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Gastrointestinal > Drugs And Treatments In Hepatic Disorders > Flashcards

Drugs And Treatments In Hepatic Disorders Flashcards

1
Q

Treatment of Ascites (4)

A
  1. Low sodium diet
  2. Diuretics
  3. Paracentesis
  4. Surgical shunt
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2
Q

Diuretic agents (2)

A
  1. Spironolactone

2. Furosemide

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3
Q

Potassium-sparing Diuretic - Spironolactone (MOA, PK, Pregnancy, Indications, ADRs)

A

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)

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4
Q

Loop Diuretic - Furosemide (MOA, PK, pregnancy, Indications, ADRs)

A

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

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5
Q

Treatment of Spontaneous Bacterial Peritonitis (1-2B)

A
  1. Occurs with large volume ascites & with variceal hemorrhage
  2. 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
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6
Q

Third-generation Cephalosporin - Cefotaxime (MOA, PK, Pregnancy, Indications, ADRs)

A

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

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7
Q

Fluoroquinolones- Ciprofloxacin, ofloxacin (MOA, PK, pregnancy, indications, ADRs)

A

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.

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8
Q

Treatment of Variceal Hemorrhage (1D-2E)

A
  1. 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
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9
Q

Beta-adrenergic antagonists - Nadolol, propranolol, carvedilol (MOA, PK, pregnancy, indications, ADRs)

A

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

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10
Q

Octreotide (MOA, PK, pregnancy, indications, ADRs)

A

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

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11
Q

Vasopressin (MOA, PK, pregnancy, indications, ADRs)

A

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

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12
Q

Treatment of Hepatic Encephalopathy (1A-2C)

A
  1. Disaccharide
    A. Lactulose
  2. Antibiotics
    A. Rifaximin
    B. Neomycin
    C. Metronidazole
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13
Q

Lactulose (MOA, PK, pregnancy, indications, ADRs)

A

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.

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14
Q

Antibiotics - Rifaximon, neomycin, metronidazole (MOA, PK, pregnancy, indications, ADRs)

A

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

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15
Q

Treatment of Hepatitis A (1-2B)

A
  1. No specific treatment options for active infection usually people recover with supportive care
  2. Vaccines: HAVRIX® and VAQTA®
    A. Inactivated virus vaccines against hepatitis A
    B. Adverse side effects: pain at injection site, nausea, fatigue, fever
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16
Q

Treatment of Hepatitis B (1a-2C)

A
  1. 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
  2. Current Infection:
    A. Not curable but need to suppress virus replication
    B. Interferon therapy
    C. Nucleotide reverse transcriptase inhibitors
17
Q

Interferon Therapy (agents, MOA, PK, pregnancy, indications, ADRs)

A

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

18
Q

Nucleotide reverse transcriptase inhibitors for Hepatitis B (agents, MOA, ADRs)

A
  1. Lamivudine
    MOA: a cytosine analog that inhibits viral reverse transcriptase and DNA synthesis
    ADRs: Headache, fatigue, nausea
  2. Tenofovir, Adefovir
    MOA: adenosine analogs that inhibits viral reverse transcriptase and DNA synthesis
    ADRs: Headache, nausea
  3. Entecavir
    MOA: guanosine analog that inhibits viral reverse transcriptase and DNA synthesis
    ADRs: Headache, nausea
  4. Telbivudine
    MOA: competitive inhibitor of viral reverse transcriptase and a more potent
    suppressor of HBV DNA than lamivudine
    ADRs: Headache, fatigue, nausea
19
Q

Treatment of Hepatitis C (1-3d)

A
  1. Curable and want to eradicate the infection
  2. Interferon therapy
  3. 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
20
Q

Hepatitis C Direct-Acting Antiviral Drug Regimens

A

4 drug regimen (ombitasvir/paritaprevir/dasaburvir/ritovair)
3 drug regimen (ombitasvir/pariaprevir/ritovair)
2 drug regimen (ledipasvir/sofosbuvir)

21
Q

Hepatitis C Direct-Acting Antivirals (agents, MOA, PK, ADRs)

A
  1. 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)
  2. Paritaprevir
    MOA: HCV NS3/4A inhibitor, an enzyme essential for viral replication and responsible for HCV protein cleavage
    PK: t1/2 – 5.5 hours
  3. Dasaburvir, Sofosbuvir
    MOA: NS5B polymerase inhibitor, an enzyme essential for replication of the viral genome
    PK: t1/2 – 6 hours (dasaburvir), 30 minutes (sofosbuvir)
  4. Ritonavir
    MOA: Inhibitor of CYP3A4 which increases serum levels of paritaprevir when used together
    PK: t1/2 – 4 hours
    ADRs: headache, nausea, fatigue
22
Q

General summary of ascites treatment

A

Pharmacological treatment of ascites involves the use of diuretics.

23
Q

General summary of peritonitis treatment

A

Spontaneous bacterial peritonitis is treated with broad-spectrum antibiotic therapy that covers the three most commonly encountered pathogens

24
Q

General summary of prophylaxis variceal hemorrhage

A

Pharmacological prophylaxis treatment of variceal hemorrhage focuses on decreasing portal vein pressure by decreasing cardiac output and causing vasodilation of the splanchnic vein

25
Q

General summary of acute variceal hemorrhage

A

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.

26
Q

General summary of hepatic encephalopathy treatment

A

Treatment of hepatic encephalopathy is focused on reducing ammonia plasma levels by using lactulose or antibiotics that decrease urease-producing bacteria.

27
Q

General summary of Hepatitis A and B treatment

A

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.

28
Q

General summary of hepatitis C treatment

A

Treatment of hepatitis C is to cure the disease through the use of direct-acting antivirals.

Gastrointestinal (7 decks)

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