pharm - hematology.txt

amplifies the anticuagulant effect of antithrombin III (inhibits factors IIa and Xa).

not big enough to bind both antithrombin III and factor IIa at the same time, only AT III (so effect largely due to influence on factor Xa)

PTT guides UFH dosing (ideally 1.5 to 2.3 times normal)

more predicitable than UFH and doesn't mess with PTT, so no routine monitoring required. can look at antifactor Xa activity if needed.

previous HIT, thrombocytopenia, active bleeding

HITS (antibodies against platelet factor 4 produced, bind to platelets, activating them = thromboses, thrombocytopenia (being used up), excessive bleeding (being used up)). osteoporosis, hyperkalemia.

heparin. warfarin not safe, revaroxaban also not safe.

danaparoid has similar MOA, but not structurally related so safe to use in pts c HIT hx.

UFH reversible c protamine (binds), LMWH has no antidote.

factor Xa converts factor II to IIa (thrombin). inhibitors stop this conversion without using antithrombin III as an intermediary (like heparins)

postsurgical VTE prophylaxis, alternative to heparin in pts with severe HIT

binds to thrombin (factor IIa), inhibiting the conversion of fibrinogen to fibrin.

postsurgical VTE prophylaxis. bivalirudin HIT.

univalent inhibitors ("-gatr-") and bivalirudin are reversible, other bivalents are irreversible

considered more predictable for anticoagulation as they are not bound to plasma proteins (heparin), are not neutralized by platelet factor 4 (heparin), and because they directly inhibit fibrin formation.

bivalirudin can be monitored using PTT.

vitamin K is a key cofactor for the activation of factors II, VII, IX, and X. To work, it must be reduced by vitamin K epoxide reductase. warfarin inhibits VKOR.

PO (unlike heparins). takes 2-3 days of tx before anticoagulation takes effect (because the inhibited proteins take that long to be cleared from the system)

platelet disorders (if you have dysfunctional clotting cells and dysfunctional clotting proteins, you'll be in real trouble if you need a clot)

temporary hypercoaguable state due to inhibition of proteins C and S when first given

2 to 3

there is significant genetic variability in response to warfarin owing to variants in 2C9 that metabolize the drug less efficiently and due to variants in VKOR

like NSAIDS, salicylates inhibit cyclooxygenase (COX) enzymes, specifically irreversibly inhibiting COX-1's formation of cyclic endoperoxide

not for use in children (Reye's syndrome)

GI (reduced PG levels causes reduced mucous -> ulcers), bleeding, tinnitus (high doses)

ASA binds to platelets irreversibly, so duration of action is 5-7 days (lifespan of a platelet)

salycilates can stimulate respiratory centers directly or by increasing CO2 production, causing a potential acid/base issue (respiratory alkalosis)

salicylate derivative that is a more potent analgesic and antiinflammatory, but isn't antipyretic

inhibit the ADP-dependent pathway of platelet activation and subsequent sequestration.

clopidogrel slow, takes 5 days to achieve plateau

hematopoietic disorders (particularly neutropenia), thrombotic thrombocytopenic purpura (TTP)

ticagrelor reversible. all others irreversible (therefore long biologic T1/2, 5-7 day life of platelet)

various responses, from "clopidogrel unresponsive" (<10%) to 90% platelet inhibition, thought to be due to alterations in PGY12 receptor (VerifyNow P2Y12 assay).

pts with CYP2C19*2 and CYP2C19*3 variants that there is reduced conversion of clopidogrel to its active thiol metabolite, resulting in ineffective protection.

fibrinogen and vWF bind to IIb/IIIa receptors, causing platelet binding and aggregation (activation and binding of other platelets). these drugs prevent this.

IV. adciximab has the shortest T1/2 (10 min), but the longest effect (1 day) because it binds to the platelets

cleave plasminogen (endogenous) to form plasmin, a protease that digests fibrin, breaking up the clot. fibrin selective drugs require the presence of fibrin to cleave plasminogen, localizing their effects to the clot (in theory).

non-selectives (streptokinase/urokinase) are both antigenic, so multiple uses are discouraged due to hypersensitivity reactions

tenecteplase more fibrin-specific than alteplase. reteplase works faster than alteplase.

stimulates the production of RBCs (endogenous, targets progenitor cells in bone marrow, typically produced in the kidneys but a little bit in the liver)

epoetin has a shorter T1/2 (4-8h) vs darbepoetin (24h -- due to AA modifications)

uncontrolled HTN

iron deficiency (use an iron supplement), thrombosis (particularly c dialysis), HTN, seizures

Hem, aim for 10 (less chance of side effects). b/c RBCs have a long T1/2, dosing adjustments won't be seen for 2-6 wks.

stimulates the production of neutrophils and monocytes by binding to myeloid progenitor cells

G-CSFs stimulate neutrophils. GM-CSFs stimulate neutrophils and monocytes, as well as the actions (phagocytosis, superoxide production, cell-mediated toxicity) or neutrophils, monocytes, and eosinophils

filgrastim T1/2 is 3-5h, the PEGgylated pegfilgrastim has an extended T1/2 of 40h (less easily titrated, but better for prophylaxis).

bone loss, joint pain, renal dysfunction, acute respiratory distress, splenomegaly, sickle cell crisis

ferrous iron (Fe2+, from animals) is better absorbed than ferric iron (Fe3+, from veggies) in duodenum

previous anaphylaxis-like rxn to IV formulation (particularly iron dextran - test dose!)

GI including black stool.

take on an empty stomach, as many foods mess with absorption. ascorbic acid (Vit C) enhances absorption

deferoxamine (chelators), phlebotomy