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95 Cards in this Set
- Front
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Goals of Transplantation
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1) Treatment of end-stage organ disease
2) Improve survival and quality of life 3) More cost-effective versus dialysis |
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Goal of Immunosuppressive Therapy
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Balance therapy in terms of patient and graft survival
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Immunosuppressive Regimens
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1) Induction therapy
2) Maintenance Therapy 3) Rejection therapy |
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Induction therapy
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potent prophylactic therapy at the time of transplant
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Maintenance therapy
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chronic immunosuppression
less potent |
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Rejection therapy
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potent therapy used in an episode
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Immunosuppressive agents
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1) Polyclonal Antibodies
2) Monoclonal Antibodies 3) IL-2a receptor antagonists 4) Calcineurin Inhibitors 5) mTOR inhibitors 6) Anti-metabolites 7) Corticosteroids |
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Polyclonal Antibodies
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1) ATGAM (equine) - test dose
2) Thymoglobulin (rabbit) |
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MOA, indications of PolyClonal Antibodies
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MOA: reduces the number of circulating T-lymphocytes and eliminates pre-activated lymphocytes
Indications: induction and/or rejection **Pre-medication required w/ APAP, diphenhydramine, +/- corticosteroid** |
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ADRs of polyclonal antibodies
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1) LEUKOPENIA, THROMBOCYTOPENIA (DLT)
2) fever, chills 3) rash, redness 4) INFECTION |
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Polyclonal antibodies
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1) monitor absolute lymphocyte count and/or absolute CD3 count, CBC, LFTs, SCr
2) infused through central vein |
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IL-2 Receptor Antagonists
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1) Basiliximab (Simulect)
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MOA, Indications of Basiliximab (Simulect)
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MOA: recombinant, chimeric monoclonal antibodies against CD25 - binds to the alpha subunit of IL-2 receptor on activated and non-resting T cells
Indication: induction |
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Monoclonal Antibodies
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1) Alemtuzumab (Campath-1H)
2) muromonab-CD3 (OKT3) 3) Rituximab (Rituxan) |
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MOA, Indications of Alemtuzumab (Campath-1H)
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MOA: anti-CD52 antibody - profound depletion of T cells and to a lesser degree B cells and monocytes
Indication: induction and/or refractory rejection |
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ADRs of Alemtuzumab (Campath-1H)
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1) Infusion related (chills, rigors, fever)
2) Infection |
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MOA, ADRs of Muromonab-CD3
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MOA: binds to CD3 antigens of T cells leading to T-cell depletion
ADRs: Infection, Cytokine Release Syndrome |
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MOA, Indication, ADRs of Rituximab
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MOA: anti-CD20 chimeric monoclonal antibody; binds CD20 antigen on B LYMPHOCYTES inducing cell lysis (Depletes B CELLS)
Indication: off label in transplant; antibody mediated rejection ADRs: infection BBW: Cytokine Release Syndrome, ARDS |
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MOA, Indication ADRs of IV IG
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MOA: modification of antibody levels thru induction of anti-idiotypic circuits; inhibits T-cell activation and complement activity; induction of B-cell apoptosis
Indication: Off label in transplant; antibody mediated rejection ADRs: infusion related, thromboembolism |
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MOA, ADRs of corticosteroids in transplant
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MOA: anti-inflammatory (inhibits prostaglandins and leukotrienes); immunosuppressive (inhibits cytokine production by T cells or macrophages)
ADRs: hyperglycemia, HTN, infection, GI disturbances, impaired wound healing, leukocytosis |
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Calcineurin Inhibitors
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1) Tacrolimus (Prograf)
2) Cyclosporin |
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Generic products of cyclosporin
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MODIFIED: Neoral, Gengraf
NON-MODIFIED: Sandimmune |
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MOA of Calcineurin Inhibitors
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inhibits first phase of T-cell activation leading to reduced circulating levels of T-cell activators
Prevents IL-2 gene transcription - inhibits T-cell IL-2 production |
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Drug Interations and Monitoring for Cyclosporin
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INT: CYP3A4 and Pgp inhibitors/inducers, statins, nephrotoxic drugs
MONITOR: 12-hr trough (CO) vs 2-hr post dose (C2) |
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ADRs of cyclosporin and Tacrolimus
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1) Nephrotoxicity
2) Neurotoxicity 3) Hyperglycemia 4) Hyperkalemia 5) Infection |
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Drug Interractions and Monitoring for Tacrolimus (Prograf)
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INT: CYP3A4 and Pgp inhibitors/inducers, nephrotoxic drugs
MONITOR: 12 hr trough levels (C0) |
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Antimetabolites
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1) Azathioprine (Imuran)
2) Mycophenolic acid (Cellcept, Myfortic) |
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MOA, ADRs, Drug interactions of Azathioprine
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MOA: incorporated into nucleic acid leads to inhibition of DNA and RNA synthesis - inhibits lymphocyte proliferation
ADRs: leukopenia, thrombocytopenia, hepatotoxicity, Infection INT: allopurinol, myelosuppressive agents |
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MOA, ADRs, Drug interactions of Mycophenolic Acid
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MOA: inhibits lymphocyte purine synthesis by reversibly and noncompetitively inhibiting inosine monophos dehydrogenase - inhibits lymphocyte proliferation
ADRs: N/V/D, neutropenia, thrombocytopenia, anemia, infection INT: aluminum containing antacids, cholestryramine, myelosuppressive agents |
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mTOR inhibitor
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Sirolimus (Rapamune)
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MOA of sirolimus (Rapamune)
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inhibits the 2nd phase of T-cell activation and proliferation
binds to FK-binding protein 12 blocks signal transduction pathways inhibiting IL-2 induced cell cycle |
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Monitoring and ADRs of Sirolimus (Rapamune)
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MONITOR: 24hr trough levels (C0) - should continue same dose for 7 days before adjusting dose
ADRs: thrombocytopenia, leukopenia, Anemia, hypertriglyceridemia, impaired wound healing, pneumonitis |
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MOA and Indication of Belatacept (Nulojix)
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binds to the CD80 and CD86 receptors - blocks the CD28 mediated costimulation of T cells
IND: maintenance |
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ADRs of Belatacept (Nulojix)
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BBW: posttransplant lymphoproliferative disorder - high risk in patients NOT exposed to Epstein-Barr virus
anemia, neutropenia, diarrhea, UTI |
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Where does Belatacept (Nulojix) work
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Signal 2
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Drugs used in Induction Therapy
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1) IL-2 receptor antagonist (Basiliximab)
2) T-lymphocyte depleting agent (Thymoglobulin/Alemtuzumab) 3) High dose maintenance therapy (Tacro, mycophenolate) |
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Drugs used in Maintenance Therapy
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1) Calcineurin Inhibitor (Tacro, cyclosporin)
2) Antimetabolite (mycophenolate, azathioprine) 3) Corticosteroid |
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Corticosteroid withdrawal or Avoidance
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Goal: decrease long-term toxicity
Increased risk of infection: <1 week post transplant taper |
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Calcineurin Inhibitor Withdrawal
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Sirolimus + Antimetabolite + Steroid
high incidence of acute rejection |
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Rejection Pathophys
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immune response causing injury through inflammation and direct tissue destruction to the transplanted tissue
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4 types of rejection
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1) Hyperacute
2) Acute T-cell mediated 3) Acute antibody mediated 4) Chronic |
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Hyperacute Rejection
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Occurs within minutes to hours
mediated by preformed circulating antibodies |
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Acute T-cell mediated Rejection
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Most common during first 3 months post transplant
mediated by allo-reactive T-cells possible causes: missing drug interactions, noncompliance, drug not reaching therapeutic levels |
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Acute Antibody Mediated Rejection (B-Cell)
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results from documented circulating anti-donor antibodies, positive C4d staining with detection in the peritubular capillaries, and mophologic evidence of acute injury
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Chronic rejection
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**MOST COMMON**
occurs over months to years may be T-cell or antibody mediated (not completely stopping production, a few are still being produced) |
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Opportunistic Infections
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being or caused by an usually harmless microorganism that can become pathogenic when the host's resistance is impaired
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AIDS surveillane case definition
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CD4 T-lymphocyte count <200
OR documentation of an AIDS-defining condition |
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AIDS-defining conditions - Opportunistic Infections
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1) Candidiasis
2) Cryptococcosis 3) Cytomegalovirus disease (CMV) 4) Mycobacterium avium-intracellulare (MAI/MAC) 5) Pneumocystis jiroveci pneumoni (PCP, PJP) 6) Toxoplasmosis |
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Prevention of OIs in HIV patients
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**CD4 T-cell count**
1) dictates the needs for OI prophylaxis 2) Affects the differential diagnosis 3) Independent indicator of prognosis |
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Primary Prophylaxis in OIs
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**Initiated before appearance**
1) PCP/PJP 2) Toxoplasma 3) MAC |
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Secondary Prophylaxis in OIs
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**prevents the recurrence **
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Pneumocystis Jeroveci Pneumonia (PJP/PCP)
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Fungus that has characteristics of a protozoa
Spreads by the airborne route Can't treat with antifungals |
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Primary Prophylaxis for PJP/PCP
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CD4 < 200
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Diagnosis of PJP/PCP
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1) history
2) clinical presentation (progressive dyspnea, fever, nonproductive cough, chest pain) |
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Diagnosis of Mild to Moderate PJP/PCP
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A-a O2 < 35
PaO2 >/= 70 |
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Diagnosis of Moderate to Severe PJP/PCP
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A-a O2 > 45
PaO2 < 70 |
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Primary Prophylaxis for PJP/PCP
CD4 < 200 |
Bactrim 1 double strand tablet PO QD
D/C: CD4 > 200 for > 3 months Restart: CD4 < 200 or PCP reoccurs |
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Treatment of PCP/PJP
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Mild-Mod: Bactrim 15-20 mg/kg/day PO divided TID x 21 days OR 2 double strength tabs TID x 21 days
Mod-Sev: Bactrim 15-20 mg/kg/day IV divided q6-8h x 21 days |
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Treatment of PJP with Corticosteroids
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Prednisone 40mg po BID days 1-5, 40mg PO qd days 6-10, then 20mg PO daily days 11-21
IV methylprednisolone 75% of prednisone dose **Preferred within 72 hours of starting treatment** |
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ADRs of TMP-SMX
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1) Rash
2) Leukopenia, thrombocytopenia 3) Hyperkalemia |
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ADRs of Dapsone and Primaquine
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Hemolysis/ hemolytic anemia - G6PD deficiency
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ADRs of pentamidine
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1) pancreatitis
2) hypo- or hyperglycemia 3) leukopenia 4) electrolyte abnormalities 5) cardiac dysrhythmia |
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ADRs of primaquine and clindamycin
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1) hemolytic anemia
2) Diarrhea |
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ADR of Atovaquone
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transaminase elevation
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Toxoplasma gondii encephalitis (TE)
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Protozoa
Occurs after eating uncooked meat, cat feces CD4 < 100 |
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Clinical presentation of TE
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1) headache
2) confusion 3) fever 4) motor weakness |
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Primary prophylaxis for TE
(+) antiToxo IgG & CD4 < 100 |
Bactrim 1 double strength tablet PO QD
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Preferred Treatment for Toxoplasma Encephalitis
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Pyrimethamine
+ Sulfadiazine + Leucovorin for 6 weeks at least |
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Alternate treatment for TE
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Clindamycin
+ Pyrimethamine + Leucovorin for 6 weeks at least |
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ADRs of pyrimethamine
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1) Bone marrow suppression (neutropenia, anemia, thrombocytopenia)
reversible by increasing Leucovorin |
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Mycobacterium avium Complex (MAC)
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ubiquitous
transmitted thru inhalation, ingestion CD4 < 50 |
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Clinical presentation of MAC
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1) fever
2) night sweats 3) weight loss 4) fatigue 5) Diarrhea 6) abdominal pain |
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Prophylaxis of MAC
CD4 < 50 |
Azithromycin 1200 mg/week PO
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Preferred Treatment for MAC
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Clarithromycin
+ Ethambutol +/- Rifabutin for life OR 12 months of treatment+asymptomatic+CD4 > 100 > 6 months |
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Alternative treatment for MAC
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Azithromycin
+ Ethambutol |
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ADRs of rifabutin
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1) GI upset
2) abnormal liver function tests 3) discoloration of skin/body fluids |
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Major cause of mucocutaneous candidiasis
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candida albicans
CD4 < 200 |
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Treatment of Pharyngeal mucocutaneous candidiasis
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Fluconazole 100mg PO QD x7-14 days
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Treatment of Esophageal mucocutaneous candidiasis
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Fluconazole 100mg (up to 400mg) PO QD x 14-21 days
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Cryptococcal meningitis
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CD4 < 50
yeast |
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Clinical Presentation of Cryptococcal Meningitis
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1) stiff neck and photophobia
2) fever 3) Headache 4) malaise 5) lethargy 6) altered mental status 7) memory loss |
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Induction treatment of Cryptococcal meningitis (1st 2 weeks)
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L-AmB 3-4 mg/kg IV
+ Flucytosine x 2 weeks |
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Consolidation treatment of cryptococcal meningitis
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fluconazole 400mg QD x 8 weeks
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Maintenance treatment of cryptococcal meningitis
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fluconazole 200mg QD x 1 year
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ADRs of AmB
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1) nephrotoxicity
2) electrolyte disturbances 3) infusion related |
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Cytomegalovirus retinitis (CMV)
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Herpes virus
CD4 < 50 |
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Clinical presentation of CMV
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1) asymptomatic
2) floaters 3) peripheral visual field defects |
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Cytomegalovirus can affect
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1) retinitis
2) colitis 3) esophagitis 4) pneumonitis 5) neurological |
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Treatment of CMV
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Valganciclovir 900mg BID x14-21 days, then 900mg QD
or Ganciclovir 5mg/kg IV q12h x14-21 days Alt: Foscarnet, Cidofovir |
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ADRs of Valganciclovir/Ganciclovir
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1) neutrompenia
2) thrombocytopenia 3) N/D |
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ADRs of Foscarnet
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1) Anemia
2) Nephrotoxicity 3) electrolyte abnormalities |
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ADRs of Cidofovir
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1) dose-related toxicity (very long half life)
give with probenacid + hydration |
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Advantages of ART in OIs
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1) preventative (improves CD4)
2) effective where effective therapy doesn't exist |
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Disadvantages of ART in OIs
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1) increase resistance
2) toxicities 3) drug-drug interactions 4) renal/hepatic dysfunction 5) IRIS |
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Immune Reconstitution Inflammatory Syndrome (IRIS)
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Increase the immune system leads to fever and worsening of OI
occurs 4-8 weeks after start of ART |