 |
|
|
Dofetilide
|
|
| Systematic (IUPAC) name | |
| N-[4-[2-[2-[4-(methanesulfonamido)phenoxy]ethyl-methyl-amino] ethyl]phenyl] methanesulfonamide | |
| Identifiers | |
| CAS number | |
| ATC code | C01 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C19H27N3O5S2 |
| Mol. mass | 441. IUPAC Nomenclature is a system of naming Chemical compounds and of describing the science of Chemistry in general CAS registry numbers are unique numerical identifiers for Chemical compounds Polymers biological sequences mixtures and Alloys They are also referred to The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs It is controlled by the WHO Collaborating Centre for Drug A section of the Anatomical Therapeutic Chemical Classification System. PubChem is a Database of chemical Molecules The system is maintained by the National Center for Biotechnology Information (NCBI a component The DrugBank database available at the University of Alberta is a unique Bioinformatics and Cheminformatics resource that combines detailed drug (i A chemical formula is a way of expressing information about the Atoms that constitute a particular Chemical compound, and how the relationship between those atoms changes Carbon (kɑɹbən is a Chemical element with the symbol C and its Atomic number is 6 Hydrogen (ˈhaɪdrədʒən is the Chemical element with Atomic number 1 Nitrogen (ˈnaɪtɹəʤɪn is a Chemical element that has the symbol N and Atomic number 7 and Atomic weight 14 Oxygen (from the Greek roots ὀξύς (oxys (acid literally "sharp" from the taste of acids and -γενής (-genēs (producer literally begetteris the Sulfur or sulphur (ˈsʌlfɚ see spelling below) is the Chemical element that has the Atomic number 16 The molecular mass (abbreviated m of a substance, more commonly referred to as molecular weight and abbreviated as MW, is the Mass of one 567 g/mol |
| Pharmacokinetic data | |
| Bioavailability | 96% (oral) |
| Protein binding | 60% -70% |
| Metabolism | ? |
| Half life | 10 hours |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. |
? |
| Legal status | |
| Routes | ? |
Dofetilide is a class III antiarrhythmic agent that is approved by the Food and Drug Administration (FDA) for the maintenance of sinus rhythm in individuals prone to the formation of atrial fibrillation and flutter, and for the chemical cardioversion to sinus rhythm from atrial fibrillation and flutter. In Pharmacology, bioavailability is used to describe the fraction of an administered Dose of unchanged drug that reaches the Systemic circulation, one of A drug's efficiency may be affected by the degree to which it binds to the proteins within Blood plasma. Drug metabolism is the Metabolism of drugs, their Biochemical modification or degradation usually through specialized enzymatic systems The biological half-life of a substance is the time it takes for a substance (drug radioactive nuclide or other to lose half of its pharmacologic physiologic or radiologic activity Excretion is the process of eliminating waste products of Metabolism and other non-useful materials The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical if it is used as directed by the mother during The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction In Pharmacology and Toxicology, a route Antiarrhythmic agents are a group of Pharmaceuticals that are used to suppress fast rhythms of the Heart ( Cardiac arrhythmias) such as Atrial fibrillation Sinus rhythm is a term used in medicine to describe the normal beating of the heart as measured by an Electrocardiogram ( ECG) Atrial fibrillation ( AF or afib) is a Cardiac arrhythmia (abnormal heart rhythm that involves the two upper chambers ( atria) of the Heart Atrial flutter is an abnormal heart rhythm that occurs in the atria of the Heart. Synchronized electrical cardioversion is the process by which an abnormally fast Heart rate or Cardiac arrhythmia is terminated by the delivery of a therapeutic dose Atrial fibrillation ( AF or afib) is a Cardiac arrhythmia (abnormal heart rhythm that involves the two upper chambers ( atria) of the Heart Atrial flutter is an abnormal heart rhythm that occurs in the atria of the Heart.
The chemical name for dofetilide is N-[4-(2-{2-[4-(methanesulphonamido) phenoxyl]-N-methylethylamino}ethyl)phenyl]- methanesulphonamide. It is marketed under the trade name Tikosyn by Pfizer, and is available in the United States in capsules containing 125, 250, and 500 µg of dofetilide. Pfizer Incorporated ( is a major Pharmaceutical company, which ranks number one in the world in sales The United States of America —commonly referred to as the In the Metric system, a microgram is 1/1000000 of a Gram (1 × 10-6 or 1/1000 of a milligram is one of the smallest units of weight/mass commonly used Due to the pro-arrhythmic potential of dofetilide, it is only available by prescription by physicians who have undergone specific training in the risks of treatment with dofetilide. In addition, it is only available by mail order or through specially trained local pharmacies to individuals who are prescribed dofetilide by a physician who is registered as being able to prescribe the pharmaceutical.
The elimination half-life of dofetilide is roughly 10 hours, however this is variable based on many physiologic factors (most significantly creatinine clearance), and ranges from 4. Half-Life (computer-game page here It's already listed in the disambiguation page Renal function, in Nephrology, is an indication of the state of the Kidney and its role in Renal physiology. 8 to 13. 5 hours.
Contents |
Mechanism of action
Dofetilide works by selectively blocking the rapid component of the delayed rectifier outward potassium current (IKr).
This causes prolongation of the effective refractory period of accessory pathways (both anterograde and retrograde conduction in the accessory pathway). It is this selective action on accessory pathways that makes dofetilide effective in the treatment of atrial fibrillation and flutter. Atrial fibrillation ( AF or afib) is a Cardiac arrhythmia (abnormal heart rhythm that involves the two upper chambers ( atria) of the Heart Atrial flutter is an abnormal heart rhythm that occurs in the atria of the Heart.
Dofetilide does not effect Vmax (The slope of the upstroke of phase 0 depolarization), conduction velocity, or the resting membrane potential. Slope is used to describe the steepness incline gradient or grade of a straight line.
There is a dose-dependent increase in the QT interval and the corrected QT interval (QTc). Because of this, many practitioners will initiate dofetilide therapy only on individuals under telemetry monitoring or if serial EKG measurements of QT and QTc can be performed.
Metabolism
A steady-state plasma level of dofetilide is achieved in 2-3 days.
80% of dofetilide is excreted by the kidneys, so the dose of dofetilide should be adjusted in individuals with renal insufficiency, based on creatinine clearance. The kidneys are complicated organs that have numerous biological roles Renal failure or kidney Renal function, in Nephrology, is an indication of the state of the Kidney and its role in Renal physiology.
In the kidneys, dofetilide is eliminated via cation exchange (secretion). Agents that interfere with the renal cation exchange system, such as verapamil, cimetidine, hydrochlorothiazide, itraconazole, ketoconazole, prochlorperazine, and trimethoprim should not be administered to individuals taking dofetilide. Verapamil (brand names Isoptin, Verelan, Calan, Bosoptin, Covera-HS) is an L-type Calcium channel blocker. Cimetidine ( INN) (sɨˈmɛtɨdiːn/ /saɪ- is a histamine H2-receptor antagonist that inhibits the production of acid in the Stomach. Hydrochlorothiazide, sometimes abbreviated HCT, HCTZ, or HZT is a popular Diuretic drug of the Thiazide class that acts by inhibiting Itraconazole (marketed as Sporanox by Janssen Pharmaceutica) invented in 1984 is a Triazole Antifungal agent that is prescribed to patients Ketoconazole is a synthetic Antifungal drug used to prevent and treat skin and fungal infections especially in immunocompromised patients such as those Prochlorperazine (marketed under the names Compazine, Buccastem, Stemetil and Phenotil) is a drug that belongs to the Phenothiazine Trimethoprim ( INN) (traɪˈmɛθəprɪm is a bacteriostatic Antibiotic mainly used in the Prophylaxis and treatment of Urinary tract infections
About 20 percent of dofetilide is metabolized in the liver via the CYP3A4 isoenzyme of the cytochrome P450 enzyme system. Cytochrome P450 3A4 (abbreviated CYP3A4) ( a member of the Cytochrome P450 mixed-function oxidase system is one of the most important enzymes involved in the metabolism Cytochrome P450 (abbreviated CYP, P450, infrequently CYP450) is a very large and diverse superfamily of Hemoproteins found in all Domains Drugs that interfere with the activity of the CYP3A4 isoenzyme can increase serum dofetilide levels. Cytochrome P450 3A4 (abbreviated CYP3A4) ( a member of the Cytochrome P450 mixed-function oxidase system is one of the most important enzymes involved in the metabolism If the renal cation exchange system is interfered with (as with the medications listed above), a larger percentage of dofetilide is cleared via the CYP3A4 isoenzyme system. Cytochrome P450 3A4 (abbreviated CYP3A4) ( a member of the Cytochrome P450 mixed-function oxidase system is one of the most important enzymes involved in the metabolism
Side effects
Torsades de pointes is the most serious side effect of dofetilide therapy. Torsades de pointes, torsades or torsade de pointes is a French term that literally means "twisting of the points" The incidence of torsades de pointes is dose-related, and is 0. 3-10. 5%. The risk appears to be dose-dependent, with an increased incidence of torsades de pointes associated with higher doses of dofetilide administered.
The risk of inducing torsades de pointes can be decreased by taking precautions when initiating therapy, such as hospitalizing individuals for a minimum of three days for serial creatinine measurement, continuous telemetry monitoring and availability of cardiac resuscitation. Creatinine is a break-down product of Creatine phosphate in Muscle, and is usually produced at a fairly constant rate by the body (depending on muscle mass Telemetry (synonymous with Telematics) is a Technology that allows the remote measurement and reporting of Information of interest to the system designer
Clinical use
Based on the results of the Danish Investigations of Arrhythmias and Mortality on Dofetilide (DIAMOND) study, dofetilide does not affect mortality in the treatment of patients post-myocardial infarction with left ventricular dysfunction. Myocardial infarction ( MI or AMI for acute myocardial infarction) also known as a heart attack, occurs when the blood supply The left ventricle is one of four chambers (two atria and two ventricles in the Human Heart. 3 Because of the results of the DIAMOND study, many physicians use dofetilide in the suppression of atrial fibrillation in individuals with LV dysfunction.
See also
References
- Thomas L. Antiarrhythmic agents are a group of Pharmaceuticals that are used to suppress fast rhythms of the Heart ( Cardiac arrhythmias) such as Atrial fibrillation The cardiac action potential is a specialized Action potential in the Heart, with unique properties necessary for function of the Electrical conduction system Lenz, Pharm. D. , and Daniel E. Hilleman, Pharm. D. , Department of Cardiology, Creighton University, Omaha, Nebraska. Dofetilide, a New Class III Antiarrhythmic Agent. Pharmacotherapy 20(7):776-786, 2000. (Medline abstract)
- Lenz TL, Hilleman DE. Dofetilide: A new antiarrhythmic agent approved for conversion and/or maintenance of atrial fibrillation/atrial flutter. Drugs Today (Barc). 2000 Nov;36(11):759-71. (Medline abstract)
- Torp-Pedersen C, Moller M, Bloch-Thomsen PE, Kober L, Sandoe E, Egstrup K, Agner E, Carlsen J, Videbaek J, Marchant B, Camm AJ. Dofetilide in patients with congestive heart failure and left ventricular dysfunction. Danish Investigations of Arrhythmia and Mortality on Dofetilide Study Group. N Engl J Med. 1999 Sep 16;341(12):857-65. (Medline abstract)
Dapyx Software network: MP3 Explorer | Ebook Manager | Zenithic