Drugs in Liver

Question 1

cirrhosis

Answer 1

reduced metabolic capacity

portal hypertension

high portal pressure and low albumin - ascites

shunting of blood by-passing liver

Question 2

causes of liver disease

Answer 2

coke
burger
booze
blood - HCV, HBV
drugs

Question 3

cirrhosis definition

Answer 3

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

Question 4

cirrhosis major factors

Answer 4

reduced liver blood flow

reduced metabolic function

reduced plasma proteins

Question 5

multiple rib fractures

Answer 5

indicates alcoholic

falling over while drunk

Question 6

portal hypertension

Answer 6

oesophageal varices and haemorrhoids

Question 7

first-pass metabolism

Answer 7

70-90% metabolised
GTN, Phenytoin, calcium blockers

don’t take orally as it wouldn’t pass liver

increased plasma levels

Question 8

saturable kinetic

Answer 8

alcohol and phenytoin

metabolism is stopped at plasma concentration

Question 9

circulation changes

Answer 9

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

Question 10

hormonal effects

Answer 10

endothelin and oestrogen levels are increased

not metabolised in damaged liver

steroid hormones

Question 11

consequences for kidneys

Answer 11

1. angiotensin 2
2. aldosterone
3. synthetic nervous system
4. ADH

potassium loss
sodium retention
water retention

1,3 and 4 = renal vasoconstrictors
renal prostaglandins leading to renal failure

2 = endothelin
hepato-renal syndrome

Question 12

moderate hepatic impairment

Answer 12

decrease renal clearance
effect on unbound drug masked by decrease protein binding

renal function reduced
creatinine and Cr clearance misleading

Question 13

moderate hepatic impairment - consequences

Answer 13

gut oedema - poor absorption

liver and kidney congestion-
reduced function

gross oedema and ascites

CHF

Question 14

spider nevi

Answer 14

increased oestrogen

normal in pregnancy

found in moderate hepatic impairment

Question 15

NSAID (nope)

Answer 15

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

Question 16

long term NSAID

Answer 16

should be co-prescribed with a proton pump inhibitor

Question 17

hypersensitive brains

Answer 17

sedative opiates

respiratory depression

Question 18

opiates

Answer 18

bad choice

Question 19

drug metabolism

Answer 19

phase 1
affected early
fat soluble drugs

phase 2
affected late

Question 20

reduced metabolism in liver disease

Answer 20

opiates
benzodiazepines
chlormethiazole
cyclosporin
metronidazole
calcium blockers

Question 21

paracetamol toxicity

Answer 21

metabolised in sulphates and glucoronides

8% - highly reactive intermediate

glutathione changes it into cysteine and mercapturic acid conjugate

limited supply of glutathione

Question 22

paracetamol in liver disease

Answer 22

reduced glutathione stores
longer half-life
increased P4502e1 in alcoholics
toxicity with ‘normal’ doses

Question 23

drug induced liver disease

Answer 23

amoxicillin and clavulanic acid-induced hepatitis

Question 24

20% of acute liver failure

Answer 24

idiopathic

Question 25

drug induced liver injury

Answer 25

infrequent
latency period: 5-90 days
more common in woman
lumiracoxib latest casualty

Question 26

diuretic medical prescription

Answer 26

frusemide
reduced intra-vascular volume
hypokalaemia, hypomagnesaemia

thiazide
hypokalaemia, hypomagnesaemia

spironolactone
BEST DRUG
with fluid restriction
aim at 1kg/day weight loss

Question 27

sedation

Answer 27

sometimes needed

small doses

phase 2 metabolised benzodiazepines
lorazepam, oxazepam, lormetazepam

Question 28

antibiotics

Answer 28

mostly safe
ahminoglycosides nephrotoxic
quinolone epileptogenic
metronidazole reduced metabolism

Question 29

work hepatic disorders

Answer 29

fulminant hepatic failure
decompensated cirrhosis
severe acute or chronic hepatitis
severe congestive heart failure

Question 30

mild/mod reduction

Answer 30

compensated cirrhosis

cholestatic jaundice

enzyme blockers

hypothyroidism

old age

Question 31

main message

Answer 31

dose reduction the general rule regardless of the route of elimination of drug or metabolite

Question 32

general principles

Answer 32

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