Exam3Lec1Toxicology Flashcards
What is toxicology?
Study of the adverse effects of xenobiotics (foreign bodies) on living sysyems.
What is the highest poison exposure for all age group/fatal outcomes
Medications
What is most frequently involved in human poisoning exposures?
Analgesics
aspirin, ibuprofen, acetomenophen
Give an example for each:
A. selective toxicity
B. non-selective toxicity
C. Immediate toxicity
D. Delayed toxicity
A. selective toxicity: enzymes, receptors (helps choose abs)
B. non-selective toxicity: acids, bases
C. Immediate toxicity: skin damage
D. Delayed toxicity: cancer (chronic exposure)
State how toxins can enter the
A. Lungs
B. Liver
C. Brain (lipophillic) and Kidney
D. Heart
A. Lungs: inhaled gases, particles
B. Liver: ingested chemicals, bioactivation, inactivation
C. Brain (lipophillic) and Kidney: ingested chemicals
D. Heart: ingested chemicals, disruption of ion gradients
What are the halogenated hydrocarbons?
CCl4 (Carbon tetrachloride) and Chloroform CHCl3
4 points regarding halogenated hydrocarbons generally
- Inhalation/ingestion
- Penetrate the BBB b/c lipid soluble
- depress the CNS
- supportive tx
Supportive tx= ABCD, Airway, BP, Circulation, Decontamination
CCl4(Carbon Tetrchloride)
A. exposure
B. irritation
c. bioactivation
d. symptoms
A. Exposure: contaminated H20
B. Irritation: Eye irritant, respiratory system
C. Bioactivation: CYP450 bioactivated (produces free radicals causing lipid peroxidation)
D. Symptoms: Depress CNS (Nausea/Vomiting (N/V), Stupor, Seizures, Coma, Death) and Liver and kidney damage with nonlethal acute exposure
Explain bioactivation of Chloroform (CHCl3 )
- ChCl3 converted to Phosgene by(reactive metabolite) CYP2E1
- Phosgene is very electrophillic and covalently binds hepatic & renal proteins & lipids,leading to hepatoxicity.
- GSH (glutathione) is very nucleophilloc and attack phosgene creating a detoxified product (prevents from toxicity)
similar to CCl4 and it faciliates catecholamine-induces arrythmias
What are the aromatic hydrocarbons?
Benzene and toluene
3 points regarding aromatic hydrocarbons generally
- Inhalation/ingestion
- CNS depression, catecholamine-induced arrhythmias
- Supportive treatment
Benzene
A. Exposure
B. Chronic exposure
A. Exposure: tobacco smoke and fossil fuels/contaminated H2O “smoking in the benz”
B. Chronic exposure: causes hematopoietic toxicity (agrunulocytosis, leukemia (AML).
Toluene
A. Exposure
B. Symptoms
C. Chronic exposure
A. Exposure: gasoline (primary), paint, polish “GPP”
B. Symptoms: CNS depression (drowsinees, ataxia, tremors, etc)
C. Chronic exposure: liver and kidney damage and death at high concentrations
A 55-year-old man who has worked in a chemical plant for 25 years has been chronically exposed to benzene. Which of the following is the most likely toxicity of chronic benzene exposure?
A. Hepatotoxicity (Liver).
B. Nephrotoxicity (Kidney)
C. Leukemia
D. Parkinson disease
C. leukemia
a and b is caused by toluene, parkinsons is mercury
What are the toxic alcohols?
Methanol (wood alchol) and Ethylene glycol (in antifreeze)
Alcohols: Methanol (wood alcohol), Ethylene glycol
2 main points
- Can cause CNS sedation
- Oxidized to toxic metabolites, Which can cause coma, seizure, hyperpnea, & hypotension -> (Sedation)
Pathway of methanol oxidation
Methanol->formaldehyde->Formic acid->Retinal inj/Blindness
Pathway of ethylene glycol oxidation
Ethylene glycol->glycoaldehyde-> glycolate-> calcium oxalate crystals->Renal failure
What is the treatment for Alcohols and state its moa?
Fomepizole: inhibits alchohol dehydrogenase and renal elimination of parent cmpds
stops the activation/oxidation to its toxic metabolite
What are the toxic pesitcides?
Organophosphates, Carbamates, Pyrethroids, Rotenone
“pesticides ORGANically ROT”
Organophosphates & Carbamate insecticides
A. MOA
B: Treatment
A. MOA: Inhibits ACHe therefore incr ACh
B. Treatments: supportive (breathing and decontaminiation
* Atropine: muscurinic receptor antag
* Pralidoxime: reactives cholinesterase, usually used for organophosphates
“AP Orgo”
## Footnote
symptoms of Organophosphate & carbamate insecticide: Salivation, lacrimation, perspiration, miosis, N/V, bronchospasm, seizures, coma
Pyrethroids(chrysanthematic, pyrethric acids)
A. MOA
B. Symptoms
C. Treatment
A. MOA: **Extend the opening time of sodium channels in the CNS & PNS ** “extend the pye”
B. Symptoms: Loss of coordination, seizures, burning/itching sensation, contact dermatitis, asthma-like symptoms
C. Treatment: supportive treatment (no antidote)
Rotenone
A. MOA
B. Symptoms
C. Treatment
A. MOA: NADH-coenzyme Q reductase (complex 1)
STOPS OXIDATIVE PHOSPHORYLATION
B. Symptoms: N/V, Seizures, Death at very high doses
C. Treatment: supportive tx (no antidote)
inhibits coenzyme Q by preventing electron shuttling during oxidative phosphorylation
True or false: CO toxic to cytochromes but the amount required is 1000X the lethal dose & thus plays no role in clinical poisoning.
TRUE
The way CO kills you is not by inhibiting energy production
What are the toxic rodenticides?
Brodifacoum, Difenacoum
rodent, pls dont Coum
Rodenticides: Brodifacoum, Difenacoum
A. Structure
B. Ingestion
C. Toxicity
D. Treatment
A. Structure: similar to warfarin (more lipophillic so longer 1/2 life)
B. Ingestion: can occur w/ intentional poisoning and suicide
C. Toxicity: internal bleeding
D. Treatment: fresh frozen plasma & phytonadione (Vit K)**
fresh plama contains clotting factors
What are the toxic metals?
- Lead (Pb)
- Mercury (Hg)
- Cadmium (Cd)
- Arsenic (As)
- Iron (Fe)
- Copper (Cu)
Heavy metals: Pb, Hg, Cd
A. Exposure concern:
B. Treatment:
A. Exposure concern: public health concern and chronic low dose exposure
B. Treatment: chelators
(except cd)
Lead (Pb)
A. Exposure
B. Children vs. adults
C. Distribution
D. 1/2 life
E. Symptoms
A. Exposure: old paint, drinking water
B. Children vs. adults: children absorb 40% of ingested dise (they absorb more than adults)
C. Distribution: inorganic Pb : Initially distributes to soft tissues, Then redistributes to bone (MAINLY), teeth & hair (Detected by x-ray)
D. 1/2 life: Blood:1-2 months. Bone 20-30 years
E. Symptoms: CNS toxicity or Pb encephalopathy
Disrupts Ca homeostasis which disrupts neurotransmission->Encephalopathy
Are children or adults more susceptible to CNS toxicity from Pb?
Children more susceptible to CNS toxicity, can ↓ IQ,
Describe GI toxicity and Blood toxicity of Pb
- Gastrointestinal (GI) toxicity:
* Sx: discomfort, constipation, or diarrhea
* Higher doses can cause painful intestinal spasms which can be treated with IV calcium gluconate - Blood toxicity:
Disrupts heme synthesis → shortens red blood cell (RBC) life span, this causes Hypochromic, microcytic anemia
Lead poisoining MOA
↑ δ-aminolevulinic acid (ALA) & protoporphyrin IX blood concentrations in urine by inhibition of δ-aminolevulinic acid dehydratase & ferrochetalase
Blood concentrations > 25 μg/dL, Diagnostic for Pb intoxication
What is a treatment for high Pb toxicity?
Dimercaprol + EDTA (edetate calcium disodium)
Chelator which forms a coordinated bond with cationic metal & the complex renally excreted
How does Lead poisoning block heme synthesis?
- It inhibits ferrochelatase and ALA dehydratase
- Protoporphyrin and ALA are secreted in the urine
hy
Protoporphyrin and ALA ARE IN URINE
Treatment of Pb poisoining with Pb concentrations
- 45-54 μg/dL → Succimer
- 55-69 μg/dL → EDTA
- 70-100 μg/dL → EDTA + Dimercaprol
Name the 3 types of Mercury (Hg)
Elemental Hg
Inorganic Hg
Organic Hg
Elemental Hg (inhaled vapors)
Symptoms
Sx: tremors, depression, memory loss, ↓ verbal skills, renal inflammation, High concentrations → corrosive to lungs
you inhale it so its corrosive to lungs
Inorganic Hg (mercury chloride) symptoms
Corrosive: mucosal mouth damage, renal damage
Organic Hg (methyl mercury)
A. exposure
B. symptoms
C. diagnosis
A. exposure: contaminated fish “ I go to whole foods for organic fish”
B. symptoms: neurological sx, very high doses can cause death (especially toxic to unborn to child)
c. Misdiagnosed Alzheimer or Parkinson disease in elderly
hy
Very high lipid solubility and less corrosive than inorganic Hg
neurological sx: visual disturbances, paresthesia, ataxia, hearing loss, mental deterioration, muscle tremors, movement disorders
Treatment for Mercury (Hg) poisining
Dimercaprol, succimer (Chelating agents)
Cadmium (Cd)
A. Exposure
B. Distrubution
C. 1/2 life
D. Treatment
A. Exposure:ingestion/inhaled. Contaminated plants, cigarette smoke, burning of fossil fuels, Industrial exposure, e.g., welding, smelting
B. Distrubution:mainly to liver & kidneys by binding to metallothionein
C. 1/2 life: 10-30 years
D. Treatment: No evidence of chelation therapy effectiveness Dimercaprol, penicillamine, & EDTA contraindicated, ↑ risk for nephrotoxicity (Kidney toxicity) !!
know industrial/welding.smelting
Especially toxic to kidney & lungs, also carcinogenic
weld and smel the cad!!!
A MSP3 student who plans on applying to medical school or pharmacy school is studying the effects of toxicants on human cell lines at the MCOM. Which of the following most likely disrupts electron transfer during oxidative phosphorylation?
A. Chloroform
B. Lead
C. Rotenone
D. Brodifacoum
C. Rotenone
Arsenic (As)
A. Exposure
B. Toxicodynamics
C. Acute toxic effects
D. Chronic toxic effects
E. Treatment
A. Exposure: H2O, ant bait
B. Toxicodynamics: interfere with enzyme activity and cell signal transduction
C. Acute toxic effects: GI,** Cardiopulmunnary: VENTRICULAR ARRYTHMIA**, CNS.PNS
D. Chronic toxic effects: hyperpigmentation, hyperkeratoses of skin on hands and feet, cancer, weight loss
E. Treatment: Dimercaprol
arrrrrrr=ant-baitr=arrythimic=acute (3 as)
Iron (Fe)
A. Acute toxicity
B. Chronic toxicity
A. Acute toxicity: large amt of polyethylene glycol. ingestion of Fe tablets by young children
* Necrotizing gastroenteritis, lethargy, dyspnea
* Subsequent improvment, then severe acidosis and death
B. Chronic toxicity:
* Pt with excessive Fe absorption(inherited hemochromatosis) or got many blood transfusions
excess Fe deposits in heart, liver, pancreas
Treatments for Iron (acute and chronic)
Treatments (for acute and chronic):
* acute: whole bowel irrigation to flush out Fe so it doesnt get absorbed (works if havent absrobed yet). Deferoaxamine (IV)
* Chronic: intermittent phlebotomy (in the absence of anemia), deferoxamine (IM, SQ), Deferasirox (PO)
all have fe
Copper (Cu)
A. Acute toxicity
B. Chronic toxicity
C. Associated disease
A. Acute toxicity
* Inhalation of Cu fumes/dust: severe cough, leukocytosis
* Ingestion of Cu salts (sulfate): Gi bleeding, gastroenteritis
B. Chronic toxicity:
* Bordeaux mixture, Fungicide with vineyard workers
* leads to Pulmonary fibrosis
C. Associated disease: Wilson disease-high concentratiojn of Cu in CNS leading to hepatic and neurologic dysfunction
wilsons: builds up copper b/c you can’t eliminate it. CLassic sign of wilsons is that they have copper color in the iris bc deposits got in there
Treatment for Copper poisoing and Wilsons disease
Copper: dimercaprol, penicillamine
Wilsons: dietary Cu, penicillamine, trientine
Chelator Summary
CaNa2EDTA
Succimer
Dimercaprol
Penicillamine
CaNa2EDTA: Pb
Succimer: Pb and Hg
Dimercaprol: Pb, Hg, As, Cu
Penicillamine: Cu
