GenpathChem&Drug

8/9/2019 GenpathChem&Drug

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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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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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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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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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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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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 !

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