< </script> MAS PHARMACY AND HEALTH REVIEW: ANTI VIRAL DRUGS-PART-I < </script> <

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Tuesday 14 June 2016

ANTI VIRAL DRUGS-PART-I

HERPES VIRUS TREATMENTS

A virus is defined as an obligate intracellular parasite. Its metabolite process such as protein and DNA synthesis depends on that of the host cell.
Most of the viruses cannot be treated by medicines because of their indistinguishable incorporation with the host cell. Many medicines cannot distinguish between the viral and host cell structures.
The steps of viral replication are as follows:-
1.Absorption and penetration of the host cells.
2.Synthesis of nonstructural enzymes such as nucleic acid polymerases.
3.Synthesis of RNA and DNA
4.Synthesis of structural proteins
5.Assembly of viral particles.
Antiviral drugs usually act by interference with any one of the above steps.

Herpes Virus Infections 

A DNA bearing virus that belongs to the family Herpesviridae.
There are five drugs used to treat these types of infections.
1.Foscarnet
2.Ganciclovir
3.Idoxuridine
4.Vidarabine
5.Acyclovir.
 As an anagram to memorize in your mind read as "For herpes, GIV acyclovir"
The following are included in the herpes family:-
1. Herpes Simplex types 1 and 2.
2.Varicella-Zoster Virus
3.Cytomegalo Virus
4.Epstein-Barr Virus.

Treatments

1.Acyclovir
It is a guanine analog.
The mechanism of action is acyclovir is monophosphorylated by an enzyme of the virus called thymidine kinase.
Later it is further phosphorylated to di and triphosphates by the host cell. The active triphosphate of the acyclovir is then combined with the viral DNA to cause premature DNA chain termination.
Uses of Acyclovir:-
1. Acyclovir is used against infections of HSV-1in the mouth, face, skin, esophagus, and brain.
2.HSV-2 infections in the genitals, rectum, skin, hands, and the meninges.
3.The varicella-Zoster virus which causes chickenpox.
It can be administered by oral, topical, and I.V. 
Acyclovir is partially metabolized to 9-carboxy methyl guanine and excreted by the kidneys. 
Side effects
Side effects depend on the route of administration.
1.I.V. injections may cause nephron and neuro toxicities
2. Oral administration may cause diarrhea and headache
3. Topical application may cause local irritation.
2.Ganciclovir 
Similar to acyclovir it is also a guanine analog.
The mechanism of action is very similar to acyclovir.
Its triphosphate inhibits viral DNA polymerase and inhibits DNA elongation.
Uses 
It is the drug of choice for treating Cytomegalovirus (CMV), retinitis, pneumonia, and esophagitis.
Route of Administration
Oral and I.V.
Kinetics
It is metabolized in the liver and excreted through the kidneys.
Side effects
1.Bone marrow suppression
2.Renal failure
3.Seizures
4.Fever
5.GI distress.
3.Idoxuridine and Trifluridine
Chemically these are thymidine analogs
Mechanism of Actions
These are converted into triphosphates by the cellular enzymes and incorporated into viral DNA and suppress its growth. 
Uses
Treatment of Herpes Simplex keratitis and vaccina virus keratitis.
Route
Only as an eye ointment or eye solution.
Trifluridine is another thymidine analog similar to idoxuridine used in ophthalmology and is more effective against herpes simplex keratitis.
Side effects
Conjunctival irritations and photophobia.
4.Vidarabine
Chemically it is an adenosine analog
Mechanism 
Very similar to the above after tri phosphorylation.
Uses
1.Treatment of HSV-1infections of
a.Encephalitis
b.Keratitis
2.Chickenpox (Varicella-Zoster)
 in HIV infected patients
This medicine is not effective against HIV-2 infections.
Route
By injection and ophthalmic 
Kinetics
Excreted by the kidneys
Side effects
1.GI effects-Anorexia and nausea
2.CNS effects-Paresthesia, and tremor
3. Inappropriate secretion of the antidiuretic hormone leads to hypokalemia
4. liver damage
5.Foscarnet
Chemically it is already a phosphoryl analog and does not need further phosphorylation 
Mechanism 
Similar to the above drugs
Route
Oral
Uses
In CMV infections in the retina
Kinetics
Excreted in urine
Side effects
1.Nephrotoxicity
2.Electrolyte imbalances like hypocalcemia and hypomagnesemia 
3.Seizures

     
 

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