Hepatic Dysfunction Flashcards

1
Q

What drugs are contradicted in severe liver disease

A
  • NSAIDS - can cause an ideosyncratic hepatitis
  • paracetamol - dose dependent acute liver injury
  • co-amoxiclav and flucloxacillin can cause cholestatic hepatitis that resolves in most cases after withdrawal of the drug
  • antituberculosis drugs - these can cause liver injury
  • methotrexate - can cause severe fibrosis and cirrhosis if not adequately monitored
  • amiodarone - can cause a steato-hepatitis
  • ACE
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2
Q

What are NSAIDS contradicted in severe liver disease

A
  • can worsen liver function and some renal function
  • in severe liver disease renal blood flow is reliant on prostacyclins in the kidney and reducing renal blood flow and can lead to deterioration in renal function
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3
Q

Why would you not give spironolactone to renal failure patients

A
  • spironolactone and can cause hyperkalaemia and renal dysfunction
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4
Q

Why is ACE contraindicated in severe liver disease (Child pugh score B and C)

A
  • patient relies in part on activation of the renin angiotensin system to maintain peripheral vascular resistance
  • administration of an ACE inhibitor can lead to a rapid drop in blood pressure and development of renal failure
  • ACE can also cause hyperkalaemia effecting renal function
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5
Q

In alcoholic liver disease what is thiamine crucial in preventing

A
  • It is crucial in preventing wernicke’s encephalopathy and korsakoff psychosis
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6
Q

What are the physical examination signs of hepatic function

A
  • Spider naevi
  • clubbing
  • jaundice
  • loss of secondary sexual hair
  • gynaecomastia
  • ascites
  • splenomegaly
  • peripheral oedema
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7
Q

what can an ultrasound scan provide in liver disease

A
  • cirrhotic liver with splenomegaly

- ascities

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8
Q

What blood tests provide clues to liver function

A
  • albumin
  • prothrombin
  • bilirubin
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9
Q

What is the child pugh score used for

A
  • evaluate operative risk in patients with liver cirrhosis
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10
Q

What 5 things are considered in the child pugh score

A
  • Biliruin
  • serum albumin
  • clotting time
  • ascites
  • encephalopathy
  • each is scored out of 3 points
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11
Q

What are the classes of the child pugh score

A
  • Class A - 5-6 points
  • Class B - 7-9 points
  • Class C - 10-15 points
  • C is the most severe
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12
Q

What is the MELD score used for

A
  • it is also used to assess liver function and used to rank patients waiting a liver transplant
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13
Q

What is the use of child pugh score

A
  • can be a useful indicator of an individuals ability to metabolise a given drug
  • evaluate operative risk in patients with liver cirrhosis
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14
Q

What information do you ask about in a drug history

A
  • Do you take any medication from the doctors
  • how long have you been taking them for
  • do you take anything else at all
  • what for
  • how long for
  • 6 month drug history
  • recreational drugs
  • boderline substances
  • injections, topical agents, inhalers, ear/eye drops
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15
Q

How likely is aspirin in causing hepatic dysfunction

A
  • positive correlation with aspirin and hepatitis

- hepatitis occurs with aspirin in a dose related manner

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16
Q

What type of liver injury does paracetamol cause

A
  • typically causes a dose dependent acute liver injury rather than cholestasis
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17
Q

Does flucloxacillin cause liver injury

A
  • hepatitis and cholestatic jaundice have been reported with flucloxacillin
  • the reaction is idiosyncratic and not dose related
  • onset may be delayed for up to two months post-treatment and the course of the reaction may last for some months
  • change in liver function tests may occur but are reversible when the treatment is discontinued
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18
Q

What can statins cause to happen

A
  • can cause a mild transaminitis - raise in ALT ro ast

- elevations in these enzymes occur in 2% of individuals taking statins

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19
Q

What can statins cause to happen

A
  • can cause a mild transaminitis - raise in ALT ro ast
  • elevations in these enzymes occur in 2% of individuals taking statins
  • can still safely prescribe statins in patients with mild liver dysfunction
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20
Q

What is the leading cause of acute liver failure in the UK

A

150 mg/kg of acutely ingested paracetamol in less than one hour can lead to liver damage in adults

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21
Q

What are risk factors of hepatotoxicity

A
  • chronic alcohol consumption
  • co-medications
  • poor nutritional intake
22
Q

What is the antitdote to paracetamol poisoning

A
  • Acetylcysteine

- this augments glutathione levels

23
Q

Describe how liver damage occurs via paracetamol overdose

A
  • paracetamol is metabolised in the liver and metabolism of paracetamol is required prior to hepatotoxicity
  • liver injury does not occur until glutathione is depleted
  • after this the reactive metabolites of paracetamol bind to cellular macromolecules causing lethal damage to the hepatocyte
24
Q

patients whose plasma paracetamol concentrates are above the treatment line should be treated with …

A

Acetylcystiene by IV infusion

- paracetamol concentration on or above the treatment line should be regarded as carrying a serious risk of liver damage

25
Q

when should treatment be commenced

A
  • Treatment should be commenced if a patient has taken more than 150 mg/kg in any 24 hour period unless
  • the plasma paracetamol concentration is undetectable
  • the patient is asymptomatic
  • LFTs, serum creatinine and INR are all normal
26
Q

How does metabolism of drugs occur

A
  • Phase 1

- phase 2

27
Q

Describe the phases of drug metabolism

A

Phase 1

  • renders the drug more polar by oxidation, reduction, or methylation so it can combine with another molecule
  • the cytochrome P450 group of enzymes is responsible for the majority of phase 1 reactions
  • in cirrhosis the activity of these enzymes can be markedly reduced

Phase 2

  • conjugation
  • this reslts in a water soluble compound that is usually inactive and more easily excreted in the urine or bile
  • some mechanisms of phase 2 reactions such as glucuronidation and sulphation have been shown to be impaired in liver disease
28
Q

what happens to drug metabolism if there is liver dysfunction

A
  • there is a reduction in metabolism

- reduced metabolism will require dose adjustment for some drugs

29
Q

Name drug doses that need adjusting after hepatic impairment

A
  • fluoxetine
  • nifedipine
  • phenytoin
30
Q

does first pass metabolism reduce oral bioavailability

A
  • First pass metabolism will pass through the liver and be partially or wholly metabolized before reaching the systemic circulation reducing oral bioavailability
31
Q

If blood flow through the liver is slowed a drug may be…

A

Subject to increased metabolism as it may stay in the liver for longer

32
Q

What happens in cirrhosis that results in decrease first pass metabolism

A
  • patients with cirrhosis develops collaterals enabling the blood to bypass the liver
  • this results in a decrease in first pass metabolism
  • this increases bioavaliability in the liver and the bioavaliability can increase to 100% as first pass metabolism is bypassed
  • therefore you would reduced drug doses to avoid toxicity
33
Q

what enzymes are important in first pass metabolism in the liver

A
  • Cytochrome P450 in the liver or wall of the gut
34
Q

What drug is the most significant in the P450 system

A

P450 3A4

- interactions can occur by induction or inhibition of other isoenzymes

35
Q

what happens if P450 enzymes are induced

A
  • extent of metabolism would increase for drugs that are a substance of the enzyme leading to lower plasma concentrations
  • a decrease in plasma concentration may reduce therapeutic effect
  • e.g. carbamazepine induces drug metabolising enzymes, co-administration of carbamazepine and the oral contraceptive pill leads to a decrease in both the oestrogen and progestogen concentration which reduces contraceptive cover
36
Q

describe what happens if P450 enzymes are inhibited

A
  • plasma concentration of the affected drug would be expected to rise
  • an increase in plasma concentrations may lead to toxicity
  • e.g. erythromycin is a potent inhibitor of P450 3A4, co-administration of erythromycin and tacrolimus has been shown to increase plasma tacrolimus concentration by up to 6 fold and can lead to tacrolimus toxicity causing acute renal failure
37
Q

How does rifampicin affect CYP3A4

A
  • induces CYP3A4
  • this results in a decrease in plasma concentration of drugs
  • therefore you need to increase the drug dose
38
Q

What does grapfruit juice do to liver enzymes

A
  • inhibits CYP3A4 - this can increase plasma concentration
39
Q

when treating someone with encephalopathy what do you have to be careful when prescribing

A

Have to be careful when prescribing drugs that have the potential to

  • cause sedation - (benzodiazepines)
  • cause agitation (antipsychotics)
  • cause constipation (opioid analgesics)
  • cause electrolyte disturbances such as diuretics (diuretics)
40
Q

In liver disease synthesis of clotting factors is reduced so what do you need to consider when prescribing drugs

A

Need to be careful when prescribing drugs that:

  • cause thrombocytopenia (sodium valproate)
  • increase the risk of bleeding ( anticoagulants, antiplatelets)
41
Q

In liver disease where there is gastric and oesophageal varices what do you need to be careful when prescribing

A

Need to be careful when prescribing drugs that have the potential to:

  • cause irritation to the gastrointestinal tract (NSAIDs)
  • increase the risk of bleeding (Anticoagulants)
42
Q

In liver disease where there is ascites what do you need to be careful of when prescribing

A

Need to be careful when prescribing drugs that have the potential to:

  • cause fluid retention such as NSAIDS
  • increase body sodium (such as sodium chloride infusion)
43
Q

What do you have to be careful of when prescribing tramadol in liver disease

A
  • Can cause constipation so encephalopathy
44
Q

What general considerations should you consider hepatic dysfunction

A
  • identify at risk patients
  • monitor LFTs, albumin, pro thrombin time and bilirubin at baseline and at regular intervals throughout treatment with drug treatments known to cause hepatotoxicity
  • monitor drug concentration where possible to avoid toxicity which can cause liver injury
  • avoid drug interactions which may increase the risk of liver injury
  • drugs that are dependent on the liver for metabolism are likely needed to have dose reduction
  • drugs that increase risk of bleeding should be avoided
45
Q

What does bioavailability give an indication of

A
  • Gives an indication of the extent of first pass metabolism
46
Q

What can decrease first pass metabolism

A
  • liver dysfunction if portosystemic shunts are present
47
Q

Half life can be…

A

extended in patients with liver dysfunction

48
Q

How is protein binding effected in liver disease

A
  • decreased serum albumin may lead to a decrease in total drug concentration for those drugs which are highly protein bound
  • but the concentration of free drug is generally unchanged
49
Q

What characteristics drugs are important when prescribing in hepatic dysfunction

A
  • bioavailability
  • metabolism
  • half-life
  • extent of protein binding
  • excretion
  • adverse effects
  • hepatotoxicity
  • nephrotoxicity
50
Q

What do you do if you suspect a drug is the cause of liver injury

A
  • stop the suspected medicine
  • give treatment where necessary
  • monitor liver function
  • if the reaction is serious or the reaction has occurred with a new drug or new indication report this to the yellow card scheme