Treatment of Viral PN Flashcards
Factors suggesting BACTERIAL cause of PN
**Age: **Adults
**History of illness: **Rapid onset
**Clinical Profile: **High fever, tachypnea
**Total WBC count: **> 15 X 109 cells per L
**[CRP] in serum: **> 60 mg/L
**[Pro-calcitonin]: **> 0.5 ug/L
**CXR: **Lobar alvelar infiltrates
**Response to ABX: **Rapid
Factors suggesting VIRAL cause of PN
- **Age: **<5
- **Epidemic situation: **ongoing viral epidemic
- **History of illness: **slow onset
- **Clinical profile: **rhinitis, wheezing
- **Total WBC count: **<10 X 109 cells per L
- **[CRP] in serum: **<20 mg/L
- **[Pro-calcitonin] in serum: **<0.1 ug/L
- **CXR findings: **Sole interstital infiltrates, bilaterally
- **Response to ABX: **Slow or non-response
Describe the influenza virus replication process
- Virus protein hemagglutinin binds to sialylated glycoprotein receptors on host-cell surface, and the virus enters the cell by receptor-mediated endocytosis
- Internalization and endosomal acidification permit fusion of the host and viral membranes by altering the conformation of hemagglutinin
- Viral ribonucleotides (RNPs) are released into cytoplasm
- In the nucleus, viral RNAs are transcribed into mRNA and replicted by viral RNA-dependent RNa polymerase
- Newly synthesized viral RNPs exported to cytoplasm, and after assembly, mature virions bud from cell surface
Describe Influenza Viral Entry/Uncoating
- Virus enters via receptor-mediated endocytosis and contained within an early endosome
- Early endosome contains H+ ATPase that acidifies endosome
- Low-pH dependetn conformational change in viral envelope hemagglutinin (HA) protein triggers fusion of viral membrane with endosomal membrane.
- Protons from low-pH endosome must enter the virus through M2, a pH gated proton channel in the viral envelope
- Dissociation of matrix protein from influenza virus ribonucleoprotein (RNP), releasing RNP into cytosol.
What is the treatment of Influenza A and B viruses?
Oseltamivir (PO)
Zanamivir (Inhalation)
These drugs target neuraminidase, which is required for release of progeny. They are selective sialic acid analogue inhibitors that produce conformational changes in the active site of Influenza A and B neuraminidases. Use of these drugs leads to viral aggregation at the cell surface and reduced virus spread within the respiratory tract.
Prevention: vaccines (inactivated; live)
What are other treatments for Influenza A virus?
Amantadine (PO) or Rimantadine (PO)
Block action of viral M2 ion channel protein during uncoating of virus. Thus, they inhibit acidification of the interior of the virion, dissociation of matrix protein, and uncoating.
What is the treatment for RSV?
Ribavirin (inhalation, IV)
Prevention: Palivizumab (IM)
What is the treatment of Adenovirus?
Cidofovir (IV)
Prevention: vaccine for types 4 and 7
What is the treatment of Rhinovirus?
NO TREATMENT
Prevention: alfa interferon (intranasal), Ribavirin (off-label)
What is the treatment for Enteroviruses?
NO TREATMENT OR PREVENTION METHODS
What is the treatment for Human metapneumovirus
Ribavirin (IV)
What is the treatment for Hantavirus?
Ribavirin (IV)
What is the treatment for Varicella-zoster virus?
Acyclovir (IV)
Valacyclovir (PO)
Prevention: vaccine available
Acyclovir
MOA: inhibition of viral DNA synthesis (DNA polymerase inhibition)
- Nucleoside analogue that targets nucleic acid synthesis.
- Require metabolic activation, usually to a triphosphate form, before incorporation of the deoxyribonucleoside triphosphate into the growing DNA chain. Their incorporation leads to termination of chain elongation.
Metabolism:
- viral cells transform acyclovir to its active triphosphate form.
- systemic elimination unchanged by glomerular filtraiton adn tubular secretion
**Toxicity: **
- headache, nausea, elevated hepatic enzymes, nasopharyngitis, neutropenia
- maintain hydration to prevent renal precipitation
- use catuiously in renal impairment or with reno-toxic drugs
Amantadine
**MOA: **inhibition of viral entry or uncoating
**Metabolism: **systemic elimination unchanged by glomerular filtraiton and tubular secretion
**Toxicity: **
- multiple adverse effects inclduign neurologic, nausea, and orthostatic hypotension
- contraindicated in narrow angle glaucoma and with breastfeeding