Genetic and Molecular Aspects of Drug-Induced QT Interval Prolongation
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The QT Interval: How Long Is Too Long?
heart matters The QT interval: How long is too long? By Natalie K. Cox, RN Staff Nurse • Coronary Care Unit • McLeod Regional Medical Center • Florence, S.C. What’s the QT interval and why’s it so the appearance that the QT interval is pro- important? In this article, I’ll answer these longed. However, a wide QRS complex questions plus show you how to measure represents depolarization, and LQTS is a dis- the QT interval and how to recognize the order of repolarization. Sometimes the end types of long QT syndrome (LQTS) and of a T wave isn’t clearly defi ned, which can their symptoms, causes, and treatments. make it diffi cult to get the QT measurement. Irregular rhythms also make it diffi cult to The long and short of it obtain a consistent QT interval measure- The QT interval on the ECG is measured ment. For example, atrial fi brillation makes from the beginning of the QRS complex to it extremely diffi cult to measure a QT inter- the end of the T wave (see ECG components). val because fi nding a T wave isn’t always It represents the time it takes for the ventricles of the heart to depolarize and repolarize, or to ECG components contract and relax. The QT interval is longer when First positive deflection after the the heart rate is slower and short- ECG components P or Q wave er when the heart rate is faster. So it’s necessary to calculate the corrected QT interval (QTc) using the Bazett formula: QT interval divided by the square root of the R-R interval. -
Veterinary Emergency & Anaesthesia Pfizer
AVA ECVA & AVEF Thank all their sponsors for this spring edition PARIS 2007 On VETERINARY EMERGENCY & ANAESTHESIA PFIZER MERIAL FORT DODGE BAYER BOEHRINGER MEDISUR COVETO OPTOMED HALLOWELL SCIL JANSSEN SOGEVAL KRUSSE TECHNIBELT MILA TEM The Organisatiors 7th AVEF European Meeting- 10th March 2007-ROISSY 2 AVA – ECVA Spring Meeting 2007 on Veterinary Emergency & Anesthesia 7 – 10 March 2007, Paris, France AVA PARIS 2007 — Wednesday March 7th RESIDENT DAY RUMINANT ANAESTHESIA Hyatt Regency Hotel, Roissy CDG, France K OTTO, D HOLOPHERNE, G TOUZOT 8.30 REGISTRATIONS 9.00-9.45 Specific anatomo-physiology to consider for ruminant peri-anaesthetic period K OTTO 10.00-10.30 COFFEE BREAK 10.30-11.15 Post-anaesthetic and pain management in ruminants K OTTO 11.30-12.15 Physical restraint and sedation of ruminants D HOLOPHERNE 12.30-1.30 LUNCH 1.30-2.15 Anaesthesia of Lamas & Alpagas G TOUZOT 2.30-3.15 Regional & local anaesthesia for ruminants D HOLOPHERNE 3.30-4.00 COFFEE BREAK 4.00-4.45 Pharmacology and protocols for ruminant anaesthesia G TOUZOT AVA-ECVA PARIS 2007, Veterinary Emergency & Anaesthesia, 7-10th March AVA-ECVA PARIS 2007, Veterinary Emergency & Anaesthesia, 7-10th March AVA – ECVA Spring Meeting 2007 on Veterinary Emergency & Anesthesia 7 – 10 March 2007, Paris, France Specific anatomo-physiology to consider for ruminants peri-anaesthetic period Klaus A. Otto Institut für Versuchstierkunde und Zentrales Tierlaboratorium, Medizinische Hochschule Hannover, D-30623 Hannover, Germany The suborder “ruminantia” includes members of the family “bovidae” such as cattle (bos taurus), sheep (ovis spp) and goats (capra spp). Members of the family “camelidae” (camelus spp, llama spp, vicugna spp) belong to the suborder “tylopodia” and therefore are not true ruminants. -
Non Commercial Use Only
Cardiogenetics 2017; volume 7:6304 Sudden death in a young patient with atrial fibrillation Case Report Correspondence: María Angeles Espinosa Castro, Inherited Cardiovascular Disease A 22-year-old man suffered a sudden Program, Cardiology Department, Gregorio María Tamargo, cardiac arrest without previous symptoms Marañón Hospital, Dr. Esquerdo, 46, 28007, María Ángeles Espinosa, while he was at rest, waiting for a subway Madrid, Spain. Víctor Gómez-Carrillo, Miriam Juárez, train. Cardiopulmonary resuscitation was Tel.: +34.91.586.82.90. immediately started using an Automated E-mail: [email protected] Francisco Fernández-Avilés, External Defibrillation that identified the Raquel Yotti Key words: KCNQ1; mutation; channelopa- presence of ventricular fibrillation and thy; sudden cardiac death; atrial fibrillation. Inherited Cardiovascular Disease delivered a shock. Return of spontaneous Program, Cardiology Department, circulation was achieved after three Contributions: MT, acquisition and interpreta- Gregorio Marañón Hospital, Madrid, attempts, being atrial fibrillation (AF) the tion of data for the work, ensuring that ques- Spain patient’s rhythm at this point (Figure 1). tions related to the accuracy or integrity of any He was admitted to our Cardiovascular part of the work is appropriately investigated Intensive Care Unit and therapeutic and resolved; MAE, conception of the work, hypothermia was performed over a period critical revision of the intellectual content, final approval of the version to be published, Abstract of 24 h. After completing hypothermia, ensuring that questions related to the accuracy rewarming, and another 24 h of controlled of any part of the work is appropriately inves- Sudden cardiac death (SCD) in young normothermia the patient awakened with no tigated and resolved; VG-C, acquisition and patients without structural heart disease is residual neurologic damage. -
What Are the Acute Treatments for Migraine and How Are They Used?
2. Acute Treatment CQ II-2-1 What are the acute treatments for migraine and how are they used? Recommendation The mainstay of acute treatment for migraine is pharmacotherapy. The drugs used include (1) acetaminophen, (2) non-steroidal anti-inflammatory drugs (NSAIDs), (3) ergotamines, (4) triptans and (5) antiemetics. Stratified treatment according to the severity of migraine is recommended: use NSAIDs such as aspirin and naproxen for mild to moderate headache, and use triptans for moderate to severe headache, or even mild to moderate headache when NSAIDs were ineffective in the past. It is necessary to give guidance and cautions to patients having acute attacks, and explain the methods of using medications (timing, dose, frequency of use) and medication use during pregnancy and breast-feeding. Grade A Background and Objective The objective of acute treatment is to resolve the migraine attack completely and rapidly and restore the patient’s normal functions. An ideal treatment should have the following characteristics: (1) resolves pain and associated symptoms rapidly; (2) is consistently effective; (3) no recurrence; (4) no need for additional use of medication; (5) no adverse effects; (6) can be administered by the patients themselves; and (7) low cost. Literature was searched to identify acute treatments that satisfy the above conditions. Comments and Evidence The acute treatment drugs for migraine generally include (1) acetaminophens, (2) non-steroidal anti-inflammatory drugs (NSAIDs), (3) ergotamines, (4) triptans, and (5) antiemetics. For severe migraines including status migrainosus and migraine attacks refractory to treatment, (6) anesthetics, and (7) corticosteroids (dexamethasone) are used (Tables 1 and 2).1)-9) There are two approaches to the selection and sequencing of these medications: “step care” and “stratified care”. -
Drug Induced QT Prolongation and Torsades De Pointes (Tdp)
Drug induced QT prolongation and Torsades de Pointes (TdP) Mark Friesen, PharmD March 13, 2013 Conflict of Interest None TdP: Learning objectives To review the pathophysiology of QT prolongation and TdP To become aware of the risk factors (including medication- related) for QT prolongation and TdP To understand and apply a systematic approach for dealing with drug interactions that may cause prolonged QT and TdP Clinical Scenario You receive an order for a patient: Levofloxacin 500 mg PO daily Fluconazole 400 mg PO daily Your drug interaction program flags this as a major interaction due to QT prolonging effect of both drugs increasing risk for TdP. What do you do? TdP: History Quinidine associated syncope since 1920’s Congenital syndromes with prolonged QT and syncope or sudden death described in 1950’s, and early 1960’s. 1966 Francois Dessertenne described a specific EKG form of polymorphic VT he termed “torsades de pointes” Over past decade single most common cause of drug withdrawal/restriction from market 9 structurally unrelated non-cardiac drugs: terfenadine, astemizole, grepafloxicin, terodiline, droperidol, terodiline, droperidol, lidoflazaine, sertindole, levomethadyl, cisapride TdP: Definition Polymorphic VT with a preexistant prolonged QT interval Ventricular Action Potential Ca++ Na+ IKr IKs IKr Channel: hERG controlled Delayed repolarization=prolonged QT interval Mechanism of Torsades de Pointes Early afterdepolarizations (extra beat) Transmural reentry (Unusual pathway) Mechanisms Of Drug - Induced QT Prolongation -
Long QT Syndrome: from Channels to Cardiac Arrhythmias
Long QT syndrome: from channels to cardiac arrhythmias Arthur J. Moss, Robert S. Kass J Clin Invest. 2005;115(8):2018-2024. https://doi.org/10.1172/JCI25537. Review Series Long QT syndrome, a rare genetic disorder associated with life-threatening arrhythmias, has provided a wealth of information about fundamental mechanisms underlying human cardiac electrophysiology that has come about because of truly collaborative interactions between clinical and basic scientists. Our understanding of the mechanisms that control the critical plateau and repolarization phases of the human ventricular action potential has been raised to new levels through these studies, which have clarified the manner in which both potassium and sodium channels regulate this critical period of electrical activity. Find the latest version: https://jci.me/25537/pdf Review series Long QT syndrome: from channels to cardiac arrhythmias Arthur J. Moss1 and Robert S. Kass2 1Heart Research Follow-up Program, Department of Medicine, University of Rochester School of Medicine and Dentistry, Rochester, New York, USA. 2Department of Pharmacology, Columbia University Medical Center, New York, New York, USA. Long QT syndrome, a rare genetic disorder associated with life-threatening arrhythmias, has provided a wealth of information about fundamental mechanisms underlying human cardiac electrophysiology that has come about because of truly collaborative interactions between clinical and basic scientists. Our understanding of the mecha- nisms that control the critical plateau and repolarization phases of the human ventricular action potential has been raised to new levels through these studies, which have clarified the manner in which both potassium and sodium channels regulate this critical period of electrical activity. -
Anemia and the QT Interval in Hypertensive Patients
2084 International Journal of Collaborative Research on Internal Medicine & Public Health Anemia and the QT interval in hypertensive patients Ioana Mozos 1*, Corina Serban 2, Rodica Mihaescu 3 1 Department of Functional Sciences, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania 2 Department of Functional Sciences, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania 3 1st Department of Internal Medicine, “Victor Babes” University of Medicine and Pharmacy, Timisoara, Romania * Corresponding Author ; Email: [email protected] Abstract Introduction: A prolonged ECG QT interval duration and an increased QT dispersion (QTd) are predictors of sudden cardiac death. Anemia is known as a marker of adverse outcome in cardiovascular disease. Objective: The aim was to assess the relationship between anemia and QT intervals in hypertensive patients. Method: A total of 72 hypertensive patients underwent standard 12-lead ECG. QT intervals and QT dispersions were manually measured. Complete blood count was also assessed. Result: Linear regression analysis revealed significant associations between prolonged QTc and increased QTd and anemia and macrocytosis, respectively. Multiple regression analysis revealed a significant association between red cell distribution width (RDW) >15% and prolonged heart rate corrected maximal QT interval duration (QTc) and QT interval in lead DII (QTIIc). The most sensitive and specific predictor of prolonged QTc and QTIIc was anisocytosis. Anemia was the most sensitive predictor of -
Concentration Dependent Cardiotoxicity of Terodiline in Patients Treated for Urinary Incontinence
Br HeartJ7 1995;74:53-56 53 Concentration dependent cardiotoxicity of terodiline in patients treated for urinary incontinence Simon H L Thomas, P Daniel Higham, Kenneth Hartigan-Go, Farhad Kamali, Peter Wood, Ronald W F Campbell, Gary A Ford Abstract Terodiline hydrochloride is an antimuscarinic Objective-Terodiline, an antimuscarinic drug with calcium antagonist properties' and calcium antagonist drug, was used to which was used for treating urinary inconti- treat detrusor instability but was with- nence caused by detrusor instability.2 The drawn in 1991 after provoking serious drug was withdrawn in 1991 after reports of ventricular arrhythmias associated with cardiac dysrhythmia including bradycardia, increases in the corrected QT interval heart block, ventricular fibrillation, and ven- (QTc). This research was performed to tricular tachycardia, usually of the torsade de relate drug induced electrocardiographic pointes-type34 and associated with QT pro- changes in asymptomatic recipients to longation. Plasma terodiline concentrations plasma concentrations of the R( +) and were very high in one affected patient. S(-) terodiline enantiomers. Predisposing factors for terodiline associated Setting-Urological and geriatric clinics torsade de pointes were old age, coexisting and wards. ischaemic heart disease, co-prescription of Subjects-Asymptomatic patients taking other cardioactive drugs, and hypokalaemia. terodiline in stable dose. Torsade de pointes is associated with Methods-Electrocardiograms (50 mm/s) abnormal prolongation of the ventricular were collected from patients while they refractory period which results in a long QT were taking terodiline and compared with interval on the electrocardiogram and is often ECGs obtained before or after terodiline. drug induced.5 Increased dispersion of ven- QT interval, heart rate corrected QT tricular recovery may be important in the interval (QTc), and QT dispersion (QTd) development of this arrhythmia and indirect were measured. -
Pharmacologyonline 2: 971-1020 (2009) Newsletter Gabriella Galizia
Pharmacologyonline 2: 971-1020 (2009) Newsletter Gabriella Galizia THE TREATMENT OF THE SCHIZOPHRENIA: AN OVERVIEW Gabriella Galizia School of Pharmacy,University of Salerno, Italy e-mail: [email protected] Summary The schizophrenia is a kind of psychiatric disease, characterized by a course longer than six months (usually chronic or relapsing), by the persistence of symptoms of alteration of mind, behaviour and emotion, with such a seriousness to limitate the normal activity of a person. The terms antipsychotic and neuroleptic define a group of medicine principally used to treat schizophrenia, but they are also efficacious for other psychosis and in states of psychic agitation. The antipsychotics are divided into two classes: classic or typical and atypical. The paliperidone, the major metabolite of risperidone, shares with the native drug the characteristics of receptoral bond and of antagonism of serotonin (5HT2A) and dopamine (D2). It's available in a prolonged release formulation and it allows the administration once daily. Besides, the paliperidone has a pharmacological action independent of CYT P450 and in such way a lot of due pharmacological interactions would be avoided to interference with the activity of the CYP2D6, that is known to have involved in the metabolism of the 25% of the drugs of commune therapeutic employment. Introduction The schizophrenia has been a very hard disease to investigate by the research. This is not surprising because it involves the most mysterious aspects of human mind, as emotions and cognitive processes. According to scientific conventions, the schizophrenia is a kind of psychiatric disease, characterized by a course longer than six months (usually chronic or relapsing), by the persistence of symptoms of alteration of mind, behaviour and emotion, with such a seriousness to limitate the normal activity of a person. -
Drugs That Can Cause Delirium (Anticholinergic / Toxic Metabolites)
Drugs that can Cause Delirium (anticholinergic / toxic metabolites) Deliriants (drugs causing delirium) Prescription drugs . Central acting agents – Sedative hypnotics (e.g., benzodiazepines) – Anticonvulsants (e.g., barbiturates) – Antiparkinsonian agents (e.g., benztropine, trihexyphenidyl) . Analgesics – Narcotics (NB. meperidine*) – Non-steroidal anti-inflammatory drugs* . Antihistamines (first generation, e.g., hydroxyzine) . Gastrointestinal agents – Antispasmodics – H2-blockers* . Antinauseants – Scopolamine – Dimenhydrinate . Antibiotics – Fluoroquinolones* . Psychotropic medications – Tricyclic antidepressants – Lithium* . Cardiac medications – Antiarrhythmics – Digitalis* – Antihypertensives (b-blockers, methyldopa) . Miscellaneous – Skeletal muscle relaxants – Steroids Over the counter medications and complementary/alternative medications . Antihistamines (NB. first generation) – diphenhydramine, chlorpheniramine). Antinauseants – dimenhydrinate, scopolamine . Liquid medications containing alcohol . Mandrake . Henbane . Jimson weed . Atropa belladonna extract * Requires adjustment in renal impairment. From: K Alagiakrishnan, C A Wiens. (2004). An approach to drug induced delirium in the elderly. Postgrad Med J, 80, 388–393. Delirium in the Older Person: A Medical Emergency. Island Health www.viha.ca/mhas/resources/delirium/ Drugs that can cause delirium. Reviewed: 8-2014 Some commonly used medications with moderate to high anticholinergic properties and alternative suggestions Type of medication Alternatives with less deliriogenic -
Pharmacology – Inhalant Anesthetics
Pharmacology- Inhalant Anesthetics Lyon Lee DVM PhD DACVA Introduction • Maintenance of general anesthesia is primarily carried out using inhalation anesthetics, although intravenous anesthetics may be used for short procedures. • Inhalation anesthetics provide quicker changes of anesthetic depth than injectable anesthetics, and reversal of central nervous depression is more readily achieved, explaining for its popularity in prolonged anesthesia (less risk of overdosing, less accumulation and quicker recovery) (see table 1) Table 1. Comparison of inhalant and injectable anesthetics Inhalant Technique Injectable Technique Expensive Equipment Cheap (needles, syringes) Patent Airway and high O2 Not necessarily Better control of anesthetic depth Once given, suffer the consequences Ease of elimination (ventilation) Only through metabolism & Excretion Pollution No • Commonly administered inhalant anesthetics include volatile liquids such as isoflurane, halothane, sevoflurane and desflurane, and inorganic gas, nitrous oxide (N2O). Except N2O, these volatile anesthetics are chemically ‘halogenated hydrocarbons’ and all are closely related. • Physical characteristics of volatile anesthetics govern their clinical effects and practicality associated with their use. Table 2. Physical characteristics of some volatile anesthetic agents. (MAC is for man) Name partition coefficient. boiling point MAC % blood /gas oil/gas (deg=C) Nitrous oxide 0.47 1.4 -89 105 Cyclopropane 0.55 11.5 -34 9.2 Halothane 2.4 220 50.2 0.75 Methoxyflurane 11.0 950 104.7 0.2 Enflurane 1.9 98 56.5 1.68 Isoflurane 1.4 97 48.5 1.15 Sevoflurane 0.6 53 58.5 2.5 Desflurane 0.42 18.7 25 5.72 Diethyl ether 12 65 34.6 1.92 Chloroform 8 400 61.2 0.77 Trichloroethylene 9 714 86.7 0.23 • The volatile anesthetics are administered as vapors after their evaporization in devices known as vaporizers. -
Effects of Nifekalant Injected Into the Pericardial Space on the Transmural Dispersion of Repolarization in Pig
Showa Univ J Med Sci 19(3), 123 135, September 2007 Original Effects of Nifekalant Injected into the Pericardial Space on the Transmural Dispersion of Repolarization in Pig Hiroyuki ITo, Taku ASANO, Youichi KOBAYASHI, Tatsuya ONUKI, Fumito MwosHI, Taka-aki MATSUYAMA, Yoshino MINOURA, Norikazu WATANABE, Mitsuharu KAWAMURA, Kaoru TANNO and Takashl KATAGIRI Abstract: Transmural dispersion of repolarization (TDR) has been implicated in the onset of ventricular arrhythmia. We investigated the effects of nifekalant (NIF) injected into the pericardial space on TDR and T wave in pig. We injected 50 or 100 mg of NIF into the pericardial space of 11 pigs, and measured the effective refractory period (ERP) between the endocardial and epicardial myocardial cells, as well as QT time and QT peak-end as an index of TDR and T waveforms, respectively. TDR decreased from 56•} 10 msec to 44•}8 msec (P < 0.01), 5.1 min after injection of 100 mg of NIF, although the QTc did not change. At a later time, QTc increased from 457 •} 44 msec before injection to 540•}49 msec (P < 0.01) and TDR recovered to the control level. When 50 mg of NIF was injected, the T wave amplitude decreased from 0.433 •}0.301 mV before injection to 0.107•}0.192 mV (P < 0.01) at 10 min after injection ; 100 mg of NIF caused the T wave amplitude to decrease more rapidly, reaching a negative value at 4.5 min after injection. Injecting NIF into the pericardial space altered ERP, QT, and T waveform, and also decreased TDR.