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Flashcards in Hepatitis & Liver Disease Deck (33)
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Hepatitis

Inflammation of the liver

Causes: viral hepatitis, drugs, alcohol

1

Symptoms

Nausea, loss of appetite, vomiting, diarrhea, malaise, abdominal pain in the upper right quadrant, yellowed skin and eyes, darkened urine, clay stool

2

Diagnostic criteria

ALT: normal (7-55 u/L)
AST: normal (8-48)
Decreased albumin
Increased Alk phos
Increased bili
Increased prothrombin time

The higher the value the worse the liver disease

3

Child-Pugh

Class A: mild disease (score <7)
Class B: moderate disease (score 7-9)
Class C: severe disease (score 10-15)

4

Natural products

Milk thistle does not significantly influence the course of a patient with alcoholic liver disease

5

Hepatotoxic drugs

Examples: acetaminophen, amiodarone, carbamazepine, estrogen, fenofibrate, gemfibrozil, isoniazid, ketoconazole, ketorolac, methimazole, methotrexate, NNRTIs, NRTIs, PIs, phenytoin, rifampin, tamoxifen

Stopped when the levels are greater than three times the upper limit of normal

6

Alcoholic liver disease

Fatty liver (steatosis): chronic consumption results in the secretion of pro-inflammatory cytokines, oxidative stress, lipid peroxidation, and acetaldehyde toxicity

Benzos used for alcohol withdrawal inpatient and anticonvulsants used outpatient

Naltrexone (ReVia), acamprosate, disulfiram (Antabuse) are used to prevent relapses

7

Treatment of alcoholic liver disease

Alcohol cessation

Proper nutrition: vitamins and trace minerals including many B vitamins (thiamine, folate, pyridoxine)

8

Complications of liver disease

1. Portal HTN and visceral bleeding:
Non-selective beta blockers (an doll land propranolol) and/or variceal ligation used for prevention

9

Nadolol (Corgard) and propranolol (inderal LA)

BB warning: do not withdrawal abruptly, gradually taper 1 to 2 weeks to avoid acute tachycardia, hypertension, and/or ischemia

Contraindications: sinus bradycardia, second or third degree heart block, sick sinus syndrome, cardiogenic shock, severe hyperactive airway disease

Side effects: decrease heart rate, hypotension, dec. libido, impotence

10

Hepatic encephalopathy

Symptoms: musty area of the breath and/or urine, changes in thinking, confusion, forgetfulness, mood changes, drowsiness, worsening tremors, sluggish movements and risk of coma

Symptoms of hepatic encephalopathy result from an accumulation of got derived nitrogenous substances in the blood (ammonia)

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Treatment of hepatic encephalopathy

Diet: reduce the amount of protein to prevent the accumulation of ammonia (plant protein preferred over animal)

Drug therapy (prevention): lactulose
Acute job therapy: rifaxamin, neomycin, metronidazole) and lactulose

12

Lactulose

Converts ammonia to ammonium which cannot pass into the blood and enhances the diffusion of ammonia into the colon for excretion

Side effects: flatulence, diarrhea, dyspepsia, abdominal discomfort, hypokalemia

13

Neomycin

Blackbox warning: neurotoxicity including hearing loss, vertigo, ataxia; nephrotoxicity; neuromuscular blockade and respiratory paralysis especially when given soon after anesthesia or with muscle relaxants

Side effects: G.I. upset, ototoxicity, nephrotoxicity

14

Rifaxamin (xifaxan)

side effects: preferable edema, dizziness, fatigue, nausea, ascites, flatulence, headache

Monitoring: mental status, ammonia

15

Metronidazole (flagyl)

Blackbox warning: possibly carcinogenic

Contraindications: first trimester pregnancy; use of disulfiram within the past two weeks; use of alcohol during therapy or within three days of therapy discontinuation

Do not use long-term due to peripheral neuropathy

Take extended release tablets on and empties stomach

16

Ascites

Fluid accumulation within peritoneal space that can result in bacterial peritonitis and hepatorenal syndrome.

Treatment: dietary sodium restriction (<2g/day), avoid NSAIDs, use diuretics (combination of furosemide and spironolactone at 40mg:100mg)

17

Spontaneous bacterial peritonitis

Target streptococci and enteric gram negative pathogens with ceftriaxone for 5-7 days

Some pts receive bactrim prophylactically

18

Hepatorenal syndrome

Occurs in pts with advanced cirrhosis

Renal vasoconstriction via RAAS

Treat with renal vasodilators: fenoldopam and dopamine

19

Viral hepatitis

Causes: HepA, HepB, HepC, herpes, CMV, Epstein-Barr virus, and adenovirus

20

Hepatitis A

Fecal-oral route through improper hand washing or via contaminated food or water

HepA vaccine: Havrix, Vaqta)

HepA vaccine is given to children at one year of age as two shots and to adults if risk factors are present

Treatment of HepA is supportive treatment and no antiviral agents are needed

21

HepB

Can lead to chronic infection, cirrhosis (scaring) of liver, liver cancer, liver failure and death.

Transmission: infectious blood, semen, or other body fluids

Vaccine: 3 IM injections (Engerix-B)

Treatment: antivirals (NRTIs) and interferons are used for chronic therapy for usually 1 year

22

HepC

Non-vaccine preventable disease

Transmission: blood and body fluid ( more common with IV drug abusers)

Treatment: peginterferon, ribavirin, PIs, and/or new agent sofosbuvir

23

Interferon Alfa:

Interferon-a-2b (intron)---HepB, HepC
Pegylated interferon-a-2b (pEG-Intron)---HepC
Pegylated interferon a-2a (pegasys)---HepB & C
Interferon alfacon-1 (infergen)---HepC
Combo of interferon a-2b and ribavirin (rebetron)

Indicated for HepB and HepC

Antiviral effects

Black box warning: May cause or exacerbate autoimmune disorders; may cause or aggravate infectious disease disorders; may cause or aggravate ischemic or hemorrhagic cerebrovascular events; combination treatment with ribavirin may cause birth defects and/or fetal mortality and/or hemolytic anemia

Contraindications: autoimmune hepatitis, decompensated liver disease and Cirrhotic patients, and infants/neonates

Warnings: neuropsychiatric, cardiovascular, endocrine disorders, retinopathy, dec. vision, pancreatitis

Adverse events:(associated with many adverse events) flulike syndrome 1 to 2 hours after administration (can pretreat with acetaminophen, antihistamine); CNS effects (fatigue, anxiety, depression), G.I. upset (nausea, vomiting, anorexia, and weight loss), increased LFTs

Note must dispense medguide and must reduce dose if thrombocytopenia or neutropenia is present

24

Interferon alfa counseling

Injection technique: prefilled refrigerated syringes; or vials with syringes

Interferons are injected into the abdomen if the patient is too thin, the top of the thigh or the outer surface of the upper arm, ALWAYS rotate sites

25

Nucleoside reverse transcriptase inhibitors (NRTIs)

FOR HEPATITIS B ONLY (inhibit HepB replication)

Dosing: decrease dose if creatinine clearance is less than 50ml/min

Blackbox warning: lactic acidosis (seek medical attention right away if you feel very weak or tired have unusual muscle pain, have trouble breathing, have stomach pain with nausea and vomiting, and feel dizzy or lightheaded) and severe hepatomegaly with steatosis which may be fatal; exacerbations of hepatitis B may occur upon discontinuation monitor closely

Drug interactions: ribavirin can increase hepatotoxic effects of all NRTIs; Bactrim can increase Lamivudine levels due to reduced excretion

26

Examples of NRTIs

Lamivudine (epivir HBV): do not use for treatment of HIV; contains too low dose of lamivudine

Adefovir (hepsera): may cause HIV resistance in patients with unrecognized or untreated HIV infection; use caution in patients with renal impairment or those at risk of renal toxicity

Tenofovir (viread): (1st line) May cause Fanconi syndrome, renal insufficiency, osteomalacia and decreased bone density
* avoid concomitant tx with didanosine due to increased risk of virologic failure

Enters or (baraclude): (first-line) take on an empty stomach (food reduces the AUC by 20%); may cause HIV resistance in patients with unrecognized or untreated HIV; may also cause peripheral edema

Telbivudine (Tyzeka): increased CPK, increased LFTs

27

Ribavirin (Copegus, Rebetol, Ribasphere, RibaPak, Virazole)

Used in combination with interferon for treating hepatitis C

Stop if there is not an early final response by week 12; not recommended for monotherapy against hepatitis C

Not recommended in patients with CrCl <50, autoimmune hepatitis, concomitant use with didanosine

28

Protease inhibitors

Indicated for the treatment of chronic hepatitis C when used in combination with Peginterferon alfa and ribavirin

Drugs: boceprevir (Victrelis), teleprevir (incivek), and simeprevir (olysio)

Notes: watch for drug interactions as is an inhibitor and substrate of cyp3A4

29

Boceprevir (Victrelis)

usually started on week 5 of peginterferon and ribavirin therapy. Contraindications include those for Peg interferon and ribavirin especially pregnancy and then his female partner is pregnant. Side effects include fatigue, anemia, neutropenia, taste distortion (dysgeusia). Never reduce the dose or interrupt therapy and never use as monotherapy

30

Teleprevir (Incivek)

Contraindications of the same as Peginterferon ribavirin and boceprevir

Side effects: serious skin rash discontinue all treatment of progression or severe, fatigue, itching, taste distortion, anemia, anorectal disorders, nausea, diarrhea

Note: never reduce the dose or interrupt therapy as treatment failure may result. Never use as monotherapy must always be combined with Peg interferon and ribavirin

31

Simeprevir (olysio)

Contraindications: same as the previous medications

Side effects: rash or photosensitivity, pruritis and nausea

Notes: NS3 Q80K polymorphism testing recommended as patients with this polymorphism will not respond and alternative therapy should be given; never uses monotherapy must always be combined with Peg interferon and ribavirin

32

Sofosbuvir (sovaldi)

Inhibitor of hepatitis C RNA dependent RNA polymerase which is essential for viral replication

Nucleotide prodrug and is indicated for hepatitis C only

Should be used with ribavirin but can be used with out Interferon alpha in certain genotypes or patients who are interferon ineligible

Drug interactions: avoid with PGP inducers such a St. John's wort and rifampin. Also avoid with carbamazepine, oxcarbazepine, phenobarbital, phenytoin, rifabutin and tipranivir/ritonavir