antivirals Flashcards
antivirals
-Viruses use host cell’s metabolic pathways for reproduction -> limits MOA for antiviral drug action
-Antibacterials & Antifungals have little or no effect on viruses
-Most antivirals are antimetabolites of endogenous nucleosides and prevent replication of viral nucleic acid
-Some antivirals inhibit the uncoating of viral nucleic acid or inhibit post translation of viral proteins
enterovirus- D68
-one of more than 100 non-polio enteroviruses
-Symptoms:
-Mild - fever, runny nose, sneezing, cough, and body and muscle aches
-Severe - wheezing and difficulty breathing
-Spreads via respiratory secretions
-Prevention – wash hands, cover sneeze & cough
-Surge – Summer & Fall
-tx - supportive
ebola
-Previously known as Ebola hemorrhagic fever
-can cause disease in humans and nonhuman primates
-spread through direct contact
-broken skin or mucous membranes in, for example, the eyes, nose, or mouth
-Wash with soap & water or use alcohol based cleanser
-Treatment
-No FDA-approved vaccine or medicine (e.g., antiviral drug) is available for Ebola
-Early supportive care
COVID-19
-SARS-Cov-2:
-Coronavirus
-Serious Acute Respiratory Syndrome
-Viral respiratory disease
COVID-19 vaccines
-mRNA:
-Comirnaty® - Pfizer/BioNTech
-Spikevax® - Moderna
-Adjuvanted: Novavax
COVID-19 tx
-Inpatient
-Remdesivir (Veklury) – Antiviral IV tx
-Tocilizumab (Actemra) - IL-6 inhibitor IV tx
-Dexamethasone – IV/PO IN COMBO ^
-Outpatient
-Molnupiravir (Lagevrio®) – Antiviral PO - EUA
-Nirmatrelvir and Ritonavir (Paxlovid®) - Antiviral PO - EUA
-< 5 days of being sick
-many DDIs
not recommended or authorized tx for COVID
Ivermectin
Doxycycline
Hydroxychloroquine
Azithromyzin
Colchicine
COVID-19 prevention
-pre-exposure prophylaxis
-pemivibart- antiviral- EUA -> single IV infusion
herpes virus infections
-Herpes viruses are DNA viruses
-Herpes Simplex Virus (HSV):
-Herpes genitalis (HSV II)
-Herpes labialis (cold sores) (HSV I)
-Herpetic keratoconjunctivitis
-Herpes encephalitis
-Varicella-zoster virus (VZV)
-Chicken pox (varicella)
-Shingles (herpes zoster)
-Cytomegalovirus (CMV)*
-CMV retinitis
-CMV esophagitis
-CMV colitis
-* most CMV diseases occur in immunocompromised pts*
drugs for herpes virus
-All are nucleoside analogs, except foscarnet & docosanol
-Most contain purine/pyrimidine base
-Prodrugs that are converted to active drug usually in infected host cell -> selective toxicity & prevention of synthesis of viral RNA
-Viral resistance develops with all, varies with drug and viral pathogen
-acyclovir
-valacyclovir
-famciclovir
-penciclovir
-docosanol
shingriz SC injection
-vidarabine
-trifluridine
-ganciclovir
-valganciclovir
-cidofovir
-foscarnet
-ganciclovir
-fomiversin
HSV and VZV: acyclovir
-PO, IV, topical
-inhibit viral replication, does not cure-only reduces the pain, severity & symptoms of the outbreak, shortens its duration and may prevent the overall number of recurrences.
-ADRs - itching, hives, nephrotoxic - elevated BUN & creatinine, N,V,D, headache, paresthesias
-PO form – low bioavailability (5 times/day)- limiting
-IV for serious or systemic infections
-Topical – used for genitalis
-Available as oral suspension for chickenpox in kids
HSV and VZV: valacyclovir
-PO
-valtrex
-ADRs- less than acyclovir, N/V, headaches
-increase bioavailability- less frequent dosing
-valacyclovir and famciclovir are more effective than acyclovir for shingles
HSV and VZV: famciclovir
-PO
-ADRs: headache, fatigue, diarrhea
-increase bioavailability – less frequent dosing
-valacyclovir and famciclovir are more effective than acyclovir for shingles
HSV and VZV: penciclovir
-topical
-Active metabolite of famciclovir
-Topical for herpes labialis
-Potentially used for Epstein-Barr virus
-ADRs – mild erythema, headache
HSV and VZV: docosanol
-First OTC topical for herpes labialis
-Limited info available
-ADRs – local irritation, headache
-NOT a nucleoside analog
varicella-zoster vaccine: shingrix SC injection
-Indications: Prevention of herpes zoster (shingles) in pts > 50 years old and in adults aged 18 years and older who are or will be at increased risk of HZ due to immunodeficiency or immunosuppression (not on test)
-Zoster Vaccine Recombinant, Adjuvanted
-More potent than chickenpox vaccine
-Can reduce shingles cases by 50% and patients who get shingles will get milder cases. Also, in pts who get shingles - 1/3 less likely to develop postherpetic neuralgia
TX of HSV (ocular infection)
-vidarabine -(ophth oint) – blocks vision, use HS (at bed)
-trifluridine -(ophth sol.)
-both used for keratoconjunctivitis and recurrent epithelial keratitis due to HSV I and II.
-ADRs: burning, irritation, lacrimation
CMV: ganciclovir
-PO, IV, implant
-Used for TREATMENT of CMV retinitis in immunocompromised pts and PREVENTION of CMV diseases in HIV and transplant pts.
-PO form has low bioavailability (use for long term suppression of CMV)
-ADRs: !bone marrow suppression! (BMS)- dose limiting, H/A, confusion, !retinal detachment!, liver and renal dysfunction, rash, fever, gi effects
-Mutagenic, long term carcinogenic effects
CMV: valganciclovir
-PO
-Same indication as ganciclovir, prodrug – can give less frequently
CMV: cidofovir
-IV
-Same indications as ganciclovir
-Reserved use for resistant viruses
-Higher incidence of more serious adverse effects (nephrotoxicity, neutropenia, metabolic acidosis)
CMV: foscarnet
-IV
-NOT nucleoside
-Tx of CMV retinitis in immunocompromised pts when ganciclovir alone has failed!!
-Often given in combo with ganciclovir to reduce toxicity
-IV hydration before to prevent renal toxicity
-Also used for acyclovir resistant HSV infx and shingles
-ADRs: fever, H/A, renal impairment, !acute renal failure, N,V,D, !hematologic deficiencies, !seizures, !cardiac arrhythmias, !heart failure and !pancreatitis
ocular antivirals for CMV
-Ganciclovir implant – CMV retinitis
-Fomiversin inj – CMV retinitis
influenza (dont need to know)
-U.S. Epidemiology:
-Annual Infections: 25-50 million
-Annual Hospitalizations: 226,000
-Annual Mortality: 19,000 -36,000
-Types A & B
-Type A - moderate/severe illness- from 0 to 100
-Type B - milder - primarily affects children
-Clinical presentation: Abrupt onset of fever, malaise, sore throat and non-productive cough. Disease peaks b/w December & March
-Complications: Pneumonia, myocarditis, Reyes syndrome
flu vaccine guidlines
-Vaccination now recommended for ALL persons > 6 months old
-All children 6 months – 8 years old being vaccinated for first time should receive 2 doses (4 weeks apart) - DONT NEED TO KNOW THIS PART
flu vaccination during vaccine shortage DONT NEED TO KNOW
-Children aged 6 months through 4 years (59 months);
-People aged 50 years and older;*
-People with chronic pulmonary (including asthma), cardiovascular (except hypertension), renal, hepatic, neurologic, hematologic, or metabolic disorders (including diabetes mellitus);
-People who are immunosuppressed (including immunosuppression caused by medications or by Human Immunodeficiency Virus);
-Women who are or will be pregnant during the influenza season and women up to two weeks after delivery;
-People who are aged 6 months through 18 years and receiving long-term aspirin therapy and who therefore might be at risk for experiencing Reye syndrome after influenza virus infection;
-People who are residents of nursing homes and other chronic-care facilities;
-American Indians/Alaska Natives;
-People with extreme obesity (body-mass index [BMI] is 40 or greater);
-Health care personnel;
-Household contacts and caregivers of children younger than 5 years and adults aged 50 years and older, with particular emphasis on vaccinating contacts of children aged younger than 6 months; and
-Household contacts and caregivers of people with medical conditions that put them at higher risk for severe complications from influenza
influenza virus vaccine inactivated (TIV)
-IM
-Provide active immunity to influenza virus strains in the vaccine
-New vaccine formulated each year, standardized by U.S. Public Health Service
-This years vaccine contains an H1N1 strain
-Do not use in pts allergic to eggs
-All flu vaccines contain small amounts of egg protein
-Pts who can tolerate eggs in baked goods can usually tolerate vaccine
-Try using vaccine w/ less egg (Agriflu or Fluarix)
-ADRs: Local reactions, fever/malaise, allergic reactions.
-THE INACTIVATED FLU VACCINE DOES NOT CAUSE THE FLU !!!
flumist- LIVE
-intranasal influenza vaccine
-Live attenuated vaccine (LAIV) -> You become a flu carrier
-About as effective as IM vaccine
-2010 guidelines: can be used in healthy patients aged 2-49 years old.
-Not approved in pts > 50 y.o or pts with chronic illness
-ADRs: runny nose, nasal congestion, fever, cough, vomiting, sore throat
-Very expensive
influenza A tx
-MOA: inhibits the replication of the Influenza A virus ONLY!! by blocking the viral membrane matrix protein (M2)
-Has been used for prophylaxis if vaccine cannot be tolerated or for treatment. Not recommended per 2009 guidelines.
-Has been used to reduce the symptoms of infection and shortens the course of disease. Not recommended per 2009 guidelines.
-ADRs: GI effects, CNS side effects:
-Examples:
-!amantadine PO
-!rimantadine PO- has lower incidence of ADRs and no dose adjustment in renal dysfunction
-good drugs but not first choice
influenza A and B
-Indications: Tx and Prevention of Seasonal Influenza and HIN1
-MOA: blocks neuraminidase, an enzyme needed for viral release from infected cell.
-ADRs -N, V, D, abdominal pain, dizziness, headache
-Effectiveness:
-Decreases the onset of symptoms and shortens duration of illness only if taken within 24 - 48 hrs of symptom onset
-Examples:
-oseltamivir (Tamiflu) (PO) (for pts >1 y.o)
-zanamivir (INH) (for pts> 7 y.o.)- Tablet that must be crushed into a powder
-first choice, tx can be worse than the flu
-good for if a whole family got sick
RSV: ribavirin
-VIRAZOLE
-inhalation
-Indications: aerosol for severe lower respiratory infections due to Respiratory Syncytial Virus (RSV) in children. It reduces duration of disease, allows children to be removed from ventilator sooner, improves arterial oxygenation
-MOA: Prevents mRNA capping and blocks RNA-dependent polymerase
-ADRs serious pulmonary and cardiovascular effects – (apnea, pneumothorax, worsening of resp status and cardiac arrest), conjunctivitis, rash
RSV: palivizumab
-SYNAGIS
-IM
-Recombinant drug – monoclonal antibody
-New drug for PREVENTION of serious lower respiratory tract infections caused by RSV in infants and children! < 2 y.o.
-ADRs – nervousness, fever, fungal dermatitis, eczema, N/V/D, anemia, otitis media, cough, wheezing
interferons
-Recombinant DNA technology drug with immunomodulating and antiproliferative effects
-Forms – alfa 2a, alfa 2b, pegylated alfa 2a
-Can be used in Tx of hepatitis B & C (all forms)
-Can also be used in Tx of certain cancers (all forms) and in Tx of anogenital warts (alfa 2a) and
-ADRs: hematological toxicity, cardiac arrhythmias, changes in BP, CNS dysfunction, gi distress, chills, fatigue, H/A, myalgia, alopecia
hepatitis: ribaviran
-PO
-Given in combo with interferon alpha 2b for the treatment of chronic hepatitis C in pts with compensated liver disease
-ADRs: CNS side effects (dizziness, H/A, fatigue), alopecia, rash, pruritis, gi effects, bone marrow suppression (all observed when given w/ interferon alfa 2b)
-Non FDA Tx – various viruses including west nile, hemorrhagic fever viruses, etc.
hepatitis B: nucleotides
-some may also be used for HIV infection
-Lamivudine (Epivir)
-Adefovir (Hepsera)
-Entecavir (Baraclude)
-Telbivudine: (Tyzeka)
hepatitis B tx
DONT NEED TO KNOW
-drugs we use for B overlap with C
HPV IM vaccine
-gardasil
-Indicated to prevent diseases caused by HPV virus types 6,11,16 and 18 (cervical cancer & genital warts) in women b/w 9-26 years old.
-Given in 3 doses at 0, 2 and 6 months.
-ADRs – local reactions, fever
-New issues regarding safety of this vaccine reported by VAERS
rotavirus vaccine
-RotaTeq
-LIVE oral vaccine for rotavirus
-Rotavirus most common cause of severe diarrhea and vomiting in young children
-Given to infants at age 2, 4 and 6 months
-Have been reports of intrasussception with this vaccine
avian flu vaccine (H5N1)
-Not available commercially
-Being reserved for distribution in the event of an outbreak
-MAY provide early limited protection in the event of a pandemic until a vaccine is developed & produced against the specific pandemic strain of the virus
A 34 year-old female with no significant past medical history presents to your office with cold sores on her lips. She asks for a recommendation for a topical OTC product. Which of the following would you recommend for this patient?
acyclovir
ganciclovir
penciclovir
docosanol*******
