Professional Documents
Culture Documents
Arenavirus
Othomyxoviruses pain, vomiting) , otitis
media, myositis, & more
o MOT: inhalation of small aerosol
frequent croup
droplets Complications of Primary viral pneumonia
o Members influenza virus infection Secondary bacterial
▪ Influenza A (pathogenic pneumonia
Myositis & cardiac
zoonotic) involvement
▪ Influenza B (pathogenic) Neurologic syndromes:
▪ Influenza C (mild disease) Guillain – Barre syndrome
Encephalopathy
o Morphology: Encephalitis
▪ Enveloped, segmented Reye syndrome
negative – sense RNA
genome Lab Diagnosis of Influenza Virus infection
▪ 2 glycoproteins,
Test Detects
hemagglutinin (HA) &
Cell culture in 1° Presence of virus;
neuraminidase (NA) monkey kidney or limited cytopathologic
▪ Membranes (M2) protein & Madin – Darby canine effects
is internally lined by the kidney cells
matrix (M1) protein Hemadsorption to Presence of
o Segmented genome promotes infected cells hemagglutinin protein
on cell surface
genetic diversity caused by Hemagglutination Presence of virus in
mutation & reassortment secretions
▪ Antigenic drift Hemagglutination Type & strain of
• Minor antigenic inhibition influenza virus or
changes specificity of antibody
Antibody inhibition of Identification of
• Accumulation of
Hemadsorption influenza type & strain
point mutations in Immunofluorescence, Influenza virus &
the gene ELISA antigens in respiratory
▪ Antigenic shift secretion or tissue
• Major antigenic culture
changes Serology: Seroepidemiology
hemagglutination,
• Result in the inhibition,
appearance of a hemadsorption
new subtype inhibition, ELISA,
• Most likely to result immunofluorescence,
complement fixation
in an epidemic
Genomics: RT-PCR Identification of
• Genetic influenza type & strain
reassortment o Tx
between human, Neuraminidase inhibitors
▪
swine, & avian (influenza A & B)
influenza viruses Oseltamivir,
• Infuenza B & C Zanamivir
viruses do not ▪ Viral uncoating inhibitors
exhibit antigenic (influenza A)
shift Amantadine,
Disorder Symptoms Rimantadine
Acute influenza infection Rapid onset of fever, Rhabdoviruses
in adults malaise, myalgia, sore o Genus
throat, & nonproductive ▪ Vesiculovirus
cough
Acute influenza infection Acute disease similar to ▪ Lyssavirus (rabies &
in children that in adults but w/ rabies – like viruses)
higher fever, GI tract
symptoms (abdominal
▪ Plant rhabdovirus group • Seizures/convulsion
(unnamed) • Major cause of
▪ Other ungrouped death: cardiorespi
rhabdoviruses of arrest
mammals, birds, fish, & o Dx
arthropods ▪ RT-PCR (preferred
o Most important pathogen: rabies method)
virus ▪ Intracytoplasmic
o MOT: transmitted in saliva & inclusions consisting of
acquired from the bite of a rabid aggregates of viral
animal nucleocapsids (Negri
o Morphology bodies)
▪ Bullet-shaped, enveloped, ▪ Animal observation:
negative-sense, single- changes in behavior for 10
stranded RNA days
o Patho
Disease Symptoms Time Viral Immunologic
▪ Replicates in the muscle at Phase (Days) Status status
Incubation Asymptomatic 60-365 Low titer, ------
the site of the bite Phase after bite virus in
muscle
▪ Length of the IP is Prodrome Fever, nausea, 2-10 Low titer, ------
phase vomiting, loss virus in
determined by the of appetite, CNS &
headache, brain
infection site to the CNS lethargy, pain
▪ IP: 1-3 months (may be as Neurologic
at site of bite
Hydrophobia, 2-7 High titer, Detectable
short as 1 week or more Phase pharyngeal
spasms,
virus in
brain &
antibody in
serum & CNS
than a year) hyperactivity,
anxiety,
other sites
o CM depression
CNS ssx: loss of
▪ Short prodromal phase coordination,
paralysis,
• 2-10 days confusion,
delirium
• Ssx: malaise, Coma Coma, HTN,
hypoventilation,
0-14 High titer,
virus in
------
anorexia, secondary
infections,
brain &
other sites
headache, Death
cardiac arrest
-------- -------- --------- -------
photophobia, N&V, o Tx
sore throat & fever ▪No proven antiviral agent
▪ Acute neurologic phase ▪Postexposure prophylaxis
• 2-7 days is the only hope for
• SSx: nervousness, preventing overt clinical
apprehension, illness in the affected
hallucinations, & person
bizarre behavior o Local tx of the wound-washed
• Inc SNS activity: immediately w/ soap & water
lacrimation, o Immunization / vaccination
pupillary dilatation, ▪ Rabies vaccine (w/in 2
& inc salivation & weeks)
perspiration ▪ Passive immunization
• Other neuro ssx: (HRIG)
• Hydrophobia (fear o Prevention: effective control of
of water) rabies in domestic & wild animals
• Aerophobia (fear through vaccination
when feeling a
breeze)
• Painful spasm of the
throat muscle
▪ Coma
o Requires phosphorylation (viral
kinases)
o MOA:
▪ Competition w/ deoxyGTP
for the viral DNA
polymerase
▪ Chain termination
following incorporation
o Route: P.O. , I.V.
o Clinical use: DOC for the ff
▪ HSV encephalitis
▪ Neonatal HSV infection
▪ Serious HSV/VZV infection
o ADR:
▪ Reversible renal toxicity
(crystalline nephropathy
interstitial nephritis)
Valacyclovir
o Chemistry: L-valyl ester of
acyclovir
o Rapidly converted to acyclovir
after oral admin. Via 1st pass
enzymatic hydrolysis in the liver
& intestine
o ADR: at high doses, confusion,
hallucinations, & seizures
Famciclovir
o Chemistry: diacetyl ester prodrug
Antivirals of 6-deoxypenciclovir
o PK: rapidly deacetylated &
oxidized by 1st pass metabolism
to penciclovir
o Spectrum: active in vitro against
HSV-1, HSV-2, VZV, EBV, & HBV
o Requires phosphorylation (viral
kinases)
o Unlike acyclovir, however,
penciclovir dose not cause chain
termination
Docosanol
o Chemistry: saturated 22 carbon
aliphatic alcohol
o MOA: inhibits fusion between the
NON RETROVIRAL host cell plasma membrane &
viral envelope
ANTIHERPES AGENTS o Dosage: 10% cream
Trifuridine
Acyclovir
o Chemistry: trifluorothymidine
o Chemistry: guanosine derivative
o MOA: intracellularly by host cell
o Spectrum: HSV-1, HSV-2, VZV
enzymes, & then competes w/
(10x more potent for HSV than
thymidine triphosphate
VZV)
Ganciclovir
o Chemistry: acyclic guanosine o C/A
analogue ▪ CMV retinitis
o Requires triphosphorylation o Route: I.V
o MOA: competitively inhibits viral o CI: px w/ renal insufficiency
DNA polymerase & causes o ADR: dose dependent proximal
termination of viral DNA tubular nephrotoxicity,
elongation ▪ Mx: prehydration using
o Spectrum: CMV normal saline
o PK: Poor oral BA
o Route: IV only ANTI INFLUENZA AGENTS
o Clinical Use: CMV retinitis in Neuraminidase Inhibitors
immunocompromised patients o Oseltamivir (PO); Zanamivir (inh);
o ADR: myelosuppression (most Peramivir (IV)
common) o Spectrum: Influenza A & B
Valganciclovir o Chemistry: sialic acid
o Chemistry: L-valyl ester prodrug o MOA: interfere w/ release of
of ganciclovir progeny influenza A & B virus
o PK: Should be taken w/ food from infected host cells, thus
o Clinical use: CMV retinitis halting the spread of infected
Foscarnet host cells
o Chemistry: phosphonoformic Adamantanes
acid; inorganic pyrophosphate o Amantadine, Rimantadine
analog o MOA: block the M2 proton ion
o MOA: inhibits herpesvirus DNA channel of the virus particle →
polymerase, RNA polymerase, & inhibit uncoating of the viral RNA
HIV reverse transcriptase o PK
o Not requiring activation by ▪ Amantadine is excreted
phosphorylation unchanged in the urine
o Route: IV only (poor oral BA) ▪ Rimantadine undergoes
o C/A: extensive metabolism
▪ End-organ CMV o C/A
▪ Ganciclovir / Acyclovir ▪ Prevention of clinical
resistant CMV illness when initiated
o ADRs before exposure
▪ Renal impairment ▪ Limit the duration of
▪ Hypo / hypercalcemia clinical illness by 1-2 days
▪ Hypo / hyperphosphatemia when administered as
▪ Hypokalemia treatment
▪ Hypomagnesemia o ADRs
o DI ▪ GIT (nausea, anorexia)
▪ Pentamidine → ▪ CNS ( nervousness, light
hypocalcemia headedness, difficulty in
▪ Zidovudine → anemia concentrating, insomnia)
Cidofovir ▪ Livedo reticularis
o Chemistry: cytosine nucleotide (amantadine – induced)
analogue
o Phosphorylation is independent ANTIHEPATITIS AGENTS
of viral enzymes
Interferon alfa
o MOA: acts both as a potent
o Ex.
inhibitor of and as an alternative
▪ Interferon alfa-2b: chronic
substrate for viral DNA
HBV & HCV infection
polymerase
▪ Interferon alfa-2a; alfacon tx of HCV
genotype 4
– 1: chronic HCV infection
Velpatasvir NS5A inhibitor 1st once-daily
o CI: single-tablet
▪ Hepatic decompensation regimen w/
▪ Autoimmune diseases pangenotypic
activity
▪ Cardiac arrhythmias Dasabuvir NS5B Fixed-dose combi
o DI: polymerase w/ ombitasvir,
▪ Didanosine: hepatic failure inhibitor paritaprevir, &
ritonavir for yx of
▪ Zidovudine: cytopenia HCV genotype 1
o ADR: Sofosbuvir NS5B Administered in
▪ Flu-like syndrome (6 hrs polymerase combi w/ several
inhibitor other anti-HCV
after admin) medications
▪ Transient elevation of Grazoprevir NS3 / 4A Combi w/ elbasvir
hepatic enzymes (8-12 protease for tx of HCV
weeks of therapy) inhibitor genotypes 1 & 4
Paritaprevir NS3 / 4A Fixed-dose combi
TX for Hepatitis B Infection protease w/ ombitasvir &
inhibitor ritonavir for tx of
Agent Uses / Properties HCV genotype 4
Adefovir dipivoxil Slower to suppress HBV Simeprevir NS3 / 4A 2nd gen protease
DNA levels; least likely to protease inhibitor
induce HBeAg inhibitor
seroconversion Ribavirin Guanosine Spectrum:
Entecavir Completely inhibits all (3) analog influenza A & B,
functions of HBV DNA parainfluenza,
polymerase transcription RSV,
of the negative strand paramyxoviruses,
Lamivudine Inhibits HBV DNA HCV, HIV-1
polymerase & HIV reverse
transcriptase
Telbivudine Induced greater rates of RETROVIRAL
virologic response than
either lamivudine or
adefovir in comparative
AGENTS
trials
Tenofovir disoproxil Antiretroviral agent, has a NRTIs
potent activity against
HBV; activity against MOA: competitive inhibiton of HIV-1
lamivudine - & enecavir – reverse transcriptase
resistant hepatitis virus Results to: premature chain
isolates
termination due to inhibition of
Tx for Hepatitis C Infections binding w/ the incoming nucleotide
Intracytoplasmic activation via
Agent Classification Uses / Properties phosphorylation by cellular enzymes
Daclatasvir NS5A inhibitor Combi w/
sofosbuvir for tx to the triphosphate form
of HCV ADRs: mitochondrial toxicity
genotypes 1, 2, & o Peripheral neuropathy
3
Elbasvir NS5A inhibitor In vitro activity o Lipoatrophy
against most o Hepatic steatosis
major HCV o Pancreatitis
genotypes
Ledipasvir NS5A inhibitor Fixed-dose combi Agent Uses / Properties
w/ sofosbuvir; not Abacavir Recommended for use of
recommended pregnancy; screening for
for tx of HCV HLA-B*5701 before
genotype 2 initiation of abacavir
infection or therapy is important
genotype 3 Didanosine (ddl) Associated w/ peripheral
Ombitasvir NS5A inhibitor Fixed-dose combi distal sensory neuropathy
w/ paritaprevir & & dose- dependent
ritonavir for the pancreatitis
Emtricitabine (FTC) Recommended for use of Nevirapine Excellent oral BA (>90%);
pregnancy; tenofovir & single dose of nevirapine
emtricitabine is (200 mg) can prevent
recommended as pre- transmission from mother
exposure prophylaxis; to newborn when
active agains HBV & HIV administered at the onset
Lamivudine (3TC) Active against HBV & HIV; of labor, then 2-mg/kg
recommended for use of dose to the neonate w/in 3
pregnancy days of delivery
Stavudine (d4T) Major toxicities: Rilpivirine Must be administered w/ a
peripheral neuropathy, meal ( preferably high fat
lactic acidosis w/ hepatic or >400 kcal); dependent
steatosis, lipodystrophy on gastric acid
Tenofovir disoproxil Activity against HIV& environment for
fumarate HBV; recommended for absorption;
use of pregnancy; serum recommended for use in
creatinine should be me pregnancy
monitored
Tenofovir alafenamide Activity against HIV & PROTEASE INHIBITORS (PI)
HBV; appears to have less
renal & bone toxicity than MOA: prevenying post-translational
tenofovir disoproxil
fumarate cleavage of the Gag-Pol polyprotein →
Zidovudine (AZT) 1st antiretroviral agent to prevent the processing of viral proteins
be approved & has been into functional conformations →
well studied;
recommended for use of production of immature, noninfectious
pregnancy; most common viral particles
AE is macrocytic anemia Pls do not need intracellular activation
& neutropenia; other AE
includes lipoatrophy, PK: All of the PIs are extensively
myopathy metabolized by
CYP3A4 (ritonavir having the most
NNRTIs pronounced inhibitory effect &
saquinavir the least)
MOA: bind directly to HIV-1 reverse
trancriptase → resulting in allosteric Agent Use / Properties
inhibition of RNA & DNA-dependent Atazanavir Recommended for use in
pregnancy; requires
polymerase acidic medium for
PK: All NNRTI agents are substrates for absorption & exhibits pH-
CYP3A4 & can act as dependent aqueous
solubility
o Inducers (Nevirapine) Darunavir Recommended for use in
o Inhibitors (Delavirdine) pregnancy; co-
o Mixed inducers & inhibitors administered w/ ritonavir
or cobistat; contains sulfa
(Efavirenz, Etravirine) moiety
AE: GIT disturbances & skin rashes Fosamprenavir Prodrug of amprenavir;
(SJS) contains sulfa moiety
Indinavir Requires acidic medium
Agent Uses / Properties for absorption; most
Delavirdine Known teratogen; skin common AE unconjugated
rashes occurs during 1-3 hyperbilirubinemia &
weeks of therapy nephrolithiasis; insulin
Efavirenz Long t ½ (40-55 hrs); resistance is noted
toxicity occurs when Lopinavir Available only in combi w/
taken w/ high fat meal low-dose ritonavir as a
(taken NPO); principal pharmacologic “booster”;
toxicity involves the CNS; recommended for use in
recommended for use in pregnancy;
pregnancy (initiated after Nelfinavir Most common AEs
8 weeks AOG) associated are diarrhea &
Etravirine Designed to be effective flatulence
against strains of HIV that Ritonavir Pharmacologic “booster”;
had developed resistance Di w/ saquinavir → QT
to 1st gen NNRTIs
prolongation, PR interval Dolutegavir Should be taken 2 hrs
prolongation before or 6 hrs after
Saquinavir Should be taken w/in 2 hrs cation-containing
after a fatty meal for antacids or laxatives,
enhanced absorption sucralfate, oral iron
Tipranavir Use for tx-experienced px supplements, oral calcium
who harbor strains supplements or buffered
resistant to other PI medications; inhibits the
agents; DI w/ ritonavir → renal organic cation
IC hemorrhage transpoter OCT, → inc
serum conc of dofetilide &
FUSION INHIBITORS metformin
Elvitegravir Requires boosting w/ an
additional drug, such as
Enfuvirtide well as certain intestinal
o HIV attachment: binding of the transport proteins or
viral envelope glycoprotein ritonavir
complex gp160 (consisting of Raltegravir Recommended for use in
pregnancy; does not
gp120 & gp41) to CD4 + cells → interact w/ CYP450
conformational changes in gp120 system; metabolized by
glucuronidation the
that enable access to the
CYP450 system but is
chemokine receptors CCR5 or metabolized by
CXCR4 → conformational glucuronidation,
particularly UGT1A1
changes in gp120, allowing
exposure to gp41 & leading to
fusion of the viral envelope w/ the OTHER ANTIVIRAL AGENTS
host cell membrane
o MOA: binds to the gp41 subunit of Agent Use / Properties
Palivizumab Prevention of RSV
the viral envelope glycoprotein → infection in high-risk
preventing fusion of the viral & infants & children
cell membrane Imiquimod Topical tx of external
genital & perianal;
o Route: SQ (the only parenteral effective for molluscum
ARV) contagiosum
o AE
▪ Injection site reaction
▪ Eosinophilia
ENTRY INHIBITORS
Maraviroc
o MOA: binds to the host protein
CCR5, one of tow chemokine
receptors necessary for entrance
of HIV into CD4+ cells
o Clinical use: approved for use in
combination w/ other ARV in
adult px infected only w/ CCR5-
tropic HIV-1
INTEGREASE INHIBITORS
MOA: integrase, a viral enzyme essential
to the replication of both HIV-1 & HIV-2
Dolutegravir, Elvitegravir, Raltegravir
ADRs: headache & GIT effects
Agent Uses / Properties