Download Chapter 16 Cholinesterase Inhibitors

Chapter 92
Antiviral Agents I: Drugs for NonHIV Viral Infections
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
2
Antiviral Therapy




Our ability to treat viral infections remains
limited
Viruses use biochemical machinery of host
cells to reproduce
Difficult to suppress viral replication without
doing significant harm to the host
Antivirals suppress biochemical processes
unique to viral reproduction
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
3
Herpesvirus

Herpes simplex virus (HSV)


Causes infection of the genitalia, mouth, face, and
other sites
Varicella-zoster virus (VZV)

Cause of varicella (chickenpox) and herpes zoster
(shingles)
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
4
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
5
Acyclovir (Zovirax)


Active only against members of the
herpesvirus family
Agent of first choice for HSV or VZV
infections



Herpes simplex genitalis
Mucocutaneous herpes simplex infections
Varicella-zoster infections
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
6
Acyclovir (Zovirax)

Herpesvirus develops resistance to acyclovir



Decreased thymidine production
Alteration in thymidine kinase
Alteration of viral DNA polymerase
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
7
Acyclovir (Zovirax) – Adverse Effects

Intravenous therapy



Oral therapy



Phlebitis
Reversible nephrotoxicity
Gastrointestinal
Vertigo
Topical

Stinging sensations
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
8
Valacyclovir (Valtrex)

Prodrug form of acyclovir




Herpes zoster
Herpes simplex genitalis
Herpes labialis
In some immunocompromised patients

Thrombotic thrombocytopenic purpural/hemolytic
uremic syndrome (TTP/HUS)
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
9
Famciclovir (Famvir)



Prodrug used to treat acute herpes zoster
and genital herpes infection
Benefits are equivalent to those of acyclovir
Adverse effects are minimal
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
10
Topical Drugs

Herpes labialis



Penciclovir (Denavir)
Docosanol (Abreva)
Ocular herpes infections


Trifluridine (Viroptic)
Vidarabine (Vir-A)
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
11
Cytomegalovirus Infection





CMV – member of herpesvirus group
Transmitted direct contact with body fluids
50%-80% of Americans age 40 and older
harbor the virus
Can remain dormant for life
Immunosuppressed patients at high risk to
reactivate dormant virus
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
12
Ganciclovir (Cytovene, Vitrasert)


Synthetic antiviral agent
Uses



Herpes simplex viruses – including CMV
Prevention and treatment of CMV infection in
immunocompromised patients
Serious side effects


Granulocytopenia
Thrombocytopenia
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
13
Ganciclovir (Cytovene, Vitrasert)

Adverse effects




Granulocytopenia
Thrombocytopenia
Reproductive toxicity
Nausea, fever, rash, anemia, liver dysfunction,
confusion, and other CNS symptoms
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
14
Valganciclovir (Valcyte)




Prodrug version of ganciclovir
Used for CMV retinitis
Oral is just as effective as IV
Adverse effects

Blood dyscrasias
• Bone marrow suppression
• Granulocytopenia, anemia, thrombocytopenia
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
15
Valganciclovir (Valcyte)

Adverse effects (cont’d)




Diarrhea, nausea, vomiting
Potential for mutagenesis and carcinogenesis
Direct contact with broken tablet should be
avoided
Should be disposed of in the same manner
as a cytotoxic drug
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
16
Cidofovir (Vistide)


IV with just one indication – CMV retinitis in
patients with AIDS who have failed on
ganciclovir or foscarnet
Adverse effects



Nephrotoxicity
Neutropenia
Ocular disorders
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
17
Foscarnet (Foscavir)


IV drug active against all known
herpesviruses
Compared with ganciclovir



More difficult to give, less well tolerated, much
more expensive
CMV retinitis in patients with AIDS
Acyclovir-resistant mucocutaneous HSV and
VZV in immunocompromised host
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
18
Fomivirsen (Vitravene)



Unique drug for treating CMV retinitis with
HIV-infected patients who are intolerant of or
unresponsive to other drugs
Direct injection into the vitreous humor
Adverse effects

Ocular inflammation
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
19
Drugs for Hepatitis




Viral hepatitis is the most common liver
disorder
Millions of Americans are infected
Six different viruses can cause acute hepatitis
(A, B, C, D, E, and G)
Only B, C, and D can also cause chronic
hepatitis
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
20
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
21
Hepatitis C Virus (HCV)






Differences in HCV – 6 genotypes; more than
50 subtypes
Transmission – primarily through exchange of
blood; controversy over sexual transmission
No symptoms, but can transmit
Slow progression can lead to liver failure,
cancer, and death
Leading reason for liver transplants
Drugs

Pegylated interferon alfa combined with ribavirin
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
22
Interferon Alfa

Interferon family





Alpha, beta, gamma
Alphas used to treat hepatitis
None can be administered orally
Conventional versus long-acting interferons
Adverse effects


Flu-like symptoms
Neuropsychiatric effects, especially depression
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
23
Ribavirin (Rebetol, Copegus)


Used in combination with subQ peginterferon
alfa for treatment of chronic hepatitis C
Adverse effects


Hemolytic anemia
Birth defects – category X
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
24
Hepatitis B Virus (HBV)





1.25 million people have chronic hepatitis B
11,000 require hospitalization for deep
fatigue, muscle pain, and jaundice
Chronic infection develops in 3%-5% infected
adults
Chronic infection can lead to cirrhosis,
hepatic failure, hepatocellular carcinoma, and
death
Transmission – blood and semen
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
25
Hepatitis B Virus (HBV)


HBV vaccine
Drugs






Interferon alfa-2b (PEG-Intron)
Peginterferon alfa-2a
Lamivudine (Epivir-HBV)
Adefovir (Hepsera)
Entecavir (Baraclude)
Telbivudine (Tyzeka)
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
26
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
27
Influenza




Serious respiratory tract infection
Major cause of morbidity and mortality
worldwide
36,000 deaths/year in the United States
Caused by influenza viruses, which are highly
variable and undergo constant evolution


Type A – more infectious than B
Type B
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
28
Influenza Management


Influenza managed by vaccination (primary
strategy) and drugs
Drugs


Adamantanes and neuraminidase inhibitors
Vaccines

Influenza vaccines change yearly based on
identification of strains by CDC, FDA, and WHO.
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
29
Influenza Vaccine

Two types of flu vaccines





Inactivated influenza vaccine
Live, attenuated influenza vaccine
Protection begins 1-2 weeks after
vaccination; generally lasts 6 months or more
Small risk for Guillain-Barré syndrome
Five influenza vaccines on the market
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
30
Influenza Vaccine

Precautions and indications





Acute febrile illness – should defer
Minor illnesses with or without fever do not
preclude vaccination
Contraindicated for hypersensitivity to eggs –
viruses are grown in eggs
Who should be vaccinated
When should vaccines be given
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
31
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
32
Drugs for Influenza

Neuraminidase Inhibitors



Oseltamivir (Tamiflu)
Zanamivir (Relenza)
Adamantanes


Amantadine (Symmetrel)
Rimantadine (Flumadine)
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
33
Drugs for Respiratory Syncytial
Virus Infection

Ribavirin (inhaled)


Broad-spectrum antiviral drug
Palivizumab (Synagis)

Monoclonal antibody for preventing RSV infection
in newborns
Elsevier Inc. items and derived items © 2010 by Saunders, an imprint of Elsevier Inc.
34