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Antiarrhythmic
Antiarrhythmic agents, also known as cardiac dysrhythmia medications, are a group of pharmaceuticals that are used to suppress abnormally fast rhythms ( tachycardias), such as atrial fibrillation, supraventricular tachycardia and ventricular tachycardia. Many attempts have been made to classify antiarrhythmic agents. Many of the antiarrhythmic agents have multiple modes of action, which makes any classification imprecise. Vaughan Williams classification The Vaughan Williams classification was introduced in 1970 by Miles Vaughan Williams.Vaughan Williams, EM (1970) "Classification of antiarrhythmic drugs". In ''Symposium on Cardiac Arrhythmias'' (Eds. Sandoe E; Flensted-Jensen E; Olsen KH). Astra, Elsinore. Denmark (1970) Vaughan Williams was a pharmacology tutor at Hertford College, Oxford. One of his students, Bramah N. Singh, contributed to the development of the classification system. The system is therefore sometimes known as the Singh-Vaughan Williams classification. The ...
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Procainamide
Procainamide (PCA) is a medication of the antiarrhythmic class used for the treatment of cardiac arrhythmias. It is classified by the Vaughan Williams classification system as class Ia; thus it is a sodium channel blocker of cardiomyocytes. In addition to blocking the ''I''Na current, it inhibits the ''I''Kr rectifier K+ current. Procainamide is also known to induce a voltage-dependent open channel block on the batrachotoxin (BTX)-activated sodium channels in cardiomyocytes. Uses Medical Procainamide is used for treating ventricular arrhythmias: ventricular ectopy and tachycardia and supraventricular arrhythmias: atrial fibrillation, and re-entrant and automatic supraventricular tachycardia. For example, it can be used to convert new-onset atrial fibrillation, and although was initially thought to be suboptimal for this purpose, a growing body of literature is amounting in support for this exact cause. It is administered by mouth, by intramuscular injection, or intravenously. ...
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Lidocaine
Lidocaine, also known as lignocaine and sold under the brand name Xylocaine among others, is a local anesthetic of the amino amide type. It is also used to treat ventricular tachycardia. When used for local anaesthesia or in nerve blocks, lidocaine typically begins working within several minutes and lasts for half an hour to three hours. Lidocaine mixtures may also be applied directly to the skin or mucous membranes to numb the area. It is often used mixed with a small amount of adrenaline (epinephrine) to prolong its local effects and to decrease bleeding. If injected intravenously, it may cause cerebral effects such as confusion, changes in vision, numbness, tingling, and vomiting. It can cause low blood pressure and an irregular heart rate. There are concerns that injecting it into a joint can cause problems with the cartilage. It appears to be generally safe for use in pregnancy. A lower dose may be required in those with liver problems. It is generally safe to use in those ...
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Phenytoin
Phenytoin (PHT), sold under the brand name Dilantin among others, is an anti-seizure medication. It is useful for the prevention of tonic-clonic seizures (also known as grand mal seizures) and focal seizures, but not absence seizures. The intravenous form, fosphenytoin, is used for status epilepticus that does not improve with benzodiazepines. It may also be used for certain heart arrhythmias or neuropathic pain. It can be taken intravenously or by mouth. The intravenous form generally begins working within 30 minutes and is effective for roughly 24 hours. Blood levels can be measured to determine the proper dose. Common side effects include nausea, stomach pain, loss of appetite, poor coordination, increased hair growth, and enlargement of the gums. Potentially serious side effects include sleepiness, self harm, liver problems, bone marrow suppression, low blood pressure, and toxic epidermal necrolysis. There is evidence that use during pregnancy results in abnormalities ...
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Cardiac Action Potential
The cardiac action potential is a brief change in voltage ( membrane potential) across the cell membrane of heart cells. This is caused by the movement of charged atoms (called ions) between the inside and outside of the cell, through proteins called ion channels. The cardiac action potential differs from action potentials found in other types of electrically excitable cells, such as nerves. Action potentials also vary within the heart; this is due to the presence of different ion channels in different cells. Unlike the action potential in skeletal muscle cells, the cardiac action potential is not initiated by nervous activity. Instead, it arises from a group of specialized cells known as pacemaker cells, that have automatic action potential generation capability. In healthy hearts, these cells form the cardiac pacemaker and are found in the sinoatrial node in the right atrium. They produce roughly 60–100 action potentials every minute. The action potential passes along t ...
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Quinidine
Quinidine is a class IA antiarrhythmic agent used to treat heart rhythm disturbances. It is the enantiomer of antimalarial agent quinine, originally derived from the bark of the cinchona tree. The drug causes increased action potential duration, as well as a prolonged QT interval. As of 2019, its IV formulation is no longer being manufactured for use in the United States. Medical uses Quinidine is occasionally used as a class I antiarrhythmic agent to prevent ventricular arrhythmias, particularly in Brugada Syndrome, although its safety in this indication is uncertain. It reduces the recurrence of atrial fibrillation after patients undergo cardioversion, but it has proarrhythmic effects and trials suggest that it may lead to an overall increased mortality in these patients. Quinidine is also used to treat short QT syndrome. Eli Lilly has discontinued manufacture of parenteral quinidine gluconate in the US, and its future availability in many countries is uncertain. Other ...
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Tocainide
Tocainide (Tonocard) is a class Ib antiarrhythmic agent. It is no longer sold in the United States. Pharmacokinetics Tocainide is a lidocaine analog, that does not have significant 1st pass metabolism. It is found in two enantiomer In chemistry, an enantiomer ( /ɪˈnænti.əmər, ɛ-, -oʊ-/ ''ih-NAN-tee-ə-mər''; from Ancient Greek ἐνάντιος ''(enántios)'' 'opposite', and μέρος ''(méros)'' 'part') – also called optical isomer, antipode, or optical ant ...s. The R isomer is 4x as potent as the S. Oral bioavailability is 0.9-1.0. In the blood tocainide is 10-20% protein bound. The Volume of distribution is 2.5-3.5 L/kg. 30-50% is excreted unchanged in the urine. The more active R-isomer is cleared faster in anephric patients or those with severe renal dysfunction. The main metabolite is the glucuronidated tocainide carbamic acid. The glucuronosyl transferase is apparently induced by rifampin. Weak inhibition of Cyp1A2 leads to a mild theophylline int ...
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Sparteine
Sparteine is a class 1a antiarrhythmic agent; a sodium channel blocker. It is an alkaloid and can be extracted from scotch broom. It is the predominant alkaloid in ''Lupinus mutabilis'', and is thought to chelate the bivalent cations calcium and magnesium. It is not FDA approved for human use as an antiarrhythmic agent, and it is not included in the Vaughan Williams classification of antiarrhythmic drugs. It is also used as a chiral ligand in organic chemistry, especially in syntheses involving organolithium reagents. Biosynthesis Sparteine is a lupin alkaloid containing a tetracyclic bis-quinolizidine ring system derived from three C5 chains of lysine, or more specifically, L-lysine. The first intermediate in the biosynthesis is cadaverine, the decarboxylation product of lysine catalyzed by the enzyme lysine decarboxylase (LDC). Three units of cadaverine are used to form the quinolizidine skeleton. The mechanism of formation has been studied enzymatically, as well as with ...
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Flecainide
Flecainide is a medication used to prevent and treat abnormally fast heart rates. This includes ventricular and supraventricular tachycardias. Its use is only recommended in those with dangerous arrhythmias or when significant symptoms cannot be managed with other treatments. Its use does not decrease a person's risk of death. It is taken by mouth or injection into a vein. Common side effects include dizziness, problems seeing, shortness of breath, chest pain, and tiredness. Serious side effects may include cardiac arrest, arrhythmias, and heart failure. It may be used in pregnancy, but has not been well studied in this population. Use is not recommended in those with structural heart disease or ischemic heart disease. Flecainide is a class Ic antiarrhythmic agent. It works by decreasing the entry of sodium in heart cells, causing prolongation of the cardiac action potential. Flecainide was approved for medical use in the United States in 1985. It is available as a generic me ...
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Ajmaline
Ajmaline (also known by trade names Gilurytmal, Ritmos, and Aritmina) is an alkaloid that is classified as a 1-A antiarrhythmic agent. It is often used to induce arrhythmic contraction in patients suspected of having Brugada syndrome. Individuals suffering from Brugada syndrome will be more susceptible to the arrhythmogenic effects of the drug, and this can be observed on an electrocardiogram as an ST elevation. The compound was first isolated by Salimuzzaman Siddiqui in 1931 from the roots of '' Rauvolfia serpentina''. He named it ''ajmaline'', after Hakim Ajmal Khan, one of the most illustrious practitioners of Unani medicine in South Asia. Ajmaline can be found in most species of the genus '' Rauvolfia'' as well as ''Catharanthus roseus''. In addition to Southeast Asia, ''Rauvolfia'' species have also been found in tropical regions of India, Africa, South America, and some oceanic islands. Other indole alkaloids found in ''Rauvolfia'' include reserpine, ajmalicine, serpen ...
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Encainide
Encainide (trade name Enkaid) is a class Ic antiarrhythmic agent. It is no longer used because of its frequent proarrhythmic side effects. Synthesis See also * Iferanserin * Cardiac Arrhythmia Suppression Trial The Cardiac Arrhythmia Suppression Trial (CAST) was a double-blind, randomized, controlled study designed to test the hypothesis that suppression of premature ventricular complexes (PVC) with class I antiarrhythmic agents after a myocardial infarc ... References Antiarrhythmic agents Benzanilides Phenol ethers Piperidines Sodium channel blockers Withdrawn drugs {{cardiovascular-drug-stub ...
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Mexiletine
Mexiletine (INN) (sold under the brand names Mexitil and Namuscla) is a medication used to treat abnormal heart rhythms, chronic pain, and some causes of muscle stiffness. Common side effects include abdominal pain, chest discomfort, drowsiness, headache, and nausea. It works as a non-selective voltage-gated sodium channel blocker and belongs to the Class IB group of anti-arrhythmic medications. Medical uses Mexiletine has several uses including the treatment of abnormal heart rhythms or arrhythmias, chronic pain, and myotonia. In general when treating arrhythmias, mexiletine is reserved for use in dangerous heart rhythm disturbances such as ventricular tachycardia. It is of particular use when treating arrhythmias caused by long QT syndrome. The LQT3 form of long QT syndrome is amenable to treatment with mexiletine as this form is caused by defective sodium channels that continue to release a sustained current rather than fully inactivating, however other forms of long QT ...
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Miles Vaughan Williams
(Edward) Miles Vaughan Williams (8 August 1918 – 31 August 2016) was a British cardiac pharmacologist and academic. He is best known for the Vaughan Williams classification of antidysrhythmic drugs. From 1955 to 1985, he was a Fellow of Hertford College, Oxford, and its Tutor in medicine. Life He was born in Bangalore to Stella and Arthur Vaughan Williams. His father, an engineer working on the railways of India, was a cousin of the composer Ralph Vaughan Williams. Schooling was at Wellington college, and university at Wadham College, where he studied philosophy and classics ( Greats). He became an ambulance officer during the second world war. Upon his return to Oxford, he switched from Greats to Medicine. In 1956 he married Marie, with whom he had three children. Scientific work He is best known for his work on beta-adrenoceptor antagonists (better known as beta blocker), and for the development of the first widely used classification system for antidysrhythmic drugs, common ...
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