L12 Approach to Prescribing in Liver Disease

Question 1

Risk of Drug Toxicity in Liver Disease?

Answer 1

In hypoalbuminemia drugs that are normally protein bound are free and able to interact with tissue => increased risk of toxicity

CYP450 metabolism and Phase II metabolism can be altered

Question 2

What is used to grade the severity of liver cirrhosis and mortality risk?

Answer 2

Child Pugh Scrore

Question 3

Common complications of Liver Disease?

Answer 3

1. Ascites
2. Variceal Bleed
3. Hepatic Encephalopathy
4. Multiorgan Dysfunction - Hepatorenal Syndrome

Question 4

Mechanisms of Ascited Acumulation?

Answer 4

Liver Function reduced =>decreased albumin (decreased oncotic pressure to draw fluids back into vascular space)

High pressure system which causes dilatation of the splanchnic system => decreases the lymphatic clearance of fluid.

Decreased cardiac output the RAAS system is activated leading to salt and water retention.

Question 5

Fluid accumulated in the peritoneal cavity?

Answer 5

Ascites

Question 6

How to Control Ascites? Therapies and their side effects?

Answer 6

Salt and Fluid Restriction

Spironolactone (Aldosterone receptor antagonist) prevents Na and Fluid uptake in the Kidney. (FIRST LINE)

• Side Effects: Blocking the RAAS system you can get electrolyte abnormalities (Hyponatremia and Hyperkalemia) and/or Hypotension.

Furosemide (Loop Diuretic acting on the Na/K/Cl- Channel) added in with Spironolactone if minimal response to Spironolactone alone (SECOND LINE)

• Side Effects: Electrolyte Derangement, Hypotension, muscle cramps, ototoxicity

Surgical Intervention: If patients are symptomatic or there is a risk of spontaneous bacterial peritonitis (SBP) fluid should be removed. This can be in the process of an ascitic TAP or DRAIN.

Question 7

Frequent and severe complication in cirrhotic patients with ascites

Answer 7

Spontaneous Bacterial Peritonitis (SBP)

Question 8

Diagnosis/Treatment of Spontaneous Bacterial Peritonitis (SBP)?

Answer 8

Diagnostic Ascitic Tap

• Neutrophil count >250 cells/mm3!!!!!!!
• Send for Culture and sensitivity – Isolate and target treatment (treat as SBP even if negative)

Treatment:

• 3rd Generation Cephalosporin (e.g. Ceftriaxone)
  or
• Quinolone (e.g. Ciprofloxacin) -oral desired/penicillin intolerant

Question 9

Management of Esophageal Variceal Bleed as a complication of Liver Disease?

Answer 9

• Prophylactic banding/sclerotherapy
• Non-selective Betablockers (Propranolol, Carvedilol, or Nadolol) that reduce portal hypertension, thus smaller varices

Question 10

Treatment of Upper GI Bleed Secondary to Varices?

Answer 10

Treatment involves 3 things:

• IV PPI
• Terlipressin/Octreotide
• IV Antibiotics– Usually Ceftriaxone

Question 11

__________________________ a brain dysfunction caused by advanced liver insufficiency and/or portosystemic shunt. It manifests as a wide spectrum of neurological or psychiatric abnormalities ranging from subclinical alterations to coma

Answer 11

Hepatic encephalopathy (HE) is a brain dysfunction caused by advanced liver insufficiency and/or portosystemic shunt. It manifests as a wide spectrum of neurological or psychiatric abnormalities ranging from subclinical alterations to coma

Question 12

Alterations in Behaviour, Mild Confusion, Slurred speech, Disordered Sleep Hepatic encephalopathy (HE) Grade?

Answer 12

Grade 1: Mild HE

Question 13

Lethargy, Moderate Confusion Hepatic encephalopathy (HE) Grade?

Answer 13

Grade 2: Moderate HE

Question 14

Stupor, Incoherent Speech, Sleeping Hepatic encephalopathy (HE) Grade?

Answer 14

Grade 3: Severe HE

Question 15

Coma, Unresponsiveness Hepatic encephalopathy (HE) Grade?

Answer 15

Grade 4: Coma

Question 16

Goal/MOA of Treatment/Prevention of Hepatic Encephalopathy?

Treatment of Acute Encephalopathy?

Answer 16

Goal of each is to reduce nitrogenous load entering the systemic system

First Line: Lactulose (non-absorbable disaccharide that softens stool through osmotic mechanics) Acidification of gut lumen inhibits ammonia-producing coliform bacteria

Second Line:Rifaximin (broad spectrum antibiotic w/ minimal system effects) Added on w/ Lactulose is thought to reduce ammonia, neurotoxin, and inflammation.

If acute encephalopathy phosphate enemas can be used

Question 17

Renal dysfunction that occurs because of reduced renal perfusion, due to hemodynamic alterations in the arterial circulation, as well as overactivity of the endogenous vasoactive systems?

Answer 17

Hepatorenal Syndrome:

• Functional disorder of the kidney (no tubular damage)!!
• Patients with liver cirrhosis are predisposed to complications and inciting events (i.e. bacterial translocation and inflammatory response) => alterations in perfusion of the kidney and an increase in creatinine=> Poor blood flow to kidney leads to overactivation of RAAS system

Question 18

Multiorgan dysfunction caused by decreased oxygenation from dilated blood vessels. Both a diffusion problem and ventilation-perfusion mismatch problem

Answer 18

Hepatopulmonary syndrome

Treatment: Liver Transplant

Question 19

Diagnosis of Hepatorenal Syndrome vs. Acute Tubular Necrosis?

Answer 19

LOW urine Na: tubules are intact and trying to absorb Na and water to increase perfusion = Hepatorenal Syndrome

HIGH urine Na: tubules have been damaged and are unable to reabsorb Na or water = Acute tubular necrosis

Question 20

Management of Hepatorenal Syndrome?

Answer 20

Step 1:

• Hold all Diuretics
• Give Albumin 1g/kg for 48 hours (colloid and will remain in the intravascular space longer=> increasing the perfusion of the kidney
• Urinary electrolytes – LOW urine Na indicates that the tubules are intact and trying to absorb Na and water to increase perfusion = HRS

Step 2:

If no improvement in renal function give terlipressin or noradrenaline (Splanchnic vasoconstriction to improve systemic blood flow towards the kidney)

The mainstay of treatment is trying to improve systemic perfusion to the kidney. Therefore, reducing portal blood flow via vasoconstriction (via terlipressin or noradrenaline) improves systemic blood flow and should improve renal function.