-
Integrin complex on platelets that serotonin, TXA2, and ADP bind to to activate platelet
GPIIb/GPIIIa
-
Collagen binds to _____ to activate platelet
GP 1a
-
Platelet turnover in ____ days
7-10
-
Irreversible acetylation blockage
Aspirin
-
COX 1
PGE2 (GI cytoprotection), TXA2 synthesis
-
COX 2
- synthesis of prostacyclin, PGE2 for inflammed tissue, no TXA2 synthesis.
- Blockade leads to hypertension and thrombosis
-
effect of low dose aspirin
- Low-dose (81-325 mg/day) is more effective in preventing platelet initiated coagulation than higher doses
- Decrease TXA2 and preserve ProstacyclinPlatelets cannot make more COX enzyme and are permanently inactive - no TXA2
-
Aspirin side effects
tinnitus, hearing loss, GI upset, bleeding defect
-
Celecoxib (Celebrex)
NSAID w/ more action at COX 2 blocker. Less GI bleed
-
Inhibits thromboxane synthesis. Also prevents bronchoconstriction and vasoconstriction.
Side effects: Vasodilation, hypotension, bleeding
Dipyridamole
-
ADP receptor (P2Y) blockers for anti clotting
- Clopidogrel
- Ticlopidine
- Prasugrel
-
Prodrug. Irreversible blockade of ADP receptor on platelets. Fibrinogen binding (platelet to platelet binding) is decreased by preventing glycoprotein IIb/IIIa expression on platelet surface.
Clopidogrel
-
Toxicity: GI upset, bleeding, rarely leucopenia
Reduced effectiveness in patients with low CYP2C19 function
Clopidogrel
-
same MOA as Clopidogrel but may cause neutropenia/agranulocytosis, thrombotic thrombocytopenic purpura (TTP) and aplastic anemia
Ticlopidine
-
MOA of Ticlopidine
Irreversible thromboxane synthesis inhibitor. Also prevents bronchoconstriction & vasoconstriction
-
should be reserved for patients who are intolerant or allergic to aspirin
It should be used when aspirin alone fails
Adjunctive therapy with aspirin to reduce stent thrombosis
Clopidogrel and Ticlopidine
-
Risk of bleeding, Renal or hepatic impairment, Geriatric patients (increased sensitivity), Neutropenia, Thrombocytopenia, Thrombotic Thrombocytopenic Purpura (TTP)
Ticlopidine
-
Prodrug. Metabolized to active form via esterase, CYP3A4 and CYP2C19. Better metabolic activation than clopidogrel. More potent, faster acting, better consistency in platelet inhibition over time than clopidogrel
Prasugrel
-
Bleeding. Various cardiovascular. Various GI. Headache, dizziness, fatigue
Discontinue at least 7 days prior to surgery
Prasugrel
-
Glycoprotein IIb/IIIa Inhibitors
- Abciximab
- Eptifibatide
- Tirofiban
-
Made from an immunoglobulin that binds platelet glycoprotein IIb/IIIa receptors. Abciximab has high affinity for the GP IIb/IIIa receptor, inhibits it. May last 24-48 hours. Used iv, in hospital, for angioplasty and stent placement to avoid ischemic events
Abciximab
-
incr risk of bleeding, esp GI hemorrhage. Can induce thrombocytopenia and may require platelet transfusion. Platelet counts can drop from 250,000-400,000 to zero
Abciximab
-
Reversibly binds to platelet surface glycoprotein IIb/IIIa. Short half life. Eptifibatide is always used together with aspirin or clopidogrel and heparin. Made from a protein found in snake venom.
Eptifibatide
-
Severe bleeding. Hypotension, heart failure, ventricular and atrial fibrillation. Anaphylaxis. Injectable, always used in hospital due to serious indications and side effects
Eptifibatide
-
Synthetic, glycoprotein IIb/IIIa inhibitor. Modified venom of the saw-scaled viper Echis carinatus, anticoagulant. IV. Rapid onset, short duration of action, reversed in 4-8 hours. Combined with heparin and aspirin. Used for unstable angina, myocardial infarction, coronary angioplasty
Tirofiban
-
Tirofiban Toxicity
severe bleeding, Thrombocytopenia and thrombotic thrombocytopenic purpura
-
Inactivate clotting factors
Heparin
-
iv anticoagulant. t1/2 1.5 hrs. High MW, powerful anticoagulant. Negatively charged, polar, will not easily cross membranes.. Short acting
heparin
-
Low molecular weight heparin. long acting
- Enoxaparin
- Dalteparin
- Tinzaparin
-
Synthetic heparin pentasaccharide binds specifically to the heparin binding site on Antithrombin III. Approved for DVT following hip and knee.
Fondaparinux (Another Heparin)
-
Heparin binds ____
Antithrombin III
-
Reverse heparin toxicity with...
protamine sulfate
-
benefit to lower molecular weight heparin
less likely for thrombocytopenia, long acting
-
Measure impact of Heparin in clotting
- Partial Thromboplastin Time (PTT)
- Activated Partial Thromboplastin Time (aPTT)
- Partial refers to action of activator which depends on intrinsic activation, also.
-
Oral anticoagulant. Blocks the synthesis of clotting factors. Benefit is delayed 1-3 days due to existing clotting factors in circulation with long t1/2
Warfarin
-
Blocks vit K epoxide reductase
warfarin
-
reversing warfarin toxicity
replace vit K, clotting factor II and X
-
Used to measure action of Warfarin. Blood is activated with prothrombin, Clotting Factor II. Clotting time is measured
PT test / INR
-
These drugs are derivatives or similar to Hirudin. Lepirudin is recombinant hirudin. Bivalirudin, Argatroban
direct thrombin inhibitors. No thrombocytopenia
-
-
-
same action as streptokinase
urokinase
-
binds and activates plasminogen to produce plasmin (peptidase) action: destruction of fibrin
Infused iv to increase survival during acute myocardial infarction
streptokinase
-
combination of plasminogen and streptokinase
Anistreplase
-
recombinant tissue Plasminogen Activators (tPA)
Altelase, Duteplase and Reteplase
-
reversing too much fibrinolysis
Use Tranexamic acid or Aminocaproic acid to stop plasmin.
-
for pregnant women, give ______ instead of warfarin
heparin. warfarin may induce loss of pregnancy
-
Iron form orally absorbed vs IV/IM
Fe 2+ for oral. Fe 3+ for IV/IM only
-
IV and IM iron toxicity
Iron Dextran can cause vasodilation (headache, dizziness, flushing), fever, joint and muscle pain, urticaria and possibly anaphylaxis and death. The dextran is the hypersensitivity culprit.
-
Iron-sucrose and Iron sodium gluconate
IV/IM iron that is safer and less likely to cause anaphylaxis
-
Oral iron therapy
- 200-400 mg for 3-6 mo. All 2+ salts are useful Ferrous sulfate
- Ferrous gluconate
- Ferrous fumarate
-
Nausea and GI distress, Abdominal Pain
Black stool. Necrotizing gastroenteritis, bloody diarrhea, shock, lethargy, dyspnea, acidosis, coma, death.
Acute iron toxicity
-
treatment for acute iron toxicity
Not activated charcoal (doesn’t bind iron), but whole bowel irrigation to purge pills and intravenous deferoxamine, a strong iron chelator.
-
very effective in chelating ferric (3+) iron. Usually well tolerated by humans. It may scavenge iron from normal tissues.
Injectable Deferoxamine
-
Med that causes bone marrow toxicity. Anemia, neutropenia and sometimes as thrombocytopenia. Thymidine analog NRTI
Zidovudine
-
rHuEpo, Epoetin alfa
Darbopoetin alfa, glycosylated long-acting
Hematopoiesis - Erythropoietin
-
filgrastim: daily injection
Peg-filgrastim: covalent conjugation of filgrastim and polyethylene glycol. This preparation is long acting and can be injected once per chemo dose cycle.
granulocyte colony stimulating factor
-
Toxicity of G-CSF
- Bone pain during the period of filgrastim or pegfilgrastim use.
- Splenic rupture is possible, rare and serious.
-
Has same effects as G-CSF on neutrophil proliferation and action. Additionally, it stimulates other cell lines to include red cells and platelets. Acts with Interleukin-2 to stimulate T-cell proliferation. Proinflammatory. Less effective than G-CSF in mobilizing peripheral blood stem cells.
GM-CSF (granulocyte-monocyte). Sargramostin
-
Toxicity of GM-CSF
Fever, Malaise, Arthralgias and myalgias, Capillary leak syndrome, Peripheral edema, Pleural effusions, Pericardial effusions, Allergy is possible
-
meds that can cause thrombocytopenia
Heparin, quinidine, quinine, sulfa-containing antibiotics, some oral diabetes drugs, gold salts and rifampin
-
Thrombopoietin synthesized in...
human liver
-
Oprelvekin
- Transfusion may be adverse and ineffective. Oprelvekin (Interleukin 11) stimulates proliferation of platelets.
- Adverse effects headache, dizzy, dyspnea (fluid), and arrhythmias.
-
effect of phenytoin
Blocks Dietary Folate absorption – Less N6-Methyl-THF
-
low levels of Methionine in pregnancy can lead to ...
neural tube defects
-
Other effects of low Methionine
- paresthesias and weakness relative to peripheral nerves, spasticity, ataxia and CNS dysfunctions.
- Swelling neurodegeneration
-
S-adenosyl-L-methionine effects
Antidepressant. High homocysteine is same as low Methionine
-
Injectable VitB12
- Cyanocobalamin
- Hydroxocobalamin is preferred
-
Dose of folic acid needed
1mg/d
-
Sideroblastic anemia inducers
- Toxins :(lead or zinc)
- Drugs: INH, chloramphenicol, VitaminB6, or copper deficiency
-
Drugs not to use for G6PD deficiency
quinolones (anti-malarials, quinidine), sulfa antibiotics, and nitrofurantoin
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