Herpes viruses are associated with diseases like cold sores and genital infections. There are several drugs that are effective against these viruses during acute infection, including acyclovir, cidofovir, foscarnet, ganciclovir, penciclovir/famciclovir, and trifluridine. These drugs work by incorporating into viral DNA or inhibiting viral polymerases. Highly active antiretroviral therapy (HAART) uses combinations of drugs from five classes to suppress HIV replication, including nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors, entry inhibitors, and integra

1. GROUP 3
1.MOHAMED ABDUKADIR 2. YAHYE ABDIRIHMAN
3.FADUMO MAHAMUUD 4.NAJAX ABDIRIHMAN
4.SAHRO MOHAMED

2. TREATMENT FOR HERPES VIRUS INFECTIONS
• Herpes viruses are associated with a broad spectrum of diseases, for example,
cold sores, viral encephalitis, and genital infections. The drugs that are effective
against these viruses exert their actions during the acute phase of viral infections
and are without effect during the latent phase.
• A. Acyclovir
• Acyclovir [ay-SYE-kloe-veer] (acycloguanosine) is the prototypic antiherpetic
therapeutic agent. Herpes simplex virus (HSV) types 1 and 2, varicella-zoster virus
(VZV), and some Epstein-Barr virus–mediated infections are sensitive to acyclovir.
It is the treatment of choice in HSV encephalitis.

3. M. O. A
• Acyclovir, a guanosine analog, is monophosphorylated in the cell by the
herpesvirus-encoded enzyme thymidine kinase (Figure 45.8). Therefore, virus-
infected cells are most susceptible. The monophosphate analog is converted to
the di- and triphosphate forms by the host cell kinases. Acyclovir triphosphate
competes with deoxyguanosine triphosphate as a substrate for viral DNA
polymerase and is itself incorporated into the viral DNA, causing premature DNA
chain termination.
• ADVERSE EFFECTS: headache, diarrhea, nausea, and vomiting

4. B. CIDOFOVIR
• Cidofovir [si-DOE-foe-veer] is approved for the treatment of cytomegalovirus (CMV)
retinitis in patients with AIDS. [Note: CMV is a member of the herpesvirus family.]
Cidofovir is a nucleotide analog of cytosine, the phosphorylation of which is not
dependent on viral or cellular enzymes. It inhibits viral DNA synthesis
C. Foscarnet
foscarnet [fos-KAR-net] is not a purine or pyrimidine analog. Instead, it is a
phosphonoformate (a pyrophosphate derivative) and does not require activation by viral
(or cellular) kinases. Foscarnet is approved for CMV retinitis in immunocompromised
hosts and for acyclovir-resistant HSV infections. Foscarnet works by reversibly inhibiting
viral DNA and RNA polymerases, thereby interfering with viral DNA and RNA synthesis.

5. D. GANCICLOVIR
• Ganciclovir [gan-SYE-kloe-veer] is an analog of acyclovir that has greater activity
against CMV. It is used for the treatment of CMV retinitis in immunocompromised
patients and for CMV prophylaxis in transplant patients.
• Mechanism of action: Like acyclovir, ganciclovir is activated through conversion to
the nucleoside triphosphate by viral and cellular enzymes. The nucleotide inhibits
viral DNA polymerase and can be incorporated into the DNA resulting in chain
termination
• Adverse effects: Adverse effects include severe, dose- dependent neutropenia.
Ganciclovir is carcinogenic as well as embryotoxic and teratogenic in
experimental animals.

6. E. PENCICLOVIR AND FAMCICLOVIR
• Penciclovir pen-SYE-kloe-veer is an acyclic guanosine nucleoside derivative that is
active against HSV-1, HSV-2, and VZV. Penciclovir is only administered topically. It
is monophosphorylated by viral thymidine kinase, and cellular enzymes form the
nucleoside triphosphate, which inhibits HSV DNA polymerase. Penciclovir
triphosphate has an intracellular half-life much longer than acyclovir
triphosphate. Penciclovir is negligibly absorbed upon topical application and is
well tolerated. Famciclovir fam-SYE-kloe-veer, another acyclic analog of 2′-
deoxyguanosine, is a prodrug that is metabolized to the active penciclovir. The
antiviral spectrum is similar to that of ganciclovir, and it is approved for treatment
of acute herpes zoster, genital HSV infection, and recurrent herpes labialis. The
drug is effective orally. Adverse effects include headache and nausea.

7. F. TRIFLURIDINE
• Trifluridine [trye-FLURE-i-deen] is a fluorinated pyrimidine nucleoside analog that
is structurally similar to thymidine. Once converted to the triphosphate, the agent
is believed to inhibit the incorporation of thymidine triphosphate into viral DNA
and, to a lesser extent, lead to the synthesis of defective DNA that renders the
virus unable to replicate. Trifluridine is active against HSV-1, HSV-2, and vaccinia
virus. It is indicated for treatment of HSV keratoconjunctivitis and recurrent
epithelial keratitis. Because the triphosphate form of trifluridine can also
incorporate to some degree into cellular DNA, the drug is considered to be too
toxic for systemic use. Therefore, the use of trifluridine is restricted to a topical
ophthalmic preparation. A short half-life necessitates that the drug be applied
frequently. Adverse effects include a transient irritation of the eye and palpebral
(eyelid) edema.

8. OVERVIEW OF THE TREATMENT
FOR HIV INFECTION
• treatment of HIV infections
• focused on decreasing the occurrence of opportunistic infections that
• caused a high degree of morbidity and mortality in AIDS patients. Today,
• the viral life cycle is understood and a combination of
• drugs is used to suppress replication of HIV and restore the number of CD4 cells
and immunocompetence to the host.

9. CONT….
• This multidrug regimen is
• commonly referred to as “highly active antiretroviral therapy,” or HAART
• There are five classes of antiretroviral drugs, each of which targets one of the
four viral processes. These classes of drugs are :
• nucleoside and nucleotide reverse transcriptase inhibitors (NRTIs),
nonnucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors
• (PIs), entry inhibitors, and the integrase inhibitors.

10. CONT….
• The preferred initial therapy is a combination of two NRTIs with a PI, an NNRTI,
or an integrase inhibitor. Selection of the appropriate combination is based on 1)
avoiding the use of two agents of the same nucleoside analog; 2) avoiding
overlapping toxicities and genotypic and phenotypic characteristics of the virus
3) patient factors,
• 4) impact of drug interactions; and 5) ease of adherence to the
• regimen.

11. NRTIS USED TO TREAT HIV INFECTION
• Mechanism of action: NRTIs are analogs of native ribosides (nucleosides or
nucleotides containing ribose), which all lack a 3′-hydroxyl group. Once they
enter cells, they are phosphorylated by
• cellular enzymes to the corresponding triphosphate analog, which
• is preferentially incorporated into the viral DNA by RNA.

12. CONT…
• Pharmacokinetics: The NRTIs are primarily renally excreted,
• and all require dosage adjustment in renal insufficiency except
• abacavir, which is metabolized by alcohol dehydrogenase and
• glucuronyl transferase.
• Adverse effects: Many of the toxicities of the NRTIs are believed
• to be due to inhibition of the mitochondrial DNA polymerase in
• certain tissues.

13. ZIDOVUDINE (AZT)
• Zidovudine (AZT)
• Zidovudine [zye-DOE-vyoo-deen], the pyrimidine analog, 3′-azido-
• 3′-deoxythymidine (AZT), was the first agent available for the treatment of HIV infection. AZT is
approved for the treatment of HIV in
• children and adults and to prevent perinatal transmission of HIV
• . Stavudine (d4T)
• Stavudine [STAV-yoo-deen] is an analog of thymidine approved for
• the treatment of HIV. The drug is well absorbed after oral administration, and it penetrates the blood–
brain barrier. The majority of the
• drug is excreted unchanged in the urine

14. CONT…
• Didanosine (ddI)
• Upon entry of didanosine
• into the host cell, ddI is biotransformed into dideoxyadenosine triphosphate (ddATP) through a series of reactions that involve
phosphorylations and aminations.
• The drug penetrates into the CSf
• Pancreatitis, which may be fatal,
• . Tenofovir (TDF)
• Tenofovir is a nucleotide analog, namely, an acyclic
• nucleoside phosphonate analog of adenosine 5′-monophosphate. It
• is converted by cellular enzymes to the diphosphate, which is the
• inhibitor of HIV RT

15. CONT…
• Lamivudine (3TC)
• Lamivudine [la-MI-vyoo-deen] (2′-deoxy-3′-thiacytidine, 3TC) inhibits
• the RT of both HIV and HBV it does not affect mitochondrial DNA synthesis or bone
marrow precursor cells, resulting in less
• toxicity.
• Emtricitabine (FTC)
• Emtricitabine [em-tri-SIGH-ta-been], a fluoro derivative of lamivudine,
• inhibits both HIV and HBV RTalso cause hyperpigmentation of the soles and palms.

16. NNRTIS USED TO TREAT HIV INFECTION
• NNRTIs are highly selective, noncompetitive inhibitors of HIV-1 RT.
They bind to HIV RT at an allosteric hydrophobic site adjacent to
the active site,
• Nevirapine (NVP)
• Nevirapine [ne-VYE-ra-peen] is used in combination with other
antiretroviral drugs for the treatment of HIV infections in adults and
children.

17. DELAVIRDINE (DLV)
• Delavirdine [de-LA-vir-deen] is not recommended as a preferred or
• alternate NNRTI in the current HIV guidelines due to its inferior antiviral efficacy and
inconvenient (three times daily) dosing.
• Efavirenz (EFV)
• Efavirenz [e-FA-veer-enz] is the preferred NNRTI. Following oral
• administration, efavirenz is well distributed, including to the CNS
• It should be administered on an empty stomach to
• reduce adverse CNS effects.

18. ETRAVIRINE (ETR)
• Etravirine [et-ra-VYE-rine] is a second-generation NNRTI active
• against many HIV strains that are resistant to the first-generation NNRTIs.
• Rilpivirine (RPV)
• Rilpivirine [ril-pi-VIR-een] is approved for HIV treatment-naïve patients
• in combination with other antiretroviral agents. It is administered orally
• once daily with meals and has pH-dependent absorption .