1 For the Subject CLINICAL PHARMACOLOGYSubmitted by-AMBADAS MANE Teacher In-ChargeDr. S. V. Tembhurne

All India Shri Shivaji Memorial Society’s College of Pharmacy,Kennedy Road, Pune-411001

An Assignment Submitted as a part of the Continuous Assessment-1on the Topic

HEPATITIS

2 CONTENTS

INTRODUCTION TYPES OF HEPATITIS Classification of drugs Therapy Conclusion References

3 INTRODUCTION

 "Hepatitis" means inflammation of the liver.

Caused by one of several viruses, such as Hepatitis A,B,C,D and E virus.

Toxins, certain drugs, some diseases, heavy alcohol use, bacterial infections, and viral infections can also cause hepatitis.

There are several types of viral hepatitis, each one caused by a different virus.

This includes: Hepatitis A ; Hepatitis B ; Hepatitis C ; Hepatitis D and Hepatitis E . Hepatitis A, B, and C are the most common types of viral hepatitis.

4 Types of hepatitis

There are following types of hepatitis:1. Hepatitis A2. Hepatitis B3. Hepatitis C4. Hepatitis D5. Hepatitis E

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7 Symptoms Fatigue Excessive tiredness Lack of appetite Nausea Diarrhea Low-grade fever Muscle pain Joint pain Sore throat

Dark urine Abdominal pain (stomach) on the right

side. Include loss of appetite Jaundice. Weight loss Spider-like blood vessels (spider

angiomas) that develop on the skin. Pale-colored stool A low-grade fever

8 Classification of drugs

Drugs used as follows:1. Hepatitis A:- hepatitis A vaccine, immunoglobulin (IG). 2. Hepatitis B:- Interferon Lamivudine Adefovir sofosbuvir

Peginterferon3. Hepatitis C:- peginterferon, ribavirin, sofosbuvir boceprevir and

telaprevir,4. Hepatitis D:-5. Hepatitis E:-

9 Treatment of hepatitis A

No antiviral drug available Get enough calories Get plenty of rest Drink plenty of fluids Avoid medicines that can harm the liver Avoid alcohol Exercise regularly

Treatment is symptomatic

10 CONTRAINDICATIONEffect of Hepatitis A Vaccination on Pregnancy

The safety of the hepatitis A vaccine during pregnancy has not been determined. However, because the vaccine is produced from inactivated hepatitis A virus (HAV), the theoretical risk to either the pregnant woman or the developing fetus is thought to be low.

The risk of vaccination should be weighed against the risk of contracting the disease in female travelers who might be at high risk for exposure to HAV. Also, immunoglobulin (IG), which is a mixture of antibodies, can be used in pregnant women for temporary protection against hepatitis.

11 Treatment of hepatitis B Acute phase – no treatment required, patients recover

12 InterferonMOA: IFN-alpha, a host cytokine produced in response to any viral invasion, has immunomodulatory, antiviral, and antifibrotic properties. It was first used in the 1980s and was the first drug to be found useful in the treatment of chronic hepatitis B.Dosage: 6 MU/ m2 (million units per meter square body surface area) given subcutaneously thrice weekly.

Duration of treatment: in cases of HBeAg positive cases it should be given for 16- 24 weeks. In case with HBeAg negativity it should be given for at least 12 months. Longer duration of treatment may increase the rate of sustained response. Side effects: An influenza-like illness (fever, chills, headache, malaise, myalgias) occurs in 25-30% of patients but rarely needs discontinuation of treatment.

13 LamivudineMOA: undergoes intracellular phosphorylation to its active metabolite

lamivudine triphosphate and inhibits viral reverse transcriptase, causing premature chain termination during viral DNA synthesis.

Dosage: 3 mg/kg/day (max up to 100 mg/day).

Duration of treatment: It should at least be given for one year.

Side effects: hemodialysis, administer afterwards headache, tiredness, dizziness, and nausea

14 AdefovirMOA:

Inhibits viral reverse transcriptase activity in both wild-type and YMDD mutant HBV.

It has also been used in patients with HBeAg positive chronic hepatitis B and HBeAg negative chronic hepatitis B, with efficacy rates at one year similar to those with Lam, albeit with no drug resistant mutations.

15 Other Recommendations

Getting enough calories Getting plenty of rest Drinking plenty of fluids Avoiding medicines that can harm the liver Avoiding alcohol Exercising regularly

16 Treatment of hepatitis C

Chronic hepatitis C is a condition that can lead to more and more liver damage over time. However, everyone's situation is a little different. So, before hepatitis C treatment is recommended, your healthcare provider will review the results of your blood work and other tests to determine several things, including:

The amount of virus in your body (see Hepatitis C Viral Load) Its genotype (see Hepatitis C Genotypes) How much liver damage has already occurred Any other medical conditions you may have.

17 Current Treatments for Hepatitis C

Previously, hepatitis C treatment usually included a couple of drugs called peginterferon and ribavirin. More recently, the hepatitis C protease inhibitors for genotype 1 became available to be used in combination with peginterferon and ribavirin. The newest hepatitis drug is sofosbuvir, which is used in combination with ribavirin for genotypes 2 and 3 or with ribavirin and peginterferon for genotypes 1 and 4.

Peginterferon is given by injection once a week. Ribavirin is a pill taken twice daily. Hepatitis C protease inhibitors include boceprevir and telaprevir, both of which are taken by mouth three times a day with food. Sofosbuvir is taken once daily by orally, with or without food.

18 PeginterferonMOA:- This alpha interferon binds to and activates human type 1 interferon receptors on

hepatocytes which activates multiple intracellular signal transduction pathways, culminating in the expression of interferon-stimulated genes that produce an array of antiviral effects, such as blocking viral protein synthesis and inducing viral RNA mutagenesis. Compared with the native interferon alfa-2a, the peginterferon alfa-2a has sustained absorption, delayed clearance, and a prolonged half life.

DOSING:- Peginterferon alfa-2a 180 mcg/1.0 ml vial for single use, a 180 mcg/0.5 ml

autoinjector for single use, and a 135 mcg/0.5 ml autoinjector for single use. In adults180 mcg subcutaneously administered once weekly in the abdomen or thigh.

ADVERSE EFFECTS:- headache, fatigue, and influenza-like symptoms, including myalgia, pyrexia,

arthralgia, nausea, and anorexia.

19 RibavirinMOA:- (1) augmentation of host T-cell immune clearance of HCV, (2) inhibition of the host enzyme inosine monophosphate dehydrogenase

(IMPDH) that results in depleted pools of guanosine triphosphate, an essential substrate for viral RNA synthesis

(3) direct inhibition of HCV replication, and (4) induction of RNA virus mutagenesis that drives HCV to an abonormally

high error rate.DOSING:- 200 mg, 400 mg, 500 mg, and 600 mg capsules and tablets.  ADVERSE EFFECTS:-Hemolytic Anemia , Birth Defects: Ribavirin can cause significant teratogenic and embyocidal effects, including potential birth defects and fetal death.

20 Boceprevir  MOA:-boceprevir inhibits the proteolytic cleavage of the HCV encoded polyprotein, an essential step in the viral life cycle for the production of mature forms of the viral proteins NS4A, NS4B, NS5A, and NS5B.

DOSING:-200 mg capsules

ADVERSE EFFECTS:-anemia, decreased neutrophil count, dysgeusia (alteration in taste), and vomiting.

21 Telaprevir MOA:-Telaprevir inhibits the proteolytic cleavage of the HCV encoded polyprotein, an essential step in the viral life cycle for the production of mature forms of the viral proteins NS4A, NS4B, NS5A, and NS5B.

DOSING:-375 mg tablets

ADVERSE EFFECTS:-rash, anorectal complaints, and anemia.

22 Things to Consider While on Hepatitis C Treatment

Follow a good eating plan every day Keep your weight in a healthy range Exercise regularly Stop the use of tobacco products Avoid alcohol.

23 Hepatitis D Treatment

There are two types of hepatitis D -- acute (recently acquired) hepatitis D and chronic (life-long) hepatitis D. Each type is treated differently.

24 Treatment of acute hepatitis D

There is no specific treatment for acute hepatitis D. In one report, all three patients treated with foscarnet for fulminant hepatitis due to HDV recovered, as did two additional patients with fulminant hepatitis due to HBV alone. Although these results are encouraging, they need to be confirmed. Foscarnet is an inhibitor of some viral DNA polymerases. However, it was shown to have a paradoxical stimulatory effect on HDV replication in vitro. Thus, the efficacy of foscarnet in fulminant hepatitis due to HBV/HDV coinfection may be secondary to its inhibition of HBV.

25 Treatment for Chronic Hepatitis D

Although many people who are exposed to hepatitis D are able to get rid of the virus, some people can develop chronic hepatitis D. This may lead to liver damage, liver cancer, and even death. There are no drugs that are approved to treat a chronic hepatitis D infection. There is some indication that certain medicines used to treat hepatitis B may be effective against hepatitis D. Among these medicines are alpha interferon and pegylated alpha interferon. However, there is no consensus on how much of these medicines should be used and for how long. It is also not known if these medicines change the natural course of the disease. For people with severe liver disease caused by hepatitis D, liver transplantation has been shown to be effective. If hepatitis D does return in a person who has had a liver transplant, liver injury is usually limited. In fact, the prognosis for liver transplantation in people with hepatitis D is better than the prognosis for liver transplantation in people who have hepatitis B without hepatitis D.

26 Treatment of hepatitis D

27 Treatment of hepatitis E There are no specific medicines that can cure hepatitis E. Therefore,

treatment of hepatitis E is focused on dealing with any symptoms or complications that may occur. This is known as supportive care. Even without specialized treatment for acute hepatitis E, most people recover completely within a few weeks. However, there are some things you can do that might help you feel better. There are also certain things that you should avoid.

28 Specific Hepatitis E Treatment Suggestions

Following are some key steps to take as part of hepatitis E treatment: Get enough calories   Get plenty of rest Drink plenty of fluids. Avoid medicines that can harm the liver.   Avoid alcohol.   Exercise regularly.

29 Reference

‘PATHOLOGY BASIS NOTES AND MORE…’ by Dr. Ashish V. Jawarkar M.D. (Pathology)

Clinical Pharmacotherapeutics Section-A by Dr. S. V. Tembhurne page no.125-148

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Thank you