CLINICAL UPDATES ON DRUG – INDUCED CARDIOTOXICITYHTML Full Text
CLINICAL UPDATES ON DRUG - INDUCED CARDIOTOXICITY
Ashif Iqubal 1, Syed Ehtaishamul Haque*2, Sumit Sharma 2, Mohd. Asif Ansari 2, Vasim Khan 2 and Mohammad Kashif Iqubal 3
Translam Institute of Pharmaceutical Education and Research 1, Mawana Road, Meerut - 250001, Uttar Pradesh, India.
Department of Pharmacology 2, Department of Pharmaceutics 3, School of Pharmaceutical Education and Research, Jamia Hamdard, New Delhi - 110062, Delhi, India.
ABSTRACT: Cardiotoxicity associated with the clinically used drugs is a global concern of safety for healthcare professionals. Various animal models have been used to study the drug-induced cardiotoxicity but the exact molecular involvement of toxicity is not much clear. Despite the recurrent occurrence of toxicities, drugs such as doxorubicin, calcium channel blockers, antiarrhythmics and immunomodulators are regularly used. Anticancer drugs mainly anthracyclines, 5- fluorouracil and cyclophosphamide exert prominent cardio-toxicity. Till date, there is only one drug approved for doxorubicin-related cardiotoxicity i.e. dexrazoxane. Few other drugs are used routinely by clinicians to reduce the severity of toxicity which includes ACE inhibitors, L-carnitine, probucol, CoQ10, N-acetylcysteine, Vitamin E and deferoxamine, whereas antidepressants drugs, specifically tricyclic antidepressants are potential candidates for cardiotoxicity. Calcium channel blockers, antiarrhythmic and beta receptor antagonist aggravate cardiac heart failure (CHF) and left ventricular arrhythmia. Interferons, mainly interferon-α is also associated with prominent and dose-dependant toxicity. Some other drugs like zidovudine, chloroquine, cocaine, minoxidil, ketoconazole, prostaglandin E2 and anagrelide are also reported to have cardiotoxic effects. A complication associated with the use of these drugs include hypoxia, coronary ischemia, calcium overload, oxidative stress, contractile dysfunction, left ventricular arrhythmia and cardiomyopathy
Left ventricular dysfunction, Oxidative stress
INTRODUCTION: Cardiotoxicity is the common side effect of many drugs 1 among which anticancer drugs, specifically anthracycline class of drugs exert severe cardiotoxicity 2. Other drugs that cause cardiotoxicity are amphetamine, mitomycin, paclitaxel and zidovudine 3, 4. The common mechanism leading to cardiotoxicity is oxidative stress, generation of free radicals and hypoxia 5.
Long-term exposure to cardiotoxic drugs further causes apoptosis and deregulation of myo-contractility. Cardiotoxic effect of drugs can be understood in two ways. (1) Drugs causing cardiac injury by affecting the performance of cardiac muscles. (2) By altering the ion channels and pump (voltage-gated sodium and potassium ion channel and Na+ - K+ ATPase pump) 4. Exposure to the cardiac-toxic drugs induces prolong cardiac repolarization (QT interval) and causes arrhythmia (Torsades de pointes) 4. Since these drugs causes cardiotoxicity as side effect, they can be used as cardiotoxicity inducing agents in preclinical experimental models 6. In this review we are going to focus on the Cardiotoxicity of drugs only and not the experimental models.
List of cardiotoxic drugs is shown in Table 1 and effect of cardiotoxic drug is displayed in Fig. 1 7.
FIG. 1: EFFECT OF CARDIOTOXIC DRUGS ON HEART THROUGH DIFFERENT MECHANISMS
TABLE 1: LIST OF CLINICALLY USED DRUGS THAT EXERT CARDIOTOXIC EFFECT 8
|S. no.||Drug||Class||Mode of action||Use|
|1||Doxorubicin||Anticancer||Inhibit progression of topoisomerase II||Breast cancer, bladder cancer, lymphoma, Kaposi's sarcoma.|
|2||Daunorubicin||Anticancer||Inhibit progression of topoisomerase II||Kaposi's sarcoma, lymphoma, myelogenous leukemia|
|3||Idarubicin||Anticancer||Inhibit progression of topoisomerase II||Acute myeloid leukemia.|
|4||Cyclophosphamide||Anticancer||Bind at 7 guanine residue and inhibit cell division||Lymphoma, multiple myeloma, ovarian, breast and lung cancer.|
|5||5 fluorouracil||Anticancer||Thymidylate synthase inhibitor, inhibit DNA replication.||Colon, stomach, esophageal, pancreatic, breast and cervical cancer|
biocrystallization of hemozoin
|Arthritis, malaria, lupus erythematosus|
|7||Cocaine||Stimulant||Inhibit MAO uptake||Numbing agent|
|8||Cytarabine||anticancer immunosuppressant||Inhibit DNA and RNA
|AML, CML and non-Hodgkin’s lymphoma|
|9||Paclitaxel||Anticancer||Act on tubulin and causes instability of cytoskeleton causes cell cycle arrest||kapski sarcoma, ovarian, breast, lung, cervical, and pancreatic cancer|
|10||Mitomycin||Anticancer||Inhibit DNA cross linking||Adenocarcinoma, anal, bladder, breast, cervical, colorectal and lung cancer.|
|11||Imatinib||Anticancer||Tyrosine kinase inhibitor||CML, gastrointestinal stromal tumors, plexiform neurofibromas.|
|12||Sunitinib||Anticancer||Tyrosine kinase inhibitor||Renal cell carcinoma and gastrointestinal stromal tumors.|
|Act through PI3K/Akt pathway||Breast cancer|
|14||Zidovudine||Antiretroviral||Inhibit HIV’s reverse
|HIV and HAART|
|15||Mitoxantrone||Anticancer||Topoisomerase II inhibitor||Metastatic breast cancer, acute myeloid and lymphoblastic leukemia|
|16||Stibogluconate||Antileishmanial||Topoisomerase I inhibitor||Leishmaniasis|
|17||Minoxidil||Antihypertensive||Potassium channel opener||Alopecia, hypertension|
|18||Calcium channel blocker||Antihypertensive||Block calcium entry into cell||Control heart Beat and prevent cerebral vasospasm|
|19||Interteron||Signaling protein||activate JAS-STAT and PI3K/ Akt pathway||Autoimmune disorder, cutenous, hairy and myeloid leukemia, hepatitis C|
|20||Cyclosporine||Immunosuppressant||Inhibit the phosphatase activity of calcineurin||Graft rejection, rheumatoid arthritis, psoriasis, UC and dry eye|
|21||Bromocriptine||Dopamine agonist||Inhibit the release of glutamate||Pituitary tumor, hyperprolactinemia, PD, type-2 diabetes|
|22||Methylphenidate||CNS stimulant||Dopamine reuptake inhibition||Bipolar disorder and major depressive disorder|
|23||Amphetamine||CNS stimulant||Enhances dopaminergic activity and inhibit MAO transport||Attention deficit hyperactivity syndrome, narcolepsy, depression|
|24||Methamphetamine||CNS stimulant||Enhances dopaminergic activity and inhibit MAO transport||Attention deficit hyperactivity syndrome, narcolepsy, obesity and depression|
|25||Anabolic steroid||Anabolic-androgenic steroid||Binds to the androgenic receptor & initiate anabolism cascade||Bone marrow, growth and appetite stimulant, male contraception, HRT|
|26||Clozapine||Atypical antipsychotic||Bind with dopamine and serotonin receptor||Psychosis, schizophrenia and parkinsonism|
|27||Anagrelide||Platelet reducing agent||Inhibit maturation of platelets from megakaryocytes||Essential thrombocytosis and chronic myeloid leukemia.|
|28||Tricyclic antidepressant||Antidepressant||Block serotonin and norepinephrine transport||Depressive disorder and dysthymia|
|29||Ephedrine||Adrenergic stimulant||Stimulate adrenergic receptor and increase activity of norepinephrine||Antihypertensive, spinal anesthesia, asthma, nasal congestion and obesity|
|30||Catecholamine||Neuromodulator||Stimulate adrenergic receptor and increase activity of norepinephrine||Bradycardia, hypotension and hypoglycemia|
|31||Isoproterenol||Non-selective beta-adrenoreceptor agonist||Stimulate adrenergic receptor||CHF, shock, treatment of airway constriction and bradycardia|
|32||Pentamidine||antimicrobial||Interfare with host DNA, RNA, protein and phospholipid synthesis||Leishmaniasis, babesiosis and pneumocystis pneumonia.|
|33||Ethanol||Addictive psychoactive||Bind with GABA and increases the activity||Antiseptic, antidote and medicinal solvent.|
|34||Arsenic||Heavy metal||Interfere with host DNA, RNA, protein and phospholipids synthesis||In antibiotics, syphilis and trypanosomiasis|
|35||Cobalt||Heavy metal||Interfere with host DNA, RNA, protein and phospholipids synthesis||Radiation treatment, metabolism regulator and cofactors.|
|36||Diazoxide||Potassium channel activator||Increase permeability to potassium and block permeability for calcium ion, modulate AMPA and kainate receptor||Malignant hypertension and insulinoma.|
|37||NSAIDs||COX inhibitor||Non-selective inhibitor of COX enzyme||Analgesic, antipyretic and anti-inflammatory|
|38||Interleukin-2||cytokines||Stimulate and growth of T cell, release histamine, anti-inflammatory activity||Autoimmune disorder|
|39||Ketoconazole||Antifungal||Interfere with the fungal ergosterol synthesis and some enzymes||Athlete's foot, ringworm, candidiasis, and other fungal infection|
|40||Prostaglandin E2||oxytocics||Activate Wnt signaling pathway||Termination of pregnancy and labor induction.|
|41||Ifosfamide||anticancer||Bind at 7 guanine residue and inhibit of cell division||Testicular, bladder, cervical, ovarian, lung and soft tissue cancer, sarcoma and osteosarcoma.|
MAO: Monoamine oxidase, AML: Acute myeloid leukemia, CML: Chronic myeloid leukemia, HAART: highly active antiretroviral therapy, UC: ulcerative colitis, PD: Parkinson’s disease, HRT: Hormonal replacement therapy, CHF: Congestive heart failure, COX: cycloxygenase
- Anthracycline and Cardiotoxicity: Anthracycline class of drugs are the first line anticancer drugs but their usage are limited due to cardiotoxicity 9. Doxorubicin (adriamycin) and daunorubicin (daunomycin or rubidomycin) are two members of anthracycline group 10. These two drugs are obtained from actinobacteria ‘Streptomyces peucetius’ 11. Anthracycline-induced cardiotoxicity can be acute which may cause arrhythmia, myocarditis, pericarditis or acute left ventricular failure. These symptoms subside just after withdrawal of treatment but restrict the further use of the drug 12.
Anthracycline can also cause cardiomyopathy on the chronic use and sometime late-onset of severe arrhythmia and ventricular dysfunction has been seen 12. It has been observed that rate of survival with anthracycline is much lesser than those of ischemic or dilated cardiomyopathy 13. Doxorubicin induced cardio-toxicity is dose dependent and controlled monitoring of dose is the best possible way to prevent toxicity 13. Now-a-days echocardiography is used to monitor doxorubicin-induced cardiotoxicity and this is considered as gold standard test 14.
1.1 Mechanism of Anthracycline - Induced Cardiotoxicity: Generally, chemotherapeutic drugs induced cardiotoxicity is associated with the myocardial cell loss, apoptosis or necrosis which may be mediated by oxidative stress directly or indirectly 15. In practice, determination of exact mechanism of doxorubicin-induced cardiotoxicity is not possible because most of the time patient are on multiple therapies 16, 17. There are four hypothesis proposed on the subject of anthracycline-induced cardiotoxicity 18.
(a) Iron and free radical theory in which occurrence of high oxidative stress and depletion of endogenous antioxidant is observed. Myocardium mitochondria are the central point of oxidative stress 18.
(b) Metabolic hypotheses in which C-13 alcoholic metabolite of anthracycline acts on the myocardium and hamper the myocardial energy pathway and intracellular calcium concentrations 18.
(c) Unifying hypothesis in which C-13 alcoholic metabolite is further acted by oxidative stress which results in increased calcium concentration at the interior of myocardial fiber and damages the cell. This may further enhance the lipid peroxidation and loss of selective membrane permeability 18.
(d) Apoptosis hypothesis in which there is upregulation of pro-apoptotic markers like Bax, caspase and cytochrome c, whereas downregulation of anti-apoptotic markers like Bcl-2, Akt, and PIKT3 pathway 18.
Keeping all these theories in view, the role of free radicals occupy the central position. It has been hypothesized that the oxidative stress not only causes myocardial death but directly affects excitation-contraction properties of cardiac muscles 9, 19. Free radicals mainly nitrite free radicals are the major culprit of oxidative stress 20.
1.2 Cardioprotective Agents Against Anthracycline - Induced Cardiotoxicity: Drugs used clinically for prevention of anthracycline (doxorubicin) induced toxicity are shown in Table 2.
TABLE 2: CLINICALLY USED DRUGS FOR PREVENTION OF ANTHRACYCLINE - INDUCED TOXICITY 21, 22
|1||ACE inhibitors: systolic heart failure
(first line therapy)
|2||Dexrazoxane: approved drugs for
Unfortunately, none of the drugs till date is clinically established as a cardioprotective agent against anthracycline (doxorubicin - induced toxicity) 22.
- Cyclophosphamide and Cardiotoxicity: Cyclophosphamide is an alkylating agent that acts on 7 guanine residue 23. The active metabolite of cyclophosphamide is responsible for anticancer activity 24. However, cardiomyopathy which is likely to be diagnosed within 2 weeks of therapy is reported as a side effect 4. Cardiotoxicity of cyclophosphamide is due to the effect of toxic metabolite on endothelial cells that causes severe myopericarditis and myocardial necrosis 25. If a patient suffers from congestive heart failure (CHF) and get exposed to cyclophosphamide, there is a high chance of death within two weeks 26. In an in-clinic study, 19 women suffering from metastatic breast cancer were given cyclophosphamide at low dose with continuous infusion for 96 hours. It was observed that low dose for the longer duration of therapy increased the therapeutic response and chance of developing CHF 26.
- Paclitaxel and Cardiotoxicity: Paclitaxel belongs to taxane class of drugs that act by promoting the polymerization of tubulin 27. Thus microtubule formed due to the activity of paclitaxel is unstable and interfere with the cell division at the interphase of the cell cycle. This interference finally leads to cell death 27. Paclitaxel is the choice of drug in ovarian and breast cancer 28, 29. Asymptomatic bradycardia is most common side effect 30. 29% of patients undergoing paclitaxel therapy are likely to suffer from bradycardia 31, 32. In a study, combined therapy of doxorubicin with paclitaxel induces CHF in six patients out of 33. This occurrence of 18% CHF in patient raised a valid question for combined therapy of paclitaxel and doxorubicin 33.
- Mitoxantrone and Cardiotoxicity: Mitoxantrone is structurally similar to doxorubicin 34. This drug is reported to be associated with left ventricular heart failure 35. In a study when mitoxantrone was used in 805 patients, 1.5% of patient developed CHF, whereas another 1.5% of the patient showed decreased left ventricular ejection fraction 36. In conclusion, mitoxantrone has potential to induce cardiotoxicity and caution must be taken while using it.
- Antimetabolite [5 –fluorouracil (5-FU), cytarabine and Capecitabine] and Cardiotoxicity: Among all antimetabolites, 5-FU is most extensively studied drugs in term of cardiotoxicity 37. It has a direct effect on myocardial cells and on endothelial cells 38. Mononuclear inflammations and myocardial necrosis have been observed in a patient who died from myocardial infarction followed by 5-FU therapy 39. 5-FU also induces myocardial hypoxia, CHF and dilated cardiomyopathy have been reported 39. Capecitabine, on the other hand, causes ischemia 40 and cytarabine has been reported for pericarditis 41.
Thus looking into features and shortcomings of these anticancer drugs, some newer drugs have been developed with the aim of targeted therapy 42. These drugs may offer an advantage in terms of selectivity for cancer cells and less systemic toxicity 42. Some of these drugs are trastuzumab, imatinib and bevacizumab 43 - 44. Some of the targeting newer drugs also showed cardiotoxicity e.g., tyrosine kinase inhibitor (sunitinib and imatinib) have been reported with CHF and hypertension 45.
- Antidepressant Drugs and Cardiotoxicity: In today’s scenario, depression is getting common etiology in most of the chronic disorders 46. More often antidepressant drugs are used by clinicians 47, which are of 3 major classes (1) tricyclic antidepressant (TCA) (2) selective serotonin reuptake inhibitor (SSRIs) and (3) monoamine oxidase inhibitor (MAO inhibitors) 26. Among these three classes of drugs, with TCA such as (amitriptyline, amoxapine, desipramine, doxepin, imipramine, nortriptyline protriptyline and trimipramine), the related cardiotoxicity is more common 48. Nearly 20% of the patient often suffers from postural hypotension 49. This side effect becomes more severe when the patient has existing cardiac co-morbid complications 50. There are reports of altering atrioventricular conduction 51. A possible mechanism was supposed to be a prolongation of the duration of QRS interval 52. Sudden death has also been reported with the use of antidepressant drugs 53. TCA is extensively concentrated in the myocardium 54 and it causes cardiotoxicity by interfering with reuptake of adrenergic amines 55, altering myocardial membrane permeability 55 and by direct action on myocardial 55. Finally, TCA leads to altered cardiac rhythm and myocardium contractility 55. There are published evidence of CHF with a number of TCA 56. On the other hand, SSRIs are related with a lesser incidence of cardiac side effect 57. Although few study has been performed on the cardio-toxicity of SSRIs 58.
- Calcium Channel Blockers and Cardiotoxicity: Calcium channel blockers (CCBs) are one of the extensively used drugs in cardiac complications, mainly in angina pectoris 59. There is an area of debate on the use of CCBs in patients with existing left ventricular dysfunction 60. Clinically used CCBs are classified into three groups 26.
(1) Phenylethylamine viz. verapamil. (2) dihydropyridines viz. nifedipine, and (3) benzothiazepines viz. diltiazem 26. There is a report of cardiotoxicity with the use of CCBs which include negative ionotropic effect, activation of rennin-angiotensin system and alteration in membrane calcium transport 61. There is always a high chance of marked hemodynamic alteration in patients of CHF taking CCBs 62. In a multicentre dilitiazem post-infarction trial (MDPIT), risk of CHF was found to be increased 63. It has been seen clinically that the chronic use of nifedipine in a patient of existing CHF exert deleterious effects 64.
- Antiarrhythmic drugs and Cardiotoxicity: Adverse effect related to antiarrhythmic drugs is related to its cardio depressant and negative ionotropic effect 65. If the patient is already suffering from left ventricular dysfunctions, antiarrhythmic drugs can further worsen the situation 66. Negative ionotropy of drugs vary from class to class, as class III antiarrhythmic drugs are devoid of negative inotropy 67. Antiarrhythmic drugs induced negative inotropy is regulated by an alteration in intracellular calcium concentration 68. There are randomized double blinded placebo controlled trials which showed the increased risk of CHF in the patients who were taking antiarrhythmic drugs 69. Thus it can be concluded that almost all antiarrhythmic drug have potential to exert a negative inotropic effect, therefore, utmost caution and monitoring is required while using antiarrhythmic drugs 65.
- Beta - Adrenoceptor Antagonist and Cardiotoxicity: Beta - Adrenoceptor antagonists are commonly known as beta blockers. These drugs cause negative chronotropic and inotropic effects and exacerbate CHF 70. Interestingly when beta blocker was used topically for treatment of glaucoma, it additionally caused CHF 71. In an epidemiological study, no association between the use of topical beta blockers and CHF was found 72. Similarly, a trial with carvedilol revealed the reduced mortality in patients suffering from CHF 26. Thus in order to control beta blocker induced cardiotoxicity (CHF), the initial dose should be low and can be gradually increased 26.
- Interferon and Cardiotoxicity: There are three types of interferon used clinically i.e. interferon alpha, beta and gamma 73. Interferon-alpha has been reported with a cardiotoxic effect which includes hypertension and arrhythmia starting from 1st day of treatment 74. It has been reported that almost 5 - 15% of patients suffer from interferon-mediated cardiotoxicity 75. Other cardio-toxicities of interferon include cardiomyopathy and cardiac ischemia 76. The possible mechanism proposed for the interferon alpha - induced cardiotoxicity is hypoxia, interference with energy metabolism and increased oxygen demand 77.
- Interleukin-2 (IL-2) and Cardiotoxicity: IL-2 is an approved drug for the treatment of metastatic renal cell carcinoma. IL-2 is associated with deleterious cardiovascular side effects 78. Reversible left ventricular dysfunction, tachycardia and hypotension are more often reported with the use of IL-2 78. Use of IL-2 initiates the production of cytokines which further affect myocardium contractility 78.
- Amphetamines / Methamphetamines and Cardiotoxicity: Amphetamine class of drugs are the common drugs used by athletes and often associated with doping 79. These drugs act centrally and cause stimulation which includes euphoria, intensifies emotions and increases sexuality 80. This drug enhances neuronal reuptake of norepinephrine, serotonin and dopamine 81. A clinical study has reported the incidence of acute coronary syndrome in 25% of patients taking these drugs 82. Methamphetamine is reported to be associated with 18% and 40% of incidence of cardiomyopathy 83, 84. Similarly, in other clinical study methamphetamine is associated with the incidence of 40% cardiomyopathy 84. There was an animal study which supported the fact that repeated administration of methamphetamine caused cardiac hypertrophy, necrosis, myocarditis, inflammation, left ventricular dysfunction and left ventricular dilatation 85. Amphetamine and methamphetamine when administered metabolize into catechol that further causes oxidative stress and cardiomyopathy 86.
- Cocaine and Cardiotoxicity: Cocaine is an alkaloid obtained from Erythroxylon coca which is a native plant of South America 87. Initially, it was used as a local anaesthetic but later its use as an ingredient in cola drink started 88. Pharmacology of cocaine consists of inhibition of catecholamine uptake by dopamine and norepinephrine transporter at the pre-synaptic neurons. This results in the accumulation of catecholamines at the postsynaptic neuron 89 which causes increased psychomotor and sympathetic activity 89. Cocaine also causes the release of norepinephrine and epinephrine from the adrenal medulla that result in severe vasoconstriction 89. Use of cocaine is associated with myocardial ischemia or myocardial infarction 90. Cocaine also causes tachycardia and increases systolic - diastolic blood pressure 91. Chronic use of cocaine causes vasoconstriction of coronary artery and thrombosis which together decreases oxygen supply to the myocardium and induces myocardial ischemia 91. Acute administration of cocaine causes an increase in intracellular calcium concentration and stimulates arrhythmia 92. Literature supports four mechanisms for the cardiotoxicity of cocaine.
13.1 Promotion of Intracoronary Thrombus Formation: Cocaine administration causes platelet aggregation and increases thromboxane - A2 production which together contributes to the development of cardiomyopathy and left ventricular dysfunction 93.
13.2 Sympathomimetic Effect of Cocaine: Cocaine use results in activation of the beta-adrenergic receptor and increases myocardial contraction which finally leads to increased blood pressure and increased wall stress 93.
13.3 Increased Calcium Flux: Increased myocardial calcium flux into the myocardial cell causes membrane instability and arrhythmia 93.
13.4 Electrophysiological Effects: Use of cocaine causes prolongation of PR, QRS and QT duration that result into arterial fibrillation and tachycardia 93.
- Anabolic - Androgenic Steroids and Cardio-Toxicity: Inappropriate use of anabolic steroid is associated with left ventricular hypertrophy 94. Anabolic steroid when administered, binds with androgenic receptors in the heart and in arteries 4. Anabolic steroid causes hypertension, dyslipidemia atherosclerosis and impaired contraction-relaxation 95. Animal studies have shown the increased risk of cardiomyopathy and apoptosis in cardiac cells 96. Further, use of anabolic steroid causes the discrete release of calcium from sarcoplasmic reticulum which additionally worsens the situation of arrhythmia and cardiomyopathy 95. Some other complications associated with the use of steroid includes endocardial and myocardial fibrosis, cardiac steatosis, myocardial necrosis, coagulation and coronary atheroma 3.
- Alcohol Abuse / Heavy Metals and Cardio-toxicity: Alcohol abuse primarily affects the central nervous system but it also exerts direct cardiotoxic effects 97, 98. There are documented evidence for dose-related cardiotoxicity for ethanol that includes left ventricular dysfunction and cardiomyopathy 99. Alcohol consumption affects the myocardial contractility, systolic-diastolic deregulations and abnormal rhythm 100. There are also documented evidence for dose-related cardiac depression 100. Ethanol when exceeds the limit of 75 mg/100 ml in plasma, the force of contraction reduces significantly 101. Some heavy metals such as cadmium, lead, and cobalt also causes cardiotoxicity 102. These heavy metal causes a structural change in cardiac cells, alter myocardial contraction and deregulation of some essential enzymes in heart muscles 102.
15.1 Trigger of Torsade de pointis and Cardiotoxicity: QT prolongation is a standard parameter to study cardiac abnormalities 103. Further, prolongation of QT may be responsible for the sudden death and is called Torsade de Pointes 104. This type of arrhythmia is defined as the polymorphic ventricular tachycardia 105. Torsades de pointis are very complicated and serious situation which often shift to ventricular fibrillation 106. Drugs associated with increased risk of Torsade de Pointes are shown in Table 3 107.
TABLE 3: DRUGS ASSOCIATED WITH INCREASED RISK OF TORSADE DE POINTES 107
CONCLUSION: Now-a-days cardiac complication is increasing day by day. Polypharmacy approach, on the other hand is responsible for the occurrence of secondary disorders such as hypertension and arrhythmia. There are many drugs which are co-administered with existing therapy and further worsen the cardiac complications. Beta blockers, calcium channel blockers, antiarrhythmic drugs, anticancer drugs and immunomodulatory drugs are routinely used by the clinician, thus appropriate monitoring is a prerequisite for the use of these drugs. Particularly in patients with left ventricular dysfunction, utmost precaution should be taken for cardiac toxicity of prescribed medicine. Although, drug - induced cardiomyopathy doesn’t occur frequently, a regular monitoring is advised to prevent any such situation while using the discussed therapeutic agents.
ACKNOWLEDGEMENT: The authors would like to thank Department of Pharmacology, Jamia Hamdard for providing the facilities.
CONFLICT OF INTEREST: Nil
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How to cite this article:
Iqubal A, Haque SE, Sharma S, Ansari MA, Khan V and Iqubal MK: Clinical updates on drug-induced cardiotoxicity. Int J Pharm Sci Res 2018; 9(1): 16-26.doi: 10.13040/IJPSR.0975-8232.9(1).16-26.
All © 2013 are reserved by International Journal of Pharmaceutical Sciences and Research. This Journal licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License.
A. Iqubal, S. E. Haque*, S. Sharma, Mohd. A. Ansari, V. Khan and M. K. Iqubal
Department of Pharmacology, School of Pharmaceutical Education and Research, Jamia Hamdard (Hamdard University), New Delhi, India.
05 May, 2017
26 July, 2017
11 August, 2017
01 January, 2018