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