Viruses Flashcards

Question

Peg-interferon Alfa - 2a Inferferon Alfa 2b

Answer 1

HBV drug MOA: activate NKC and macrophages ; inhibits viral protein production Peg - administered SQ ; hepatic dosing Interfron - administered IV, IM, SQ **CNS EFFECTS Monitor: - Anemias - CBC w/ diff - Infections - chest x-ray - Arrhythmias - EKG - LFTs - Hypothyroidism - thyroid function - PSYCH CHANGES - moods not using these d/t arrhythmias, mood changes & secondary infections

Answer 2

HBV - effective against Iamivudine - resistant HBV *** 184 mutation seeing used the most Oral tablet MOA: prodrug metabolized by cellular kinases - preventing DNA synthesis Renal Dosed** , when CrCl < 50 - HD dosing 10mg PO every 7 days after HD Monitor - Renal function - LFTs - HBV labs (viral load, serologies) DO NOT USE WITH TENOFOVIR

Answer 3

HBV : 100 mg PO HIV-1 , HIV-2 : 300 mg PO Classified as Nucleoside Reverse Transcriptase inhibitor *** Cross coverage if no resistance mutation ; if someone has 184 mutation in HIV and then gets HBV it will also have 184 so can't use Oral tab = oral solution Renal dosed ; CrCL < 50 Monitor : - Blood glucose - CBC with Diff - HIV VL/CD4 count - HBV VL - LFTs - Renal function

Answer 4

HBV Inhibits HBV RT - suppressed DNA replication ; weak activity towards HIV RT Oral tab does not = oral solution * * decrease dose switching from tab to solution * * MUST take on empty stomach for optimal absorption Renal dosed CrCl < 50 Monitor: - Renal function - LFTs - T.bili - Bfs (especially in DM patients)

Answer 5

HBV Oral tab Renal dosed when CrCl <50 ADR - LFTs rarely used

Answer 6

ssRNA objective for Hep C is to cure ROT = contaminated devices , IV needles ; sexual contact higher prevalence in MSM All person between 1945-1965 IVDU, HIV, MSM For all patient with chronic HCV initiate treatment exception short life expectancy <12 month that cannot be treated with transplantation or with remediated treatment - Fatigue / headache/ GI - No renal dosing ; caution in ClCr <30

Answer 7

SOfosbuvir nucleoside analoe incorporate into HCV RNA leading to chain termination = stops HCV replication

Answer 8

Inhibits the cleavage of polyproteins into nonstructural proteins essential in HCV replication LOWER barrier to resistance (Q80K) "Previr"

Answer 9

inhibits the phosphorylation of proteins required for HCV RNA replication preventing HCV RNA replication Associated with resistance mutation = decreases activity 'Asvir"

Answer 10

MOA: NS5B RNA nucleotide polymerase inhibitor: nucleoside analoe incorporate into HCV RNA leading to chain termination = stops HCV replication genotype 1,2,3,4 - Prodrug - Pangenotypic Metabolism - hydrolysis - NO CYP450 interactions Substrate p-gp efflux pump & BRCP - DDI with inducers Pregnancy - Category B Male mediated teratogenicity d/t ribavirin exposure * NOT for monotherapy * increased renal toxicity with Tenofovir

Answer 11

Ledipasvir - NS5A inhibitor ;inhibits the phosphorylation of proteins required for HCV RNA replication preventing HCV RNA replication Associated with resistance mutation = decreases activity - metabolized via oxidation - No DDI by CYP450 - Elimination - pop efflux pumps and BCRP ADR - Asthenia - Hyperbilirubinemia - Fatigue / headache/ GI - No renal dosing ; caution in ClCr <30 - No hepatic dosing DDI - Acid suppressants - Tenofovir - nephrotoxicity - Amiodarone - symptomatic bradycardia Recommended for non-black, non-HIV, with HCV VL <6 mill without cirrhosis (with cirrhosis not recommended)

Answer 12

NEW GOLD STANDARD IN HCV MANAGMENT Velpatasvir - NS5A inhibitor ;inhibits the phosphorylation of proteins required for HCV RNA replication preventing HCV RNA replication Pangenotypic for genotypes 1 - 6 Metabolized - 3A4 Eliminated in feces ``` ADRs - Anemia - Gi, headache, fatigue - No hepatic dosing - No renal dosing Caution in eGFR < 30 ``` ** Lots of DDIs

Answer 13

``` Voxilaprevi = NS3/4A protease inhibitor Velpatasvir = NS5A inhibitor ``` Pangenotype for genotype 1 - 6 Once daily w/ foot Metabolized CYP3A4 = DDI Significant DDI with ACID suppressants - need to separate dose by 4 hours Renal issues = do NOT used when eGFR < 30 ADRs - headache, fatigue, GI - Rash - Depression - Elevated lipase , CPK, t.billi "Think 3" cyp3a4 , eGFR <30, 3 elevations

Answer 14

Elbasvir - NS5A inhibitor Grazoprevir - NS3/4A protease inhibitor metabolized - CYP3A4 ADRs - GI - Fatigue - Headache - Anemia - Elevated LFTs, hyperbilirubinemia - No renal or hepatic doing LOTs of DDIs

Answer 15

Inhibits all non structural proteins in one Paritaprevir - major DDIs Ritonavir Ombitasvir Dasbuvir Must be taken with food very complicated dosing schedule No renal or hepatic dosing ADR - GI , rash, LFTs Pak is 3 pills in morning 1 in evening XR is 1 pill 3x a day with food

Answer 16

Genotypes 1a and 1b only must be taken with food too Manny DDIs Viekira Pak is not = to XR cannot interchange them

Answer 17

NS3/4A protease inhibitor for Genotype 1 only Q80K resistance mutation = reduction in efficacy based on SVR - more effective in 1b Metabolized via 3A4 - interactions Asians >> Caucasians and AA patients Take with food SULFOnamide allergy ADRs: - Rash, LFTs, GI, hyperbilirubinemia "Simple but not quite effective" Simple Genotype 1 only Quite = Q80K But ~ B > effect

Answer 18

NS5A inhibitor Indication - HCV genotype 3 MUST BE COADMINISTERED W/ SOFOSBUVIR Metabolism CYP3A4 - DDI Coadministered with 3A4 inhibitor = reduce 30 mg coadministered with 3A4 inducer = increase 90 mg Pgp efflux pump substrate and inhibit - DDI ADRs - Anemia, fatigue, GI effects, headache

Answer 19

Glecaprevir = NS3/4A protease inhibitor Pibrentasvir - NS5A inhibitor Pangenotypic for genotype 1 - 6 1 tab daily w/ food Glec - minimal 3A4 pib - met via bilirary fecal route No renal dosing ADRs - Headache, fatigue, gi, elevated t.bili

Answer 20

MOA: Induces the innate antiviral immune response side effects - flu like symptoms BBW - neuropsychiatric Weekly SQ injection HCV

Answer 21

MOA: increase mutation frequency and inhibits HCV polymerase Indication: use in combo with PEG-IFN therapy Side effects - GI symptoms, neutropenia BBW - hemolytic anemia & teratogenicity

Answer 22

Genotype 1 - more resistant to therapy 1a - NS3/4A mutation - Q80K polymorphism - decreases activity of simeprevir - NS5A mutations - 5 fold reduction in NS5A inhibits

Answer 23

Assess Child Turcotte Pugh Liver score (CTP) - Avoid NS3 PI : current or prior h/o decompen liver disease or CTP > 7 Avoid paritaprevir/ritonavir : CTP score of 5 or 6 if the patient cannot be closed monitored All pt should be assessed for HBV infection Assess potential DDI with DAA Check labs 12 weeks prior to starting DAA (CBC, INR, LFTs, eGFR, HCV genotype, HCV VL, resistance testing)

Answer 24

Prior to therapy (within 12 weeks) - CBC, INR, complete LFT panel, TSH, eGFR On therapy - Check HCV VL at week 4 and 12 weeks - Discontinue therapy of detectable at week 6 or alter - check routine labs SVR = sustained virology cure - undetectable HCV VL at least 12 weeks after the completion of therapy

Answer 25

ss-RNA therapy at any CD4 count INSTI-based ART is preferred

Answer 26

Competitively inhibits of HIV-1 RT MOA: target catalytic site on RT - stops DNA prolongation competitive, TEMPORARY inhibition (endogenous nucleotide competes for site) ``` Class effect - Renal dosed (except Abacavir) - Mitochondrial toxicity (due to inhibitor of mitochondrial DNA polymerase, lactic acidosis, hepatic steatosis) - Lipoatrophy - fat wasting - extremities, buttock, face ```

Answer 27

NRTI - HIV - Hypersensitivity reaction , occasionally fatal - CVD risk - DO NOT USE : baseline HIV VL > 100k copies - testing for HLA-B5701 allele before initiation to ID pt with increased risk of hypersensitivity reactions

Answer 28

NRTI - HIV Dose dependent pancreatitis* peripheral neuropathy * lipoatrophy

Answer 29

NRTI - HIV ``` *bone marrow suppression Myelosuppresion macrocytic anemia neutropenia high level resistance seen ```

Answer 30

NRTI- HIV *well tolerated, headache also active against HBV rapidly selects for mutation - M184V

Answer 31

NRTI - HIV *Hyperpigmentation (A-A) Active against HBV

Answer 32

NRTI - HIV * weight based pancreatitis, peripheral neuropathy - lactic acidosis w/ hepatic steatosis - lipodystrophy

Answer 33

NRTI - HIV formulated in lactose ; LACTOSE INTOLERANCE PT caution - nephropathy - renal failure - fanconi syndrome - osteomalacia

Answer 34

Prodrug of tenofovir Safer vs TDF no renal changes no bone mineral changes

Answer 35

taret allosteric site on RT - conformational change - stop DNA prolongation, non-competitive binds noncompetitivelty to alleosteric site baseline genotypic resistance testing recommended adherence forgiving d/t long t1/2 resistance occurs rapidly with mono therapy and results from single mutation - lowest genetic barrier to resistant most common NNRTI resistant mutation = K103N PERMANENT inhibition good for noncompliant pt

Answer 36

1st generation NNRTI - HIV Qhs dosing ; take on empty stomach ADRs - CNS effects - somnolence, fatigue, psych changes, SI/SA - rash, LFTs Metabolized by CYP3A4; induces and inhibits CYp3A4 Recommended for pregnancy after 1st trimester **caution in someone with undiagnosed psy issues or suicide

Answer 37

1st generation NNRTI - HIV Do not use in females with CD4 >250 cells Do not use in males with CD4 >400 cells metabolized by CYP3A4 and induced ADR- rash , liver toxicity**

Answer 38

2nd gen NNRTI - HIV active against K103 N ADR: Rash , LFTs, minor CNS effects < efavirnzr

Answer 39

2nd gen NNRTI - HIV Active against K103N virus must take with food ; 900 kcal ADRs: rash, LFTs, CNS effects Do not use : Baseline HIV VL >100K

Answer 40

MOA: inhibit the activation of immature proteins block the GAG - POL region within protease inhibit the cleave of proteins Class effect: - Rash, LFTs, - increased BGs -- DM - increases TG and LDL - Lipodystrophy (central adiposity) - increases CVD risk All metabolized by CYP3A4 most a potent inhibitor high genetic barrier to resistance

Answer 41

Most 3A4 potent inhibitor PI Agent - HIV ADR - GI

Answer 42

PI agent - HIV ADR - PR interval prolongation hyperilirubinemia GI neutral lipid neutral "Tasmanian devil" - trying to keep that hyper devil neutral for awhile

Answer 43

PI agent - HIV must co - admin w/ ritonavir Sulfonamide cautious with sulfa allergy GI lipid neutral

Answer 44

PI agent - HIV Sulfonamide - cautious with sulfa allergy ADR = GI

Answer 45

PI agent - HIV Nephrolithiasis hyperbilirubinemia Hydrate

Answer 46

PI agent - HIV ADR - GI

Answer 47

PI agent - HIV ADR - GI CVD risk - own independent risk

Answer 48

PI agent - HIV Only CYP3A4 inducer Must co-admin w/ ritonavir sulfonamide - cautious with sulfa allergy ADR - intracranial hemorrhage

Answer 49

Fosamprenavir Darunavir Tipranavir DTF

Answer 50

Atazanavir Darunavir Indinavir

Answer 51

Darunavir Tipranavir DTR

Answer 52

PK booster used as a 3A4 booster 3A4 inhibitor FDA to boost atazanavir and darunavir only at 800 mg not approved for darunavir 600mg NO HIV activity DDI = Ritonavir ADE = renal impairment Do not use COBI + TDF when CrCl <70

Answer 53

Fusion inhibitor HIV only SQ product inhibits QP41 and prevents fusion of HIV to CD4 cell surface ADR injection site reaction , GI

Answer 54

Entry inhibitor HIV inhibits HIV co receptor CCR5 - tropic HIV - 1 infection Must rest for co receptor tropism prior to using Dose - 300 mg q 12 h with inhibitor 150 mg po with inducer 600 mg po ADRs: LFTs , rash, pyrexia, orthostasis

Answer 55

HIV integrase inhibitor MOA: blocks the catalytic activity of HIV encoded inters preventing integration of virus DNA into host metabolized by glucuronidation and does not interact with CYP450 eliminated by p-gp ADR - rash, LFTs, increase CPK, pyrexia

Answer 56

"quad pill"" Treatment naive patients cannot use ClCr >70 due to TDF with COBI ADR: - new or worsening renal function - bone mineral density losses - GI DDI - too many contraindications

Answer 57

Genvoya Safe in patients with CrCl >30

Answer 58

if pt resistant to raltegravir or elvitegravir can still use this drug most potent HIV drug ADR: - hypersensitivity reaction - LFTs (esp in HBV or HCV coinfections) - insomnia - hyperglycemia (>125) - hypertriglyceridemia DDI polyvalent cations space DVG 2 hours or 6 hours after cations

Answer 59

treatment naive and as SWITCH regiment 1 tab po once daily Renal issue CrCl <30 = due to TAF ADR: GI and headache