Andersons pediatric cardiology 1574

HeartDiseaseInducedbyToxins
Adversereactionstodrugsandothersubstancescanaffecttheheartindifferent
ways.Thesecanbeclassifiedashypersensitivitymyocarditis,toxicmyocarditis,
cardiomyopathy,orendocardialfibrosis(Boxes59.2to59.4).


Box59.2

DrugsProducingHypersensitivity
Myocarditis
Acetazolamide
Amitriptyline
Amphotericin(amphotericinB)
Carbamazepine
Chloramphenicol
Clozapinea
Indomethacin(indometacin)
Isoniazid
Methyldopa
Minocyclinea
Para-aminosalycilicacid
Penicillin
Phenindione
Phenylbutazone
Phenytoin(diphenylhydantoin)
Smallpoxvaccine
Spironolactone
Streptomycin
Sulfonamides
Sulfonylureas
Tetracyclines

Thiazidediuretics
Tetanustoxoid


aUpdatedtoincludeclozapineandminocycline.377

ModifiedfromBillinghamME.Morphologicchangesindrug-inducedheart
disease.In:BristowMRed.Drug-InducedHeartDisease.Amsterdam:Elsevier;
1980:127–149;andTaliercioCP,OlneyBA,LieJT.Myocarditisrelatedtodrug
hypersensitivity.MayoClinProc.1985;60:463–468.


Box59.3

DrugsandAgentsProducingToxic
Myocarditis
Antimony
Anthracyclineantibiotics
Arsenicals
Barbiturates
Caffeine
Catecholamines
Cyclophosphamide
Emetine
5-Fluorouracil
Lithiumcarbonate
Hydralazine
Paraquat
Phenothiazines
Plasmocid

Quinidine
Rapeseedoil
ModifiedfromBillinghamME.Morphologicchangesindrug-inducedheart
disease.In:BristowMR,ed.Drug-InducedHeartDisease.Amsterdam:
Elsevier;1980:127–149.




Box59.4

DrugsandAgentsProducingEndocardial
Fibrosis
Serotonin
Methysergide
Mercury
Busulfan
Irradiation
ModifiedfromBillinghamME.Morphologicchangesindrug-inducedheart
disease.In:BristowMR,ed.Drug-InducedHeartDisease.Amsterdam:Elsevier,
1980:127–149.
Thelistofdrugsinconnectionwithwhichhypersensitivitymyocarditishas
beendescribedisverylong(seeBox59.2).Thetrueincidenceisunknown,since
hypersensitivitymyocarditisisrarelyrecognizedclinicallyandthereforetendsto
beapostmortemfinding.Inappropriatesinustachycardia,mildradiographic
cardiomegaly,andST-segmentandT-wavechangesontheECGinthepresence
ofotherallergicreactionsandhypereosinophiliashouldraisesuspicionfor
clinicaldiagnosis.Diagnosisisimportant,sincesuddendeathfromheartblock
orventriculartachycardiacanoccur.350Hypersensitivitymyocarditisisnotdosedependentandcanoccuratanytimeduringtheadministrationofdrugs.A
delayedhypersensitivityreactionistheacceptedmechanism.Histopathologic

examinationrevealsaninterstitialinflammatoryinfiltratewitheosinophils,
atypicallymphocytes,andplasmacells;thismainlyaffectstheventricles.
Myocyticdamageisseenbutnecrosisisuncommon.Severecasesmayexhibita
nonnecrotizingvasculitis.Theselesionsarereversibleuponstoppingthedrug.
Fibrosis,therefore,isnotseen.Treatmentiscenteredondiscontinuingthe
offendingdrugcombinedwithuseofcorticosteroidsorimmunosuppressive
therapy.
Manysubstanceshavebeenimplicatedintheproductionoftoxicmyocarditis.
Thisisadose-relatedconditioninwhichtheeffectsarecumulative.Clinical
presentationisthatofacutemyocarditis.Extensivecellularnecrosisoccursover
ashortperiod.Histopathologicsignsincludemyocardialdamage,inflammatory