Drugs And Treatments In Hepatic Disorders Flashcards
Treatment of Ascites (4)
- Low sodium diet
- Diuretics
- Paracentesis
- Surgical shunt
Diuretic agents (2)
- Spironolactone
2. Furosemide
Potassium-sparing Diuretic - Spironolactone (MOA, PK, Pregnancy, Indications, ADRs)
MOA: Inhibits the effects of aldosterone on the distal renal tubules. Aldosterone antagonism enhances sodium, chloride, and water excretion, and reduces the excretion of potassium, ammonium, phosphate.
PK: t1/2: 1.4 hours
Pregnancy: Not recommended because of potential to feminize male fetuses
Indications: Liver cirrhosis ascites, hypertension
ADRs: Hyperkalemia, gynecomastia (decreased testosterone production)
Loop Diuretic - Furosemide (MOA, PK, pregnancy, Indications, ADRs)
MOA: Inhibits sodium and chloride resorption by competing with chloride for the Na +/K+/2Cl- co-transporter in the ascending limb of the loop of Henle. Diuresis results from increased urinary excretion of sodium, chloride, potassium, and hydrogen ions.
PK: t1/2: 2 hours
Pregnancy: C
Indications: Liver cirrhosis ascites, CHF – edema, hypertension
ADRs: Hypomagnesemia, hyperuricemia, BLACK BOX WARNING - potent diuretic and in excessive amounts can lead to profound diuresis with water and electrolyte depletion
Treatment of Spontaneous Bacterial Peritonitis (1-2B)
- Occurs with large volume ascites & with variceal hemorrhage
- Use broad-spectrum antibiotic therapy to cover 3 most commonly encountered pathogens (E. coli, K. pneumoniae, and pneumococci)
A. Drug of choice is cefotaxime (third-generation cephalosporin)
B. Alternative treatments ciprofloxacin, ofloxacin (fluoroquinolone); patients who previously receive prophylaxis quinolone therapy should be treated with an alternative agent to avoid creation of quinolone-resistant flora
Third-generation Cephalosporin - Cefotaxime (MOA, PK, Pregnancy, Indications, ADRs)
MOA: Inhibit bacterial cell wall synthesis in a wide range of gram-positive and gram-negative microorganisms
PK: t1/2: 1 hour
Pregnancy: B
Indications: Infectious disease of abdomen
ADRs: Diarrhea, vomiting
Fluoroquinolones- Ciprofloxacin, ofloxacin (MOA, PK, pregnancy, indications, ADRs)
MOA: Inhibits DNA synthesis through a specific action on the enzyme DNA gyrase
PK: t1/2: 3 to 6 hours
Pregnancy: C
Indications: Community acquired pneumonia, bacterial infectious disease
Adverse Side Effect: Nausea, vomiting, diarrhea, BLACK BOX WARNING - fluoroquinolones are associated with tendinitis and tendon rupture, peripheral neuropathy and CNS effects.
Treatment of Variceal Hemorrhage (1D-2E)
- Prophylaxis treatment
A. Beta-adrenergic antagonists: Nadolol, propranolol, carvedilol
B. Band ligation or sclerotherapy
C. Endoscopic Variceal Ligation (use of rubber bands) or variceal sclerotherapy (injection of sodium tetradecyl sulfate and polidocanol)
D. Endoscopic variceal ligation safer than sclerotherapy
2. Acute Bleed A. Antibiotic prophylaxis B. Octreotide or Vasopressin C. Omperazole D. Band ligation or sclerotherapy E. Adequate blood volume resuscitation
Beta-adrenergic antagonists - Nadolol, propranolol, carvedilol (MOA, PK, pregnancy, indications, ADRs)
MOA: Reduced portal pressure and portal vein flow due to reduced cardiac output
PK: t1/2: 20-24 hrs (nadolol), 3-6 hrs, (propranolol), 7-10 hrs (carvedilol). Duration: 24 hrs (nadolol), 12 hrs (propranolol), 7-10 hrs (carvedilol)
Pregnancy: C
Indications: Hypertension, Variceal hemorrhage (off-label)
ADRs: Bronchospasm, nausea, hypotension
Octreotide (MOA, PK, pregnancy, indications, ADRs)
MOA: Inhibits release of glucagon. Glucagon is a splanchnic vasodilator. Reduces splanchnic blood flow and portal vein pressure
PK: t1/2: 1.5 hours (IV) • Duration: 12 hours (IV)
Pregnancy: B
Indications: Diarrhea, Variceal hemorrhage
ADRs: hypoglycemia, bradycardia, and pancreatitis
Vasopressin (MOA, PK, pregnancy, indications, ADRs)
MOA: Dual mechanism for bleeding esophageal varices. Reduces portal vein pressure through splanchnic vasoconstriction and causes contraction of the esophageal musculature
PK: t1/2: 10 minutes (IV), duration: 20 min (IV)
Pregnancy: C
Indications: Vasodilatory Shock, Variceal hemorrhage (off-label)
ADRs: heart failure, decreased cardiac output, mesenteric ischemia
Treatment of Hepatic Encephalopathy (1A-2C)
- Disaccharide
A. Lactulose - Antibiotics
A. Rifaximin
B. Neomycin
C. Metronidazole
Lactulose (MOA, PK, pregnancy, indications, ADRs)
MOA: In colon, bacterial flora degrade lactulose into lactic acid. Acid production decreases pH in colonic lumen. Converts ammonia into ammonium ion and the ion becomes trapped in colon and excreted in stool. Reduces blood ammonia levels by 25-50%. There is also a decrease in the growth of urease-producing bacteria. Increase in colonic propulsive motility.
PK: Onset 8 to 48 hours, t1/2: 1.5-2 hours
Pregnancy: B
Indications: Constipation, Hepatic encephalopathy
ADRs: flatulence, abdominal pain and cramping, diarrhea. *Note: diarrhea is suggestive of excessive dose.
Antibiotics - Rifaximon, neomycin, metronidazole (MOA, PK, pregnancy, indications, ADRs)
MOA: Decrease in the growth of urease-producing bacteria. Urease can be broken down to carbon dioxide and ammonia.
PK: t1/2: 5 – 6 hrs (rifaximin), 2-3 hrs (neomycin), 6 – 8 hrs (metronidazole)
Pregnancy: B
Indications: Constipation, Hepatic encephalopathy
ADRs: nausea, dizziness, abdominal pain
Treatment of Hepatitis A (1-2B)
- No specific treatment options for active infection usually people recover with supportive care
- Vaccines: HAVRIX® and VAQTA®
A. Inactivated virus vaccines against hepatitis A
B. Adverse side effects: pain at injection site, nausea, fatigue, fever
Treatment of Hepatitis B (1a-2C)
- Vaccines:
A. Recombivax HB ® and Engerix-B ® for adults
B. Comvax ® and Pediarix ® for children
C. TWINRIX ® is combination of Viral hepatitis A and B for adults
a. Adverse side effects: pain at injection site, nausea, fatigue, fever - Current Infection:
A. Not curable but need to suppress virus replication
B. Interferon therapy
C. Nucleotide reverse transcriptase inhibitors
Interferon Therapy (agents, MOA, PK, pregnancy, indications, ADRs)
Agents: Pegylated interferon-alpha, Interferon-alpha
MOA: Enhance host immune system to increase activated T lymphocytes, natural killer cells, and macrophages
PK: t1/2: 4-16 hours (Interferon-alpha), 3 days (pegylated interferon-alpha)
Pregnancy: C
Indications: Chronic Hepatitis B and C
ADRs: Fever, headache, chills, generalized aches and pains
Nucleotide reverse transcriptase inhibitors for Hepatitis B (agents, MOA, ADRs)
- Lamivudine
MOA: a cytosine analog that inhibits viral reverse transcriptase and DNA synthesis
ADRs: Headache, fatigue, nausea - Tenofovir, Adefovir
MOA: adenosine analogs that inhibits viral reverse transcriptase and DNA synthesis
ADRs: Headache, nausea - Entecavir
MOA: guanosine analog that inhibits viral reverse transcriptase and DNA synthesis
ADRs: Headache, nausea - Telbivudine
MOA: competitive inhibitor of viral reverse transcriptase and a more potent
suppressor of HBV DNA than lamivudine
ADRs: Headache, fatigue, nausea
Treatment of Hepatitis C (1-3d)
- Curable and want to eradicate the infection
- Interferon therapy
- Direct-acting antivirals
A. Target specific steps in the HCV life cycle
B. Define by their mechanism of action and therapeutic target
a. Nonstructural proteins 3/4A (NS3/4A) protease inhibitors
b. NS5B nucleoside polymerase inhibitor (NPIs)
c. NS5B non-nucleoside polymerase inhibitors (NNPIs)
d. NS5A inhibitors
Hepatitis C Direct-Acting Antiviral Drug Regimens
4 drug regimen (ombitasvir/paritaprevir/dasaburvir/ritovair)
3 drug regimen (ombitasvir/pariaprevir/ritovair)
2 drug regimen (ledipasvir/sofosbuvir)
Hepatitis C Direct-Acting Antivirals (agents, MOA, PK, ADRs)
- Ombitasvir, ledipasvir
MOA: HCV NS5A inhibitor, an enzyme needed for viral RNA replication and assembly of virions
PK: t1/2 – 21 to 25 hours (ombitasvir), 4 – 4.5 hours (ledipasvir) - Paritaprevir
MOA: HCV NS3/4A inhibitor, an enzyme essential for viral replication and responsible for HCV protein cleavage
PK: t1/2 – 5.5 hours - Dasaburvir, Sofosbuvir
MOA: NS5B polymerase inhibitor, an enzyme essential for replication of the viral genome
PK: t1/2 – 6 hours (dasaburvir), 30 minutes (sofosbuvir) - Ritonavir
MOA: Inhibitor of CYP3A4 which increases serum levels of paritaprevir when used together
PK: t1/2 – 4 hours
ADRs: headache, nausea, fatigue
General summary of ascites treatment
Pharmacological treatment of ascites involves the use of diuretics.
General summary of peritonitis treatment
Spontaneous bacterial peritonitis is treated with broad-spectrum antibiotic therapy that covers the three most commonly encountered pathogens
General summary of prophylaxis variceal hemorrhage
Pharmacological prophylaxis treatment of variceal hemorrhage focuses on decreasing portal vein pressure by decreasing cardiac output and causing vasodilation of the splanchnic vein
General summary of acute variceal hemorrhage
Acute variceal hemorrhage is treated pharmacologically using octreotide or vasopressin which decreases portal vein pressure. Add omeprazole to reduce the risk of acid in the esophagus while
healing occurs.
General summary of hepatic encephalopathy treatment
Treatment of hepatic encephalopathy is focused on reducing ammonia plasma levels by using lactulose or antibiotics that decrease urease-producing bacteria.
General summary of Hepatitis A and B treatment
A person can be vaccinated against Hepatitis A and B.
Patients with hepatitis A usual fully recover without clinical sequelae.
Treatment of hepatitis B is to suppress viral load through the use of interferon therapy or nucleotide reverse transcriptase inhibitors. Preferred nucleotide agents have a high barrier to resistance. Interferon therapy is administered for a predefined duration and nucleotide agents are used until the specific goal of treatment is achieved.
General summary of hepatitis C treatment
Treatment of hepatitis C is to cure the disease through the use of direct-acting antivirals.
