Antiarrythmatics Flashcards
Procainamide Quinidine, disopyramide: MOA
- Class Ia Na+ Channel Blockers
- Preferentially bind Na+ channel in active state (I-Na)
- Also reduce the outward K+ current responsible for repolarization
- Secondary I-Kr block
- decrease the phase 0 upstroke velocity
- Slows conduction velocity and pacemaker rate
- decreased conduction velocity & increased refractory period
- decrease re-entry.
- ProlongsAP duration and dissociates from I-Na channel
- Direct depressant on SA and AV nodes
- Decreases Contractility
Lidocaine, tocainide, and mexiletine: MOA
- Class Ib Na+ Channel blockers
- preferentially bind Na+ channels in both active state and inactivated states
- dissociate very fast from the bound Na+ channels
- decrease of repolarization period in ventricular AP
- Doesn’t Increase QT interval
- Doesn’t prolong AP
Flecainide, encainide, propafenone
- Class Ic Na+ channel blockers
- Strong Na+ channel blockade
- No change in AP duration
- no effect on repolarization period.
- Flecainide doesn’t increase QT interval.
- Clinical uses:
- Supraventricular arrhythmias w/ normal heart
- DO NOT use post-MI
- PK:
- Oral
- liver and kidney metabolism
- Toxicity:
- proarrhythmic
Beta Blockers
- Class II – β-Blockers
- propranolol
- 1st generation β-blocker
- Non-selective
- Direct membrane effects, Na channel blocker
- Prolongs AP duration
- Slows SA automaticity and AV conduction velocity
- Use: Atrial arrhythmias and preventing recurrent MI and SCD
- atenolol, metoprolol, acebutolol, and bisoprolol
- 2nd generation β- blockers
- β1-selective
- β1-selective with vasodilation
- 3rd generation β-blockers
- labetalol and carvedilol (also block α-adrenergic receptor),
- pindolol (also act as a β2-receptor partial agonist).
Amiodarone
-acts as a class I, class II, and class IV antiarrhythmic. MOA: -alters lipid membrane -Blocks I-Kr, I-Na, I-CaL Effects: -Prolongs AP duration and QT interval -Slows HR and AV node conduction -Low incidence of torsades de pointes Clinical uses: -serious ventricular arrhythmias -Supraventricular arrhythmias PK: -Oral, IV -Hepatic metabolism and elimination Toxicity: -bradycardia and heart block -peripheral vasodilation -pulmonary and hepatic toxicity Interactions: -Many based on CYP metabolism Dronedaronez: -newly approved non-iodinated analog of amiodarone for atrial fibrillation. -I-Kr block -Prolongs AP and effective refractory period
Sotalol
- Class III and class II antiarrhythmic drug.
- nonselectively antagonizes β-adrenergic receptors.
- Also blocks I-Kr
- Prolongs AP
- used to treat severe ventricular arrhythmias
- especially in patients who cannot tolerate amiodarone.
- also used to prevent recurrent atrial flutter or fibrillation to maintain normal sinus rhythm.
Procainamide Clinical Uses
-Clinical Applications
*Atrial and ventricular arrhythmias
*First choice for A. fib w. conduction thru accessory pathway
*2nd choice for sustained Ventricular Arrhythmias post-MI
*PSVT
*VT
VF
Ibutilide
- class III antiarrhythmic drug
- enhances a slow inward Na+ current that prolongs repolarization
- K+ channel blocker
- used to terminate atrial fibrillation and flutter.
- major side effect: increase QT interval, resulting in torsades de pointes
Procainamide Pharmacokinetics
- Pharmacokinetics:
- Oral, IV, IM
- hepatic metabolism and renal elimination
- metabolite can cause torsades de pointes in pts w/ renal failure
Bretylium
-class III antiarrhythmic drug and an antihypertensive
-concentrated in the terminals of sympathetic neurons
-causes initial release of NE then inhibits further release of NE
“chemical sympathectomy”
i-ncreases the AP duration in normal and diseased cardiac cells.
-Acts in Purkinje fibers and secondarily in ventricular myocytes
-no effect on atrial tissue.
-indicated only in patients with recurrent ventricular tachycardia or fibrillation after lidocaine and defibrillation measures have failed.
Procainamide Toxicities
- Toxicity:
- HTN
- LUPUS like symptoms
- Quinidine is similar to procanimide but more toxic (rarely used)
verapamil
- Class IV – Ca2+ Channel Blockers
- Blocks I-CaL
- preferentially act on SA and AV nodal tissues (pacemaker tissues)
- Slows SAN automaticity and AVN conduction velocity
- Diltiazem
- Decreases cardiac contractility
- Reduces BP
Lidocaine Clinical Uses
- Drug of 1st choice to terminate VT w/ remote MI
- prevent ventricular fibrillation after cardioversion
Adenosine
- Binds specific P1 class of purinergic GPCRs
- activates ACh- sensitive I-Kr channels
- Blocks I-Ca
- Very brief AV blockade
- shortens AP duration
- hyperpolarization
- slows normal automaticity.
- antiarrhythmic by increasing AV nodal refractoriness and by inhibiting DADs elicited by sympathetic stimulation.
- Often used through bolus IV injection to terminate PSVT
- PK:
- IV only: 15s duration
- Toxicity: flushing, chest tight, dizzy
Lidocaine Pharmacokinetics
- PK:
- IV
- hepatic metabolism
- Reduce dose in pts in heart failure or liver disease
