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cardiotoxicity
Exam 1
36
Pharmacology
Professional
02/09/2013

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Term
heart as a target of toxicity
Definition
blood flow to the heart brings in toxins, highly dependent on ionic flow to create action potentials that make the heart work properly
Term
risk factors for cardiotoxicity
Definition
age, pre-existing disease
Term
antagonism of M2 receptors
Definition
increases conduction at the SA and AV nodes to increase heart rate, can exacerbate angina because of the increased oxygen demand of heart when drug is administered
Term
certain drugs predispose the heart to have arrhythmias
Definition
drugs can set up the heart so that it is more likely to have something go wrong, drugs that fix arrhythmias can predispose heart to getting other types of arrhythmias
Term
inhibition of Na/K ATPase
Definition
Digitalis: increased intracellular Na will drive Na/Ca exchanger causing there to be increased intracellular Ca causing positive ionotropy (increased contractility)
Term
Ca channel blockade
Definition
Verapamil and diltiazem: negative ionotropic effect due to reduce Ca-induced Ca release in sarcoplasmic reticulum, causing BRADYcardia and (AV node) heart block
Term
L-type Ca blockade
Definition
contributes to excitation-contraction coupling
Term
T-type Ca blockade
Definition
Contributes to Pacemaker potential in SA node
Term
K channel blockade
Definition
blockade of hERG, which regulates rapid delayed rectifier current, results in prolongation of cardiac action potential (Q-T interval) producing torsades de pointes
Term
hERG
Definition
potassium channel protein/ expression-regulator gene
Term
antipsychotics, antihistamines (non-drowsy), zithromax, viagra and Cialis
Definition
cause blockade or alteration of hERG functions that can result in arrhythmias
Term
Q-T interval
Definition
time required to achieve ventricular depolarization and time to the onset of repolarization and time required to complete repolarization
Term
P wave
Definition
atrial depolarization
Term
Q-R-S wave
Definition
ventricular contraction (atrial repolarization)
Term
T wave
Definition
ventricular repolarization
Term
Q-T prolongation due to hERG interference
Definition
torsades de pointes
Term
torsades de pointes
Definition
atypical form of ventricular tachycardia initiated only in the presence of long Q-T interval and can progress to ventricular fibrilation, can lead to sudden death
Term
antiarrhythmic class IA: quinidine, procainamide, disopramide
Definition
causes Q-T prolongation
Term
Antiarrhythmic class IC: encainide, flecainide
Definition
causes Q-T prolongation
Term
Antiarrhythmic class III: sotalol, amiodarone
Definition
causes Q-T prolongation
Term
oxidative stress
Definition
reactive free radical generated during metabolism of parent molecule, often due to mitochondrial damage and disruption of ATP production (electron transport interrupted to produce ROS)
Term
action of ROS
Definition
DNA, Lipids and Proteins
Term
Doxorubacin-induced cytotoxicity
Definition
doxorubicin smiquinone radical produced forming complex with iron becoming doxorubicin-free radical complex, hydrogen peroxide dismutates complex and results in fromation of peroxynitrite which causes cardiotoxicity
Term
organellular dysfunction
Definition
disruption of electron transport chain results in ROS formation and contributes to dysfunction and shut down of mitochondria and interference with calcium handling of the cells which is needed for heart action potential function
Term
consequences of mitochondrial dysfunction
Definition
interferance: beta oxidation, NADH synthesis, electron transport chain, proton gradient, and mitochondrial permeability transition
Term
doxorubacin (oxidative stress) and carvedilol (long period of time)
Definition
drugs that cause mitochondrial dysfunction
Term
hypersensitivity myocarditis
Definition
inflammatory and necrotic disease of myocardium with a wide range of clinical prentation leading to heart failure and arrhythmia
Term
clozapine
Definition
NOT dose-dependent and within therapeutic range it can cause hypersensitivity myocarditis
Term
endothelial cell properties and functions
Definition
source of anticoag, prothrombic, production of extracellular matrix, modulatoin of blood flow through vasodilators and inflammation/ immunity , growth factors and oxidation of LDL
Term
mechanisms of drug-induced vascular injury
Definition
biochemical injury, toxicity following direct pharmacological/ chemical perturbation, injury via immune-mediated mechanisms
Term
methylxanthines (caffeine and theophylline), potassium channel activators (minoxidil, diazoxide)
Definition
vasodilators affecting (large/ medium) arteries...drug induced vascular injury with long-term use
Term
vasopressin, angiotensin II, Epi, phynylephrine, methoxamine
Definition
vasoconstrictors affecting (small) arteries and arterioles...drug induced vascular injury with long-term use
Term
cholesterol and oxygenated derivatives, organophosphates, cadmium. arsenic and mercury
Definition
exacerbation of pre-existing pathology (atherosclerosis)...drug induced vascular injury with long-term use
Term
drug-induced vasculitis
Definition
heterogeneous group of disorders characterized by inflammatory destruction of both arteries and veins
Term
vasculitis
Definition
changes in blood vessels, induced thickening, weakening, narrowing and scarring...drug hypersensitivity that evolves into ischemia and necrosis of vessels
Term
propylthiouracil and ciprofloxacin
Definition
drug-induced vasculitis; binding of drug (hepten)and protein (carrier-antigen)
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