Procainamide

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Procainamide
Procainamide.svg
Systematic (IUPAC) name
4-amino-N-(2-diethylaminoethyl) benzamide
Clinical data
AHFS/Drugs.commonograph
Pregnancy cat.C (US)
Legal statusPOM (UK)
RoutesIV, IM, oral
Pharmacokinetic data
Bioavailability85% (oral)
Protein binding15 to 20%
MetabolismHepatic (CYP2D6-mediated)
Half-life~2.5 to 4.5 hours
ExcretionRenal
Identifiers
CAS number51-06-9 YesY
ATC codeC01BA02
PubChemCID 4913
DrugBankDB01035
ChemSpider4744 YesY
UNIIL39WTC366D YesY
KEGGD08421 YesY
ChEBICHEBI:8428 YesY
ChEMBLCHEMBL640 YesY
Chemical data
FormulaC13H21N3O 
Mol. mass235.325 g/mol
 YesY (what is this?)  (verify)
 
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Procainamide
Procainamide.svg
Systematic (IUPAC) name
4-amino-N-(2-diethylaminoethyl) benzamide
Clinical data
AHFS/Drugs.commonograph
Pregnancy cat.C (US)
Legal statusPOM (UK)
RoutesIV, IM, oral
Pharmacokinetic data
Bioavailability85% (oral)
Protein binding15 to 20%
MetabolismHepatic (CYP2D6-mediated)
Half-life~2.5 to 4.5 hours
ExcretionRenal
Identifiers
CAS number51-06-9 YesY
ATC codeC01BA02
PubChemCID 4913
DrugBankDB01035
ChemSpider4744 YesY
UNIIL39WTC366D YesY
KEGGD08421 YesY
ChEBICHEBI:8428 YesY
ChEMBLCHEMBL640 YesY
Chemical data
FormulaC13H21N3O 
Mol. mass235.325 g/mol
 YesY (what is this?)  (verify)

Procainamide INN (/prˈknəmd/; trade names Pronestyl, Procan, Procanbid) is a pharmaceutical antiarrhythmic agent used for the medical treatment of cardiac arrhythmias, classified by the Vaughan Williams classification system as class Ia.

History[edit]

Procainamide was approved by the US FDA on June 2, 1950, under the brand name Pronestyl.[1] It was launched by Bristol-Myers Squibb in 1951.[2]

Mechanism[edit]

It is a sodium channel blocker which blocks open sodium channels and prolongs the cardiac action potential (outward potassium (K+) currents may be blocked). This results in slowed conduction, and ultimately the decreased rate of rise of the action potential, which may result in widening of QRS on electrocardiogram.[3]

Medical uses[edit]

This drug is used for both supraventricular and ventricular arrhythmias. For example, it can be used to convert new-onset atrial fibrillation, though it is suboptimal for this purpose.[4] It can also be used to treat Wolff-Parkinson-White syndrome by prolonging the refractory period of the accessory pathway.[5]

Administration[edit]

Procainamide is administered intravenously or orally. When administered intravenously, a loading dose should first be given, though care should be taken not to cause hypotension.

Procainamide's major active metabolite is N-acetylprocainamide (NAPA), which is approximately equipotent with the parent drug as an antiarrhythmic agent.[6] NAPA has an elimination half-life about twice that of procainamide, and it can reach somewhat higher plasma levels during chronic procainamide administration.[7] The loading dose is 100 mg IV bolus given slowly over five minutes. The maximum dose is 17 mg/kg. Use is discontinued when dysrhythmia is suppressed, or if hypotension ensues, the QRS complex widens by 50% or more, or the maximum dose is achieved.

Side effects[edit]

Adverse effects include rash, myalgia, hypersensitivity reactions (fever, agranulocytosis), drug-induced lupus erythematosus[8] (particularly in slow-acetylators), and proarrhythmic effects (e.g., torsades de pointes). Treatment with procainamide can cause antibody production against cellular components, accounting for the systemic lupus erythematosus-like adverse reactions. The Systemic Lupus Erythematosus reaction may present months or years after the initiation of the drug. A positive anti-histone antibody blood test may be useful in determining whether an SLE presentation is drug induced.[9]

Synthesis[edit]

Procainamide synthesis:[10][11]

References[edit]

  1. ^ US Food and Drug Administration. "Drugs at FDA: FDA Approved Drug Products". USA: U.S. Food and Drug Administration (FDA). Retrieved 2012-08-13. 
  2. ^ Hollman A (February 1992). "Procaine and procainamide". Br Heart J 67 (2): 143. doi:10.1136/hrt.67.2.143. PMC 1024743. PMID 18610401. 
  3. ^ Zamponi, G. W.; Sui, X.; Codding, P. W.; French, R. J. (1993). "Dual actions of procainamide on batrachotoxin-activated sodium channels: Open channel block and prevention of inactivation". Biophysical Journal 65 (6): 2324–2334. doi:10.1016/S0006-3495(93)81291-8. PMC 1225974. PMID 8312472.  edit
  4. ^ Fenster, P. E.; Comess, K. A.; Marsh, R.; Katzenberg, C.; Hager, W. D. (1983). "Conversion of atrial fibrillation to sinus rhythm by acute intravenous procainamide infusion". American Heart Journal 106 (3): 501–504. doi:10.1016/0002-8703(83)90692-0. PMID 6881022.  edit
  5. ^ Sellers Jr, T. D.; Campbell, R. W.; Bashore, T. M.; Gallagher, J. J. (1977). "Effects of procainamide and quinidine sulfate in the Wolff-Parkinson-White syndrome". Circulation 55 (1): 15–22. doi:10.1161/01.cir.55.1.15. PMID 830205.  edit
  6. ^ Dutcher, JS; Strong, JM; Lucas, SV; Lee, WK; Atkinson Jr, AJ (1977). "Procainamide and N-acetylprocainamide kinetics investigated simultaneously with stable isotope methodology". Clinical pharmacology and therapeutics 22 (4): 447–57. PMID 902457. 
  7. ^ Drayer, DE; Reidenberg, MM; Sevy, RW (1974). "N-acetylprocainamide: An active metabolite of procainamide". Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine 146 (2): 358–63. doi:10.3181/00379727-146-38104. PMID 4834444. 
  8. ^ Kameda H, Mimori T, Kaburaki J, et al. (November 1998). "Systemic sclerosis complicated by procainamide-induced lupus and antiphospholipid syndrome". Br. J. Rheumatol. 37 (11): 1236–9. doi:10.1093/rheumatology/37.11.1236. PMID 9851277. 
  9. ^ Clinical Medicine for the MRCP Paces. Volume 1: Core Clinical Skills. Mehta and Iqbal. Oxford University Press.2010.
  10. ^ Baltzly, Richard (1942). "New Compounds. Some Diamino Peptides". Journal of the American Chemical Society 64 (9): 2231–2231. doi:10.1021/ja01261a600.  edit
  11. ^ "Syntheses of N1-(2-diethylaminoethyl)-p-aminobenzamide (Procainamide)". YAKUGAKU ZASSHI. 1953. Retrieved 2014-08-11. 

External links[edit]