Hepatitis - Pharm Exam 2 PDF

Hepatides Defining ‘Hepatitis’ ○ Inflammation of the liver ○ Characterized by inflammatory cells in tissue of liver ○ Limited or no symptoms; often leads to jaundice, poor appetite and malaise ○ Acute < 6 mon, chronic >6 months Chronic hepatitis...

Hepatides Defining ‘Hepatitis’ ○ Inflammation of the liver ○ Characterized by inflammatory cells in tissue of liver ○ Limited or no symptoms; often leads to jaundice, poor appetite and malaise ○ Acute < 6 mon, chronic >6 months Chronic hepatitis ○ May have no symptoms initially ○ Progresses to fibrosis (‘scarring’) and cirrhosis (chronic liver failure) ○ Increases risk of hepatocellular carcinoma Causes of Hepatitis ○ Viral hepatitis (m/cc liver inflammation worldwide) ○ Alcoholic hepatitis ○ Toxic/drug-induced hepatitis ○ Autoimmune hepatitis ○ Non-alcoholic fatty liver disease (often assoc c DM, metabolic syndrome) ○ Ischemic hepatitis (often assoc c HF) ○ Giant cell hepatitis (rare, newborns & children) Pathophysiology ○ Virus targets hepatocytes, causing them to express abnormal protein on their surface ○ Immune cells destroy infected hepatocyte ○ Main mechanism behind inflammation of liver and liver damage Symptomatology ○ Fever, malaise, nausea related to immune system mounting attack ○ Hepatomegaly and leaking transaminases into blood causes increased serum transaminases (ALT > AST) ○ Atypical lymphocytosis common due to stimulation from viral antigens ○ Jaundice, increased bilirubin (conj & unconj), increased urobilinogenuria HAV Serology ○ HAV IgM = active infection ○ HAV IgG = protective Ab, recovery or previous vaccination HCV serology ○ HCV RNA testing using PCR – GOLD STANDARD Can detect virus early, even 1-2 weeks after infection Detects levels of viral RNA in the blood If decrease, know patient is recovering; if stays the same, probably chronic HCV ACute infection ○ HBsAg (+)  ○ Total anti-HBc (+) ○ IgM anti-HBc (+) ○ Anti-HBs (-) → ??? The drugs Anti-HBV NRTIs Adefovir (Hepsera) Entecavir (Baraclude) Telbivudine (tyzeka) (anti-HIV NRTIs are also used) Ribavirin (Virazole) ○ Discovered in 1972, guanosine analog used to stop viral RNA synthesis (some effects on DNA viruses too) ○ Used for severe RSV infection, HCV, hemorrhagic fevers, and some other viral infections ○ Interacts with some antiretroviral medications (anemia with AZT, mitochondrial tox with didanosine) ○ Contraindicated in pregnancy Pegylated interferon ○ PEG-IFN has 3 different forms … Pegylated interferon-alpha-2a Pegylated interferon-alpha-2b Pegylated interferon-beta-1a ○ Interferons Proteins released in the body in response to viral infections Through complex pathways, elicits an immune response ○ Given via injection ○ Used to treat HBV, HCV, and MS ○ Many side effects ranging from HA, rigor, dizziness, N/V/D, neutropenia, weakness, arthralgia, fever … ○ Warnings for marrow suppression (aplastic anemia), CNS depression, allergic rxn (SJS), hemorrhagic colitis, neuropsychiatric disorders (BBW), pancreatitis, pulmonary effects ‼ New Anti-HCV drugs Sofosbuvir (Sovaldi) Sofosbuvir/ledipasvir (harvoni) Ombitasvir/paritaprevir/ ritonavir + dasabuvir (Viekira Pak) Sofosbuvir (Sovaldi) ○ Anti-HCV RNA polymerase inhibitor ○ Approved by FDA in December 2013 ○ High cure rate, fewer adverse effects, and shorter duration of treatment  ○ Super expensive ($84 to 168k for course of treatment) Ledipasvir ○ Combination with sofosbuvir called Harvoni®, approved by FDA in December 2014 ○ Inhibitor of HCV NS5A protein which is involved in viral replication ○ Well tolerated with minimal side effects ○ Also super expensive ($1,125 per pill so >$90k for 12 week course) Elbasvir + grazoprevir (Zepatier) ○ Approved in the US in 2016 ○ Once-a-day combo pill used to treat genotypes 1 or 4 in treatment-naive or treatment-experienced pt ○ Sometimes used in pt with concomitant HIV, late-stage ○ kidney dz Treatments Treating HAV ○ Maintain appropriate nutrition/hydration ○ Watch personal hygiene to prevent spread ○ No antiviral medications indicated because spontaneous resolution in almost all patients ○ Post-exposure ppx to people within 2 weeks of exposure for people not vaccinated Hepatitis A vaccine to people between 1-40 y/o Immunoglobulin to people 40 y/o Treating HCV ○ Treatment c antiviral medications is recommended for all people with proven chronic HCV not at high risk of dying from other causes ○ Initial treatment guideline depends on genotype of HCV identified  Effectiveness ○ Sofosbuvir (Sovaldi®) with ribavirin and interferon is 90% effective in those with genotypes 1, 4, 5, or 6 ○ Sofosbuvir with just ribavirin is 70-95% effective in types 2 and 3 (but has a ton of adverse reactions) ○ Treatments with ledipasvir (combo with sofosbuvir is Harvoni®) for genotype 1 are 93-99% effective but super expensive ○ Ribavirin and peginterferon is 60-90% effective for type 6 Drugs used to treat HBV ○ Lamivudine [3TC] ○ Adefovir (Hepsera®) ○ Entecavir (Baraclude®) ○ Telbivudine (Tyzeka®) ○ Tenofovir [TDF] (Viread®) ○ Peg interferon (bolded are first line agents for treating HBV)