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Environmental pathology:
chemical & drug injuries
Ma. Minda Luz M. Manuguid, M.D.
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Chemical & drug injuries
*All chemicals & drugs are capable of causing injury or death.*
accidental exposure
self-administration
accidental overdose non-medical use of street drugs
unanticipated result of self-administered or prescribed use ofstandard medicines.
exaggeration of an intended pharmacologic effect or an
accompanying side effect
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Adverse drug reactions (ADRs)
any response to a drug that is noxious &unintended, occurring at doses used in humans
for prophylaxis, diagnosis, or therapy,excluding failure to accomplish the intended
purpose; [mechanisms: direct toxicity to cells;immunologic/idiosyncratic reactions; or due toimmunologic / hormonal host defenses] Predictable ADRs: known side-effects; dose-related,
severity depends on route ofadministration
Unpredictable ADRs: unanticipated, usuallyimmunologic/idiosyncratic; dose & route ofadministration do not affect the severity ofmanifestations
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Therapeutic agents: aspirin
Therapeutic dose: 0.5-1.0 gm./day Lethal dose: 2-4 gm./day in children 10-30 gm./day in adults
Acute toxicity: initial alkalosis--- fluid & electrolyteimbalance--- metabolic acidosis--- death Chronic toxicity: (3 gm/day): dizziness, nausea,
vomiting, diarrhea, drowsiness, hallucinations,convulsions, coma
Known effects: analgesic; anti-platelet aggregation;gastric irritant--- acuteerosive gastritis
Unpredictable ADRs: hypersensitivity: rashes,urticaria, exfoliative dermatoses
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Therapeutic agents: analgesics
Aspirin + PhenacetinToxicity: nephropathy : renal
papillary necrosis
NSAIDS:
known sideeffect: gastricirritation;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 injurypathology: hepatic necrosis;
renal/myocardial damage
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Therapeutic agents: anti-neoplastics
Anti-metabolites
Bone marrow suppression
GI mucosal injury
Hairfollicle injuryImmunosuppression
Nonlethal mutations
Initiation ofsomeform ofCancer
Immunosuppressives susceptibility to infections, esp.
opportunistic
risk of malignant lymphoma
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Therapeutic agents:
antimicrobials/antibiotics
Hypersensitivity rashes, urticaria,
exfoliative dermatoses
anaphylaxis Emergence of
microbial resistance super-infections
Eradication ofnormalflora 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 AcutePneumonitis Interstitial fibrosis Asthma
CARDIAC Theophylline Hydantoin
Doxorubicin, Daunorubicin HEPATIC
Tetracycline Chlorpromazine, Estrogens Halothane, Acetaminophen,
INH
PULMONARY Salicylates Nitrofurantoin Busulfan, Bleomycin
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Common adverse drug reactions & major offenders
RENAL Glomerulonephritis
Tubulointerstitial
nephritis Acute tubular
nephritis
SYS
TEMIC Anaphylaxis
Lupus erythematosussyndrome
RENAL
Penicillamine
Phenacetin
Salicylates Aminoglycosides,
Cyclosporine,Amphotericin B
SYS
TEMIC
Penicillin, Aspirin
Hydralazine,Procainamide
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Common agents implicated in fatal reactions
Tricyclic anti-depressants
Alprazolam
Ipramine, Desipramine
Nortriptyline
Acetaminophen
Halothane Aspirin
CNS depression
Hepatic necrosis
Hepatic necrosis Metabolic acidosis;
Fluid & Electrolyteimbalance
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non-medical use of street drugs
Marijuana:
delta-9-tetrahydrocannabinol
in theresin ofCannabissativa
Shabu: metampethamine
Ecstasy:MethyleneDioxyMetAmpethamine
Euphoria; cognitive,psychomotor, & sensoryalteration; but can reducenausea in CA chemoTx,
relieve pain in ticdoloreaux, can treatglaucoma, convulsiveseizures, & asthma
Sympathomimetic : Euphoria,Tachycardia, Hyperytension
Sympathomimetic: Euphoria,Tachycardia, Hypertension
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Non-medical use of street drugs
Cocaine: alkaloid extractfrom the leaves oftheCoca plant: pure- Crack;Cocaine hydrochloride
Heroin: opiate derivedfrom thePoppy plant; the
most hazardous streetdrug- produces TrueAddiction (physicaldependence) & intensefear ofwithdrawal (Illdie without it)
potent CNS stimulant;cardiorespiratory toxicity;perinatal morbidity &mortality; but effective
local anesthetic
Feelings ofwell-being,tranquility, sedation;multisystem toxicity;infections, granulomas;sudden death fromoverdose
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Non-therapeutic chemicals
Ethyl Alcohol: Acetaldehyde10 gm in 12 oz beer, 4 oz unfortified wine, or1.5 oz 80-
proofliquor
rapidly absorbed in the stomach & small intestines
Metabolized by the liver at therate of10gm/hr
Acute intoxication: mainly affects the CNS & Stomach 20-30mg/dL= powerful depressant effect on cortical
inhibitory centers= loss ofinhibitions= party syndrome;Euphoria; disordered cognitive & motorfunctions
100mg/dL= legal level ofintoxication= Ataxia
200-250mg/dL= narcosis= drowsiness
300-400mg/dL= coma; profound anesthesia; death
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Non-therapeutic agents:
ethyl alcohol
Chronic Alcoholism:Liver- most commonly & severely affected= fatty
change, acute hepatitis--- Cirrhosis
CNS Wernickes encephalopathy- ataxia, globalconfusion, ophthalmoplegia, loss ofneuropil &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 malformations
Misc.: neuropathies; congestive cardiomyopathy;frequency of cancer in the larynx, oropharynx, esophagus,rectum, lung
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alcoholism
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Uncommon potentially fatal nontherapeutic agents
ARSENIC- in rat poison,fruit sprays, weed killer;
binds sulfhydril
CARBON MONOXIDE-odorless, tasteless, incigarette smoke, fossilfuel exhaust
CARBONTETRACHLORIDE &CHLOROFORM
Nausea,vomiting,visceral hemorrhages,liver & lung CA
Systemic asphyxia: 1%fatal in 10-20 min, 7%fatal in 5 min: cherryreddiscoloration ofmucosae
Centrilobular necrosis,Liver; renal ATN
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Uncommon potentially fatal nontherapeutic agents
CYANIDE- gas causes deathwithin minutes; salts(100mg), within hours;antidote: Nitrite
INSECTICIDES Chlorinated hydrocarbons:
chlordane, Aldrin, DDT
Organophosphates: Malathion,
Pyrophosphates, Dimpylate
Polychlorinated biphenyls:PCBs
Histotoxic hypoxia; bindscytochrome oxidase-cherryred discoloration,
bitter almond odor Insecticides
Toxic neuronal injuryhyperexcitability,delirium,convulsions, coma
Muscle twitching, flaccid
paralysis, cardiacarrhythmias
Chloracne, impotence,infertility
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Uncommon potentially fatal nontherapeutic agents
KEROSENE- accidentalingestion or inhalation offumes
LEAD- paint, water (pipes),newsprint, pottery glazes,gas exhaust, tin cans,moonshine whiskey,occupational exposure
MERCURY- contaminatedfish, grain,fungicides,dermatologic ointments,interior latex paints
Fulminantbronchopneumonia; lipoidpneumonia; CNSdepression
Lead colic; lead line ongums; basophilic stipplingofRBC; anemia;encephalopathy;demyelinating neuropathy
Eosinophilic globules inrenal tubules; neuronaltoxicity; gingival deposits;Minamata dse-
blindness, hearing loss,spasticity, paralysis
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Uncommon potentially fatal nontherapeutic agents
METHANOL- in solvents,paint removers, & anti-freeze; toxic metabolite is
Formalin POISONOUS MUSHROOMS
Amanita muscaria rarelylethal; active metabolite ismuscarin
Amanita phalloides deathrate is 30-50%; activemetabolite is amanitin
Metabolic acidosis; CNSdepression; retinalganglion necrosis=
blindness MUSHROOMS
Immediateparasympathomimeticeffects: salivation, sweating,
miosis, bradycardia,hypotension, GI Sx
Cardiovascular collapse;convulsions, coma, ATN,centrilobular necrosis
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Thank you !