Therapeutics Winter Final

Front 1

Goals of Transplantation

Back 1

1) Treatment of end-stage organ disease
2) Improve survival and quality of life
3) More cost-effective versus dialysis

Front 2

Goal of Immunosuppressive Therapy

Back 2

Balance therapy in terms of patient and graft survival

Front 3

Immunosuppressive Regimens

Back 3

1) Induction therapy
2) Maintenance Therapy
3) Rejection therapy

Front 4

Induction therapy

Back 4

potent prophylactic therapy at the time of transplant

Front 5

Maintenance therapy

Back 5

chronic immunosuppression

less potent

Front 6

Rejection therapy

Back 6

potent therapy used in an episode

Front 7

Immunosuppressive agents

Back 7

1) Polyclonal Antibodies
2) Monoclonal Antibodies
3) IL-2a receptor antagonists
4) Calcineurin Inhibitors
5) mTOR inhibitors
6) Anti-metabolites
7) Corticosteroids

Front 8

Polyclonal Antibodies

Back 8

1) ATGAM (equine) - test dose
2) Thymoglobulin (rabbit)

Front 9

MOA, indications of PolyClonal Antibodies

Back 9

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**

Front 10

ADRs of polyclonal antibodies

Back 10

1) LEUKOPENIA, THROMBOCYTOPENIA (DLT)
2) fever, chills
3) rash, redness
4) INFECTION

Front 11

Polyclonal antibodies

Back 11

1) monitor absolute lymphocyte count and/or absolute CD3 count, CBC, LFTs, SCr

2) infused through central vein

Front 12

IL-2 Receptor Antagonists

Back 12

1) Basiliximab (Simulect)

Front 13

MOA, Indications of Basiliximab (Simulect)

Back 13

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

Front 14

Monoclonal Antibodies

Back 14

1) Alemtuzumab (Campath-1H)
2) muromonab-CD3 (OKT3)
3) Rituximab (Rituxan)

Front 15

MOA, Indications of Alemtuzumab (Campath-1H)

Back 15

MOA: anti-CD52 antibody - profound depletion of T cells and to a lesser degree B cells and monocytes

Indication: induction and/or refractory rejection

Front 16

ADRs of Alemtuzumab (Campath-1H)

Back 16

1) Infusion related (chills, rigors, fever)
2) Infection

Front 17

MOA, ADRs of Muromonab-CD3

Back 17

MOA: binds to CD3 antigens of T cells leading to T-cell depletion

ADRs: Infection, Cytokine Release Syndrome

Front 18

MOA, Indication, ADRs of Rituximab

Back 18

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

Front 19

MOA, Indication ADRs of IV IG

Back 19

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

Front 20

MOA, ADRs of corticosteroids in transplant

Back 20

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

Front 21

Calcineurin Inhibitors

Back 21

1) Tacrolimus (Prograf)
2) Cyclosporin

Front 22

Generic products of cyclosporin

Back 22

MODIFIED: Neoral, Gengraf

NON-MODIFIED: Sandimmune

Front 23

MOA of Calcineurin Inhibitors

Back 23

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

Front 24

Drug Interations and Monitoring for Cyclosporin

Back 24

INT: CYP3A4 and Pgp inhibitors/inducers, statins, nephrotoxic drugs

MONITOR: 12-hr trough (CO) vs 2-hr post dose (C2)

Front 25

ADRs of cyclosporin and Tacrolimus

Back 25

1) Nephrotoxicity
2) Neurotoxicity
3) Hyperglycemia
4) Hyperkalemia
5) Infection

Front 26

Drug Interractions and Monitoring for Tacrolimus (Prograf)

Back 26

INT: CYP3A4 and Pgp inhibitors/inducers, nephrotoxic drugs

MONITOR: 12 hr trough levels (C0)

Front 27

Antimetabolites

Back 27

1) Azathioprine (Imuran)
2) Mycophenolic acid (Cellcept, Myfortic)

Front 28

MOA, ADRs, Drug interactions of Azathioprine

Back 28

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

Front 29

MOA, ADRs, Drug interactions of Mycophenolic Acid

Back 29

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

Front 30

mTOR inhibitor

Back 30

Sirolimus (Rapamune)

Front 31

MOA of sirolimus (Rapamune)

Back 31

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

Front 32

Monitoring and ADRs of Sirolimus (Rapamune)

Back 32

MONITOR: 24hr trough levels (C0) - should continue same dose for 7 days before adjusting dose

ADRs: thrombocytopenia, leukopenia, Anemia, hypertriglyceridemia, impaired wound healing, pneumonitis

Front 33

MOA and Indication of Belatacept (Nulojix)

Back 33

binds to the CD80 and CD86 receptors - blocks the CD28 mediated costimulation of T cells

IND: maintenance

Front 34

ADRs of Belatacept (Nulojix)

Back 34

BBW: posttransplant lymphoproliferative disorder - high risk in patients NOT exposed to Epstein-Barr virus

anemia, neutropenia, diarrhea, UTI

Front 35

Where does Belatacept (Nulojix) work

Back 35

Signal 2

Front 36

Drugs used in Induction Therapy

Back 36

1) IL-2 receptor antagonist (Basiliximab)
2) T-lymphocyte depleting agent (Thymoglobulin/Alemtuzumab)
3) High dose maintenance therapy (Tacro, mycophenolate)

Front 37

Drugs used in Maintenance Therapy

Back 37

1) Calcineurin Inhibitor (Tacro, cyclosporin)
2) Antimetabolite (mycophenolate, azathioprine)
3) Corticosteroid

Front 38

Corticosteroid withdrawal or Avoidance

Back 38

Goal: decrease long-term toxicity

Increased risk of infection: <1 week post transplant taper

Front 39

Calcineurin Inhibitor Withdrawal

Back 39

Sirolimus + Antimetabolite + Steroid

high incidence of acute rejection

Front 40

Rejection Pathophys

Back 40

immune response causing injury through inflammation and direct tissue destruction to the transplanted tissue

Front 41

4 types of rejection

Back 41

1) Hyperacute
2) Acute T-cell mediated
3) Acute antibody mediated
4) Chronic

Front 42

Hyperacute Rejection

Back 42

Occurs within minutes to hours

mediated by preformed circulating antibodies

Front 43

Acute T-cell mediated Rejection

Back 43

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

Front 44

Acute Antibody Mediated Rejection (B-Cell)

Back 44

results from documented circulating anti-donor antibodies, positive C4d staining with detection in the peritubular capillaries, and mophologic evidence of acute injury

Front 45

Chronic rejection

Back 45

**MOST COMMON**

occurs over months to years

may be T-cell or antibody mediated (not completely stopping production, a few are still being produced)

Front 46

Opportunistic Infections

Back 46

being or caused by an usually harmless microorganism that can become pathogenic when the host's resistance is impaired

Front 47

AIDS surveillane case definition

Back 47

CD4 T-lymphocyte count <200
OR
documentation of an AIDS-defining condition

Front 48

AIDS-defining conditions - Opportunistic Infections

Back 48

1) Candidiasis
2) Cryptococcosis
3) Cytomegalovirus disease (CMV)
4) Mycobacterium avium-intracellulare (MAI/MAC)
5) Pneumocystis jiroveci pneumoni (PCP, PJP)
6) Toxoplasmosis

Front 49

Prevention of OIs in HIV patients

Back 49

**CD4 T-cell count**
1) dictates the needs for OI prophylaxis
2) Affects the differential diagnosis
3) Independent indicator of prognosis

Front 50

Primary Prophylaxis in OIs

Back 50

**Initiated before appearance**

1) PCP/PJP
2) Toxoplasma
3) MAC

Front 51

Secondary Prophylaxis in OIs

Back 51

**prevents the recurrence **

Front 52

Pneumocystis Jeroveci Pneumonia (PJP/PCP)

Back 52

Fungus that has characteristics of a protozoa

Spreads by the airborne route

Can't treat with antifungals

Front 53

Primary Prophylaxis for PJP/PCP

Back 53

CD4 < 200

Front 54

Diagnosis of PJP/PCP

Back 54

1) history
2) clinical presentation (progressive dyspnea, fever, nonproductive cough, chest pain)

Front 55

Diagnosis of Mild to Moderate PJP/PCP

Back 55

A-a O2 < 35

PaO2 >/= 70

Front 56

Diagnosis of Moderate to Severe PJP/PCP

Back 56

A-a O2 > 45

PaO2 < 70

Front 57

Primary Prophylaxis for PJP/PCP

CD4 < 200

Back 57

Bactrim 1 double strand tablet PO QD

D/C: CD4 > 200 for > 3 months

Restart: CD4 < 200 or PCP reoccurs

Front 58

Treatment of PCP/PJP

Back 58

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

Front 59

Treatment of PJP with Corticosteroids

Back 59

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**

Front 60

ADRs of TMP-SMX

Back 60

1) Rash
2) Leukopenia, thrombocytopenia
3) Hyperkalemia

Front 61

ADRs of Dapsone and Primaquine

Back 61

Hemolysis/ hemolytic anemia - G6PD deficiency

Front 62

ADRs of pentamidine

Back 62

1) pancreatitis
2) hypo- or hyperglycemia
3) leukopenia
4) electrolyte abnormalities
5) cardiac dysrhythmia

Front 63

ADRs of primaquine and clindamycin

Back 63

1) hemolytic anemia
2) Diarrhea

Front 64

ADR of Atovaquone

Back 64

transaminase elevation

Front 65

Toxoplasma gondii encephalitis (TE)

Back 65

Protozoa

Occurs after eating uncooked meat, cat feces

CD4 < 100

Front 66

Clinical presentation of TE

Back 66

1) headache
2) confusion
3) fever
4) motor weakness

Front 67

Primary prophylaxis for TE

(+) antiToxo IgG & CD4 < 100

Back 67

Bactrim 1 double strength tablet PO QD

Front 68

Preferred Treatment for Toxoplasma Encephalitis

Back 68

Pyrimethamine
+
Sulfadiazine
+
Leucovorin

for 6 weeks at least

Front 69

Alternate treatment for TE

Back 69

Clindamycin
+
Pyrimethamine
+
Leucovorin

for 6 weeks at least

Front 70

ADRs of pyrimethamine

Back 70

1) Bone marrow suppression (neutropenia, anemia, thrombocytopenia)

reversible by increasing Leucovorin

Front 71

Mycobacterium avium Complex (MAC)

Back 71

ubiquitous

transmitted thru inhalation, ingestion

CD4 < 50

Front 72

Clinical presentation of MAC

Back 72

1) fever
2) night sweats
3) weight loss
4) fatigue
5) Diarrhea
6) abdominal pain

Front 73

Prophylaxis of MAC

CD4 < 50

Back 73

Azithromycin 1200 mg/week PO

Front 74

Preferred Treatment for MAC

Back 74

Clarithromycin
+
Ethambutol
+/-
Rifabutin

for life OR 12 months of treatment+asymptomatic+CD4 > 100 > 6 months

Front 75

Alternative treatment for MAC

Back 75

Azithromycin
+
Ethambutol

Front 76

ADRs of rifabutin

Back 76

1) GI upset
2) abnormal liver function tests
3) discoloration of skin/body fluids

Front 77

Major cause of mucocutaneous candidiasis

Back 77

candida albicans

CD4 < 200

Front 78

Treatment of Pharyngeal mucocutaneous candidiasis

Back 78

Fluconazole 100mg PO QD x7-14 days

Front 79

Treatment of Esophageal mucocutaneous candidiasis

Back 79

Fluconazole 100mg (up to 400mg) PO QD x 14-21 days

Front 80

Cryptococcal meningitis

Back 80

CD4 < 50

yeast

Front 81

Clinical Presentation of Cryptococcal Meningitis

Back 81

1) stiff neck and photophobia
2) fever
3) Headache
4) malaise
5) lethargy
6) altered mental status
7) memory loss

Front 82

Induction treatment of Cryptococcal meningitis (1st 2 weeks)

Back 82

L-AmB 3-4 mg/kg IV
+
Flucytosine x 2 weeks

Front 83

Consolidation treatment of cryptococcal meningitis

Back 83

fluconazole 400mg QD x 8 weeks

Front 84

Maintenance treatment of cryptococcal meningitis

Back 84

fluconazole 200mg QD x 1 year

Front 85

ADRs of AmB

Back 85

1) nephrotoxicity
2) electrolyte disturbances
3) infusion related

Front 86

Cytomegalovirus retinitis (CMV)

Back 86

Herpes virus

CD4 < 50

Front 87

Clinical presentation of CMV

Back 87

1) asymptomatic
2) floaters
3) peripheral visual field defects

Front 88

Cytomegalovirus can affect

Back 88

1) retinitis
2) colitis
3) esophagitis
4) pneumonitis
5) neurological

Front 89

Treatment of CMV

Back 89

Valganciclovir 900mg BID x14-21 days, then 900mg QD
or
Ganciclovir 5mg/kg IV q12h x14-21 days

Alt: Foscarnet, Cidofovir

Front 90

ADRs of Valganciclovir/Ganciclovir

Back 90

1) neutrompenia
2) thrombocytopenia
3) N/D

Front 91

ADRs of Foscarnet

Back 91

1) Anemia
2) Nephrotoxicity
3) electrolyte abnormalities

Front 92

ADRs of Cidofovir

Back 92

1) dose-related toxicity (very long half life)

give with probenacid + hydration

Front 93

Advantages of ART in OIs

Back 93

1) preventative (improves CD4)
2) effective where effective therapy doesn't exist

Front 94

Disadvantages of ART in OIs

Back 94

1) increase resistance
2) toxicities
3) drug-drug interactions
4) renal/hepatic dysfunction
5) IRIS

Front 95

Immune Reconstitution Inflammatory Syndrome (IRIS)

Back 95

Increase the immune system leads to fever and worsening of OI

occurs 4-8 weeks after start of ART