Cardio (Elsaid) STUDY - IE 2

LECTURE 1: Antiarrhythmics

Electrical Conduction of Heart

SA —> atrium contraction/spontaneous depolarization —> AV node —> atria repolarization/relaxation —> ventricles contraction & repolarization

Channels

• Resting —> opens leaky Na+ channels —> slow influx of Na+ —> open Ca+2 channels —> Ca+2 influx —> depolarization —> K+ channels open —> repolarization

Na —> Ca —> K

Refractory Period

Waves

• P-wave: atrial depol

• QRS: ventricular depol

• T-wave: ventricular repol

• PR Interval: atria to ventricles

• QT Interval: ventricular depol to ventricular repol

Fast-Response Tissues

• Atria

• Ventricles

• His-Purkinje cells

Slow-Response Tissues

• SA Node

• AV Node

Slow Response Cells

• Phase 0: Depolarization (Ca+2)

• Phase 3: Repolarization (K+)

• Phase 4: Slow spontaneous depolarization

Atropine Sulfate

• MOA: anticholinergic receptor (M2 antagonist)

  • Manage bradycardia

4 Causes of Arrythmias

1. Electrolyte Imbalances

• Structural defect in Na+ or K+ —> congenital long QT syndrome

2. Enhances Automaticity

• Beta-adrenergic overstimulation

• Hypokalemia

• Mechanical stretch of cardiac muscle cells —> accelerate pacemaker

2. Triggered Automaticity

   1. Delayed Afterdepolarization (DAD) —> Ca+2 overload

   2. Early Afterdepolarization (EAD) —> low K+

3. Re-entry

   1. Electrical impulse → tissue activated → tissue repolarizes → impulse circles back → tissue activated again → repeated cycle (re-entry)

AV Block Types

• 1st degree: prolonged PR interval

• 2nd degree: prolonged PR interval & lower CO

• 3rd degree: complete heart block —> cardiac arrest

Atrial Flutter

• Sawtooth P-wave (atrial depol)

Atrial Fibrillation

• No P-wave

Ventricular Tachycardia

• Wide QRS complex (ventricular depol)

Ventricular Fibrillation

• Erratic disorganized EKG

Antiarrhythmic Drugs

• Class I: Na+ Channel Blockers

  • [slow depolarization in FAST action potential cells]

    • IA: binds to activated/inactivated channels

      • Na+ AND K+ Channel Blocker

      • [↑ QRS, ↑QT] longer ventricular conduction

      • Intermediate dissociation from channels

        • Quinidine

        • Procainamide

    • IB: binds to ONLY inactivated channels

      • [↓ QT] faster ventricular depolarization/repolarization

      • Selective for ischemic myocardium

      • Fast dissociation from channels

        • Lidocaine

        • Mexileiine

    • IC: binds to activated/inactivated channels

      • [↑ ↑ QRS] longer ventricular conduction

      • Slow dissociation from channels

        • Flecainide

        • Propafenone

• Class II: BB

  • [slow depolarization in SLOW action potential cells]

    • [↑ PR, block AV]

      • Sotalol (II + III)

      • Esmolol (II)

• Class III: K+ Channel Blockers

  • [K+ = repolarization, blocking K+ will prolong the AP duration; FAST cells]

    • [↑ QT]

      • Amiodarone (I-IV)

      • Dronedarone (I-IV)

      • Bretyllium

      • Ibutilide

      • Dofetillide

      • Sotalol (II, III)

• Class IV: CCB

  • [slow depolarization in SLOW action potential cells]

    • [↑ PR, block AV]

      • NON-DHP CCB:

        • Verapamil

        • Diltiazem

      • Magnesium

        • Slow AV and SA → slow HR, does NOT affect CO

• Misc

  • Adenosine —> [SLOW]

    • [↑ PR] —> decrease HR

    • Manage supraventricular tachycardia (SVT)

  • Digoxin —> [SLOW]

    • MOA: Na/K ATPase inhibition

    • Positive ionotropic effect (increase CO)

    • Negative chronotropic effect (decrease HR)

LECTURE 2: Anticoagulants

Indirect Thrombin Inhibitors

[Binds to antithrombin]

• Warfarin - Oral

• UFH - monitoring —> IIa > Xa - IV, SC

• LMWH - renally/hepatically adjusted —> IIa, Xa

  • Enoxaparin - SC

  • Dalteparin

  • Tinzaparin

• Fondaparinux - CI: renal/hepatic impairment —> Xa - SC

Warfarin

• MOA: Vitamin K antagonist

• Oral

• Site of action: Liver

Unfractionated Heparin (UFH)

• Longer —> Antithrombin (ATIII) binds to Thrombin (IIa) and Xa

  • Inhibits Thrombin (IIa) to a GREATER extent

• Short half-life

• No renal/hepatic dose adjustment

Low Molecular Weight Heparin (LMWH)

Inhibit thrombin/IIa and Xa

• Enoxaparin (Lovenox)

  • DVT: 1 mg/kg SC q12h

  • Prophylaxis: 40 mg SC QD OR 30 mg SC BID

  • Renal dose adjustment

• Dalteparin

• Tinzaparin

Fondaparinux

Inhibit factor Xa

SC

Direct Thrombin Inhibitors

[Binds to thrombin]

• Dabigatran (Pradaxa) - Oral

• Bivalirudin - IV

• Argatroban -IV

Direct Factor Xa Inhibitors

• Rivaroxaban - Oral

• Apixaban - Oral

• Edoxaban - Oral

Reversal Agents for Warfarin

• Vitamin K - Oral or IV

• Kcentra

  • MOA: Prothrombin Complex Concentrate

Protamine

Reversal for:

• Heparin (UFH)

• Enoxaparin (LMWH)

Andexxa

Reversal for:

• Rivaroxaban

• Apixaban

Praxbind

Reversal for:

• Dabigatran

LECTURE 3: Antiplatelets & Fibronolytics

Aspirin (Salicylate)

• IRREVERSIBLY inhibit COX-1 —> inhibit thromboxane A2 synthesis

• Use:

  • Pain, arthritis, headache, angina, MI, TIA, PCI

• ADE:

  • GI hemorrhage

  • Hypersensitivity

• Toxicity:

  • N/V

  • Tinnitus

  • Metabolic acidosis

  • Convulsions

P2Y12 Antagonists

• Clopidogrel (Plavix) - IRREVERSIBLE

  • PRODRUG

  • CI: 2C19 inhibition prevents active metabolite conversion

• Prasugrel (Effient) - IRREVERSIBLE

  • More potent than clopidogrel —> high bleeding risk

• Ticagrelor (Brilinta) - REVERSIBLE

  • More potent than clopidogrel —> but less bleeding risk

  • CI: 3A4 inhibitors

• Cangrelor (Kengreal) - REVERSIBLE

  • IV

  • Bridge therapy

• TICLODIPINE

GP IIb/IIa Inhibitors

• Eptifibatide

• Abciximab

• Tirofiban

————————————————————————————--

• Block final common pathway of platelet aggregation

• Adjunct to anticoag and P2Y12 inhibitor —> PCI

• CI: Bivalirudin

Fibrinolytic

• Alteplase

• Tenectaplase

LECTURE 4: Dyslipidemia

Cholesterol

• Steroid/sex hormones

• Vitamin D synthesis

• Cell membrane structure/fluidity

Triglyceride

• 3 FA + 1 glycerol

Liver vs. Intestine: LDL-C Lowering Agents

LIVER

• Statins (HMG CoA Reductase Inhibitor)

  • Longest Half-Life: Atorvastatin, Rosuvastatin, Pitavastatin

• Bempedoic Acid (ACL Inhibitor)

• PCSK9 Inhibitors

  • Alirocumab

  • Evolocumab

  • Inclisiran

INTESTINE

• Ezetimibe (Cholesterol absorption Inhibitor)

• Bile Acid Sequestrants (BAS)

  • Colesevalam

  • Colestipol

  • Cholestyramine

TG Lowering Agents

• Fibrates

  • Gemfibrozil

  • Fenofibrate

• Omega-3 FA

  • EPA+DHA Ethyl Ester (Lovaza)

  • EPA+DHA FA (Epanova)

  • Icosapent Ethyl (Vascepa)

• Niacin