Anti-Arrhythmetic Drugs Flashcards
What is the rationale or goal for Anti-Arrhythmetic drugs considering that there is no cure
- Normalize conduction velocity
- rectify altered exciteablity of cardiac cells
- Maintain normal sinus rhythm
Torsade de Pointes, a persistant EAD tachyarrhythmia pathology can be induced by prolonged use of what drugs
Prolonged use of:
1) Antiarhythmic drugs
2) Tricyclic Antidepressants
3) antiviral drugs –> gene mutations
How does prolonged use of Antiviral drugs lead to Torsade de Pointes
What are the 3 specifics
Antiviral drugs can lead to mutations in genes for ion channels:
A) KCNQ1 & HERG; –> K+ CHANNEL Mutation
B) SCN5A –> Na+ CHANNEL mutation
An Inotropic HF drug known as _____ induces TdP
What is used to treat this drug induced TdP
(anatomy word)
Digitalis is the Inotropic HF drug which causes TdP
Treated by MgSO4 infusion/ bolus dose
4 classes of drugs associated with QT prolongation (ventricular cycle long) and TdP
(all anti)
Antiarrhythmatics
Antimicrobials
Antidepressants
Antipsychotics
Class 1A Antiarrhythmics - MOA, CI
MOA:
-Moderately blocks Na channels (preferentially open channels than inactive)
-Also, K channel blocking (increase ERP)
-Decrease phase 0 upstroke
-decreases myocardial conduction
CI: QT prolongation (can cause TDP)
Quinidine
Class 1A
- Moderately Blocks Na Channels
- Strong Anticholinergic effect
CI: Atrial Flutter, b/c increases nodal conduction
DDI: Digoxin, b/c same CYP Digoxin toxicity
AE: -ocular toxicity
Disopyramide
Class 1A
-Moderately blocks Na channels
-Severe Anticholinergic effects
CI: Uropathy, Glaucoma
AE: ocular toxicity
Procainamide
Class 1A
-Moderately blocks Na channels
- less anticholinergic effect
-Acetylated to active form in the liver N-acetylprocainamide
DDI: Digoxin
Class 1B Antiarrhythmics
MOA:
- Blocks Na channels, open and inactive, (prefer inactive) (weakest in class 1)
- Decreases ERP
- Decreases AP duration
AE: unwanted CNS effects, dizziness and seizure, b/c cross BBB
Lidocaine
Class 1B
- blocks Na channels (weak)
-also local anesthetic for ocular and dental procedures
Mexiletine
Class 1B
-blocks Na channels
(weak)
-Analog of Lidocaine
with negligible QT influence compared to Lidocaine, and less vagolytic effects
Phenytoin
Class 1B
-blocks Na channels (weak)
-Also used as epileptic medication
-CYP3A4 inducer
Class 1C Antiarrhythmics
MOA:
-Blocks Na channels (Most potent blocker) (mostly open/active state)
-Decrease phase 0 upstroke (ventricular cells)
No change in ERP
ONLY FOR LIFE THREATENING, like Paroxysmal Supraventricular Arrhythmia
b/c can worsen pre-existing arrhythmia
Class 1C safety warning
Encainide or Flecainide tx for average 10 months developed cardiac arrest or mortality in CAST study
Propafenone also has mortality warning
Class 1 comparisons
-1C is strongest Na channel blocker (mostly open channels)
-1B is weakest Na channel blocker (both open and inactive, but mostly inactive channels)
-1A is moderate Na channel blocker (open channels preferred)
ERP effect
-1A increase (b/c K channel blocking)
-1B decrease
-1C no change
Class 2 Antiarrhythmic
Beta Blockers
MOA:
-act on both SA and AV nodes
- slows phase 4 in PM cells
- prolongs ERP, decreasing rate of automaticity
-Propranalol
-Sotalol
Non-specific Beta blocker (beta 1 and 2)
-WARNING: life threatening proarrhythmia
AE:
-beta 1: bradycardia and block
-beta 2: bronchospasm
-Atenolol
-Metaprolol
Beta 1 specific blocker
- Preferred B/c only acts on SA node
AE:
-beta 1: bradycardia and block
-Labetalol
-Carvedilol
Beta and Alpha 1 blocker
- if also vascular complication and SA node 100+
Class 3 Antiarrhythmic
K channel blockers
MOA:
-prevent K efflux, slows rate of outward flow
- Longer plateau phase
- ERP increased
Used when K efflux is high and phase 2,3,4 are too fast
AE: Prolonged plateau can cause EAD and lead to TDP
Sotalol
mixed class 2 and class 3
- nonselective beta blocker and K channel blocker
Amiodarone
K channel blocker
-DEA metabolite is active form, longer half life
AE:
- toxic to thyroid follicular cells
-37% iodine, affinity to thyroid gland
- causes hypothyroidism if long term
- inhibits 5-deiodonase activity and prevents T4 to T3 conversion
Ophthalmic toxicity: corneal deposits, keratopathy
- optic neuropathy
CI: Skin, eye, thyroid conditions
- Dronedarone
- Ibutilide
- Dofetilide
Dronedarone:
Substitute for Amiodarone with reduced toxic effects, less iodine, and decreased half life
- Ibutilide
- Dofetilide
also alternatives
Class 4 Antiarrhythmics
Ca channel blockers
- SA and AV nodal tissue predominant
- slows AP
- slows conduction of impulses
-regulated AV node mediated re-entry phenomenon
-Verapamil
-Diltiazem
Ca channel blockers
AE: AV nodal block (Rare)
CI: beta blockers, b/c HF problems
DDI: Digoxin, Digoxin toxicity
Class 0
Ivabradine:
Inhibits Na entry, inward funny current through HCN
Used for Arrhythmias due to SA nodal origin: Sinus Tachycardia
Digoxin
Misc. group
-HF drug with antiarrhythmic property
-Reduces PM firing frequency (SA node)
- Effective in A-fib and Paroxysmal Supraventricular Tachycardia
Stringent monitoring narrow therapeutic window
Adenosine
Misc. group
- stim purinergic receptor
- Decrease SA and AV nodal conductance
Atropine
Anti muscarinic agent
- inhibits M2 receptors in SA and AV nodes, normalize sinus rhythm and reverse AV nodal block
AE: Tachycardia
urinary retention,constipation
CI: glaucoma
Potassium
irregularity in heartbeat results from K out of range(3.5-5 mM)
Stroke
Multiple re-entries, blood not pumped from atrium, results in clot
1. anticoagulants (Dabigatran, Rivaroxaban, Apixaban)
2. HR control (B-Blocker: Atenolol; or Ca channel blocker: Diltiazem.
3. Rhythm control ( Na channel blocker: flecainide, or K channel blocker Amiodarone.
