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41 Cards in this Set
- Front
- Back
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What are the different kinds of drugs approved for HBV therapy?
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Interferon alpha
NucleoSide analogs NucleoTide analogs |
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What are the three nucleoside analogs used in the treatment of hepatitis B?
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Lamivudine
Entecavir Telbivudine |
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What are the nucleotide analogs used in the treatment of hepatits B?
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Adefovir
Tenofovir |
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Prior to pharmacological activity, what needs to happen to the nucleoside/nucleotide analogs?
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Phosphorylation
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What is the selectivity of nucleoside/nucleotide analogs in HBV drugs? How are they selective?
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Very selective for the HBV
Only the virus has the kinase to activate the nucleosides in the first phosphorylation step. The triphosphate versions of the drugs are active only against the viral polymerase. |
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What enzyme is the target of nucleotie/nucleoside analogs in HBV?
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Reverse transcriptase
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What is the general mechanism of action of action in nucleosides/nucleotides in HBV?
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Incorporation of the drug into the genetic material, abortion of the replication process.
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What is the difference between a nucleoside and a nucleotide?
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A nucleoside doesn't have a phosphate on it yet. It's naked!
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What structure does Lamivudine imitate?
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Deoxycytidine
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What is the difference between + and - lamivudine?
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The negative form has the sugar upside-down!
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Which form of lamivudine is activated more efficiently?
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The negative form.
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What is the bioavilaibility of Lamivudine, a nucleoside analog?
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85% bioavailable
Doesn't penetrate the CSF! |
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What is the metabolism and half life of Lamivudine?
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Long half life for the PHOSPHORYLATED FORM: > 10 hr.
It's important to think of the half-life of the pharmacologically active compound |
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What are the adverse effects of Lamivudine, a nucleoside analog?
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Almost none; low toxicity to normal tissues due to being very selective to the viral RT:
headache arthralgias myalgias |
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Against what viruses is Lamivudine used?
Why? |
HBV
HIV It's able to inhibit the reverse transcriptase of both! |
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What class of drugs does Tenofovier belong to?
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NucleoTide analog: doesn't have a phosphate on it for HBV
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What is the oral bioabailability of Tenofovir?
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25-50% orally bioavailable
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What is the metabolism of Tenofovir in the tissues?
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Little metabolism
Doesn't interact with the P450 enzymes |
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What is the elimination of Tenofvir?
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Renally
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What are the adverse effects of Tenofvir?
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Generally, they're safe drugs
GI irritation headache Abdomina/back pain Increase in transaminase, thrombocytopenia are rare |
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What are the clinical uses of Tenofvir?
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HBV
HIV |
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What structure is Ribavirin imitating?
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RNA Purines
Imitates the ring system Has ribose on the base |
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What processes can Ribavirin disrupt?
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Purine biosynthesis
RNA synthesis ATP metabolism |
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Does ribavirin need to be activated?
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Yes!
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What is the bioavailability of Ribavirin/
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Good oral bioavailability (45%)
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What is the distribution of Ribavirin
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Good distribution to most body tissues
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What is the metabolism of ribavirin?
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Hepatically
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What is the excretion of ribavirin?
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Renally
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What are the adverse effects of ribavirin?
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Serious!
Hemolytic anemia Increase in serum billirubin, uric acid Bone marrow toxicity BAD FOR BABIES - DON'T GIVE TO PREGGO WOMEN! |
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What is the clinial use of Ribavirin?
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Hepatitis C
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What is the mechanism of action for interferons?
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Inhibition of many viral processes:
Synthesis of mRNA Translation of proteins Viral assembly/release Mostly, blocks protein synthesis |
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What are the adverse effects of interferons?
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Acute viral-like systems
Bone marrow toxicity CNS toxicity (depression, suicidal thoughts) Decrease of P450 activity |
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What are the clinical uses of interferons?
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Hepatitis B
Hepatitis C (usually given with ribavirin) Genital warts (papillomavirus) |
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What type of hepatitis is treated with protease inhibitors?
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Hepatitis C
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What is the structure of protease inhibitors?
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Peptide-like
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What drugs are used in combination with protease inhibitors in HCV infection?
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Interferon alpha and ribavirin
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What is the absorption of HCV protease inhibitors?
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Orally administered
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What is the distribution of HCV protease inhibitors?
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Great distribution to the liver
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What is the metabolism and half life of HCV protease inhibitors?
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Extensively metabolized in the liver: INTERACTS WITH THE P450s
T1/2 = 3-4 hrs. |
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What is the effect of adding HCV protease inhibitors to interferon/ribavirin in this disease?
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Hepatitis C virus
Sustained virologic response Decreased rate of relapse |
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What are the adverse effects of telaprevir and boceprevir?
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The drugs are fairly benign.
Fatigue GI irritation Rash CNS (boceprevir only) Hematologic (anemia, neutropenia, thrombocytopenia) |
