LiverTox activity

What is a likelihood score?

Likelihood that a medication is associated with drug induced liver injury

What are the categories of Likelihood scores?

A- well known

B- known or highly likely

C- probably

D- possible

E- not believed/unlikely

E*- unproven, but suspected

[H]- toxic at HIGH doses

X- unknown

What is valproate’s likelihood score? What is the mechanism of hepatotoxicity?

A- due to mitochondrial toxicity

What is the antidote to valproate?

carnitine

What is the BBW for valproate?

BBW- hepatotoxicity, fetal abnormalities, mitochondrial injury, pancreatitis

What is lamotrigine’s likelihood score? Who is more susceptible to toxicity?

A- women, children and pts. taking valproic acid are more susceptible.

If a patient develops hepatotoxicity with lamotrigine, what other medications should they avoid?

• phenytoin

• phenobarbital

• carbamazepine

• aka anticonvulsants

What does adjustments are required for hepatic impairment with lamotrigine?

• Mild impairment- no dosage adjustment

•   Moderate/severe impairment- decrease initial, escalation, and maintenance doses by 25%

• Moderate/severe impairment with ascites- decrease initial, escalation, and maintenance doses by 50%

What is amiodarone’s likelihood score? How often should LFTs be monitored on this drug? What is the antidote available for toxicity?

• A

• LFTs monitored at baseline and semiannually (every 6 months)

• no ANTIDOTE

What is sulfamethoxazole-trimethoprim’s likelihood score? What is the mechanism of injury? What kind of injury occurs?

• NO SCORE AVAILABLE

• mechanism: drug-allergy/hypersensitivity

• CAUSES A MIXED INJURY (cholestatic+hepatocellular)

What is vitamin A’s likelihood score? What is the recommended daily allowance for vitamin A?

• A

• daily allowance: 700-800 mcg/day (~2300 to 4300 IU)

What is St. John’s Wort’s likelihood score? Why might St. John’s Wort be implicated in a drug-induced liver injury?

• E

• it may increase the likelihood of OTHER DRUGS causing drug induced liver injury

What is St. John’s Wort an inducer of?

• CYP3A4

• CYP2C9

• CYP2C19

• CYP1A

• p glycoprotein

What medication classes in general can interact with St. John’s Wort?

• birth control pills

• transplant rejection agents

• antiretroviral agents

• digoxin

• platelet inhibitors

• anticoagulants

• psychotropic agents

What is acetaminophen’s likelihood score? What is the antidote?

• A

• N-acetylcysteine