Antiarrhythmics Flashcards
Outline the Vaughan Williams classification of antiarrhythmic drugs
CLASS 1: Na+ channel blockers
- Lidocaine (1B)*
- Flecainide (1C)*
CLASS 2: Beta blockers
- Bisoprolol*
- Metoprolol*
CLASS 3: K+ channel blockers
- Amiodarone*
- Sotolol*
CLASS 4: Ca2+ channel blockers
- Diltiazem*
- Verapamil*
CLASS 5: others
- Adenosine*
- Digoxin*
- Atropine*
- Ivabradine*
What is torsades de pointes?
Torsades de pointes is a specific form of polymorphic ventricular tachycardia in patients with a long QT interval. It is characterized by rapid, irregular QRS complexes
How is the coordination of a heart beat achieved?
Coordinated sequence of changes in membrane potentials; initiated in the SA node
Briefly describe how arrhythmias arise
Heart condition due to disturbances in:
- Pacemaker impulse generation (SA or AV node)
- Contraction impulse conduction (abnormal conduction through tissue)
- Combination of the two
Results in rate/timing of contraction of the heart muscle being _insufficient to maintain the normal CO_
Describe the generation of the resting membrane potential
- Transmembrane potential maintained; interior of cell -ve with respect to outside the cell
- Caused by unequal distribution of ions inside vs outside a cell
- Maintenance by ion selective channels, active pumps, exchangers
Via passive diffusion, ligand-gated ion channels, voltage-gated eg Ca2+ channels
Where does the fast cardiac action potential exist?
Cardiac tissue
Role of Na+/K+ ATP ase in restarting the action potential once reverted back to resting state
Describe the effects of Class 1 drugs (blocking Na+ channels)
C1: Na+ channel blockers
(Flecainide; used in AF, narrow complex tachycardias)
- Slowing conduction in cardiac tissue (phase 0)
- Minor effects on action potential duration (APD)
- Phase 0 (upright phase) shifted to right
Describe the effects of Class 2 drugs (B-blockers)
- Diminish phase 4 depolarisation and automaticity (any automatic or focal arrhythmias)
- Inhibit Ca2+ inflow into the heart, thus affect the plateau
Give some other ways by which B-blockers have antiarrhythmic effects
- Reducing HR
- Reducing AV conduction velocity
- Reducing delayed/early afterdepolarisations
- Reducing conduction velocity
- Reduce action potential duration (APD)
- Reduce effective refractory period (ERP)
- Reduce re-entry
Describe the effects of Class 3 drugs (K+ channel blockers)
- Increase action potential duration (APD)
- Increase refractory period
Increased refractory period leads to an extended QT interval- can lead to proarrhythmias/dangerous arrhythmias
Potassium Channel Blockers. A class of drugs that act by inhibition of potassium efflux through cell membranes. Blockade of potassium channels prolongs the duration of ACTION POTENTIALS. They are used as ANTI-ARRHYTHMIA AGENTS and VASODILATOR AGENTS
Mechanism of Class 3 drugs
K+ channel blockers (Class 3)
Describe the effects of Class 4 drugs (Ca2+ channel blockers)
- Decrease inward Ca2+ currents
- Resulting in decreased phase 4 spontaneous depolarisation
- Affect the plateau phase of action potential
Where does the slow cardiac action potential occur?
SA and AV node (pacemaker potential)
Upstroke due to Ca2+ NOT Na+!
Describe the effect of Ca2+ channel blockers on the slow cardiac action potential
- Reduce conduction velocity (slope of phase 0 = CV)
- Slowing SA and AV node conduction velocity
- Increase refractory period
Mechanism of Ca2+ channel blockers on slow cardiac AP
Give some examples of drugs affecting the automaticity of the SLOW cardiac AP
B-agonist (eg salbutamol) - leads to sinus tachycardia (affecting SA node thus in sinus rhythm)
B-agonists increase the slope of the pacemaker potential (stimulation of sympathetic activity)
Muscarinic agonists (eg ADENOSINE) - affects slope of AP
Muscarinic agonists decrease the slope of the pacemaker potential (stimulation of parasympathetic activity)
REMEMBER
Fast AP in CARDIAC TISSUE
Slow AP in SA or AV node
Give the 2 main mechanisms of arrhythmogenesis
- Abnormal impulse generation (automatic rhythms)
- Abnormal conduction - re-entry
Explain the pathophysiology of Wolf-Parkinson-White syndrome
- Presence of an accessory pathway (Bundle of Kent); connects the atrium + ventricle
- Impluses are allowed to travel back up to the atrium, generating a re-entry loop
- WOLK-PARKINSON-WHITE SYNDROME: in small population, congenital abnormality
- Leads to pre-excitation
Treatment: catheter ablation to destroy accessory pathway (in high risk pt’s)
What is the conduction ratio?
Proportion of atrial contractions to ventricular contractions
Eg 2:1 ratio implies that 2 atrial contractions lead to 1 ventricular contraction
Why can patients get a ventricular arrhythmia post MI?
Due to scar tissue formation in the heart post MI
Scar tissue can spontaneously depolarise and generate localised entry
This can lead to ventricular arrhythmias eg ventricular tachycardia
Give an overview of the main actions of antiarrhythmic drugs
In case of ABNORMAL GENERATION:
- Raises threshold
- Decreases phase 4 slope (in pacemaker cells)- ie decreases slope of pacemaker potential (slow cardiac AP); mainly B-blockers, Ca2+ channel blockers
In case of ABNORMAL CONDUCTION:
- Decreases conduction velocity (phase 0); mainly Na+ channel blockers
- Increases effective refractory period (ERP) so cell won’t be re-excited again; mainly class 3 drugs
Give the main mechanisms by which antiarrhythmics work
- Reduce abnormal impulse generation
- Slow conduction through tissue
What are the pharmacological goals that antiarrhythmics achieve?
- Restore normal sinus rhythm (cardiovert)
- Prevent lethal arrhythmias
- Decrease conduction velocity
- Change the duration of ERP
- Suppress abnormal automaticity
Give an overview of the Vaughan-Williams classification and give some examples of drugs within each class
Which class does lidocaine belong to?
Class 1b
Given IV only
Describe the effects of lidocaine on cardiac activity
- No change in phase 0 in normal tissue
- APD slightly decreased (normal tissue)
- Increased threshold (Na+)
- Decreased phase 0 conduction in fast beating or ischaemic tissue
No effects on ECG in normal, increased QRS in fast beating/ischaemic
Fast binding offset kinetics; rapidly dissociates in time for next action potential
Give some uses of Class 1b drugs eg lidocaine
- (acute) Ventricular tachycardia (eg post MI/during ischaemia)
- NOT used in atrial arrhythmias/AV junctional arrhythmias
Give some side effects of Class 1b drugs eg lidocaine
- Less proarrhythmic than class 1a (less QT effect)
- CNS effects; dizziness, drowsiness
- Abdominal upset
Which class does flecainide belong to?
Class 1c (Na+ channel blocker)
Oral or IV (absorption and elimination)
Describe the effects of flecainide on cardiac activity
- Slow binding offset kinetics
- Substantially decreases phase 0 (Na+) in normal
- Reduced automaticity (increased threshold)
- Increased action potential duration (K+) and increased refractory period
- Works esp in RAPIDLY DEPOLARISING ATRIAL TISSUE
Increases PR, QRS AND QT interval (Torsades, lethal arrhythmia)
Give some uses of flecainide (Class 1c)
Wide spectrum;
- Supraventricular arrhythmias; atrial fibrillation, flutter (slowed conduction through atrial tissue) – give medication to slow AV conduction alongside
- Premature ventricular contractions
- Wolf-Parkinson-White syndrome - binds to Bundle of Kent + slows down conduction through atrial tissue
DO NOT USE IN ASCHAEMIA/POST MI (ie structural/ischaemic heart disease– sudden death)
Give some side effects of flecainide (Class 1c)
- Proarrhythmia + sudden death; esp with chronic use + STRUCTURAL HEART DISEASE
- Increased ventricular response to supraventricular rhythms (flutter)
- CNS effects
- Gastrointestinal effects
Give some examples of Class 2 agents
B-blockers
Propanolol (oral/IV)
Bisoprolol (oral)
Metoprolol (oral/IV)
Describe the cardiac effects of B-blockers
- Increased action potential duration in AV node to slow AV conduction velocity
- Decreased phase 4 depolarisation (catecholamine eg adrenaline dependent) in slow cardiac AP
Effects of ECG:
- Increased PR
- Decreased HR
Give some uses of Class 2 agents (B-blockers)
- Sinus and catecholamine dependent tachycardia
- Converting re-entrant arrhythmias at AV node
- Protecting ventricle from high atrial rates (slow AV conduction) in atrial flutter/fibrillation
Give some side effects of B-blockers
- Bronchospasm
- Hypotension
- DON’T USE IN PARTIAL AV BLOCK OR ACUTE HEART FAILURE (are used in stable heart failure)
Give 2 examples of Class 3 agents (K+ channel blockers)
Amioderone
Sotalol
Oral or IV
Describe the cardiac effects of Class 3 agents (K+ channel blockers)
- Increase refractory period and increase APD (K+)
- Decreased phase 0 and conduction (Na+)– Na+ channels inactivated due to prolonged repolarisation
- Increased threshold (for AP’s)
- Decreased phase 4 (B block and Ca2+ block)
- Decreased speed of AV conduction
Effects on ECG:
Increased PR
Increased QRS
Increased QT
Decreased HR
Why must Class 3 agents (B-blockers) like amioderone and sotalol be given via a central line, and not peripherally?
Due to thrombophlebitic effects if given peripherally
Give some uses and side effects of amioderone (class 3)
USES:
- Wide spectrum; efective for most arrhythmias (esp life threatening eg ventricular tachycardias)
SIDE EFFECTS:
- Pulmonary fibrosis; SOB
- Hepatic injury (scarring); thus monitor liver function
- Increased LDL cholestrol
- Thyroid disease (AS CONTAINS IODINE)
- OPTIC NEURITIS (TRANSIENT BLINDNESS)
Describe the cardiac effects of sotalol (Class 3)
Oral absorption
- Increases APD and refractory period in atrial and ventricular tissue
- Slow phase 4 (as B-blocker at lower doses)
- Slow AV conduction
ECG effects:
Increased QR (risk Torsades)
Decreased HR
Give some uses and side effects of sotalol (class 3)
USES:
- Wide spectrum; supraventricular and ventricular tachycardia
SIDE EFFECTS:
- Proarrhythmia
- Fatigue
- Insomnia (due to B-antagonist effects)
Give 2 examples of Class 4 agents
Ca2+ channel blockers
Verapamil (oral/IV)
Diltiazem (oral)
Describe the cardiac effects of Class 4 agents (Ca2+ channel blockers)
- Slow conduction through AV (Ca+)
- Increase refractory period in AV node
- Increase slope of phase 4 in SA to slow HR
Effects on ECG:
- Increased PR
- Increased/decreased HR (depdending on BP response; baroreflex)
Give some uses and side effects of Class 4 agents (Ca2+ channel blockers)
USES:
- Control ventricles in supraventricular tachycardia (as slow conduction through AV node)
- Convert supraventricular tachycardia (re-entry around AC)
SIDE EFFECTS:
- Caution; partial AV block
- ASYSTOLE IF B-BLOCKER PRESENT; THUS DO NOT GIVE VERAPAMIL + B-BLOCKER (as excessive bradycardic effects on heart, thus heart may stop!)
- Hypotension, decreased CO, sick sinus
- GI problems (constipation)
Describe the properties, mechanism, cardiac effects and uses of adenosine (class V agent)
Rapid, IV bolus, v short T 1/2
- Natural nucleoside that binds A1 receptors and activates K+ currents in AV + SA node
- Decreases action potential duration
- Causes hyperpolarisation
- Thus, decreased HR
- Descreases Ca2+ currents- increased refractory period in AV node
Cardiac effects:
Slows AV conduction; terminates rhythms eg re-entry in WPW dependent on AV node
USES:
- Convert re-entrant supraventricular arrhythmias
- Diagnosis of coronary artery disease (SCANS); as heart normally speeds up after administration of adenosine
Descibe the mechanism, cardiac effects, side effects and uses of ivabradine (Class V agent)
Oral administration
Blocks If ONLY IN SA NODE; thus no hypotensive effects
Blocks If current highly expressed in sinus node
Slows sinus node BUT DOES NOT AFFECT BLOOD PRESSURE
SIDE EFFECTS:
- Flashing lights
- Teratogenicity (avoid in pregnancy)
USES:
- Reduce inappropriate sinus tachycrdia
- Reduce heart rate in angina + heart failure
**AVOIDING BP DROPS
Describe the mechanism and uses of digoxin
Cardiac glycoside; used as last resort
Enhances vagal activity - increased K+ currents, decreased Ca2+ currents, increased refractory period
Slows AV conduction + slows HR
USES:
- Tx to reduce ventricular rates in atrial fibrillation + flutter
Describe the mechanism, cardiac effects and uses of atropine
IV administration only
SELECTIVE MUSCARINIC ANTAGONIST
**RENALLY EXCRETED; CAUTION IN RENAL FAILURE
Blocks vagal activity to speed AV conduction and increase HR
USES:
To treat VAGAL BRADYCARDIA
Which channels does amioderone block?
Na+, K+ and Ca2+ channels
Thus, amioderone acts as a NON-SELECTIVE B-BLOCKER
