Antiarrhythmic Drugs Flashcards
What is the value of cardiac action potential
What is it produced by
-90mV
K+ channels - High permeability to K+ ions
What are the phases of cardiac myocyte action potential
Phase 0 - VG Na channels, fast depolarising current
Phase 1 - K channels, transient repolarisation
Phase 2 - L type Ca channels, slow depolarising current, systole
Phase 3 - K channels, repolarisation
Phase 4 - resting membrane potential, diastole
What are the main causes of arrhythmias
Abnormal impulse generation
Abnormal impulse conduction
What are the phases of pacemaker action potential
Phase 0: L type Ca channel, slow depolarising current
Phase 3: K channel, repolarisation
Phase 4: HCN channel, Funny current If, automatic gradual depolarisation to threshold
What are the mechanisms of abnormal impulse formation
Automatic rhythms
Triggered rhythms
What are the types of abnormal automatic rhythms
Enhanced automaticity - pacemaker cells of nodes
Ectopic focus - pacemaker cells at sites other than nodes
What are types of triggered rhythms
Delayed after-depolarisations: AP arising immediately after previous AP
Early after-depolarisation: AP arising from plateau phase
What are types of abnormal impulse conduction
Conduction block
Re entry: incomplete unidirectional conduction block causing circus of depolarisation
Accessory pathway: WPW syndrome - pathway between A+V bypassing AVN
What is effective refractory period
Period after AP initiation when Na channels are inactivated and another AP cannot be generated
What are the classes of antiarrhythmic drugs
Class I: Na channel blockers
Class II: Beta blockers
Class III: K channel blockers
Class IV: Ca channel blockers
What is the mechanism of action of class I agents
Inhibit VG Na channels
Slow conduction of phase 0
Slow depolarisation
Prolong ERP
How are Class I agents classified
According to rate of dissociation
Give examples of Class Ia agents
Procainamide
What is the mechanism of action of class Ia
Moderate rate of dissociation
What are ECG changes with Class Ia agents
Broad QRS
Prolonged QT
What are indications of Class Ia agents
Procainamide
Acute IV for SVT + VT
What are side effects of Class Ia agents
Hypotension Proarrhtymic: Torsades de Pointes Dizziness Confusion Seizure Lupus like syndrome
Give examples of class Ib agents
Lidocaine
What is mechanism of action of Class Ib agents
Rapid dissociation rate
Inhibits inactivated Na channels
Inhibits depolarisations too close to previous AP in fast/ischaemic tissue
Minimal effect on conduction in normal tissue
What are indications of Class Ib agents
VT - especially post MI
NOT in atrial arrhythmias
What are contraindications of Lidocaine
HF
Seizures
Nystagmus
Give examples of class Ic agents
Flecainide
What is mechanism of action of class Ic agents
Slow dissociation rate
What are indications of Class Ic agents
AF
Atrial flutter
Premature ventricular contractions
WPW Syndrome
What must Flecainide be prescribed with when treating for Atrial flutter
Beta blockers
Slowed rate of flutter in atria leads to increased conduction of flutter at AVN
Increase ventricular response to SVT
Thus need to block conduction at AVN
What are contraindications of Flecainide
Structural heart disease, IHD
Associated with arrhythmias and sudden deaths
Give examples of Class II agents
Bisoprolol Propranolol Atenolol Esmolol Sotalol
What are PK properties of Class II agents
Bisoprolol: long Acting, once daily regime, oral
Propranolol: short acting, oral or IV
Esmolol: v short acting(seconds)
What is mechanism of action of Class II agents
Inhibit Beta1 adrenoceptor Slow rate of depolarisation of pacemaker potential to threshold Slow conduction velocity at Phase 4 Decrease HR Slow conduction at AVN Negative inotropic effect
What are indications for Class II agents
Sinus tachycardia
Convert AVNRT
Protect ventricles from high atrial rates
What are side effects of Class II agents
Bronchospasm
Hypotension
What are contraindications of Class II agents
Asthma
What is mechanism of action of Class III agents
Block K channels Slow repolarisation (phase 3) Prolong ERP
Give examples of class III agents
Amiodarone
Sotalol
What are PK properties of amiodarone
Oral, IV
T1/2 3 months
What is mechanism of action of amiodarone
Inhibit K channels: prolong ERP
Inhibit Na channels: slow conduction, prolong ERP
Inhibit Beta adrenoceptor: slow AVN conduction
What are indications of amiodarone
Most arrhythmias: atrial, nodal, ventricular
When other drugs failed
What are side effects of amiodarone
Optic neuritis (transient) Photosensitivity Thrombophlebitis at injection site (use central veins) Pneumonitis/pulmonary fibrosis Hepatitis/liver fibrosis Raised LDL Hyperthyroidism (contains iodine)
What monitoring is required for amiodarone
LFT, TFT, ECG, U+E, CXR at baseline
TFT+LFT 6 monthly
What is mechanism of action of sotalol
Inhibit K channels: prolong ERP
Inhibit beta adrenoceptor: slow AVN conduction
What are indications for sotalol
SVT
VT
What are side effects of sotalol
Torsades de Pointes Insomnia Fatigue Bronchspasm Hypotension
Give examples of Class IV agents
Verapamil
Diltiazem
What is mechanism of action of Class IV agents
Inhibit L type Ca channels Slow conduction velocity at Phase 0 Decrease HR Slow conduction at AVN Negative inotropic effect
What are indications for Class IV agents
SVT Prophylaxis Convert SVT (replaced by adenosine due to negative inotropic effect)
What are contraindications of Class IV agents
Use with beta blockers: cumulative negative inotropic effect
AF in pt w WPW: conduction block at AVN causes increased transmission through Bundle thus risk of VF
What is mechanism of action of adenosine
Bind to A1 GPCR in AVN Inhibit adenylyl cyclase Activate K channels Inhibit Ca channels Slow conduction at AVN
What are indications for Adenosine
Convert AVNRT
Distinguish between SVTs
What are PK properties of adenosine
Admin: rapid IV bolus
Short T1/2 (seconds)
How can adenosine be used to distinguish between SVTs
If SVT continues after IV bolus treatment, re-entry loop unlikely to occur at AVN
What is mechanism of action of Vernakalant
Inhibits atrial specific K channels
Prolong ERP in atria
Thus slow atrial conduction
What are indications of Vernakalant
Convert AF
What are side effects of Vernakalant
Taste disturbances
Hypotension
AV block
What is mechanism of action of Ivabradine
Inhibit HCN channels at SAN
Slow HR
Without affecting BP
What are side effects of Ivabradine
Flashing lights
Teratogenicity
What are indications of Ivabradine
Sinus tachycardia
Tachycardia in HF and IHD
What is mechanism of action of Digoxin
Cardiac glycoside
Stimulate vagal activity
Slow HR, Slow AVN conduction
What are indications of Digoxin
AF
Atrial flutter
(Not first line - ineffective)
What is mechanism of action of Atropine
Selective muscarinic antagonist
Block vagal activity
Increase HR, increase AVN conduction
What are indications for Atropine
Sinus bradycardia
