genPathChemInj

8/9/2019 genPathChemInj

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Chemical & Drug Injuries


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Chemical & drug injuries

***All chemicals & drugs are capable of causinginjury or death.***

accidental exposureself-administrationaccidental overdosenon-medical use of street drugs

unanticipated result of self-administered orprescribed use of standard medicines.exaggeration of an intended pharmacologic effect

or an accompanying side effect


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Adverse drug reactions (ADRs)

any response toa drug that is noxious &unintended, occuringat doses used in humans forprophylaxis, diagnosis, or therapy, excluding failure

toaccomplish theintendedpurpose; [mechanisms:direct toxicity to cells; immunologic/idiosyncraticreactions; or due toimmunologic / hormonal hostdefenses]

P

redictable ADRs: knownside-effects; dose-related,severity dependson routeofadministrationUnpredictable ADRs: unanticipated, usually

immunologic, idiosyncratic; dose & routeofadministration do notaffect theseverity


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Therapeutic agents

ANALGESICS

Aspirin

Aspirin + Phenacetin

NSAIDS (non-steroidal anti-inflammatory drugs): Ibuprofen,Diclofenac,

Acetaminophen/Paracetamol

ANTIMICROBIALS

ANTI-NEOPLASTICAGENTS Anti-metabolites

Immunosuppressives


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Therapeutic agents: aspirinTherapeutic dose: 0.5-1.0 gm./dayLethal dose: 2-4gm./dayin children

10-30 gm./dayinadultsAcute toxicity:initialalkalosis--- fluid &

electrolyteimbalance--- metabolicacidosis---deathChronic toxicity: (3gm/day): dizziness, nausea,

vomiting, diarrhea, drowsiness, hallucinations,

co

nvulsio

ns, coma

Known effects:analgesic; anti-plateletaggregation;gastricirritant--- acute erosivegastritis

UnpredictableADRs:hypersensitivity: rashes,urticaria, exfoliative dermatoses


6/23

Therapeutic agents: analgesics

Aspirin + Phenacetin Toxicity: nephropathy : renal papillary necrosis

NSAIDS: known side effect: gastric irritation;

UADR: hypersensitivity

Acetaminophen:

therapeutic dose: 0.5 gm q 4 hrs.(up to 3gm/day) toxic dose: 15-25 gm;

toxicity: nausea, vomiting, diarrhea; shock; hepatic injury

pathology: hepatic necrosis; renal/myocardial damage


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Therapeutic agents: anti-neoplastics

Anti-metabolites Bone marrow suppression

GI mucosal injury

Hair follicle injury Immunosuppression

Nonlethal mutations

Initiation of some form of Cancer

Immunosuppressives susceptibility to infections, esp. opportunistic

risk of malignant lymphoma


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Therapeutic agents:

antimicrobials/antibioticsHypersensitivity rashes, urticaria, exfoliative dermatoses

anaphylaxis

Emergenceofmicrobial resistance super-infections

Eradicationofnormalflora vitamin K deficiency--- bleeding diathesis


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Common adverse drug reactions

& major offenders BLOOD (DYSCRACIAS)

Granulocytopenia

Aplastic anemia

Pancytopenia

Hemolytic anemia

thrombocytopenia

CNS

Tinnitus, dizziness

Acute dystonic reactions

Parkinsons syndrome

CUTANEOUS Urticaria

Petechia

Exfoliative dermatitis

BLOOD DYSCRACIAS Anti-neoplastics

Immunosuppressants

Chloramphenicol

Quinidine

Methyldopa

CNS

Salicylates

Phenothiazine antipsychotics

Sedatives

CUTANEOUS Sulfonamides

Hydantoin

Anti-neoplastics


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Common adverse drug reactions &

major offenders CARDIAC Arrhythmias

Cardiomyopathy

HEPATIC

Fatty change

Cholestasis

Hepatocellular damage

PULMONARY Acute Pneumonitis

Interstitial fibrosis

Asthma

CARDIAC Theophylline

Hydantoin

Doxorubicin, Daunorubicin

HEPATIC

Tetracycline

Chlorpromazine, Estrogens

Halothane, Acetaminophen,INH

PULMONARY Salicylates

Nitrofurantoin

Busulfan, Bleomycin


11/23

Common adverse drug reactions &

major offenders RENAL Glomerulonephritis

Tubulointerstitial nephritis

Acute tubular nephritis

SYSTEMIC

Anaphylaxis

Lupus erythematosus

syndrome

RENAL

Penicillamine

Phenacetin, Salicylates

Aminoglycosides,Cyclosporine, Amphotericin B

SYSTEMIC

Penicillin, Aspirin

Hydralazine, Procainamide


12/23

Common agents implicated in

fatal reactions Tricyclicanti-depressants Alprazolam

Ipramine, Desipramine

Nortriptyline

Acetaminophen Halothane Aspirin

CNS depression

Hepatic necrosis Hepatic necrosis Metabolicacidosis; Fluid &

Electrolyteimbalance


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non-medical use of street drugs

Marijuana:delta-9-tetrahydrocannabinolin the resin ofCannabissativa

Shabu: metampethamine

Ecstasy:MethyleneDioxyMetAmpethamine

Euphoria; cognitive,psychomotor, &sensoryalteration; but can reducenauseain CA chemoTx, relievepainin tic doloreaux, can treatglaucoma, convulsiveseizures,&asthma

Sympathomimetic:Euphoria,T

achycardia,H

yperytension Sympathomimetic:Euphoria,

Tachycardia, Hypertension


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Non-medical use of street drugs

Cocaine:alkaloid extractfrom theleavesoftheCocaplant:pure- Crack;C

ocainehydrochloride

Heroin:opiate derivedfrom the Poppyplant; the

mosthazardousstreetdrug- produces TrueAddiction (physicaldependence) &intensefearofwithdrawal (Ill diewithoutit)

potentCNSstimulant;cardiorespiratory toxicity;perinatalmorbidity &mortality; but effective

localanesthetic

Feelingsofwell-being,tranquility, sedation;multisystem toxicity;

infections, granulomas;sudden deathfromoverdose


15/23

Non-therapeutic

chemicals

EthylAlcohol:Acetaldehyde10 gm in 12 oz beer, 4 oz unfortified wine, or 1.5 oz 80-proof liquor

rapidly absorbed in the stomach & small intestines

Metabolized by the liver at the rate of 10gm/hr

Acute intoxication: mainly affects the CNS & Stomach

20-30mg/dL= powerful depressant effect on cortical inhibitorycenters= loss of inhibitions= party syndrome; Euphoria;

disordered cognitive & motor functions 100mg/dL= legal level of intoxication= Ataxia

200-250mg/dL= narcosis= drowsiness

300-400mg/dL= coma; profound anesthesia; death


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Non-therapeutic agents:

ethyl alcohol

ChronicAlcoholism:inducesinjuriesinall tissuesLiver - most commonly & severely affected= fatty change, acute

hepatitis--- Cirrhosis

CNS Wernickes encephalopathy- ataxia, global confusion,ophthalmoplegia, loss of neuropil & demyelination (vit B1 def) &Korsakoff syndrome- profound memory deficit both recent &remote; cerebellar degeneration; cerebral atrophy

Fetal Alcohol Syndrome: microcephaly, cardiac defects, mental

deficiency, facial malformationsMisc.: neuropathies; congestive cardiomyopathy; frequency of

cancer in the larynx, oropharynx, esophagus, rectum, lung


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Uncommon potentially fatal

nontherapeutic agents ARSENIC- in ratpoison,

fruitsprays, weed killer;bindssulfhydril

CA

RBON

M

ON

OXI

DE-

odorless, tasteless, incigarettesmoke, fossilfuelexhaust

CARBONTETRACHLORIDE &CHLOROFORM

Nausea, vomiting, visceralhemorrhages, liver &lungCA

S

ystemicasphyxia:1%

fatalin10-20 min, 7%fatalin 5min: cherry reddiscolorationofmucosae

Centrilobular necrosis,Liver; renalATN


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nontherapeutic agents

CYANIDE- gas causes deathwithinminutes; salts(100mg), withinhours;

antidote:N

itrite INSECTICIDES Chlorinated hydrocarbons: chlordane,

Aldrin, DDT

Organophosphates: Malathion,

Pyrophosphates, Dimpylate

Polychlorinated biphenyls: PCBs

Histotoxichypoxia; bindscytochromeoxidase- cherryred discoloration, bitter

almondodor Insecticides Toxic neuronal injury

hyperexcitability,delirium,convulsions, coma

Muscle twitching, flaccid paralysis,

cardiac arrhythmias Chloracne, impotence, infertility


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KEROSENE- accidentalingestionorinhalationoffumes

LEAD- paint, water (pipes),newsprint, potteryglazes, gasexhaust, tin cans, moonshinewhiskey, occupationalexposure

MERCURY- contaminatedfish, grain,fungicides,dermatologicointments,interiorlatexpaints

Fulminantbronchopneumonia; lipoidpneumonia; CNS depression

Lead colic; leadlineongums; basophilicstipplingofRBC; anemia;encephalopathy;demyelinating neuropathy

Eosinophilicglobulesinrenal tubules; neuronaltoxicity; gingival deposits;Minamata dse- blindness,hearingloss, spasticity,paralysis


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METHANOL- insolvents,paint removers, &anti-freeze;toxicmetaboliteis Formalin

POISONOUSMUSHROOMSAmanitamuscaria rarely

lethal; active metabolite ismuscarin

Amanitaphalloidesdeath rateis30-50%; active metabolite isamanitin

Metabolicacidosis; CNSdepression; retinalganglionnecrosis=blindness

MUSHROOMSImmediate

parasympathomimeticeffects: salivation, sweating,miosis, bradycardia,

hypotension, GI Sx

Cardiovascular collapse;convulsions, coma, ATN,centrilobular necrosis


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Poisonous mushrooms

Amanita muscaria Amanita phalloides


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