toxicology lect 8 Flashcards
arises from a single or multiple exposure to an agent over 1-2 days
acute toxicity
occurs from repeated exposures of a agent over a period no longer than 3 months
subacute toxicity
occurs from repeated exposures over a period greater than 3 months
chronic toxicity
synergism effect of drugs
when two drugs that have the same effect are used together and the response is greater than what would be expected by adding the responses to the drugs used alone
effect of volume of distribution (Vd) of a toxin on the ability to purify a drug
the larger the Vd of a toxin the harder it is purify the blook through hemodialysis because the toxin is accumulated in the periphery
at very high and toxic concentrations, elimination process may become saturated and toxins or drugs normally elimited by first order kinetics become elimiated via what
zero order kinetics
what are the primary determinants of toxicity
- dose and dose rate
- duration of exposure (AUC)
- route of exposure
what is the mechanism of toxicity of cyanide
interfere with cellular energy function
necrosis
- acute, traumatic premature death of cells in living tissue
- caused by factors external to the cell or tissue
- lack of a proper immune response leads to a buildup of dead tissue and cell debris
when is gastric lavage not recommended after acute poisoning
- 4 hours after consumption
- 30 min have elapsed since ingestion of a corrosive material
- ingestion of hydrocarbon solvents
- coma, stupor, delirium or convulsions are present
what is ipecac syrup used for
induces emesis; treatment of acute poisoning
what can be done to increase the rate of excretion following an acute poisoning
- osmosis diuretics
- alter urinary pH (bicarbonate, ammonium chloride)
- hemodialysis and hemoperfusion
** small the Vd, the more effective the dialysis
what drug can be administered to reduce the absorption or enhance the elimination of chemicals
activated charcoal
what drug can be administered to reduce the absorption or enhance the elimination of bases
ammonium chloride: acidify urine
what drug can be administered to reduce the absorption or enhance the elimination of acids
sodium bicarbonate: alkalinize the urine
Dimercaprol chelates what metals
arsenic
penicillamine chelates what metal
copper
*used in Wilson’s disease and resistant cases of rheumatoid arthritis
Deferoxamine chelates what metal
iron
calcium disodium edetate chelates what metal
lead
what drug can be given to inactivate the toxins with acetaminophen poisoning
acetylcysteine
what drug is used to treat cholinesterase inhibitor poisons (OPs)
atropine
what drug is used to treat sodium nitrite, Na+ thiosulfate, and amyl nitrite poisoning
cyanide antidote
what drug is used to treat methanol or ethylene glycol poisoning
ethanol
what drug is used to treat ethylene glycol poisoning
fomepizole
mechanism of bleach (3-6% sodium hypochlorite in water) poisoning. what are the symptoms?
- oxidative stress
- symptoms
- severe irritation
- hypotension
- delirium
- coma
treatment of bleach poisoning
remove from skin by flooding with water
- do not use emesis or lavage
- use mik, melted ice cream or beaten eggs
- antacids
mechanism of ethylene glycol poisoning
- converted to oxalic acid by alcohol dehydrogenase
- alters calcium homeostasis
symptoms of ethylene glycol poisoning
- CNS depression
- kidney damage due to calcium oxalate crystals
treatment of ethylene glycol poisoning
- gastric lavage
- give ethanol IV
- fomepizole- alcohol dehydrogenase inhibitor
mechanism of botulinus toxin (produced by clostridium botulinum)
inhibits the release of Ach
symptoms of of botulinus toxin
- 8 hr to 8 days
- vomiting
- double vision
- muscular paralysis
treatment of of botulinus toxin
- emesis, gastric lavage
- draw blood to measure toxin concentration
- give equine trivalent antitoxin (ABE)
mechanism of organophosphate (parathion and malathion) poisoning (found in insecticides and pesticides)?
irreversible cholinesterase inhibitor
symptoms of organophosphate poisoning
SLUD
- salvation
- lacrimation
- urination
- defecation
chronic exposure of organophosphate poisoning may contribute to what disease
parkinsons disease
treatment of organophosphate poisoning
atropine to block cholinergic effects
mechanism of organochlorine pesticide (DDT, Dieldrin) poisoning
interfere with the inactivation of sodium channel and enhance neuron excitability causing rapid repetitive firing
symptoms of organochlorine pesticide (DDT, Dieldrin) poisoning acute and chronic exposure
- acute:
- CNS stimulation
- tremors
- chronic
- association with brain CA, tesicular CA, non-hodgkin’s lymphoma, alzheimers
treatment after organochlorine pesticide (DDT, Dieldrin) poisoning
none, symptomatic
mechanism of chlorophenoxy compounds (TCDD): 2,3,7,8 tetrachloro-p-dioxin (herbicide) poisoning
agonist for aryl hydrocarbon (AH) receptor, induces gene expression
mechanims of paraquat poisoning
oxidative stress
symptoms of paraquat poisoning
- hematemesis
- ocular surface toxicity; skin irritant
- pulmonary edema and fibrosis
treatment of paraquat poisoning
- lavage, cathartics, charcoal
mechanism of carbon tetrachloride (CCl4) poisoning
metabolized by a CYP450 to free radicals -> apoptotic cell death
symptoms of carbon tetrachloride (CCl4) poisoning
- CNS depression
- cardiac arrhythmias
- liver and kidney damage
- carcinogenic
treatment of carbon tetrachloride (CCl4) poisoning
remove contaminated clothing and treat symptoms
mechanism of mineral acid (corrosive) poisoning
oxidative stress
symptoms of mineral acid (corrosive) poisoning
- inflammation and necrosis of GI tract
- hypovolemic shock due to massive hemorrhage
treatment of mineral acid (corrosive) poisoning
- do not use gastric lavage or emetic compounds
- dilute acid with water
- milk of magnesia
mechanism of arsenic (heavy metal) poisoning
binds to SH groups on metabolic enzymes, increased oxidative stress
acute and chronic symptoms of arsenic (heavy metal) poisoning
- acute
- G.I. effects; CNS effects, ventricular arrhythmias
- chronic
- polyneuritis, nephritis, cardiac failure, liver cirrhosis
treatment of arsenic (heavy metal) poisoning
dimercaprol
mechanims of lead poisoning
oxidative stress
*primarily bound to erythrocytes, redistributed and accumulates in other tissues, especially bone
neuromuscular effects of lead poisoning
wrist drop and ankle drop
treatment of lead poisoning
chelation (edetate calcium disodium)
mechanismof iron poisoning
oxidative injury; corrosive effect in GI tract
symptoms of iron poisoning
- severe G.I irritation
- mucosal block is destroyed
- hypotension, shock
treatment of iron poisoning
deferoxamine
mechanism of copper poisoning
redox cycles, increases oxidative stress
wilson’s disease
genetic disorder in which the body cannot eliminate copper and it accumulates in tissue
treatment of copper poisoning
penicillamine
mechanism of asbestos
- redox cycles, increases oxidative stress
- chronic inflammatory action
treatment of asbestos poisoning
symptomatic
mechanism of carbon monoxide poisoning
impairs ability of oxyhemoglobin to transport O2
treatment of carbon monoxide poisoning
administer O2 by best means available
mechanism of cyanide poisoning
complexes with ferric iron of cytochrome oxidase, produces cellular anoxia by inhibiting oxygen utilization in mitochondria
treatment of cyanide poisoning
- rapid
- cyanide antidote = sodium nitrite or amyl nitrite
- then give sodium thiosulfate and rhodanese
symptoms of chronic lead poisoning
CNS effects: hyperirritability, behavior disturbances and intellectual deficits, finally coma and intractable convulsions
Role of Rhodanese in cyanide metabolism
CN- + S (thiosulfate) → SCN- (excreted)
