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Drugs and 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?.

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Drugs and prescribing in Liver disease

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  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 36.5% 70% HAV 4.9% 4% HBV + HDV 9.0% 45% Other 0.6% 3% Indeterminate 16.5% 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. Treatment • N-acetylcysteine (Parvolex)

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

  9. 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?

  10. Treat???

  11. 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?

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

  13. 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

  14. 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!

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

  16. 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

  17. Acute liver failure • Support • CNS • Respiration • Circulation • Renal • Coagulation • Infection • Metabolism

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

  19. Alcohol withdrawal

  20. 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

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

  22. Severity of alcohol dependence questionnaire (SADQ) • Physical withdrawal symptoms • Affective withdrawal symptoms • Relief drinking • Frequency

  23. 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)?

  24. 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

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

  26. 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

  27. 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

  28. 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

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

  30. 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

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

  32. Consider the analgesic options • Paracetamol? • NSAIDS? • Codeine? • Stronger Opiates?

  33. 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)

  34. 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

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

  36. 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!

  37. 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!

  38. 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

  39. 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

  40. The home run!Take home points

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

  42. 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.

  43. 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

  44. 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!!

  45. Thank you for your attention!

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