Prajmaline Explained

Prajmaline (Neo-gilurythmal)[1] is a class Ia antiarrhythmic agent[2] which has been available since the 1970s.[3] Class Ia drugs increase the time one action potential lasts in the heart.[4] Prajmaline is a semi-synthetic propyl derivative of ajmaline, with a higher bioavailability than its predecessor.[5] It acts to stop arrhythmias of the heart through a frequency-dependent block of cardiac sodium channels.[2]

Mechanism

Prajmaline causes a resting block in the heart.[6] A resting block is the depression of a person's Vmax after a resting period. This effect is seen more in the atrium than the ventricle.[6] The effects of some Class I antiarrhythmics are only seen in a patient who has a normal heart rate (~1 Hz).[7] This is due to the effect of a phenomenon called reverse use dependence.[7] The higher the heart rate, the less effect Prajmaline will have.

Uses

The drug Prajmaline has been used to treat a number of cardiac disorders. These include: coronary artery disease,[8] [9] angina,[8] [9] paroxysmal tachycardia and Wolff–Parkinson–White syndrome.[1] Prajmaline has been indicated in the treatment of certain disorders where other antiarrhythmic drugs were not effective.[1]

Administration

Prajmaline can be administered orally,[9] parenterally[8] or intravenously.[8] Three days after the last dose, a limited effect has been observed. Therefore, it has been suggested that treatment of arrhythmias with Prajmaline must be continuous to see acceptable results.[1]

Pharmacokinetics

The main metabolites of Prajmaline are: 21-carboxyprajmaline and hydroxyprajmaline. Twenty percent of the drug is excreted in the urine unchanged.

Daily therapeutic dose is 40–80 mg.Distribution half-life is 10 minutes.Plasma protein binding is 60%.Oral bioavailability is 80%.Elimination half-life is 6 hours.Volume of distribution is 4-5 L/kg.[3]

Side Effects

There are no significant adverse side-effects of Prajmaline when taken alone and with a proper dosage.[1] [8] [9] Patients who are taking other treatments for their symptoms (e.g. beta blockers and nifedipine) have developed minor transient conduction defects when given Prajmaline.[8]

Overdose

An overdose of Prajmaline is possible. The range of symptoms seen during a Prajmaline overdose include: no symptoms, nausea/vomiting, bradycardia, tachycardia, hypotension, and death.[3]

Other Potential Uses

Due to Prajmaline's sodium channel-blocking properties, it has been shown to protect rat white matter from anoxia (82 +/- 15%).[10] [11] The concentration used causes little suppression of the preanoxic response.[10] [11]

Notes and References

  1. Janicki K, Orski J, Kakol J . [Antiarrhythmic effects of prajmaline (Neo-Gilurythmal) in stable angina pectoris in light of Holter electrocardiographic monitoring] . Polish . Przegląd Lekarski . 52 . 10 . 485–491 . 1995 . 8834838.
  2. Weirich J, Antoni H . Differential analysis of the frequency-dependent effects of class 1 antiarrhythmic drugs according to periodical ligand binding: implications for antiarrhythmic and proarrhythmic efficacy . Journal of Cardiovascular Pharmacology . 15 . 6 . 998–1009 . June 1990 . 1694924 . 10.1097/00005344-199006000-00019. free .
  3. Köppel C, Oberdisse U, Heinemeyer G . Clinical course and outcome in class IC antiarrhythmic overdose . Clinical Toxicology . 28 . 4 . 433–44 . 1990 . 2176700 . 10.3109/15563659009038586.
  4. Milne JR, Hellestrand KJ, Bexton RS, Burnett PJ, Debbas NM, Camm AJ . Class 1 antiarrhythmic drugs--characteristic electrocardiographic differences when assessed by atrial and ventricular pacing . European Heart Journal . 5 . 2 . 99–107 . February 1984 . 6723689 . 10.1093/oxfordjournals.eurheartj.a061633.
  5. Hinse C, Stöckigt J . The structure of the ring-opened N beta-propyl-ajmaline (Neo-Gilurytmal) at physiological pH is obviously responsible for its better absorption and bioavailability when compared with ajmaline (Gilurytmal) . Die Pharmazie . 55 . 7 . 531–2 . July 2000 . 10944783.
  6. Langenfeld H, Weirich J, Köhler C, Kochsiek K . Comparative analysis of the action of class I antiarrhythmic drugs (lidocaine, quinidine, and prajmaline) in rabbit atrial and ventricular myocardium . Journal of Cardiovascular Pharmacology . 15 . 2 . 338–45 . February 1990 . 1689432 . 10.1097/00005344-199002000-00023. free .
  7. Langenfeld H, Köhler C, Weirich J, Kirstein M, Kochsiek K . Reverse use dependence of antiarrhythmic class Ia, Ib, and Ic: effects of drugs on the action potential duration? . Pacing and Clinical Electrophysiology . 15 . 11 Pt 2 . 2097–102 . November 1992 . 1279606 . 10.1111/j.1540-8159.1992.tb03028.x. 25864256 .
  8. Sowton E, Sullivan ID, Crick JC . Acute haemodynamic effects of ajmaline and prajmaline in patients with coronary heart disease . European Journal of Clinical Pharmacology . 26 . 2 . 147–50 . 1984 . 6723753 . 10.1007/bf00630278. 20512025 .
  9. Handler CE, Kritikos A, Sullivan ID, Charalambakis A, Sowton E . Effects of oral prajmaline bitartrate on exercise test responses in patients with coronary artery disease . European Journal of Clinical Pharmacology . 28 . 4 . 371–4 . 1985 . 4029242 . 10.1007/bf00544352. 521671 .
  10. Stys PK . Protective effects of antiarrhythmic agents against anoxic injury in CNS white matter . Journal of Cerebral Blood Flow and Metabolism . 15 . 3 . 425–32 . May 1995 . 7714000 . 10.1038/jcbfm.1995.53. free .
  11. Malek SA, Adorante JS, Stys PK . Differential effects of Na-K-ATPase pump inhibition, chemical anoxia, and glycolytic blockade on membrane potential of rat optic nerve . Brain Research . 1037 . 1–2 . 171–9 . March 2005 . 15777766 . 10.1016/j.brainres.2005.01.003. 29226181 .

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