Anti-arrhythmics Flashcards
What are the general causes of arrhythmias?
Problem in pacemaker impulse formation
Problem in contraction impulse conduction
Combination if the above
= rate/timing of contraction of heart muscle that is insufficient to maintain cardiac output
Outline the stages of the cardiac muscle action potential.
4 = open K+ rectifier channels keep membrane potential stable at -90mV
(K+ moves out)
0 = rapid Na+ influx through open fast Na+ channels
(Na+ moves in)
1 = transient K+ channels open and K+ efflux returns membrane potential to 0mV
(K+ moves out)
2 = influx of Ca2+ through L-type Ca2+ channels balanced by K+ efflux through delayed rectifier K+ channels
(Ca2+ moves in and K+ moves out)
3 = Ca2+ channels close; K+ delayed rectifier channels return membrane potential to -90mV
(K+ moves out)
Outline the stages of the SAN action potential.
4 = Na+ influx (funny current) activated via HCN channels at -50mV
(Na+ moves in)
0 = Ca2+ influx; HCN channels closed
(Ca2+ moves in)
2 = Ca2+ influx
(Ca2+ moves in)
3 = K+ efflux and inactivation of Ca2+ channels —> unstable resting potential
(K+ moves out)
Outline the different mechanisms of arrhythmias.
ABNORMAL IMPULSE GENERATION
- –> AUTOMATIC RHYTHMS
- –> TRIGGERED RHYTMS
AUTOMATIC RHYTHMS:
—> Enhanced normal automaticity —> increased APs from SAN —–> tachycardia
—> Ectopic focus —> APs arise from sites other than the SAN ——-> abnormal conduction pathways (impulse uses these pathways instead of the slower SAN conduction pathway)
TRIGGERED RHYTHMS (abnormal ion channels) ---> delayed afterdepolarisation
—> early afterdepolarisation
ABNORMAL CONDUCTION
—> conduction block (impulse not conducted from atria to ventricles; 1st-3rd degree)
—> re-entry (alternate movement of conduction e.g. along fast and slow pathways) —> circus movement or reflection
What is the abnormality in Wolff-Parkinson-White syndrome?
Accessory pathway (Bundle of Kent)
How can MI lead to arrhythmias?
Area of infarct creates alternate conduction pathway
What is the general purpose of anti-arrhythmic drugs in different arrhythmias?
Overall goals:
- restore normal sinus rhythm and conduction
- prevent more serious and lethal arrhythmias from occurring
ABNORMAL GENERATION:
- decrease phase 4 slope in pacemaker cells —> reduce automaticity —> bradycardia
- raise threshold
ABNORMAL CONDUCTION:
- reduce conduction velocity (e.g. prevent VT following MI)
- increase effective refractory period (e.g. prevent ectopic beats)
Describe the mechanism of action and pharmacokinetics associated with class 1a anti-arrhythmics. Give some examples of drugs in this class. When are they indicated? Give some examples of ADRs associated with these drugs.
e.g. quinidine, procainamide
MECHANISM OF ACTION:
- marked slow conduction in phase 0 (blocks Na+ influx)
- minor effects on AP duration
- increases threshold
- reduces automaticity (reduced phase 4 slope)
note: quinidine also has anti-cholinergic action (increases AV conduction) and is an alpha-receptor antagonist
PHARMACOKINETICS:
- PO or IV
- ECG: lengthen QRS interval, lengthen QT interval
INDICATIONS:
- quinidine used to maintain sinus rhythm in AF and atrial flutter
- quinidine used to prevent recurrent tachycardia and fibrillation
- procainamide used as acute treatment of supraventricular and ventricular arrhythmias
ADRs:
- hypotension
- proarrhythmic e.g. lengthened QT interval —> torsades de pointes
- high dose = dizziness, confusion, insomnia, seizure
- GI disturbances
- SLE-like syndrome
Describe the mechanism of action and pharmacokinetics associated with class 1b anti-arrhythmics. Give some examples of drugs in this class. When are they indicated? Give some examples of ADRs associated with these drugs.
e.g. lidocaine, phenytoin, tocainide, mexiletine
MECHANISM OF ACTION:
- increases Na+ threshold in phase 0 in fast-beating/ischaemic tissue —> reduced conduction
- AP duration slightly decreased
PHARMACOKINETICS:
- lidocaine is IV only, tocainide and mexiletine are PO
- ECG = lengthened QRS interval in fast-beating/ischaemic tissue
INDICATIONS: acute treatment of VT and VF (especially during ischaemia)
ADRs:
- proarrhythmic (but less so than class 1a; less effect on QT interval)
- CNS = dizziness, drowsiness
Describe the mechanism of action and pharmacokinetics associated with class 1c anti-arrhythmics. Give some examples of drugs in this class. When are they indicated? Give some examples of ADRs associated with these drugs.
e.g. flecainide, propafenone
MECHANISM OF ACTION:
- increases Na+ threshold —> reduced automaticity
- substantially reduces phase 0 conduction
- increases refractory period (esp. in rapidly depolarising atrial tissue) —> increases AP duration
PHARMACOKINETICS:
- PO or IV
- ECG = lengthened PR interval, QRS interval, QT interval
INDICATIONS:
- supraventricular arrhythmias (AF and atrial flutter)
- premature ventricular contractions not associated with abnormal structure, ischaemia, or infarct
- Wolff-Parkinson-White syndrome
ADRs:
- proarrhythmic —> sudden death
- increases ventricular response to supraventricular arrhythmias e.g. atrial flutter (slowing of flutter circuits means AVN conducts all flutters, instead of the occasional one)
- CNS = dizziness, drowsiness
- GI disturbances
Describe the mechanism of action and pharmacokinetics associated with class 2 anti-arrhythmics. Give some examples of drugs in this class. When are they indicated? Give some examples of ADRs associated with these drugs.
Beta-blockers e.g. propanolol (B1 and B2 receptors), esmolol (B1 specific), bisoprolol
MECHANISM OF ACTION:
- block K+ efflux and Ca2+ influx in phase 2
- reduces phase 4 depolarisation (catecholamine dependent)
- increases refractory period in AVN —> increases AP duration ——–> slows AV conduction velocity
PHARMACOKINETICS:
- propanolol PO or IV; esmolol IV only, bisoprolol PO
- ECG = lengthened PR interval, reduced heart rate
INDICATIONS:
- treatment of sinus and catecholamine dependent tachyarrhythmias
- converting re-entrant arrhythmias in AVN
- protecting ventricles from high atrial rates (flutter and AF) by slowing AV conduction
ADRs:
- bronchospasm (contraindicated in asthma)
- hypotension —> exacerbates partial AV block and ventricular failure
Describe the mechanism of action and pharmacokinetics associated with class 3 anti-arrhythmics. Give some examples of drugs in this class.
e.g. amiodarone, sotalol, dofetalide, ibutilide
MECHANISM OF ACTION:
- block K+ efflux in phase 2 and 3
- increases refractory period —> increases AP duration
Describe the mechanism of action, pharmacokinetics, indications, and ADRs associated with amiodarone.
MECHANISM OF ACTION:
- reduces phase 0 conduction
- increases threshold
- reduces phase 4 conduction
- reduces AV conduction
PHARMACOKINETICS:
- PO or IV (t1/2 = ~ 3 months; give large divided loading dose IV over 24hrs —> redistributes into body —> maintenance doses)
- ECG = lengthened PR interval, QRS interval, QT interval; reduced heart rate
INDICATIONS: effective for most arrhythmias
ADRs:
- pulmonary fibrosis
- reversible hepatic injury (monitor LFTs)
- increased LDL cholesterol
- hypothyroidism (monitor TFTs)
- photosensitivity (wear sunscreen)
note: may need to reduce doses of digoxin, class 1 anti-arrhythmics, and warfarin (CYP450 interactions)
Describe the mechanism of action, pharmacokinetics, indications, and ADRs associated with sotalol.
MECHANISM OF ACTION:
- increases refractory period —> increases AP duration
- reduces phase 4 conduction
- reduces AV conduction
PHARMACOKINETICS:
- PO
- ECG = lengthened QT interval, reduces heart rate
INDICATIONS: supraventricular and ventricular tachycardias
ADRs:
- proarrhythmic (due to lengthened QT interval)
- fatigue
- insomnia
Describe the mechanism of action and pharmacokinetics associated with class 4 anti-arrhythmics. Give some examples of drugs in this class. When are they indicated? Give some examples of ADRs associated with these drugs
e.g. verapamil, diltiazem
MECHANISM OF ACTION:
- blocks Ca2+ influx
- slows AV conduction
- increases refractory period at AVN
- increases phase 4 slope in SAN —> slows heart rate
PHARMACOKINETICS:
- verapamil PO or IV; diltiazem PO
- ECG = lengthened PR interval, reduced heart rate (can also increase dependency on BP and baroreceptor response)
INDICATIONS:
- controls ventricles during supraventricular tachycardia
- converts supraventricular tachycardia by preventing re-entry around AVN
ADRs:
- asystole when taking beta-blocker in partial AV block
- caution req. when hypotensive, reduced cardiac output, sick sinus syndrome
- GI disturbances e.g. constipation
What is sick sinus syndrome?
Types of arrhythmias caused by SAN malfunction
Give some examples of drugs in class 5 of the Singh-Vaughan Williams classification system.
Adenosine
Digoxin
Atropine
Magnesium
Describe the mechanism of action and pharmacokinetics associated with adenosine. When is it indicated? Give some examples of ADRs associated with adenosine.
MECHANISM OF ACTION:
- binds to alpha-1 receptors and activates K+ currents in SAN and AVN —> reduces AP duration
- hyperpolarisation —> reduces heart rate
- reduces Ca2+ currents —> increases refractory period in AVN
- slows AV conduction
PHARMACOKINETICS:
- rapid IV bolus during episode of arrhythmias (right atrium —> ventricles —> lungs)
INDICATIONS:
- covert re-entrant supraventricular arrhythmias
- hypotension during surgery
Describe the mechanism of action of digoxin. When is it indicated?
MECHANISM OF ACTION:
Inhibits Na+/K+-ATPase —> increase in [Na+]i (initial increase in rate of APs) —> NCE reverses —> increase in [Ca2+]i (+ve ionotropy and increased K+ conductance) —> lengthens phase 4 and 0 (refractory period) —> reduced heart rate
- enhances vagal activity
- –> increases K+ currents
- –> reduces Ca2+ currents
- ———–> increases refractory period
- slows AV conduction (increased in atria)
- slows heart rate (-ve chronotropy)
INDICATIONS: treat AF and atrial flutter
Describe the mechanism of action of atropine. When is it indicated?
MECHANISM OF ACTION:
- selective muscarinic antagonist
- blocks vagal activity
- –> increases AV conduction
- –> increases heart rate
INDICATIONS: vagal bradycardia e.g. vasovagal syncope, whilst waiting to put in a pacemaker
Describe the mechanism of action of magnesium. When is it indicated?
Stabilise receptors in the heart
Treat tachycardia resulting from long QT/torsades de pointes
Contrast the differences between muscle types regarding dependency on calcium to contract.
CARDIAC MUSCLE =
- influx of Ca2+ required to contract
- lots of mitochondrial Ca2+ recycling
SKELETAL MUSCLE =
- nAChR stimulates Ca2+ release from stores in mitochondria
VASCULAR SMOOTH MUSCLE =
- influx of Ca2+ required
- limited mitochondrial Ca2+ recycling
Give examples of ADRs associated with digoxin.
- N&V
- diarrhoea
- arrhythmias
- conduction disturbances
- dizziness
- blurred/yellow vision
- rash
- eosinophilia
- renal impairment (digoxin toxicity increased in hypokalaemia)
What are the treatment options for atrial fibrillation?
Warfarin
- reduce risk of thromboembolism due to stasis of blood in atria
Statins
- reduce CVS risk
Rate-controlling drugs (AVN):
- beta-blockers
- OR Ca2+ channel blockers
- OR digoxin (PO loading dose of 0.75mg-1.5mg over 24hrs in divided doses, then maintenance of 125-250 micrograms)
Rhythm-controlling drugs (SAN):
- class 3 anti-arrhythmics e.g. amiodarone, soletal
- class 1 anti-arrhythmics
Cardioversion:
- young patients with re-entrant loops AND rate-controlling has not been successful/failed to control symptoms
What are the most common causes of atrial fibrillation?
Hypertension Coronary artery disease e.g. MI Hyperthyroidism PE Chest infection Rheumatic fever ---> mitral stenosis Cardiomyopathy Congenital defect Idiopathic Alcohol
