Anti Viral Agents pdf - د. نجلاء

Anti Viral Agents

Antiviral Agents

Viral replication



Adsorption



Penetration



Uncoating



Biosynthesis



Maturation



Release

Antiviral Agents

Viral replication



Adsorption



Penetration



Uncoating



Biosynthesis



Maturation



Release

Antiviral Drugs

Classification of Antiviral Drugs:



Drugs directly impair viral replication



Drugs modulate the host I

Drugs modulate the host I -- system

system

Agents to treat HSV and VZV infections

(Acyclovir,

(Acyclovir, Valacyclovir

Valacyclovir, and

, and Famciclovir

Famciclovir))

Pharmacokinetic of

Acyclovir



Oral,

Oral, i.v

i.v,, topical.

topical.



Bioavailability is

Bioavailability is 15

15--20

20%.



Cleared primarily by

glomerular filtration and

tubular secretion.



TT11\\22==33hr



Cerebrospinal fluid

concentrations are

concentrations are 50

50%

% of

serum values.

Pharmacokinetic of

Acyclovir



Oral,

Oral, i.v

i.v,, topical.

topical.



Bioavailability is

Bioavailability is 15

15--20

20%.



Cleared primarily by

glomerular filtration and

tubular secretion.



TT11\\22==33hr



Cerebrospinal fluid

concentrations are

concentrations are 50

50%

% of

serum values.

Administration and

metabolism of acyclovir

Indications for Acyclovir

1. Herpes simplex virus

Herpes simplex virus

2. Varicella

Varicella -- zoster virus:

zoster virus:



Chickenpox



Shingles

Adverse reactions



Stinging sensation and a diffuse

superficial punctate

superficial punctate keratopathy

keratopathy..



Gastrointestinal symptoms,

Gastrointestinal symptoms, headache

headache

and neuropsychiatric reactions,

severe local inflammation with

severe local inflammation with i.v.

i.v.

Agents to treat

Cytomegalovirus

Cytomegalovirus (CMV)

(CMV)

Infections

Infections Ganciclovir

Ganciclovir,,

Valganciclovir

Valganciclovir,, Cidofovir

Cidofovir

Ganciclovir



Orall

Orall or

or i.v

i.v,,



Poor bioavailability.



Eliminated in the urine,

mainly unchanged (

mainly unchanged (tltl//2 4

2 4h).

h).

Agents to treat

Cytomegalovirus

Cytomegalovirus (CMV)

(CMV)

Infections

Infections Ganciclovir

Ganciclovir,,

Valganciclovir

Valganciclovir,, Cidofovir

Cidofovir

Ganciclovir



Orall

Orall or

or i.v

i.v,,



Poor bioavailability.



Eliminated in the urine,

mainly unchanged (

mainly unchanged (tltl//2 4

2 4h).

h).

Administration and

metabolism of

metabolism of ganciclovir

ganciclovir

Indications for

Indications for Ganciclovir

Ganciclovir Include

Include



Life

Life -- threatening (CMV) infection

threatening (CMV) infection



For maintenance suppressive treatment

of retinitis in patients with AIDS



Prevention (CMV)

Prevention (CMV) following organ

following organ

transplantation

Adverse Reactions of

Adverse Reactions of Ganciclovir

Ganciclovir



Neutropenia and thrombocytopenia

fever, rash, gastrointestinal symptoms,

confusion and seizure



Concomitant use of potential marrow

Concomitant use of potential marrow --

depressant drugs, e.g.

depressant drugs, e.g. cotrimoxazole

cotrimoxazole,,

zidovudine

zidovudine,, should be avoided.

should be avoided.

Adverse Reactions of

Adverse Reactions of Ganciclovir

Ganciclovir



Neutropenia and thrombocytopenia

fever, rash, gastrointestinal symptoms,

confusion and seizure



Concomitant use of potential marrow

Concomitant use of potential marrow --

depressant drugs, e.g.

depressant drugs, e.g. cotrimoxazole

cotrimoxazole,,

zidovudine

zidovudine,, should be avoided.

should be avoided.

Antiretroviral Agents



Nucleoside reverse transcriptase

inhibitors (NRTIs).



Non nucleoside reverse transcriptase

inhibitors (NNRTIs).



Protease inhibitors (PIs).

Zidovudine

Zidovudine (NRTIs)

(NRTIs)



Well absorbed



Distributed to most body tissues and

fluids.



Eliminated primarily by renal excretion

following

following glucuronidation

glucuronidation in the liver.

in the liver.

Indications for

Indications for Zidovudine

Zidovudine



HIV infection in patients with acquired

immunodeficiency syndrome (AIDS) or

AIDS related complex.

Drug Interaction of

Drug Interaction of Zidovudine

Zidovudine



Myelosuppressive

Myelosuppressive drugs such as

drugs such as

ganciclovir

ganciclovir,, ribavirin,

ribavirin, and cytotoxic

and cytotoxic

agents

agents



toxicity.



Probenecid

Probenecid,, 



Serum levels of

zidovudine

zidovudine acid through decreased

acid through decreased

its clearance.

Drug Interaction of

Drug Interaction of Zidovudine

Zidovudine



Myelosuppressive

Myelosuppressive drugs such as

drugs such as

ganciclovir

ganciclovir,, ribavirin,

ribavirin, and cytotoxic

and cytotoxic

agents

agents



toxicity.



Probenecid

Probenecid,, 



Serum levels of

zidovudine

zidovudine acid through decreased

acid through decreased

its clearance.

(NNRTIs)

(NNRTIs) Nevirapine

Nevirapine



It used in combination

with at least two other

antiretroviral



It penetrates the CSF



HHepatic metabolism.

epatic metabolism.



Rash and hepatitis are

the commonest side

effects.

(NNRTIs)

(NNRTIs) Nevirapine

Nevirapine



It used in combination

with at least two other

antiretroviral



It penetrates the CSF



HHepatic metabolism.

epatic metabolism.



Rash and hepatitis are

the commonest side

effects.

Administration, metabolism,

and toxicity

and toxicity of nevirapine

Protease Inhibitors

((Ritronavir

Ritronavir,, Indinavir

Indinavir,, Saquinavir

Saquinavir))

HIV produces protein and also a protease

which cleaves the protein into component

parts that are subsequently reassembled

into virus particles; protease inhibitors

disrupt this essential process.

Protease Inhibitors

((Ritronavir

Ritronavir,, Indinavir

Indinavir,, Saquinavir

Saquinavir))

HIV produces protein and also a protease

which cleaves the protein into component

parts that are subsequently reassembled

into virus particles; protease inhibitors

disrupt this essential process.

Some

Some Adverse effect of HIV protease inhibitors

Adverse effect of HIV protease inhibitors

Drug Interactions with protease

inhibitors

1. Enzyme inducer P

Enzyme inducer P450

450 (( e.g

e.g))

rifampicin.

2. Enzyme inhibitors (

Enzyme inhibitors (e.g

e.g))

ketoconazole, cimetidine.

Drug Interactions with protease

inhibitors

1. Enzyme inducer P

Enzyme inducer P450

450 (( e.g

e.g))

rifampicin.

2. Enzyme inhibitors (

Enzyme inhibitors (e.g

e.g))

ketoconazole, cimetidine.

Anti

Anti--influenza Agents

influenza Agents

Amantadine



Active against influenza A virus



Mechanism of action: interfering with

the

the uncoating

uncoating and release of viral

and release of viral

genome into the host cell.

PK:



Well absorbed from the GIT.



It Is eliminated in the urine.

Anti

Anti--influenza Agents

influenza Agents

Amantadine



Active against influenza A virus



Mechanism of action: interfering with

the

the uncoating

uncoating and release of viral

and release of viral

genome into the host cell.

PK:



Well absorbed from the GIT.



It Is eliminated in the urine.

Amantadine Adverse Reactions



Dizziness, insomnia, headedness and

nervousness, Drowsiness, hallucinations,

delirium, coma may occur in patients with

impaired renal function. Convulsions may

be induced, and amantadine should be

avoided in epileptic patients.

Amantadine Adverse Reactions



Dizziness, insomnia, headedness and

nervousness, Drowsiness, hallucinations,

delirium, coma may occur in patients with

impaired renal function. Convulsions may

be induced, and amantadine should be

avoided in epileptic patients.

Respiratory Syncytial Virus (RIBAVIRIN)

Interferons

Interferons (Hepatic Viral Infection)

(Hepatic Viral Infection)

1. Directly on uninfected cells to induce

Directly on uninfected cells to induce

enzymes that degrade viral RNA.

2. Indirectly by stimulating the immune

Indirectly by stimulating the immune

system.

Uses of

Uses of Interferon

Interferon



AAlfa Interferon used for hairy cell

lfa Interferon used for hairy cell

leukaemia

leukaemia, recurrent or metastatic renal

, recurrent or metastatic renal

cell carcinoma, Kaposi's sarcoma in AIDS

patients



Alfa

Alfa--22αα and

and --22b improve the

b improve the

manifestations of viral hepatitis, B and C.

hepatitis C may need prolonged therapy.

Uses of

Uses of Interferon

Interferon



AAlfa Interferon used for hairy cell

lfa Interferon used for hairy cell

leukaemia

leukaemia, recurrent or metastatic renal

, recurrent or metastatic renal

cell carcinoma, Kaposi's sarcoma in AIDS

patients



Alfa

Alfa--22αα and

and --22b improve the

b improve the

manifestations of viral hepatitis, B and C.

hepatitis C may need prolonged therapy.

Adverse reactions of

Adverse reactions of interferon

interferon



An influenza

An influenza--like syndrome

like syndrome



Fatigue &

Fatigue &anoroxia

anoroxia



Convulsions, depression



Hypotension, hypertension, cardiac

arrhythmias



Bone marrow depression.



It inhibit the metabolism of theophylline

Adverse reactions of

Adverse reactions of interferon

interferon



An influenza

An influenza--like syndrome

like syndrome



Fatigue &

Fatigue &anoroxia

anoroxia



Convulsions, depression



Hypotension, hypertension, cardiac

arrhythmias



Bone marrow depression.



It inhibit the metabolism of theophylline

Inosine

Inosine Pranobex

Pranobex



Mucocutaneous

Mucocutaneous herpes simplex

herpes simplex

and genital warts.



It is administered by mouth and

metabolised

metabolised to uric acid.

to uric acid.