oral medicne anti viral

7/29/2019 Oral Medicne Anti Viral

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Submitted to : Sumitted by :

Harjot Kaur Mavi

Roll no 21

Final year

Department of oral medicne

& maxillofacial Radiology


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1. Viruses, what are they, who are they?

2. Virus Classification

3. Drug Development

4. Antiviral Drugs5. Conclusions and Overview

6. Refrences


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STAGES OF REPLICATION(DNAvirus)

Attachment

Penetration

Uncoating

Transfer of DNA to cell nucleus


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Viruses have no cell wall and made up ofnucleic acid components

Viruses containing envelopeantigenic innature

Viruses are obligate intracellular parasite

They do not have a metabolic machinery oftheir ownuses host enzymes


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Certain viruses multiply in the cytoplasmbut others do in the nucleus

Most multiplication take place before

diagnosis is made


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Defination

Many antiviral drugs arePurine or Pyrimidineanalogs.

Many antiviral drugs areProdrugs. They mustbe phosphorylated by viral or cellular enzymes

in order to become active. Anti-viral agentsinhibits active replicationso

the viral growth resumes after drug removal.


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ANTI

HERPES VIRUS

Acyclovir

Farciclovir Ganciclovir

foscarnet


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Retro viral Drugs

Specific retroviral drugs

Reverse transcriptase inhibitors

Nucleosides (NRTIs)

Non-nucleosides (NNRTIs)

Protease inhibitors


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Anti Retro Virus

Nucleoside reverse transcriptase inhibitors

Zidovudine (AZT)

Didanosine

Lamivudine

Non-nucleoside reverse transcriptase inhibitors

nevirapine


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Protease inhibitors

Ritonavir

ANTIINFLUENZA VIRUS

Amantadine

NON-SELECTIVE ANTIVIRAL DRUGS

Ribavirin

Lamivudine

Interferon a


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ANTI HERPES VIRUS

Anti-herpes virusAcyclovir / Valacyclovir

Famciclovir / Penciclovir

Ganciclovir / CidofovirFoscarnet

Trifluridine / Vidarabine


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ACYCLOVIR & CONGENERS

Valacycloviris a prodrug of Acyclovir with better

bioavailability. Famciclovir is hydrolyzed to Penciclovir and has

greatest bioavailability. Penciclovir is used only topically whereas Famciclovir

can be administered orally.


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Acyclovir

These drugs are predominately acyclicanalogues of Guanosine

Derived from thimadine kinase(TK)enzymes.

It is slowly and incompletely absorbed by Oral

dosing.

Much better levels are achieved by I.V.

Or by useof prodrug Valaciclover


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PHARMACOLOGY OF ACYCLOVIR :


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MECHANISM OF ACTION OF ACYCLOVIR

All drugs are phosphorylated by a viralthymidine-kinase, then metabolized by host cellkinases to nucleotide analogs.

The analog inhibits viral DNA-polymerase Only actively replicating viruses are inhibited


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ROUTES OF ADMINISTRATION OFACYCLOVIR

TOPICAL(ZOVIRAX)

used in Herpes Labialis.

DOSAGE- 5% cream qid for 4days.

CONTRA INDICATIONS-Hypersensitivity.

SIDE EFFECT- pain& burning.


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ORAL ROUTE

INDICATION-

Chicken pox (esp. in immunosuppressed).

DOSAGE- 200-400mg 5 times a day.

SIDE EFFECTS-

Toxicity


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INTRAVENOUS

INDICATIONS-

Herpes Simplex infection

Genital tract infection.

Eye infection. SIDE EFFECTS-

Increase in urea & creatinine.


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PHARMACOLOGY OF ACYCLOVIR ANDCONGENERS

Acyclovir, Valacyclovir, Ganciclovir,Famciclovir, Penciclovir all are guaninenucleoside analogs.


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PHARMACOKINETICS OF ACYCLOVIR

Oral bioavailability ~ 20-30%

Distribution in all body tissues including CNS

Renal excretion: > 80% Half lives: 2-5 hours

Administration: Topical, Oral , IV


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Adverse effects of Acyclovir

Nausea, vomiting and diarrhea

Nephrotoxicity - haematuria, renalinsufficiency

Renal dysfunction

CNS Disturbance- Hallucination

Rashes & Headache

Gastrointestinal Toxicity Neurotoxicity.


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THERAPEUTIC USES

Acyclovir is the drug of choice for:

HSV Genital infections

HSV encephalitisHSV infections in immunocompromised patient

Ganciclovir is the drug of choice for:

CMV retinitis in immunocompromised patient

Prevention of CMV disease in transplant patients


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GANCICLOVIR

It is an Analogue of Acyclovir.

It is more active than Acyclovir againstCMV.

It has a same activity as Acycloviragainst HSV-1&2.

It is intravenous medication for

CytomegaloVirus infection inHIVdisease.


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ROUTES OF DRUG ADMINISTRATION

By Intravenous.

By Oral route.


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ADVERSE EFFECTS

Bone Marrow suppression

Thrombocytopenia

Neutropenia.

Nephrotoxicity.


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PHARMACOLOGY OF VIDARABINE

Vidarabine is a nucleoside analog.(adenosine)

HSV-1, HSV-2 and VZV.Its use is limited to HSV keratitis only


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VIDARIBINE

The drug is converted to its triphosphateanalog which inhibits viral DNA-polymerase.

Oral bioavailability ~ 2%

Administration:Ophthalmic ointment

Used in HSV keratoconjunctivitis inimmunocompromised patient.

Anemia and SIADH are adverse effects.


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TRIFLURIDINE

PHARMACOLOGY OF TRIFLURIDINE Trifluridine is a Pyrimidine nucleoside

analogs - inhibits viral DNA synthesis.

HSV-1, HSV-2 and VZV. Use is limited to Topical - Ocular HSV

Keratitis


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FOSCARNET

PHARMACOLOGY OFFOSCARNET Foscarnet is an inorganic pyrophosphate

analog

It directly inhibits viral DNA and RNA -polymerase and viral inversetranscriptase (it does not requirephosphorylation for antiviral activity)


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INDICATIONS & ROUTES OFADMINISTRATION

Foscarnet HSV-1, HSV-2, VZV, CMV and HIV.


Distribution to all tissues including CNS Administration: IV


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ADVERSE EFFECTS OF FOSCARNET

Hypocalcemia and hypomagnesemia(due to chelation of the drug withdivalent cations) are common.

Neurotoxicity (headache, hallucinations,seizures)

Nephrotoxicity (acute tubular nephrosis,interstitial nephritis)


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THERAPEUTIC USES OF FOSCARNET

Therapeutic uses of Foscarnet It is an alternative drug for

HSV infections (acyclovir resistant /

immunocompromised patient ) CMV retinitis (ganciclovir resistant /

immunocompromised patient )


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RETRO VIRUSES

A family of RNA viruses containing a reversetranscriptase enzyme which allows the viruses'genetic information to become part of thegenetic information of the host cell upon

replication. Any member of a large family of RNA viruses

that includes theLENTIVIRUSESandcertainONCOVIRUSES, given this name becausethey carryREVERSETRANSCRIPTASE
http://medical-dictionary.thefreedictionary.com/lentivirushttp://medical-dictionary.thefreedictionary.com/oncovirushttp://medical-dictionary.thefreedictionary.com/reverse+transcriptasehttp://medical-dictionary.thefreedictionary.com/reverse+transcriptasehttp://medical-dictionary.thefreedictionary.com/reverse+transcriptasehttp://medical-dictionary.thefreedictionary.com/reverse+transcriptasehttp://medical-dictionary.thefreedictionary.com/reverse+transcriptasehttp://medical-dictionary.thefreedictionary.com/reverse+transcriptasehttp://medical-dictionary.thefreedictionary.com/oncovirushttp://medical-dictionary.thefreedictionary.com/lentivirus


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ANTI- RETROVIRUSES

NUCLEOSIDE REVERSE TRANSCRIPTASEINHIBITORS.

Zidovudine(AZT)

Didanosine

NONO- NUCLEOSIDE REVERSETRANSCRIPTASE INHIBITORS-

Nevirapine.


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ZIDOVUDINE (1987) The first drug to enter clinical

practice in 1987.

It is a Thymidine Analogue MECHANISM OF ACTION-

It iself gets incorporated into thegrowing Viral DNA & termintes chain

elongation.


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INDICATION

In HIV infected patients incombination with atleast 2 otherAnti-Retrovirus drugs.


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PHARMACOKINETICS

Absorbed orally.

Bioavailability- 65%.

15-20% of drug is excreted un

urine.


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ADVERSE EFFECTS

AnaemiaNeutropenia.

Nausea.

Anorexia.

Abdominal pain

Hepatomegaly.

Insomnia

Myalgia.


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Latest Anti viral Drugs

Epivir (lamivudine)

Viramune (neviripine)


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ANTI INFLUENZA DRUGS

Respiratory viral infectionsInfluenza

Amantadine / Rimantadine

Oseltamivir / Zanamavir

RSV bronchiolitis

Ribavirin


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AMANTADINE & RIMANTADINE

Amantadine and Rimantadine : Influenza Prevention & Treatment of influenza A

Inhibition of viral uncoatingby inhibitingthe viral membrane protein M2

Influenza A virus Amantadine has anti-parkinsonian effects.


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PHARMACOKINECTICS OF AMANTADINE


Amantadine cross extensively BBB whereasRimantadine does not cross extensively .

Administration: Oral


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NON SELECTIVE ANTI VIRAL DRUGS

Ribavirin.

Lamivudine.

Interferon-a


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RIBAVIRIN

PHARMACOLOGY OF RIBAVIRINRibavirinis a guanosine analog.

Inhibition of RNA polymerase

Antiviral spectrum :DNA and RNA viruses are

susceptible, including influenza, parainfluenzaviruses, RSV,Lassa virus


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RIBAVIRIN :RSV

Distribution in all body tissues, except CNS

Administration : Oral, IV, Inhalational in RSV.

Anemia and jaundice are adverse effects

Not advised in pregnancy.


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THERAPEUTIC USES OF RIBAVIRIN

Ribavirin is the drug of choice for:

RSV bronchiolitis and pneumonia in hospitalizedchildren (given by aerosol)

Lassa feverRibavirin is an alternative drug for:

Influenza, parainfluenza, measles virus infectionin immunocompromised patients


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HEPATIC VIRAL INFECTIONS

Interferons

Lamivudine cytosine analog HBV

Entecavir guanosine analog HBVlamivudine resistance strains

Ribavirin Hepatitis C (with interferons)


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INTERFERONSInterferons

Interferons (IFNs) are low molecular naturalglycoproteins cytokines produced by hostcells of the immune systems in response to

challenges by foreign agents such asviruses, bacteria, parasites and tumor cells.

Antiviral, immune modulating andanti-proliferative actions

Three classes of interferons , ,


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INDICATIONS

Therapeutic uses Interferons Chronic hepatitis B and C (complete

disappearance is seen in 30%).

HZV infection in cancer patients (to prevent the

dissemination of the infection) CMV infections in renal transplant patients.

Hairy cell leukemia (in combination withzidovudine)

AIDS related Kaposis sarcoma


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INTERFERONS and interferons are produced by all

the cells in response to viral infections

interferons are produced only by Tlymphocyte and response to cytokinesimmune regulating effects

has less anti-viral activity compared to and interferons


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AntiVIRAL spectrum:Interferon a

Antiviral spectrum : Interferon

Includes HBV, HCV and HPV.

Anti-proliferative actions may inhibit thegrowth of certain cancers - like hairycell leukemia.


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PHARMACOKINETICS :Interferons

Oral bioavailability: < 1%

Administered Intralesionally, S.C,

and I.V

Distribution in all body tissues,except CNS and eye.

Half lives: 1-4 hours


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ADVERSE EFFECTS OFINTERFERONS

Acute flu-like symptoms (fever,fatigue,dizziness,visual & taste

disturbance headache) Bone marrow suppression(granulocytopenia, thrombocytopenia)

Neurotoxicity (confusion, seizures,convulsions)

Cardiotoxicity - arrhythmia Impairment of fertility Hypotension, liver dysfunction.


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