Drugs and Liver disease Flashcards
what affect does alcohol have on MI mortality?
halves it
what are 4 causes of liver disease?
diet/obesity
alcohol
HCV or HBV
Drugs
how is degree of liver disease established?
child pugh classification
score of 5-6 = Grade A
7-9 = grade B
10-15 = grade C
what is cirrhosis?
liver gets encapsulated in fibrous capsules
small and shrunken liver
what are 3 major factors in cirrhosis?
reduced liver blood flow (causes portal hypertension)
reduced metabolic function
reduced plasma proteins
what painkiller should be used if the patient has cirrhosis?
not NSAIDs as switches off renal prostaglandins
not opiate
not paracetamol
lesser of all evils = small dose of paracetamol short term
why is the shunting of blood in portal hypertension significant?
blood by-passes liver so does not get filtered and cleaned
drugs, toxins etc can go through circulation and reach brain etc
what contributes of ascites?
high portal pressure and low albumin
name some highly metabolised drugs, what impact does this have?
GTN, calcium blockers, phenytoin
don’t work well if swallowed as immediately metabolised so given enterally etc so they last longer
what clue indicates that a drug is very highly metabolised?
if the oral dose is much higher than IV dose
which order is alcohol metabolised?
first order until a point then zero order
i.e - drinking slowly every hour alcohol is metabolised at same rate as ingestion, if drinking quicker it isn’t metabolised as quickly
what does low albumin do to circulation?
low albumin causes baroreceptors to perceive plasma volume as low activating RAAS producing more aldosterone
Why is aldosterone so high in cirrhosis?
People with aldosterone cant metabolise aldosterone causing secondary aldosteronism
what causes spider naevi?
increases oestrogen as cirrhotic liver cant metabolise oestrogen (in men and women)
what are the consequences of cirrhosis on the kidney?
angiotensin 2 and aldosterone, sympathetic activity and ADH act on kidney causing constriction
results in sodium retention and potassium loss
what causes sodium retention in cirrhosis?
vasopressin
what reverses the actions of cirrhosis on the kidney?
spironolactone
fluid restriction
regular weight check to see what fluid has been lost
why does alcohol intake not cause bad effects in normal people?
the same substances which act on the liver also stimulate it to produce renal prostaglandins which dilate the kidney
what are some possible consequences of cirrhosis?
gut oedema (poor absorption) swollen kidneys liver and kidney congestion gross oedema and ascites CHF
what are the negative results of NSAID’s?
reduce renal prostaglandins
increase peptic ulcers (risk of bleed etc)
what is long term aspirin (COX 2/1? inhibitor) always prescribed with?
PPI
what is the prescription cascade?
using drugs to counteract the side effects of other drugs in a cascade
what is the prescription cascade?
using drugs to counteract the side effects of other drugs in a cascade
which phase do drugs for liver disease affect?
phase 2
which drugs have a reduced metabolism?
opiates (eg. codeine) Benzodiazepines Chlormethiazole Cyclosporin Metronidazole Calcium blockers
how does paracetamol toxicity occur?
8% is metabolised into N- acetyl - p - benzoquinonimime (via P450) which is highly reactive and dangerous
.
why is paracetamol not as dangerous if youre drunk?
alcohol sits on CYP2E1 so paracetamol cant be absorbed
what counteracts paracetamol overdose?
glutathione
is paracetamol more dangerous in alcoholics?
yes
they produce more P450 so more is converted to toxic N-acetly-p-benzoquinonimine
what is the most common drug induced liver disease?
amoxicillin and clavaulonic acid
what is Hy’s rule?
Describes risk of fatal drug induced liver disease
ALT/AST > 5 X ULN and bilirubin > 3
which diuretic is best in liver disease?
spironolactone
what are the worst hepatic disorders?
fulminant hepatitis
which secretion pathway is best for liver disease drugs?
renal excretion
what is the general rule for prescribing in liver disease?
start low, go slow
what is phase 1 of drug metabolism?
biotransformation
P450
oxidation, reduction and hydrolysis
affected early by fat soluble drugs
what is phase 2 of drug metabolism?
conjugation
affected late
