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Drugs and prescribing in Liver disease Esther Unitt Consultant Hepatologist.

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Presentation on theme: "Drugs and prescribing in Liver disease Esther Unitt Consultant Hepatologist."— Presentation transcript:

1 Drugs and prescribing in Liver disease Esther Unitt Consultant Hepatologist

2 Objectives Paracetamol hepatotoxicity Paracetamol hepatotoxicity Management of alcohol withdrawal Management of alcohol withdrawal Chronic liver disease Chronic liver disease What pain relief can I give?What pain relief can I give? DiureticsDiuretics The confused liver patientThe confused liver patient What do I do What do I do Role of sedatives? Role of sedatives?

3 Paracetamol Overdose

4 Aetiology of Acute Liver Failure in UK and Europe. UKEurope Paracetamol hepatotoxicity54.1%2% Viral36.5%70% HAV4.9%4% HBV + HDV9.0%45% Other0.6%3% Indeterminate16.5%18% Drug reaction6.9%14.5% Miscellaneous3.9%12

5 Paracetamol as cause of acute liver failure Commonest cause of ALF in UK (>50%) Commonest cause of ALF in UK (>50%) Usually taken with suicidal intent Usually taken with suicidal intent 8% due to unintentional overdosing in high risk patients 8% due to unintentional overdosing in high risk patients ALF occurs in 2-5% of patients who present following paracetamol OD ALF occurs in 2-5% of patients who present following paracetamol OD Median dose 40g (range 5-210g) Median dose 40g (range 5-210g)

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

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

8

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

10 Case 1 25 year girl 25 year girl 30 paracetamol, 01.00am 30 paracetamol, 01.00am PMH: epilepsy, on carbamazepine PMH: epilepsy, on carbamazepine Admitted 9.00am Admitted 9.00am Clinically well, obs normal Clinically well, obs normal Para level: 80mg/L Para level: 80mg/L Treat? Treat?

11 Treat???

12 Case 2 35yr male 35yr male 60 paracetamol taken 24hours ago 60 paracetamol taken 24hours ago O/E vomiting, abdo tender O/E vomiting, abdo tender P 120/min, BP 120/80P 120/min, BP 120/80 What else do you want to know? What else do you want to know? What are you going to do? What are you going to do?

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

14 Case 2 PT 24 PT 24 Bili 30, ALP 130, ALT 9000, Alb 40 Bili 30, ALP 130, ALT 9000, Alb 40 Na 145, K 3.0, Ur 19, Cr 190 Na 145, K 3.0, Ur 19, Cr 190 Glu 3.5 Glu 3.5 pH 7.38, O 2 13, CO 2 3, HCO 3 12 pH 7.38, O 2 13, CO 2 3, HCO 3 12 Lactate 3.0 Lactate 3.0

15 Management of paracetamol overdose Monitor paracetamol levels > 4 hours after ingestion Monitor paracetamol levels > 4 hours after ingestion If below treatment line, repeat level If below treatment line, repeat level Give NAC if over treatment line Give NAC if over treatment line ?high risk line?high risk line Treatment lines not valid for staggered OD Treatment lines not valid for staggered OD If in doubt, give NAC! Dont wait! If in doubt, give NAC! Dont wait!

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

17 Other management If features of liver failure develop, continue N-acetylcysteine If features of liver failure develop, continue N-acetylcysteine PPIPPI Careful monitoring of fluid balance (CVP/U.O), haemodynamicsCareful monitoring of fluid balance (CVP/U.O), haemodynamics Broad spectrum antibiotics (anti-fungals)Broad spectrum antibiotics (anti-fungals) Monitor and correct electrolytes (Ca, Mg, PO4)Monitor and correct electrolytes (Ca, Mg, PO4) Monitor glucoseMonitor glucose Look for signs of confusionLook for signs of confusion

18 Acute liver failure Support Support CNSCNS RespirationRespiration CirculationCirculation RenalRenal CoagulationCoagulation InfectionInfection MetabolismMetabolism

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

20 Alcohol withdrawal

21 Alcohol Withdrawal Signs and symptoms range widely Signs and symptoms range widely tremulousness (shakes), insomnia, anxiety, hyperreflexia, mild autonomic hyperactivity, and GI upsettremulousness (shakes), insomnia, anxiety, hyperreflexia, mild autonomic hyperactivity, and GI upset Delerium Tremens usually > 48 hours after cessation of drinking Delerium Tremens usually > 48 hours after cessation of drinking Disorientation, agitation, and hallucinations; with severe autonomic hyperactivity (tremulousness, tachycardia, tachypnoea, hyperthermia)Disorientation, agitation, and hallucinations; with severe autonomic hyperactivity (tremulousness, tachycardia, tachypnoea, hyperthermia) Hallucinations Hallucinations Persecutory, auditory, or (most commonly) visual and tactile hallucinationsPersecutory, auditory, or (most commonly) visual and tactile hallucinations Seizures Seizures

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

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

24 CAGE questionnaire Have you ever felt you should cut down on your drinking? Have you ever felt you should cut down on your drinking? Have people annoyed you by criticising your drinking? Have people annoyed you by criticising your drinking? Have you ever felt bad or guilty about 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)? 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 Benzodiazepine Controls symptoms of alcohol withdrawal Controls symptoms of alcohol withdrawal Patients admitting to >10u per day are likely to require treatment 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 Dose/level and length of treatment will depend on severity of dependence and on patient factors

26

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

28 Wernickes encephalopathy Thiamine deficiency Thiamine deficiency Classic triad of encephalopathy, ataxia, and ophthalmoplegia (10%) Classic triad of encephalopathy, ataxia, and ophthalmoplegia (10%) Consider diagnosis: Consider diagnosis: long-term alcohol abuse or malnutritionlong-term alcohol abuse or malnutrition acute confusion, decreased conscious level, ataxia, ophthalmoplegia, memory disturbance, hypothermia with hypotension, and delirium tremens acute confusion, decreased conscious level, ataxia, ophthalmoplegia, memory disturbance, hypothermia with hypotension, and delirium tremens

29 Wernickes encephalopathy Beware of administering dextrose in a thiamine-deficient state 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 Exacerbates the process of cell death by providing more substrate for biochemical pathways that lack sufficient amounts of coenzymes Start thiamine concurrently or prior Start thiamine concurrently or prior Iv pabrinex (vitamins B + C) Iv pabrinex (vitamins B + C) 2 pairs tds for 3 days2 pairs tds for 3 days Thiamine 100mg tds Thiamine 100mg tds Vitamin B co forte 2 tabs daily Vitamin B co forte 2 tabs daily

30 Korsakoff psychosis Characterized by retrograde amnesia (inability to recall information), Characterized by retrograde amnesia (inability to recall information), Inability to assimilate new information Inability to assimilate new information Decreased spontaneity and initiative Decreased spontaneity and initiative Confabulation. Confabulation. Other manifestations of thiamine deficiency Other manifestations of thiamine deficiency Wet beri beriWet beri beri Nutritional polyneuropathyNutritional polyneuropathy

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

32 Case You are called to see the following man who is c/o abdominal pain You are called to see the following man who is c/o abdominal pain 48yr man, alcoholic liver disease 48yr man, alcoholic liver disease Bili 150, Alb 30, PT 16 Bili 150, Alb 30, PT 16 Ascites Ascites

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

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

35 Analgesia in chronic liver disease Paracetamol Paracetamol Safe in small quantitiesSafe in small quantities Probably the safest analgesic for these patients!!!!Probably the safest analgesic for these patients!!!! Reduce maximum daily intake and avoid regular dosing for >5 days)Reduce maximum daily intake and avoid regular dosing for >5 days) ie 500mg – 1g qds prn (max 2g daily) ie 500mg – 1g qds prn (max 2g daily)

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

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

38 Diuretics Why do we prescribe? Why do we prescribe? To control ascites? To control ascites? Why do we need to control ascites? Why do we need to control ascites? Patient comfort! Patient comfort! (Rarely respiratory distress) (Rarely respiratory distress) REMEMBER: REMEMBER: Ascites does not kill patients, but diuretics can!

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

40 The Confused Liver Patient Consider: Consider: EncephalopathyEncephalopathy Grades 1-4 (daytime somnolence, agitation, liver flap, decreased conscious level, coma) Grades 1-4 (daytime somnolence, agitation, liver flap, decreased conscious level, coma) Alcohol withdrawalAlcohol withdrawal Sub-dural haematoma or other neurological eventSub-dural haematoma or other neurological event

41 Encephalopathy - causes Drugs (including alcohol) Drugs (including alcohol) Check drug chart for night sedation, opiates, chlordiazepoxideCheck drug chart for night sedation, opiates, chlordiazepoxide Electrolyte abnormalities Electrolyte abnormalities Low sodium, low potassium, dehydrationLow sodium, low potassium, dehydration Hypoglycaemia Hypoglycaemia Sepsis (including SBP) Sepsis (including SBP) Constipation (Give lactulose + enemas) Constipation (Give lactulose + enemas) GI bleeding GI bleeding

42 The home run! Take home points

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

44 Take home points (Alcohol withdrawal) Take a proper alcohol history Take a proper alcohol history Think about alcohol withdrawal before symptoms develop Think about alcohol withdrawal before symptoms develop Monitor patient daily and review dosage of chlordiazepoxide! Monitor patient daily and review dosage of chlordiazepoxide! All dependent patients must receive Pabrinex and vitamin B. 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 Paracetamol is safe in small quantities and should be first choice Caution with other groups Caution with other groups Diuretics Diuretics Think carefully before prescribingThink carefully before prescribing No urgency in this situationNo urgency in this situation Monitor electrolytes and renal functionMonitor electrolytes and renal function

46 Confused liver patients Management of encephalopathy is usually straightforward if you remember the checklist! Management of encephalopathy is usually straightforward if you remember the checklist! Check for sepsisCheck for sepsis LactuloseLactulose FluidsFluids Replace electrolytesReplace electrolytes Check drug chartCheck drug chart Do not sedate them!! Do not sedate them!!

47 Thank you for your attention!


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