CV Arrhythmias notes PDF

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13.CV ARRHYTHMIAS1. CARDIAC ELECTRICAL ACTIVITY2. CARDIAC MYOCYTE AP3. CARDIAC NODAL AP4. ELECTROCARDIOGRAM5. DYSRHYTHMIA CLASSIFICATIONS6. CAUSES OF ARRHYTHMIAA. After-polarisation: i. Abnormally high [Ca2+]i triggering trains of Aps. Often causes ectopic beats. B. Re-entry: i. Impulse re-excites p...

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13.12.18

CV ARRHYTHMIAS 1. CARDIAC ELECTRICAL ACTIVITY

2. CARDIAC MYOCYTE AP

3. CARDIAC NODAL AP

4. ELECTROCARDIOGRAM

5. DYSRHYTHMIA CLASSIFICATIONS

6. CAUSES OF ARRHYTHMIA A. After-polarisation: i. B.

Abnormally high [Ca2+]i triggering trains of Aps. Often causes ectopic beats. Re-entry:

i. C.

Impulse re-excites previously active tissue; AP circulation. Often associated with damaged heart tissue Ectopic pacemaker activity:

i.

Excessive automaticity; overactivity of nodes or ectopic activity outside nodes

7. TRIGGERED ACTIVITY

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8. RE-ENTRY

9. EXCESSIVE AUTOMATICITY

10.

OLD SCHOOL CARDIAC PARMACOLOGY Vaughan-Williams classification (1970s; outdated). Define by electrophysiological effects. A. Class I (a, b, c): VG Na+ channel blockers B. Class II: Anti-sympathetic (“beta blockers”) C. Class III: VG K+ channel blockers D. Class IV: VG Ca2+ blockers E. Class V: Anything else (e.g. digoxin, adenosine)

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CLASS 1 MOAS Block VG Na+ channel – main effect to slow AP conduction in myocytes

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Na + CHANNEL BLOCKER USE DEPENDENCY

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A. The faster the cell fires Aps, the more drug binds and slows AP generation B. Therefore, minimal effect at low heart rate

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CLASS 1A MOA A. Quinidine (classic, but obsolete) – high TdP risk B. Procainamide (obsolete) C. Disopyramide:

14.

i.

Can be used for atrial & ventricular tachycardias

ii.

Anticholinergic side effects (especially disopyramide)

iii.

Negative inotropic effect (= reduced contractility) due to ↓ Ca2+ entry: avoid with hypotension or low ventricular output

CLASS 1B DRUGS A. Lidocaine (IV only; also used as local anaesthetic) B. Mexiletine (orally available, rare in UK) C. Tocainide (obsolete) D. Rapid dissociation means little effect except at fast heart rates E. Used for ventricular tachycardia & fibrillation; minimal effectiveness for atrial tachycardias

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CLASS 1C MOA A. Rapid dissociation means little effect except at fast heart rates B. Used for ventricular tachycardia & fibrillation; minimal effectiveness for atrial tachycardias C. Used for atrial fibrillations and ventricular tachycardia (AV nodal re-entrant tachycardia) D. Potent negative inotropes – risk of heart failure if weak heart

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CLASS 2 MOA Adrenergic b receptor antagonism: ↓ cAMP, ↓ Ca2+ (possibly also ↓ Na+?)

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CLASS II DRUGS: “BETA-BLOCKERS” Reduce mortality following MI; reduce arrhythmias due to excessive sympathetic activity A. Propranolol (has some class I activity) B. Sotalol (some class III activity) C. …lol (many others, although often not favoured for arrhythmias) D. Side effects:

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i.

Dizziness, fatigue, hypotension, nausea, diarrhoea, peripheral vasoconstriction

ii.

Sotalol may be more potent where class III effects useful, but should otherwise be avoided (e.g. TdP risk)

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CLASS III: MOA Block K+ channels. Reverse use dependency – potentially pro-arrhythmic in bradycardia. A. Effect on myocyte (& nodal) AP: i.

Delays repolarisation (phase 3)

ii.

Negative chronotropic, positive inotropic

B. Class III drugs are highly effective although also have severe side effects

19.

CLASS III DRUGS A. Amiodarone (has some class 1a, class II & class IV activity) i.

Toxicity (lungs, liver), thyroid dysfunction, TdP, skin discolouration & photosensitivity

B. Dronedarone similar to amiodarone but less lipophilic & safer. C. Sotalol; less effective class III effects D. Use in atrial & ventricular tachycardias (usually when patients refractory to other drugs); Wolfe-Parkinson-White syndrome

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WOLFE-PARKINSON-WHITE SYNDROME

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21.

CLASS IV: MOA Block voltage-gated Ca2+ channels (L-type) mainly at nodes. Use dependent. (Rapid depolarisation by T-type channels) A. Therapeutic effect on nodal AP: i.

Decreases amplitude of AP

ii.

Increases length of nodal AP*

iii.

Negative inotrope (myocytes)

B. Note: decreases length of myocyte AP – may be dangerous with ventricular tachycardias.

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CLASS IV DRUGS Used in atrial fibrillations and (rarely these days) paroxysmal super ventricular tachycardia. Ca2+ blockers also dilate blood vessels. A. Verapamil (also a-blocker and Na+ channel blocker) B.

Diltiazem

C. Side effects: i.

constipation, dizziness, hypotension, oedema, risk of heart failure

D. May also be used as antihypertensive & antianginal medication

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CARDIAC GLYCOSIDES: DIGOXIN II To get started right away, just tap any placeholder text (such as this) and start typing. A. Na+ / K+ pump inhibitor (from foxglove) B. Degrades K+ and Na+ concentration gradients; depolarises vagus nerve C. Increased ACh release → M2 receptors D. ↑ K+ in nodal cells = hyperpolarisation E. Unsafe: very low TI; dizziness, confusion, fatigue, nausea & vomiting.

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CARDIAC GLYCOSIES: DIGOXIN II

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i.

Also inhibits Na+ / K+ pump in myocytes

ii.

Increased intracellular Na+ reduces efficacy of Na+ / Ca2+ antiporter

iii.

Increased intracellular Ca2+; positive inotrope – also used in heart failure

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ADENOSINE A. Preferred to verapamil for acute paroxysmal superventricular tachycardia; IV, very short-acting. B. Activates A1 receptors in AV node: C. Increased K+ permeability, hyperpolarisation D. Side effects: chest pain, shortness of breath, dizziness, nausea E. Adenosine also a potent vasodilator

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DRUGS FOR BRADYARRHYTHMIAS i.

IV Atropine (non-specific muscarinic antagonist) -

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First line treatment for bradycardia; reduce vagal nerve influence

ii.

IV Adrenaline (non-specific adrenergic agonist – b1 in heart)

iii.

IV Dopamine (non-specific adrenergic agonism – b1 in heart)

iv.

(IV isoprenaline)

v.

For chronic bradycardia, a pacemaker.

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RATE CONROL & RHYTHM CONTROL A. Key is to ensure an orderly activation of ventricles; prevent atrial tachycardia being passed to ventricles B. In practice, treatment for A-fib and atrial flutter are very similar C. Rate control: negative chronotropic agents to prevent atrial tachycardia being passed to ventricles D. Rhythm control: Cardioversion to restore sinus rhythm, drugs to maintain sinus rhythm

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RATE CONTROL Target nodal (AV node) cells A. First line treatment: i.

Class II (β-blockers except sotalol)

ii.

Class IV (diltiazem / verapamil)

B. Digoxin for patients with sedentary lifestyles C. Two of digoxin, class II or diltiazem D. Two of digoxin, class II or diltiazem

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RHYTHM CONTROL Prevent atrial fibrillations occurring A. First line treatment: Class II (β-blockers except sotalol) B. Class III (amiodarone, dronedarone, sotalol) or class 1C (flecainide, propafenone) i.

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Patients with paroxysmal A-fib (i.e. intermittent, recurring) may be given class 1c to take as required for cardioversion

SUMMARY 10

A. Anti-arrhythmic work by altering the characteristics of cardiac action potentials: i.

Class 1: lengthens rapid depolarisation (myocytes)

ii.

Class 2: lengthens slow depolarisation (mostly nodes)

iii.

Class 3: delays repolarisation

iv.

Class 4: lengthens nodal AP

v.

Digoxin & Adenosine

B. General effects are to: i.

Lengthen refractory period

ii.

Decrease likelihood of AP generation

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31.

PICTORAL SUMMARY

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