Cardiovascular adverse effects of antipsychotic drugs. 2000

N A Buckley, and P Sanders
Department of Clinical Pharmacology, Royal Adelaide Hospital, South Australia, Australia. nbuckley@hypertox.com

Minor cardiovascular adverse effects from antipsychotic drugs are extremely common. They include effects such as postural hypotension and tachycardia due to anticholinergic or alpha1-adrenoceptor blockade, and may occur in the majority of patients at therapeutic dosages. There are a number of pharmacological effects that are of uncertain clinical significance, such as blockade of calmodulin, sodium and calcium channels and alpha2-adrenoceptors in the central nervous system. The most serious consequences of treatment, arrhythmias and sudden death, are probably uncommon and are most likely to be caused primarily by blockade of cardiac potassium channels such as HERG. Incomplete evidence suggests that arrhythmias and sudden death are a particular problem with certain drugs (thioridazine and droperidol), high risk populations (elderly, pre-existing cardiovascular disease, inherited disorders of cardiac ion channels or of antipsychotic drug metabolism) or people taking interacting drugs (such as drugs that prolong the QT interval, e.g. tricyclic antidepressants, drugs that inhibit antipsychotic drug metabolism, or diuretics). Clozapine may be unique in also causing death from myocarditis and cardiomyopathy. Much further research is required to more clearly identify high risk drugs and the populations that are at risk of sudden death, as well as the mechanisms involved and the extent of the risk.

UI MeSH Term Description Entries
D007024 Hypotension, Orthostatic A significant drop in BLOOD PRESSURE after assuming a standing position. Orthostatic hypotension is a finding, and defined as a 20-mm Hg decrease in systolic pressure or a 10-mm Hg decrease in diastolic pressure 3 minutes after the person has risen from supine to standing. Symptoms generally include DIZZINESS, blurred vision, and SYNCOPE. Hypotension, Postural,Orthostatic Hypotension,Postural Hypotension
D002147 Calmodulin A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels. Calcium-Dependent Activator Protein,Calcium-Dependent Regulator,Bovine Activator Protein,Cyclic AMP-Phosphodiesterase Activator,Phosphodiesterase Activating Factor,Phosphodiesterase Activator Protein,Phosphodiesterase Protein Activator,Regulator, Calcium-Dependent,AMP-Phosphodiesterase Activator, Cyclic,Activating Factor, Phosphodiesterase,Activator Protein, Bovine,Activator Protein, Calcium-Dependent,Activator Protein, Phosphodiesterase,Activator, Cyclic AMP-Phosphodiesterase,Activator, Phosphodiesterase Protein,Calcium Dependent Activator Protein,Calcium Dependent Regulator,Cyclic AMP Phosphodiesterase Activator,Factor, Phosphodiesterase Activating,Protein Activator, Phosphodiesterase,Protein, Bovine Activator,Protein, Calcium-Dependent Activator,Protein, Phosphodiesterase Activator,Regulator, Calcium Dependent
D002319 Cardiovascular System The HEART and the BLOOD VESSELS by which BLOOD is pumped and circulated through the body. Circulatory System,Cardiovascular Systems,Circulatory Systems
D002986 Clinical Trials as Topic Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries. Clinical Trial as Topic
D003645 Death, Sudden The abrupt cessation of all vital bodily functions, manifested by the permanent loss of total cerebral, respiratory, and cardiovascular functions. Sudden Death
D004347 Drug Interactions The action of a drug that may affect the activity, metabolism, or toxicity of another drug. Drug Interaction,Interaction, Drug,Interactions, Drug
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000328 Adult A person having attained full growth or maturity. Adults are of 19 through 44 years of age. For a person between 19 and 24 years of age, YOUNG ADULT is available. Adults
D000368 Aged A person 65 years of age or older. For a person older than 79 years, AGED, 80 AND OVER is available. Elderly
D014150 Antipsychotic Agents Agents that control agitated psychotic behavior, alleviate acute psychotic states, reduce psychotic symptoms, and exert a quieting effect. They are used in SCHIZOPHRENIA; senile dementia; transient psychosis following surgery; or MYOCARDIAL INFARCTION; etc. These drugs are often referred to as neuroleptics alluding to the tendency to produce neurological side effects, but not all antipsychotics are likely to produce such effects. Many of these drugs may also be effective against nausea, emesis, and pruritus. Antipsychotic,Antipsychotic Agent,Antipsychotic Drug,Antipsychotic Medication,Major Tranquilizer,Neuroleptic,Neuroleptic Agent,Neuroleptic Drug,Neuroleptics,Tranquilizing Agents, Major,Antipsychotic Drugs,Antipsychotic Effect,Antipsychotic Effects,Antipsychotics,Major Tranquilizers,Neuroleptic Agents,Neuroleptic Drugs,Tranquillizing Agents, Major,Agent, Antipsychotic,Agent, Neuroleptic,Drug, Antipsychotic,Drug, Neuroleptic,Effect, Antipsychotic,Major Tranquilizing Agents,Major Tranquillizing Agents,Medication, Antipsychotic,Tranquilizer, Major

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