WordNet

limit, block, or decrease the action or function of; "inhibit the action of the enzyme"; "inhibit the rate of a chemical reaction"
control and refrain from showing; of emotions, desires, impulses, or behavior (同)bottle up, suppress
limit the range or extent of; "Contact between the young was inhibited by strict social customs"
a substance that retards or stops an activity
tiny bits of protoplasm found in vertebrate blood; essential for blood clotting (同)blood_platelet, thrombocyte

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〈感情・欲望・行動・作用など〉‘を'抑制する / (…しないように)〈人〉‘を'抑制する,妨げる《+『名』+『from』+『名』(do『ing』)》
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/04/22 21:42:16」(JST)

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An antiplatelet drug (antiaggregant) is a member of a class of pharmaceuticals that decrease platelet aggregation ^[1] and inhibit thrombus formation. They are effective in the arterial circulation, where anticoagulants have little effect.^{[citation needed]}

They are widely used in primary and secondary prevention of thrombotic cerebrovascular or cardiovascular disease.

Choice of antiplatelet drug

A 2006 review ^[2] states: "...low-dose aspirin increases the risk of major bleeding 2-fold compared with placebo. However, the annual incidence of major bleeding due to low-dose aspirin is modest—only 1.3 patients per thousand higher than what is observed with placebo treatment. Treatment of approximately 800 patients with low-dose aspirin annually for cardiovascular prophylaxis will result in only 1 additional major bleeding episode."

Antiplatelet drugs

The class of antiplatelet drugs include:

Irreversible cyclooxygenase inhibitors
- Aspirin
Adenosine diphosphate (ADP) receptor inhibitors
- Clopidogrel (Plavix)
- Prasugrel (Effient)
- Ticagrelor (Brilinta)
- Ticlopidine (Ticlid)
Phosphodiesterase inhibitors
- Cilostazol (Pletal)
Glycoprotein IIB/IIIA inhibitors (intravenous use only)
- Abciximab (ReoPro)
- Eptifibatide (Integrilin)
- Tirofiban (Aggrastat)
Adenosine reuptake inhibitors
- Dipyridamole (Persantine)
Thromboxane inhibitors
- Thromboxane synthase inhibitors
- Thromboxane receptor antagonists
  - Terutroban

Usage

In dental implants procedures

Dental implant procedures can be safely performed in patients on long-term antiplatelet medication, with no interruption or alteration of their medication. Such patients do not have an increased risk of prolonged or excessive postoperative bleeding.^[3]

Prevention and treatment of arterial thrombosis

Treatment of established arterial thrombosis includes the use of antiplatelet drugs and thrombolytic therapy. Antiplatelet drugs alter the platelet activation at the site of vascular damage crucial to the development of arterial thrombosis.

Aspirin irreversibly inhibits the enzyme COX, resulting in reduced platelet production of TXA₂ (thromboxane - powerful vasoconstrictor that lowers cyclic AMP and initiates the platelet release reaction).
Dipyridamole inhibits platelet phosphodiesterase, causing an increase in cyclic AMP with potentiation of the action of PGI₂ – opposes actions of TXA₂
Clopidogrel affects the ADP-dependent activation of IIb/IIIa complex
Glycoprotein IIb/IIIa receptor antagonists block a receptor on the platelet for fibrinogen and von Willebrand factor. 3 classes:
- Murine-human chimeric antibodies (e.g., abciximab)
- Synthetic peptides (e.g., eptifibatide)
- Synthetic non-peptides (e.g., tirofiban)
Epoprostenol is a prostacyclin that is used to inhibit platelet aggregation during renal dialysis (with or without heparin) and is also used in primary pulmonary hypertension.

Thrombolytic therapy is used in myocardial infarction, cerebral infarction, and, on occasion, in massive pulmonary embolism. The main risk is bleeding. Treatment should not be given to patients having had recent bleeding, uncontrolled hypertension or a hemorrhagic stroke, or surgery or other invasive procedures within the previous 10 days.

Streptokinase forms a complex with plasminogen, resulting in a conformational change that activates other plasminogen molecules to form plasmin.
Plasminogen activators (PA), tissue-type plasminogen activators (alteplase, tenecteplase) are produced by recombinant technology.

Drug toxicity

Drug toxicity may be increased when multiple antiplatelet drugs are used. Gastrointestinal bleeding is a common adverse events seen in many patients.^[4]

References

^ "Antiplatelet agents" at Dorland's Medical Dictionary^{[dead link]}
^ The American Journal of Medicine, Volume 119, Issue 8 , Pages 624-638, August 2006: Systematic Review and Meta-analysis of Adverse Events of Low-dose Aspirin and Clopidogrel in Randomized Controlled Trials Retrieved 2013-02-08
^ Mihai Bogdan Bucur (Nov 2011). "Antiplatelet treatment implications in oral implantology" (HTML). Rev. chir. oro-maxilo-fac. implantol. (in (Romanian)) 2 (3): 6–9. ISSN 2069-3850. 39. Retrieved 2012-04-15. (webpage has a translation button)
^ Shehab, Nadine; Laurence S. Sperling, Scott R. Kegler, Daniel S. Budnitz (2010-11-22). "National Estimates of Emergency Department Visits for Hemorrhage-Related Adverse Events From Clopidogrel Plus Aspirin and From Warfarin". Arch Intern Med 170 (21): 1926–1933. doi:10.1001/archinternmed.2010.407. PMID 21098354. Retrieved 2010-11-23.

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UpToDate Contents

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1. ST上昇型心筋梗塞における抗血小板剤 antiplatelet agents in acute st elevation myocardial infarction
2. 血小板機能検査 platelet function testing
3. クロピドグレル耐性とクロピドグレル治療不奏効 clopidogrel resistance and clopidogrel treatment failure
4. 血小板輸血療法の臨床上および検査上の特徴 clinical and laboratory aspects of platelet transfusion therapy
5. 止血の概要 overview of hemostasis

English Journal

Platelet-Derived Growth Factor BB Mimics Serum-Induced Dispersal of Pancreatic Epithelial Cell Clusters.

Hiram-Bab S1, Katz LS, Shapira H, Sandbank J, Gershengorn MC, Oron Y.Author information 1Department of Physiology and Pharmacology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.AbstractWe showed previously that proliferating human islet-derived de-differentiated cells (DIDs) exhibit many characteristics of mesenchymal stem cells. Dispersed DIDs can be induced by serum deprivation to undergo mesenchymal-to-epithelial transition and aggregate into epithelial cell clusters (ECCs). Conversely, ECCs can be induced to disperse and undergo epithelial-to-mesenchymal transition (EMT) by re-addition of mammalian sera. In this study, we show that platelet-derived growth factor BB (PDGF-BB) mimics and mediates serum-induced ECCs' dispersal accompanied by accumulation of cytoplasmic β-catenin and a decrease in the levels of insulin and glucagon mRNAs. Moreover, we show that PDGF-BB-induced dispersal of ECCs is a more general phenomenon that occurs also with bone marrow mesenchymal stem cells (BM-MSCs) and dermal fibroblasts (DFs). In DIDs, BM-MSCs, and DFs, PDGF decreased the levels of DKK1 mRNA, suggesting involvement of the Wnt signaling pathway. PDGF-BB stimulated a significant increase in S473 phosphorylation of Akt and the PI3K specific inhibitor (PIP828) partially inhibited PDGF-BB-induced ECC dispersal. Lastly, the PDGF-receptor (PDGF-R) antagonist JNJ-10198409 inhibited both PDGF-BB-and serum-induced ECC dispersal. Epidermal growth factor (EGF), which shares most of the PDGF signaling pathway, did not induce dispersal and only weakly stimulated Akt phosphorylation. Our data suggest that PDGF-BB mediates serum-induced DIDs dispersal, correlated with the activation of the PI3K-Akt pathway. J. Cell. Physiol. 229: 743-751, 2014. © 2013 Wiley Periodicals, Inc.
Journal of cellular physiology.J Cell Physiol.2014 Jun;229(6):743-51. doi: 10.1002/jcp.24493.
We showed previously that proliferating human islet-derived de-differentiated cells (DIDs) exhibit many characteristics of mesenchymal stem cells. Dispersed DIDs can be induced by serum deprivation to undergo mesenchymal-to-epithelial transition and aggregate into epithelial cell clusters (ECCs). Co
PMID 24129818

Grape seed extracts inhibit platelet aggregation by inhibiting protein tyrosine phosphatase.

Jin JW1, Inoue O, Suzuki-Inoue K, Nishikawa G, Kawakami Y, Hisamoto M, Okuda T, Ozaki Y.Author information 11Department of Clinical and Laboratory Medicine, Faculty of Medicine, University of Yamanashi, Yamanashi, Japan.AbstractPlatelets play an important role in various thrombotic diseases, including myocardial infarction. Because red wine consumption is inversely associated with death due to ischemic heart diseases, the effects of grape components on platelet function have been extensively investigated. Grape seed extracts (GSEs) reportedly inhibit platelet aggregation; however, the underlying mechanism has not been elucidated. We discovered that GSEs inhibit platelet aggregation induced by collagen and thrombin-receptor agonist peptide and increase basal levels of tyrosine phosphorylation, which was also observed in the presence of a protein tyrosine phosphatase (PTP) inhibitor. An in vitro phosphatase assay indicated that GSE dose dependently inhibited PTP-1B and Src homology 2 domain-containing phosphatase-1 activity, which positively regulates platelet aggregation. We propose that GSEs inhibit platelet aggregation by inhibiting tyrosine phosphatase activity. Moreover, we showed that GSE ingestion inhibited platelet aggregation in mice without enhancing tail bleeding, implying that GSE supplementation might be beneficial to prevention of thrombotic diseases.
Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.Clin Appl Thromb Hemost.2014 Apr;20(3):278-84. doi: 10.1177/1076029613481103. Epub 2013 Mar 10.
Platelets play an important role in various thrombotic diseases, including myocardial infarction. Because red wine consumption is inversely associated with death due to ischemic heart diseases, the effects of grape components on platelet function have been extensively investigated. Grape seed extrac
PMID 23478570

Angiotensin II activation of TRPC6 channels in rat podocytes requires generation of reactive oxygen species.

Anderson M1, Roshanravan H, Khine J, Dryer SE.Author information 1Department of Biology and Biochemistry, University of Houston, Houston, Texas.AbstractAngiotensin II (AII) plays a major role in the progression of chronic kidney diseases. Podocytes are essential components of the ultrafiltration apparatus, and are targets for AII signaling. AII has been shown to increase generation of reactive oxygen species (ROS) in podocytes. Canonical transient receptor potential-6 (TRPC6) channels stimulate Ca(2+) influx in podocytes, and have been implicated in glomerular disease. We observed that AII increased cationic currents in rat podocytes in an isolated glomerulus preparation in which podocytes are still attached to the underlying capillary. This effect was completely blocked by SKF-96365, by micromolar La(3+) , and by siRNA knockdown of TRPC6, indicating that TRPC6 is the primary source of Ca(2+) influx mobilized by endogenously expressed angiotensin II receptors in these cells. These responses were also blocked by the AT1R antagonist losartan, the phospholipase C inhibitor D-609, and by inhibition of G protein signaling. The pan-protein kinase C inhibitor chelerythrine had no effect. Importantly, pretreating podocytes with the ROS quencher manganese (III) tetrakis (4-benzoic acid) porphyrin chloride (MnTBAP) eliminated AII activation of TRPC6. Significant reductions of AII effects on podocyte TRPC6 were also observed after pretreatment with NADPH oxidase inhibitors apocynin or diphenylene iodonium (DPI). These data suggest that ROS production permits activation of TRPC6 channels by G protein and PLC-dependent cascades initiated by AII acting on AT1Rs in podocytes. This pathway also provides a basis whereby two forms of cellular stress-oxidative stress and Ca(2+) overload-converge on common pathways relevant to disease.
Journal of cellular physiology.J Cell Physiol.2014 Apr;229(4):434-42. doi: 10.1002/jcp.24461.
Angiotensin II (AII) plays a major role in the progression of chronic kidney diseases. Podocytes are essential components of the ultrafiltration apparatus, and are targets for AII signaling. AII has been shown to increase generation of reactive oxygen species (ROS) in podocytes. Canonical transient
PMID 24037962

Japanese Journal

Protooncogene TCL1b functions as an Akt kinase co-activator that exhibits oncogenic potency in vivo

Hashimoto M,Suizu F,Tokuyama W,Noguchi H,Hirata N,Matsuda-Lennikov M,Edamura T,Masuzawa M,Gotoh N,Tanaka S,Noguchi M
Oncogenesis 2(9), e70, 2013-09-16
… Moreover, TCL1b structure-based inhibitor 'TCL1b-Akt-in' inhibited Akt kinase activity in in vitro kinase assays and PDGF (platelet-derived growth factor)-induced Akt kinase activities—in turn, 'TCL1b-Akt-in' inhibited cellular proliferation of sarcoma. …
NAID 120005385329

Clinical Trend 選択的セロトニン再取り込み阻害薬と消化管出血

山本貴嗣,阿部浩一郎,久山泰
日本臨床 71(4), 751-756, 2013-04
NAID 40019631025

Chronic Graft-versus-Host Disease: Disease Biology and Novel Therapeutic Strategies

Nishimori Hisakazu,Maeda Yoshinobu,Tanimoto Mitsune
Acta Medica Okayama 67(1), 1-8, 2013-02
… Standard treatment is 1-2mg/kg/day of prednisone or an equivalent dose of methylprednisolone, with continued administration of a calcineurin inhibitor for steroid sparing. … We are now faced with a more complex picture, involving possible roles for thymic dysfunction, transforming growth factor-β (TGF-β) and platelet-derived growth factor (PDGF), B cells and autoantibodies, and Th1/Th2/Th17 cytokines, as well as regulatory T cells (Tregs), in chronic GVHD. …
NAID 120005232331