Toxicology Flashcards

1
Q

If a drugs T1/2 is 12 hours, then doses are typically given how often?

A

12 hours

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2
Q

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?

A

5

*after 5 doses give at intervals of 1 half-life each

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3
Q

T/F: In the steady state, drug concentration is lowest right before a dose (trough), and highest shortly after (peak).

A

True

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4
Q

What types of drugs remain confined to the vascular space?

A

Hydrophilic

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5
Q

Volume of distribution (Vd) - High or Low:

  • Hydrophobic
  • Hydrophilic
A
  • Hydrophobic - High Vd

- Hydrophilic - Low Vd

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6
Q

Describe Ethanol metabolism

A
  • Metabolized by Hepatic Alcohol Dehydrogenase to Acetaldehyde
  • Converted by Aldehyde Dehydrogenase to Acetic Acid
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7
Q

What are markers of alcohol consumption>

A

y-glutamyl transferase (GGT)
-Increased in heavy users; 4 weeks to normalize

Carbohydrate deficient transferrin (CDT)
-as sensitive, and more specific than GGT

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8
Q

Common Toxidromes - Anticholinergic:

  • Signs/Symptoms
  • Agents
A

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
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9
Q

Common Toxidromes - Cholinergic:

  • Signs/Symptoms
  • Agents
A

“SLUDGE”

  • Salivation, Lacrimation, Urination, Diarrhea, GI cramps, Emesis
  • Organophosphates
  • Pilocarpine
  • Carbamate
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10
Q

Common Toxidromes - Adrenergic:

  • Signs/Symptoms
  • Agents
A

Hypertension, Tachycardia, mydriasis, anxiety, hyperthermia

  • Amphetamines
  • Cocaine
  • Ephedrine
  • PCP
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11
Q

Toxic agents - Sign/Symptoms:

-Pin-point pupils (miosis) (3)

A

Miosis

  • Cholinergics
  • Opiates
  • Benzos
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12
Q

Toxic agents - Sign/Symptoms:

-Dilated pupils (mydriasis) (3)

A

Mydriasis

  • Anticholinergics
  • Sympathomimetics (cocaine, amphetamines)
  • Carbon monoxide
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13
Q

Toxic agents - Sign/Symptoms:

-Garlic odor (2)

A
  • Organophosphates

- Arsenic

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14
Q

Abnormally high venous oxygen content (arterialization of venous blood) is seen in what type of poisoning? (2)

A
  • Cyanide

- Hydrogen sulfide

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15
Q

Antifreeze is what?

A

Ethylene glycol

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16
Q

What substances contain Methanol?

A
  • Wiper fluid
  • Paint removers
  • Wood alcohol
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17
Q

Isopropyl alcohol is found in what?

A

Rubbing alcohol

18
Q

Ethylene glycol and Methanol both cause what? (2)

A
  • Increased anion gap

- Increased osmolal gap

19
Q

What alcohols do NOT cause acidosis but do cause an osmolal gap?

A
  • Ethanol

- Isopropyl alcohol

20
Q

What is ethylene glycol metabolized to?

-What does this cause?

A
  • Oxalate

- Oxalate crystals in urine

21
Q

What are the characteristics of oxalate crystals?

A
  • Envelop shaped
  • Translucent
  • Birefringent
22
Q

What is methanol metabolized to?

A

Formaldehyde then formic acid

23
Q

Isopropyl alcohol is metabolized to?

A

Acetone

24
Q

Treatment for methanol or ethylene glycol poisoning?

A

Ethanol or Fomepizole

-inhibiting activity of alcohol dehydrogenase

25
Q

What are the two general mechanisms of Lead toxicity?

A
  • Inhibits enzymes with sulfhyryl groups

- Directly toxic to mitochondria

26
Q

Lead inhibits what two key enzymes in heme synthesis?

-What does this lead to?

A
  • 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)
27
Q

Lead also binds inhibits sodium channel ATPases, that lead to what?

A

Increased osmotic fragility

-Decreased RBC survival

28
Q

Basophilic stippling results from inhibition of what?

-What is the normal function

A

Inhibition of 5’ nucleotidase

-Break down RNA

29
Q

Lead toxicity manifestations:

  • P.smear
  • Neurologic
  • Renal
A
  • Microcytic, hypochromic anemia with basophilic stippling
  • Bilateral wrist drop
  • Renal insufficiency (aminoaciduria, glycosuria, phosphaturia)

*Abdominal pain

30
Q

Acetaminophen (Tylenol) poisoning:

-Manifestations (4 phases)

A

I- Nausea/abdominal pain; abates within hours
II- Progressive liver injury (+/-24 hours)
III- Fulminant hepatic failure
IV- Recover, Transplant, or Death

31
Q

What can be used to predict acetaminophen poisoning risk?

A

Rumack-Matthew nomogram

32
Q

What is the toxic metabolite in acetaminophen poisoning that induces centrilobular (zone 3) hepatic necrosis?

A

N-acetyl-P-benzoquinone imine (NAPQI)

33
Q

What is the mechanism of cyanide poisoning?

A

Inhibits cytochrome a3

  • uncouples ETC
  • causes severe anion gap metabolic (lactic) acidosis
34
Q

In cyanide poisoning, oxygen accumulates in the blood which gives rise to what characteristic finding?

A

Bright cherry red skin color

35
Q

Salicylate (aspirin) poisoning:

-Manifestations (4)

A

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)

36
Q

Salicylate (aspirin) poisoning mortality is best correlated with what?

A

6 hour plasma salicylate concentration

- >130 mg/dL (high mortality)

37
Q

MOA of arsenic poisoining?

A

Inhibits oxidative production of ATP

38
Q

What is the most reliable test for Arsenic poisoning?

A

Quantitative 24 hour urinary arsenic excretion

*blood arsenic level is highly unreliable

39
Q

Organophosphates:

  • Source
  • MOA
A
  • Insecticides

- Inhibihts acetylcholinesterase

40
Q

Mercury toxicity:

  • Acute (2)
  • Chronic (2)
A

Acute

  • Respiratory distress
  • Renal failure

Chronic (“Mad Hatter’s disease”)

  • Acrodynia (Feer syndrome)
  • Erethism (personality changes)
41
Q

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)

A
  • Neonates
  • Pregnancy
  • Liver failure
  • Renal failure
42
Q

How does Aminoglycosides (e.g. Gentamicin) toxicity manifest?

A

Nephrotoxicity and Ototoxicity