Toxicology

Question 1

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

Answer 1

12 hours

Question 2

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?

Answer 2

5

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

Question 3

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

Answer 3

True

Question 4

What types of drugs remain confined to the vascular space?

Answer 4

Hydrophilic

Question 5

Volume of distribution (Vd) - High or Low:

• Hydrophobic
• Hydrophilic

Answer 5

• Hydrophobic - High Vd

- Hydrophilic - Low Vd

Question 6

Describe Ethanol metabolism

Answer 6

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

Question 7

What are markers of alcohol consumption>

Answer 7

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

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

Question 8

Common Toxidromes - Anticholinergic:

• Signs/Symptoms
• Agents

Answer 8

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

Question 9

Common Toxidromes - Cholinergic:

• Signs/Symptoms
• Agents

Answer 9

“SLUDGE”

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

Question 10

Common Toxidromes - Adrenergic:

• Signs/Symptoms
• Agents

Answer 10

Hypertension, Tachycardia, mydriasis, anxiety, hyperthermia

• Amphetamines
• Cocaine
• Ephedrine
• PCP

Question 11

Toxic agents - Sign/Symptoms:

-Pin-point pupils (miosis) (3)

Answer 11

Miosis

• Cholinergics
• Opiates
• Benzos

Question 12

Toxic agents - Sign/Symptoms:

-Dilated pupils (mydriasis) (3)

Answer 12

Mydriasis

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

Question 13

Toxic agents - Sign/Symptoms:

-Garlic odor (2)

Answer 13

• Organophosphates

- Arsenic

Question 14

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

Answer 14

• Cyanide

- Hydrogen sulfide

Question 15

Antifreeze is what?

Answer 15

Ethylene glycol

Question 16

What substances contain Methanol?

Answer 16

• Wiper fluid
• Paint removers
• Wood alcohol

Question 17

Isopropyl alcohol is found in what?

Answer 17

Rubbing alcohol

Question 18

Ethylene glycol and Methanol both cause what? (2)

Answer 18

• Increased anion gap

- Increased osmolal gap

Question 19

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

Answer 19

• Ethanol

- Isopropyl alcohol

Question 20

What is ethylene glycol metabolized to?

-What does this cause?

Answer 20

• Oxalate

- Oxalate crystals in urine

Question 21

What are the characteristics of oxalate crystals?

Answer 21

• Envelop shaped
• Translucent
• Birefringent

Question 22

What is methanol metabolized to?

Answer 22

Formaldehyde then formic acid

Question 23

Isopropyl alcohol is metabolized to?

Answer 23

Acetone

Question 24

Treatment for methanol or ethylene glycol poisoning?

Answer 24

Ethanol or Fomepizole

-inhibiting activity of alcohol dehydrogenase

Question 25

What are the two general mechanisms of Lead toxicity?

Answer 25

- Inhibits enzymes with sulfhyryl groups | - Directly toxic to mitochondria

Question 26

Lead inhibits what two key enzymes in heme synthesis? | -What does this lead to?

Answer 26

- 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)

Question 27

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

Answer 27

Increased osmotic fragility | -Decreased RBC survival

Question 28

Basophilic stippling results from inhibition of what? | -What is the normal function

Answer 28

Inhibition of 5' nucleotidase | -Break down RNA

Question 29

Lead toxicity manifestations: - P.smear - Neurologic - Renal

Answer 29

- Microcytic, hypochromic anemia with basophilic stippling - Bilateral wrist drop - Renal insufficiency (aminoaciduria, glycosuria, phosphaturia) *Abdominal pain

Question 30

Acetaminophen (Tylenol) poisoning: | -Manifestations (4 phases)

Answer 30

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

Question 31

What can be used to predict acetaminophen poisoning risk?

Answer 31

Rumack-Matthew nomogram

Question 32

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

Answer 32

N-acetyl-P-benzoquinone imine (NAPQI)

Question 33

What is the mechanism of cyanide poisoning?

Answer 33

Inhibits cytochrome a3 - uncouples ETC - causes severe anion gap metabolic (lactic) acidosis

Question 34

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

Answer 34

Bright cherry red skin color

Question 35

Salicylate (aspirin) poisoning: | -Manifestations (4)

Answer 35

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)

Question 36

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

Answer 36

6 hour plasma salicylate concentration | - >130 mg/dL (high mortality)

Question 37

MOA of arsenic poisoining?

Answer 37

Inhibits oxidative production of ATP

Question 38

What is the most reliable test for Arsenic poisoning?

Answer 38

Quantitative 24 hour urinary arsenic excretion *blood arsenic level is highly unreliable

Question 39

Organophosphates: - Source - MOA

Answer 39

- Insecticides | - Inhibihts acetylcholinesterase

Question 40

Mercury toxicity: - Acute (2) - Chronic (2)

Answer 40

Acute - Respiratory distress - Renal failure Chronic ("Mad Hatter's disease") - Acrodynia (Feer syndrome) - Erethism (personality changes)

Question 41

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)

Answer 41

- Neonates - Pregnancy - Liver failure - Renal failure

Question 42

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

Answer 42

Nephrotoxicity and Ototoxicity