hantiarrhythmics
History of use of anti-arrhythmic agents
History of anti-arrhythmic drugs:
- Noted that pts on cinchona for malaria treatment were occasionally cured of AF - the 1st recorded use of this was in 1749 by Jean-Baptiste de Sénac.
- Wenckeback (1914) reported on effects of quinine alkaloids in certain arrhythmias which impressed Frey (1918) who studied use of cinchonine, quinine & quinidine in AF & found quinidine the most effective;
- Mautz (1936) demonstrated application of procaine incr. ventricular muscle threshold to electrical stimulation & this was later demonstrated to be similar action to quinidine;
- procainamide discovered in 1951 after a search of congeners of procaine which was rapidly hydrolysed & had CNS effects;
- Procainamide however tended to produce a SLE-like syndrome thus prompted search for other drugs with quinidine-like activity:
- Disopyramide introduced in 1978 but had significant antimuscarinic & -ve inotropy;
- Moricizine developed in USSR in 1960's is a recent candidate;
- lignocaine used as a LA was introduced as antiarrhythmic in 1962 for emergency Rx of VT/VF after cardiac Sx or AMI;
- 2 orally effective relatives of lignocaine became available:
- tocainide in 1984;
- mexiletine in 1986;
- phenytoin has been used since 1938 for seizures, & was found to be effective in VT in expt. AMI in dogs in 1950, & has since been used in man esp. for VT/VF assoc. with digoxin & tricyclic toxicity;
- flecainide was introduced in 1986 (US), & later encainide was introduced;
- Bretylium was approved for resist. VT/VF in 1978 (US);
- amiodarone was approved for resistant VT or recurrent VF in 1986 (US);
- sotalol introduced for Mx of AF.
- CAST study reported in 1991, 2-fold increased mortality in pts with PVCs post-AMI receiving flecainide & encainide than with placebo!
hantiarrhythmics.txt · Last modified: 2008/08/28 07:45 by 127.0.0.1