He has seen several dangerous arrhythmias during treatments, though, including torsades de pointes and ventricular fibrillation.
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Ibogaine also appeared to affect the heart, causing bradycardia and increasing the risk of a life-threatening arrhythmia called torsades de pointes.
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The treatment of torsades de pointes aims to restore a normal rhythm and to prevent the arrhythmia recurring. While torsades may spontaneously revert to a normal sinus rhythm, sustained torsades requires emergency treatment to prevent cardiac arrest. The most effective treatment to terminate torsades is an electrical cardioversion - a procedure in which an electrical current is applied across the heart to temporarily stop and then resynchronise the heart's cells. Treatment to prevent recurrent torsades includes infusion of magnesium sulphate, correction of electrolyte imbalances such as low blood potassium levels (hypokalaemia), and withdrawal of any medications that prolong the QT interval.
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It has been implicated in causing ventricular arrhythmia (torsades de pointes).
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Torsades de pointes is the most serious side effect of dofetilide therapy. The incidence of torsades de pointes is 0.3-10.5% and is dose-related, with increased incidence associated with higher doses. The majority of episodes of torsades de pointes have occurred within the first three days of initial dosing. Patients should be hospitalized and monitored for the first three days after starting dofetilide.
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Treatments used to prevent torsades in specific circumstances include beta blockers or mexiletine in long QT syndrome. Occasionally a pacemaker may be used to accelerate the heart's own sinus rhythm, and those at risk of further torsades may be offered an implantable defibrillator to automatically detect and defibrillate further episodes of the arrhythmia.
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In larger plasma concentrations, it may lead to toxic effects on the heart's rhythm (e.g. ventricular tachycardia and torsades de pointes).
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François Dessertenne is a French physician who first described the special type of Ventricular tachycardia in 1966 known as Torsades de pointes.
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Torsades occurs as both an inherited (linked to at least 17 genes) and as an acquired form caused most often by drugs and/or electrolyte disorders that cause excessive lengthening of the QT interval. Common causes for torsades de pointes include drug-induced QT prolongation and less often diarrhea, low serum magnesium, and low serum potassium or congenital long QT syndrome. It can be seen in malnourished individuals and chronic alcoholics, due to a deficiency in potassium and/or magnesium. Certain drugs and combinations of drugs resulting in drug interactions are common contributors to torsades de pointes risk.
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Not recommended: combinations with lithium, potassium-sparing diuretics, potassium (salts), antiarrhythmic drugs which can cause torsades de pointes, anesthetic drugs, cytostatics or immunosuppressive agents.
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The fluoroquinolones, including ciprofloxacin, are associated with an increased risk of cardiac toxicity, including QT interval prolongation, torsades de pointes, ventricular arrhythmia, and sudden death.
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Lead II electrocardiogram (known as "rhythm strip") showing torsades de pointes being shocked by an implantable cardioverter-defibrillator back to the patient's baseline cardiac rhythm.
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Torsades de pointes is common in overdose. Amisulpride is moderately dangerous in overdose (with the TCAs being very dangerous and the SSRIs being modestly dangerous).
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Magnesium sulfate may be used as an antiarrhythmic agent for torsades de pointes in cardiac arrest under the ECC guidelines and for managing quinidine-induced arrhythmias.
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Other risk factors for developing torsades de pointes among those with LQTS include female sex, increasing age, pre-existing cardiovascular disease, and abnormal liver or kidney function.
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Torsades de pointes, torsade de pointes or torsades des pointes (TdP) (, translated as "twisting of peaks") is a specific type of abnormal heart rhythm that can lead to sudden cardiac death. It is a polymorphic ventricular tachycardia that exhibits distinct characteristics on the electrocardiogram (ECG). It was described by French physician François Dessertenne in 1966. Prolongation of the QT interval can increase a person's risk of developing this abnormal heart rhythm.
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In 2001, the FDA changed the labeling requirements for droperidol injection to include a Black Box Warning, citing concerns of QT prolongation and torsades de pointes. The evidence for this is disputed, with 9 reported cases of torsades in 30 years and all of those having received doses in excess of 5 mg. QT prolongation is a dose-related effect, and it appears that droperidol is not a significant risk in low doses. A study in 2015 showed that droperidol is relatively safe and effective for the management of violent and aggressive adult patients in hospital emergency departments in doses of 10mg and above and that there was no increased risk of QT prolongation and torsades de pointes.
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Dysphoria, sedation, hypotension resulting from peripheral alpha adrenoceptor blockade, prolongation of QT interval which can lead to torsades de pointes, and extrapyramidal side effects such as dystonic reactions/neuroleptic malignant syndrome.
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Enhances effects of CNS depressants e.g. alcohol, barbiturates, hypnotics, opioid analgesics, anxiolytics and antipsychotics. Can mask signs of ototoxicity caused by aminoglycosides. QT prolongation (which can lead to torsades de pointes arrhythmia) reported with spiramycin.
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Efavirenz may lengthen the QT interval so should not be used in people with or at risk of torsades de pointes. Efavirenz may cause convulsions in adult and pediatric populations who have a history of seizures.
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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.
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As lenvatinib moderately prolongs QT time, addition of other drugs with this property could increase the risk of a type of abnormal heart rhythm, namely torsades de pointes. No relevant interactions with enzyme inhibitors and inducers are expected.
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Quinidine is also an inhibitor of the cytochrome P450 enzyme 2D6, and can lead to increased blood levels of lidocaine, beta blockers, opioids, and some antidepressants. Quinidine also inhibits the transport protein P-glycoprotein and so can cause some peripherally acting drugs such as loperamide to have central nervous system side effects, such as respiratory depression, if the two drugs are coadministered. Quinidine can cause thrombocytopenia, granulomatous hepatitis, myasthenia gravis, and torsades de pointes (dangerous heart rhythm),Rapid Interpretation of EKG's 6th Ed., Dubin so is not used much today. Torsades can occur after the first dose.
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Hypokalemia is an important cause of acquired long QT syndrome, and may predispose the patient to torsades de pointes. Digitalis use may increase the risk that hypokalemia will produce life-threatening arrhythmias. Hypokalemia is especially dangerous in patients with ischemic heart disease.
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The use of levosimendan is contraindicated in patients with moderate-to-severe kidney impairment, severe liver impairment, severe ventricular filling or outflow obstruction, very low blood pressure and fast heart rate, and/or history of the abnormal heart rhythm torsades de pointes.
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Magnesium therapy is recommended for people with ventricular arrhythmia associated with torsades de pointes who present with long QT syndrome as well as for the treatment of people with digoxin intoxication-induced arrhythmias. There is no evidence to support omega-3 fatty acid supplementation.
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There are concerns of higher rates of QT prolongation and torsades de pointes compared with other SSRIs.Drugs To Avoid 2017 PDF Download The U.S. Food and Drug Administration and Health Canada did not similarly order restrictions on escitalopram dosage, only on its predecessor citalopram.
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Lapatinib-Related Rash and Breast Cancer Outcome in the ALTTO Phase III Randomized Trial.J Natl Cancer Inst. 2016 Apr In clinical studies elevated liver enzymes have been reported. QT prolongation has been observed with the use of lapatinib ditosylate but there are no reports of torsades de pointes.
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Azimilide has been studied for its anti-arrhythmic effects: its converts and maintains sinus rhythm in patients with atrial arrhythmias; and it reduces the frequency and severity of ventricular arrhythmias in patients with implanted cardioverter-defibrillators. Azimilide's most important adverse effect is torsades de pointes, which is a form of ventricular tachycardia.
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Rare but serious adverse effects that may occur as a result of moxifloxacin therapy include irreversible peripheral neuropathy, spontaneous tendon rupture and tendonitis, hepatitis, psychiatric effects (hallucinations, depression), torsades de pointes, Stevens–Johnson syndrome and Clostridium difficile-associated disease, and photosensitivity/phototoxicity reactions. Several reports suggest the use of moxifloxacin may lead to uveitis.
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This effect can be directly linked to QT prolongation mediated predominantly by inhibition of the hERG channel and, in some cases, augmentation of the late sodium channel.Yang, T., Chun, Y. W., Stroud, D. M., et al. Screening for Acute IKr Block is Insufficient to Detect Torsades de Pointes Liability: Role of Late Sodium Current. Circulation (2014) 130:224–234.
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Pimozide overdose presents with severe extrapyramidal symptoms, hypotension, sedation, QT interval prolongation and ventricular arrhythmias including torsades de pointes. Gastric lavage, establishment of a patent airway and, if necessary, mechanically assisted respiration is the recommended treatment for pimozide overdose. Cardiac monitoring should be continued for at least 4 days due to the long half-life of pimozide.
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Gastrointestinal disturbances, such as diarrhea, nausea, abdominal pain, and vomiting, are very common because erythromycin is a motilin agonist. Because of this, erythromycin tends not to be prescribed as a first-line drug. More serious side effects include arrhythmia with prolonged QT intervals, including torsades de pointes, and reversible deafness. Allergic reactions range from urticaria to anaphylaxis.
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Rhythm discrimination will see how regular a ventricular tachycardia is. Generally, ventricular tachycardia is regular. If the rhythm is irregular, it is usually due to conduction of an irregular rhythm that originates in the atria, such as atrial fibrillation. In the picture, an example of torsades de pointes can be seen; this represents a form of irregular ventricular tachycardia.
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The usage of prokinetic agents such as metoclopramide, domperidone, and erythromycin are recommended for those who are septic and unable to tolerate enteral feeding. However, these agents may precipitate prolongation of the QT interval and consequently provoke a ventricular arrhythmia such as torsades de pointes. The usage of prokinetic agents should be reassessed daily and stopped if no longer indicated.
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Magnesium sulfate as a medication is used to treat and prevent low blood magnesium and seizures in women with eclampsia. It is also used in the treatment of torsades de pointes, severe asthma exacerbations, constipation, and barium poisoning. It is given by injection into a vein or muscle as well as by mouth. As epsom salts, it is also used for mineral baths.
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Terodiline is a drug used in urology as an antispasmodic. It relaxes the smooth muscle and used to reduce bladder tone in treatment of urinary frequency and incontinence. Muscle relaxation caused by terodiline, is probably due to its anticholinergic and calcium antagonist activity. However, it also blocks IKr (Kv11.1) channels (see hERG gene) so can pose a risk for torsades de pointes.
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QT-prolonging medications such as clarithromycin, levofloxacin, or haloperidol, when taken concurrently with cytochrome P450 inhibitors, such as fluoxetine, cimetidine, or particular foods including grapefruit, can result in higher-than-normal levels of medications that prolong the QT interval in the bloodstream and therefore increase a person's risk of developing torsades de pointes. At least one mention of the common over-the- counter medication loperamide causing TdP has been made in the literature, although the dose preceding this particular cardiac event was well beyond the therapeutic range of the medication. Loperamide Induced Torsades de Pointes: A Case Report and Review of the Literature In addition, patients with inherited long QT syndrome have a very high risk of episodes of TdP and that risk can be further increased by drugs and electrolyte disorders that further prolong QT.
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The singular and plural forms (torsade de pointes, torsades de pointes and torsades des pointes) have all often been used. The question of whether each one is grammatically "correct" and the others "incorrect" has repeatedly arisen. This is seen among major medical dictionaries, where one enters only the plural form, another enters the plural form as the headword but lists the singular as a variant, and yet another enters the singular form as the headword and gives a usage comment saying that the plural is not preferred. One group of physicians has suggested that it would make the most sense to use the singular form to refer to the arrhythmia entity (where an arrhythmia may involve one or multiple episodes), and that one might best reserve the plural form for describing repeated twisting during a single episode.
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The term ventricular arrhythmia refers to the group of abnormal cardiac rhythms originating from the ventricle, which includes ventricular tachycardia, ventricular fibrillation, and torsades de pointes. In those who have normal blood pressure and strong pulse, the antiarrhythmic medication procainamide may be used. Otherwise, immediate cardioversion is recommended. In those in cardiac arrest due to ventricular tachycardia, cardiopulmonary resuscitation (CPR) and defibrillation is recommended.
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AZCERT focuses on drugs and drug–drug interactions, especially those that cause QT prolongation and Torsades de Pointes (TdP) arrhythmia, and provides its research and its lists of drugsQTdrugs.org free of charge to the public, healthcare providers, and researchers for personal, professional, and non-commercial purposes. To maintain the independence of its work, AZCERT does not receive funding from companies that have a commercial interest in medications.
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Prolonged QTc causes premature action potentials during the late phases of depolarization. This increases the risk of developing ventricular arrhythmias, including fatal ventricular fibrillation. Higher rates of prolonged QTc are seen in females, older patients, high systolic blood pressure or heart rate, and short stature. Prolonged QTc is also associated with ECG findings called Torsades de Pointes, which are known to degenerate into ventricular fibrillation, associated with higher mortality rates.
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Romano–Ward syndrome increases the risk of abnormal heart rhythms or arrhythmias. These are typically a form of ventricular tachycardia known as Torsades de Pointes which can cause faints, seizures, or even sudden death. Less dangerous arrhythmias such as atrial fibrillation also occur, causing symptoms of heart racing or palpitations. However, many of those with Romano–Ward syndrome will remain free from arrhythmias and therefore free from symptoms.
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McDonald was diagnosed with Long QT Syndrome at a young age, which is a rare heart condition that causes delayed repolarization of the heart following a heartbeat which in turn increases the risk of episodes of torsades de pointes. He is also a supporter of Scottish football club Rangers F.C. On 31 August 2019, he got engaged to his American girlfriend, Brandi Sommer, and they married a week later.
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Other factors beyond the QT interval should be taken into account when making a diagnosis, some of which have been incorporated into scoring systems such as the Schwartz score. These factors include a history of characteristic abnormal heart rhythms (Torsades de Pointes), unexplained blackouts (syncope), and a family history of confirmed LQT syndrome. Genetic testing to identify variants in the KCNQ1 or KCNE1 genes can also be used.
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There was a significant reduction in the rate of cardiovascular death, but not in the rate of death from any cause. Later post- hoc analysis of the ATHENA-results showed a significant reduction in the rate of stroke. Patients randomized to dronedarone were more likely to develop bradycardia and QT-interval prolongation (but only 1 case of Torsades). Nausea, diarrhea, rash, and creatinine elevation also were more common in the dronedarone arm.
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Early afterdepolarizations (EADs) occur with abnormal depolarization during phase 2 or phase 3, and are caused by an increase in the frequency of abortive action potentials before normal repolarization is completed. Phase 2 may be interrupted due to augmented opening of calcium channels, while phase 3 interruptions are due to the opening of sodium channels. Early afterdepolarizations can result in torsades de pointes, tachycardia, and other arrhythmias.Cranefield, PF: The Conduction of the Cardiac Impulse.
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These factors include a history of characteristic abnormal heart rhythms (Torsades de Pointes), unexplained blackouts (syncope), and a family history of confirmed LQT syndrome. Other investigations that may suggest a diagnosis of the LQT1 form of Romano–Ward syndrome include paradoxical lengthening of the QT interval in response to exercise (QTc >470 ms at 2–4 minutes of recovery) or during an artificial infusion of adrenaline (lengthening of the absolute QT interval >30 ms during low dose adrenaline).
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Events recorded on electrocardiogram before death included torsades de pointes, premature ventricular contraction (PVC), premature atrial contraction (PAC), supraventricular tachycardia (SVtach), and ventricular tachycardia (Vtach). Most of the children had inguinal hernias, and the majority had, at least, unilateral cryptorchidism. All had neonatal hypotonia progressing to hypertonia, and cerebral atrophy on MRI; several, but not all, had neurogenic scoliosis. Death occurred prior to 2 years in all cases and prior to 1 year in the majority.
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Like other antiarrhythmics, ibutilide can lead to abnormal heart rhythms due to its ability to prolong the QT interval, which can lead to the potentially fatal abnormal heart rhythm known as torsades de pointes. Consequently, the drug is contraindicated in patients that are likely to develop abnormal heart rhythms; this includes persons that have had polymorphic ventricular tachycardia in the past, have a long QT interval, sick sinus syndrome, or a recent myocardial infarction, among others.
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Ventricular tachycardia, which describes a heart rate of over 100 beats per minute with at least three irregular heartbeats as a sequence of consecutive premature beats, can degenerate into ventricular fibrillation, which is rapidly fatal without cardiopulmonary resuscitation (CPR) and defibrillation. Long QT syndrome can cause syncope when it sets off ventricular tachycardia or torsades de pointes. The degree of QT prolongation determines the risk of syncope. Brugada syndrome also commonly presents with syncope secondary to arrhythmia.
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This is because dopamine plays a primary role in regulating prolactin release by binding to D2 receptors on prolactin-secreting cells in the anterior pituitary. Thus, when tiapride blocks these receptors these cells are disinhibited and release more prolactin. The side-effect reported most commonly to the U.S. Food and Drug Administration (FDA) is rhabdomyolysis, a condition characterized by muscle tissue breakdown. Cardiac abnormalities such as prolongation of the QT interval and torsades de pointes have also been observed.
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In one report, 9 of 294 cases of overdose were fatal, and all nine patients had also taken other central nervous system (CNS) depressants. When trazodone overdoses occur, clinicians should carefully monitor for low blood pressure, a potentially serious toxic effect. In a report of a fatal trazodone overdose, torsades de pointes and complete atrioventricular block developed, along with subsequent multiple organ failure, with a trazodone plasma concentration of 25.4 mg/L on admission. There is no specific antidote for trazodone.
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Due to the narrow therapeutic index of flecainide, physicians should be alert for signs of toxicity before life-threatening arrhythmias occur like torsades de pointes. While the toxic effects of flecainide are closely related to the plasma levels of the drug, it is unfeasible to check the plasma concentration in an individual on a regular basis. Signs of flecainide toxicity include marked prolongation of the PR interval and widening of the QRS duration on the surface ECG. There may be signs and symptoms attributable to overt heart failure secondary to sudden decreased myocardial contractility.
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Tendon damage may manifest during and up to a year after fluoroquinolone therapy has been completed. Fluoroquinolones prolong the QT interval by blocking voltage-gated potassium channels. Prolongation of the QT interval can lead to torsades de pointes, a life-threatening arrhythmia, but in practice, this appears relatively uncommon in part because the most widely prescribed fluoroquinolones (ciprofloxacin and levofloxacin) only minimally prolong the QT interval. Clostridium difficile-associated diarrhea may occur in connection with the use of any antibacterial drug, especially those with a broad spectrum of activity such as clindamycin, cephalosporins, and fluoroquinolones.
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Fenspiride (INN, brand names Eurespal, Pneumorel and others) is an oxazolidinone spiro compound used as a drug in the treatment of certain respiratory diseases. The pharmacotherapeutic classification is antitussives. In Russia it was approved for the treatment of acute and chronic inflammatory diseases of ENT organs (ear, nose, throat) and the respiratory tract (like rhinopharyngitis, laryngitis, tracheobronchitis, otitis and sinusitis), as well as for maintenance treatment of asthma.. Russia, Romania, France and other European countries withdrew fenspiride-based drugs from the market due to the risk of QT prolongation and torsades de pointes.
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Prediction of the Risk of Torsade de Pointes Using the Model of Isolated Canine Purkinje Fibres. British Journal of Pharmacology (2005) 144.3:376–385. The anti-emetic agent ondansetron may also increase the risk of developing TdP. It has also been shown as a side effect of certain anti-arrhythmic medications, such as sotalol, procainamide, quinidine, ibutilide, and dofetilide In one example, the gastrokinetic drug cisapride (Propulsid) was withdrawn from the US market in 2000 after it was linked to deaths caused by long QT syndrome-induced torsades de pointes.
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Acquired long QT syndrome Many people with long QT syndrome have no signs or symptoms. When symptoms occur, they are generally caused by abnormal heart rhythms (arrhythmias), most commonly a form of ventricular tachycardia called Torsades de pointes (TdP). If the arrhythmia reverts to a normal rhythm spontaneously the affected person may experience lightheadedness (known as presyncope) or faint which may be preceded by a fluttering sensation in the chest. If the arrhythmia continues, the affected person may experience a cardiac arrest, which if untreated may lead to sudden death.
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T-wave alternans and prolonged QT interval in a male patient found to be in a narrow-complex tachycardia and ruled in for an acute myocardial infarction. Administered Ibutilide and converted to sinus rhythm but subsequently had an episode of Torsades de Pointes which required DC cardioversion back into sinus rhythm. T wave alternans (TWA) is a periodic beat-to-beat variation in the amplitude or shape of the T wave in an electrocardiogram (ECG or EKG) TWA was first described in 1908. At that time, only large variations ("macroscopic" TWA) could be detected.
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Besides becoming an important alternative to organ transplants, ESCs are also being used in field of toxicology and as cellular screens to uncover new chemical entities (NCEs) that can be developed as small molecule drugs. Studies have shown that cardiomyocytes derived from ESCs are validated in vitro models to test drug responses and predict toxicity profiles. ES derived cardiomyocytes have been shown to respond to pharmacological stimuli and hence can be used to assess cardiotoxicity like Torsades de Pointes. ESC-derived hepatocytes are also useful models that could be used in the preclinical stages of drug discovery.
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A 2008 British Medical Journal article highlights that the combination of some macrolides and statins (used for lowering cholesterol) is not advisable and can lead to debilitating myopathy. This is because some macrolides (clarithromycin and erythromycin, not azithromycin) are potent inhibitors of the cytochrome P450 system, particularly of CYP3A4. Macrolides, mainly erythromycin and clarithromycin, also have a class effect of QT prolongation, which can lead to torsades de pointes. Macrolides exhibit enterohepatic recycling; that is, the drug is absorbed in the gut and sent to the liver, only to be excreted into the duodenum in bile from the liver.
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After a contraction has taken place, the cell restores its polarity (or repolarises) by allowing positively charged ions such as potassium to leave the cell, restoring the membrane to its relaxed, polarised state. In long QT syndrome it takes longer for this repolarisation to occur, shown in individual cells as a longer action potential while being marked on the surface ECG as a long QT interval. The prolonged action potentials can lead to arrhythmias through several mechanisms. The arrhythmia characteristic of long QT syndrome, Torsades de Pointes, starts when an initial action potential triggers further abnormal action potentials in the form of afterdepolarisations.
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Some research suggests that delayed afterdepolarisations, occurring after repolarisation has completed, may also play a role in long QT syndrome. This form of afterdepolarisation originates from the spontaneous release of calcium from the intracellular calcium store known as the sarcoplasmic reticulum, forcing calcium out of cell through the sodium calcium exchanger in exchange for sodium, generating a net inward current. While there is strong evidence that the trigger for Torsades de Pointes comes from afterdepolarisations, it is less certain what sustains this arrhythmia. Some lines of evidence suggest that repeated afterdepolarisations from many sources contribute to the continuing arrhythmia.
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Tendon damage may manifest during, as well as up to a year after fluoroquinolone therapy has been completed. FQs prolong the QT interval by blocking voltage-gated potassium channels. Prolongation of the QT interval can lead to torsades de pointes, a life-threatening arrhythmia, but in practice this appears relatively uncommon in part because the most widely prescribed fluoroquinolones (ciprofloxacin and levofloxacin) only minimally prolong the QT interval. Clostridium difficile-associated diarrhea may occur in connection with the use of any antibacterial drug, especially those with a broad spectrum of activity such as clindamycin, cephalosporins, and fluoroquinolones.
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A variety of drugs can present prolongation of the QT interval as a side effect. Prolongation of this interval is a result of a delay in sodium and calcium channel inactivation; without proper channel inactivation, the threshold potential is reached prematurely and thus arrhythmia tends to result. These drugs, known as pro-arrhythmic agents, include antimicrobials, antipsychotics, methadone, and, ironically, antiarrhythmic agents. The use of such agents is particularly frequent in intensive care units, and special care must be exercised when QT intervals are prolonged in such patients: arrhythmias as a result of prolonged QT intervals include the potentially fatal torsades de pointes, or TdP.
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At lower doses, the person may only experience a headache due to an increase in blood pressure. In response to these adverse effects, a different type of MAOI has been developed: the reversible inhibitor of monoamine oxidase A (RIMA) class of drugs. Their primary advantage is that they do not require the person to follow a special diet, while being purportedly effective as SSRIs and tricyclics in treating depressive disorders. Tricyclics and SSRI can cause the so-called drug-induced QT prolongation, especially in older adults; this condition can degenerate into a specific type of abnormal heart rhythm called torsades de points which can potentially lead to sudden cardiac arrest.
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Fluoxetine can affect the electrical currents that heart muscle cells use to coordinate their contraction, specifically the potassium currents Ito and IKs that repolarise the cardiac action potential. Under certain circumstances, this can lead to prolongation of the QT interval, a measurement made on an electrocardiogram reflecting how long it takes for the heart to electrically recharge after each heartbeat. When fluoxetine is taken alongside other drugs that prolong the QT interval, or by those with a susceptibility to long QT syndrome, there is a small risk of potentially lethal abnormal heart rhythms such as Torsades de Pointes. As of 2019, the drug reference site CredibleMeds lists Fluoxetine as leading to a conditional risk of arrhythmias.
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Prenylamine (Segontin) is a calcium channel blocker of the amphetamine chemical class which was used as a vasodilator in the treatment of angina pectoris; it was introduced in the 1960s by German manufacturer Albert-Roussel pharma gmbh which was acquired by Hoechst AG in 1974 and which in turn became part of Sanofi Aventis in 2005. It was withdrawn from market worldwide in 1988 because it caused QT prolongation and Torsades de pointes which in turn caused sudden death. The cardiac side effects were not detected during clinical development, but only emerged after the drug was widely used. Prenylamine has two primary molecular target in human, Calmodulin and Myosin light-chain kinase 2 found in skeletal and cardiac muscle.
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If a person with WPW experiences episodes of atrial fibrillation, the ECG shows a rapid polymorphic wide-complex tachycardia (without torsades de pointes). This combination of atrial fibrillation and WPW is considered dangerous, and most antiarrhythmic drugs are contraindicated. When an individual is in normal sinus rhythm, the ECG characteristics of WPW are a short PR interval (less than 120 milliseconds in duration), widened QRS complex (greater than 120 milliseconds in duration) with slurred upstroke of the QRS complex, and secondary repolarization changes (reflected in ST segment-T wave changes). In individuals with WPW, electrical activity that is initiated in the SA node travels through the accessory pathway, as well as through the AV node to activate the ventricles via both pathways.
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Quinine can cause unpredictable serious and life-threatening blood and cardiovascular reactions including low platelet count and hemolytic-uremic syndrome/thrombotic thrombocytopenic purpura (HUS/TTP), long QT syndrome and other serious cardiac arrhythmias including torsades de pointes, blackwater fever, disseminated intravascular coagulation, leukopenia, and neutropenia. Some people who have developed TTP due to quinine have gone on to develop kidney failure. It can also cause serious hypersensitivity reactions include anaphylactic shock, urticaria, serious skin rashes, including Stevens–Johnson syndrome and toxic epidermal necrolysis, angioedema, facial edema, bronchospasm, granulomatous hepatitis, and itchiness. The most common adverse effects involve a group of symptoms called cinchonism, which can include headache, vasodilation and sweating, nausea, tinnitus, hearing impairment, vertigo or dizziness, blurred vision, and disturbance in color perception.
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Clomipramine may interact with a number of different medications, including the monoamine oxidase inhibitors which include isocarboxazid, moclobemide, phenelzine, selegiline and tranylcypromine, antiarrhythmic agents (due to the effects of TCAs like clomipramine on cardiac conduction. There is also a potential pharmacokinetic interaction with quinidine due to the fact that clomipramine is metabolised by CYP2D6 in vivo), diuretics (due to the potential for hypokalaemia (low blood potassium) to develop which increases the risk for QT interval prolongation and torsades de pointes), the selective serotonin reuptake inhibitors (SSRIs; due to both potential additive serotonergic effects leading to serotonin syndrome and the potential for a pharmacokinetic interaction with the SSRIs that inhibit CYP2D6 [e.g. fluoxetine and paroxetine]) and serotonergic agents such as triptans, other tricyclic antidepressants, tramadol, etc. (due to the potential for serotonin syndrome).
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