember for Class 1C?
Flecainide
Why is there limited use of Flecainide?
limited utility proarrythmogenic effects, leading to inc. sudden death post- MI and when used prophylactically in VT
Indications for Flecainide?
used for paroxysmal A fib rhythm control, paroxysmal SVTs, sustained ventricular tachycardia
MOA of Class II anti-arrythmics.
Beta blockers
Name the nonselective and cardioselective B-blocking agents typically used as antiarrythmics.
nonselective: propranolol
cardioselective: acebutolol and esmolol
Why can’t esmolol be used prophylactically?
very short half life used in acute cases only
What is the ROA for esmolol?
IV only
Indications for Class II anti-arrythmics?
prophylaxis post-MI and SVTs
Esmolol for acute SVTs
Class III drugs MOA?
K+ channel blockers
What is the effect of the Class III drugs on APD and ERP?
inc. APD and ERP esp Purkinje ventricular fibers
What are the 2 most effective anti-arrythmics that are also in Class III anti-arrhythmic class?
amiodarone and dronedarone
Amiodarone and dronedarone mimic what other anti-arrhythmic classes of drug?
All of them
What is the 1/2 life of amiodarone?
about 80 days
1/2 life of Dronedarone?
about 24 hours
Describe Vd in both Dronedarone and amiodarone?
High Vd
S/E of Dronedarone and amiodarone?
- interstitial pneumonitis and pulmonary fibrosis
- phototoxicity (so look for rash on face necks sun exposed areas)
- corneal deposits
- hepatic necrosis
*iodine related S/Es (only amiodarone) blue skin pigmentation and thyroid dysfunction (could be hypo or hyper)
What tests should be run when giving a person amidoarone or dronedarone?
PFTs
LFTs
eye exams
TFT in case of amiodarone because dronedarone doesn’t contain iodine
Do the drugs amiodarone and dronedarone cause torsade?
could but not as likely as many of other K+ blocking agents
What is the rule for drugs likely to cause torsade?
all class III and drugs more selective for K+ more highly likely
What drugs are at highest risk for causing torsade in the class III category?
Ibutilide and Dofetilide
What are some drugs to avoid when someone has long QT syndrome?
- K+ blocking drugs (Class 1A and III)
- antipsychotics (thioridazine)
- TCAs
What are some treatments for torsades that you need to remember?
- correct hypokalemia
- use Mg2+
- correct hypomagnesemia
- discontinue drugs that prolong QT interval
What effect do Class IV anti-arrythmics have on ECG?
prolong PR interval
What are the CCBs we used for anti-arrhythmic drugs?
verapamil
diltiazem
Why can’t we use dyhydropyridines in the treatment of anti-arrythmics?
they are more selective for vasodilation of vascular smooth muscles and therefore could cause reflex tachy
What are the indications of CCBs?
SVTs
S/E for CCBs?
verapamil (constipation)
dizziness (vasodilator to some extent)
flushing
AV block
hypotension
What are some drug interactions to remember when taking CCBs?
- Digoxin and B blockers can cause additive AV block
- verapamil can displace digoxin > toxicity
How is adenosine used as anti-arrhythmic? (Meaning receptor type and target activity)
its found in nodes of heart and is Gi coupled therefore dec. cAMP > dec. SA and AV node activity
Use of adenosine?
DOC for paroxysmal SVT and AV nodal arrythmias
Describe t1/2 of adenosine?
short
S/E adenosine?
flushing, sedation, dyspnea
What is adenosine antagonized by? Why?
methylxanthines (theophylline and caffeine) because they inc. cAMP
Can Digoxin be an antiarrythmic?
yes
What are the goals in management of atrial fibrillation?
- ventricular rate control with beta blockers, CCBs, or digoxin
- anticoagulation
