Toxicology Flashcards
If a drugs T1/2 is 12 hours, then doses are typically given how often?
12 hours
The steady state exists when the amount of drug leaving the body equals the amount entering, this point is reached after how many half-lives?
5
*after 5 doses give at intervals of 1 half-life each
T/F: In the steady state, drug concentration is lowest right before a dose (trough), and highest shortly after (peak).
True
What types of drugs remain confined to the vascular space?
Hydrophilic
Volume of distribution (Vd) - High or Low:
- Hydrophobic
- Hydrophilic
- Hydrophobic - High Vd
- Hydrophilic - Low Vd
Describe Ethanol metabolism
- Metabolized by Hepatic Alcohol Dehydrogenase to Acetaldehyde
- Converted by Aldehyde Dehydrogenase to Acetic Acid
What are markers of alcohol consumption>
y-glutamyl transferase (GGT)
-Increased in heavy users; 4 weeks to normalize
Carbohydrate deficient transferrin (CDT)
-as sensitive, and more specific than GGT
Common Toxidromes - Anticholinergic:
- Signs/Symptoms
- Agents
Hot as a hare (hyperthermia), Dry as a bone (dry skin), Red as beet (flusing), Mad as a Hatter (AMS, psychosis)
- Atropine
- Antihistimine
- Tricyclic antidepressants
- Scopolamine
Common Toxidromes - Cholinergic:
- Signs/Symptoms
- Agents
“SLUDGE”
- Salivation, Lacrimation, Urination, Diarrhea, GI cramps, Emesis
- Organophosphates
- Pilocarpine
- Carbamate
Common Toxidromes - Adrenergic:
- Signs/Symptoms
- Agents
Hypertension, Tachycardia, mydriasis, anxiety, hyperthermia
- Amphetamines
- Cocaine
- Ephedrine
- PCP
Toxic agents - Sign/Symptoms:
-Pin-point pupils (miosis) (3)
Miosis
- Cholinergics
- Opiates
- Benzos
Toxic agents - Sign/Symptoms:
-Dilated pupils (mydriasis) (3)
Mydriasis
- Anticholinergics
- Sympathomimetics (cocaine, amphetamines)
- Carbon monoxide
Toxic agents - Sign/Symptoms:
-Garlic odor (2)
- Organophosphates
- Arsenic
Abnormally high venous oxygen content (arterialization of venous blood) is seen in what type of poisoning? (2)
- Cyanide
- Hydrogen sulfide
Antifreeze is what?
Ethylene glycol
What substances contain Methanol?
- Wiper fluid
- Paint removers
- Wood alcohol
Isopropyl alcohol is found in what?
Rubbing alcohol
Ethylene glycol and Methanol both cause what? (2)
- Increased anion gap
- Increased osmolal gap
What alcohols do NOT cause acidosis but do cause an osmolal gap?
- Ethanol
- Isopropyl alcohol
What is ethylene glycol metabolized to?
-What does this cause?
- Oxalate
- Oxalate crystals in urine
What are the characteristics of oxalate crystals?
- Envelop shaped
- Translucent
- Birefringent
What is methanol metabolized to?
Formaldehyde then formic acid
Isopropyl alcohol is metabolized to?
Acetone
Treatment for methanol or ethylene glycol poisoning?
Ethanol or Fomepizole
-inhibiting activity of alcohol dehydrogenase
What are the two general mechanisms of Lead toxicity?
- Inhibits enzymes with sulfhyryl groups
- Directly toxic to mitochondria
Lead inhibits what two key enzymes in heme synthesis?
-What does this lead to?
- gamma-ALA-dehydratase
- Ferrochelatase
- leads to accumulation of precursor protoporphyrin (FEP), which binds to Zinc protoporphyrin (ZPP).
- FEP and ZPP are increased in lead toxicity (and in iron deficiency)
Lead also binds inhibits sodium channel ATPases, that lead to what?
Increased osmotic fragility
-Decreased RBC survival
Basophilic stippling results from inhibition of what?
-What is the normal function
Inhibition of 5’ nucleotidase
-Break down RNA
Lead toxicity manifestations:
- P.smear
- Neurologic
- Renal
- Microcytic, hypochromic anemia with basophilic stippling
- Bilateral wrist drop
- Renal insufficiency (aminoaciduria, glycosuria, phosphaturia)
*Abdominal pain
Acetaminophen (Tylenol) poisoning:
-Manifestations (4 phases)
I- Nausea/abdominal pain; abates within hours
II- Progressive liver injury (+/-24 hours)
III- Fulminant hepatic failure
IV- Recover, Transplant, or Death
What can be used to predict acetaminophen poisoning risk?
Rumack-Matthew nomogram
What is the toxic metabolite in acetaminophen poisoning that induces centrilobular (zone 3) hepatic necrosis?
N-acetyl-P-benzoquinone imine (NAPQI)
What is the mechanism of cyanide poisoning?
Inhibits cytochrome a3
- uncouples ETC
- causes severe anion gap metabolic (lactic) acidosis
In cyanide poisoning, oxygen accumulates in the blood which gives rise to what characteristic finding?
Bright cherry red skin color
Salicylate (aspirin) poisoning:
-Manifestations (4)
1-Respiratory Alkalosis - Directly stimulates respiratory center within medulla
2-Metabolic acidosis (compensation)
3-Uncouples oxidative phosphorylation and inhibits Kreb cycle (metabolic acidosis)
4-CNS depression (may result in respiratory acidosis)
Salicylate (aspirin) poisoning mortality is best correlated with what?
6 hour plasma salicylate concentration
- >130 mg/dL (high mortality)
MOA of arsenic poisoining?
Inhibits oxidative production of ATP
What is the most reliable test for Arsenic poisoning?
Quantitative 24 hour urinary arsenic excretion
*blood arsenic level is highly unreliable
Organophosphates:
- Source
- MOA
- Insecticides
- Inhibihts acetylcholinesterase
Mercury toxicity:
- Acute (2)
- Chronic (2)
Acute
- Respiratory distress
- Renal failure
Chronic (“Mad Hatter’s disease”)
- Acrodynia (Feer syndrome)
- Erethism (personality changes)
Endogenous substances that cross react with Digoxin, termed Digoxin-Like Immunoreactive Substances (DLIS), are found in blood of individuals NOT taking Digoxin. What situations do these occur? (4)
- Neonates
- Pregnancy
- Liver failure
- Renal failure
How does Aminoglycosides (e.g. Gentamicin) toxicity manifest?
Nephrotoxicity and Ototoxicity
