Hepatitis Treatment – Antiviral Drugs

00:00 Let's move on to anti-hepatitis drugs.

00:03 Now the anti-hepatitis drugs really the main say of therapy has been the interferon alpha agents.

00:12 Now interferon alpha seems to work in viral penetration.

00:16 And by inhibiting viral penetration, you are inhibiting probably the first or second step in viral replication.

00:23 Anti-hepatitis B drugs are suppressive not curative.

00:28 So we are not necessary curing the patient with hepatitis B.

00:32 Anti-hepatitis C drugs are targeted for viral eradication.

00:38 And in fact we have seen eradication in many patients.

00:40 Let's talk about interferon alpha.

00:45 Now interferon alpha is a cytokine.

00:48 And it acts through the Janus kinases.

00:51 So Janus was mythical god, who had two heads.

00:58 And so we talk about Janus kinases as being those agents that seem to have a whole bunch of faces to them.

01:05 Now the Janus kinase is phosphorylate STAT that stands for Signal Transducers and Activators of Transcription.

01:13 So we call these JAK STAT receptors.

01:18 And you can see the JAK portion down at the bottom.

01:21 Now this causes an increase production of antiviral proteins.

01:26 There is a specific activation of ribonuclease that degrades the viral messengerRNA when you activate these agents.

01:35 This promotes the formation of natural killer cells that destroy infected liver cells.

01:39 So that's why interferon alpha is such an important component of our immune system.

01:45 Now, intramuscular injections, interferon alpha are usually how we administer this medication.

01:52 The formulations vary from time and place.

01:56 Now the absorption is relatively slow.

01:59 It's given about two or three times per week.

02:01 We do have something called pegylated forms that can be given once a week.

02:06 Pegylated forms are first to encasing the inferon in certain types of almost mycells or liposomes.

02:13 The elimination is through hydrolysis and proteolysis in the kidney.

02:18 In terms of where we use these medications, they are most commonly used in chronic hepatitis B.

02:24 In less common uses, we've used it in Kaposi's sarcoma in HIV patients.

02:31 We've also used in papillomatosis and genital warts as well.

02:34 Although that's actually much less commonly used.

02:39 Now I have another category here called "Others" under anti-hepatitis drugs.

02:44 It's actually quite a large category.

02:46 Now we already spoke about interferon alpha.

02:49 So I'm not going to go through it again.

02:51 Now the other drugs that we use with hepatitis includes the DNA polymerase agents, the nucleoside inhibitors, the broad spectrum replication inhibitors and another set of drugs that I just call miscellaneous.

03:07 Let's take a look at the DNA polymerase inhibitors.

03:10 The prototypical drug of the DNA polymerase inhibitors is adefovir.

03:17 It inhibits DNA polymerase of hepatitis B virus which results in chain termination of -- results in chain termination after incorporation of the virus into the cell.

03:29 It has good oral bioavailability and it's unaffected by foods.

03:34 You can do dose reduction in renal dysfunction because it is excreted by the kidney.

03:39 It works quite well against viruses that are resistant to lamivudine which is another antiviral agent that I'll talk about.

03:50 In fact let's talk about lamivudine now.

03:52 It's a nucleoside inhibitor.

03:55 And if you recall nucleoside inhibitors are working on that very important step of nucleic acid synthesis.

04:01 It inhibits HIV reverse transcriptase.

04:04 It's a very long acting agent in hepatitis B infected cells.

04:08 Compared to say it's limited activity in HIV infected cells.

04:14 It's often used as monotherapy in hepatitis B.

04:19 It's relatively non-toxic and it causes a rapid suppression of hepatitis B viruses.

04:27 Other agents that are active against hepatitis include the broad spectrum replication inhibitors.

04:35 We also know this is ribavirin and it's actually quite a well known drug.

04:40 It inhibits replication of a wide range of DNA and RNA.

04:45 It effects influenza A and B.

04:48 It effects parainfluenza and respiratory syncytial virus.

04:53 It also is active against paramyxoviruses and hepatitis C as well as HIV.

04:59 In terms of the mechanisms of action, we're not entirely sure how this particular drug works.

05:06 We'll believe that it acts directly with guanine triphosphate to somehow cause an inhibition and capping of the viral messengerRNA.

05:13 It also blocks RNA dependent polymerases which is why we use it so often.

05:20 Now in terms of using this medication, remember that in order to improve it's absorption we actually want more acidity in the stomach.

05:32 So we tend to tell patients to avoid antacids when you're taking ribavirin.

05:37 It's eliminated by the kidney so we have to act dose reductions if there is renal failure.

05:43 We often use it with interferon alpha in chronic hepatitis C.

05:48 Remember that monotherapy with this particular agent is not very effective.

05:54 In terms of toxicity, there's a dose dependent hemolytic anemia that's associated with this drug.

06:00 And it is contraindicated in pregnancy.

06:05 Miscellaneous drugs use to treat hepatitis patients include the following.

06:12 Now we have nucleoside analogs that work against DNA polymerase.

06:20 We have agents that are approved for lamivudine resistance.

06:26 We have agents that inhibit RNA polymerase. This particular agent is quite active in hepatitis C virus. It is used in conjunction with ledipasvir to treat chronic hepatitis C infection.

06:37 Boceprevir is also a protease inhibitor and it's used with ribavirin as well.