FA Notes Flashcards
Hereditary cause of sideroblastic anemia? Treatment?
X linked delta-ALA synthase
B6, pyridoxine
How does lead poisoning leads to anemia?
Lead inhibits ferrochelatase and ALA dehydratase decreasing heme synthesis and inc RBC protoporphyrin
What are the effects of LEAD poisoning? Treatment?
Lead lines on gingivae and long bone
Encephalopathy and Erythrocyte basophilic stippling (blocked rRNA degradation)
Abdominal colic and sideroblastic Anemia
Drop of wrist or foot, Dimercaprol and EDTA
Kids: Succimer
What causes orotic aciduria? What’s the clinical manifestation? How is it differentiated from ornithine transcarbamylase def?
Treatment?
Inability to convert orotic acid to UMP from UMP synthase, causes megaloblastic anemia, no hyperammonemia
Treatment: uridine monophosphate
What does heparin do? How is it reversed?
It activates antithrombin, decreasing both thrombin and factor Xa. Reversal by protamine sulfate
What is HIT?
Heparin-induced thrombocytopenia, IgG antibodies against heparin bound PF4. The complex activates platelets and causes thrombosis and thrombocytopenia
What do Argatroban, bivalrudin, and dabigatran do? When are they used?
Inhibit thrombin directly, used for patients with HIT
What apixaban, rivaroxaban do?
Bind directly to Xa
Which anticoagulant is safe in pregnancy?
heparin (not warfarin). It does not cross the placenta
What is warfarin’s toxicity? How is it reversed?
Skin/tissue necrosis. Reversed by vit K. Rapidly by FFP
What do alteplase, streptokinase do? How is toxicity treated?
They are thrombolytics. They aid activation of plasminogen to plasmin causing cleavage of thrombin and fibrin clots. . Treat toxicity with aminocaproic acid (inhibits fibrinolysis)
What does aspirin do? Toxicity?
Irreversible inhibition of COX1 and 2, decreases TXA2 and prostaglandins.
-Causes ulcers, tinnitus, acute renal failure, interstitial nephritis, and Reye syndrome in kids with viral illness
What does overdose look like (acid-base)?
Hyperventilation and respiratory alkalosis -> mixed metabolic acidosis and respiratory alkalosis
What does clopidogrel do?
It inhibits platelet aggregation by blocking ADP receptors, prevents IIb/IIIa expression on platelet
What cilostazol and dipyridamole do?
They are phosphodiesterase III inhibitors. By dec cAMP in platelets, they inhibit aggregation. Vasodilators.
What do abciximab, eptifibatide, and tirofiban do?
Bind to IIb/IIIa receptor on activated platelets to prevent aggregation
What does vemurafenib do?
It inhibits BRAF positive melanoma
What is trastuzumab? Toxicity?
It is a monoclonal antibody against HER-2, tyrosine kinase receptor. Cardiotoxicity
What is tamoxifen, raloxifine? Tamoxifen inc risk of which cancer?
Selective estrogen receptor modulator (antagonist in breast, agonist in bone). Tamoxifen inc risk of endometrial cancer
What does rituximab do? Toxicity?
monoclonal antibody against CD20, inc risk of progressive multifocal leukoencephalopathy
What is imatinib?
Tyrosine kinase inhibitor of BCR-ABL (Philadelphia in CML)
What is erlotinib?
EGFR tyrosine kinas inhibitor
Bevacizumab
Monoclonal antibody against VEGF, inhibits angiogenesis
What does Cisplastin/carbolatin do?
cross-links DNA, can cause nephrotoxicity (prevent with amifostine and chloride diuresis) or ototoxicity
What do etoposide and teniposide do?
It inhibits topoisomerase II, causing DNA degredation
What does irrnotecan/toptecan do?
inhibits topoisomerase I, preventing DNA winding and replication
What does hydroxyurea do?
Inhibits ribonucleotide reductase, decreases DNA synthesis, increases HbF
What cancer drugs are microtubule inhibitors?
Paclitaxel, vincristine, vinblastine
What does paclitaxel do?
It hyperstabilizes polymerized microtubules in M phase, prevents breakdown of mitotic spindle
What does vincristine/vinblastine do? Toxicity?
Binds to Beta-tubulin and inhibits microtuble polymerization (M phase arrest). Neurotoxic (vincristine) and marrow suppression (vinblastine)
What drugs are alkylating agents?
Busulfan, cyclophosphamide, nitrosoureas
What does busulfan do?
Cross-links DNA
What does cyclophosphamide/ifosfamide do? Important toxicity?
Cross-links DNA at guanine N-7, hemorrhagic cystitis
What do nitrosoureas do? Toxicity?
Cross blood brain barrier to cross link DNA. Causes CNS toxicity (convulsions, dizziness, ataxia)
What does bleomycin do?
Induces free radical formation
What does dactinomycin do?
Intercalates in DNA, used for childhood tumors
What does Doxorubicin do? Important toxicity?
Generates free radicals, dilated cardiomyopathy
What is methotrexate? Important toxicity?
Folic acid analog, competitive inhibition of dihydrofolate reductase, dec DNA synthesis. Myelosuppresion, reversible with leucovorin
What is 5-fluorouracil? Toxicity?
Pyrimidine analog activated to dUMP, inhibits thymidylate synthase, myelosuppression, not revesible
What is cytarabine? Toxicity?
Pyrimidine analog, inhibits DNA polymerase, causes pancytopenia
What is cladribine?
Purine analog, used for hairy cell leukemia
What is azathioprine/6-MP? Toxicity?
Purine analog, activated by HGPRT, myelosuppression. Metabolized by xanthine oxidase
First step of Heme synthesis? Co-factor?
Glycine + succinyl CoA -> aminovulinic acid. Pyroxidine
Defective enzyme in acute intermittent porphyria?
Prophobilinogen deaminase
Defective enzyme in porphyria cutanea tarda?
Uroporphyrinogen decarboxylase
