Anemia and Hematopoietic Flashcards
Anemia caused by deficiency of Vit B12 or Folic Acid
Megaloblastic Anemia
What is the most common type of anemia?
Microcytic Hypochromic Anemia (Iron Deficiency)
What is the typical laboratory picture of IDA?
Low Fer, Low Ferritin, High TIBC
Transport protein of Iron
Transferrin
Storage protein of Iron
Ferritin
Which Iron Supplement has the highest Elemental Iron Content?
Ferrous Fumarate
Excess iron causes what reaction?
Fenton Reaction
Signs and symptoms of Acute Iron Overdose
Necrotizing gastroenteritis, abdominal pain, bloody diarrhea, shock, lethargy dyspnea
Effects of chronic iron overload
Hemochromatosis
Organ Failure
Death
Treatment for Acute Iron Intoxication
Deforxamine
Correct acid-base abnormalities
Remove unabsorbed tablets from the gut
What is triad of Hemochromatosis?
Cirrhosis
Diabetes Mellitus
Skin Pigmentation
Oral form of Deferoxamine?
Deferasirox
Which vitamin deficiency causes anemia and neurologic defecits?
Vitamin B12 deficiency
What are the neurologic deficits of Pernicious Anemia?
Ataxic Gait
Impaired position and vibratory sense
Spasticity
What part of the GIT is Vitamin B12 absorbed?
Distal Ileum
What is needed to absorb vitamin B12?
Intrinsic Factor
What protein transports Vit b12 in plasma?
Transcobalamin II
What are the 2 forms of Vitamin B12?
Cyanocobalamin
Hydroxycobalamin
Which is the synthetic and natural form of Vit B9?
Folate = Natural
Folic Acid = Synthetic
Vitamin B12 is essential in what 2 reactions?
Conversion of methylnalonyl-CoA to Succinyl CoA
Conversion of Homocysteine to Methionine
Folates accumulate as what metabolite?
N-Methyltetrahydrofolate
Exogenous folic acid does not correct?
Neurologic deficits of Vit B12 Def
Whatdo WBCs look like in Megaloblastic Anemia?
Hypersegmented Neutrophils (>5 lobes)
Folic acid is absorbed in what part of the GIT?
Proximal Jejunum
Enumerate the pathway of Folic Acid Synthesis
PABA -> (Dihydropteroate synthase) -> Dihydrofolic acid -> (Dihydrofolate reductase) -> Tetrahydrofolic Acid -> Purines -> DNA
What is Sargramostim or Pegfilgrastim?
G-CSF (Myeloid growth factor)
A megakaryocyte growth factor
Oprelvekin (IL-11)
What is Oprelvekin used for?
Secondary prevention of thrombocytopenia in patients undergoing cytotoxic chemotherapy for non-myeloid cancers
What are the 4 mechanisms of hemostasis?
- Vasoconstriction
- Platelet plug formation
- Formation of clot via blood coagulation
- Fibrous organization
Factors involved in 1st step: Vasoconstriction
Thromboxane A2
Endothelin
Essential for binding subendothelial collagen to platelets by Gp1b receptor in the platelet surface
vWF
Factors involved in the Intrinsic Pathway or PTT
V, VIII, IX, X, XI, XII, Prothrombin, Fibrinogen
Factors involved in the extrinsic pathway or PT
V, VII, Prothrombin, Fibrinogen
The rate limiting factor in blood coagulation?
Prothrombin activator
Aspirin is asso. with what syndrome?
Reye Syndrome
What is the toxic dose of aspirin?
150 mg/kg
What is the lethal dose of aspirin?
500 mg/kg
What is the triad of aspirin hypersensitivity?
SAMTER TRIAD
Asthma
Aspirin
Nasal Polyps
Effects of Aspirin intoxication
Increased respiratory drive leads to hyperventilation and respiratory alkalosis
Uncoupling of oxidative phosphorylation leads to increased anaerobic metabolism via lactic acidosis and HAGMA
What is the expected acid-base abnormality in salicylate poisoning?
Respiratory Alkalosis with HAGMA
What is the difference in presentation if aspirin intoxication in children and adults?
Adults: mixed acid-base disorder (Respiratory Alkalosis with HAGMA)
Children: pure acid-base disorder (HAGMA)
Inhibits platelet aggregation by interfering with GPIIb/IIIa binding to fibrinogen and other ligands
Abciximab / Eptifibatide / Tirofiban
What is the MOA of Abciximab / Eptifibatide / Tirofiban?
Inhibits platelet aggregation by interfering with GPIIb/IIIa binding to fibrinogen and other ligands
What is Abciximab used for?
Used during PCI to prevent thrombosis
Acute Coronary syndromes
Irreversibly inhibits binding of ADP to platelet receptors, reducing platelet aggregation
Clopidogrel
What is the MOA of Clopidogrel?
Irreversibly inhibits binding of ADP to platelet receptors, reducing platelet aggregation
Inhibits phosphodiesterase III and increases cAMP in platelets and blood vessels
Dipyridamole
MOA of Dipyridamole?
Inhibits phosphodiesterase III and increases cAMP in platelets and blood vessels
Side effects of Dipyridamole?
Headache because its a vasodilator, Palpitations
What are the 2 major types of anticoagulants?
Indirect Thrombin Inhibitors: Heparin, Enoxaparin, LMWH
Direct Thrombin Inhibitors: Coumarin Derivatives
Describe the structure of Heparins and Warfarins
Heparin: large acidic polysaccharide
Warfarin: small lipid-soluble molecule
How is Heparin and warfarin given?
Heparin: parenteral
Warfarin: Oral
Where is the site of action of Heparin vs Warfarin?
Heparin: blood
Warfarin: liver
Compare the onset of heparin vs warfarin
Heparin: rapid (minutes)
Warfarin: slow (days)
Compare the MOA of heparin vs warfarin
Heparin: activates antithrombin III
Warfarin: impairs posttranslational modification of factors II, VII, IX, X (Vit K dependent) Protein C and S
Which is safe in pregnancy? heparin vs warfarin
Heparin
What is the antidote of heparin and warfarin?
Heparin: Protamine
Warfarin: vitamin k, FFP
What is the similar drug of Dipyridamole?
Cilostazol
Another drug for Clopidogrel
Ticlopidine, Prasugel
What is the difference between an inhibitor and an uncoupler of oxidative phosphorylation?
Inhibitors completely halt ETC
Uncouplers dissipate proton gradient without interrupting the ETC
Give 8 examples of CYP450 Inducers
Ethel Booba takes Phen-Phen and reduces greasy carb shakes ETHANOL BARBITURATES PHENYTOIN RIFAMPICIN GRISEOFULVIN CARBAMAZEPINE ST JOHN's WORTH SMOKING
Give 9 examples of CYP450 inhibitors
Inhibitors stop cyber kids from Eating GRApefruit Q ISONIAZID SULFONAMIDES CIMETIDINE KETOCONAZOL ERYTHROMYCIN GRAPEFRUIT JUICE RITONAVIR AMIODARONE QUINIDINE
Warfarin inhibits what enzyme?
Epoxide reductase
Which anticoagulant does not require aPTT monitoring?
Enoxaparin, Fondaparinux
Which has a narrow therapeutic window, Heparin or Warfarin?
Warfarin
What is the antidote for Lepirudin?
No reversal agent exists
