4.13 GI Pharm Flashcards
What viral forms of hepatitis have no pharm treatment?
HAV, HDV, HEV
What viral form of viral hepatitis can be cured?
HCV
What makes it more likely that a patient will develop chronic HBV (Antigen marker detected for over 6 months) ?
The younger the patient is (children)
Because some HBV drugs target the DNA reverse transcriptase, they can also be used to treat what?
HIV
What is the goal for treating HBV?
Suppress HBV within patients (prevent reactivation) and prevent associated damage of chronic HBV (cirrhosis, HCC, etc.)
What kind of liver cirrhosis if there is some damage but liver is still able to functional adequately with minimal complication?
Compensated cirrhosis
Why is it important to screen and treat for HBV in pregnant women?
High likelihood of passing it onto child and newborns have highest risk 90% of developing chronic HBV
Can be used to treat HBV and HCV?
Interferon a 2A
Immunomodulatory and inhibition of viral processes, type 1 interferons lead to activation of Jak/Stat pathways and transcription of specific mRNAs that help cells respond to viruses
Interferon a 2A
What is done to interferon a 2A to increase its half-life?
Pegylated
BBW for interferon Alfa 2A?
Fatal neuropsychiatric, autoimmune, ischemic and infectious disorders (esp elderly)
ADME and ADSE interferon Alfa 2A?
Once a week subcutaneous
Flue like symptoms in 90%
Long term risk of neuropsych, myelosuppresison, etc.
Who should use PEG interferon alpha 2A?
Younger, well compensated cirrhosis, patients who don’t want long term treatment
An absolute contra for PEG interferon alpha 2A?
Pregnant women with HCV
What are drugs that can be used for treating both HBV and HIV?
Tenofovir & Lamivudine
What is a first line HBV for naive patients?
Entecavir
Guanine nucleoside analog that inhibits HBV DNA polymerase
Entecavir
Why is Entecavir first line for HBV naive?
High potency and low resistance (unless resistant to Lamivudine)
BBW for lactic acidosis and severe hepatomegaliy with steatosis and exacerbation of HBV when discontinued?
Entecavir
ADME and ADSE for enetcavir?
Oral, 15hr half life, renal excretion
Well tolerated but some headaches, fatigue, dizziness, nausea
Adenosine nucleotide analog?
Tenofovir
Which version of Tenofovir is preferred due to reduced serious side affects?
TAF > TDF (bone problems)
What are Tenofovir ADSE?
GI effects, renal tubulopathy
What does Tenofovir interfere with when HBV is resistant against entecavir or Lamivudine?
Viral RNA dependent DNA polymerase
Incorporated into the viral DNA by HBV polymerase resulting in DNA chain termination (cytidine analog)
Lamivudine
What are the HBV specific ADSE for Lamivudine?
Longer half life in liver cells so given at lower concentrations than for ART (HIV therapy)
BBW for Lamivudine?
Lactic acidosis, severe hepatomegaly, exacerbations of Hep B when discontinued
Has some relatively normal respiratory ADSE (cough, sore throat, nasal effects)?
Lamivudine
What drugs can be used to treat HCV?
PEG interferon 2A
Ribavirin
Sofosbuvir - NS5B
Velpatasvir - NS5A
Glecaprevir - NS3/4A protease inhib
What are the treatment options for HCV?
Interferon + ribavirin
Duo: NS5A inh.ib + NS5B inhib OR protease inhib.
Triple/Quad
N5A inhibitor + NS5B inhib + protease inhib+ CYP3A4 inhib
Guanosine analog that interferes with viral mRNA capping, inhibits synthesis of guanosine synthesis, inhibits viral RNA dependent polymerase
Ribavirin
What drugs needs to be phosphorylated to become active and can be admin orally or by inhaler?
Ribavirin
Ribavirin inhalation is used to treat what?
RSV
BBW: NOT monotherapy, hemolytic anemia PO), teratogenic
Ribavirin
Uracil analog that inhibits the RNA dependent RNA polymerase found in genotypes 1-6 (NS5B) of HCV?
Sofosbuvir
ADSE for Sofosbuvir?
LOTS but especially patients on amiodarone can cause severe bradycardia
Inhibits NS5A that may be involved in induction of viral RNA dependent RNA polymerase?
Velpatasvir
What is approved to be used in conjunction with Sofosbuvir?
Velpatasvir
This combination is considered pangenotypic and curative for HCV?
Velpatasvir + Sofosbuvir
What do you need to be cautious for in patients taking Velpatasvir?
HBV reactivation bc of Sofosbuvir AND hypoglycemia in medicated diabetics
Potent pan genotypes inhibitor of HCV NS3/4A protease that cleaves the encoded polyprotein essential for viral replication
Glecaprevir
What is the Glecaprevir BBW?
HBV reactivation on discontinuation
What do you monitor with patients on Glecaprevir?
LFTs, liver dysfunction signs, and diabetes improvement
What is the liver extraction rate?
ER = ([before]-[after]) / [before]
What does a low ER indicate?
Very little drug is extracted
What is teh hepatic clearance?
HC = ER X Q
Q= how much blood goes to liver
Volume of blood that passes through and is cleared by the liver
Low ER drug characteristics?
Minimal metabolism by liver, low first pass effects, high serum binding, changes in liver perfusion rates don’t affect extraction that much
What are conditions that can alter hepatic blood flow (and thus High ER drugs)?
CHF, hypotension
What are some high ER drugs?
Morphine
Nitro
Propranolol
Isoniazid
Low ER ratio drug examples?
Phenytoin
Diazepam
Digitoxin
Warfarin
Theophylline
TRENDS: zero order drugs
