Liver drugs Flashcards
Is ascites a transudate or an exudate?
Normally transudate
What does the Child score assess?
Ascites, Bilirubin, Albumin, PT or INR and encephalopathy
When the liver is cirrhosed enlarged or smaller?
Smaller.
Initially with liver failure, the liver is enlarged but the in cirrhosis it shrinks.
Why is a low sodium seen in liver failure?
ADH- Normally released when the blood is concentrated and not when the blood is diluted but this is over ridden by a low plasma volume present in liver failure due to low albumin meaning plasma water moves into the interstitium. => Retention of Na+ and water but this dilutes the Na+ and K+ so they appear low
Why is a low popotassium seen in liver failure?
Aldosterone removes K+ and blood is diluted by ADH activity which further lowers K+ concentration
Why is a low albumin seen in liver failure?
Low metabolic rate
Why should you not give NSAIDs for pain (related or unrelated) in liver failure?
NSAID will inhibit production of renal prostaglandins which are trying to dilate renal arteries to increase glomerular filtration and decrease renin release. If you give NSAIDs then you will proporgate ascites and fluid retention, right heart failure and hepatorenal syndrome. Also risk of cirrhotic peptic ulcers
Why should you not give paracetamol for pain (related or unrelated) in liver failure?
It has a longer half life and is not well metabolised by a liver in failure => increased risk of paracetamol toxicity
Why should you not give opiates for pain (related or unrelated) in liver failure?
Liver disease = at risk of encephalopathy
If you give sedative/opites this will make their brain function worse and put them at risk of respiratory depression.
How can you tell if a drug undergoes lots of first pass metabolism?
If the oral dose is massive and the IV dose is smaller.
Give some examples of drugs that are subject to extensive first pass metabolism?
GTN, Phenytoin
Calcium channel blockers
Why does the dosing of drugs (especially those with fist pass metabolism) have to be adjusted in liver failure?
Decreased metabolic function
Portal systemic shunting (anastamosis)
=> The plasma concentrations are much higher.
Which drugs show saturation (zero order) kinetics?
Alcohol and phenytoin
Why do heavy drinkers have a higher threshold for alcohol (threshold before entering saturation kinetics)?
They have induced liver enzymes so are better adapted to metabolising alcohol.
What are the circulation changes in liver failure (Due to low albumin)?
1) Low albumin = low plasma volume (decreased osmolarity)
2) Kindeys release renin and reninconverts angiotensinogen (liver) to angiotensin 1
3) Angiotensin 1 is converted to angiotensin 2 by ACE in pulmonary endothelium
4) Angiotensin 2 causes the release of aldosterone from adrenal glands => salt and water retention (ascites)
5) The liver is not able to metabolise the aldosterone well so plasma concentrations remain high (more salt and water)
SECONDARY ALDOSTERONISM.
Angiotensin 2 is also a potent vasoconstrictor.
What induces spider navi in liver failure?
Oestrogen (women get them in pregnancy)
Oestrogen is not metabolised by the liver in men and women with liver failure => Spider navi and gynacomastia
WHy is there an increase in endothelin in liver failure and what are the consequences?
Endothelin is not metabolised by the liver.
Potent vasoconstrictor increasing hypertension and oedema
What happens to the kidney in liver failure?
1) Angiotensin 2 causes renal artery constriction and decreases glomerular filtration rate => increased renin release
2) Aldosterone removes K+ and retains Na+
3) Systemic nervous system causes increased renal artery constriction, increasing BP and renin release
4) ADH- Normally released when the blood is concentrated and not when the blood is diluted but this is over ridden by a low plasma volume present in liver failure due to low albumin meaning plasma water moves into the interstitium. => Retention of Na+ and water but this dilutes the Na+ and K+ so they appear low
How is ascites treated in liver failure?
Fluid restriction and Spirilactone (aldosterone inhibator)
Weigh the patient daily to check fluid balance. Don’t want to lose more then 1kg a day
What does the kidney produce in response to vasoconstrictors to dilate the renal arteries?
Renal prostaglandins which act locally.
What is hepatorenal syndrome?
a life-threatening medical condition that consists of rapid deterioration in kidney function in individuals with cirrhosis or fulminant liver failure.
WHat are the consequences of moderate liver failure?
Gut oedema and poor absorbtion.
Liver and kidney congestion.
Ascites
Right heart failure
Who should NOT be given asprin and why?
Children under 16
Reye’s syndrome => brain and liver damage
If a patient requires a long term NSAID or COX 2 inhibator, what should be co prescribed?
A PPI
What percentage of asthmatics are allergic to Cox 1 inhibators (NSAIDs)
5%- they can take selective Cox 2 drugs though
What are the adverse drug reactions for NSAIDs?
UGI ulcers CV toxicity Hypertension CHF Sodium retention Asthma Diarrhoea/colitis Renal Failure
What causes hepatic encephalopathy?
Amino acids in the brian. As they were shunted or not metabolised in the liver.
Amino acids displace neurotransmitters
Why are drugs metabolised in phase 2 conjugation (glucoranidation) preferred to drugs metabolised in phase 1 P450 (biotransformation) in liver disease?
Effected later.
Reduced liver function effects phase 1 drugs first.
Fat soluble drugs tend to be metabolised by phase 1.
Which drugs are phase 1 metabolised and therefore plasma concentrations increase in liver disease?
Opiates Benzodiazepines Chlormethiazole Cyclosporin Metronidazle Calcium blockers
Codeine is a prodrug to morphine. Why does it provide better pain relief for some than others?
Genetic polymorphisms- depends how much is metabolised to morphine
How is paracetamol metabolised?
Paracetamol is metabolised by P4502E1 into N-acetyl-p-benzoquinonimine - TOXIC.
Glutathione then binds to the toxic metabolite
Is paracetamol a good drug for oesteoarthritis?
No
Are the outcomes of a paracetamol overdose better when drunk and why?
Yes because you can’t metabolise the paracetamol to the toxic intermediate well.
What worsens the outcomes of paracetamol overdose?
Reduced glutathione stores (anorexia) Increased P4502E1 (alcoholics not drunk as they have induced enzymes) Liver failure (longer half life)
Can normal paracetamol doses cause liver damage?
Yes if taken over 14 days.
What drugs should you give someone with liver failure in pain?
Lesser of all evils:
Paracetamol 1 g twice daily.
Codeine 30mg three times daily (watch for sedation)
AVIOD NSAIDs
What are the most common drugs for inducing liver disease?
Co amoxiclav
Augmentin
NSAIDs
What percentage of acute liver failure is idiopathic?
20%
What is Hy’s Rule?
ALT greater than 5 times upper limit of normal
And bilirubin >3mg/dl
BAD sign
What is the latency period for drug induced liver injury?
5-90 days
More common in women.
Which is the best diuretic to use in liver failure?
Spirilactone with fluid restriction
Both thiazide and loop diuretics will cause hypokalaemia
If you needed to give sedation to a patient in liver failure what drugs whoul you use?
Phase 2 metabolised benzodiazepines: Lorazepam, Oxazepam and Lormetazepam
Small doses
Which antibiotics are not really safe in liver failure?
Aminoglycosides are nephrotoxic
Quinnalones are epileptogenic
Metronidazole has reduced metabolism
What does grapefruit do?
Blocks Cytochrome P450 enzyme and prevents metabolism of some drugs.
What is the best practice advice for prescribing in liver failure?
Aviod prodrugs Use drugs with renal excretion Be careful with sedatives, CNS drugs, NSAIDs, anticoagulants, aminoglycasides Lots of individual variability Start low and go slow.
