Prescribing in liver disease Flashcards
What happens in cirrhosis?
= liver gets small and shrunken
- reduced metabolic capacity
- portal hypertension
- high portal pressure & low albumin = ascites
what are risk factors for liver disease?
- alcohol
- obesity
- drugs
what are 3 major factors involved in liver problems?
- reduced liver blood flow
- reduced metabolic function
- reduced plasma proteins
what happens when highly metabolised drugs, e.g. GTN, phenytoin, calcium blockers, are taken when the liver is slightly messed up?
= they first-pass metabolism and result in portal-systemic shunting
= lead to high toxic levels
what circulatory changes happen in cirrhosis?
- low albumin = low plasma volume
- increasing renin levels
- more aldosterone is produced
- the liver cannot metabolise the aldosterone, therefore secondary aldosteronism arises
describe endothelia and oestrogen effect when there is cirrhosis/liver damage?
- increased endothelin
- increased oestrogen
what are the consequences for the kidneys when the liver has increased angiotensin II, aldosterone, SNS and ADH?
- potassium loss
- sodium retention
- water retention
= renal vasoconstriction
= fewer renal prostaglandins are produced
what is hepato-renal syndrome?
when you are unable to stop liver and renal failure
what does moderate hepatic impairment cause?
- decreased renal clearance
- effects on unbound drug masked by decreased protein binding
- renal function is reduced
(creatinine & Cr clearance misleading)
what are consequences of hepatic impairment?
1) gout oedema
= poor absorption
2) liver & kidney congestion
= reduced function
3) gross oedema & ascites
4) CHF
why would you NOT give NSAIDS?
= renal prostaglandin synthesises is decreased
- worsen renal impairment
- further sodium retention
- risk of hepato-renal syndrome
- worsening of CHF
= cirrhosis peptic ulcers increase
- risk of GI bleed or perforation
what other complications do NSAIDs do?
- hypertension
- sodium retention
- asthma
- diarrhoea/colitis
- CHF
- CV toxicity
how would you ideally treat liver diseases?
- standard NSAID or COX-2 inhibitor
= both co-prescribed with a proton pump inhibitor
what are the affects of NSAIDs, diuretics and metoclopramide?
NSAIDS
= hypertension
- ant-hypertension
DIURETICS
= gout
- gout Rx
Metoclopramide (anti-emetic)
= parkinsons
- L-DOPA
what drugs would you use to treat reduced drug metabolism?
1) opiates
= codeine
2) benzodiazepines
3) chlormethiazole
4) cyclosporin
5) metrondiazole
6) calcium blockers
what does 8% of paracetamol get converted into?
= a highly reactive intermediate
N-acetyl-p-benzoquinonimine by P4502E1
= liver failure
what happens if you have a loss of glutathione?
= failure to break down of N-acetyl-p-benzoquinomine
Resulting in
= cysteine and mercapturic acid conjugates
describe paracetamol in liver disease?
- reduced glutathione stores
- longer half-life
- increased P4502E1 in alcoholics
- toxicity with ‘normal’ doses
Describe Hy’s rule?
= used for drug induced liver failure
ALT/AS > 5 x ULN
AND
Bilirubin > 3mg/dI
describe who is most likely to get drug induced liver injuries?
- women
what diuretics could you give to some with oedema and ascites?
- Loop
- thiazide
- spironolactone
why is sprinolactone the best drug of choice?
Frusemide
= reduced intra-vascular volume
= hypokalaemia, hypomagnesaemia
Thiazide
= hypokalaemia
= hypomagnesaemia
Spironolactone
= best drug
= with fluid restriction
= Aim at 1kg/day weight loss
describe antibiotics use in disease?
- mostly safe
- amino-glycosides nephrotoxic
- quinolone epileptogenic
- metronidazole reduced metabolism
what are 4 bad hepatic disorders?
- fulminant hepatic failure
- decompensated cirrhosis
- severe or acute chronic hepatitis
- severe congestive heart failure
what are mild/moderate problems with the liver?
- compensated cirrhosis
- cholestatic jaundice
- enzyme blockers:
= non-specific: cimetidine, ketoconazole, grapefruit juice
= specific: erythromycin, quinolones - hypothyroidism
- old age
