L13 Therapeutics in Liver Disease Flashcards
Therapeutic dose of paracetamol is based on _______
Max dose in adults is ___in 24 hours!!
Overdose Classifications
- ______: Excessive paracetamol ingested in < 1 hour
- ______: Excessive paracetamol ingested over a period >1 hour
Weight Based: Severe toxicity usually occurs when >________/Kg in 24 hours is taken.
Pregnancy – ____________________________
Obesity –__________________________
Therapeutic dose of paracetamol is based on age
Max dose in adults is 4g in 24 hours!!
Overdose Classifications
- Acute: Excessive paracetamol ingested in < 1 hour
- Staggered: Excessive paracetamol ingested over a period >1 hour
Weight Based: Severe toxicity usually occurs when >150mg/Kg in 24 hours is taken.
Pregnancy – Use pre-pregnancy weight
Obesity – If the patient weighs >110kg use 110kg as weight
Treatment of Paracetamol Overdose?
N-Acetylcysteine (NAC): Precursor to Glutathione metabolizing toxic intermediate (NAPQI) => reduces NAPQI => non-toxic conjugates
- Given in 3 bags
- Side effect: Anaphylaxis: Give it anyways and treat anaphylaxis: (Steroids, Adrenaline, Anti-histamines)
IF IN DOUBT JUST GIVE NAC
Criteria for Liver Transplant?
King’s College Criteria for Liver Transplant
Complications of Alcoholics and Treatments?
Withdrawing Patients
- Tachycardic with tremor => High Seizure Risk (CIWA Score indicative of risk of seizing!!!)
- Treatment = Diazepam 20mg (helps stimulate receptors deprived of GABA preventing seizures)
Patients often MALNOURISHDED!!!
- High risk of Re-feeding Syndrome + Wernicke’s Encephalopathy (acute)
- Treatment: Pabrinex (IV Thiamine) Vials for 3-5 days then Thiamine 100mg PO
Management/Risks of Treating Alcoholic Malnourishment?
High risk of Re-feeding Syndrome (Shifting of electrolytes into cell when fed hartmens w/ glucose=> hyponatremia, hypokalemia) and Wernicke’s Encephalopathy (acute)
Treatment:
- Pabrinex (IV Thiamine) for 3-5 days then Thiamine PO
- IMPORTANT TO GIVE BEFORE FLUIDS w/ GLUCOSE as toxic metabolites formed when glucose is given before thiamine pools restored
Severity/Prognosis of Alcoholic Hepatitis?
- Maddrey discriminany function (MDF) Score or
- Prescence of Encephalopathy
Presentation of Alchoholic Hepatitis?
Acute inflammation of liver on a background of liver disease (alcoholic
hepatosteatosis) + alcohol use
Worsening Jaundice + tender abdomen +/- encephalopathy and Ascites
Indication for whether to give steroids to treat Alcoholic Hepatitis?
Course of Treatment?
Who to avoid steroid therapy with?
MDF Score (Indication for whether to give steroids)
- > 32 GIVE Steroids
- <32 DO NOT give steroids
At day 7 calculate the Lillie Score
- Score > 0.45 = STOP STEROIDS
- Score <0.45 = CONTINUE (Low Lillie =High mortality)
Avoid Steroids in patients with active infection, GI bleeding, and Hepatorenal syndrome
Therapies for Primary Biliary Cholangitis?
First Line:
Ursodeoxycholic acid (UDCA) – naturally occurring hydrophilic bile acid that reduces bile duct destruction by removing toxic bile acids from the liver into the canaliculus
Second Line
Obeticholic Acid: Bile acid analogue that is a farnesoid X receptor (nuclear receptor in liver and intestine) agonist that drives decreased bile acid synthesis from cholesterol and increases bile acid transport out of hepatocytes into the biliary system.
Given with UDCA (if non-responders to UDCA) or as monotherapy
Epidemiology/Symptoms/Treatment of Primary Sclerosing Cholangitis?
- Autoimmune condition: Men > Female (2:1)
- Associated with Inflammatory Bowel Disease (typically Ulcerative Colitis) and Autoimmune Hepatitis
- Pruritis (Bile acid builds up in skin leading to itch) is the most common symptom => Treated with bile acid sequestrant: Colestyramine
Wilson’s Disease Pathogenesis/Diagnosis?
Autosomal recessive disease of copper accumulation via mutation in ATP7B gene
Excess copper => inflammation=> cellular damage primarily in:
- Brain – Preferential deposition in basal ganglia
- Liver – Leads to hepatic failure
Diagnosis:
- 24-Hr urinary Copper
- Blood caeruloplasmin – transport protein of copper. (Low in Wilson’s Disease)
- Slit light exam for Kayser-Fleischer Rings
- Liver biopsy and DNA test can be performed
Treatment of Wilson’s Disease?
First Line: Zinc 50mg Oral + Diet Restriction
- Zinc acts by inducing metallothionein, which binds copper in the gut and prevents its release into circulation. Thus, copper is lost in the stool.
Second Line: Trientine + Diet Restriction (Used if Zinc not Tolerated)
- Trientine is a Copper-chelating agent which aids in the elimination of copper by forming a stable soluble complex that can be excreted by the kidney. Also chelates in the bowel and prevents absorption.
If advanced liver disease at presentation, then usually a combination of Zinc + Trientine
Most common liver infection globally?
Hepatitis B
Presentation of Hep B?
Most people are asymptomatic and present when there are late secondary complications (e.g. hepatocellular carcinoma, liver cirrhosis, liver failure)
CANNOT Cure as it integrates itself into the DNA (Can get remission)
Acute Hep B Serology Peaks/Trough?
Serological markers are essential for diagnosis and evaluating disease activity:
- Symptoms weeks 10-20
- HBs: Peaks first (Week 12): Anti-HBs: Peaks Week 32
- HBe: Weeks 4-12, Anti-Hbe: Week 12 onwards
- IgM anti-HBc: Peaks Week 15, Gone by week 32
