Prescribing in hepatic dysfunction Flashcards
What are the clinical examination findings associated with chronic liver disease? (8)
Spider naevi Clubbing Jaundice Loss of secondary sexual hair Gynaecomastia Ascites Splenomegaly Peripheral oedema
If someone with chronic liver failure was to undergo an ultrasound, what would the ultrasound show that would indicate liver failure?
cirrhotic liver with splenomegaly, and sometimes ascites.
Liver function tests are incorrectly named as they do not provide you with information regarding the function of the liver. Which tests are able to provide this information?
Blood tests for-
- Albumin
- Prothrombin
- Bilirubin
Which score is able to provide you with information on the risk of operating on someone with liver Cirrhosis? Describe the parameters of the score.
Child Pugh score - assesses Serum Bilirubin severity 1 Point = <34 2 points = 35-50 3 points = >50
Serum albumin (How low) 1 point = >35 2 points = 28-35 3 points = <28
INR (how high)
1 point = <1.7
2 points = 1.71- 2.20
3 points = >2.20
Ascites severity
1 point = None
2 points = moderate
3 points = moderate or sever
Hepatic encephalopathy
1 point = none
2 points = grade 1-3 (surpressed with medication)
3points = grade 3 to 4
Class A Mild 5-6
Class B Moderate 7-9
Class C Sever 10-15
Which antibiotics is associated with hepatic and cholestatic jaundice? What would you do under these circumstances?
flucloxacillin and Co-amoxiclav
The onset may be delayed for up to two months post-treatment, and the course of the reaction may last for some months
Discontinue the drug
When taking a drug history, how many months of a drug history should you ask for?
As about drugs taken in the last 6 months
Which drugs are known to cause liver injury, there are many but list 6. Which of these drugs cause dose dependant damage? And which type of liver damage can they cause?
Paracetamol - dose dependant acute liver injury which cause cause liver failure
NSAIDS - ideosyncratic hepatitis that resolves in most cases after stopping drug (can cause hepatotoxicity or cholestatic hepatitis but this is rare. Ibuprofen can cause cholestatic hepatitis)
Aspirin - Dose dependant hepatitis
Antituberculosis drugs (rifampicin) - can cause liver injury
Methotrexate - can cause severe fibrosis and cirrhosis if not adequately monitored.
Amiodarone - can cause a steato hepatitis.
Co-amoxiclav and flucloxacillin - cholestatic hepatitis (hepatitis and cholestatic jaundice) that resolves in most cases after stopping drug
When taking a drug history - list all the drugs you should ask about
- Medication
- Vitamines
- Herbal
- Eye/Ear drops
- Inhalers
- Injections
- Topical agents
- Recreational drugs
- Food and dietary supplements
Can stains cause liver injury? Can it be prescribed in those with liver dysfunction?
Statins causes a mile increase in transaminase (AST AND ALT)
Can be prescribed in those with mild liver dysfunction (e.g non-alcoholic fatty liver disease patients) as long as you monitor the LFTs
What is the amount of paracetamol that can lead to liver damage in adults?
150mg/kg of paracetamol in under 1h
Where is paracetamol mainly metabolised?
In the liver
In the case of liver injury caused by paracetamol, what has to be depleted before the paracetamol can cause liver damage?
glutathione
After this, the reactive metabolites of paracetamol bind to cellular macromolecules, causing lethal damage to the hepatocyte.
What is the antidote to paracetamol poisoning and how does it work?
acetylcysteine, which augments glutathione levels.
Increase the synthesis of glutathione
Treatment for paracetamol overdose should be commenced if a patient has taken more than 150 mg/kg in any 24-hour period, unless what>?
The plasma-paracetamol concentration is undetectable
The patient is asymptomatic
LFTs, serum creatinine and INR are all normal
Which graph is used to assess if a patient should be give acetylcysteine to treat paracetamol overdose?
MHRA’s paracetamol overdose treatment graph
If a patient has taken toxic amounts of paracetamol but you have no access to their plasma concentration levels, should they still be given acetylcysteine?
only for Patients presenting after 8 hours who have taken potentially toxic amounts of paracetamol - even if plasma concentrations are not available.
Describe the 2 main phases of drug metabolism in the liver
Phase 1- makes drug more polar via 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. Enzyme activity reduced in cirrhosis
Phase 2- Conjugation which produces a water soluble compound which is usually inactive and more easily excreted in urine or bile. Some mechanisms of Phase 2 reactions, e.g. glucuronidation and sulphation, have been shown to be impaired in liver disease.
Give examples of some drugs that would require dose adjustment if patient has sever liver failure
Fluoxetine (selective serotonin reuptake inhibitor - antidepressant)
Nifedipine (calcium channel blocker)
Phenytoin ( anticonvulsant used for tonic clonic, convulsive status epilepticus, partial seizures with or without generalisation )
What is first pass metabolism?
A drug gets metabolized (partially or completely) at a specific location in the body that results in a reduced concentration of the active drug when it reaches its site of action or the systemic circulation. The first pass effect is often associated with the liver but it can also occur in the lungs, vasculature, GI tract,
How does liver dysfunction and failure effect first pass metabolism? What are the implications of this?
Liver is a very common site for first pass metabolism.
If the blood flow through the liver is slowed, a drug may be metabolised faster, as it may stay in the liver for longer.
Patients with cirrhosis can develop collaterals. This enables blood to bypass the liver (shunts). This reduces first pass metabolism.
In patients with this condition, drugs which should have a reduced bioavailability due to first pass metabolism will have a higher plasma concentration than usual. Bioavailability may approach 100% as opposed to a fraction of this amount (10,15,2030%)
You may need to prescribe reduced doses to avoid toxicity
What are the side effects of morphine and how can they effect someone with liver disease or failure?
Side effects- Constipation, confusion , drowsiness
Morphine causes liver failure. This increases the risk of hepatic encephalopathy in someone with liver failure, to counter act this, increase the dose of laxative e.g lactulose. This should already be prescribed to a patient at risk of hepatic encephalopathy
The confusion and sedation caused by morphine and other opioids like tramadol may also mask the signs of encephalopathy so must be careful
Which isoenzymes are responsible for phase 1 reactions in the liver?
Cytochrome P450 enzymes
Most significant is the P450 3A4
What can happens if Cytochrome P450 enzymes are induced? Give an example of a drug which can induce the enzyme and how it can effect other drugs.
Extent of metabolism would increase for drugs that are a substrate of the enzyme, leading to lower plasma concentrations.
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.
What can happens if Cytochrome P450 enzymes are inhibited? Give an example of a drug which can inhibit the enzyme and how it can effect other drugs.
Plasma concentration of the affected drug would be expected to rise.
An increase in plasma concentrations may lead to toxicity
Erythromycin is a potent inhibitor of P450 3A4. Co-administration of erythromycin and tacrolimus (imunisuprrssant used for organ transplants and atypical for eczema) has been shown to increase plasma tacrolimus concentrations by up to 6-fold and can lead to tacrolimus toxicity, causing acute renal failure.
