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D2, Fall Quarter > BMS Exam III > Flashcards

BMS Exam III Flashcards

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1
Q

activated clotting factors

A

serine proteases

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2
Q

factor VIII deficiency

A

hemophilia A

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3
Q

tissue factor

A

thromboplastin

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4
Q

Warfarin/coumarin affects:

A

extrinsic pathway - blocks VKOR (vitamin K exposide reductase

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5
Q

Vitamin K, required cofactor

A

GLUTAMATION RXN for factors 2, 7, 9, 10 & Proteins C&S; post-translational MODIFICATION of several coagulation factors necessary for Ca+2 binding

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6
Q

reduced Vit K + clotting factors

A

γ-carboxyglutamate (GLA) = has high affinity binding site for Ca+2, which binds to coagulation factor

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7
Q

Anti-thrombin III (endogenous inhibitor)

A

inhibits all clotting factors (2, 7, 9, 10) that need factors that need Ca+2

HEPARIN activates anti-thrombin III

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8
Q

Protein C&S (endogenous inhibitor) inhibits

A

Va & VIIIa

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9
Q

TFPI (endogenous inhibitor)

A

inhibits TF-7A (similar to anti-thrombin III) = factors 2, 7, 9, 10 are inactivated

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10
Q

Intracellular PO4

A

intermediary metabolism in cells

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11
Q

Extracellular PO4

A

essential matrix mineralization

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12
Q

HIGH Ca+2 and PO4 in blood

A

CaPO4 = limited solubility – precipitate in soft tissue

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13
Q

1α-hydroxylase synthesizes (in kidneys)

A

calcitriol/vitD3 – rate limiting step: renal failure = major problem ; PTH simulates 1α-hydroxylase!

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14
Q

24-hydroxylase

A

deactivates vitD3 into calcitroic acid (regulation)

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15
Q

Ca+2 movement in intestine

A

paracellular + transcellular (Ca+2 channels)

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16
Q

Vitamin D deficiency

A

osteomalacia in adults, rickets in children

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17
Q

Vit D receptors

A

nuclear receptors = increase efficiency of translation

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18
Q

PTH

A

maintains plasma Ca+2 via GPCR signaling (Gs –> cAMP –> decreasing Gq, increaseing PLC

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19
Q

LOW plasma Ca+2

A

INCREASE in PTH release –> INCREASE plasma Ca+2 –> directly INCREASE bone resoprtion; DECREASE plasma PO4 because of PO4 excretion in urine (via Vit D)

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20
Q

PTH GPCR signaling

A

Uniquely DECREASES PTH release (negative feedback)

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21
Q

Majority Iron stored as

A

Ferritin (marcrophages + hepatocytes) – good indicator of iron levels

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22
Q

When iron is LOW in cells, IRP binds

A

mRNA binds 5’ to block translation of Ferritin (down regulation); binds 3’ end to increase synthesis of transferrin receptors

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23
Q

IRP bind 5’

A

down regulation = block Ferritin translation

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24
Q

IRP bind 3’

A

up regulation = increases transferrin receptors

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25
IDA (Iron Deficiency Anemia)
Low serum ferritin, high level of transferrin -- tx: ferrous sulfate + ascorbic acid
26
Anemia of Chronic Disease (ACD)
Cytokines stimulation hepcidin (inhibit ferroportin = down regulates intestinal absorption + releases Fe from macrophages) + inhibits erythropoiesis (decreased RBC production)
27
HIGH ferritin
ACD
28
Hemochromatosis
HFE defect, too much iron uptake inside cells; hepcidin cannot inhibit ferroportin
29
First substrates of heme metabolism
Succinyl CoA + glycine in mitochondria
30
First heme biosynthesis enzyme
ALA synthase
31
Acute Intermittent Porphyria (most common)
Defective PBG deaminase = neuropsychiatric symptoms + abdominal -- TX: Hemin = repress ALA synthase
32
Porphyria cutanea tarda
Defective uroporphyrinogen decarboxylase -- uroporphyrinogen build-up = photosensitivity
33
Heme Catabolism via macrophages in spleen, liver + red bone marrow
RBC --> hemoglobin --> heme --> biliverdin --> bilirubin --> (conjugated, more soluble) --> binds bile -->urobilinogen --> sterecobilin --> excreted in feces
34
Unconjugated (indirect) hyperbilirubinemia
Neonatal jaundice = UDP-glucuronyltransferas deficiency; Gilbert syndrom; hemolysis
35
Conjugated (direct) hyperbilirubinemia
Hepatobiliary disease + bile stones (bile duct obstruction)
36
G6P dehydrogenase
Rate limiting step in nucleotide metabolism in PPP
37
Two PPP defects
G6PD deficiency = cannot produce NADPH, gluthathion not reduced >> build up of H2O2 >> hemolytic anemia (associated with Type I hypersensitivity)
38
Anti-coagulant Drugs
Heparin; Thrombin II & Factor X Inhibitors (dabigatran or rivaroxaban = not better than heparin); Coumarin/Warfarin
39
Hemophilia B
Factor IX deficient
40
Heparin (IV, parenteral)
Bind anti-thrombin III (interferes with all steps of coagulation) --> inactiavtes thrombin (HMW, long) and factor Xa (LMW, short + HWM, long) --- tx: venous thrombosis, pulmonary embolism, myocardial infarction, unstable angina --- sf(x): bleeding, heparin induced thrombocytopenia (HIT anemia) = low platelet count
41
Reverse Heparin
Protamine (binds Heparin)
42
Warfarin *increases coagulation risk for first 3 days
Inhibits Vit K Epoxide Reductase (VKOR) -- interferes w/ clotting factor production in liver... bleed out; DDI = aspirin + preggo women b/c vitamin K for bone development (teratogen) -- tx: venous thrombosis, ishemic stroke, pulmonary embolism -- sf(x): increases coagulation risk for first 3 days... prevent via heparin bridge or thrombosis due to protein C deficiency
43
Reverse Warfarin
Vitamin K
44
aPTT
Monitor bleeding time on pts on heparin or thrombin II inhibitor (dabigatran)
45
PT, INR
Monitor bleeding for Warfarin
46
Lepirudin
Alternative to heparin -- Thrombin (Factor IIa) + prothrombin (Factor X) inhibitor -- sf(x): bleeding (aPTT)
47
RivaroXaban MOA
Factor X (prothrombin) inhibitor -- clincal use: nonvalvular atrial fibrillation; sf(x): bleeding
48
DabigaTran MOA
Factor IIa (thrombin) inhibitor
49
Anti-Platelet Drugs
Aspirin + Clopidogrel, blocks platelet activation and aggregation
50
Aspirin MOA
Blocks TXA2 (platelet AGGREGATION) --> reduces production of platelets
51
Clopidogrel (Plavix)
Prevents ADP from binding to receptor on platelets (blocks platelet ACTIVATION) -- tx: acute coronary syndrome, prevents restenosis after percutaneous coronary intervention (PCI), arterial thrombosis
52
Prevent + tx of atererial thrombosis
Aspirin + Clopidogrel
53
Abciximab (parenterally, IV)
Anti-Platelet Drug, interferes with GP IIb/IIIa -- binding to fibrinogen and other ligands
54
Percutaneous coronary intervention (PCI)
Abciximab -- only given parenterally -- sf(x): bleeding, thrombocytopenia (anemia)
55
Fibrinolytic drugs
Urokinase or tPA; Alteplase, Reteplase, Streptokinase -- tx: coronary artery thrombosis, ischemic stroke, pulmonary embolism
56
tPA, MOA
plasminogen --> plasmin (cleaves fibrin = reverses blood clot) -- sf(x): cerebral hemorrhage -- ANTIDOTE: Aminocarproic acid
57
Vitamin D supplements
Cholecalciferol, ergocalciferol, calcitriol -- tx: osteoporosis, rickets/osteomalacia, renal failure, malabsorption
58
Vitamin D
inhibits PTH, increases Ca+2 and PO4 serum, prevents excretion?
59
Calcidiol
produced in liver, measurable levels of vitamin D
60
Vit D toxicities
Hypercalcemia, hypercalciuria (excretion of Ca+2)
61
Osteoclast action, vit D and PTH
INCREASE
62
Furosemide
For hypercalcemia = inhibition of the Na/K/2Cl transporter in the ascending loop of Henle → (↑) Ca+2 excretion, (↑) urine Ca+2 and Mg -- sf(x): hypokalemia, ototoxicity, hyperuricemia, hypomagnesmia
63
Ototoxicty
Furosemide
64
Bisphosphonate, MOA
Suppreses bone resorption (inhibits osteoclast activity via inhibition of farnesyl pyrophosphate synthesis) -- tx: Paget's disease, osteoporosis, hypercalcemia, bone metastasis -- sf(x): GI irritation, renal failure, osteonecrosis of jaw
65
Bisphosphonates = "dronate"
*Fosomax = Alendronate, Risendronate, Ibandronate, Zolendronic acid
66
Raloxifene (SERM)
Selectively interacts w/ estrogen receptors = bone (agonist), breast + endometerium (antagonist) = Used for osteoporosis, reduces vertebral fracture risk -- sf(x): thromboembolism, hot flashes
67
Calcitonin (nasal spray)
Hormone that acts via cognate GCPR = tx: osteoporosis + hypercalcemia
68
Denosumab (monoclonal Ab, given subcutaneous injection every 6 months)
Blocks bone resorption (binds RANKL = stimulates osteoclast) -- tx: osteoporosis -- sf(x): increased risk of infection
69
Terparatide (PTH, not parathyroid hormone) via subcutaneous injection
Amino acid 1-34 or all 84 PTH, regulates Ca+2 and PO4 metabolism in bone + kidney. Stimulates bone turnover --> net bone formation!
70
Side effects of Terparatide (PTH)
Prolonged use can match bone formation and resorption, hyper calcemia, hypercaluria
71
Sulfonamide, MOA
Block folate production, targets bacterial PABA
72
Trimethoprim
Anti-folate: selectively inhibits DHFR
73
Metrotrexate
Blocks DHFR --> interferes with biosynthesis of dTMP and purines == tx: inflammatory bowel disease, rheumatoid disease, cancer chemotherapy
74
5-FU (flurodeoxyuryidale)
Blocks thymidylate synthase so blocks dUMP → dTMP

D2, Fall Quarter (3 decks)

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