Toxicology Flashcards
Bioaccumulation
Increasing concentration of a substance in the environment resulting from environmental persistence and physical properties
Biomagnification
is the fold increase in concentration of a substance that occurs in a food chain as a consequence of bioaccumulation
Endocrine disruptors
Chemicals in the environment that have endocrine effects (estrogen/anti-androgen/thyroid). Potential cause of infertility, reproductive cancers or birth defects.
Environmental toxicology
EPA Environmental Protection Agency regulates toxicology and environmental exposure to chemicals
Acceptable daily intake (ADI)
Daily intake of chemical which during lifetime appears to be without appreciable risk.
Occupational toxicology
OSHA Occupational Safety and Health Agency regulates exposure of workers to chemicals
Threshold limit value (TLV)
Exposure limit to a specific agent for a stated period of time-(shorter time = higher level). Used for occupational control.
Carbon Monoxide Poisoning
Description of CO Symptoms Mechanism Prevention Treatment
Description of CO
- Odorless, colorless gas
Symptoms
- Headache, loss of judgement, dizziness, nausea, convulsion & death
Mechanism
- Competes avidly with oxygen for hemoglobin (200 fold greater affinity) -affinity for fetal hemoglobin even higher.
Diagnosis
A CO-oximeter must be used to determine carboxyhemoglobin (COHb) levels. A regular pulse oximeter will misrepresent carboxyhemoglobin for oxyhemoglobin
Treatment
- 100% oxygen and hyperbaric oxygen
Solvents–benzene and toluene
Source
Acute exposure symptoms
Chronic exposure symptoms
Inhaltion effects
Common – many consumer products, gasoline, manufacturing etc.
Acute exposure: CNS depression with ataxia and coma.
Chronic exposure: Neuro- and bone marrow toxicity, leukemia.
Inhalation can cause chemical pneumonitis.
Difference in lethal dose of gasoline/benzene when taken by lung or digestion
GIT needs larger LD 50 than lungs even in children so be careful of making patient who swallowed gasolone vomit since there is a risk they could aspirate it into his lungs
Name 2 classes of agents in pesticide toxicology
with examples
Chlorinated hydrocarbons (DTT, DDD, dioxin etc)
Cholinesterase inhibitors (carbamates-carbaryl, organophosphates-malathion, parathion)
Cholinesterase inhibitors (carbamates-carbaryl, organophosphates-malathion, parathion)
Mechanism
Side Effects
Treatment
Chlorine confers environmental stability
Moderately toxic, bioaccumulate, concerns about endocrine disruption, no specific treatment
Cholinesterase inhibitors (carbamates-carbaryl, organophosphates-malathion, parathion)
Mechanism
Symptoms
Treatment
Environmentally less stable than chlorinated pesticides
Muscarinic and nicotinic activators, SLUDGE (Salivation, Lacrimation, Urination, Defecation, GI upset, Emesis).
Treatment = Atropine blocks receptor activation + Pralidoxime to regenerate cholinesterase.
Name 3 agents in herbicide toxicology
Chlorophenoxy Acids (2,4-dichlorophenoxiacetic acid and 2,4,5-trichlorophenoxyacetic acid)
Glyphosate
Paraquat-bipyridyl herbicide.
Chlorophenoxy Acids (2,4-dichlorophenoxiacetic acid and 2,4,5-trichlorophenoxyacetic acid)
In Vietnam War, above combination code-named Agent Orange -associated with chronic disease- to date association inclusive
Glyphosate
Most widely used herbicide in the world. Causes eye and skin irritation. No specific treatment.
Paraquat-bipyridyl herbicide
Ingestion can be fatal. GI irritation, hematemesis and bloody stools. Within days pulmonary impairment can lead to pulmonary fibrosis and possibly death. Treatment supportive. Gastric lavage if recent ingestion and dialysis.
Common sources of CO
Motor vehicle exhaust Spillage from appliances Building fires Forklift trucks, snow blowers Generators, heaters Zamboni, (oh, yes!)
Clues of CO posining
More than one person affected
Pets affected
Temporal relation of symptoms and use of combustion appliances
Main indoor pollutant causing headaches is CO, but
Tobacco smoke, volatile organics
Lead Age group at risk Chronic exposure signs Histological signs Treatment
Children - paint chip ingestion
Chronic exposure
- peripheral neuropathy
- wrist-drop)
- anorexia
- anemia
- tremor
- GI symptoms
- children: growth delay, neurocognitive deficits, and developmental delay
- Lead line seen in chronic lead poisoning on gums just above teeth in 50-70% patients.
Histoligical signs
- Basophilic stippling in red blood cells.
Treatment
- Oral succimer used as preferred chelator in children
Arsenic
Acute poisoning
Chronic poisoning
Acute
- severe GI discomfort
- Rice water stools
- Vomiting
- Capillary damage with dehydration and shock (similar to typhoid and cholera)
Chronic
- Groun water/private wells/soil
- Skin changes
- Hair loss
- Bone marrow depression
- Anemia
- Nausea
- GI distress
Mee’s lines
Transverse white lines that run across the nail, following the shape of the nail moon.
Arsenic poisoning.
Mercury
Acute poisoning
Chronic poisoning
Organic mercury
Treatment
Acute Poisoning
- Acute poisoning causes chest pain shortness of breath, nausea, vomiting, kidney damage, gastroenteritis and CNS damage.
Chronic Poisoning
- Neurological and behavioral changes
Organic Mercury
- Anti-fungal agent and has high potential to bioaccumulate. Generally, more toxic than ionic or metallic mercury compounds. Highly fetal toxic.
Treatment
Succimer or IM dimercaprol
Fe
Acute (Early and Late)
Treatment
Acute
Early
- GI bleeding, lethargy and grey cyanosis
Late
- GI necrosis can occur, pneumonitis, jaundice, seizures and coma
Treatment
- Deferoxamine
- Charcoal does not bind iron therefore use gastric lavage if within 60 minutes, if longer than an hour use whole bowel irrigation(Polyethylene glycol bowel prep (GoLYTELY, Colyte))
CHelators mechanism of action
Have 2 (bidentate) or more (polydentate) electronegative groups to complex with cationic metal atoms.
2 limitations of chelators
1) Organometals not chelated e.g. lead additive in gas, organic mercury through bioaccumulation (e.g. fish).
2) Chelators cannot reverse damage only prevent further damage caused by heavy metals.
Acetaminophen
Treatment and treatment mechanism
When should it be given?
Other items that can be given
N-acetylcysteine
When acetaminophen is taken n overdose it is metabolized by the liver into a toxic metabolite
- N-acetylcysteine increases glutathione stores
- Combines directly with acetaminophen’s reactive metabolite as a glutathione substitute
- Enhances sulfate conjugation
- Within 1-2 hours after ingestion of acetaminophen
- Activated chacoal
- Supportive therapy: IV fluids, oxygen, and cardiac monitor.
Aspirin
Mechanism of toxicity
Symptoms
Treatment
Mechanism of toxicity
- uncoupling of oxidative phosphorylation
- increased oxygen consumption
- Increased carbon dioxide production
- Accelerated activity of the glycolytic and lipolytic pathways
- Depletion of hepatic glycogen
- Hyperpyrexia
Symptoms
- Respitory alkalosis with anion gap metabolic acidos
- Tinnitus
- Hyperthermia
- Hypernea
Treatment
- Less than 60 minutes: Gastric lavage
- More than 60 minutes:
- activated charcoal
- Alkanalize urine to encourage secretion
- Furosemide (supplement K lost)
- Hemodialysis
- Whole bowel irrigation if a large mass of pills is ingested
Benzodiazapine
Treatement
Flumazenil
Flumazenil blocks site of benzodiazepine action. Avoid in patients with seizures, benzodiazepine dependence or tricyclic overdose
Methanol, ethylene glycol
Treatment
Fomepizole
To reduce production of toxic metabolites this drug competes for alcohol dehydrogenase. Methanol causes severe vision disturbances.
Beta-blockers
Glucagon
Acts on cardiac cells to raise intracellular cAMP independently of β adrenoceptors.
Cholinesterase inhibitors-Organophosphates, carbamates, malathion
Treatment
Atropine and pralidoxime (2-PAM)
Atropine competes for muscarinic receptors and 2-PAM given early can regenerate cholinesterase activity
Acetaminphen
Treatment
N-acetylcysteine (NAC)
Give within 8-10 hours, follow liver function tests and drug levels. NAC acts as a glutathione substitute and binds hepatotoxic metabolite as it is made.
Asprin
Treatment
IV Na bicarbonate
Respiratory alkalosis followed by metabolic acidosis. For moderate cases IV sodium bicarbonate alkalizes urine promoting salicylate excretion. Severe cases: hemodialysis
Hypertension and tachycardia
Amphetamines, cocaine and anticholinergics
Hypotension and bradycardia
Calcium channel blockers, beta-blockers, clonidine and sedative hypnotics
Hypotension and tachycardia
Tricyclic antidepressants, vasodilators and beta-agonists
Rapid respiration
Salicylates, carbon monoxide, other toxins that cause metabolic acidosis or cellular asphyxia.
Hyperthermia
sympathomimetics, anticholinergics, salicylates, and drugs producing seizures or muscular rigidity
Hypothermia
Any CNS-depressant drug, especially when accompanied by exposure to a cold environment
Widening of the QRS complex duration
tricyclic antidepressant and quinidine
QTc interval prolonged
quinidine, antidepressants and antipsychotics, lithium, and arsenic
Variable atrioventricular (AV) block plus atrial and ventricular arrhythmias
digoxin and other cardiac glycosides
Ischemic changes
Hypoxemia due to carbon monoxide
Which drugs to focus on for this lecture
- Carbon monoxide
- Organophosphate (carbamyl/malathion/parathion)
- Iron
- Lead
- Arsenic
- Acetaminophen
- Aspirin
- Benzodiazepines
- Methanol. ethylene glycol
