Comparative pharmacology of antiarrhythmic agents
Question 12 from the first paper of 2006 and Question 9 from the second paper of 2002 discussed and compared the utility of lignocaine, magnesium and amiodarone in the management VT. This is a very specific subject. A very specific answer is offered, consisting only of what the college asked for. Antiarrhythmic pharmacology is a deep rabbit hole, and one could become lost there - just look what happened when this author tried to explain it to himself for the Part One exam. An ideal resource to read quickly before the exam would have to be the 1998 review article by Kovey.
Lignocaine, magnesium and amiodarone for VT
|
Features |
Lignocaine |
Magnesium |
Amiodarone |
|
Class |
Class 1b antiarrhytmic |
Divalent cation |
Class 3 antiarrhytmic (though it has effects of all 4 classes) |
|
Administration |
IV Then, 4 mg/kg for the first hour, then tapering infusion to 1mg/kg for 24 hrs |
IV 10-20mmol/L given over 15-60 minutes, or 5 mmol boluses followed by 20mmol infusion |
IV 150-300mg, followed by an infusion of 900mg over 24 hrs |
|
Pharmaco-kinetics |
Rapid hepatic metabolism into inactive metabolites. |
Rapid distribution; some proportion becomes intracellular; the rest is renally excreted. |
Rapid distribution, with a vas volume of dsitribution; becomes bound to tissue proteins. |
|
Mechanism |
Inhibits voltage-gated sodium channels, decreasing the duration of action potentials and decreasing the duration of repolarisation |
Mechanism uncertain; appears to act as an antagonist to the entry of calcium into depolarising cells. |
Beta-blockade |
|
Adverse effects |
Neurological disturbances eg. paraesthesia, seizures |
Muscle weakness, decreased reflexes, hypotension |
Prolongation of QT interval, risk of Torsades. |
Classification of antiarrhythmic agents
Vaughan-Williams classification (1970)
Class 1 antiarrhythmic drugs all depress phase zero of the action potential by decreasing membrane conductance of Na+. These are split into 3 subclasses, according to what they do to the action potential duration. The classes are 1a, 1b and 1c.
- Class 1a prolong the action potential duration. (quinidine, procainamide and disopyramide)
- Class 1b shorten the action potential duration. (lignocaine and mexelitine)
- Class 1c keep the action potential duration virtually the same (flecainide and propafenone)
Class 2 antiarrhythmic drugs are beta blockers (eg. propanolol, metoprolol)
Class 3 antiarrhythmic drugs are potassium channel blockers (eg. amiodarone and sotalol)
Class 4 antiarrhythmic drugs are calcium channel blockers (eg. verapimil and diltiazem)
Obviously this classification has problems.
- Where do digoxin and adenosine fit? What about sodium lactate? The classification omits them.
- The system does nothing to suggest which class is useful for which role
- Many of the drugs have multiple effects and could just as easily be classified in another group
Pharmacological properties of antiarrhythmic agents
From the abovelinked 1998 review article by Kovey, the following table was shamelessly stolen, flaunting copyright for all the right reasons (FOAMED).
It says "adapted with permission from Siddoway". That book is no longer in print; it appears as a reference in the list below.
References
Nawrath, H., et al. "Class I Antiarrhythmic Drug Effects: What Is the Basis for Subgroups Ia, Ib and Ic." Cardiac Arrhythmias: The Management of Atrial Fibrillation (2013): 39.
Vaughan-Williams, E. M. "Classification of antiarrhythmic drugs." Cardiac arrhythmias 449 (1970).
Rosen, Michael R. "The sicilian gambit-a new approach to the classification of antiarrhythmic drugs based on their actions on arrhythmogenic mechanisms." Circulation 84.4 (1991): 1831-1851.
Kowey, Peter R. "Pharmacological effects of antiarrhythmic drugs: Review and update." Archives of internal medicine 158.4 (1998): 325-332.
Siddoway, L. A., P. J. Podrid, and P. R. Kowey. "Pharmacologic principles of antiarrythmic drugs." (1995): 355-368.