Disopyramide
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| Systematic (IUPAC) name |
| (RS)-4-(diisopropylamino)-2-phenyl-2-(pyridin-2-yl)butanamide |
| Clinical data |
| Trade names |
Norpace |
| AHFS/Drugs.com |
monograph |
| MedlinePlus |
a682408 |
| Pregnancy cat. |
B2 (AU) C (US) |
| Legal status |
POM (UK) ℞-only (US) |
| Routes |
Oral, intravenous |
| Pharmacokinetic data |
| Bioavailability |
High |
| Protein binding |
50% to 65%
(concentration-dependent) |
| Metabolism |
Hepatic (CYP3A4-mediated) |
| Half-life |
6.7 hours (range 4 to 10 hours) |
| Excretion |
Renal (80%) |
| Identifiers |
| CAS number |
3737-09-5 Y |
| ATC code |
C01BA03 |
| PubChem |
CID 3114 |
| DrugBank |
DB00280 |
| ChemSpider |
3002 Y |
| UNII |
GFO928U8MQ Y |
| KEGG |
D00303 Y |
| ChEBI |
CHEBI:4657 Y |
| ChEMBL |
CHEMBL517 Y |
| Chemical data |
| Formula |
C21H29N3O |
| Mol. mass |
339.475 g/mol |
SMILES
- O=C(N)C(c1ncccc1)(c2ccccc2)CCN(C(C)C)C(C)C
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InChI
-
InChI=1S/C21H29N3O/c1-16(2)24(17(3)4)15-13-21(20(22)25,18-10-6-5-7-11-18)19-12-8-9-14-23-19/h5-12,14,16-17H,13,15H2,1-4H3,(H2,22,25) Y
Key:UVTNFZQICZKOEM-UHFFFAOYSA-N Y
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Y (what is this?) (verify)
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Disopyramide (INN, trade names Norpace and Rythmodan) is an antiarrhythmic medication used in the treatment of Ventricular Tachycardia.[1] It is a sodium channel blocker and therefor classified as a Class 1a anti-arrhythmic agent.[2]’[3] Disopyramide has a negative inotropic effect on the ventricular myocardium, significantly decreasing the contractility.[4]'[5] Disopyramide also has an anticholinergic effect on the heart which accounts for many adverse side effects. Disopyramide is available in both oral and intravenous forms, and has a low degree of toxicity.[6]
Mechanism of Action: Disopyramide’s Class 1a activity is similar to that of Quinidine in that it targets sodium channels to lengthen the action potential.[7]’[8] Disopyramide depresses the increase in sodium permeability of the cardiac Myocyte during Phase 0 of the cardiac action potential, in turn decreasing the inward sodium current. This results in an increased threshold for excitation and a decreased upstroke velocity.[9] Disopyramide prolongs the PR interval by lengthening both the QRS and P wave duration.[10] This effect is particularly well suited in the treatment of ventricular tachycardia as it slows the action potential propagation through the atria to the ventricles. Disopyramide does not act as a blocking agent for beta or alpha adrenergic receptors, but does have a significant negative inotropic effect on the ventricular myocardium.[11] As a result, the use of disopyramide may reduce contractile force up to 42% at low doses and up to 100% in higher doses leading to heart failure.[12] Levites proposed a possible secondary mode of action for Disopyramide, against reentrant arrhythmias after an ischemic insult. Disopyramide decreases the inhomogeneity between infarcted and normal myocardium refractory periods; in addition to lengthening the refractory period.[13]This decreases the chance of re-entry depolarization, because signals are more likely to encounter tissue in a refractory state which can’t be excited.[14] This provides a possible treatment for atrial and ventricular fibrillation, as it restores pacemaker control of the tissue to the SA and AV nodes.[15]
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Contents
- 1 Cardiac adverse effects
- 2 Extracardiac effects
- 3 Chemistry
- 4 References
- 5 External links
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Cardiac adverse effects
- Acute heart failure[16][dead link]
- Severe hypotension
- Dry mouth
- Constipation
- Urinary retention
- Blurred vision
- Glaucoma
- Rash
- Agranulocytosis
Additionally, disopyramide may enhance the hypoglycaemic effect of gliclazide, insulin, and metformin.[citation needed]
Chemistry
Disopyramide can be synthesized from benzyl cyanide and 2-bromopyridine:[17]
References
- ^ Guyton, Arthur C., Hall, John E. (2006). Textbook of Medical Physiology (11th ed.). Philadelphia: Elsevier Saunders
- ^ Rizos, I. I., et al. "Effects of Intravenous Disopyramide and Quinidine on Normal Myocardium and on the Characteristics of Arrhythmias: Intraindividual Comparison in Patients with Sustained Ventricular Tachycardia." European heart journal 8.2 (1987): 154-63. Biological Sciences. Web. 10 Feb. 2012
- ^ Kim, S. Y. SY, and N. L. NL Benowitz. "Poisoning due to Class IA Antiarrhythmic Drugs. Quinidine, Procainamide and Disopyramide." Drug safety : an international journal of medical toxicology and drug experience 5.6 (1990): 393-420. Biological Sciences; Environmental Science and Pollution Management. Web. 12 Feb. 2012.
- ^ Levites, R. R., and G. J. GJ Anderson. "Electrophysiological Effects of Disopyramide Phosphate during Experimental Myocardial Ischemia." American Heart Journal 98.3 (1979): 339-44. Biological Sciences. Web. 15 Feb. 2012.
- ^ Mathur, P. P. PP. "Cardiovascular Effects of a Newer Antiarrhythmic Agent, Disopyramide Phosphate." American Heart Journal 84.6 (1972): 764-70. Biological Sciences; Environmental Science and Pollution Management. Web. 15 Feb. 2012
- ^ Mathur, P. P. PP. "Cardiovascular Effects of a Newer Antiarrhythmic Agent, Disopyramide Phosphate." American Heart Journal 84.6 (1972): 764-70. Biological Sciences; Environmental Science and Pollution Management. Web. 15 Feb. 2012
- ^ Mathur, P. P. PP. "Cardiovascular Effects of a Newer Antiarrhythmic Agent, Disopyramide Phosphate." American Heart Journal 84.6 (1972): 764-70. Biological Sciences; Environmental Science and Pollution Management. Web. 15 Feb. 2012.
- ^ Kim, S. Y. SY, and N. L. NL Benowitz. "Poisoning due to Class IA Antiarrhythmic Drugs. Quinidine, Procainamide and Disopyramide." Drug safety : an international journal of medical toxicology and drug experience 5.6 (1990): 393-420. Biological Sciences; Environmental Science and Pollution Management. Web. 12 Feb. 2012.
- ^ Kim, S. Y. SY, and N. L. NL Benowitz. "Poisoning due to Class IA Antiarrhythmic Drugs. Quinidine, Procainamide and Disopyramide." Drug safety : an international journal of medical toxicology and drug experience 5.6 (1990): 393-420. Biological Sciences; Environmental Science and Pollution Management. Web. 12 Feb. 2012.
- ^ Mathur, P. P. PP. "Cardiovascular Effects of a Newer Antiarrhythmic Agent, Disopyramide Phosphate." American Heart Journal 84.6 (1972): 764-70. Biological Sciences; Environmental Science and Pollution Management. Web. 15 Feb. 2012.
- ^ Hulting J, Rosenhamer G: Hemodynamic and electrocardiographic effects of disopyramide in patients with ventricular arrhythmia. Acta Med Scand 199:41-51, 1976.
- ^ Mathur, P. P. PP. "Cardiovascular Effects of a Newer Antiarrhythmic Agent, Disopyramide Phosphate." American Heart Journal 84.6 (1972): 764-70. Biological Sciences; Environmental Science and Pollution Management. Web. 15 Feb. 2012.
- ^ Levites, R. R., and G. J. GJ Anderson. "Electrophysiological Effects of Disopyramide Phosphate during Experimental Myocardial Ischemia." American Heart Journal 98.3 (1979): 339-44. Biological Sciences. Web. 15 Feb. 2012.
- ^ Guyton, Arthur C., Hall, John E. (2006). Textbook of Medical Physiology (11th ed.). Philadelphia: Elsevier Saunders.
- ^ Katzung, Bertram G., Masters, Susan B., Trevor, Anthony J. (2009). Basic and Clinical Pharmacology (11th ed.). New York: McGraw Hill
- ^ [1]
- ^ U.S. Patent 3,225,054
External links
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Antiarrhythmic agents (C01B)
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| Channel blockers |
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class I
(Na+ channel blockers)
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class Ia (Phase 0→ and Phase 3→)
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- Procainamide #
- Quinidine #
- Ajmaline
- Disopyramide
- Prajmaline
- Lorajmine
- Sparteine
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class Ib (Phase 3←)
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- IV (Lidocaine #)
- enteral (Mexiletine
- Tocainide
- Aprindine)
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class Ic (Phase 0→)
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- Encainide‡
- Flecainide
- Lorcainide
- Moracizine‡
- Propafenone
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class III
(Phase 3→, K+ channel blockers)
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- Amiodarone
- Dronedarone
- Bretylium
- Bunaftine
- Dofetilide
- Ibutilide
- Nifekalant
- Sotalol
- Tedisamil
- Vernakalant
- E-4031
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class IV
(Phase 4→, Ca2+ channel blockers)
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Receptor agonists
and antagonists |
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class II
(Phase 4→, β blockers)
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- Propranolol
- Nadolol
- Pindolol
- cardioselective (Atenolol
- Metoprolol
- Acebutolol
- Esmolol)
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A1 agonist
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M2
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- muscarinic antagonist: Atropine
- Quinidine
- Disopyramide
muscarinic agonist: Digoxin
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α receptors
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- Quinidine
- Verapamil
- Amiodarone
- Bretylium
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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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References:
- ^ Guyton, Arthur C., Hall, John E. (2006). Textbook of Medical Physiology (11th ed.). Philadelphia: Elsevier Saunders
- ^ Rizos, I. I., et al. "Effects of Intravenous Disopyramide and Quinidine on Normal Myocardium and on the Characteristics of Arrhythmias: Intraindividual Comparison in Patients with Sustained Ventricular Tachycardia." European heart journal 8.2 (1987): 154-63. Biological Sciences. Web. 10 Feb. 2012
- ^ Kim, S. Y. SY, and N. L. NL Benowitz. "Poisoning due to Class IA Antiarrhythmic Drugs. Quinidine, Procainamide and Disopyramide." Drug safety : an international journal of medical toxicology and drug experience 5.6 (1990): 393-420. Biological Sciences; Environmental Science and Pollution Management. Web. 12 Feb. 2012.
- ^ Levites, R. R., and G. J. GJ Anderson. "Electrophysiological Effects of Disopyramide Phosphate during Experimental Myocardial Ischemia." American Heart Journal 98.3 (1979): 339-44. Biological Sciences. Web. 15 Feb. 2012.
- ^ Mathur, P. P. PP. "Cardiovascular Effects of a Newer Antiarrhythmic Agent, Disopyramide Phosphate." American Heart Journal 84.6 (1972): 764-70. Biological Sciences; Environmental Science and Pollution Management. Web. 15 Feb. 2012
- ^ Mathur, P. P. PP. "Cardiovascular Effects of a Newer Antiarrhythmic Agent, Disopyramide Phosphate." American Heart Journal 84.6 (1972): 764-70. Biological Sciences; Environmental Science and Pollution Management. Web. 15 Feb. 2012
- ^ Mathur, P. P. PP. "Cardiovascular Effects of a Newer Antiarrhythmic Agent, Disopyramide Phosphate." American Heart Journal 84.6 (1972): 764-70. Biological Sciences; Environmental Science and Pollution Management. Web. 15 Feb. 2012.
- ^ Kim, S. Y. SY, and N. L. NL Benowitz. "Poisoning due to Class IA Antiarrhythmic Drugs. Quinidine, Procainamide and Disopyramide." Drug safety : an international journal of medical toxicology and drug experience 5.6 (1990): 393-420. Biological Sciences; Environmental Science and Pollution Management. Web. 12 Feb. 2012.
- ^ Kim, S. Y. SY, and N. L. NL Benowitz. "Poisoning due to Class IA Antiarrhythmic Drugs. Quinidine, Procainamide and Disopyramide." Drug safety : an international journal of medical toxicology and drug experience 5.6 (1990): 393-420. Biological Sciences; Environmental Science and Pollution Management. Web. 12 Feb. 2012.
- ^ Mathur, P. P. PP. "Cardiovascular Effects of a Newer Antiarrhythmic Agent, Disopyramide Phosphate." American Heart Journal 84.6 (1972): 764-70. Biological Sciences; Environmental Science and Pollution Management. Web. 15 Feb. 2012.
- ^ Hulting J, Rosenhamer G: Hemodynamic and electrocardiographic effects of disopyramide in patients with ventricular arrhythmia. Acta Med Scand 199:41-51, 1976.
- ^ Mathur, P. P. PP. "Cardiovascular Effects of a Newer Antiarrhythmic Agent, Disopyramide Phosphate." American Heart Journal 84.6 (1972): 764-70. Biological Sciences; Environmental Science and Pollution Management. Web. 15 Feb. 2012.
- ^ Levites, R. R., and G. J. GJ Anderson. "Electrophysiological Effects of Disopyramide Phosphate during Experimental Myocardial Ischemia." American Heart Journal 98.3 (1979): 339-44. Biological Sciences. Web. 15 Feb. 2012.
- ^ Guyton, Arthur C., Hall, John E. (2006). Textbook of Medical Physiology (11th ed.). Philadelphia: Elsevier Saunders.
- ^ Katzung, Bertram G., Masters, Susan B., Trevor, Anthony J. (2009). Basic and Clinical Pharmacology (11th ed.). New York: McGraw Hill
- ^ [1]
- ^ U.S. Patent 3,225,054
1. Guyton, Arthur C., Hall, John E. (2006). Textbook of Medical Physiology (11th ed.). Philadelphia: Elsevier Saunders. 2. Rizos, I. I., et al. "Effects of Intravenous Disopyramide and Quinidine on Normal Myocardium and on the Characteristics of Arrhythmias: Intraindividual Comparison in Patients with Sustained Ventricular Tachycardia." European heart journal 8.2 (1987): 154-63. Biological Sciences. Web. 10 Feb. 2012. 3. Katzung, Bertram G., Masters, Susan B., Trevor, Anthony J. (2009). Basic and Clinical Pharmacology (11th ed.). New York: McGraw Hill 4. Levites, R. R., and G. J. GJ Anderson. "Electrophysiological Effects of Disopyramide Phosphate during Experimental Myocardial Ischemia." American Heart Journal 98.3 (1979): 339-44. Biological Sciences. Web. 15 Feb. 2012. 5. Hulting J, Rosenhamer G: Hemodynamic and electrocardiographic effects of disopyramide in patients with ventricular arrhythmia. Acta Med Scand 199:41-51, 1976. 6. Mathur, P. P. PP. "Cardiovascular Effects of a Newer Antiarrhythmic Agent, Disopyramide Phosphate." American Heart Journal 84.6 (1972): 764-70. Biological Sciences; Environmental Science and Pollution Management. Web. 15 Feb. 2012. 7. Kim, S. Y. SY, and N. L. NL Benowitz. "Poisoning due to Class IA Antiarrhythmic Drugs. Quinidine, Procainamide and Disopyramide." Drug safety : an international journal of medical toxicology and drug experience 5.6 (1990): 393-420. Biological Sciences; Environmental Science and Pollution Management. Web. 12 Feb. 2012.