[Ref: SH(H)2:p375]
Tow major physiological mechanism for ectopic arrhythmias
* Reentry
* Enhanced automaticity
Beta-blocker decreases mortality after acute MI
--> Mechanism not known
Further subdivided based on actions on refractory periods
Prolongs AP duration
Patients on class IC drugs experience higher incidence of sudden cardiac death
--> Treatment with amiodarone results in fewer life-threatening cardiac events
Associated with class IA (quinidine, disopyramide) and class III (amiodarone)
Predisposing factors:
* Hypokalaemia
* Hypomagnesaemia
* Poor LV function
* Other drugs that prolong QTc
Precipitated by class IA and class IC
--> Continuous venticular tachycardia re-entry circuit
Often associated with class IC in the setting of structural heart disease
For treatment of acute and chronic SVT
Decreases the slope of phase 4 depolarisation
Low therapeutic index
As effective as quinidine in treatment of ventricular tachyarrhythmia
Not as effective in treatment of atrial tachyarrhythmia
Used principally for suppression of ventricular arrhythmias
Minimal effects on supraventricular tchyarrhythmias
Delays rate of spontaneous phase 4 depolarsation
* By preventing the gradual decrease in K+ ion permeability
Metabolised by liver
* Metabolite may possess antiarrhythmic property
Side effects include:
* Hypotension
* Bradycardia
* Seizures
* CNS depression, apnoea, cardiac arrest
Used from chronic suppression of ventricular tachyarrhythmias
Fluorinated local anaesthetic analog of procainamide
Suppresses ventricular premature beats and ventricular tachycardia
* More effective than quinidine and disopyramide
Also effective in treating atrial tachyarrhythmias
Significant proarrhythmic side effect
Effective for treatment of arrhythmias due to enhanced activities of sympathetic nervous system
* e.g. Perioperative stress, thyrotoxicosis, pheochromocytoma
Mechanism of action
Prevants the cardiac beta-receptor from responding to sympathetic nervous system stimulation and the circulating catecholamines
--> Spontaneous phase 4 depolarisation is decreased and SA node discharge decreased
Propanolol (PO) is extensively metabolised in liver
Variation in liver metabolism accounts for variation in plasma concentration
Readily crosses the blood-brain barrier
Principle metabolite is 4-hydroxypropranolol
--> Weak beta-adrenergic antagonist activity
Structurally similar to thyroxine
Has anti-adrenergic effect
* Non-competitive blockade of alpha and beta-receptors
* Minor negative inotropic effect
Effective against refractory supraventricular and ventricular tachyarrhythmias
5mg/kg IV over 2-5 minutes
--> Antiarrhythmic effect lasting up to 4 hours
Effect may last 60 days after discontinuation
Elimination half-time = 29 days
Large Vd
Principle metabolite is desethylamiodarone
* Pharmacologically active
* Longer elimination half-time than amiodarone
Pulmonary toxicity
--> Pulmonary alveolitis (5-15% of patients)
* Gradual onset of dyspnoea, cough, and pulmonary infiltrates on XRay
* Acute onset (???)
Cardiotoxicity
* Prolonged QTc interval
* AV heart block
Inhibition of P-450 enzymes
--> Could lead to increased plasma concentration of digoxin and warfarin
Endocrine effects
* Hypothyroidism
* Hyperthyroidisim (as late of 5 months after discontinuation)
Others
* Corneal micro deposits
* Photosensitivity
* Peripheral neuropathy
* Increase in plasma transaminase
Used for treating sustained ventricular tachycardia or ventricular fibrillation
At low dose
--> Non-selective beta-blocker
At high dose
--> Prolongs cardiac action potential in atria, ventricles, and accessory pathway
Proarrhymic potential
--> Used only in life-threatening cases
Renally excreted
Onset of action faster than amiodarone
No longer recommended for treatment of VF during CPR
Amiodarone is more effective and has less side effects
Verapamil and diltiazem have the greatest efficacy for treatment of cardiac arrhythmias
Inhibition of slow calcium channel on smooth muscles and cardiac cells
--> Decreased rate of spontaneous phase 4 depolarisation
Stablise atrial electrical activity
Treatment of atrial tachyarrhythmias
Slows conduction through AV node
An effective alternative to calcium channel blockers (e.g. verapami) in treatment of paroxysmal SVT
* Also depresses accessory pathways
--> Can be used in WPW syndrome (unlike verapmil)
NOT effective in treating AF, atrial flutter, and VT
Stimulates cardiac adenosine1 receptors
--> Increase potassium flow
--> Hyperpolarise cardiac cell membrane
--> Shortens AP
Short duration of action
* Elimination half-time = 10 seconds
* Due to carrier-mediated cellular uptake
Metabolised to inosine by adenosine deaminase