Procainamide
|
Systematic (IUPAC) name |
4-amino-N-(2-diethylaminoethyl) benzamide |
Clinical data |
AHFS/Drugs.com |
monograph |
Pregnancy cat. |
C (US) |
Legal status |
POM (UK) |
Routes |
IV, IM, oral |
Pharmacokinetic data |
Bioavailability |
85% (oral) |
Protein binding |
15 to 20% |
Metabolism |
Hepatic (CYP2D6-mediated) |
Half-life |
~2.5 to 4.5 hours |
Excretion |
Renal |
Identifiers |
CAS number |
51-06-9 Y |
ATC code |
C01BA02 |
PubChem |
CID 4913 |
DrugBank |
DB01035 |
ChemSpider |
4744 Y |
UNII |
L39WTC366D Y |
KEGG |
D08421 Y |
ChEBI |
CHEBI:8428 Y |
ChEMBL |
CHEMBL640 Y |
Chemical data |
Formula |
C13H21N3O |
Mol. mass |
235.325 g/mol |
SMILES
- O=C(c1ccc(N)cc1)NCCN(CC)CC
|
InChI
-
InChI=1S/C13H21N3O/c1-3-16(4-2)10-9-15-13(17)11-5-7-12(14)8-6-11/h5-8H,3-4,9-10,14H2,1-2H3,(H,15,17) Y
Key:REQCZEXYDRLIBE-UHFFFAOYSA-N Y
|
Y (what is this?) (verify) |
Procainamide INN (//; 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.
Contents
- 1 History
- 2 Mechanism
- 3 Medical uses
- 4 Administration
- 5 Side effects
- 6 Synthesis
- 7 References
- 8 External links
History
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
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
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
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
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
Procainamide synthesis:
[10][11]
References
- ^ US Food and Drug Administration. "Drugs at FDA: FDA Approved Drug Products". USA: U.S. Food and Drug Administration (FDA). Retrieved 2012-08-13.
- ^ Hollman A (February 1992). "Procaine and procainamide". Br Heart J 67 (2): 143. doi:10.1136/hrt.67.2.143. PMC 1024743. PMID 18610401.
- ^ 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
- ^ 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
- ^ 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
- ^ 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.
- ^ 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.
- ^ 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.
- ^ Clinical Medicine for the MRCP Paces. Volume 1: Core Clinical Skills. Mehta and Iqbal. Oxford University Press.2010.
- ^ Baltzly, Richard (1942). "New Compounds. Some Diamino Peptides". Journal of the American Chemical Society 64 (9): 2231–2231. doi:10.1021/ja01261a600. edit
- ^ "Syntheses of N1-(2-diethylaminoethyl)-p-aminobenzamide (Procainamide)". YAKUGAKU ZASSHI. 1953. Retrieved 2014-08-11.
External links
Antiarrhythmic agents (C01B)
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Channel blockers |
class I
(Na+ channel blockers)
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class Ia (Phase 0→ and Phase 3→)
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- Ajmaline
- Disopyramide
- Lorajmine
- Prajmaline
- Procainamide#
- Quinidine#
- Sparteine
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class Ib (Phase 3←)
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- IV (Lidocaine#)
- enteral (Aprindine
- Mexiletine
- Tocainide)
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class Ic (Phase 0→)
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- Encainide‡
- Ethacizine
- Flecainide
- Indecainide‡
- Lorcainide
- Moracizine‡
- Propafenone
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class III
(Phase 3→, K+ channel blockers)
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- Amiodarone
- Bretylium
- Bunaftine
- Dofetilide
- Dronedarone
- E-4031†
- Ibutilide
- Nifekalant
- Sotalol
- Tedisamil
- Vernakalant
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class IV
(Phase 4→, Ca2+ channel blockers)
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Receptor agonists
and antagonists |
class II
(Phase 4→, β blockers)
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- Nadolol
- Pindolol
- Propranolol
- cardioselective (Acebutolol
- Atenolol
- Esmolol
- Metoprolol)
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A1 agonist
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- Adenosine
- Benzodiazepines
- Barbiturates
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M2
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- muscarinic antagonist: Atropine
- Disopyramide
- Quinidine
muscarinic agonist: Digoxin
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α receptors
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- Amiodarone
- Bretylium
- Quinidine
- Verapamil
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Ion transporters |
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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noco/cong/tumr, sysi/epon, injr
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proc, drug (C1A/1B/1C/1D), blte
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