Acyclovir

Acyclovir and ganciclovir are variants of acycloguanosine and are used to treat herpes simplex virus and cytomegalovirus infections, respectively. Both agents are viricidal and act by interfering with viral polymerase activity. In the case of herpes simplex virus infection, the virally- coded thymidine kinase  monophosphorylates the acyclovir. Cellular kinases then add two more phosphates, creating a nucleotide that is accepted by the virally-coded DNA polymerase. The structural analog is incorporated into the growing DNA  chain  and  elongation  is  terminated. Ribavirin, used to treat paramyxovirus (respiratory syncytial virus) infection, works by interferring with viral messenger RNA (mRNA) capping. Amantadine, used to treat influenza A infections, blocks viral un coating. It is most effective when given before viral infection occurs. Reverse transcriptase inhibitors (e.g., azidothymidine, didioxycytocine, didioxyinosine) directly interfere with normal enzyme activity. These agents are virostatic, and virus growth occurs when the agents are removed. Interferons are induced as a result of viral infection of a cell. Products of viral nucleic acid replication activate genes that code for interferons, which directly prevent virus growth by inducing an antiviral protein within virus- infected cells.

Antiviral therapy for prophylaxis against varicella should be started 7 days after the intense exposure, using acyclovir.

Corticosteroids is the most common management for Bell’s palsy. Patients with Bell’s palsy are commonly treated with Antiviral agents in addition to prednisolone if presented early, although a definite proof of efficacy is lacking.

All of the above

Ans. is ‘a’ i.e., HSV encephalopathy is treated with acyclovir; ‘b’ i.e., Oropharyngeal involvement is common in HSV-1; ‘c’ i.e., Recurrent genital involvement is seen in HSV – 2 

.  As a general rule, HSV-1 produces lesions above the waist and HSV-2 produces lesions below the waist

– Oral facial infections                                 more common with HSV -1

– Genital infections                                       more common with HSV – 2

• Both viral subtypes can cause genital and oral-facial infections. The frequency of reactivation of infection is influenced by anatomical site and virus type :

– Genital reactivation is more common with HSV-2

– Oral-facial reactivation is more common with HSV-1

.  Drug of choice for HSV is acyclovir.

Ans. is ‘b’ i.e., It is effective against influenza

Acyclovir

It is a deoxygunosine analogue – inhibits DNA synthesis by ‑

1. Inhibits herpes virus DNA polymerase competitively.
2. Gets incorporated in viral DNA and stops lengthening of DNA strand. The terminated DNA inhibits DNA polymerase irreversibly.

• It is preferentially taken up by the virus infected cells. Because of selective generation of the active inhibitor in the virus infected cells and its greater inhibitory effect on viral DNA synthesis, acyclovir has low toxicity for host cells.
• It is active against herpes group of virus (HSV-l> HSV-2 > VZV = EBV. CMV is not inhibited).
• Acyclovir is primarily excreted unchanged in urine, both by glomerular filtration and tubular secretion. Renal impairment necessitates dose reduction.

Ans. is ‘a’ i.e., Acyclovir

Ans. is ‘a’ i.e., Thymidine kinase

Both HSV and VZV have been found to develop resistance to acyclovir during therapy the former primarily due to mutants deficient in thymidine kinase activity and the latter primarily by change in specificity of virus directed enzyme so that its affinity for acyclovir is decreased.

Ans. is ‘d’ i.e., Foscarnet

o Foscarnet is used in all Acyclovir and Gancyclovir resistent Herpes infections.

Ans is ‘c’ i.e. Acyclovir-inhibit viral DNA polymerase

o Rifampicin inhibits bacterial RNA polymerase (not DNA polymerase).

o Terbinafine acts as non-competitive inhibitor of sequalene expoxidase, an early step enzyme in ergosterol biosynthe­sis by fungus. Accumulation of squalene within fungal cells is responsible for the fungicidal activity. o Acyclovir inhibits herpes virus DNA polymerase.

o Cytarabine is phosphorylated to the corresponding nucleotide which inhibits DNA synthesis by inhibiting DNA polymerase.

A. i.e. Foscarnet

Acyclovir is drug of primary choiceQ for herpes infection and foscarnet is drug of choice for acyclovir resistance HSV, herpes zoster & varicella zoster infectionQ.

Medical Management

I. Steroid therapy:

• Oral prednisolone has been used extensively to treat patients with Bells palsy.
• Proof of efficacy is however controversial.
• Steroids are considered useful because they have an anti inflammatory response.
• Because the cost of therapy is less and it has low risk of side effects, predinosolone is commonly started at the initial visit
• Initiation of therapy during the first 24 hours of symptom confers a higher likelihood of recovery

II. Antiviral therapy:

• It represents a newer adjunct in treating acute facial palsy of viral origin (Both Bells palsy and Ramsay hunt syndrome)
• Oral acyclovir is the DOC
• Some studies have shown that patients who receive prednisolone plus oral acyclovir have a higher recovery rate and reduced rates of synkinesis in comparison to those who receive prednisolone alone.
• Based on above evidence most surgeons advocate combination of steroids and antiviral drugs.

The usual recommended regime is predisolone 1mg/kg/day for five days followed by a ten day taper and oral acyclovir (200-400 mg 5 times daily) for ten days.

Physical Management

Includes :

Electrical stimulation: It is done to maintain membrane conductivity and reduce muscle atrophy

• It is generally used in patients left with partial defects

Eye care:The cornea is vulnerable to drying and foreign body irritation in acute facial palsy due to orbicularis oculi dysfunction. So measures conferring corneal protection are recommended such as

• Artificial tears drops at daytime
• Ocular ointment at night
• Use of sunglasses etc

In long standing cases: Reducing the area of exposed cornea by implanting a gold weight in the upper lid (tarsorapphy) is done.

Surgical Management

Nerve decompression

• Axonal ischemia can be reduced by the decompression of nerve segments presumed to be inflammed and entrapped.
• Decompression of the facial nerve is done in cases who have a poor prognosis for complete recovery with medical treatment alone.

Answer is A (Acyclovir):

Ans. When started immediately after the onset of rash

Ans. D i.e. All of the above

Ans. is ‘a’ i.e., Acyclovir

Ans. is ‘a’ i.e., Acyclovir

Drugs Causing Oliguria

• Drugs causing decreased renal perfusion – diuretics.
• Drugs causing nephrotoxicity – aminoglycosides and chemotherapeutic agents.
• Urine retention – adrenergic and anticholinergic drugs.
• Urinary obstruction associated with precipitation of urinary crystals – sulfonamides and acyclovir.