Arrhythmia Drugs Flashcards
What are the four classes of arrhythmia drugs?
1 - Na channel blocker
2 - beta blocker
3 - potassium blocker
4 - Ca blocker
‘No boys kick constantly’
What can calcium channel blockers be divided into? Give examples, boths mechanism of action and uses
Dihydropyridines:
E.g. amlodipine, felodipine
Acts selectively on vascular smooth muscle -> reduces systemic resistance and arterial pressures
Used in HTN (hypertension)
Non-dihydropyridines: E.g. verapamil, diltiazem -ve inotrophic/ chronotrophic/ dromotrophic (force, rate, cardiac conduction velocity) Used in HTN, angina, arrhythmias Don’t use with beta b (-> ❤️block)
What does each part of the ECG represent?
P - contraction of atria PR segment (end of P to start Q) - through AVN QRS - contraction ventricles ST segment (end S to start T) - break T wave - depolarisation ventricles
Also have PR interval (start of P to start Qj QT interval (start Q to end of T)
What is an arrhythmia?
Heart condition where disturbances in pacemaker impulse formation &/or contraction impulse conduction -> rate &/or timing of contraction may be insufficient to maintain normal CO
E.g. bradycardia, tachycardia, atrial fibrillation, atrial flutter, PSVT, ventricular fibrillation, V-tachycardia, long QT syndrome, sinus node dysfunction, ❤️block
How is a transmembrane electric gradient maintained within the cardiac cells in which the interior of the cell is negative with respect to the outside of the cell?
- Na+ higher outside
- Ca2+ much higher outside
- K+ higher INSIDE
(Salty caramelised banana)
-90mV resting potential
How is the ventricular/ cardiac action potential achieved?
RMP -90mV (mostly due to background Na/ K ATPase (3Na out, 2K in)
- V-gated Na+ channels open upstroke
- Transient outward K+ current
- V-gated Ca2+ channels open plateau (L-type)
- Ca2+ channels inactive, V-gated K+ channels open repolarisation
- Na/ K ATPase (3Na out, 2K in) -> RMP
- Na influx
- K+ efflux
- Ca efflux
- more K efflux
See slide 11
How is the SA node action potential achieved?
If funny current/ pacemaker potential activated at membrane potentials more negative than -50mv (more negative = more activates)
HCN channels:
1. Influx Na+ depolarises cell
2. V- gated Ca2+ channels influx upstroke
3. V- gated K+ channels efflux downstroke repolarisation
See slide 11
How does the SAN action potential lead to the ventricular/ cardiac action potential?
SAN APs -> increase in cytosol Ca2+ -> actin and myosin interaction -> contraction
How do class 1 anti arrhythmia drugs work?
Block Na channels in cardiac action potential so no influx of Na+ and
Marked slowing conduction in tissue (upstroke shifted right) - slide 13
How do class 2 antiarrhythmia drugs work?
Beta blockers
Decrease sympathetic drive -> reduces SAN/ AVN firing -> decrease Ca2+ influx into ❤️-> increase plateau duration & diminishes phase 4 depolarisation & automaticity
Slide 15
How do class 3 antiaarrhythmia drugs work?
Block K+ channels so extend refractory period (QT interval longer)
Increase AP duration (APD)
Slide 16
How do class 4 anti arrhythmia drugs work?
Calcium channel blockers
Decrease inward Ca currents -> decrease phase 4 spontaneous depolarisation (plateau phase lasts longer)
Slide 17
Mechanisms of arrhythmogenesis
Slide 22/ 23
How is Wolf- Parkinson white caused?
Heart beats abnormally fast for periods of time
Accessory pathway called bundle of Kent connects atria to ventricles so AP can re-enter (down purkinje fibres -> BOK -> atria)
Where can re-entry occur in everyone?
At the AVnode
50% of people have a fast and slow pathway, 50% just a fast pathway
Ectopic beat travels down part pathway -> refractory -> pushes rhythm back up other way -> creating circuit constant loop -> tachycardia
How can we get micro- reentries?
If patient has MI -> damaged imperfect tissue -> localised rentry within scar tissue -> ventricular tachycardia
Which classes of drugs are used for abnormal generation and which for abnormal conduction and why?
Abnormal generation:
Decrease of phase 4 slope (in pacemaker cells) - reduces SAN/ AVN firing/ spontaneous depolarisation
E.g. class 2 beta blockers & class 4 Ca blockers
Abnormal conduction: Decrease conduction velocity e.g. class 1 Na channel blockers slow depolarisation
Or increase effective refractory period so the cell won’t be reexcited again e.g. class 3 K channel blockers
What is Vaughan-Williams classification? Give examples in each class
All 1 block Na
1a - moderate phase 0 e.g. Quinidine, procainamide
1b - no change in phase 0 e.g. lidocaine
1c - marked phase 0 e.g. Flecainide, propafenone
2 beta adrenergic blockers e.g. bisoprolol, metoprolol, propranolol
3 prolong repolarisation e.g. amiodarone, sotalol
4 Ca channel blockers e.g. Varepamil, diltiazem
Class 1A agents, absorption and elimination, effects on cardiac activity, effects on ECG, uses, side effects
Procainamide, quinidine, disopyramide
Oral or IV
Decreased conduction (decreased phase 0 of AP) and automaticity (slope phase 4)
Increased refractory period and threshold
Quinidine - anticholinergic to speed up AV conduction used with digitalis, beta blocker or CCB
ECG: increased QRS, +/- PR, increased QT
Uses: quinidine - atrial fibrillation/ flutter, brugada syndrome
Procainamide - supraventricular/ ventricular arrhythmias
Side effects: hypotension, proarrhythmia, insomnia, GI, lupus like syndrome
Class 1B agents, absorption and elimination, effects on cardiac activity, effects on ECG, uses, side effects
Lidocaine - IV
mexiletine - oral
Fast binding offset kinetics
No change phase 0 normal tissue
APD slightly decreased
Increased threshold
Decrease phase 0 conduction in fast beating/ ischaemic tissue
ECG: none in normal, in fast/ ischaemic increased width QRS
Uses: acute ventricular tachycardia
Side effects: less proarrhythmic, abdo upset
Class 1C agents, absorption and elimination, effects on cardiac activity, effects on ECG, uses, side effects
Flecainide and propafenone
Oral or IV
Very slow binding offset kinetics
Decreased phase 0 normal tissue/ automaticity
Increased APD and refractory period
ECG: increased PR/ QRS/ QT
Uses: supraventricular arrhythmias, premature ventricular contractions, Wolff Parkinson white syndrome
Side effects: proarrhythmia, sudden death with chronic use, structural/ ischaemic heart disease increased ventricular response to supraventricular arrhythmias
Investigations for atrial fibrillation pneumonic and causes
ATRIAL BP
Alcoholic liver disease - LFTs Thyroid disease - T3/T4 Rheumatic HD - Hx Ischaemic HD - Hx Atrial myxoma - cancer Lung disease BP Pherocromcytoma
How to remember the names of cardioselective beta blockers
MANBABE
Beta 1
Metoprolol Atenolol Nebivolol Bisoprolol Acebutolol Betaxolol Esmolol
Mixed alpha beta - doesn’t end in olol e.g. carvediol, labetalol
Non selective: propranolol, nadolol
Class 2 agents, absorption and elimination, effects on cardiac activity, effects on ECG, uses, side effects
Propranolol oral/ IV, bisoprolol oral, metoprolol IV/ oral, esmolol IV
Increased APD/ refractory period in AVN
Decreased phase 4 depolarisation
ECG: increased PR, decreased HR
Uses: sinus and catecholamine dependent tachycardia, reentrant arrhythmias, slow AV conduction in atrial fibrillation/ flutter
Side effects: bronchospasm, hypotension, don’t use partial av block or acute heart failure
