Transcript Prescribing in Liver disease

Drugs and prescribing in
Liver disease
Esther Unitt
Consultant Hepatologist
Objectives



Paracetamol hepatotoxicity
Management of alcohol withdrawal
Chronic liver disease
• What pain relief can I give?
• Diuretics
• The confused liver patient


What do I do
Role of sedatives?
Paracetamol Overdose
Aetiology of Acute Liver Failure in UK and Europe.
Paracetamol hepatotoxicity
UK
54.1%
Europe
2%
Viral
36.5%
70%
4.9%
9.0%
0.6%
16.5%
4%
45%
3%
18%
Drug reaction
6.9%
14.5%
Miscellaneous
3.9%
12
HAV
HBV + HDV
Other
Indeterminate
Paracetamol as cause of acute
liver failure





Commonest cause of ALF in UK (>50%)
Usually taken with suicidal intent
8% due to unintentional overdosing in ‘high risk’
patients
ALF occurs in 2-5% of patients who present
following paracetamol OD
Median dose 40g (range 5-210g)
Paracetamol



Nausea/vomiting (after 24hours)
RUQ pain/tenderness
Liver damage maximal 3-4 days after
ingestion
• Encephalopathy, haemorrhage,
hypoglycaemia, sepsis, cerebral oedema
and death
Treatment

N-acetylcysteine (Parvolex)
Metabolism of paracetamol
Paracetamol
Glucuronide and
Sulphate conjugates
60-90%
Hepatocyte
damage
Excretion
Enhanced activity
Enzyme inducers
Alcohol
Cytochrome P450
5-10%
Reactive metabolite
Glutathione
Depletion in
Malnutrition
Replenish stores
N-acetlycysteine
Methionine
Case 1







25 year girl
30 paracetamol, 01.00am
PMH: epilepsy, on carbamazepine
Admitted 9.00am
Clinically well, obs normal
Para level: 80mg/L
Treat?
Treat???
Case 2



35yr male
60 paracetamol taken 24hours ago
O/E vomiting, abdo tender
• P 120/min, BP 120/80


What else do you want to know?
What are you going to do?
Case 2








Blood glucose
ABG, lactate
PT
U&Es, LFTs, Amylase
Paracetamol level
Urine output
Other medication?
Suicidal intent?, family support?
Case 2






PT 24
Bili 30, ALP 130, ALT 9000, Alb 40
Na 145, K 3.0, Ur 19, Cr 190
Glu 3.5
pH 7.38, O2 13, CO2 3, HCO3 12
Lactate 3.0
Management of paracetamol
overdose



Monitor paracetamol levels > 4 hours after
ingestion
If below treatment line, repeat level
Give NAC if over treatment line
• ?high risk line


Treatment lines not valid for
staggered OD
If in doubt, give NAC! Don’t wait!




Monitor PT, creatinine, amylase,
lactate, pH, LFTs daily
If abnormal, PT twice daily
iv fluids – patients will be dry!
Seek precipitating factors for
overdose
Other management

If features of liver failure develop,
continue N-acetylcysteine
• PPI
• Careful monitoring of fluid balance (CVP/U.O),
haemodynamics
• Broad spectrum antibiotics (anti-fungals)
• Monitor and correct electrolytes (Ca, Mg, PO4)
• Monitor glucose
• Look for signs of confusion
Acute liver failure

Support
•
•
•
•
•
•
•
CNS
Respiration
Circulation
Renal
Coagulation
Infection
Metabolism
Indications for liver transplant




pH < 7.3
lactate > 3.2
PT > 180
creatinine > 300+PT >100 +grade 3
or 4 coma prognosis very poor
Alcohol withdrawal
Alcohol Withdrawal

Signs and symptoms range widely
• tremulousness (shakes), insomnia, anxiety,
hyperreflexia, mild autonomic hyperactivity, and GI
upset

Delerium Tremens usually > 48 hours after
cessation of drinking
• Disorientation, agitation, and hallucinations; with severe
autonomic hyperactivity (tremulousness, tachycardia,
tachypnoea, hyperthermia)

Hallucinations
• Persecutory, auditory, or (most commonly) visual and
tactile hallucinations

Seizures
History





Physical symptoms
Moods/state of mind
Morning drinking habits
Degree (and longevity) of drinking
Any suggestion of withdrawal
symptoms
Severity of alcohol dependence
questionnaire (SADQ)




Physical withdrawal symptoms
Affective withdrawal symptoms
Relief drinking
Frequency
CAGE questionnaire




Have you ever felt you should cut down
on your drinking?
Have people annoyed you by criticising
your drinking?
Have you ever felt bad or guilty about
your drinking?
Have you ever had a drink first thing in
the morning to steady your nerves or get
rid of a hangover (eye-opener)?
Chlordiazepoxide




Benzodiazepine
Controls symptoms of alcohol
withdrawal
Patients admitting to >10u per day
are likely to require treatment
Dose/level and length of treatment
will depend on severity of
dependence and on patient factors
Adverse effects






Drowsiness, sedation
Unsteadiness, ataxia
Confusion
Dizziness, vertigo, syncope
Usually dose related
More common in elderly or in
patients with liver disease
Wernicke’s encephalopathy



Thiamine deficiency
Classic triad of encephalopathy,
ataxia, and ophthalmoplegia (10%)
Consider diagnosis:
• long-term alcohol abuse or malnutrition

acute confusion, decreased conscious level,
ataxia, ophthalmoplegia, memory
disturbance, hypothermia with hypotension,
and delirium tremens
Wernicke’s encephalopathy

Beware of administering dextrose in a
thiamine-deficient state



Exacerbates the process of cell death by providing
more substrate for biochemical pathways that lack
sufficient amounts of coenzymes
Start thiamine concurrently or prior
Iv pabrinex (vitamins B + C)
• 2 pairs tds for 3 days


Thiamine 100mg tds
Vitamin B co forte 2 tabs daily
Korsakoff psychosis





Characterized by retrograde amnesia
(inability to recall information),
Inability to assimilate new information
Decreased spontaneity and initiative
Confabulation.
Other manifestations of thiamine
deficiency
• Wet beri beri
• Nutritional polyneuropathy
Chronic liver disease
• What pain relief can I give?
• Diuretics
• The confused liver patient


What do I do
Role of sedatives?
Case




You are called to see the following
man who is c/o abdominal pain
48yr man, alcoholic liver disease
Bili 150, Alb 30, PT 16
Ascites
What concerns me?

What is the cause of his pain?
• Has SBP been excluded?
• Would a paracentesis relieve his pain?



Renal function?
Varices?
Encephalopathy?
Consider the analgesic options
• Paracetamol?
• NSAIDS?
• Codeine?
• Stronger Opiates?
Analgesia in chronic liver disease

Paracetamol
• Safe in small quantities
• Probably the safest analgesic for these
patients!!!!
• Reduce maximum daily intake and avoid
regular dosing for >5 days)

ie 500mg – 1g qds prn (max 2g daily)

NSAIDs
• NEVER! Variceal haemorhage, renal
failure

Codeine/Tramadol
• Risk of encephalopathy
• Need to balance risk versus need for
analgesia
• Co-prescribe lactulose
• Use lower doses, avoid regular dosing
Stronger opiates

Never without consultation with
consultant in charge of patient
• High risk of over-sedation and
encephalopathy
• Effects may be delayed/prolonged
Diuretics






Why do we prescribe?
To control ascites?
Why do we need to control ascites?
Patient comfort!
(Rarely respiratory distress)
REMEMBER:
Ascites does not kill patients, but diuretics
can!
Which diuretic and why?

Spironolactone
• Liver disease is a cause of secondary
hyperaldosteronism
• Aldosterone inhibitor

Dose is 100 -200 mg once daily
• No need to split doses

Contraindications?
• Hyperkalaemia, hyponatraemia
• Renal impairment

Use cautiously and monitor closely!
The Confused Liver Patient

Consider:
• Encephalopathy

Grades 1-4 (daytime somnolence, agitation,
liver flap, decreased conscious level, coma)
• Alcohol withdrawal
• Sub-dural haematoma or other
neurological event
Encephalopathy - causes

Drugs (including alcohol)
• Check drug chart for night sedation, opiates,
chlordiazepoxide

Electrolyte abnormalities
• Low sodium, low potassium, dehydration




Hypoglycaemia
Sepsis (including SBP)
Constipation (Give lactulose + enemas)
GI bleeding
The home run!
Take home points
Take home points
(Paracetamol OD)




Para OD = Parvolex
PT is most sensitive indicator of liver
injury
Careful attention to fluid balance
Early discussion!
Take home points
(Alcohol withdrawal)




Take a proper alcohol history
Think about alcohol withdrawal
before symptoms develop
Monitor patient daily and review
dosage of chlordiazepoxide!
All dependent patients must receive
Pabrinex and vitamin B.
Take home points
(Analgesia in CLD)



Paracetamol is safe in small
quantities and should be first choice
Caution with other groups
Diuretics
• Think carefully before prescribing
• No urgency in this situation
• Monitor electrolytes and renal function
Confused liver patients

Management of encephalopathy is
usually straightforward if you
remember the checklist!
• Check for sepsis
• Lactulose
• Fluids
• Replace electrolytes
• Check drug chart

Do not sedate them!!
Thank you for
your attention!