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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. 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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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 ...
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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 i ...
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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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Disopyramide
Disopyramide (INN, trade names Norpace and Rythmodan) is an antiarrhythmic medication used in the treatment of ventricular tachycardia. It is a sodium channel blocker and therefore classified as a Class 1a anti-arrhythmic agent. Disopyramide has a negative inotropic effect on the ventricular myocardium, significantly decreasing the contractility. 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. Mechanism of action Disopyramide's Class 1a activity is similar to that of quinidine in that it targets sodium channels to inhibit conduction. 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. Disopyramide prolongs the PR int ...
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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 Antiarrhythmic agent#Vaughan Williams classification, Vaughan Williams classification of antidysrhythmic drugs. From 1955 to 1985, he was a Fellow (Oxbridge), Fellow of Hertford College, Oxford, and its Tutorial (Oxbridge), 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, Berkshire, Wellington college, and university at Wadham College, Oxford, Wadham College, where he studied philosophy and classics (Literae Humaniores, 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 ...
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Arrhythmia
Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults – is called tachycardia, and a resting heart rate that is too slow – below 60 beats per minute – is called bradycardia. Some types of arrhythmias have no symptoms. Symptoms, when present, may include palpitations or feeling a pause between heartbeats. In more serious cases, there may be lightheadedness, passing out, shortness of breath or chest pain. While most cases of arrhythmia are not serious, some predispose a person to complications such as stroke or heart failure. Others may result in sudden death. Arrhythmias are often categorized into four groups: extra beats, supraventricular tachycardias, ventricular arrhythmias and bradyarrhythmias. Extra beats include premature atrial contractions, premature ventricular con ...
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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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Supraventricular Tachycardia
Supraventricular tachycardia (SVT) is an umbrella term for fast heart rhythms arising from the upper part of the heart. This is in contrast to the other group of fast heart rhythms – ventricular tachycardia, which start within the lower chambers of the heart. There are four main types of SVT: atrial fibrillation, atrial flutter, paroxysmal supraventricular tachycardia (PSVT), and Wolff–Parkinson–White syndrome. The symptoms of SVT include palpitations, feeling of faintness, sweating, shortness of breath, and/or chest pain. These abnormal rhythms start from either the atria or atrioventricular node. They are generally due to one of two mechanisms: re-entry or increased automaticity. Diagnosis is typically by electrocardiogram (ECG), holter monitor, or event monitor. Blood tests may be done to rule out specific underlying causes such as hyperthyroidism or electrolyte abnormalities. A normal resting heart rate is 60 to 100 beats per minute. A resting heart ...
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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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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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Beta Blockers
Beta blockers, also spelled β-blockers, are a class of medications that are predominantly used to manage abnormal heart rhythms, and to protect the heart from a second heart attack after a first heart attack ( secondary prevention). They are also widely used to treat high blood pressure, although they are no longer the first choice for initial treatment of most patients. Beta blockers are competitive antagonists that block the receptor sites for the endogenous catecholamines epinephrine (adrenaline) and norepinephrine (noradrenaline) on adrenergic beta receptors, of the sympathetic nervous system, which mediates the fight-or-flight response. Some block activation of all types of β-adrenergic receptors and others are selective for one of the three known types of beta receptors, designated β1, β2 and β3 receptors. β1-adrenergic receptors are located mainly in the heart and in the kidneys. β2-adrenergic receptors are located mainly in the lungs, gastrointestinal tract, l ...
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