Liver: managing patients with hepatic disease Flashcards

Question

Explain how acetaminophen (paracetamol) leads to a non toxic and toxic compound

Answer 1

Acetaminophen can conjugate into: glucuronide- moiety (non toxic) sulfate- moiety (non toxic) N-acetyl-p-benzo-qunone mine NAPQI (toxic) This NAPQI can be converted to cysteine and mercapturic acid conjugates that are non toxic via glutathione with NAC

Answer 2

Review all potential medicines taken- herbal, OTC, P, POM, vitamins Still taking which drugs - Frequency, dose Started, stopped Drug reactions occur within first 3-6 months treatment (5-90 days from first dose, 15 days from last dose) Presenting signs and symptoms - pattern of liver disease- pre-treatment - suspect drug if presents with jaundice until proven otherwise - some can cause jaundice, others none

Answer 3

Main elimination route for many drugs Can alter response to drugs in several ways Drugs can affect metabolism of other drugs by induction and inhibition of cytochrome P450 (CYP450) enzymes in liver: - Inhibitors of erythromycin, amiodarone, ketoconazole, ciprofloxacin - Increased effect and toxicity of affect drug unless it is prodrug- warfarin Inducers: Barbiturates, carbamazepine, ethanol, phenytoin, rifampicin, St John Wort - Increased hepatotoxic metabolites of other drugs - Decreased pharmacological effect of affected drug

Answer 4

Most drugs are safe in stable liver disease Use older and more established drugs Consider patient factors Avoid drugs in severe disease- especially if hepatotoxic Consider renally excreted Start with smaller doses and increase slowly or give PRN Choose best option and monitor clinical response

Answer 5

Kept to minimum, smallest effective dose at greatest interval Paracetamol- 500mg- 1g TDS Overdose- severe liver damage Common reason for liver transplant Avoid NSAIDS and COX-2 inhibitors Bleed, altered platelet function, GI irritation, ascites Caution opioids Sedation, hepatic encephalopathy Tramadol then sevredol Oramorph Caution- soluble 10% ethanol TCAs- low dose fine, nortriptyline Gabapentin okay- neuropathic pain

Answer 6

TCAS- avoid- sedating- risk of hepatic encephalopathy SSRI- confer to bleeding risk, hyponatraemia, use low dose or increased interval Sertraline 25-50mg OM Citalopram max 20mg Mirtazepine 15mg ON- lowest bleeding risk but sedating

Answer 7

All can cause elevations in transaminases (transient or persistent) Monitor LFTs in all patents No link between elevation in LFTs and developing toxicity IF ALT > 3 x upper limit normal, asymptomatic repeat test Avoid in acute liver and decompensated chronic liver disease Can be used safely if no or mild synthetic dysfunction Statins may be beneficial in NAFLD by improving transaminases

Answer 8

Increased bilirubin, AST, ALP, GGT, PT Decreased albumin and Hb Jaundiced, weakness in legs, palmar erythema, haematoma, spider naevi Ascites, muscle wasting

Answer 9

Normal Fatty liver or steatosis- reversible with abstinence, rarely symptomatic, occur after a few days Steatohepatitis/ acute alcoholic hepatitis: Accumulation of fat + hepatocellular injury, may or may not improve with abstinence, can occur several weeks after stopping drinking Fibrosis or cirrhosis

Answer 10

``` Anxiety Decrease respiratory rate GI disturbance Impaired judgement Loss of consciousness Impotence Acute poisoning Unintentional injury ```

Answer 11

``` Liver disease Cancer Pancreatitis GI ulceration Osteoporosis Infertility Heart disease Stroke Hypertension Obesity Dementia ```

Answer 12

``` Minor withdrawals: Sweating Shaking Depression Anxiety Irritability Nausea and vomiting Restlessness Poor concentration ``` ``` Delirium tremens: Severe agitation Delirium Course tremor Large increases in pulse, blood pressure, respiratory rate Auditory and visual hallucinations Disorientation and reduced consciousness Excessive sweating (diaphresis) ```

Answer 13

Chlordiazepoxide PRN Pabrinex IV HP 1 pair OD (3 days) Then multivitamin 1 OD, thiamine 100mg BD Spironolactone 100mg OD Furosemide 40mg OD Lactulose 30mL TDS Chlorphenamine and aqueous cream and menthol Dalteparin 5000 units OD

Answer 14

Benzodiazepine - Chlordiazepoxide, lorazepam, diazepam Thiamine (IV pabrinex and/or oral) Multi-vitamins Nutrition Fluid and electrolyte replacement Document history of alcohol intake- AUDIT or CAGE questionnaire Referral to community support where possible

Answer 15

``` Day 1: 30mg QDS, 10mg (max 200mg/24 hours) PRN Day 2: 20mg QDS, 10mg (max 200mg/24 hours) PRN Day 3: 20mg TDS Day 4: 20mg BD Day 5: 10mg BD Day 6: STOP ``` - Appropriate if previous delirium tremens, seizures or moderate alcohol withdrawal syndrome (AWS) - Anxiolytic and anticonvulsant - Review daily - Individual titration - Monitor for over sedation, respiratory depression, hypotension - Can fit as dose is tailed off - Risk of chest infection - Reassess reducing dose if >3 prn doses are needed in 24 hours - Maximum 10mg BD for 24 hours on discharge

Answer 16

Tailored to individual requirements based on severity of withdrawal Benzodiazepine dosed and administered via validated assessment tool: clinical institute withdrawal assessment scale for alcohol (CIWA-Ar) - calculate every 2-4 hours- severity linked to frequency of assessment - 10 item assessment to quantify severity and monitor and medicate appropriately - Score 8+ an accepted trigger for PRN dosing Several studies show lower total dose and shorter hospitalisation periods vs fixed dose regimen

Answer 17

IV diazepam 5-10mg into large vein every 15-30 minutes until patient is calm Parenteral diazepam repeated after 5 minutes Lorazepam IV 1-4mg 15-60 minutes Patients may need high doses

Answer 18

Complication of withdrawal, can occur if benzodiazepine is tailed off too quickly Options: IV lorazepam or PR diazepam Status epilepticus: IV diazepam Pabrinex Chlordiazepoxide Increase dose of oral benzodiazepine (BDZ) to reduce further seizure risk Phenytoin not appropriate

Answer 19

Unlicensed in UK Adjunctive to benzodiazepine Not as mono therapy- do not treat alcohol withdrawal since can lower seizure threshold Exclude Wernike's encephalopathy and hepatic encephalopathy before starting Use of haloperidol or olanzepine

Answer 20

Nutrition: Poor intake, chronic pancreatitis, chronic liver disease, poor absorption Consider NG feeding (caution varicose) Risk of re-feeding syndrome- electrolytes ``` Thiamine: Prevent polyneuritis and wernike's encephalopathy (confusion, ataxia, memory loss, opthlmoplegia and subsequent Korsakoffs psychosis) IVI pabrinex PO thiamine Other multivitamins ```

Answer 21

Maximum 24 hour benzodiazepines Oral B vitamins Referral to drug and alcohol support services Needle exchange

Answer 22

Psychological support- local drug and alcohol services ``` Drugs given: Disulfiram Acamprosate Naltrexone Nalamefene ``` Be aware of alcohol containing drugs, toiletries, mouthwashes

Answer 23

Presented with marked inflammation of the liver presented with jaundice Occur on background of a normal liver or complicate cirrhosis Occur several weeks after stopping drinking Reversible with abstinence but often underlying cirrhosis Characterised by fever, hepatomegaly, leucocytosis, signs of liver failure e.g. ascites, raised ALT Short term mortality among patients

Answer 24

``` Age White cell count Urea Prothrombin ratio bilirubin ```

Answer 25

Ascites and peripheral oedema Causes: low albumin, impaired aldosterone metabolism, reduced renal blood flow, portal hypertension, increased hepatic lymph production Avoid drugs that can exacerbate: NSAIDs, saline, high salt, fluid restriction Natural history in chronic liver disease - Diuretic sensitive than resistant, associate with HRS and hyponatraemia 50% mortality over 2 years

Answer 26

``` Treatment: Fluid and salt restriction- bed rest Spironolactone- Aldosterone antagonist Furosemide- add cautiously for peripheral oedema Paracentesis (+ albumin) TIPSS Peritonea-Venous shunt ``` ``` Monitoring: Weight loss Urine output/renal function Yes (Na, K, Cr) BP and encephalopathy Diagnostic ascitic tap SBP- temp and WCC ```

Answer 27

Hepatic encephalopathy

Answer 28

Reversible changes in mental state secondary to failure of liver to metabolise digestive products or toxins; toxins bypass liver to brain Neuropsychiatric changes- four reversible stages: Stage 1: forgetfulness, confusion, agitation (day night muddle) Stage 4: coma, unresponsive to painful stimulus

Answer 29

Remove and avoid precipitants Reduce protein intake Decrease bacterial ammonia product and enhance elimination Lactulose: Prevents constipation and inhibits colonic bacteria to convert NH3 to NH4 Phosphate enemas Rifaximin- poorly absorbed antibiotic that eliminates colonic bacteria

Answer 30

Pruritus: due to bile acids within skin, up regulation of endogenous opioids, serotonergic pathways Generally less severe than with pure chloestasis ``` Other options: Colestyramine Ursodeoxycholic acid Rifampicin Sertraline Ondansertron Naltrexone ```

Answer 31

VTE prophylaxis Liver- synthesis of clotting factors Used as an indicator for prothrombin time Acute and chronic liver disease elevated Increase prolongation of clotting time if clotting factor deficient Avoid intramuscular injections- haematoma Usually used in more advanced cirrhosis with low albumin levels

Answer 32

Decreased blood flow through liver Portal hypertension >12mmHg Collateral vessels Varices (stomach, oesophagus, rectum)

Answer 33

Resuscitate Terlipressin- until haemostasis for five days Prophylactic antibiotics Oesophageal varices Banding Consider transjugular intrahepatic portosystemic shunts (TIPSS) if bleeding not controlled by banding Gastric varices Endoscopic injection of N-butyl-2-cyanoacrylate Uses TIPS if not controlled by injection

Answer 34

Bacterial sepsis- must use ceftriaxone 2g for 2 days of the week Ascites- tx once BP is stable Ulceration around scope site- oral PPI alcohol withdrawal syndrome- pabrinex + benzodiazepine

Answer 35

Weekly endoscopies until varicies are eradicated then every 2 years Carvedilol or propranolol reduces portal pressure Laxatives- POST TIPS TIPS/Transplant

Answer 36

Keep medication to minimum and review regularly Once daily timings Stop drinking- support groups Help with prescription costs Counsel on indications and importance of medication prescribed Medication charts (MDS) District nurses support e.g. enemas for hepatic encephalopathy Advise on OTC, herbals, illicit (no NSAIDS)

Answer 37

Communicate with and offer evidence on based prescribing advice to multi-drug therapy Check drug dosing in liver disease and potential induced liver disease Drug history reviews Check for cytochrome p450 interactions for hepatitis C patient and carer medication education Specifying drug regimens- adherence, pill burden Contribute to production of guidelines- local and national Monitor drug expenditure- HCV expensive Audit- against local and national prescribing guidelines