Week 3 Flashcards by Ginelle Zimmerman

What are the 3 types of APCs?

Dendritic cells (most effective)
Macrophages
B cells

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What 2 classes of drugs are both CCS?

Plant alkaloids (G2-M)
DNA synthesis inhibitors (S)

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What 2 classes of drugs are CCNS?

Crosslinking agents

Anthracycline antibiotics

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What enzyme creates somatic mutation in forming both Ig and T cell receptor molecules?

Rag 1 and 2

-no somatic hypermutation in T cell receptor formation

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What type of reactions are hypersensitivity type 1-4?

type 1 = immediate (anaphylaxis, IgE antibody)
type 2 = antibody mediated (production of IgG, IgM leading to phagocytosis or lysis- Goodpasture Syndrome)
type 3 = immune complex mediated (deposition Ag-Ab complex recruits leukocytes - SLE, serum sickness)
type 4 = T cell mediated (contact dermatitis, type 1 diabetes, MS, TB, granuloma formation)

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What drug can be used to treat breast cancer patients positive for HER-2/NEU gene?

-monoclonal Ab to Her2/neu receptor = trastuzumab (Herceptin)

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Where does a T cell receptor receive its 2 activating “hits”?

1 via TCR/CD3 complex

- 1 from dendritic cell cytokines

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What cytokine do CTLs need to become activated? convert to memory cells?

activated by IL-2 from Th1

- convert to memory cells by IL-21

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Co-receptors bind on TCR for MHC/peptide complex bind what?

CD2
LFA-1
CD28
CD45R

CD2 binds LFA-3
LFA-1 binds ICAM-1
CD28 binds B7 (CD80/86)
CD45R binds CD22

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HLA-B27 individuals at risk for what?

alkylosing spondylities (destruction of vertebral cartilage)
also psoriasis, inflammatory bowel disease, Reiter’s syndrome

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HLA-DR2 individuals at risk for?

narcolepsy

-also MS, hay fever, and SLE

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HLA-A3/B14 individuals at risk for?

hemochromatosis

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HLA-DQ2/GQ2 individuals at risk for?

Celiac disease

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HLA-DR3 is linked to…

diabetes mellitus type 1, Grave’s disease

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HLA-DR4 is linked to….

rheumatoid arthritis, diabetes melliuts type 1

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What drug(s) are most likely to cause Radiation Recall Reaction?

-“rubicin” drugs (especially Doxorubicin in breast cancer treatment)

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What 2 main drug categories are CCS?

Plant alkaloids (G2/M)

- Antimetabolites (S)

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What 2 main drug categories are CCNS?

alkylating agents

- anthracycline antibiotics

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What enzyme is needed to converte UMP to UDP in the pyrimidine synthesis pathway and is important in resistance to 5-FU?

-pyrimidine monophosphate kinase

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What enzyme is involved in degradation of pyrimidines and without it, patient is more sensitive to 5-FU?

-dihydropyrimidine dehydrogenase

What is used for treatment of cyanide poisoning?

hydroxocobalamin

What action in cells gives MTX differential sensitivity for cancer cells?

-polyglutamination (traps folate in cell and increases affinity for enzyme thymidylate synthase

Antimetabolites: analogues of what?

-CCS or CCNS?

analogues of folate, pyrimidine, or purine

- CCS for S phase

What drugs cause Tumor Lysis Syndrome?

-treatment

any drug that causes sudden, rapid death of millions of cells (Ex: leukemia and lymphoma drugs)
Allopurinol to treat (prevents hyperuricemia)

What are the main resistance mechanisms for folic acid analogues (MTX, Pemetrexed, Pralatrexate)

- change target enzyme - increase DHFR expression - decrease polyglutamination - decrease accumulation (decrease RFC expression)

Can Leucovorin be given intrathecally?

No. that would be fatal

What are main resistance mechanisms of pyrimidine analogues? (5-FU and Capecitabine) -blocking which enzyme can block drug?

- change target enzyme (TS) - decrease activation of drug (enters pathway as UMP or dUMP) - increase inactivation - blocking pyrimidine monophosphate kinase= resistance

What are the 2 ways to make purines? How do 6-MP and 6-TG fit in?

1. primary purine synthesis pathway (enzymes PRPS and GPAT) 2. salvage pathway (enzyme HGPRT) - 6MP and 6TG block guanylyl kinase (when activated by HGPRT to T-IMP and 6-thioGMP- poor substrates for guanylyl kinase); IMP and GMP accumulate triggering "pseudofeedback inhibition" of PRPS, GPAT, HGPRT enzymes

What drug can cause hemorrhagic cystitis? How to treat

- Cyclophosphamide | - add Mesna

What is the common unique side effect of Anthracycline Antibiotics?

- cardiomyopathy corresponding with total amount of drug taken - ex: doxorubicin

What is unique about Bleomycin's mechanism? What major toxicity?

- generates free radicals to cut DNA strands ("blasts DNA") | - causes skin and lung damage (those tissues lack hydrolase enzyme to metabolize Bleomycin)

What are the common resistance mechanisms for crosslinking agents? -MOA?

-increased DNA repair -increased glutathione production (trapping agent) -oral = decreased activation MOA: must be activated so nucleophile can attack DNA and cause damage

What are main resistance mechanisms for intercalating agents- anthracycline antibiotics?

- decreased accumulation due to P-glycoprotein (MDR) - decreased topo 2 activity (temporarily) - increased inactivation

What drug is associated with nephrotoxicity?

Cisplatin | -should also be avoided with renal insufficiency)

``` What drug class is associated with neurons/ RBCs -peripheral neuropathy ```

vinca alkaloids | -ex: Vincristine

Which species of malaria are the most common?

-P. vivax and P. falciparum

Which specie of malaria is the most deadly?

Plasmodium flaciparum (able to infect RBCs of any age; Rosettes form, impede blood flow)

Which 2 species of malaria cause relapses?

-P. vivax and P. ovale

Basic life cycle of malaria?

injected as sporozoites, released from liver as merozoites -enter RBC, trophozoite (ring form), schizont, merozoites released from RBC and either infect new RBC or become gametocytes

What is the main prophylactic drug for malaria? Alternative?

Chloroquine | -alternative: Atavaquone/ proguanil

What drug is for the "radical cure" but may cause hemolytic anemia in people with G6PD deficiency?

Primaquine

What drugs are used for treating chloroquine resistant P. falciparum?

- Mefloquine (also for prevention) | - Quinine and Quinidine

What is the main drug for prevention of malaria in Chloroquine resistant areas?

- Atovaquone/ proguanil | - alternative: Doxycycline or Mefloquine

What classification of AML has Auer rods?

-AML M1 | acute myeloblastic leukemia without maturation

What AML classification has Faggot cells?

-AML M3 (acute promyelocytic leukemia) -all have t(15;17) translocation

Which AML classification is associated with t(8;21) translocation?

-AML-M2 | acute myeloblastic leukemia with maturation

Which AML classification is associated with inv(16) inversion?

-AML M4 (acute myelomonocytic leukemia) -extramedullary tumors

Which new classification of AML is associated with the elderly and pancytopenia?

- AML with multi-lineage dysplasia | - poor prognosis

Most common acute leukemia in children?

Acute lymphoblastic leukemia (ALL)