Therapeutics GI Ronald Flashcard

Jaundice Pathophysiology

  • Inability of liver cells to conjugate and excrete bilirubin leads to build-up of bilirubin in the blood

Portal HTN Pathophysiology

  • Hepatocellular injury progresses -> fibrous material develops within the hepatic lobules -> disrupts normal blood flow through the liver
  • Fibrous tissue accumulates -> resistance to portal blood flow increases -> persistent and progressive elevations in portal blood pressure
  • Also increases endothelin (vasoconstrictor) and decreases in nitric oxide (vasodilator) attenuate increases in portal venous pressure

Varices Pathophysiology

  • Blood “backs up” from portal HTN and finds an alternative route back to the systemic circulation
  • Most clinically significant route is the gastric vein and development of esophageal varices
  • Risk of variceal bleeding begins when portal venous pressure reaches 12 mmHg > inferior vena cava pressure

Clinical Manifestations of Portal HTN/Varices

  • Upper GI Bleed — variceal hemorrhage
  • Hemorrhoids
  • Caput medusa — abdominal veins that “stick out”

Primary Prophylaxis for Portal HTN/Varices

1.  Non-Selective Beta-Blocker (first line)

  • Beta1 receptor inhibition leads to decreased CO
  • Beta2 receptor inhibition leads to decreased splanchnic blood flow
  • The combined effects produce a decreased portal pressure

2.  Endoscopic Band Ligation (EBL)

  • For patients with contraindications or intolerance to non-selective beta-blockers
  • Superior to both beta-blockers and nitrates for preventing first bleed — BUT since not proven to improve survival and long-term benefits are still uncertain
  • Therapy is reserved for those intolerant to beta-blockade

3.  Nitrates

  • Smooth muscle vasodilation -> decreased portal pressure
  • Used as add-on therapy to patients that have inadequate response to beta-blockers as monotherapy
  • Isosorbide mononitrate

Acute Variceal Hemorrhage Pathophysiology

  • Rupture of varices into the GI tract leading to blood loss -> can progress to hypovolemic shock
  • Hemorrhage is complicated by the hypocoagulable state that accompanies liver disease

Clinical Manifestations of Acute Variceal Hemorrhage 

  • Hematemesis or melena
  • Decrease in hemoglobin and hematocrit
  • Possible hypotension, dizziness, etc.

Treatment of Acute Variceal Hemorrhage

1.  Supportive Measures

  • Adequate fluid resuscitation — PRBCs, crystalloids
  • Correction of coagulopathies and thrombocytopenia — fresh frozen plasma, platelets, vitamin K

2. Vasoactive Therapy

  • Octreotide — preferred agent

-Naturally occurring somatostatin analog

-Inhibits vasoactive intestinal peptide  -> mesenteric vasoconstriction

-Decreases splanchnic blood flow -> decreased portal and variceal pressure

  • Vasopressin

-Non-selective vasoconstrictor with the vasoconstricting effects not restricted to the splanchnic vessels

-ADRs: coronary ischemia, AMI, arrhythmias

  • Terlipressin

Analog of vasopressin with longer t1/2

Allows for q 4hr dosing rather than continuous infusion

Not available in US

 

3.  Antibiotics

  • All patients with variceal hemorrhage get antibiotics
  • Increased risk due to: aspiration, placement of multiple IV access devices, sclerotherapy, translocation, defects in immune system
  • Reduces the risk of sepsis –> reduces the risk of rebleeding and increase short-term survival
  • Screen for infection

4.  Endoscopic Interventions

  • Guidelines recommend as primary diagnostic and treatment strategy for upper GI tract hemorrhage secondary to portal HTN and varices
  • Sclerotherapy
  • Band Ligation

5.  Surgical Interventions

  • If standard therapy fails, use this
  • Transjugular Intrahepatic Portosystemic Shunt (TIPS) — placement of one or more stents between the hepatic vein and portal vein -> decompresses portal system by shunting blood around the liver

6.  Secondary Prophylaxis

  • Endoscopic Management (EBL, Endoscopic Injection Sclerotherapy)
  • Non-Selective Beta-Blockers
  • Non-Selective Beta-Blockers + nitrates
  • TIPS procedure

 

Spontaneous Bacterial Peritonitis Pathophysiology

  • Likely a result from seeding of ascitic fluid via the blood, lymph, or bacteria crossing the gut wall

Spontaneous Bacterial Peritonitis Risk Factors

  • Low protein levels in the ascitic fluid
  • High bilirubin
  • Variceal hemorrhage
  • Prior SBP

Spontaneous Bacterial Peritonitis Clinical Manifestations

  • Fever
  • Increase WBC count
  • Abdominal pain
  • Guarding
  • Hypoactive/absent bowel sounds
  • Rebound tenderness
  • Some pts are asymptomatic

Spontaneous Bacterial Peritonitis Primary Prophylaxis Indications

  • Low ascitic protein levels (< 1 g/dL)
  • Variceal hemorrhage
  • Prior SBP

Primary Prophylaxis and Treatment of Spontaneous Bacterial Peritonitis

Antibiotics and Albumin

 

Antibiotics

  • 3rd Gen Cephalosporins (Cefotaxime, Ceftriaxone)
  • Fluoroquinolones (Cipro, Levo)

Duration of therapy:

5 days if repeat paracentesis @ 48 hrs reveals sterile ascitic fluid

10-14 days in no follow-up paracentesis performed

Primary prophylaxis x 7 days

 

 

Hepatic Encephalopathy Pathophysiology

  • Accumulation of gut-derived nitrogenous substances (ammonia) bypass the liver via portal-to-systemic shunting –> enter the CNS and alter neurotransmitter
  • Elevated arterial ammonia levels are the most commonly cited causative agent although there is poor correlation with ammonia levels and severity of HE
  • Clinical symptoms range from subtle mental status changes to deep coma

Hepatic Encephalopathy Clinical Manifestations

1.  Cognitive

  • confusion
  • agitation
  • euphoria
  • restlessness, insomnia
  • reversal of day-night sleep pattern
  • somnolence, coma

2.  Motor

  • fine tremor
  • slowed coordination
  • asterixis
  • posturing and flaccidity

3.  Increased serum ammonia levels

 

Hepatic Encephalopathy Treatment

1.  Lactulose

  • Removes nitrogen-containing compounds from GI tract
  • Lowers GI pH — bacteriostatic effect reduces the number of ammonia-producing bacteria
  • Decreasing ammonia content in GI tract leading to diffusion of additional ammonia into the GI tract from the serum and then subsequent GI removal
  • ADR: flatulence, diarrhea, abdominal pain

2.  Antibiotics

  • Inhibits activity of urease-producing bacteria
  • Place in therapy: patients refractory to lactulose, can use in combo w/ lactulose or substitution
  • Neomycin — ADR: ototoxicity, nephrotoxicity
  • Metronidazole — ADR: Disulfiram-Like Rxn
  • Rifaximin — ADR: GI

Coagulopathy Pathophysiology

  • Reduces synthesis of clotting factors
  • Decrease absorption of vitamin K

Coagulopathy Clinical Manifestations

  • Bleeding
  • Increased PT/INR

Coagulopathy Treatment

  • Vitamin K
  • Fresh Frozen Plasma — give if pt. is actively bleeding or before invasive procedure to decrease bleeding

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