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drug immuno II Flashcards

1
Q

empiric ABX for nocardiosis ไล่ตามอาการ

A
  1. mild disease (e.g. skin infection), immcpt host: TMP-SMX monotherapy
  2. immcpm or those w disseminated but no brain involve: TMP-SMX+amikacin / imipenem+amikacin ถ้าเยินมาก
  3. isolated cerebral disease: TMP-SMX+imipenem (เพราะเข้าสมองดีกว่า ami)
  4. life-threatening disease ยมแบบจะม่องเท่ง: TMP-SMX+imipenem+amikacin (or ceftri in renal failure pt)
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2
Q

ABX for actinomycosis (ในเคสเป็นเชื้อ: actinomyces meyeri)

A
  • extensive successful clinical experience: penicillin, amox แต่ถ้าแพ้ penicillin อาจใช้พวก erythro, tetra, doxy, clinda แทนได้ ๆ
  • anecdote นิด ๆ: ceftri, imipenem-cilastatin, pipe-tazo
  • agent predicted to be efficacy based-on in vitro: vanco, linezolid, ertapenem, azithro, tigecycline
  • AVOIDE using: metronidazole, cephalexin, dicloxacillin, aminoglycosides, fluoroquinolones
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3
Q

febrile neutropenia & septic shock

A
  • definition of febrile neutropenia: fever ≥38.3c or ≥38.0 sustain over 1hr period / neutropenia - absolute netrophil count (ANC) <500 or expected to decrease to <500 during next 48hrs
  • risk for MDROs in febrile neutropenic host: prolong hospitalized, presence of medical device, fluoroquinilones prophylaxis ให้หลายครั้ง risk เพิ่ม เสี่ยงติดกว่าไม่ให้อีก, previous expose w broad-spectrum ABX, previous infect MDROs เหมือนมัน colonization พี่จะอยู่!
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4
Q

emperic ABX for febrile neutropenia

A
  1. antipseudomonal beta-lactam: pip/tazo, carbapenem (ไม่นับ erta), ceftazidime, cefepime
  2. in combined w
    • anti-gram negative ABX (if in high prevalence of MDR gram neg): amikacin, colistin
    • anti-methicillin-resistant staphylococci (esp pt w device e.g. c-line, pneumonia, skin and soft tissue infection): vanco

ในสไลด์ใช้: meropenem + amikacin or colistin +/- vanco ที่กลัวดื้อยาจัด

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5
Q

how sepsis affecting plasma ABX conc

A
  • increase Vd
  • augmented renal clearance (ARC): increase drug clearance by kidney ทำให้ plasma drug conc ลด

แก้ด้วย: larger 1st dose (loading) → ละค่อยดูอีกทีว่าจะเพิ่มหรือลด maintenance dose

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6
Q

antifungal รวม ๆ

A
  • target of antifungal agent: ampho B and other polyenes (e.g. nystatin) → bind to ergosterol and increase membrane permeability / azole → inh 14-$a$-sterol demethylase for prevent ergosterol synthesis and lead to accumulate toxic (14-$a$-methylsterol) / echinocandins → inh 1,3-β-D-glucan formation in cell wall / flucytosine → disrupt fungal RNA DNA synthesis
  • ampho B (IV): broad spectrum, many ADR ∼ เคแม้กไตไข้สั่นซีด / เค้าเลยมี form ใหม่คือ lipid formulation ซึ่ง less nephrotoxic
  • azole — ทุกอัน affect CYP หมด มากน้อยต่างกันไป
    • fluconazole (PO IV): tx invasive candidiasis, crypto / high level in CSF
    • itraconazole (PO): tx dimorphic fungi / vary oral absorption
    • voriconazole (PO IV): แพง / tx invasive candidiasis, invasive asper / CYP2C19 inh and substrate / ADR visual disturbance, photosensitivity
    • posaconazole (PO): แพง / tx invasive candidiasis, invasive asper, mucormycosis / take w high-fat meal
  • echinocandins (caspofungin micafungin anidulafungin): tx invasive candidiasis, salvage therapy for invasive asper and invasive mucor / IV form, well tolerated, minimal unchange drug recover in urine, poor CNS penetrate
  • flucytosine: ไม่ใช่ยาหลักในการรักษา / tx crypto (only combine w ampho B or fluco) / ADR bone marrow toxic w anemia leukopenia thrombocytopenia
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7
Q

antifungal therapy in neutropenia pt

A
  • empirical: neutropenia expected to be >7 days AND persistent or recurrent fever after 4-7 days of ABX
  • prophylaxis: in high risk group such as allogeneic HSCT recipient, acute leukemia undergoing intensive remission-induction or salvage-induction chemotherapy
  • drug of choices: ampho B (ไว้เกิดไรขึ้นค่อยสวิตช์ไปตัวอื่น), ตัวอื่นที่พอได้ก็พวก fluco itra vori
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8
Q

crypto meningitis tx and crypto prophylaxis in PLWH

A

tx guideline for crypto meningitis
- induction phase [recommend]: liposomal ampho B (1 dose) + flucytosine (2wk) + fluconazole (2wk)
- consolidation or maintenance phase: fluco

crypto prophylaxis in PLWH - using fluconazole
- primary: start when CD4<100 / stop when initiate ART
- secondary (maintenance): start after consolidation tx finished / stop when CD4>100-200 and viral suppress on ART

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9
Q

antiparasite รวม ๆ

A

mechanism of all drug คือ inh folate metabolism (ยกเว้น pentamidine ที่ไม่รู้ mechanism)

  • TMP/SMX (PO IV): tx PCP toxoplasma / ADR hemato disorder, G6PD, dermatologic
  • dapsone (PO): tx PCP toxoplasma / ADR hemolysis, methemoglobinemia
  • pentamidine (IV): tx PCP / ADR infusion related ∼ hypotension tachycardia headache, hypogly, nephrotoxicity
  • pyrimethamine (PO): tx PCP toxoplasma / ADR dermato hemato anaphylaxis
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10
Q

PCP tx and PCP prophylaxis in PLWH

A

PCP tx
- mild-mod (A-a gradient≤35, PaO2>70): TMP-SMX / alternative → TMP+dapsone
- mod-severe (A-a gradient>35, PaO2≤70): TMP-SMX / alternative → primaquine+clindamycin, OR pentamidine / adjunct steroid within 72 hrs after tx initiate

PCP prophylaxis in PLWH (ภูมิต่ำอื่น ๆ ที่ไม่ใช่ HIV ก้ใช้ได้): TMP-SMX / alternative → dapsone
- primary: start when CD4<200 or 2-4wk after ART
- secondary: start after rx finished

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11
Q

other OIs prophylaxis in PLWH: talaromycosis, histoplasmosis, toxoplasmosis

A

talaromycosis (T) / histoplasmosis (H): itraconazole
- primary: start when CD4<100 (T) or CD4<150 (H) / stop after initiate ART
- secondary: start after tx finished / stop when CD4≥100 for≥3mo and undetected VL

toxoplasmosis
- primary: TMP-SMX / start when CD4<100 / stop when CD4>200 for≥3mo OR CD4≥100 but undetected VL for≥3-6mo
- secondary: pyrimethamine+sulfadiazine+folinic acid / start after tx finished / stop when CD4≥200 for≥6mo and undetected VL

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12
Q

antiviral รวม ๆ

A

anti-CMV agent — all drug inh herpesviral DNA polymerase
- ganciclovir (IV) valganciclovir (PO): tx CMV / ADR bone marrow suppression esp myelosuppression, CNS ∼ headache to behavior change to convulsion and coma, nephrotoxicity
- foscarnet (IV): tx CMV, acyclovir-resistant HSV, VZV / ADR nephrotoxicity, hypocal, CNS ∼ tremor irritability seizure hallucinosis
- cidofovir (IV): tx CMV, papilloma, polyoma, pox, adenovirus / ADR nephrotoxicity

HSV VZV
- acyclovir (IV): ADR nephrotoxicity (crystalline nephropathy) ค่อย ๆ ดริปจ้า / ห้ามใช้ PO มันห่วย
- valacyclovir (PO): ADR well-tolerated, headache, nausea, diarrhea, nephrotoxicity, CNS symptom ∼ confusion hallucination

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13
Q

NRTIs: lamivudine, emtricitabine, abacavir

A
  • lamivudine (3TC): ADR → nausea, headache, dizziness, fatigue
  • emtricitabine (FTC): ADR → headache, diarrhea, nausea, rash, hyperpigmented
  • abacavir (ABC): ตรวจ HLA-B*5701 ก่อนเสมอ / ADR → rash, hypersen, nausea ซึ่งพวกนี้อาจ increase in MI pt
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14
Q

NtRTIs: tenofovir ~ TDF, TAF (แทฟดีกว่า)

A
  • tenofovir disoproxil fumarate (TDF): ADR → n/v, diarrhea, flatulence, headache, renal insuff, bone loss
  • tenofovir alafenamide (TAF): ADR → GI symptom, headache, increase SCr, proteinuria, bone loss, weight gain

TAF ดีกว่าเพราะเข้าไปใน HIV target cell เต้ม ๆ และจะเหลือใน plasma น้อย while TDF ต้องใช้โดสเยอะกว่ามากเพราะเข้า cell น้อย เหลือใน plasma เพียบ

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15
Q

nonnucleoside reverse-transcriptase inh (NNRTIs): efavirenz, rilpivirine

A
  • efavirenz (EFV): take on empty stomach, at bedtime / ADR → neuropsychiatric, rash, liver enz สูง, headache, nausea
  • rilpivirine (RPV): take w food แบบจานใหย่ / ADR → headache, insomnia, depression, rash, liver enz สูง
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16
Q

integrase strand-transfer inh (INSTIs): dolutegravir, bictegravir, elvitegravir/cobicistat

A

ทุกตัวต้อง separate dosing from antacid by ≥2hr

  • dolutegravir (DTG): separate dosing from polyvalent cation by ≥2hr / taken once daily ดื้อยายาก กินคลาดไป 30 นาทีก้ไม่ดื้อ / ADR insomnia, headache, hypersen, liver enz สูง, weight gain
  • bictegravir (BIC): separate dosing from polyvalent cation by ≥2hr / once daily / ADR nausea, headache, diarrhea, rash, total bilirubin and SCr สูง
  • elvitegravir/cobicistat (EVG/c): take w food / once daily / ADR diarrhea, rash, liver enz สูง
17
Q

protease inh (PIs): lopinavir/ritonavir, atazanavir/ritonavir, darunavir/ritonavir

A
  • lopinavir/ritonavir (LPV/r): once daily / ADR diarrhea, nausea, hypertriglyceridemia, liver enz สูง, cholesterol สูง
  • atazanavir/ritonavir (ATV/r): take w food, separate dosing acid reducing agent by ≥10hr / once daily / ADR nausea, rash, indirect hyperbilirubinemia, diarrhea, liver enz สูง, prolong PR
  • darunavir/ritonavir (DRV/r): take w food / once daily / ADR diarrhea, nausea, headache, rash, hyperlipidemia, liver enz สูง, serum amylase สูง
18
Q

ART regimen

A
  1. backbone 2 agent: TXF+XTC (or ABC+3TC or AZT+3TC)
    • 3rd agent: DTG (or EFV or RPV)

ตัวอย่างยา ( / คือเม็ดเดียวกัน, + คือคนละเม็ด)
- TDF/3TC/DTG: once daily ดีสุด
- TDF/FTC +DTG: 2 tap once daily
- TDF/FTC/EFV
- ABC/3TC/DTG: ตรวจ HLA ก่อง

19
Q

when to start ART in PLWH w OIs คือส่วนมากก้ 2-4 4-6wk อะ ถ้าข้อสอบลงลึกค่อยมาสรุป

A

ช่าย

20
Q

prevention มาต่อออ

A
  • PrEP (pre) — TDF/FTC, TAF/FTC, cabotegravir every 2mo, lenacapavir twice a year
    • daily: TDF/FTC 1 tab once daily ถ้ายัง having SI → after last SI ให้กินยาไปอีก 28 วัน
    • on-demand: TDF/FTC 2 tab (2-24hr before SI) → 1 tab once daily ถ้ายัง having SI → 24hr after last SI 1 tab → after 24hr 1 tab
  • PEP (post)
    • type
      • oPEP (occupation): เข็มตำ มีดบาด
      • nPEP (non-occupation): anus receptive เสี่ยงสุด when no condom
    • regimen: TDF/3TC/DTG (TLD) or TAF/FTC/DTG (kocitaf) or TDF/FTC+DTG
21
Q

glucocorticoids: prednisone, prednisolone, and other glucocorticoids

A
  • mechanism: bind to intracellular receptor and regulate transcription of numerous other genes → inh T cell proliferative and inh making of IL-2
  • use: combine w other immunosuppressive, routine used to treat autoimmune
  • toxic: ก้ทั่วไปตามสเตปสเตียรอยด์
22
Q

calcineurin Inhibitors (CNI): tacrolimus, cyclosporin A

A

tacrolimus
- from macrolide ABX
- mechanism: bind to intracellular protein (FKBP12) ~ inh T cell activation by inh calcineurin
- ADME: food decrease rate and extent of absorption, metabolized by CYP3A & excrete in feces
- use: prophylaxis of solid organ allograft rejection
- toxic: nephrotoxicity, (not adversely affect uric acid or LDL cholesterol)
- drug monitor is a must

cyclosporin A
- from fungus
- mechanism: form complex w cytoplasmic receptor protein (cyclophilin) in target cell
- ADME: food delay and decrease absorption, metabolized by CYP3A & excrete through bile into feces (ลงฉี่บ้าง 6%)
- hepatic dysfx → need dose adjust (no need for renal failure or dialysis)
- use: solid organ, rheumatoid arthritis, psoriasis, xerophthalmia [spectrum กว้างกว่า tacro]
- toxic: nephrotoxicity, HT, hyperlipidemia, hyperuricemia
- drug monitor is a must
- DI: sirolimus aggravates cyclosporine-induced renal dysfunction while cyclosporine increases sirolimus-induced
hyperlipidemia and myelosuppression — ถ้าจะใช้คู่กัน ให้โดย separated by time

23
Q

antiproliferative and antimetabolic drugs: sirolimus (rapamycin), everolimus

A

sirolimus (rapamycin)
- from macrocyclic lactone
- mechanism: mammalian target of rapamycin (mTor) inh
- ADME: high fat meal decrease Cpeak = should take w/o food, metabolized by CYP3A and transport by P-glycoprotein, excrete in feces
- use: prophylaxis organ transplant rejection, combine w reduced dose of CNI and glucocorticoid
- toxic: dose-dependent increase in serum CHO and TG that may require treatment, use w cyclosporin cause impair renal fx, worsen proteinuria เลยต้องระวังเวลาให้กับ pt GFR below 30% or proteinuria
- DI: dose adjust may required when use w CYP3A4 and P-glycoprotein inh (e.g. diltiazem) or strong inducer (e.g. rifampin)

everolimus
- ปรับโมเลกุลมาจาก sirolimus อีกที
- mechanism: form complex w cyclophilin
- ADME: shorter t1/2 and shorter time to achieve steady-state conc
- toxic: dose-dependent increase in serum CHO and TG that may require treatment

24
Q

antiproliferative and antimetabolic drugs: azathioprine, mycophenolate mofetil

A

azathioprine
- source: purine antimetabolite
- action: 6-thio-IMP convert to 6-thio-GMP and finally to 6-
thio-GTP, which can inh de novo purine synthesis
- use: adjunct for prevention of organ transplant rejection and in severe rheumatoid arthritis
- toxic: BM suppression (esp คนไทย NUDT15)
- DI: blocked by allopurinol, when use w other myelosuppressive agents or angiotensin converting enz inh (which lead to leukopenia, thrombocytopenia, anemia)

mycophenolate mofetil (MMF)
- source: 2-morpholinoethyl ester of mycophenolate (MPA)
- action: prodrug**, noncompetitive, reversible inhibitor of inosine
monophosphate dehydrogenase (IMPDH) คือเปน enz ที่กก de novo guanine synthesis ซึ่งพอไม่มี protein สร้างใหม่ พวก T cell B cell ก้ไม่มีพลังงาน ไรเง้
- use: prophylaxis of transplant rejection, combine w glucocorticoid and CNI but not w azathioprine
- toxic: GI (diarrhea, vomit) hemato (leukopenia, pure red cell aplasia)
- DI: tacrolimus delay elimination of MMF ทำให้ท้อกซิก / decreased absorption of MMF when use w antacids containing aluminum or magnesium hydroxide ถ้าจะกินก้กินให้ห่าง ๆ กัน / NOT use w cholestyramine or other drugs that affect enterohepatic circulation เพราะจะ decrease plasma MPA conc / acyclovir and ganciclovir may compete w MPAG for tubular secretion สรุปไม่มีใครได้ออก conc สูงคู่

25
Q

other antiproliferative and cytotoxic agents: methotrexate, cyclophosphamide, thalidomide

A
  • ปกติ used in cancer chemotherapy
  • methotrexate used for prophylaxis against GVHD, and tx of rheumatoid arthritis, psoriasis, bullous pemphigoid, and some cancers
  • cyclophosphamide and chlorambucil are used in leukemia, lymphomas, and various other malignancie
26
Q

immunosuppression antibodies and fusion receptor protein: antithymocyte globulin (ATG) ไม่ค่อยครบเพราะฉันงง

A
  • 1st gen murine mAbs have been replaced by newer humanized or fully human mAbs that lack antigenicity, have a prolonged t1/2, and can be mutagenized to alter their affinity to Fc receptors
  • mechanism: antithymocyte globulin contains cytotoxic Ab that bind to CD2,3, 4, 8, 11a, 18, 25, 44, 45, and HLA class I & II ทำให้ deplete circulating lymphocytes by direct cytotoxicity (both complement and cell-mediated) and block lymphocyte fx
  • use: induction immunosuppression (ตัวที่ผ่านมาเปน maintenance หมด)
  • toxic: polyclonal Ab are xenogeneic proteins that can elicit major side effect (e.g. fever and chills with the potential for hypotension)
27
Q

monoclonal antibody: alemtuzumab, basiliximab, belatacept

A

alemtuzumab
- mechanism: Anti-CD52 mAb (binding to CD52 induces an antibody-dependent lysis of cells and a profound leukopenia)
- use: induction of immunosuppressive therapy and allows
the avoidance of early high dose of steroids
- toxic: neutropenia (most common), thrombocytopenia, anemia

basiliximab
- mechanism: anti-IL-2 receptor (anti-CD25) Ab
- use: induction therapy in solid organ transplantation, conjunct w cyclosporine and corticosteroids for prophylaxis of acute organ rejection in pt who receiving renal transplants
- toxic: safe, adverse reactions rate comparable to placebo

belatacept
- mechanism: selective T-cell co-stimulation blocker that potently binds to CD80 and CD86 present on APCs, interrupting their interaction with CD28 on T cells
- use: alternative to CNI as a strategy to prevent long-term CNI toxicity / prophylaxis of organ rejection in adult pt who receiving kidney transplant in combination w basiliximab induction, MMF, corticosteroids
- toxic: increased risk of post-transplant lymphoproliferative disorder (PTLD) in EBV seronegative แต่ถ้า seropositive ใช้ได้ปกติ ดังนั้นก่อนให้ยาต้องตรวจก่อนน้า

immuno II (2 decks)

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