Rankin - General Toxicology Flashcards
Fact:
Remember, ALL SUBSTANCES are toxic.
A principle of Toxicology is the dose dictates toxicity.
______ is the lethal dose in 50% of population. It is the dosage causing death in 50% of exposed animals.
The lower the ______, the more toxic the substance.*****
LD50
What toxic substance?
- colorless, odorless and tasteless gas
- exposure not detected by senses
Major Sources: incomplete combustion of fossil fuels (i.e. car exhausts; kerosene heaters) and fires (i.e. home fires)
Other Sources: cigarette smoke, hemolytic anemia, biotransformation of paint removers (i.e. methylene chloride)
Carbon Monoxide (CO)
Mechanism of Carbon Monoxide (CO) Toxicity.
- binds to ferrous (Fe2+) iron in Hb to form _________________ (COHb)
- ___________ Color in mucus membranes
- binds 250x tighter to Fe2+ in Hb than O2 reducing the O2 carrying capacity of the blood
- O2 bound to COHb is released _________ (faster/slower) than from Hb to further reduce O2 delivery to tissues
Result: Anoxia - decrease oxygen floating around in the body
carboxyhemoglobin
Cherry Red
slower
What is the #1 cause of death from poisoning in the US?
Death is due to _____________ failure.
What is the target organ in the CNS?
Carbon Monoxide (CO)
Respiratory failure
****Globus pallidus in the cerebellum
Fact: Clinical Effects of CO
Carbon Monoxide toxicity is reveresible.
At what level of COHb % would you begin to treat with 100% Oxygen?
20-30% mild poisoning
What toxic substance?
-exists as solid (Salt form), liquid (HCN) or gas
-occupational exposure during mining, chemical synthesis and electroplating
- ingestion of apricot or peach pits, bitter almond
- excess dose of certain drugs, laetrile
- fires
Cyanide (CN) and CN releasing agents
What toxic substance?
- mitochondrial toxin inhibiting electron transport chain
- binds to Ferric (Fe3+) iron of mitochondrial cytochrome oxidase inhibiting ETC between Cyta2 and Cyta3
- Lethal Dose: 50 mg adults (1 tsp); 1.5 mg children
Cyanide (CN)
Symptoms for what toxicity?
- rapid progression from onset of symptoms to death
- Nausea, lightheadedness, hyperventilation, feelings of suffocation, convulsions, coma
- HR increased followed by decreased HR
Cyanide Toxicity
Cyanide Poisoning.
Death from ____________ failure.
In recovered patients, what kind of damage might you see?
respiratory failure
Brain damage
Normal Detoxification of Cyanide in the Body occurs in the _________ (what organ)?
Liver (80%)
Treatment for CN Toxicity is a 2 Step Process.
Step 1: Administer __________ or ______________ to convert Hemoglobin (Hb-Fe2+) to Methemoglobin (Hb-Fe3+).
Methemoglobin binds the CN- forming cyanomethemoglobin (Hb-Fe3+-CN-).
Step 2: Administer ____________. Why?
nitrite (NaNO2 3% IV) or amyl nitrite ampule
Thiosulfate; allows the liver enzyme, su;fotransferase to lessen the toxicity of Cyanide and prepare if for excretion from the body.
What is the antidote for increased levels of methemoglobin in the blood?
Note: Methemoglobin can cause similar symptoms as Carbon Monoxide poisoning.
Methlyene Blue***
Insecticides.
Name 2 Organophosphate Insecticides.
Which is more toxic?
Name the Carbamate Insecticide.
1. Diazinon LD50 100-150 mg/kg (*MORE TOXIC)
2. Malathion LD50 1000-1375 mg/kg
Carbaryl (Sevin Dust)
Death from Insecticides occur due to _____________ failure.
respiratory
What is the mechanism of Organophosphate Toxicity?
inhibits acetylcholine esterase (both humans and insects)
increasing ACh levels at receptors
resulting in exaggerated cholinergic effects
What are Muscarinic (Parasympathetic) symptoms seen in Organophosphate Poisoning?
What is the mnenomic?
****SLUD
- *S**alivation
- *L**acrimation
- *U**rination frequency increased (Bladder)
- *D**efecation, nausea, vomiting, cramps (GI)
Eyes: Miosis, blurred vision
Bronchial Tree: wheezing, tightness of chest, rhinitis, inc. secrections, cough
What are Nicotinic (Sympathetic and Somatic Motor Neurons) symptoms resulting from Organophosphate poisoning?
- muscle twitching (face), cramps, muscle weakness
- elevated HR, BP
What is the treatment for Organophosphate poisoning?
Atropine and Pralidoxime (2-PAM)
Pralidoxime (2-PAM) is a regenerating agent if given early enough.
What is the mechanism of toxicity of Carbamate Insecticides?
Reactivates faster or slower than organophosphates?
-inhibits acetylcholine esterase (same as organophosphates)
BUT carbamoylated enzyme reactivates faster in H2O than phosphorylated enzyme from organophosphates
-Reactivation half life is 1 hour
What is treatment for Carbamate toxicity?
Atropine
NOT 2-PAM*
Name the Insecticide.
Mechanism of toxicity: redox cycling molecule and as it shifts back from reduced form to oxidized form it generates free radicals leading to lipid peroxidation, membrane damage and tissue death
Paraquat
Symptoms for what Insecticide toxicity?
Inhaled: Acute irritation, shortness of breath, pulmonary edema –> Chronic Pulmonary Fibrosis***
Oral: Acute irritation and ulceration of mucous membranes (which allows it to be absorbed in to the body)
Dermal and Ocular: Acute Erythema, ulceration, Chronic Cataract formation*
DEATH: multi-organ failure*
Paraquat
Treatment for Paraquat?
- Gastric aspiration and lavage - not very useful
- Kaolin (Fuller’s Earth) to bind up Paraquat - limited use
3. Hemodialysis or Hemoperfusion
****Paraquat can be detected by the addition of 1 ml of 1% solution of sodium dithionite in 2N sodium hydroxide to 10 ml urine.
*****A ________ color indicates Paraquat.
A ________ color suggests Diquat.
blue
blue-green
What substance toxicity?
- a solvent
- aromatic hydrocarbon
- component of Gasoline
Acute toxicity: CNS depression and/or pulmonary irritation/edema
Chronic toxicity: anemia, leukemia and lymphomas
Benzene
What substance toxicity?
- organic solvents
- in paint thinners and glues
Acute Toxicity: CNS depression
- no evidence of cancer
- biotransformation route determines the decreased toxicity
Toluene and Xylenes
