Drugs in Liver Flashcards
cirrhosis
reduced metabolic capacity
portal hypertension
high portal pressure and low albumin - ascites
shunting of blood by-passing liver
causes of liver disease
coke burger booze blood - HCV, HBV drugs
cirrhosis definition
condition in which the liver does not function properly due to long-term damage
This damage is characterized by the replacement of normal liver tissue by scar tissue
END STAGED
liver gets small and shrunken
cirrhosis major factors
reduced liver blood flow
reduced metabolic function
reduced plasma proteins
multiple rib fractures
indicates alcoholic
falling over while drunk
portal hypertension
oesophageal varices and haemorrhoids
first-pass metabolism
70-90% metabolised
GTN, Phenytoin, calcium blockers
don’t take orally as it wouldn’t pass liver
increased plasma levels
saturable kinetic
alcohol and phenytoin
metabolism is stopped at plasma concentration
circulation changes
low albumin = low plasma volume
renin causes angiotensinofen into AT1 which is changed in AT2 and then aldosterone
liver disease can’t be metabolised
aldosterone changed into secondary aldosteronism
hormonal effects
endothelin and oestrogen levels are increased
not metabolised in damaged liver
steroid hormones
consequences for kidneys
- angiotensin 2
- aldosterone
- synthetic nervous system
- ADH
potassium loss
sodium retention
water retention
1,3 and 4 = renal vasoconstrictors
renal prostaglandins leading to renal failure
2 = endothelin
hepato-renal syndrome
moderate hepatic impairment
decrease renal clearance
effect on unbound drug masked by decrease protein binding
renal function reduced
creatinine and Cr clearance misleading
moderate hepatic impairment - consequences
gut oedema - poor absorption
liver and kidney congestion-
reduced function
gross oedema and ascites
CHF
spider nevi
increased oestrogen
normal in pregnancy
found in moderate hepatic impairment
NSAID (nope)
decreased renal PGE synthesis worsen renal impairment further sodium retention risk of hepatic-renal syndrome worsening of CHF
increased cirrhosis peptic ulcers
risk of GI bleeding or perforation
long term NSAID
should be co-prescribed with a proton pump inhibitor
hypersensitive brains
sedative opiates
respiratory depression
opiates
bad choice
drug metabolism
phase 1
affected early
fat soluble drugs
phase 2
affected late
reduced metabolism in liver disease
opiates benzodiazepines chlormethiazole cyclosporin metronidazole calcium blockers
paracetamol toxicity
metabolised in sulphates and glucoronides
8% - highly reactive intermediate
glutathione changes it into cysteine and mercapturic acid conjugate
limited supply of glutathione
paracetamol in liver disease
reduced glutathione stores
longer half-life
increased P4502e1 in alcoholics
toxicity with ‘normal’ doses
drug induced liver disease
amoxicillin and clavulanic acid-induced hepatitis
20% of acute liver failure
idiopathic
drug induced liver injury
infrequent
latency period: 5-90 days
more common in woman
lumiracoxib latest casualty
diuretic medical prescription
frusemide
reduced intra-vascular volume
hypokalaemia, hypomagnesaemia
thiazide
hypokalaemia, hypomagnesaemia
spironolactone
BEST DRUG
with fluid restriction
aim at 1kg/day weight loss
sedation
sometimes needed
small doses
phase 2 metabolised benzodiazepines
lorazepam, oxazepam, lormetazepam
antibiotics
mostly safe
ahminoglycosides nephrotoxic
quinolone epileptogenic
metronidazole reduced metabolism
work hepatic disorders
fulminant hepatic failure
decompensated cirrhosis
severe acute or chronic hepatitis
severe congestive heart failure
mild/mod reduction
compensated cirrhosis
cholestatic jaundice
enzyme blockers
hypothyroidism
old age
main message
dose reduction the general rule regardless of the route of elimination of drug or metabolite
general principles
avoid pro-drugs
use drugs with renal excretion
be wary of sedatives, CNS drugs, anticoagulants NSAIDs, theophylline, ahminoglycosides
high inter-individual variability
liver tests not predictive
start low, go slow
