Exam 4 Drugs

Procainamide

• Class 1a

• MOA: Sodium channel blocker

  • slow upstroke of action potential

  • slow conduction and prolong QRS

  • prolong action potential (bc it also blocks K+)

• less effective than quinidine in suppressing abnormal ectopic pacemaker activity, more ffective in blockers sodium channels in depolarized cells

Quinidine

• Class 1A

• MOA: Sodium channel blocker

  • slows upstroke of action potential

  • slows conduction

  • prolong QRS

  • prolong action potential (blocks K channel)

• toxicity: excessive QT prolongation, torsades, excessively slowed conduction

Disopyramide

• Class 1A

• MOA: sodium channel blocker

  • cardiac antimuscarinic effects

Lidocaine

• Class 1B

• MOA: sodium channel blocker

  • block activated and inactivated sodium channels rapidly

  • greater effect on long action potential (Purkinje and ventricular cells)

  • rapid kinetics → recovery from block btwn action potentials, no effect on conduction

Mexiletine

• Class 1B

• MOA: sodium channel blocker

• used to treat ventricular arrhythmias

Flecainide

• Class 1C

• MOA: sodium and potassium channel blocker

  • slow unblocking kinetics

  • does NOT prolong action potential or QT interval

Amiodarone

• Class 3

• MOA: Potassium channel blocker

  • prolong action potnetial

  • prolong QT interval

  • block inactivated sodium channels

  • weak adrenergic and calcium channel blocking actions

  • slow heart rate, AV node conduction

• high efficacy, low incidence of torsades despite significant QT-interval prolongation

Sotalol

• Class 2 and 3

• MOA: beta blocker and potassium channel blocker

  • prolong action potential

  • not cardioselective

• racemic mixture

  • beta blocker activity: L isomer

  • potassium channel blocking activity: D and L

Verapamil

• Class 4

• MOA: calcium channel blocker

  • block activated and inactivated L-type calcium channel

  • effect in tissues that fire frequently, are less polarized at rest, and those in which activation depends on calcium current (SA, AV nodes)

  • prolong AV conduction and refraction

  • slow SA node directly, hypotensive action may result in small reflex increase

• can suppress both early and delayed afterdepolarization

Apixaban

• Factor Xa inhibitor

• AFib dose: 5 mg PO BID

  • adjust to 2.5 mg PO BID → 80+, ≤ 60 kg, SCr ≥ 1.5 (2 out of 3)

• Monitor: CBC, renal fx, hepatic fx

• AE: bleeding

• CI: hypersensitivity, active pathological bleeding

Dabigatran

• MOA: direct thrombin inhibitor

• AFib Dose: 150 mg PO BID

  • Renal dosing:

    • CrCl 15-30: 75 mg PO BID

    • avoid if CrCl < 15

• AE: GI sx (dyspepsia, gastritis), hemorrhage

• CI: hypersensitivity, active pathological bleeding, mechanical heart valves

• Pearls: do not cut, chew, open; tartaric acid may cause dyspepsia

Edoxaban

• MOA: factor Xa inhibitor

• AFib dose: 60 mg PO daily

  • Renal adjustment:

    • CrCl 15-50: 30 mg PO daily

    • CrCl < 15: avoid

    • CrCl > 95: avoid

• AE: bleeding

• CI: bleeding

• Monitor: CBC, renal fx, hepatic fx

Rivaroxaban

• MOA: Factor Xa inhibitor

• AFib dose: 20 mg PO daily

  • renal adjustment:

    • CrCl 15-50: 15 mg PO daily

    • CrCl < 15: avoid

• AE: bleeding

• CI: hypersensitivity, active bleed

• Monitor: CBC, renal fx, hepatic fx

• Pearls: Give with BIGGEST MEAL

Warfarin

• dose for AFib: individualized, based on INR (goal 2-3)

• AE: hemorrhage, hematuria, anemia, retroperitoneal hematoma

• CI: hypersensitivity, active bleeding, pregnancy (UNLESS pt w mechanical heart valve)

• monitor: CBC, INR

• pearls: genetic consideration on labeling, Vitamin K reversal agent,

Idarucizumab

• praxbind

• dabigatran reversal agent

Andexanet alfa

• Andexxa

• Apixaban or rivaroxaban reversal agent

• used off-label for edoxaban associated life-threatening bleeding

4-Factor PCC

• Kcentra

• urgent reversal of acute major bleeding or need for urgent surgery in pts recieving warfarin

• off-label: reverse factor Xa inhibitors in pts w life-threatening bleed, need urgent surgery

Activated PCC

• control and prevention of bleeding episodes, preoperative management, prophylaxis to prevent or reduce bleeding frequency in pts with hemophilia A and B

• used off-label for dabigatran associated bleeds

Amiodarone

• MOA: Class 1, 2, 3, 4 effects (classified as Class 3)

• Indication: supraventricular and ventricular tachyarrhythmias

• PK: variable bioavailability, delayed onset, long half-life

• Interaction: warfarin

• AEs:

  • torsades, QT prolongation, bradycardia

  • photosensitivity, blue-gray skin discoloration

  • hyper/hypo-thyroidism

  • elevation of AST/ALT

  • tremors, ataxia, peripheral neuropathy, insomnia

  • corneal microdeposites, optic neuropathy

  • pulmonary toxicity

• Monitor: ECG, physical exam, Thyroid fx, LFTs, eye exams, pulmonary function test, chest X-ray

Dofetilide (Tikosyn)

• MOA: Class 3 (potassium channel blocker)

• Indication: maintenance of normal sinus rhythm in highly symptomatic AF

• Dose: 500 mcg PO BID

  • renal adjustment based on actual BW

    • CrCl 40-60: 250 mcg PO BID

    • CrCl < 40: 125 mcg BID

    • CrCl < 20: avoid

• CI: long QT syndrome, baseline QTc > 440 msec, concurrent use with verapamil, cimetidine, hctz, trimethoprim, itraconazole, ketoconazole, prochlorperazine, megesterol

  • increased risk of torsades

• AE: headache, dizziness, syncope, insomnia, QT prolongation, Torsades (0.9-3.3%)

• Monitor: Mg, K, SCr

• Pearls:

  • hold previous antiarrhythmic at least 3 half lives before initiation

  • in hospital initiation

  • wait at least 3 days to 12 hours after conversion (5 doses)

    • can increase risk of torsades

Dronedarone (Multaq)

• MOA: Class 3 (potassium channel blocker)

  • analog of amiodarone

• Dose: 400 mg PO BID

• Indication: paroxysmal or persistent afib, aflutter

  • NOT used for permanent Afib, ventricular arrhythmias

  • does NOT interact w warfarin

• PK: shorter half life vs amiodarone

• Boxed warning: increased risk of death, stroke, and HF

• CI: Class ¾ HF, decompensated HF in past 4 weeks

• AE: abdominal pain, bradycardia, N/V/D, QT prolongation, Torsades, hepatotoxicity

Ibutilide (Corvert)

• MOA: Class 3 (potassium channel blocker)

• Dosing (IV)

  • < 60 kg: 0.01 mg/kg over 10 min

  • 60+ kg: 1 mg over 10 min

• Indication: cardioversion only, NOT for chronic management

• AE: nonsustained ventricular tachycardia, QT prolongation, torsades

• Monitor: EKG for at least 4H after admin, or until QT returned to baseline

Sotalol

• MOA: Class 2/3 (beta blocker, potassium channel blocker)

• Dosing: loading and maintenance, renally adjusted

• AE: AV block, bradycardia, bronchospasm, HF exacerbations, fatigue, QT prolongation, torsades

• Admin: admit for at least 3 days in patient

Flecainide

• MOA: Class 1cv (sodium channel blocker)

• Dosing:

  • cardioversion: weight based

  • maintenance

• AE: atrial flutter, AV block, dizziness, dyspnea, HF exacerbation, headache, QT prolongation, Ventricular tachycardia, visual disturbances

• CI/warning: structural heart disease

• Monitor: continuous EKG with initiation or first dose for Pill in the pocket dosing

Propafenone (Rhythmol)

• MOA: Class 1c (sodium channel blocker)

• dosing: cardioversion and maintenance

• AE: atrial flutter, bradycardia, dizziness, dyspnea, HF exaceration, taste and visual disturbances, ventricular tachycardia

• monitor: continuous EKG monitoring with first dose for pill in the pocket dosing