Pharmacology of drug treatments in liver disease Flashcards
What do LFTs/liver profiles indicate?
- Test for liver dysfunction
- Low albumin means poor diet, losing albumin in gut or kidneys or not making enough in liver
- PT good indication of Vit K activity, if small then fast coagulation time
Why do you do LFTs before prescribing drugs?
If liver function disrupted will effect drug processing/metabolism, might need to reduce dose or avoid drug altogether
Define bioavailability?
Fraction of drug which makes it into circulation system
What do the Phase one reactions do?
Redox hydrolytic reaction makes drug more chemically reactive so in phase two can become water soluble
What are the enzyme inducers of CYP450?
PC BRAGS Phenytoin Carbamazepine Barbituates Rifampicin Alcohol Glucocorticoids St John's Wort
What do enzyme inducers do?
- Increase synthesis or decrease breakdown of CYP450 isoenzymes
- which will then increase metabolism of other drugs
- change DNA of enzymes so take time to come into effect and to wear off
- can also get enzyme inhibitors
What do Phase two reactions do?
- Join water water soluble molecule to drug which changes shape and structure and so function usually less active
- can then be excreted in bile
What enzyme catalyses conjugation in phase two?
- Transferase enzymes
- Specific enzyme depends on the joining molecule
Which aspect of LFTs show presence of hepatotoxic drugs?
Increased ASTs
What are the hepatotoxic drugs?
- Alcohol
- Paracetamol (most common cause of drug induced liver failure, need to take large amounts)
- Isoniazid
- Statins
- Methotrexate
- Amiodarone
- Chorpromazine
- Halothane
How is paracetamol normally metabolised?
- Normally metabolised into NABQE
- then joined with glucoronyl sulphate
- if system overwhelmed NABQE can be moped up by glutathione
- if no glutathione then NABQE left
- NABQE hepatotoxic
What can Cirrhosis lead to?
- ascites
- encephalopathy
- coagulopathy
- Hepatorenal syndrome
- Varices/ Portal Hypertension
What scoring system is used to assess cirrhosis?
- Child-Turcotte-Pugh scoring system
- classed into A,B and C A best C worst
How are ascites treated?
- Ascites = gathering of fluid in wrong area
- Remove fluid using banano catheter
- sodium restricted diet, less salt = less fluid
- TIPS (transjugular intrahepatic portosystemic shunt) bypass liver into systemic system
- diuretics (spironolactone or furosemide)
What are the triggers for encephalopathy?
Avoid triggers for encephalopathy:
- Avoid large protein meals
- Avoid bleeding from varices as blood protein rich
- Avoid constipation as faster food goes through less opportunity for conversion to ammonia
- Lactulose laxative to avoid constipation
