Question 1(p.2)

College Answer

This question again highlighted the importance of candidates utilising a predetermined format
or structure to their questions. Well structured responses were less likely to overlook
important details, which was the predominate weakness for some candidates. A table format
was one useful way of displaying a good answer, for example 

Reference Text: Goodman and Gillman Chp 34

Discussion

• Vaughan Williams classification of antiarrhythmic agents:
  • Class I: fast sodium channel blockers:
    • Class Ia: prolong the action potential (eg. quinidine)
    • Class Ib: shortens the action potential (eg. lignocaine)
    • Class Ic: no effect on the action potential (eg. flecainide)
  • Class II: Beta-blockers (eg. metoprolol)
  • Class III: Potassium channel blockers (eg. sotalol and amiodarone)
  • Class IV: calcium channel blockers (eg. verapamil and diltiazem)
• Antiarrhythmic effects and the agents that exert them:
  • Reduction of pacemaker automaticity: agents which decrease the calcium currents in pacemaker cells, i.e. Class II and Class IV agents
  • Reduction of abnormal automaticity: agents which decrease the membrane resting potential in ventricular myocytes, i.e. mainly Class II agents
  • Reduction of early afterdepolarisations: agents which reduce the action potential and repolarisation duration, i.e. Class II and Ib agents
    • Some agents actually increase early afterdepolarizations by delaying repolarisation
    • These are the same agents that prolong the QT interval (i.e. Class Ia and Class III agents)
  • Reduction of delayed afterdepolarisations:
    • Agents which decrease the availability of intracellular calcium (i.e. Class II and IV agents)
    • Agents which decrease the availability of intracellular sodium (i.e. Class I agents)
  • Reduction of reentry currents:
    • Agents which slow AV nodal conduction (i.e. adenosine, digoxin, Class II and Class IV agents)
    • Agents which slow the velocity of conduction (i.e. Class Ia and Ic agents)
    • Agents which increase the refractory period (i.e Class III, Ia and Ic agents)

Capucci, Alessandro, Daniela Aschieri, and Giovanni Quinto Villani. "Clinical pharmacology of antiarrhythmic drugs." Drugs & aging 13.1 (1998): 51-70.

Carmeliet, Edward, and Kanigula Mubagwa. "Antiarrhythmic drugs and cardiac ion channels: mechanisms of action." Progress in biophysics and molecular biology 70.1 (1998): 1-72.

Vaughan Williams, E. M. "Classification of antiarrhythmic drugs." Symposium on Cardiac Arrhythmias. Sweden, Astra 1970. 1970.

Williams, EM Vaughan. "A classification of antiarrhythmic actions reassessed after a decade of new drugs." The Journal of Clinical Pharmacology 24.4 (1984): 129-147.

Lei, Ming, et al. "Modernized classification of cardiac antiarrhythmic drugs." Circulation 138.17 (2018): 1879-1896.