WEEK 12 - Liver Pharmaceutical Care Flashcards
Liver impairment
Has a broad spectrum of conditions
- Liver disease = actual damage to liver
- Liver dysfunction = elevated liver blood tests, but no scarring, fibrosis etc to liver
- Drug-induced liver disease = medicine cause liver problems
What is the Child-Pugh scoring system used for?
To classify cirrhotic liver function:
- Child-Pugh A: Compensated cirrhosis
- Child-Pugh B: Significantly compromised liver function
- Child-Pugh C: Decompensated cirrhosis
Compensated = well functioning liver
Decompensated = liver not functionig how it should
How does drug handling and ADME differ in special patient groups (SPG)
SPG = child, pregnancy, elderly, renal/ liver impairment, critically ill
List key considerations for managing drug therapy in SPG
Problems of ADRs in SPG
Principles of safe medicines use in people with liver impairment
Things to consider
Liver-related:
- Classification / severity
- comp vs decomp, fibrosis, cirrhosis
- child pughs score
- Liver blood tests
- Cause of liver disease
- Signs and symptoms
Non-Liver related:
- Patient age
- PMH, co-morbidities
- Allergies
- Medication (Rx, OTC, herbal)
Drug Factors:
- Pharmcokinetics
- Pharmacodynamics
- SEs
- Therpautic index
- Route of administartion
Diagnostics: Liver blood tests
Example tests, problems
To diagnose liver dysfunction MUST have 2-3 elevated liver test results
- result must be 2x the normal limit
Examples:
- Transaminases (ALT / AST)
- ALP (Alkaline phosphatase )
- Albumin
- Bilirubin
- GGT (γ-glutamyltransferase)
- Cirrhosis specifc = PT, INR, Platelets
- Prothrombin time
PROBLEM:
- Liver blood tests are non-specifc
- Abnormal tests do not always indicate liver dysfunction
- Not all lier dysfuntions produce abnormal tests
- Need to consider trends, not isolation
What factors need to be considered when adjusting medication dosages in people with liver impairment
- Pharmocokinetics e.g. ADME
- Pharmacodynamics
Pharmocokinetics: ADME
factors to consider when adjusting medication dosages
- Absorption
- ascites may ↓ absorption - Distribution
- ↓ protein binding
- - Metabolism
- may ↓ as cirrhosis causes ↓ cell mass
- ↓ metabolism = drug accumulation = ↑ SE
- affected by hepatic blood flow + functioning cell mass
- ↓ blood flow due to portosystemic shunting (blood diverted from lier)
- ↑ plasma conc. of drugs with high 1st pass metabolsim = ↑ bioavailability
- cirrhosis patients can still metabolise + excrete drugs - Excretion
- drug accumulation due to extensive billary clearance
- may also affect renal excretion if eGFR is overstimulated (cirrhotic pts)
Pharmacodynamics
factors to consider when adjusting medication dosages
- ↑ SE risk
- ↑ toxicity
- Exaggerated or reduced responses
- Hepatic encephalopthy alters BBB permeability = brain is sensitive to sedating effects
What drugs should be used with caution in cirrhotic patients
Drugs causing:
1. Sedation
- can worsen encephalopathy (confusion)
- e.g. opioid analgesics, bdz, hypnotics
- GI Ulceration
- ↑ risk of GI bleeding / damage
- e.g. NSAIDs, Aspirin, Bisphosphonates
- Clotting
- ↑ risk of bleeding
- e.g. Aspirin, Warfarin, Clopidogrel, NSAIDs
- Fluid retention / electorlyte imbalance
- can worsen encephalopathy
- e.g. diruetics
- High sodium content
- can worsen ascites
- e.g. antacids, soluble talets
- Constipation
- can worsen encephalopathy
- e.g. opioid analgesics, sedating antihistamines, antimuscarinics
What route of administartion should be used or avoided
ORAL = most PREFFERED
MR / Long-acting = AVOID
- if patient has SE they will be prolonged compared to standard dosing
IM = avoid if have high INR
TOPICAL = caution
- if have puritis or ascites may cause further irritation
What Analgesia is safest to use in cirrhotic patients
PARACETAMOL
- if weigh < 50kg can NOT take 500mg QDS MUST TAKE 500mg TDS
OPIOIDS
- not 1st line but are preffered over NSAIDs
AVOID NSAIDs due to SE
- e.g. ibuprofen
What resources can be used to help make decisions about medicines use
- BNF/SPC recommendations
- NICE CKS
- Specialist Pharmacy Service (SPS)
- Medicines Monitoring Tool
- Summary of product characteristics - https://www.medicines.org.uk/emc/
- LiverTox https://www.ncbi.nlm.nih.gov/books/NBK547852/
- https://britishlivertrust.org.uk/
Explain how DILI occurs
DILI = drug induced liver injury
When a drug is hepatotoxic can cause acute or chronic liver disease
RISK FACTORS:
- Female
- Age
- Genetics
- Polypharmacy
NOTE: patients with underlying liver disease don’t have increased susceptibility BUT effects of hepatotoxicity may be more severe
What are the 2 types of reactions DILIs can be classified under
- Intrinsic Reactions
- Predictable
- Reproducible
- Dose dependent
- Tend to cause necrosis
- Occur rapidly (within hours) - Idiosyncratic Reactions
- Not predictable
- Not reproducible
- Not dose dependent
- Can cause any type of liver injury
- Occurs slower (weeks to months)
How is DILI managed
- Early identification of medication causing DILI
- signs and symptoms e.g. jaundice, elevated results - Stop drug
- Give general supportive or specifc treatment
- supportive = symptomatic relief i.e. hydration - Specialist referral
List 5 common complications of liver disease
- Ascites
- Hepatic encephalopathy
- Portal hypertension
- Pruritus
- Alcohol withdrawal
How is Ascites managed
inc. recommendations, monitoring and follow-up
Ascites - fluid build up in abdomen (belly)
Recommendations:
- Diuretic e.g. Spironolactone 100-400mg PO
- Prophylatic Abx for SBP
- PRN Analgesia
- Restrict sodium or fluid intake
Monitoring:
- Weight loss daily (AIM: 0.5-1kg loss daily)
- Creatine level for AKI
- Renal function
- Serum electrolytes
- Serum potassium for hyperkalemia
- ADR and SE
Follow-up:
- After hospital discharge for refactory ascities
How is Hepatic Encephalopathy managed
inc. recommendations, monitoring and follow-up
Hepatic Encephalopathy - brain dysfunction due to liver disease
- caused by build up of ammonia
Recommendations:
- Lactulose 20-30ml BD
- laxative helps remove excess ammonia in gut + reduce ammonia production
- Oral Rifaxamin 550mg BD (prevent recurrence)
Monitoring:
- Ammonia in plasma
- Passing 2-3 soft stools daily
- Lactulose SE e.g N&V, abdominal pain
Follow-up:
- Psychiatrist test ~ check cognitive status, ensure no decline after discharge
How is Portal hypertension managed
inc. recommendations, monitoring and follow-up
Recommendations:
Monitoring:
Follow-up:
How is Pruitus managed
Pruritus (itching) - caused by a build up of bile salts
Recommendations:
- Cholestyramine 4-8g OD, PO
- ↓ cholesterol levels
- Emoilent if pt develops dry skin
- Advise to refrain from itching
Monitoring:
- How often pt expereinces itching (assess if treatment is effective)
- Vitamin A, D and K levels
- Folic acid levels
Follow-up:
- 2-4 weeks GP after discharge, if still experiencing itching
How is Alcohol Withdrawal managed
inc. recommendations, monitoring and follow-up
Recommendations:
Monitoring:
Follow-up:
