Liver 2 Flashcards
How does the liver handle and affect drugs
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
What are the prescribing tips for someone with liver diease?
- Most drugs are safe in
stable liver disease - Use older and more established drugs
- Consider patient factors
- Avoid drugs in severe disease esp if hepatotoxic
- Consider renally excreted (caution HRS)
- Start with small dose & increase slowly or give prn
- Choose best option & monitor clinical response
What is the analgesia of choice in chronic liver disease?
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
What is the anti-depressant of choice in chronic liver disease
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
Describe the use of statins in liver disease, is it okay to use?
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
What are signs of cirrhosis
Increased bilirubin, AST, ALP, GGT, PT
Decreased albumin and Hb
Jaundiced, weakness in legs, palmar erythema, haematoma, spider naevi
Ascites, muscle wasting
What are the stages of alcoholic liver disease
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
What are the short term effects of alcohol on the body (8)
- Anxiety
- Decrease respiratory rate
- GI disturbance
- Impaired judgement
- Loss of consciousness
- Impotence
- Acute poisoning
- Unintentional injury
What are the long term effects of alcohol on the body
Liver disease Cancer Pancreatitis GI ulceration Osteoporosis Infertility Heart disease Stroke Hypertension Obesity Dementia
What are the withdrawal signs and symptoms from alcohol
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)
What drug treatments should be started
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
What should the acute alcohol withdrawal policy include
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
Describe the fixed dose regimen of chlordiazepoxide
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
Describe the “symptom triggered flexible regimen”
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
Describe what you should do when oral route is unavailable or inadequate for instance delirium tremens (DT) occurs?
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
Describe seizures in complications of withdrawal of benzodiazepine
Complication of withdrawal, can occur if 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
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What antipsychotics be used in Delirium tremens
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
What other considerations do you consider in patients with liver disease
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
What do you give a patient when they are discharged
Maximum 24 hour benzodiazepines
Oral B vitamins
Referral to drug and alcohol support services
Needle exchange
How do you encourage abstinence from alcohol in a patient
Psychological support- local drug and alcohol services
Drugs given: Disulfiram Acamprosate Naltrexone Nalamefene
Be aware of alcohol containing drugs, toiletries, mouthwashes
Describe acute alcoholic hepatitis: markings and characterisation
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
What does the glasgow alcoholic hepatitis score look at (5)
- Age
- White cell count
- Urea
- Prothrombin ratio
- Bilirubin
What can spironolactone and furosemide be used for in liver disease patients
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
How do you treat and monitor ascites
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
What is lactulose used for (in liver)
Hepatic encephalopathy
Define encephalopathy and what are the neuropsychiatric changes
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
How do you treat encephalopathy
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
Describe what chlorphenamine and aqueous cream with menthol is used for
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
Describe what dalteparin is used for and in terms of liver disease too
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
What is the aetiology of a Variceal haemorrhage
Decreased blood flow through liver
Portal hypertension >12mmHg
Collateral vessels
Varices (stomach, oesophagus, rectum)
What is the acute treatment of bleeding varicies that include oesophageal varies and gastric varices
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
In prophylactic treatment, what are the complications post bleeding
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
In prophylactic treatment, how do you prevent rebleed
Weekly endoscopies until varicies are eradicated then every 2 years
Carvedilol or propranolol reduces portal pressure
Laxatives- POST TIPS
TIPS/Transplant
How do you help adherence
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)
What is the role of the pharmacist in liver disease
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
