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Case 9: Liver > Drugs & Liver > Flashcards

Drugs & Liver Flashcards

1
Q

Explain drug metabolism & the forms of the metabolites

A
  1. The drugs enter as lipophilic molecules to be able to cross cell membrane to reach site of action
  2. Metabolism required to generate hydrophilic molecule to be eliminated via urine or bile
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2
Q

Where does most of drug metabolism occur

A

Liver

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3
Q

Explain how the activity of a metabolite change

A

Most metabolite lose activity
While some become more active than parent drug like prodrug

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4
Q

What is the most common phase 1 enzyme

A

Cytochrome P450

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5
Q

Where does oxidative metabolism of CYP450 occur

A

Endoplasmic reticulum

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6
Q

What substance does CYP450 metabolise

A

Endogenous & exogenous substances

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7
Q

What is first pass effect

A

Pre-systemic elimination of drug & metabolised by liver or GIT before entering circulation

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8
Q

What is the solution for high first pass effect

A

Increase dosage

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9
Q

What is the significance of portal hypertension & drug concentration

A

The liver is bypasses therefor no/little first pass effect & higher concentrations that can lead to toxicity

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10
Q

Explain enterohepatic circulation of drugs

A

Drugs gets conjugated in the liver & secreted into bile to GIT
In GIT some bacteria can deconjugate the metabolites & gets reabsorbed into liver that prolongs drug effect

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11
Q

Name 3 drugs make use of enterohepatic circulation

A

Oral contraceptives
Morphine
Warfarin

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12
Q

What can be used in an overdose

A

Charcoal consumption

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13
Q

What score is used to predict impaired liver function

A

Child-Pugh score

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14
Q

What is the problem w/ liver damage & drug use

A

The liver is damaged & decreased functions
Less ability to detoxify & prolonged half life or elimination resulting in toxicity

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15
Q

What is the best way of drug prescription in someone w/ liver damage

A

A drug that does not require hepatic metabolism or metabolised by CYP450 as it is not that affected by liver disease

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16
Q

What is the second best option for drug prescriptions & liver damage & why

A

Decrease the dose of drug as the first pass effect is bypassed due to vascular shunting

17
Q

For what is people w/ liver disease at higher risk of w/ drugs

A

Drug-induced hepatotoxic reactions

18
Q

Is mild transient elevation of liver enzymes normal & why

A

Yes it is normal due to adaptation

19
Q

What is the 3 most common causes for drug-induced hepatotoxicity

A

Toxic intermediate metabolites
Genetic susceptibility
Dose-dependent

20
Q

How longs does it take for idiosyncratic drug reactions to occur

A

W/i 2 weeks

21
Q

What does rechallening mean

A

Restarting a drug that was thought to be reason for side effects but can lead to more severe reactions

22
Q

What is 4 clinical feature of hepatitis

A

Malaise
N/V
Jaundice
RUQ pain/tenders

23
Q

Does clinical features of hepatocellular damage resolve once drug is discontinued

A

Yes sometime fulminant & rare chronic disease

24
Q

What is the most common drug-induced cholestasis

A

Acute cholestasic hepatitis

25
Q

What is a severe form of drug-induced cholestasis

A

Varnishing bile duct syndrome

26
Q

What 2 biochemical marker is elevated w/ drug-induced cholestasis

A

ALT <2
Conjugated bilirubin

27
Q

How long does it take for drug-induced cholestasis to resolve

A

W/i 1 months

28
Q

What is the 4 symptoms of systemic hypersensitivity caused by hepatotoxicity

A

Rash
Fever
Eisonophilia
Potentially life threatening reactions

29
Q

When is drug induced hepatic steatosis considered

A

When excessive alcohol use is excluded

30
Q

How is steatosis diagnosed

A

Hepatic imaging or biopsy

31
Q

What is common drugs causing steatosis

A

Nucleoside analogue, RT inhibitors, corticosteroids & valproate

32
Q

What is a clinical & biochemical sign of hepatic steatosis

A

Clinical mild hepatomegaly
Biochemical liver enzymes (ALT>AST)

33
Q

Is hepatic steatosis reversible

A

Yes potentially

34
Q

What spectrum of disorders does drug-induced hepatic steatosis cause

A

Abnormal fat accumulation that can be benign or inflammation leading to fibrosis & lastly cirrhosis

Case 9: Liver (8 decks)

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