antiviral treatments Flashcards
What are many viral infections?
Many viral infections are actually self limiting
Therefore, not worthwhile creating specific antiviral tx for them
Hence symptomatic or supportive tx may be sufficient
What are some viral causes of the common cold?
When are these more common infections important?
Rhinovirus (50%)
Coronavirus (15%)
influenza (15%)
Parainfluenza (5%)
RSV (5%)
human metapneumovirus (hMPV)
Adenovirus
These are important in the immunosupressed patient ( haematological cancers, bone marrow transplants). Diseases can be significant then and gaining correct diagnosis useful despite limited tx, also helps prevent transmission to other immunosupressed pts.
What are common self resolving viral infections?
Common cold: rhinovirus, parainfluenza, human metapneumovirus (hMOV), adenovirus
HSV (cold sore) , VSV (chickenpox), EBV, CMV infection
Hepatitis A virus and hepatitis E infection
How many members of the herpes viral family are there?
What does each member commonly cause?
8 members of the herpes virus family.
- Herpes viradae 1 : HSV1 –> cold sores
- Herpes viradae 2: HSV -2 –> common cause of genital ulcers
- Herpes viradae 3: VSV –> chicken pox and shingles (over 75 yrs vaccination given to prevent shingles, highly painful which is often diagnostic.)
- herpes viradae 4: EBV –> glandular fever
- Herpes viradae 5: CMV –> cytomegalovirus, causes blueberry muffin lesions in children, not self limiting
- Herpes viradae 6: HHV 6 –> causes roseola infantum, a disease of childhood that affects nearly the entire population and (2) a disease of reactivation in profoundly immunosuppressed individuals.
- Herpes viradae 7: HHV 7 –>Human herpesvirus 7 (HHV-7), like HHV-6, appears to be principally acquired in infancy and childhood and able to cause roseola. HHV-7 has been associated with febrile seizures and has been implicated as a possible cause of encephalitis.
- Herpes viradae 8: HHV 8 –> kaposi’s sarcoma associated virus, Kaposi’s sarcoma (KS) is a type of cancer that can form masses in the skin, lymph nodes, or other organs, also associated w castlemans disease. Castleman disease is a rare disorder that involves an overgrowth of cells in your body’s lymph nodes
What is the molluscum virus?
- molluscum contagioscum is a is a skin infection caused by the molluscum contagiosum virus
- it is common and generally harmless, often affecting children, and those with excezma
- Can affect those that are immunosuppressed
- looks like small pox, usually self resolving –> often doesnt require treatment but treatment can help clear it sooner
- Range of topical tx –> salicyclic acid and potassium hydroxide (irritates the skin inducing immune response to clear virus), frozen w liquid nitrogen, or scraped off after local anaesthetic
What are the physical tx for HPV/ molluscum viral infection?
- Physical tx include caustic chemicals, heat and cold tx
- creams and topical chemicals (warticon)
- cryotherapy
- surgical removal
- Often used for localised HPV infection (warts)
- but these dont only burn away the infected tissue
- most viral infections are overcome by the immune system
- using physical tx helps expose HPV to the immune sx
- improves immune response and prevents recurrence
- universal HPV vaccination should reduce number of cases in the future
How can viral HBV become chronic?
how is HCV dominantly transmitted?
how is HBV dominantly transmitted?
Where are the distributions of these viruses?
viral hepatitis from HBV cannot be fought by the immune system if caught at a young age, more likely to develop into a chronic infection if caught early (pre age of 6 yrs). If caught during adulthood, less likely infections become chronic, most self limiting.
HCV dominantly transmitted sexually or through IV drug use.
HBV very contagious sexually (33% change if exposed through sexual contact as opposed to HCV 3% and HIV 0.3%).
Hepatitis B the most common viral disease because of chronic form, distribution across SE asia, China and middle east throught vertical transmission.
Hep C sporadic across the world but common in IV drug users.
What can untreated / chronic HBV/ HCV lead to the development of?
both can lead to liver cirrhosis and hepatocellular carcinoma. Chronic infection of the liver also acts as a resevoir of infection that can be transmitted on.
Who is at risk of chronic hep B infection?
- likelihood that infection becomes chronic depends on age at which individual becomes infected
- Children less than 6 yrs of age are the most likely to develop chronic infections
In infants and children:
- 80–90% of infants infected during the first year of life develop chronic infections; and
- 30–50% of children infected before the age of 6 years develop chronic infections.
In adults:
- less than 5% of otherwise healthy persons who are infected as adults will develop chronic infections; and
- 20–30% of adults who are chronically infected will develop cirrhosis and/or liver cancer.
What it the tx for acute hepatitis B?
what is the tx for chronic hepatitis B?
- no specific tx for acute Hep B, suppress only to reduce the risk of hepatocellular carcinoma.
- care aimed at maintaining comfort, adequate nutrition, replacement of fluids lost from vomiting/ diarrhoea
- avod unnecessary medication
- Chronic hepatitis B can be tx with oral antiviral agents –> slows progression of cirrhoses and reduce incidence of liver cancer, improves long term survival
- tenofovir or entecavir suppress replication of the virus
- (Tenofovir and entecavir belongs to a class of antiretroviral drugs known as nucleotide analog reverse transcriptase inhibitors (NtRTIs), which block reverse transcriptase, an enzyme necessary for viral production in HIV-infected individuals.)
- Chronic HBV infection –> pEF IFN-a for 48 weeks +/- other drugs
What is the tx of acute hepatitis C?
What is the tx of chronic hepatitis C?
new infection with HCV does not always require tx, immune response in some will clear the infection
if HCV becomes chronic tx is necessary –> with pan genotypic (acts on all genotypes of hep C virus with different efficacy) direct acting antivirals (DAA’s). tx normally 12-24 weeks depending on presence of cirrhosis.
From lecture: Use pegylated interferon based treatment:
- IFN-a helps clear chronic infection, addition of PEG molecules improves drug efficacy
- pegylated IFN-a now used for tx of chronic HBV and HCV
- For chronic HCV infection –> PEG IFN a for 48 weeks +/- other drugs
what are the SE of PEG IFN-a tx?
Flu like sx, fever, lethargy and depression due to night sweats
what is the ebola virus?
What is the tx for ebola virus?
- Ebola - viral haemorrhagic fever
- zoonotic virus, causes severe pathology in humans –> sudden onset of fever, headache joint and muscle pain, sore throat, intense weakness, significant vomiting and diarrhoea.
- Some develop rash, red eyes, hiccups, impaired kidney/ liver function, internal and external bleeding
- fatal in 40-90% of cases
- highly transmissible in all body fluids, first transmission through contact with secretions from infected animal
- Tx: monoclonal antibodies
- REGN-EB3
- mAb114
- vaccine VSV-EBOV now supersedes tx and may have a place in post exposure prophylaxis too.
Three key signs of ramsay hunt syndrome?
- vesicular rash on external ear (50% population)
- lower motor neurone paralysis of facial nerve
- loss of tast sensation over anterior 2/3 of tongue
- small white vesicles on the inside of the mouth, unilaterally on diseased side.
How can you treat HSV (1/2) and VZV infection (HSV 3)?
HSV and VZV tx with aciclovir and related drugs can be used for both tx and prophylaxis.
Aciclovir works less and less well as you go down the herpes viral family group.
What is the MOA of aciclovir?
- Aciclovir is converted to its triphosophate form, acyclovir triphosphate (ACV-TP) –> competitively inhibits viral DNA polymerase
- ACVTP incorporates into and terminates the growing viral DNA chain and inactivates the viral DNA polymerase
Why is drug therapy better at targeting HCV infection than HBV?
What are some of the approaches to tx?
- HCV replicates within the cell cytoplasm, therefore drug therapy is better at eliminating it as it hasn’t integrated within the genome within the nucleus
- pan genomic direct acting antivirals:
- inhibit viral entry
- inhibit cleavage of viral polyprotein (protease inbibitors, oligonucleotides and siRNA)
- replication inhibitors e.g. polymerase inhibitor)
- inhibit virion maturation and release (alpha glycosidase inhibitors)
What is the tx for rabies?
HRIG = human rabies immunoglobulin
