DDM 7 Exam 3 Kulkarni/Heyliger
Most NRTIs excreted unchanged in urine except?
AZT- Glucuronidation Abacavir- Alcohol Dehydrogenase
NRTI Drug interactions
Alcohol and Abacavir: EtOH ↑ Abacavir levels AZT and drugs which cause bone marrow suppression Didanosine, Stavudine, Zalcitabine w/ (vincristine, cisplatin, isoniazid= neurotox Didanosine, Stavudine, Zalcitabine w/ alcohol, pentamidine, valproic acid = pancreatox
Emtricitabine FTC
More potent than 3TC, Emtricitabine is administered once daily Indicated for Treatment Experience HIV patients unlabeled HBV Black box; exacerbate Hep B in pt with d/c
Adjunct Dronabinol, THC
-synthetic oral prepation preparation of delta9THC
viral load log scale
1 log change= 10 fold change viral load changes less than 1 are not clinically significant
HIV life cycle 7 steps
1.) hiv binds to CD4 2.) fuses with lipid outer layer 3.) HIV gains entry into CD4 cell 4.) removes outer coat (capsid), exposes RNA, releases reverse transcriptase, converts RNA to DNA 5.) HIV DNA enters nucleus of CD4 for DNA replication 6.) HIV protein and RNA assemble into immature HIV 7.) HIV virus buds out of host cell, proteases converts immature HIV to infectious HIV
Drugs which cause myelosuppression
1.Ganciclovir 2. Acyclovir 3. Steroids 4. Anti-cancer medications 5. Pentamidine
RNA Test
10 days after infection peak 1-2 wks; 200,000 copies qualitative screening APTIMA assay detection 98% for 30 copies 82.6 for 10 42.5 for 3 quantitative diagnostic pcr; high sensitivity lower limit of detection cost & technical complexity viral load; proportional to risk of transmission
Influenza D
2016 cattle
Fluzone High-Dose Vaccine
3 component , 4 times the antigen of standard dose prevention of influenza disease caused by influenza A subtype viruses and type B virus in patient 65 or older
tertiary syphilis
3-15 years after primary infection non contagious but highly destructive gummatous syphilis (gummas soft tumor) neurosyphilis (CNS syphilitic meningitis) cardiovascular syphylis (syplaortitis) high mortality
secondary syphilis
4-10 weeks after primary infection spread over skin, mucous membrane lymph reddish non itchy rash on trunk on palm and soles lesions harbor bacteria (bacteremia) symptoms resolve within 6 weeks or come and go for a year
Goal of ART
: HIV RNA below limit of detection (ie, <20-75 copies/mL, depending on assay)
NRTI toxicity rank
: ddC/ddI/d4T > 3TC > ZDV > ABC for effects on mitochondrial DNA polymerase gamma1 Tenofovir has low affinity for mitochondrial polymerase gamma2, causes hyperlactatemia
What viruses will the 2020-2021 flu vaccines protect against?
A/Guangdong-Maonan/SWL1536/2019 (H1N1)pdm09-like virus A/Hong Kong/2671/2019 (H3N2)-like virus B/Washington/02/2019 (B/Victoria lineage)-like virus B/Phuket/3073/2013-like (B/Yamagata lineage)
COVID structure
ACE 2, transmembrane protease serine 2 TMPRSS2 ACE2 opposses ACE acctivity ACE2 is elevated in patients with comorbidities (HTN, CKD, CHF, T1@T2DM)
INSTI advantages and disadvantages
ADVANTAGES fewer adverse events than with efv or pi DISADVANTAGES RAL,EV lower genetic barrier to resistance COBI many drug drug interactions, worsen renal impairment myopathy, rhabdomyolysis, skin rxn
PI Advantages and disadvantages
ADVANTAGES higher genetic barrier to resistance DISADVANTAGES gi intolerance metabolic complications
NNRTI Advantages and disadvantages
ADVANTAGES less metabolic toxicity, single pill DISADVANTAGES low genetic barrier to resistance, high rates of resistance in ART naive patients
DUAL NRTI pair advantages and disadvantages
ADVANTAGES • Established backbone of combination therapy • Minimal drug interactions DISADVANTAGES • Lactic acidosis and hepatic steatosis reported with most NRTIs (rare) low geentic barries to resistance
Osteomalacia and TDF
AVOID TDF use ABC or TAF only use ABC if HLAB5701 Negative
what causes nail,palms, soles of feet to be discolored
AZT
NRTI protoype
AZT or Zidovudine
Maraviroc CI
Asians(inc drug levels) Patients with renal failure, dialysis CYPs PgP inhibitors: tacrolimus, quiniine, propafenone
Hepatitis B
Associated with 100-fold increase in risk for development of hepatocellular cancer (HCC)
Special Properties of PI
Atazanavir; once daily Tipranavir: Effective in Treatment (PI) experienced patients, Black box warning: fatal and non-fatal intracranial hemorrhage Darunavir: Indicated for the of experienced patients who are resistant to other Protease inhibitors(cause SJS)
Treat Pi induces osteopenia/osteoporosis
BISPHOSPHONATES alendronate
Pfizer COVID mRNA
BNT162b2 mrna vaccine .3 ml 2 doses 21 days apart store in ultra cold freezer refrigerate between 36-46 for 5 days
Influenza polymerase inhibitors
Baloxavir
HIV Drug Efficacy
Based on Viral Load Viral Load is determined by the RT-PCR (reverse transcriptase polymerase chain reaction)
Non-nucleoside Reverse Transcriptase Inhibitors indications
Bind noncompetitively (on an allosteric site) to reverse transcriptase Active only against HIV-1 HIV becomes resistant more quickly than any other drug class
Thalidomide monitoring parameters
CBC with diff platlet count pregnancy test
NNRTI Drug interactions
CCB BZD Protease inhibitors St john's wort Rifabutin Rifampin Anticonvulsants
Adequate Cd4 response:
CD4 increase 50-150 cells/µL per year
Amantadine ADE
CNS: neurotoxicity, cardiotoxocity, coma , seizure arrythmia N/V Anxiety
NNRTI ADE
CNS; drowsiness, hallucinations, depression, suicidal ideations rash: steven johnson's (nevirapine) fatal hypersensitivity elevated liver enzymes (Nevir>Efavir>Delavir)
CD4 monitoring
Check at baseline (x2) and at least every 3-6 months check immediatley before initiatin ART ◼ Every 3-6 months during first 2 years of ART or if CD4 <300 cells/µL More frequent testing if on medications that may lower CD4 count, or if clinical decline after 2 years on ART
Nucleoside Reverse Transcriptase Inhibitors
Competitively inhibit reverse transcriptase Causes premature termination of DNA synthesis when incorporated into the nascent DNA strand structurally simmilar to thymidine
COVID Treatment
Dexamethasone & Remdesivir
NRTI Features
Didanosine ◼ given on an empty stomach because acid labile ◼ avoid in PKU pts Once-A- Day Dosing (lower pill burden) ◼ Emtricitabine ◼ Tenofovir Lamivudine: ◼ indicated for both HIV and HBV Tenofovir: ◼ used in AZT resistant patients
No evidence that ________ is effective at OTC concentration for shortening duration or preventing the flu or COVID
Echinacea
NNRTI
Efavirenz (EFV) Delavirdine (DLV) Doravirine (DOR) Etravirine (ETR) Nevirapine (NVP) Rilpivirine (RPV)
FUSION/ENTRY INHIBITORS
Enfuvirtide (Fuzeon) Maraviroc (Selzentry)
PrEP (pre-exposure prophylaxis)
For people at very high risk for HIV take HIV medicines daily to lower their chances of getting infected (Tenofovir and Emtricitabine), sold under the name Truvada recommended for: gay or bisexual man who have anal sex heterosexual man or woman who dont regularly use condoms women considering getting pregnant with HIV + partners
Post attachment inhibitors
Fosetemsavir Ibalizumab-uiyk
Zanamivir ADE
Gi upset Headache Dizziness NO drug drug inteaction
Treponema
Gr- spirochetes unable to synthesize fatty acids, nucleotides transport protein present stealth T. pallidum human pathogen syphillis
Neisseria
Gram - catalase positive N gonorrhoeae & N meningititis N gonorrhoeae = gonococcus N meningititis=meningococcus
quadrivalent vaccine components
H1N1 H3N2 & B strain Victoria & Yamigata; standard dose
Trivalent influenza components
H1N1 H3N2 & B victoria high dose; higher antigen higher immune response in >65yr
Influenza A
H1N1 spanish flu (pneumonia) pork doesnt cause, 1918 2009 flu H5N1 current pandemic threat, high mutation
Egg based influenza vaccines
HA NA injected into hen's eggs and replicated ; fluid harvested IIV= inactivated antigen LAIV virus is weakened
hemagglutinin & neuraminidase
HA facilitates attachment of the virus to the host cell cause rbc to clump; Diagnostics test use this • NA is involved in the release of progeny virus from infected cells facilitating the spread • Targets for antiviral drugs cleaves mucin exposing sialic acid -promotes release of viron from infected cells penetrates virus into respiratory epithelium
Hepatitis B Antigens: HBsAg
HBsAg HbeAg HBcAg
what form of HIV is more common world wide with higher viral load and lower CD4 counts?
HIV 1
what HIV is transmitted through the same routes with similar opportunistic infection?
HIV 1 & HIV 2
HIV accessory protein Regulator of virion Rev
HIV protein expression, without REV HIV mRNA doesn't get translated
Retrovir indication
HIV with CD4 <500 prevent perinatal transfer HIV infection prophylaxis asymptommatic HIV not given as mono tx except for pregnant women
Ibalizumab-uiyk (Trogarzo) indication
HIV-1 failing their current ART IV injection WARNING: IRIS immune reconstitution inflammatory syndrome
What HIV is less pathogenic, less easily transmitted and present in West African, Mozambique, and Angola?
HIV2
PI and CYP substrates
HMGcoa Statins BZD (Midazolam , triazolam) CCB (nifedipine) Cisapride(arrythmia) ergot alkaloid(vasospasm) psychiatric medication manage; monitor ADE
Herpes Statistics
HSV 1 47.8% HSV 2 11.9% both higher amongst females HSV 1 higher with mexicans lower with non hispanic whites HSV2 higher with blacks lower with non hispanic asians
Influenza Structure
Ha, NA, M2 membrane protein drug targets M1 matrix protein Core 8 RNA ; 3 protein (PA, Pb1, PB2), viral replication NEP nuclear export protein
Peramivir (Rapivab)
IV treats uncomplicated influenza, must be given with 48 hours post exposure 600mg iv over 15-30 min
herd immunity
If sufficient numbers of population vaccinated, that can prevent endemic/pandemic outbreaks
gonococcal virulence factor
IgA protease antibiotic resistance: encoded beta lactamase, chromosomally mediated changes in cellular permeability inhibit PCN, TetraCyc, ErythroMy, AminoGly
Influenza prophylaxis
Inactivated im, trivalent or quadrivalent Live attenuated intranasal trivalent duration of immunity at least year
what ingibits the metabolism of methadone
Indinavir
Pharmacokinetic Enhancer: Cobicistat
Inhibit CYP3A enzymes (including CYP3A4) inhibitor • Has no anti-viral activity • Also inhibits p-glycoprotein and CYP2D6 interactions: 3A4 and 2D6 substrates ADE rash, gi upset, kidney fail, hypercholesterolemia
Clinical resistance to abacavir is associated with:
K65R, L74V, Y115F, and M184V.
Opportunistic infections mean CD4 150-200
Kaposi's sarcoma lymphoma cryptosporidisis
Combination products & arv therapy
Most are commonly use are Truvada/ Descovy based: ▪ ARV with FTC + TDF (Truvada) or FTC + TAF (Descovy)
HAART includes two major therapeutic regimens:
NNRTI-based therapy: consists of 2 NRTIs with 1 NNRTI or PI-based therapy: consists of 2 NRTIs with 1 or 2 PIs ("boosted PI") INSTI-based Therapy: consists of 2 NRTIs with INSTI NRTI pair should include 3TC or FTC
NRTIs Lack the _________ functional group at the 3' position on ribose, therefore cannot form phosphodiester bonds with new bases once drug inserted into cDNA
OH
Mechanism of Action: Importance of Phosphorylation
OH at the 3' position (in DNA bases) is used to link the succeeding base via phosphodiester bonds (3' to 5')
Doravirine select features
One 100mg tablet once a day ◼ Psychiatric effects less than other NNRTIs
What antiviral drugs are recommended this flu season?
Oseltamivir Zanamivir Peramivir Baloxavir
HPV Testing
PAP smear pre cancer on cervix that become cancerous normal (neg) unclear (ASCUS) atypical squamous abnormal (low grade or high grade) HPV neg (hpv not linked to cancer) pos (hpv linked to cancer)
Fostemsavir ADE
QTc prolongation at high doses elevation in hepatic transaminases in pt with Hep B or C
How does flu keep coming back?
RNA replication prone to error than DNA, high mutation rate, evolves faster, mutations accumulate, antibody can no longer bind, RNA viruses drift faster
Types of HIV tests
RNA/Viral load/Nucleic Acid Antigen Antibody Combo 4th generation test
Integrase strand transfer inhibitors
Raltegravir (Isentress) Elvitegravir (component of Stribild) Dolutegravir (Tivicay) Bictegravir (component of Biktarvy) Cabotegravir (component of Cabenuva)
HLA-B*5701 screening
Recommended before starting Abacavir (ABC), to reduce risk of hypersensitivity reaction (HSR) HLA-B*5701-positive patients should not receive ABC Positive status should be recorded as an ABC allergy If HLA-B*5701 testing is not available, ABC may be initiated after counseling and with appropriate monitoring for HSR
marketed as a combination drug Complera
Rilpivirine Tenofovir, Emtricitabine and Rilpivirine
To enhance levels in plasma Protease Inhibitors can be "boosted" with?
Ritonavir or Cobicistat • Lopinavir* +Ritonavir • Tipranavir* +Ritonavir • Darunavir* +Ritonavir • Saquinavir (Invirase)+ Ritonavir • Darunavir + Cobicistat • Atazanavir+ Cobicistat
Herpes types
STD; herpes simplex virus HSV HSV1 (lips cornea ) HSV 2 (genitals) AVOID TRIGGERS: sun and kissing SWAB SORE SAMPLE AND CULTURE
Coreceptor tropism assay
Should be performed when a CCR5 antagonist is being considered ◼ Phenotype assays have been used; genotypic test now available but has been studied less thoroughly ◼ Consider in patients with virologic failure on a CCR5 antagonist (though does not rule out resistance to CCR5 antagonist)
__________by itself is not an adjuvant, but emulsions of __________ with surfactants do enhance the immune response
Squalene
Products Containing Cobicistat
Stribild: Emtricitabine; TDF, Cobicistat , Elvitegravir • Genvoya: Emtricitabine; TAF, Cobicistat , Elvitegravir • Prezcobiz: Darunavir; Cobicistat • Evotaz: Atazanavir; Cobicistat
Methods for diagnosing genital herpes
Swab area to detect virus -culture -PCR draw blood to look for antibodies
Raltegravir Drug Drug interactions
UDT inducers: Rifampin UDT inhibitors: Tipranavir CI pt <16yo, breastfeeding
HPV Papillomavirus
Vaccine; quadriavalent, bivalent 2-3 dose series HPV L1 capsid 11-12 yrs old catch up vaccination through 26 years not recommended over 26 years old not licensed over 45 years old
Baricitinib CI & ADE
active TB inc infection thrombosis lipid elevations liver enzyme elevation
M protein inhibitor drugs (Adamantanes)
active against influenza A Amantadine Rimantadine
Neurainidase inhibitors
active against influenza A & B Zanamivir Oseltamivir Peramivir
Tesamorelin contraindication
active neoplastic disease pregnant women (drug category X) tesmorelin hypersensitivity
Zanamivir (Relenza)
acute A & B influenza in symptomatic adults for no more than 2 days
COVID can cause
acute lung injury, acute respiratory distress syndrome, pulmonary failure and fatality
what population is appropriate to administer the antigen test to?
acute stage, newborns
Presence of _______ is generally interpreted as indicating recovery and immunity from HBV infection
anti-HBs
Dronabinol THC MOA
antiemetic: bind to cannabinoid receptor in vomiting center of medulla, subpostrema of nucleus tractus solitarii ASNTS preventing emesis appetite stimulation: bind to cannabinoid receptors in HPA to stimulat appetite
genesis of new influenza
antigenic reassortment, subtype from parent virus pigs are mixing vessel lack of immunity no vaccines cause lethal pandemic
HIV Accessory protein viral infectivity factor Vif
attacks host defense in APOBEC(antiviral)
HSV transmission to infant
autobodies in 20 % pregnant women transmission in utero, during birth, after birth can cause encephalitis systemic infection babies have permanent neurological damage highly fatal if untreated 50%
AIDS defining conditions
bacterial infection candidiasis of bronchi, trachea, lung, esophagus cervical cancer; invasive coccidioidomycosis, diseminated or extra pulmonary cryptococcus extrapulmonary cryptosporidiosis chronic intestinal >1month cytomegalovirus (other than liver, spleen, nodules) >1month old cytomegalovirus retinitis with vision loss herpes simplex chronic ulcer >1 month duration isoporiasis chr. intestinal >1 month duration kaposi sarcoma lymphoma mycobacterium pneumocystis pneumonia leukoencephalopathy salmonella toxoplasmosis wasting syndrome of HIV
window period
between aquisition and detection in all patients to rule out infection 12 wks/90 days
Ibalizumab-uiyk moa
bind CD4 and interfere with attachment srepts for entry of HIV-1,prevents the normal structural shifts that occur in gp120 that result in gp120-coreceptor binding
Gp 120
bind to CD4 receptor
Fostemsavir MOA
binds directly to the gp120 subunit selectively inhibits the interaction between the virus and cellular CD4 receptors
M Protein inhibitors MOA
block uncoating of virus by interfering with M2, interfere with cell wall penetration
AZT Retrovir side effects
bone marrow suppression anemia 2-4 weeks esophageal ulcer myopathy/cardiomyopathy nail pigmentation (higher in black pt)
HIV Viral Enzymes Reverse Transcriptase RT
builds copy from viral RNA
influenza A source
certain wild ducks, geese, swans, gulls, shorebirds and terns HPA1 H5N1 H7N9 HPAI H7N8
Maraviroc
chemokine antagonist, blocks CCR5 preventing HIV from interacting=inhibits viral fusion treats CCR5 HIV-1 Treats pt with multi drug resistant virus
IFV Endonuclease inhibitors
cleaves host Mrna to initiate viral transcription
Live attenuated vaccines
closely mimics true infection superior long lasting immunity one dose required inexpensive
antigen antibody test
combo 4th gen antigen p24 present during acute HIV infection detect infection significantly earlier than antibody based positive in 50% at 17.8 days and 99% at 44.3 positive result needs confirmative test
Viral Hepatitis
common cause of liver disease in the world • Chronic viral hepatitis (CVH) accounts for 75% of chronic liver disease • CVH is the leading cause of cirrhosis, liver failure and hepatocellular CA
swine flu
commonly circulate in swine variant viruses H1N1, H3N2, H1N2m
Tenofovir MOA
competitively inhibits RNA- and DNA-directed reverse transcriptase competes with the natural substrate deoxyadenosine 5'- triphosphate (dATP) active against HBV because it lacks 3' hydroxyl
reiters syndrome
complication autoimmune inflammation of joints and bones
Oseltamavir (Tamiflu)
converted to oseltamivir carboxylate by hepatic esterase PRODRUG
Detecting herpes virus using swab of lesion / infected area
culture: if results are non type specific; request for lab to perform typing Pcr; more sensitive less expensive (not for intra lesional)
culture based influenza vaccines
cvv grown in cultured mammalian cells
Opportunistic infections mean CD4 <50
cytomegalovirus retinitis
HIV Accessory protein Viral protein Vpu
degrades Cd4, weakens interactions of envelope with cell surface receptors, helps virus escape host during budding
CI of PI's
diabetes hepatic disease hemophelia
Baloxavir ADE
diarrhea bronchitis nausea nasopharyngitis headache
Peramivir ADE
diarrhea constipation neutropenia psychosis
Raltegravir
diarrhea and fever elevated creatininie rhabdomyolysis IRS
Remdesivir RDV
direct acting antiviral inhibits RNA synthesis monophosphoramidate prodrug metabolized by GS-704277 & GS-441524 (active metabolite)
herpes spreads by ?
direct contact with sores; some which cannot be seen
Primary syphilis
directed sexual or skin to skin incubation period 3-90 days chancre; painless hidden itchy skin lesion multiple lesion coinfected with HIV cervix, penis, rectum can heal itself in 6 weeks
CDC
disease classification based on immune function clinical status
human papillomavirus
dsDNA 200 subtypes epithelial cells, skin wart majority resolve spontaneously persistent infection develop into anogenital, cervical, oropharyngeal cancer low risk HPV, high risk HPV type 16 and 18=66%
Abacavir and M493T allele
e HLA-B*5701 locus and the M493T allele in the heat-shock locus Hsp70-Hom. Hsp gene is implicated in antigen presentation and is associated with TNFα release
HIV Structural protein capsule CA p24
early biomarker; undetectable after seroconversion
chlamydia summary
easily treated and cured with antibiotics 7 day course/abstinence women-pelvic inflammatory disease, ectopic pregnancy resting every 3 months
syphilis treatment
easy to cure if diagnosed early single penicillin dose for infection less than a year abstinence/practicing safe sex testing in pregnant women/newborns treatment before 16th weeks prevents congenital syphilis treatment after 16th week inadequate, child needs to be treated with penicillin
Echinacea
enhance immune function in individuals who have colds and other respiratory tract infections Cichoric acid, Echinaforce & Echinacoside
HIV structural protein Gp120 Su, Gp41TM
envelope proteins bind to receptors on host cell
viral load
escribes the number of copies of HIV RNA per mL of blood 50,000 copies= 25,000 viruses/mL of blood Goal: <50 copies per mL of blood
Stavudine and Zalcitabine most likely cause
esophaeal ulcerations
antigen test generations
first : IgG 6-12 weeks post infection; false positives; need western blot to confirm second : recombinant third: IgM detection; 3 weeks post infection fourth: p24 50% infections detected in 17.8 days
vesicle HSV transmission
fluid accumulation between dermal and epidermal
Tenofovir black box warning
for acute exacerbations of hepatitis B following discontinuation of the drug
Fuzeon
for advanced hiv in combo with other drugs interferes with entry of HIV1 into cells; binds gp41 of viral envelope SC injection >=16yrs old 42.6kg 90mg SC bid 6-16 yrs old <42.6kg 2mg/kg bid up to max of 90mg
Baricitinib (Oulmiant)
for emergency use in combination with Veklury (Remdesivir) JAK 1 & @ inhibitor
HIV accessory protein negative regulator factor Nef
forces infected cell to stop making defense protein MHC1 for high viral load and progression to AIDS.
HIV structural protein Nucleocapsid NC
forms structurally stable complex with RNA protecting it
seroconversion window
from aquisition HIV to time anti HIV antibodies are detectable 28 days
Gp41
fuses viral membrane with CD4
NRTI ADE
gi upset mitchonondrila dysfunction fatal reaction endocrine lactic acidosis; cause by mitochondira poisoning
trachoma
granular conjunctivitis leading to blindness; transmission can be direct through fomites or arthropods
Adjunct therapies for HIV Tesamorelin
growth releasing factor analogue tx excess abdominal fat in HIV pt with lipodystrophy 2mg SC once a day
HIV Accessory protein viral protein r Vpr
guides viral genome into host nucleus
Oseltamivir ADE
headaches dizziness N/V give with food
NNRTI Contraindications
hepatic failure hypersentritivity mental illness
N meningititis low incidence
high mortality
prognostic information for providers
how patients fit along the continuum
Influenza B
human infection less common than A slow mutation rare pandemics
Influenza C
human, dogs, pigs, less common than A& B
Remdesevir ADE
hypersensitivity rxn prothrombin inc ALT AST increase NOT FOR PT WITH eGFR<30 Interactions; chloroquine hydroxychloroquine
why use ART?
improves and preserves immune function, regardless of baseline CD4 count Reduction in AIDS- and non-AIDS-associated morbidity and mortality ◼ Reduction in HIV-associated inflammation and associated complications
influenza vaccine types
inactivated IIV live LAIV recombinant RIV
viral load blips
increase in viral load for short duration of time before dropping
Gonorrhea
incubation period (2-5 days) purulent discharge from infected site (penis, vagina, anus, lips) chronic infections leading to sterility drug resistant gonorrhea on the rise
what causes pi induced diabetes, and decreased insulin sensitivity by inhibiting glut4 and ppar gamma
indinavir
flue vaccine
influenza A H1N2 A H3N2 and one or 2 B viruses depending on the vaccine, are included in each year's vaccine
influenza virus
influenza viruses are RNA making up orthomyxovirdae Influenza ACBD A&B- epidemics C minor respiratory illness D cattle
Echinacea Pharmacology
inhibited the rise in pro-inflammatory cytokines and interleukins-6 and -8 • increased phagocytosis, total circulating monocytes, neutrophils, and natural killer cells • demonstrated virucidal activity avian influenza virus (H5N1, H7N7) and swine-origin influenza virus (H1N1), Herpes Viruses
Crofelemer MOA
inhibits cystic fibrosis transmembrane conductance regulator ion channel, calcium activated chloride ion channel at luminal membrane of enterocytes
Baricitinib MOA
inhibits intracellular pathways elevated in severe covid 19. (IL2,6,10, interferon gamma, and granulocyte)
Protease Inhibitors MOA
inhibits protease protease processes HIV and assists in HIV virion assembly
HIV viral enzyme Integrase IN
integrates DNA of viral genome with DNA of host
what happens to patient once AIDS diagnosis has been made?
it remains with patient even if the CD4 count returns above 200
why does flu kill?
juvenile elderly sick patients release of cytokines; fever and fatigue
IgM
largest and first antibody appears in response to antigen
Baloxavir drug interactions
laxatives antacids oral supplements
NRTI ADE Dyslipidemia
lipoatrophy loss of fat lipodystrophy abnormal fat distribution; cushings;hyperlipidemia, high cholesterol
Betaherpesvirus
long cycle slow spread Cytomegalovirus CMV HHV5 retinitis, mononucleosis HHV6, HHV fever rash in young children
primary herpes lesion
longer to form , persist longer
lactic acidosis causes
loss of DNA polymerase Y dysfunctional mitochondrial 9no atp lactic acid build up, anerobic metabolism)
Unique COVID symptoms
loss of taste and smell could take long to develop symptoms contagious for long period more transmissible less likely to produce disease in children school children=high risk for multisystem inflammatory syndrome MIS-C blood clot in veins, arteries, lungs, heart, legs, brain
N gonorrhoeae high incidence
low mortality
Moderna COVID vaccine
mRNA 1273 2 shots one month apart 100microgram/.5ml refrigerate 36-46 up to 30 days
antibody test why use it?
may or may not distinguish HIV 1 and HIV 2 rapid test and home test early as 3 weeks 4 weeks detect 95% infection window: 12 weeks confirms neg status
RNA viral load test
measure amount of HIV in 1ml of blood 2-3 months apart to determine baseline repeat every 3-6 months withs cd4 count monitor viral load and t cell repeat every 4-6 weeks after starting or changing art to determine effect on viral load
antigen test
measures capsid core p24 detectable earlier than HIV antibody acute stage p24 antigen present for short time then anitbody p24 appears detectable 10-14 days post exposure peak 3-4 weeks, not detectable after 5-6 weeks, detectable during AIDS stage NOT for routine screening
chlamydia reticulate bodies
metabolically active; replicating non infectious enclosed by a vacuole replicates through binary fission
Abacavir ABC
metabolized by alcohol dehydrogenase (to form the 5'- carboxylic acid) and undergoes glucuronidation
congenital syphilis
miscarriage, still birth, premature or death no primary chancre, secondary rash baby born to mother with syphilis snuffles with t pallidum latent-damage to teeth, eye, ear , brain
Remdesevir MOA
misintegration of nucleoside triphosphate into replicating RNA by RdRp prevent further elongation after NTP plus 3 additional nucleotides premature termination of RNA synthesis
IgG
most abundant antibody takes longer to develop
Dronabinol THC ADE
most common ADE; dizziness, euphoria,paranoid rxn, somnolence, thinking abnormal, N/V/D neurological; psychiatric and cognitive effects and impairs mental abilities hemodynamic instability; pt with cardiac disorders experience hypoTension, syncoe, bradycardia, tachycardia
what s best predictor of disease progression
most recent CD4
HSV2
mostly by young adults genital (oral rare) frequent asymptotic shedding very low risk of HSV1 aquisition inc risk of fetal newborn trans inc risk for HIV infection
HSV 1
mostly children adults are seropositive small proportion recrudescence mostly orolabial (cold sores and blisters) inc in sexually active shorter initial and recurrent outbreaks than HSV2 cont risk for HSV2 aquisition
NRTIs Activation
must be activated bt host cell kinase drug converted to triphosphate nucleotide triphosphae nucleotide incorpirated into viral cDNA duing RT synthesis
adjunct crofelemer ADE
n/v elevated liver enzymes life threatning constipation: Alosetron antagonize PK effects of Libiprostone
Johnson & Johnson covid vaccine
nanoparticle mRNA 1 dose store in fridge up to 3 months
infant pneumonia
neonatal , 4-12 weeks afebrile
recombinant influenza vaccines
no candidate vaccine virus derived using DNA coding sequence for HA
If herpes viral swab is negative?
no detectable virus ; doesnt mean patient doesnt have GH. False negatives are common ; low sensitivity especially when collected 3 days after outbreak when viral count it low
Eclipse period
no diagnostic test can detect HIV 10 days
Echinacea Cautions
no immunocompromised patients, HIV, immunosuppressant patients
chlamydia elementary bodies
non replicating infectious particle released rupture of infectious cells rigid outer membrane helps binding to host cell resisting immune response
Maraviroc (Selzentry)
not effective against CXCR4 or dual tropic HIV-1 strains—tropism assay may be needed before beginning treatment Caution when using with CYP3A and PgP inhibitors
killed or inactivated vaccine diasadvantages
not for certain age groups immunity doesn't last long, boosters needed some chemicals used are dangerous avoid in yeast allergy patients may need adjuvant
inactivated (killed)
nucleic acid whole cell fractional : toxoid, subunit, polysaccharide
classification system
numbers reflective of CD4 count, letter reflective of clinical status
Opportunistic infections mean CD4 250-500
oral candidiasis TB
cytokine storm
overproduction of immune cells and activating cytokines disproportionate release causes fever and fatigue t cells sworm in and block air pathways, lungs inflame, respiratory distress leads to infections
cytolytic infection HSV transmission
pathologic changes due to cell necrosis, inflammatory
If herpes viral swab is positive
patient likely has GH ; false positives are rare
Amantadine drug interactions
phenothiazines psychostimulants antimuscarinics and antihistamine
Mechanism of Action: Chain Termination
phosphorylated drug is added to growing cDNA chain at 5' end but another base can not be added after insertion of drug because there is no 3' OH group on the NRTI
Opportunistic infections mean CD4 75-125
pneumocystis cariniii pneumonia toxoplasmosis cryptococcal meningitis MAC diseminated recurrent herpes simplex ulceration esophageal candidiasis
Baloxavir Marboxil (Xofluza)
polymerase acidic endonuclease ir required cleaves host and inhibits endonuclease activity of polymerase acidic protein
HIV accessory protein transactivator of transcription Tat
positive feedback cycle increases transcription of HIV dsDNa
what statin is leask likely to interact with ARV
pravastatin
thalidomide precaution
pregnant women given to women after 2 pregnancy tests
Zinc Supplementation
preserving tissue barriers reduced symptom severity, reduced frequency, and duration of the common cold after zinc administration Zinc deficiency results in altered numbers and dysfunction of all immune cells, subjects with suboptimal zinc state have an increased risk for infectious diseases, autoimmune disorders, and cancer
Fostemsavir (rukobia)
pro drug hydrolyzed by active metabolite Temsavir for tx of multi drug resistant HIV-1
Baloxavir PK
prodrug asians 35% higher concentration in comparison to non asians
Tenofovir Alafenamide (TAF)
prodrug renofovir inhibits Cyp3a higher active metabolite in cells and lower plasma levels than TDF
adjuvant
prolongs or potentiates immune response
Rimantadine indications
prophylaxis and treatment of influenza A
what increase or decrease oral contraceptives levels
protease inhibitors
Amantadine contraindications
psychoses history of epilepsy
Dronabinol THC contraindications
pt with seizures pt with history of multiple substance abuse pt with propylene glycol sensitivity
live vaccine disadvantages
random mutations occur, lead to virulence contamination possible during growth fragile-must be stored carefully needs organism to replicate in body, not given to immunocompromised severe allergic reactions
Advanced/AIDS stage 3 involves?
rapid depletion of immune system aids defining condition or CD$ under 200cells/cm or CD4+Tcell percentage of total lymphcytes less than 14
ARV Therapy
rarely monotherapy given as cocktails HAART, ART
thalidomide moa
reduces levels of tumor necrosis factor alpha reduces angiogenesis
Permavir CI
renal dysfunction; should be used after dialysis
Rimantadine (Flumadine) MOA
same as amantadine but has no CNS effects
what causes life threatening pancytopenia
saquanivir
Abacavir and HLA-B*5701
screeninig needed before start of drug to reduce hypersensitivity HLA pos patient cant recieve drug if testing not available ABC can be initiated with hypersensitivity monitoring
lymphogranuloma
self limited painless genital ulcer, inoculation at mucous lining sex organs
HSV disease: Herpes Simplex Keratitis
self transmission (autoinoculation) to eye causes lesion scars impair vision lead to eye autoimmune responses
HSV virus travels from sit of infection in sin or mucosa to ?
sensory dorsal root and remains latent until recurrent outbreak HSV1 trigeminal ganglia HSV2 sacral ganglia
Intermediate/Latent/Asymptomatic/Chronic Infection stage 2 involves?
seroconversion often no symptoms t cell destruction weakens immune system over time gradual immune function decline if untreated over 8-10 years monitored by lab test of CD4 count (decreased)
lactic acidosis clinical presentation
serum lactate levels greater than 2.0 mmol/L and pH <7.30 ◼ Lethargy, fatigue, seizures, death (rare) Didanosine, Stavudine, Zalcitabine major offenders Lamivudine and Tenofovir least likely
COVID official name
severe acute respiratory syndrome SARS COv-2
pathogens of Neisseria gonorrhoeae
sexual contact mucous membrane urethra in male cervix in female fimbrated cells attach to intact membrane epithelium
Alphaherpesvirus
short cycle; rapid spread HSV1 HSV1 VZV (varicella zoster) HHV3 Chickenpox
Negative regulatory factor Nef deleted strands have slow or fast progression?
slow
chlamydia
small obligate intracellular parasites energy parasites STD congenital transfer C trachomatis process inner and outer membrane similar to gram-negative bacteria and a lipolysaccaride but do not have a peptidoglycan layer lack of symptoms burning sensation for men; odor and itch for women
gammaherpesvirus
specific for B & T lymphocytes EBV epstein barr virus HHV4 mononucleosis HHV8 Kaposi's Sarcoma
HSV 2 transmission
spread by genital contact, mucous membrane, open or damaged skin
HSV 1 transmission
spread by respiratory droplets or infected saliva
HIV Structural protein Matrix Ma p17
stabilizing protein forming a coat on inner surface of lipid membrane; replication
Tenofovir is then taken up by cells and undergoes phosphorylation to form
tenofovir diphosphate (PMPApp).
thalidomide ADE
teratogenesis (cat 10) birth defecrs, male mediated (found in semen)
why do Pi's cause osteoporosis
they inhibit osteogenesis and attentuate the function and recruitment of osteoblasts increasing bone loss, as well as mitochondrial toxicity
Ralteglavir Indication
treat experienced patients treat patients reistant to multiple ARV for children with HIV disease
Adjunct therapy Crefelemer
treat non infectious diarrhea in adult patients with hiv on ART
Dronabinol THC indication
treatment of CINV refractory to antiemetic treat anorexia associated with weight loss in pt with AIDS
Lamivudine, 3TC
treatment of Hepatitis B and HIV MOST POTENT ADE: headache, pancreatitits Inc liver enzyme
Amantadine (symmetrel)
treatment of symptomatic and prophylactic influenza A tx parkinsons tx EPS tx carbon monoxide poisoning unlabelled enuresis neuroleptic malignant syndrome manage cocaine dependency and withdrawal ADJUST dose for renal impair
Patients who are vaccinated will have antiHBsAg only. true or false
true
HSV transmission via outbreaks
ultraviolet radiation trauma, emotional, physical stress immunosuppression
m protein
uncoat viral nucleic acid
NRTI for CKD
use ABC or TAF ▪ ABC not associated with renal dysfunction ▪ TAF has less impact on renal function and proteinuria than TDF; may be used if eGFR >30 mL/min when ABC or TAF cannot be used ▪ LPV/r + 3TC ▪ DRV/r + RAL (if HIV RNA <100,000 copies/mL and CD4 >200 cells/µL)
vaccine strategies: killed or inactivated
uses cultured organisms that are killed with heat, radiation, or chemicals: acetone, formalin, thimerosal,phenol advantages: can be given to immunocompromised, no threat of virulence regained
live attenuated vaccine
viral bacteria
HIV viral enzymes Protease PR
virus matures, cleave polypeptide into functional protein
Acute Early Infection stage 1 involves?
window period immune system produces antibodies (seroconversion (3-12 weeks) 70% develop flu like symptoms -swollen gland -oral ulcer -sore throat -diarrhea n/v -rash -muscle ache -headache
Can HSV be shed despite absence of lesions?
yes
Quadrivalent Flu Vaccines
• Afluria Quadrivalent: given either with a needle or with a jet injector • Flucelvax Quadrivalent & Flublok Quadrivalent: egg free vaccine • FLUAD Quadrivalent & Fluzone High-Dose; approved for patients 65 and older
PIs Containing Sulfa Moieties
• Darunavir (Prezista®) • Fosamprenavir (Lexiva®) • Tipranavir (Aptivus®) just sue with caution in sulfa allergy patients
Raltegravir (Isentress)
• First medication of class (INSTIs) prevents provirus formation
Why the limited effectiveness of Flu vaccine?
• Flu vaccine based on previous year prediction • Virus constantly mutating particularly H3N2 • Though may not completely protect against getting virus, may reduce severity and need for hospitalization
Maraviroc ADE
• Hepatotoxicity accompanied by anaphylactoid reactions (rash) • Fever (most common) and cough • Upper respiratory tract infections • Elevated Liver enzymes • IgE mediated reactions • Stevens-Johnson syndrome
protease inhibitors
• Saquinavir (SQV) (Invirase [Hard gel capsule]or Fortovase [soft gel capsule]) Prototype • Ritonavir (Norvir, RTV) • Indinavir (Crixivan) • Nelfinavir (Viracept): most popular • Amprenavir (Agenerase) • Fosamprenavir (Lexiva ) is the phosphate ester prodrug • Atazanavir (Reyataz) • Tipranavir (Aptivus, TPV) • Darunavir (Prezista, DRV) • Ritonavir/Lopinavir (Kaletra)
HBsAg
• The Hepatitis B surface antigen (HBsAg) is the most abundant of the antigens • Is detectable at the onset of clinical symptoms. Presence of HBsAg indicates the person is infectious.
Adjunct Therapy: Thalidomide
• treatment of AIDS-associated wasting syndrome and cancer cachexia • treatment of AIDS-related Kaposi's sarcoma indications; tx multiple myeloma
Protease Inhibitors: Adverse Effects
•Hypercholesterolemia •Hypertriglyceridemia •Reduced Bone Mineral Density (BMD) and osteoporosis
NRTI
▪ Abacavir (ABC) ▪ Didanosine (ddI) ▪ Emtricitabine (FTC) ▪ Lamivudine (3TC) ▪ Stavudine (d4T) ▪ Tenofovir DF (TDF) ▪ Tenofovir alafenamide (TAF)* ▪ Zidovudine (AZT, ZDV
PI
▪ Atazanavir (ATV) ▪ Darunavir (DRV) ▪ Fosamprenavir (FPV) ▪ Indinavir (IDV) ▪ Lopinavir (LPV) ▪ Nelfinavir (NFV) ▪ Saquinavir (SQV) ▪ Tipranavir (TPV)
Integrase Inhibitor (INSTI)
▪ Bictegravir ▪ Dolutegravir (DTG) ▪ Elvitegravir (EVG) ▪ Raltegravir (RAL)
NNRTI
▪ Delavirdine (DLV) ▪ Doravirine (DOR) ▪ Efavirenz (EFV) ▪ Etravirine (ETR) ▪ Nevirapine (NVP) ▪ Rilpivirine (RPV)
Fusion Inhibitor
▪ Enfuvirtide (ENF, T-20)
CCR5 Antagonist
▪ Maraviroc (MVC)
Nevirapine select features
◼ Fatal hepatotoxicity/ hepatitis especially common during first weeks of therapy ◼ Prevents perinatal transmission ◼ CYP inducer
Tenofovir ADE
◼ GI, Headaches, ◼ Renal impairment and renal failure especially in patients with pre-existing renal disease ◼ Elevated liver enzymes Tenofovir Induced renal toxicity ◼ Osteomalacia ◼ Rhabdomyolysis ◼ Electrolyte Imbalances ◼ Fanconi syndrome ◼ Angioedema (associated with Hypersensitivity) ◼ Pancreatitis
NRTIs and Special Populations Prego
◼ ZDV*+ 3TC ◼ ddI + d4T not recommended because high incidence of lactic acidosis ◼ Tenofovir: not recommended, bone deformities in fetus
Tenofovir drug interactions
◼ inc ddI levels ◼ dec atazanavir levels