Prescribing in Hepatology Flashcards
Functions of the liver?
Immunological Metabolic Homeostasis Storage Bile production Biosynthesis - albumin, clotting factors Metabolism of drugs, ammonia
Phase 1 metabolism in the liver
By cytochrome p450 enzyme family
- prodrugs are activated by the enzyme
- enzyme can reduce the bioavailability of some drugs= first pass metabolism
- can deactivate drugs
Phase 2 metabolism in the liver
CONJUGATION
- makes metabolite water soluble so it can be excreted
Symptoms of acute alcohol withdrawal
Anxiety Nausea Vomiting Confusion Anorexia Delirium tremens if severe Seizures
CIWA-Ar Chart
Used to manage alcohol withdrawal
List of different symptoms with scores to determine severity
Score determines Tx
If >10 = give benzodiazepine
What is the first line benzodiazepine?
Chlordiazepoxide
When is lorazepam used?
In alcohol withdrawal if patient has cirrhosis
Benzodiazepines metabolism
- metabolised via p450 enzyme in liver
MOA of benzodiazepines
- sedative by enhancing GARA (gamma aminobutyric acid) which is an inhibitory neurotransmitter
Side effects of benzodiazepines
Addiction in LT use Suicide ideation Falls/fracturs in elderly Confusion Drowsiness Respiratory Depression Hallucinations Rare = agitation
Chlordiazepoxide properties
Long acting
Half life 6-30 hours
How to prescribe chlordiazepoxide?
First 24 hours - PRN, 25-50mg depending on CIWA-Ar chart, 2 hourly, maximum dose in 24 hours is 250mg
Day 2 = stop PRN basis, calculate total administered in first 24 hours and prescribe in 4 divided doses reducing by 20% or 10mg QDS daily until reaches 0
Lorazepam
Short acting
12 hour half life
Minimal risk of excess which is needed if liver failure
If cirrhosis
How to prescribe lorazepam?
PRN 1-2mg 2 hourly as per CIWA-Ar
If >10mg/24 hours reviews as this is maximum
What dose of chlordiazepoxide is equivalent to 1mg of lorazepam?
25mg
10mg of diazepam
Dangerous side effect of benzodiazepines to look out for?
Respiratory depression if in excess (either overdose or accumulated in body) - ITU!
Treatment for seizures from acute alcohol withdrawal
Lorazepam 2-4mg slow IV up to 8mg in 24 hours max
Treatment for psychotic symptoms from acute alcohol withdrawal
haloperidol
0.5-1.5mg IM or 1-2mg PO 2-3 times daily
Only in combination with chlordiazepoxide
Pabrinex
High strength vitamin B and C
To prevent Wernicke’s and Korsakoff’s
Dose of pabrinex
2 pairs IV TDS for 3-5 days
Prophylactic dose = 1 pair TDS
Side effects/cautions with pabrinex
Anaphylaxis/allergic reaction
Need to be careful if giving a glucose infusion at the same time as pabrinex or thiamine (e.g. if diabetic patient) as can deplete thiamine reserves = Wernicke’s
What to give after Pabrinex course?
Need to continue supplementation
- thiamine 100mg TDS PO
- dietician review and nutritional supplements
- Vitamin B co-strong needed if poor nutritional intake but risk of refeeding
Signs of decompensated liver cirrhosis
Spider naevi Jaundice Palmar Erythema Splenomegaly Gynaecomastia Encephalopathy Ascites Bleeding varices
How to go about treating encephalopathy?
Build up of toxins/ammonia in the body
- treat triggers of it
- eliminate ammonia through gut
- target for 2 soft stools a day
Lactulose MOA
Osmotic laxative
Local osmotic effect in colon = increased faecal bulk & peristalsis
High doses = reduction in colon pH reducing absorption and increasing excretion of ammonia
How to prescribe lactulose?
Prophylaxis vs treatment different
Need to ensure patient is producing 2 loose bowel motions per day
- can take 48-72 hours to work
- 15-50ml TDS varied dose
Compliance issues with lactulose?
Bloating
Abdominal Pain
Nausea
Bad taste
Phosphate enemas
Alongside lactulose as a STAT if patient in encephalopathic
Means lactulose is fast acting
When patient passes stools - PRN BD
Rifaxmin MOA
Antibiotic
Inhibits bacterial DNA dependent RNA polymerase
Poorly absorbed from GI tract so not much systemic effect
Resistance high risk
Metabolism by liver
Used alongside lactulose or recurrent encephalopathy only
Dose of rifaximin
550mg BD
Side effects of rifaximin
Constipation Abdominal pain Ascites Hyperkalaemia Neutropenia Depression Dizziness
Issues with rifaximin
Withhold if patient is on systemic ABs
- interacts with ciclosporin
Drugs for ascites
Diuretic combination = furosemide and spironolactone
Also = fluid and sodium restriction, improve nutrition, manage liver disease
Furosemide MOA
Loop diuretic
Bind to chloride site of Na-K-2Cl co-transporter in ascending LOH
Inhibits sodium reabsorption increasing diuresis
Furosemide dose
40mg OM
Up to 80mg BD if possible
Give second dose at lunch not night as will keep needing to go toilet
Risk of furosemide
Tend to avoid IV usage as risk of AKI
Hypokalaemia
Spironolactone MOA
Aldosterone Antagonist
Inhibits aldosterone dependent Na-K exchange site in DCT
Dose of spironolactone
100mg
Up to 400mg if possible
Much higher doses than HF dose
Side effects of spironolactone
Painful gynaecomastia
Consider switch to amiloride but less effective in cirrhosis patients
Hyperkalaemia
Monitoring need for diuretics
- monitor BP as can reduce it =consider falls risk
- when use spiro + furosemide K+ problems cancel out but good to monitor
Treatment for gastro-oesophageal varices
Endoscopy
Then vasoconstrictor start = terlepressin
MOA of terlepressin
Vasopressin analogue 4-6 hour half life Reduced effect on kidneys and diuresis Contraction of smooth oesophageal muscle = compression of varices Increase in blood pressure
What patients to be cautious with when on terlepressin?
Those with: HTN - especially if renal HTN or vessel sclerosis Atherosclerosis Cardiac dysrhythmias Coronary insufficiency!
What to monitor with terlepressin?
ECG
BP
Serum sodium and potassium
Fluid balance
Dose of terlepressin
2mg IV bolus
Then 1-2mg every 4-6 hours until bleeding controlled
Continue until haemostasis achiever or up to 5 days
Can taper dose down
Beta blockers
Prophylaxis post variceal bleed
Non cardioselective preferred as increased effect on portal pressures
MOA of beta blockers
Competitive antagonists of beta adrenergic beta receptor sites
What beta blocker is used for variceal bleed proophylaxis?
Carvediol
- complementary mild anti-alpha 1 adrenergic activity
Types of injury drugs can cause to the liver?
Cholestatic
Hepatic
Acute liver failure
Paracetamol overdose
7.5g = acute liver toxicity
3 weeks of 4g/day = ALP rise in 1/3 patients
24-72 hours marked elevations in ALT and AST
48-96 hours symptoms appear
Symptoms of paracetamol overdose
Jaundice
Confusion
Hepatic failure
Potentially death
What is the mechanism of hepatocellular injury?
Forms a toxin = N-acetyl-p-benzoquinoneimine
- conjugated with glutathione, detoxified and secreted
- high doses = acculumation of toxin
RF of drug induced hepatocellular injury
Increase p450 metabolism - due to chronic alcohol or certain drugs
Decreased glutathione = fasting, malnutrition, alcoholism
Treatment for paracetamol overdose
N-acetylcysteine IV infusion
- restores glutathione levels or acts as alternative conjugation substrate
- antioxidant properties
Dose of IV NAC
- within 8 hours of overdose effective
- glucose 5% as diluent or NaCl 0.9%
- first infusion = add 150mg/kg to 200mL over 1 hour
- second = 50mg/kg to 500mL over 4 hours
- third = 100mg/kg to 1000mL over 16 hours
- may need continuation at third dose and rate
Hep B treatment target
HBV DNA to undetectable levels and ALT to normalise
Hep B treatment drugs
Tenofovir or entercavir to suppress virus
Then PEG-IFN but no longer used
To suppress not cure so need lifelong Tx
Tenofovir
Nucleotide monophosphate analogue
Competitive inhibition
Replaces deoxyribonucleotide substrate in HBV DNA and acts as a chain terminator
Eliminated through kidney
Safe in pregnancy
Faster than entecavir at reducing viral DNA initially but after 1 year similar
Entecavir
Competes with dexoyguanosine triphosphate inhibiting reverse transcription of HBV DNA
Eliminated through kidney
Toxic in pregnancy
Women of childbearing age should not be started on it
Side effects/cautions with antivirals
- LT = nephrotoxicity with lactic acidosis, Fanconi syndrome, reduction in bone mineral density
- tenofovir = higher nephrotoxicity
- monitor creatinine and phosphate levels
Hep C Treatment
Short course oral anti-viral - very effective!
Tx based on genotype as multiple agents available and 6 possible genotypes
Also based on if patient has cirrhosis
In combination with ribavarin?
Frequent monitoring
NS5A inhibitors
End in svir
Inhibit RNA polymerase
NS5B inhibitors
End in buvir
Inhibit RNA polymerase
NS3/4A protease inhibitors
End in previr
