General (Malaria, HLA, Cancer) Flashcards
Capecitabine
converted to 5-FLUOROURACIL in cancer cells
decrease the biosynthesis of pyrimidine nucleotides by inhibiting thymidylate synthase, the enzyme that catalyzes the rate limiting step in DNA synthesis. This results in the “thymineless death” of rapidly growing cells.
LEUCOVORIN increases binding of 5-FU to thymidylate synthase thereby increasing 5-FU t1/2
HLA-B27
(MHC class I) individuals are 90x more likely to develop ankylosing spondylitis (destruction of the vertebral cartilage). • Also linked to psoriasis, inflammatory bowel disease, and Reiter’s syndrome
HLA-DR2
(MHC II) individuals are 130x more likely to develop narcolepsy.
• Also linked to multiple sclerosis, hay fever, and SLE.
HLA-A3/B14
MHC I
individuals are 90x more likely to develop hemochromatosis (too much iron adsorption which can lead to internal organ damage).
HLA-DQ2/GQ8
MHC II
linked to Celiac disease.
HLA-DR3
MHC II
linked to diabetes mellitus type I, Grave’s disease
HLA-DR4
MHC II
linked to rheumatoid arthritis and diabetes mellitus type 1
What is the gold standard for diagnosis of Malaria?
blood smear
Resistance readily occurs in what two types of malaria?
vivax and falciparum
suppressive prophylaxis of malaria uses what drug(s)?
chloroquine
alternate = atovaquone/proguanil
Supportive prophylaxis of chloroquine resistant malaria uses what drug(s)?
atovaquone/proguanil
alternate = doxycycline
Drugs to treat an acute attack of nonresistant malaria…
chloroquine phosphate (oral)
Drug to treat chloroquine resistant P. falciparum or P. vivax?
quinine + doxycycline
A child patient arrives in the ED with a severe onset of Plasmodium (malaria) like symptoms. You don’t have time to do a work up to determine the exact species. What is the most likely species? Parenteral Tx?
P. falciparum
IV quinidine + doxycyline
chloroquine
parasitized RBCs concentrate chloroqine at least 25x
binds ferriprotoporphyrin IX inside vacuole and prevents conversion to hemozoin via heme polymerase.
large doses for prolonged periods cause severe eye damage
Quinine
chloroqine resistant P. falciparum
MOA same as chloroquine
cinchonism – permanent vision damage, balance, hearing problems
Quinidine
IV for severe malaria (parenteral)
blocks Na and K currents (antiarrhythmic)
Tox; cardiac problems
Mefloquine
Indicated only for the prophylaxis of chloroquine resistant P. falciparum
MOA same as chloroquine
neuropsychiatric reactions (wild dreams +)
Atovaquone + Proguanil
slow onset
replacing mefloquine for prophylaxis
Atovaquone – depolarizes parasitic mito inhibiting ETC
Proguanil – inhibits DHFR (*increased affinity for malarial DHFR)
GI disturbances
Artemisinins and Combinations
MOA: heme iron in malarial pigment acts on the drug to produce free radicals
rapid onset
replaces quinidine for severe disease
Primiquine
drug of choice to eliminate hepatic forms (hypnozoite) of P. vivax/ovale
generates ROS (possibly interfering with ETC)
Tox: hemolytic anemia in G6PD deficiency… antimalarials are bad in people with G6PD def.
AML with genetic abnormalities…
t(8, 21)
AML M2 (neutrophilic series)-- good prognosis (myeloblasts over 20%, but not high)
AML with genetic abnormalities…
inv(16)
AML M4 (monocytic series)– good prognosis
Look for BOTH increased myeloblasts and moncytic cells
AML with genetic abnormalities…
t(15, 17)
AML M3 (neutrophilic series) – good prognosis
high [promyelocytes] and faggot cells (lots of auer rods)
this type of translocation occurs in all cases!
AML with genetic abnormalities…
11q23
usually monocytic (M4 or M5) – bad prognosis
AML with FLT-3 mutation
FLT-3 = tyrosine kinase mutation
⅓ of AML cases
AML with multilineage dysplasia
All three lines (RBCs, mon, granulocytes) dysfunctional
severe pancytopenia
AML, therapy related
previous chemo alkylating agents -- Busulfan TOPO II inhibitor (Etopaside) sometimes (11q23) very hard to treat
4 general things you must know about Acute Lymphoblastic Leukemia
- malignant proliferation of lymphoid blasts in blood/bone marrow (begins in lymph node!)
- classified by immunophenotype (B vs. T)
- more common in children
- prognosis good
T-lymphoblastic leukemia/lymphoma (MUST KNOW)
teenage male with mediastinal mass
WBC usually v. high
bad prognosis
B-lymphoblastic leukemia/lymphoma
several subtypes
TdT+
Rarely Ph+ (philidelphia chromosome positive (this is usually in CML t(9,22))