Prescribing in liver disease Flashcards
what are the main features of cirrhosis
reduced metabolic capacity
portal hypertension
shunting of blood to by pass the liver
reduced liver blood flow
reduced plasma proteins
what is the result of portal hypertension + low albumin
ascites
why does a blood shunt affect drug dose
as drugs dont undergo first pass metabolism and remain in blood
how can you tell if a drug is highly metabolised
if its oral dose is much higher than its IV dose
what are the two orders of saturable kinetics
first order- plasma concentration increasing
zero order- plasma concentration remains contrast as fully saturated
what does a low albumin cause
baroreceptors think the body has low plasma volume so trigger renin to convert angiotensinogen to ATI to ATII to retain sodium and water and increase oncotic pressue=re
why do people with cirrhosis have very high aldosterone levels- secondary aldosteronism
as liver cant metabolism steroids well + produced in excess in cirrhosis
what hormone causes spider naevi
oestrogen- not being metabolised in cirrhosis
what do endothelin do, is it increased or decreased in cirrhosis
vasoconstrictor- increased as hormone not metabolised by the liver
what vasoconstrictors act on the kidney
angiotensin II and aldosterone
what is vasopressin
ADH
what does ADH do
retains water
what do the effects of the symp nevous system, angiotensin II, aldosterone and ADH have on the kidneys in cirrhosis
potassium loss, sodium and water retention
vasopressin is usually controlled by osmolarity but what can override this
low plasma volume
how do you treat the adverse effects (sodium and water retention) of the kidneys in cirrhosis
high levels or spirolactone and stop giving fluids
what is spirolonlactone
aldosterone antagonist
what do renal prostaglandins do
stimulate the kidney to vasodilate in normal people
what can high endothelin cause
hepato-renal syndrome
what will NSAIDs shut off in the kidney
renal prostaglandins
what are the consequences of moderate hepatic impairment
decreased renal clearance, renal function reduced:
-gut oedema (poor absorption
-liver and kidney congestion
reduced function
-gross oedema and ascites
-CHF
what is hepatorenal syndrome
rapid deterioration of kidney function in individuals with cirrhosis or fulminant liver disease
what causes gynaecomastea
oestrogen not broken down by liver
what is the result of using NSAIDs in people with cirrhosis
reduced renal prostaglandin synthesis:
- worsens renal impairment
- further sodium retention
- risk of hepao renal syndrome
- worsening of CHF
increase in cirrhosis peptic ulcers
-risk of GI bleed or perforation
what are the adverse drug reactions of NSAIDs
UGI ulcer complications,
CV toxicity,
hypertension,
CHF,
sodium retention,
asthma (Cox 1),
diarrhoea/colitis,
renal failure
what should NSAIDs or COX-2 inhibitors be prescribed with
PPI
what metabolises drugs in phase I
P450
what happens in phase II of drug metabolism
conjugation
drugs that are metabolised in what phase should be prescribed in liver disease
phase II
what is codeine metabolised by
P450
how much of paracetamol dose in metabolised into highly reactive intermediate
8%
how is the highly reactive intermediate removed by the body
gluthanthione stores in the body
what metabolises paracetamol into highly reactive intermediate
P4502E1
what does gluathione turn the highly reactive paracetamol intermediate into
cysteine and mercapturic acid conjugates
why does alcohol reduce paracetamol toxicity
as prevents binding
why is paracetamol more toxic if you havent eaten recently
as less glutathione in the liver
what happens when you deplete your liver glutathione store (e.g in very large paracetamol dose)
will then attack liver
why is paracetomal more dangerous in alcoholics who are not drunk
they have increased P4502E1
are intentional or unintentional paracetamol overdoses more common
unintentional
what does paracetamol toxicity cause
fulminant hepatitis
what is the risk associated with opiates in cirrhosis
sedation as plasma levels high, encephalopathy and depressed respiratory drive
how do you treat pain in cirrhosis
paracetamol 1g 2x daily, codeine 30mg 3x daily (watch for sedation), AVOID NSAIDs
what antibiotics can cause induced hepatitis
amoxicillin and clavulanic acid
what antigen determines induced hepatitis
HLA surface antigen
what is hy’s rule
that a patient is at risk of developing fatal drug induced liver injury if given a medication that causes hepatocellular injury
when ALT/AST> 5x ULN
AND
bilirubin> 3mg/dl
who is drug induced liver injury more common in
women
what is the negative of a loop diuretic (frusemide)
damages kidney, reduced intra-vascular volume, hypokalaemia and hypomagnesaemia
what is the diruetic of choice in liver disease
spironolactone
what is the negative of a thiazide diuretic
hypokalaemia, hypomagnesaemia
how much fluid should you aim to loose a day
1kg
what drugs achieve sedation in cirrhosis
phase II metabolised benzodiazepines
what are the negatives of the antiobiotics;
- aminoglycosides
- quinolones
- metronidazole
in cirrhosis
aminoglycosides- nephrotoxic
quinolones- epilptogenic (causes epilepsy)
metronidazole- reduced metabolism
what are the worst hepatic disorders
fulminant hepatic failure,
decompensated cirrhosis,
severe acute/ chronic hepatitis,
sever congestive heart failure
what causes a mild/mod reduction in liver function
compensated cirrhosis,
cholestatic jaundice,
enzyme blockers (quinolones, grapefruit juice),
hypothyroidism, old age
what are the general rules in prescribing in cirrhosis
dose reduction regardless of the route of elimination of drug or metabolite
avoid pro drugs
use drugs with renal rather than liver excretion
be wary of sedatives, CNS drugs, anticoagulants, NSAIDs, theophyllines, aminoglycosides
start low go slow
what is a pro drug
drug that is metabolised into active form
