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Drugs and prescribing in Liver disease

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Presentation on theme: "Drugs and prescribing in Liver disease"— Presentation transcript:

1 Drugs and prescribing in Liver disease
Esther Unitt Consultant Hepatologist

2 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?

3 Paracetamol Overdose

4 Aetiology of Acute Liver Failure in UK and Europe. UK Europe
Paracetamol hepatotoxicity 54.1% 2% Viral % 70% HAV % 4% HBV + HDV 9.0% 45% Other % 3% Indeterminate % 18% Drug reaction 6.9% 14.5% Miscellaneous 3.9% 12

5 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)

6 Paracetamol Nausea/vomiting (after 24hours) RUQ pain/tenderness
Liver damage maximal 3-4 days after ingestion Encephalopathy, haemorrhage, hypoglycaemia, sepsis, cerebral oedema and death

7 N-acetylcysteine (Parvolex)
Treatment N-acetylcysteine (Parvolex)


9 Metabolism of paracetamol
Enhanced activity Enzyme inducers Alcohol Glucuronide and Sulphate conjugates 60-90% Cytochrome P450 5-10% Hepatocyte damage Reactive metabolite Glutathione Depletion in Malnutrition Excretion Replenish stores N-acetlycysteine Methionine

10 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?

11 Treat???

12 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?

13 Case 2 Blood glucose ABG, lactate PT U&Es, LFTs, Amylase
Paracetamol level Urine output Other medication? Suicidal intent?, family support?

14 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

15 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!

16 Monitor PT, creatinine, amylase, lactate, pH, LFTs daily
If abnormal, PT twice daily iv fluids – patients will be dry! Seek precipitating factors for overdose

17 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

18 Acute liver failure Support CNS Respiration Circulation Renal
Coagulation Infection Metabolism

19 Indications for liver transplant
pH < 7.3 lactate > 3.2 PT > 180 creatinine > 300+PT >100 +grade 3 or 4 coma prognosis very poor

20 Alcohol withdrawal

21 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

22 History Physical symptoms Moods/state of mind Morning drinking habits
Degree (and longevity) of drinking Any suggestion of withdrawal symptoms

23 Severity of alcohol dependence questionnaire (SADQ)
Physical withdrawal symptoms Affective withdrawal symptoms Relief drinking Frequency

24 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)?

25 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


27 Adverse effects Drowsiness, sedation Unsteadiness, ataxia Confusion
Dizziness, vertigo, syncope Usually dose related More common in elderly or in patients with liver disease

28 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

29 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

30 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

31 Chronic liver disease What pain relief can I give? Diuretics
The confused liver patient What do I do Role of sedatives?

32 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

33 What concerns me? What is the cause of his pain? Renal function?
Has SBP been excluded? Would a paracentesis relieve his pain? Renal function? Varices? Encephalopathy?

34 Consider the analgesic options
Paracetamol? NSAIDS? Codeine? Stronger Opiates?

35 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)

36 NSAIDs Codeine/Tramadol NEVER! Variceal haemorhage, renal failure
Risk of encephalopathy Need to balance risk versus need for analgesia Co-prescribe lactulose Use lower doses, avoid regular dosing

37 Stronger opiates Never without consultation with consultant in charge of patient High risk of over-sedation and encephalopathy Effects may be delayed/prolonged

38 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!

39 Which diuretic and why? Spironolactone Dose is 100 -200 mg once daily
Liver disease is a cause of secondary hyperaldosteronism Aldosterone inhibitor Dose is mg once daily No need to split doses Contraindications? Hyperkalaemia, hyponatraemia Renal impairment Use cautiously and monitor closely!

40 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

41 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

42 The home run! Take home points

43 Take home points (Paracetamol OD)
Para OD = Parvolex PT is most sensitive indicator of liver injury Careful attention to fluid balance Early discussion!

44 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.

45 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

46 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!!

47 Thank you for your attention!

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