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
