Transplant Drugs & HIV Antiretrovirals

Question 1

organ rejection that happens within days due to reactivation of sensitized T cells

Answer 1

accelerated

Question 2

refers to organ rejection that develops over days to weeks in association with primary activation of T cells in response to antigens expressed on the surface of allograft cells and/or on antigen presenting cells that have phagocytosed allograft cell proteins

Answer 2

acute

Question 3

can cause a prolonged and potentially life-threatening asystole in a transplanted (=denervated) heart

Answer 3

adenosine

Question 4

blocking this is a reason to take drugs such a s prednisone, cyclosporine and mycophenolate

Answer 4

allograft rejection

Question 5

xanthine oxidase inhibitor used to prevent gouty arthritis and uric acid nephropathy in patients predisposed to hyperuricemia or having it due to excess cell turnover from cancer +/- chemotherapy; its use mandates a reduction in azathioprine dosage

Answer 5

allopurinol

Question 6

developed in horses or rabbits, administered to selectively inactivate/destroy T cells as part of transplant induction therapy or when they are causing acute rejection of a transplanted organ despite other immunosuppressive therapy

Answer 6

antithymocyte globulin

Question 7

anti-proliferative agent that helped make allogeneic transplantation possible, it is somehow more effective at blocking de novo purine synthesis and DNA replication than direct administration of its active metabolite, 6-mercaptopurine

Answer 7

azathioprine

Question 8

mouse monoclonal antibody against human IL-2 receptor that can be used to inhibit T cell activation/proliferation as part of transplant induction therapy, tolerability was improved by creating a chimera in which the antibody contains a human constant region

Answer 8

basiliximab

Question 9

proliferate and differentiate into antibody-producing plasma cells when fragments of a molecule that was captured by the surface expression of their unique antibody and then inserted into MHC class II antigens on their surface is recognized as foreign by a helper T cell

Answer 9

B cells

Question 10

major adverse effect of most anti-proliferative drugs, increases susceptibility of transplant recipient to infection and bleeding

Answer 10

bone marrow suppression

Question 11

most effective immunosuppressive drugs in routine use

Answer 11

calcineurin inhibitors

Question 12

T cell population that surveys MHC class II molecules for unrecognized peptide fragments derived from phagocytosis, and, upon recognizing a foreign molecule, activates macrophages, stimulates production of antibodies, etc.

Answer 12

CD4

Question 13

T cell population that surveys cell protein synthesis by examining fragments of those proteins inserted into the MHC class 1 proteins on their cell surface, and destroys those cells that are recognized as synthesizing foreign proteins

Answer 13

CD8

Question 14

refers to organ rejection occurring over months to years for which there is ~no effective therapy, characterized by interstitial fibrosis, thickened vascular walls, etc.

Answer 14

chronic

Question 15

pharmacological dosages of exogenous glucocorticoids can also cause this

Answer 15

Cushing Syndrome

Question 16

first drug discovered that caused immunosuppression without bone marrow suppression, its binding to cyclophilin blocks calcineurin-mediated dephosphorylation of NFAT

Answer 16

cyclosporine

Question 17

refers to the unpleasant consequences (e.g., fever, chills, dyspnea, nausea, possibility of anaphylactoid shock) associated with the administration of an antibody generated in a different species; can be especially bad during initial administration but then decreases over time, in part because of concurrent administration of glucocorticoids

Answer 17

cytokine release syndrome

Question 18

risk of developing this is significant following renal transplantation, especially when immunosuppressive drugs are added to glucocorticoids

Answer 18

diabetes

Question 19

a sirolimus-like drug but with a shorter half-life (~30 hrs vs 62 hrs), means steady-state levels can be achieved faster and also that drug will disappear faster if discontinued due to adverse effects

Answer 19

everolimus

Question 20

pharmacological doses blunt acute organ rejection in part by suppressing NFkappaB driven gene expression in cells triggered by the recognition of a foreign antigen

Answer 20

glucocorticoids

Question 21

its de novo synthesis is blocked by mycophenolate; stops proliferation of lymphocytes since they cannot use purine salvage pathways like other cells

Answer 21

guanine

Question 22

potential cosmetic challenge with cyclosporine that is not a problem with tacrolimus

Answer 22

hirsutism

Question 23

organ rejection that occurs within minutes due to preformed antibodies and complement activation

Answer 23

hyperacute

Question 24

side effect of therapy with cyclosporine and sirolimus but not tacrolimus

Answer 24

hypercholesterolemia

Question 25

consequence of the renal afferent arteriolar constriction caused by cyclosporine and tacrolimus in solid organ transplant recipients

Answer 25

hypertension

Question 26

proinflammatory signaling molecule released by antigen-presenting cells that facilitates activation of lymphocytes

Answer 26

IL-1

Question 27

molecule released by activated T cells that binds to receptors on their surface to promote the characteristic T cell response (= growth, proliferation and differentiation of effector T cells)

Answer 27

IL-2

Question 28

the first and still by far most transplanted organ

Answer 28

kidney

Question 29

organ in addition to liver for which sirolimus is contraindicated as anti-rejection therapy after transplantation

Answer 29

lung

Question 30

accumulation of lymph in unusual space (e.g., retroperitoneal cavity after renal transplant), risk is increased by sirolimus

Answer 30

lymphocele

Question 31

cell population unable to use guanine salvage pathways, therefore must synthesize new guanine during proliferation (= reason for cell-selectivity of mycophenolate)

Answer 31

lymphocytes

Question 32

approved for use only when there is a glucocorticoid-resistant flare-up in the acute rejection of a transplanted organ

Answer 32

muromonab CD3

Question 33

non-competitive reversible inhibitor of inosine monophosphate dehydrogenase used for its antiproliferative effects in lymphocytes (they need this enzyme to synthesize guanosine nucleotides)

Answer 33

mycophenolate

Question 34

dose-limiting for both cyclosporine and tacrolimus, especially cyclosporine

Answer 34

nephrotoxicity

Question 35

its migration into the lymphocyte nucleus after its dephosphorylation by calcineurin is crucial for the generation of gene products such as IL-2 that are characteristic of T cell activation

Answer 35

NFAT

Question 36

among the cells that contributes to acute allograft rejection, for example, via antibody-dependent cell-mediated cytotoxicity

Answer 36

NK cells

Question 37

widely known name for muromonab-CD3 ("nab" rather than "mab" is correct spelling), the original and still-used mouse monoclonal antibody against human CD3 (= T cell receptor) that causes its rapid internalization and thereby prevents T cell activation

Answer 37

OKT3

Question 38

example of a drug that causes sequestration of circulating lymphocytes and also decreases their number via apoptosis

Answer 38

prednisone

Question 39

wise to take extra measures to prevent this if taking anti-proliferative agents

Answer 39

pregnancy

Question 40

reason, for example, for administering basiliximab or rATG immediately before kidney transplantation and for a few days after, during what is referred to as "transplant induction therapy"

Answer 40

prophylaxis

Question 41

does not occur when nifedipine or hydralazine are administered to a heart transplant recipient

Answer 41

reflex tachycardia

Question 42

attempts to minimize this are the reason that sirolimus is added to lowered doses of cyclosporine or tacrolimus

Answer 42

renal damage

Question 43

binds to FKB12, but inhibits protein kinase mTOR, which in lymphocytes is an important downstream signaling component of IL-2 receptor-stimulated proliferation and differentiation

Answer 43

sirolimus

Question 44

aka FK-506, binds to the immunophilin FKB12 to inhibit calcineurin phosphatase activity; exerts beneficial effects in organ transplantation similar to those caused by cyclosporine

Answer 44

tacrolimus

Question 45

effect observed with sirolimus, means that foreign antigens present during its use are not rejected immediately when/if sirolimus is discontinued

Answer 45

tolerizing

Question 46

encompasses the dream of transplanting pig organs into humans

Answer 46

xenotransplantation

Question 47

the only NRTI that is a guanosine analog, relatively safe in most but can cause a unique and potentially fatal hypersensitivity syndrome in those with the HLA-B*5701 locus

Answer 47

abacavir

Question 48

symptoms of this appear when HIV RNA copy numbers are high in plasma and CD4+ lymphocyte numbers are low

Answer 48

AIDS

Question 49

government run website that provides latest consensus guidelines for treatment of HIV in the US

Answer 49

aidsinfo

Question 50

when boosted, a first-choice protease inhibitor for treatment-na‹ve HIV patients due to its long half-life and reduced side effects, but can cause unconjugated hyperbilirubinemia not associated with hepatitis

Answer 50

atazanavir

Question 51

carries by far the greatest risk of transmitting HIV, but now a negligible cause for HIV transmission in the US (risk ~ 1:1.4 million)

Answer 51

blood transfusion

Question 52

having this fall to <350 cells/mm3 currently has an AI level of support for initiation of antiretroviral therapy

Answer 52

CD4 count

Question 53

common side effect of efavirenz, but typically subsides and rarely leads to discontinuation of the drug

Answer 53

CNS toxicity

Question 54

emergence of this tropism in HIV renders it resistant to maraviroc

Answer 54

CXCR4

Question 55

cytochrome P450 isozyme that is inhibited, induced, etc., by a wide range of drugs including several antiretroviral drugs, which leads to potentially troublesome drug interactions

Answer 55

CYP3A4

Question 56

when boosted, a first-choice protease inhibitor for treatment-na‹ve HIV patients due to its long half-life and reduced side effects, but can cause sulfa drug hypersensitivity reactions

Answer 56

darunavir

Question 57

prodrug formulation of tenofovir, a phosphorylated adenosine analog, to overcome its otherwise poor bioavailability

Answer 57

disoproxil

Question 58

HIV integrase strand inhibitor with ~ 14 hr half-life (i.e., suitable for once per day dosing)

Answer 58

dolutegravir

Question 59

the current NNRTI of choice for treatment-na‹ve HIV patients, in part because it is co-formulated with tenofovir and emtricitabine for convenient once/day dosing; teratogen

Answer 59

efavirenz

Question 60

HIV integrase strand inhibitor with suitable for once per day dosing due to prolongation of half-life with cobicistat

Answer 60

elvitegravir

Question 61

cytidine analog, one of the least toxic anti-retroviral drugs and an NRTI of first choice for HIV treatment-na‹ve patients due to its long half-life and co-formulation with tenofovir +/- efavirenz

Answer 61

emtricitabine

Question 62

a 36 aa peptide that inhibits formation of a 6-helix bundle critical for HIV fusion with the host cell membrane, drug is a last resort since expensive and must be administered subQ 2X/day

Answer 62

enfuvirtide

Question 63

HIV gene that encodes for gp120 and gp41

Answer 63

env

Question 64

NNRTI approved for use in treatment-experienced people infected with HIV since it still works after HIV mutations that cause resistance to some other NNRTI

Answer 64

etravirine

Question 65

HIV gene that contains the nucleocapsid core and matrix proteins

Answer 65

gag

Question 66

also sensitive to some HIV drugs such as tenofovir disoproxil fumarate and emtricitabine; discontinuation of these drugs can cause a disease flare-up

Answer 66

HBV

Question 67

cells infected with HIV typically only have one copy of this, unlike the virion which characteristically possess two copies of its precursor

Answer 67

HIV DNA

Question 68

early protease inhibitor requiring 3X/day dosing, now perhaps more noteworthy for its ability to cause crystaluria

Answer 68

indinavir

Question 69

enzyme responsible for insertion of retroviral DNA into the human genome, and an excellent drug target since mammalian genomes lack enzymes with this capability

Answer 69

integrase

Question 70

risk of acquiring HIV infection during this is fortunately much lower than during childbirth or blood transfusion

Answer 70

intercourse

Question 71

earlier cytidine-like NRTI, interesting in that HIV can develop resistance to it relatively quickly but doing so increases reverse transcriptase fidelity, slows replication, and thereby helps to increase the long-term effectiveness of zidovudine

Answer 71

lamivudine

Question 72

~irreversible disfiguring re-distribution of body fat associated with HIV and its treatment

Answer 72

lipodystrophy

Question 73

HIV protease inhibitor only available as a boosted combination, inhibits both HIV-1 and HIV-2, and often works after failure of another PI-containing regimen

Answer 73

lopinavir

Question 74

will block HIV entry if an expensive test with a long turnaround time shows that the virion requires the CCR5 co-receptor

Answer 74

maraviroc

Question 75

blockade of DNA polymerase here is thought to be responsible for some of the adverse effects associated with some NRTI

Answer 75

mitochondria

Question 76

typically 4-5 are required for HIV to develop resistance to protease inhibitors, reason resistance is slow to develop and seldom a cause for treatment failure

Answer 76

mutations

Question 77

among the toxicities associated with some NRTI that is thought to be due to inhibition of DNA polymerase gamma

Answer 77

myopathy

Question 78

ending of generic drug name that identifies the drug as an HIV protease inhibitor

Answer 78

navir

Question 79

an NNRTI, early studies with it demonstrated the importance of combination therapy in treating HIV after the virusin ~1/3 of patients developed resistance to it after a single monotherapy exposure

Answer 79

nevirapine

Question 80

class of drugs that selectively inhibits only HIV-1 reverse transcriptase; binds to a distant hydrophobic pocket in a manner that causes a conformational change and noncompetitively inhibits enzymatic activity

Answer 80

NNRTI

Question 81

a two-drug combination from this antiretroviral drug therapy class with zidovudine as its prototype provides the backbone for current HIV treatment strategies

Answer 81

NRTI

Question 82

aka MDR1, a transporter that interacts with many drugs and site at which competition can influence the drug toxicities

Answer 82

p-glycoprotein

Question 83

required of NRTI for them to be active

Answer 83

phosphorylation

Question 84

HIV gene that contains reverse transcriptase, protease, integrase, etc.

Answer 84

pol

Question 85

the combination of tenofovir disoproxil fumarate and emtricitabine is this for treatment-naive HIV patients due to its safety and efficacy, and also due to the convenience of a once/day co-formulation +/- efavirenz

Answer 85

preferred NRTI backbone

Question 86

should be given anti-retroviral therapy as soon as possible, irrespective of viral load or CD4 count, but efavirenz should not be used during the first trimester

Answer 86

pregnant woman

Question 87

HIV enzyme that cleaves at the N-terminal side of Pro residues in the long polypeptides (e.g., gag, pol) packaged into newly budded virions to release the enzymes and cell components required for their metamorphosis into a mature virus capable of causing infection

Answer 87

protease

Question 88

first generation integrase inhibitor, seems likely to be displaced from preferred therapy list by new drugs elvitegravir and dolutegravir since their longer half-lives permit once daily dosing

Answer 88

raltegravir

Question 89

reason to avoid some antiretroviral drugs such as indinavir and enofovir and/or decrease the dosages/use with caution

Answer 89

renal insufficiency

Question 90

weaker HIV protease inhibitor discovered to be a potent inhibitor of CYP3A4, reason it is now routinely used to "boost" other protease inhibitors

Answer 90

ritonavir

Question 91

first HIV protease inhibitor, its short half-life caused a troublesome pill burden and it is among the agents well-known for promoting irreversible lipodystrophy with long-term use

Answer 91

saquinavir

Question 92

among early thymidine NRTI, notable for causing many of the toxicities associated with the drug class including CNS toxicity, fat wasting, and the ability to cause lactic acidosis and hepatic steatosis

Answer 92

stavudine

Question 93

portion of generic drug name indicating that the drug is an HIV integrase inhibitor

Answer 93

tegravir

Question 94

adenosine analog that is the only NRTI nucleotide (i.e., has a phosphate already attached, so only needs 2 more to be active), an NNRTI of choice due to its relative safety, long half-life and co-formulation in once/day pills

Answer 94

tenofovir

Question 95

NRTI do this during reverse transcriptase mediated synthesis of proviral DNA

Answer 95

terminate elongation

Question 96

reason for a thorough evaluation of patient history and contemplation of new strategy rather than adding a single new drug to an HIV treatment regimen or stopping treatment altogether

Answer 96

treatment failure

Question 97

thymidine analog and the first anti-retroviral drug discovered, this NRTI is still in widespread use in resource-poor settings due to its well-known tolerability, toxicity and efficacy profiles

Answer 97

zidovudine