Drugs Acting on Blood Coagulation system and their
Mechanism of Action: A review
Srividya B*
*Department of Pharmaceutical Analysis, Yalamarthy Pharmacy College, Andhra University,
Vishakapatnam, India
- *Corresponding Author:
- Srividya B
Department of Pharmaceutical
Analysis
Yalamarthy Pharmacy
College, Andhra University
Vishakapatnam, India
Email: vidyacps@gmail.com
Received date: 13/09/2016; Accepted date: 13/09/2016; Published date: 15/09/2016
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Abstract
This review mainly explains about the different classes of the drugs which affects the blood coagulation and mechanism of action of the drugs on the coagulation of the blood system. The mechanism of blood coagulation is explained. The impact of different drugs on the blood coagulation system, their way of action on blood clots, the inhibition action on the receptors is clearly discussed.
Keywords
Blood coagulation, Anticoagulants, Fibrinolysis, Antiplatelet drugs
Introduction
Coagulation is the process of blood clotting, which is mainly used to heal an injury or lesion or wound which finally stops bleeding. The body should have ability to control the flow of blood. The process of blood clotting and then the subsequent dissolution of the clot and repair of the injured tissue is termed as haemostasis. Coagulation involves platelet association and coagulation factor [1-6]. Usually, the process of coagulant is under the inhibitory control of several inhibitors that limit the clot formation, thus avoiding the thrombus propagation. Anticoagulants are agents are used to prevent the formation of blood clots. The mechanism of action of anticoagulation varies from drug to drug. This thrombohaemmorhagic balance is maintained in the body by complicated interactions between coagulation and the fibrinolytic system as well as platelets and vessel wall. It is important to maintain the haemostatic system. This balance sometimes may be disturbed by surgery, trauma or infectious agents [7-13].
Anticoagulants therapy is used for the prevention of coagulation and treatment of thrombosis [14-17]. The drugs like heparin, fondaparinux, and warfarin are commonly used anticoagulants; they are used as thrombin inhibitors. Novel oral anticoagulants have been invented in clinical development to treat blood coagulation disorders. Hemorrhage is the adverse effect with all anticoagulants [18-22].
Blood Coagulation
It is the process by formation of blood clot to stop bleeding. This process is called hemostasis, which is the very process for survival [23-24].
Mechanism of Blood Coagulation
The first step in the process of the blood coagulation is the vascular constriction, which limit the blood flow in the injured area. Then the platelets are activated by thrombin, then these platelets and aggregate at the site of injury, forming a temporary, loose platelet plug [25-28]. Then these platelets clump by binding to collagen, finally these platelets release the nucleotide, ADP and the eicosanoid, TXA2 serotonin, phospholipids, lipoproteins, and other proteins important for the coagulation cascade. Then fibrin mesh forms and entraps the loose plug to make it stable. If the plug contains only platelets it is called as white thrombus, if contains red blood cells, it is called a red thrombus [29-32].
Different Classes of The Drugs Which Act on Blood Coagulation System Coagulation
Drugs which Inhibit Platelet Function (Anti Platelet Drugs)
Platelets aggregate and form platelet to platelet adhesion. After adhesion of platelets, these platelets are activated by number of agonists such as adenosine diphosphate (ADP) which are present at the sites of vascular injury [33-37].
When a blood vessel wall is injured, platelets adhere to the collagen and von Willebrand factor in the wall via platelet receptors which leads to platelet activation [38-45]. Activated platelets release the contents of their granules including ADP and secrete TXA2 → activates nearby platelets to produce further accumulation of more platelets, then platelet aggregate and forms a platelet plug [46-51].
After this platelets are stimulated to aggregate, arachidonic acid is released from platelet phospholipids, which is converted to thromboxane A2 by the cyclooxygenase and thromboxane synthetase. As this occurs, platelet levels of cyclic AMP decrease, and ADP is released [51-59]. Both ADP and thromboxane A2 are potent stimuli for platelet aggregation [60-61]. Anti-platelet drugs acts in three ways.
Drugs act inhibiting cyclooxygenase
These drugs inhibits platelet cyclooxygenase-1, which is the key enzyme involved in the synthesis of thromboxane A 2 and there by decrease the action of aggregation of platelets [62-68]. e.g., Aspirin.
Drugs act by Inhibiting Phosphodiesterase
These drugs inhibits phosphodiesterase in platelets, thereby increase in cAMP concentration in cells which prevents the synthesis of thromboxane A 2, thereby decrease in platelet aggregation [69-73]. e.g., Dipyridamole.
Drugs act by inhibiting ADP-mediated aggregation
These drugs blocks purinergic receptors for ADP in platelet membranes thereby inhibits the ADP-induced expression of glycoprotein (GP) IIb/IIIa receptors in platelet membrane decrease in platelet aggregation [74-79]. e.g., Ticlopidine.
Drugs act by expanding plasma
These drugs are plasma expanders which lead to decrease in the vascular stasis, there by decrease platelet adhesiveness [80-86]. e.g., Dextran.
Drugs which Decrease Fibrin Formation (Anticoagulants)
These are the drugs which act by Inhibit clotting mechanism or by fibrin formation.
Drugs act Activation of anticlotting factors especially antithrombin III
These drugs binds to the antithrombin III , a protease inhibitor that complexes with activated clotting factors II, IX, X and XI and enhances the action Antithrombin III which inhibits clotting factor proteases, by forming stable complexes. Thereby prevents platelet binding [87-90]. e.g., Heparin
Drugs act by fibrin formation
These drugs act by binding to thrombin thereby by inhibiting fibrin formation. There by stops coagulation. e.g., Hirudin
Drug act by Inhibition of synthesis of blood coagulation factor precursors
These drugs act by interfering with the synthesis of Vitamin k by inhibiting epoxide hydrase. This leads to
inhibition of activation of vitamin K-dependent clotting factors (II, VII, IX, X). e.g., Warfarin [91-95]
Drug Act by Activation of Fibrinolysis (Thrombolytic Drugs)
These are the drugs act by stimulating the conversion of endogenous plasminogen to plasmin, degradation both of fibrin and fibrinogen which leads stemic activation of fibrinolysis which thereby causes the dissolution of the thrombus [95-99]. e.g., Streptokinase, urokinase.
Drugs which are Used to Affect Hemostasis
Aminocaproic acid, tranexamic acid, Desmopressin, Dihydroergotamine mesylate and Pentoxifyllin.
Conclusion
The vast research studies have been conducted to understand the mechanisms of different drugs which act on blood coagulation system, which helped in invention of many anticoagulant therapies. These therapies helped to improve the management of the bleeding in patient. The mechanism of the action still more drugs should be discovered and more anticoagulant drug should be invented to improve the quality of therapies.
References
- Lisboa da Silva RMF. Novel Anticoagulants in Non-Valvular Atrial Fibrillation: An Evidence-Based Analysis. Evidence Based Medicine and Practice. 2015;1:1000e101.
- Pérez-Sánchez H. Virtual Screening for the Discovery of New Anticoagulants. Drug Design 2013; S1:e001.
- Bhatia S, et al. Safety and Efficacy of New Oral Anticoagulants in Patients with Atrial Fibrillation: A Literature Review. J Diabetic Complications. 2015;1:101.
- Carnes EB, et al. Role of Novel Oral Anticoagulants in Primary and Secondary Thromboprophylaxis in Cancer. J Hematol Thrombo Dis. 2015;3:222.
- Lu DY, et al. Plasma Fibrinogen Concentrations in Patients with Solid Tumors and Therapeutic Improvements by Combining Anticoagulants or Fibrinolytical Agents. Adv Pharmacoepidemiol Drug Saf. 2015;4:e133.
- Micco PD, et al. Baseline Analysis on the Outcome of Patients with Deep Vein Thrombosis (DVT) Before the Global Impact of New Oral Anticoagulants in Italy: Data from RIETE Registry. J Blood Lymph. 2014;4:129.
- Shiga T. Persistence of Oral Anticoagulants in Japanese Patients with Atrial Fibrillation: Non-Vitamin K Antagonist Oral Anticoagulant versus Warfarin. Arrhythm Open Access. 2016;1:e102.
- Marri PR, et al. Hereditary Thrombocytosis in 3 Kuwaiti Siblings with Homozygous MPL Pro106Leu Mutation and Abnormal Platelet Aggregation. J Genet Disor Genet. 2013;2:2.
- Teixeira CA, et al. An 18-Year-Old Asthmatic Woman with Pneumomediastinum and Pneumorrhachis. Prensa Med Argent. 2015;101:1.
- Iannaccone M, et al. Possible Role of the Transglutaminase-Catalyzed Reactions in the Pathogenesis of Neurodegenerative Diseases. Prensa Med Argent. 2015;101:1.
- Kumar SK, et al. Acute Necrotising Pneumonia with Bronchiectatic Changes and Transaminitis following Kerosene Ingestion: An Unusual Acute Presentation. Prensa Med Argent. 2015;101:1.
- MAROY B. Acute Cytolytic Hepatitis Probably due to Lercadinipine. Prensa Med Argent. 2015;101:1.
- Kumar SK, et al. Influence of Speed of Fentanyl Citrate Injection before Induction of Anesthesia on Fentanyl-Induced Cough: a Prospective, Randomized, Double Blinded Study. Prensa Med Argent. 2015;101:1.
- Silver RT and Hasselbalch HC. Optimal Therapy for Polycythemia Vera and Essential Thrombocythemia: A Different Perspective. J Blood Res Hematol Dis. 2015;1:1.
- Massimo LM. Caring for a Sick Child. J Blood Res Hematol Dis. 2016;1:1.
- Maeda Y, et al. Relationship between Cellular Senescence and Redox Potential on Adult T-Cell Leukemia Cells. J Blood Res Hematol Dis. 2016;1:1.
- Paulsrud C, et al. Autoimmune Thyroid Disease in Patients with Philadelphia-Negative Chronic Myeloproliferative Neoplasms Treated with Interferon-Alpha. J Blood Res Hematol Dis. 2016;1:1.
- Sadras T, et al. The Role of β -Catenin Signaling in Normal and Malignant Hematopoiesis. J Blood Res Hematol Dis. 2016;1:1.
- Abdulmoein EA and Ihab A.A. The Combined Use of Intracaval and Oral Calcium for the Treatment of Hereditary Vitamin D Resistant Rickets (HVDRR). Prensa Med Argent. 2015;101:2.
- Finn Friis L. Retinopathy in Diabetic Pregnancy-IGF and Progression. Prensa Med Argent. 2014;100:4.
- Parmar P, et al. Drug Abuse and Illicit Drug Trafficking Vis-A-Vis Human Life – A Review. Prensa Med Argent. 2015;101:1.
- Geramy A and Sheikhzadeh S. Torque Control of Upper Incisor in Intrusive Loads and Comparison of the Lingual and Labial Bracket Systems: A Finite Element Analysis. Prensa Med Argent. 2015;101:2.
- Hugo R, et al. Foreign Bodies in the Airway in Children: Experience in Argentina. Prensa Med Argent. 2015;101:2.
- Mayur S, et al. Role of Lactic Acid Bacteria as Probiotics in Health and Disease. Prensa Med Argent. 2015;101:2.
- Al-BiltagiM. Diet and Childhood Asthma. Prensa Med Argent. 2014;100:3.
- Choudhuri R, et al. Can Undiagnosed Parkinson’s disease become Uncovered in Perioperative Phase? A Case Report of Stormy Postoperative Event. Prensa Med Argent. 2014;100:3.
- Fakhraei B and Farjam M. Evidence- Based Hypotheses about Levels of Prevention of Multiple Sclerosis: Current Findings, Future Prospects. Prensa Med Argent, 2014;100:3.
- Tumram NK. Fatal Poisoning in Man due to Oral Use of Nerium Oleander for Medicinal Purpose. Prensa Med Argent 2014;100:3.
- Choudhuri R, et al. Effect of Paracetamol Intravenous Infusion on Duration and Quality of Spinal Blockade in Patients Undergoing Major Gynaecological Surgeries: A Prospective, Randomised, Double-Blinded, Placebo-Controlled Study. Prensa Med Argent 2014;100:3.
- Unver B, et al. Factors Related to the Frequency of Citation of the Physical Therapy Journal. Prensa Med Argent. 2014;100:3.
- Svetoslav NS,et al. Chikungunya Virus (Chikv): General Characteristics and Possible Impact on Hemotherapy. Prensa Med Argent. 2015;101:5.
- Kedar SS, et al. Evaluation of Intraperitoneal and Port Site Infiltration of Bupivacaine in Combination with Fentanyl for Management of Postoperative Pain following Laparoscopic Cholecystectomy: A Double Blind Randomized Study. Prensa Med Argent. 2015;101:5.
- Lars TN, et al. Might a Systematic Reading of the Thickest GP Patient Medical Records Improve our Understanding of Functional Disorders. Prensa Med Argent. 2015;101:5.
- Bianchi D, et al. Athanasopoulou E, Venditti D, et al. Spontaneous Retroperitoneal Hemorrhage: a Case Report and an Overview of the Literature. Prensa Med Argent. 2015;101:5.
- Amelia MG and Mihnea AG. A Diffuse Large B cell Lymphoma (DLBCL);With Central Nervous System Involvement in a HIV Positive Patient. La PrensaMedica Argentina. (2015);101:5.
- Farzad B and Hamed A The Consequences of Falling Among Older Adults. Prensa Med Argent. 2015;101:5.
- Tanmoy G and Sandeep Kumar K. Postoperative Pneumoscrotum in a Cardiac Surgery Patient: A Case Report. Prensa Med Argent. 2015;101:5.
- Dhiman A, et al. Laparoscopic Bilateral Adrenalectomy in a Patient of Cushing Disease due to Pituitary Microadenoma: a Challenge for the Anaesthesiologist. Prensa Med Argent. 2015;101:5.
- Tanmoy G, et al. Thoracic Gunshot Wound: A Report of 3 Cases and Review of Management. Prensa Med Argent. 2015;101:5.
- Benetti F, et al. Surgical Implantation of Stem Cells in Heart Failure Patients due to Idiophatic Cardiomyopathy. Prensa Med Argent. 2015;101:5.
- Hosam G, et al. Evaluation of Overlap Anal Sphincter Repair (OASR);in Patients with Post-Traumatic Fecal Incontinence. Prensa Med Argent. 2015;101:5.
- Abdollah MS, et al. The Frequency of Allergic Rhinosinusitis in Patients Referred to Ear, Nose Throat Clinic due to Chronic Rhinosinusitis. Prensa Med Argent. 2015;101:5.
- Kumar SK, et al. Robotic Cardiac Surgery: A Systematic Review of the Past and Present. Prensa Med Argent. 2015;101:5.
- Khodarahimi S and Johnston CA. The Role of Adolescence Stages and Physical puberty on Mental Health and Hope in an Iranian Sample. Prensa Med Argent. 2015;101:5.
- Farhadi M, et al. Y Role of Helicobacter pylori in Nasal Polyp Formation: A Case-Control Study in Tehran, Iran. Prensa Med Argent. 2015;101:5.
- Deguenonvo REA, et al. Surgical Management of Differentiated Thyroid Carcinomas: Experience in a Low-Income Country. Prensa Med Argent. 2016; 102:3.
- Anis Z, et al. Absence of Palmaris Longus in Medical Students of Karachi. Prensa Med Argent. 2016;102:3.
- Cano M et al. Micro deletion with Cleft Lip. Prensa Med Argent. 2016;102:3.
- Alenezy A and Alenzi FQ. Attitudes of Patients with Hypercholesterolemia in a Primary Health Care Center in the North of Saudi Arabia. Prensa Med Argent. 2016;102:3.
- Regonne PEJ, et al. Thyroidectomies in the Elderly: A Multi Centric Study at ENT Department of Cheikh Anta Diop University of Dakar. Prensa Med Argent. 2016;102:3.
- Khouzam HR, et al. I-A SPECIAL: A Mnemonic for DSM-5 Borderline Personality Disorder Diagnostic Criteria. Prensa Med Argent. 2016;102:3.
- Al-Bukhari TA, et al. The Expression of BCL-G in Leukemia and Gastrointestinal Tissues. Prensa Med Argent. 2016;102:3.
- Ferekidis E, et al. Evolutions in our Practice on the Management of the Chronic Ear Diseases through the Years. Prensa Med Argent. 2016;102:3.
- KnoringBE, et al. Features of Cytokine Profile in Patients with Progressive TB-Induced Pulmonary Fibrosis Characterized by Various Intensities of Pulmonary Destructive Changes. Prensa Med Argent. 2016;102:2.
- Al-Jaroudi D, et al. A Belief of Nutrition and Healthy Lifestyle among Women in a Hospital Setting. Prensa Med Argent. 2016;102:2.
- Qi X, et al. Asymptomatic Umbilical Hernia in Liver Cirrhosis. Prensa Med Argent. 2016;102:2.
- Alanazi B, et al. Total Knee Replacement in the Presence of Proximal Tibial Non-Union: A Report of Two Cases. Prensa Med Argent. 2016;102:2.
- Delvecchio L, et al. Reliability of Squat Jump and Countermovement Jump Performance in Masters Athletes. Prensa Med Argent. 2016;102:2.
- Khashaba O, et al. Alqudaimi HYM Oro-Periodontal Manifestations of Langerhans Cell Histiocytosis (EosinophilicGranuloma). Prensa Med Argent. 2016;102:2.
- Deguenonvo REA, et al. Laryngotracheoplasty for Laryngotracheal Stenosis Post Intubation and Post Tracheostomy: A Case of Stenting with Airway Exchange Catheter. Prensa Med Argent. 2016;102:2.
- Keskek SÖ, et al. Prevalence of Thyroid Dysfunction in Turkish Patients with Metabolic Syndrome: A Cross- Sectional Study. Prensa Med Argent. 2014;100:2.
- Kale S, et al. A Rare Case of Right Paravertebral Myoepithelioma with Intradural Extension Causing Cord Compression. Prensa Med Argent. 2014;100:2.
- Karakaya AD, et al. Congenital Absence of Right Internal Carotid Artery: Demonstration of Collateral Circulation by Computed Tomography Angiography. Prensa Med Argent. 2014;100:2.
- Troncoso A. Scientific Progress and Ethic Stumbles: Tuskegee’s Research. Mol Med Ther. 2014;1:1.
- Ribeiro KD, et al. A 34-Year-Old Man with Porphyria CutaneaTarda. Prensa Med Argent. 2014;100:2.
- Mlika M, et al. Is It Necessary to Subdivide the pN2 Group of Non-Small Cell Lung Cancer? Prensa Med Argent. 2014;100:2.
- Aljaied S, et al. Congenital Hypothyroidism Diagnosed At 9 Years Old. Prensa Med Argent. 2014;100:2.
- Saith SE, et al. All-cause Mortality of High-normal Random Blood Glucose using Basic Demographics. J Cardiovasc Dis Diagn. 2016;4:248.
- Taira J, et al. Relationship between the Status of Blood Supply in the Non-hypervascular Hepatocellular Nodules among Chronic Liver Diseases and the Hypervascular Change. J Liver. 2016;5:197.
- Oladosu TO, et al. CD4 Profile and Relationship with Bacterial Isolates from the Blood of HIV-1 Patients attending art Clinic at a Tertiary Healthcare Institution in Southwest, Nigeria. HIV Curr Res. 2016;1:109.
- Kolawole AK. Effect of Organic Turmeric Supplemented-diet in Rabbits Acutely Exposed to Ultraviolet Radiation: Oxidative Stress in the Blood. Anat Physiol. 2016;6:229.
- Ojo BA, et al. Assessment of Blood CD4 Count and Antibiogram Profile of Bacteria Isolated from HIV Patients. HIV Curr Res. 2016;1:107.
- Carr BI, et al. An HCC Aggressiveness Index and Blood GTP, Bilirubin and Platelet Levels. J IntegrOncol. 2016;5:172.
- Pezzella F. Cancer and Blood Vessels: A Complex Relationship. J Lung Cancer Diagn Treat. 2016;1:104.
- Freedman J. TransfusionMedicine: Time for a Change: Patient Blood Management and the Ontario ONTraC Program. J PerioperCrit Intensive Care. 2016;2:123.
- Lee A and Rajaratnam R. Tailoring the Novel Anticoagulants to the Stroke Patient – One Size Does Not Fit All Novel Anticoagulants in Stroke. J NeurolNeurophysiol. 2014;5:248.
- Cox JL. Practical Management of Stroke Prevention in Patients with Atrial Fibrillation and Renal Impairment Receiving Newer Oral Anticoagulants: Focus on Rivaroxaban. J Gen Pract. 2014;2:144.
- Patel S, et al. Effectiveness of Pharmacy Run Anticoagulation Clinics Compared to Large Clinical Trials of New Oral Anticoagulants. J Pharma Care Health Sys. 2014;1:101.
- Sairaku A, et al. How to Use Novel Oral Anticoagulants during the Periprocedural Period of Atrial Fibrillation Ablation. Pharm Anal Acta. 2014;5:294.
- Rosnah B, et al. The Level of Natural Anticoagulants in Transfusion Dependent Thalassemia Patients in Kelantan, Northeastern Malaysia. J Hematol Thrombo Dis. 2014;2:140.
- Jhansi K and Vanita P. A Review on Antiplatelet Drugs and Anticoagulants. AdvPharmacoepidemDrug Safety. 2014;3:R003.
- Kamali F. Are Novel Oral Anticoagulants (Noacs);as Safe as They are Said to Be? AdvPharmacoepidemiol Drug Saf. 2014;3:e126.
- Rachel C, et al. The -765G>C Cyclooxygenase-2 Promoter Polymorphism is associated with Type 2 Diabetes Mellitus, Low High-density Lipoprotein and Manifest Angina. J Diabetes Metab. 2016;7:686.
- Asif M, et al. A Review on Pyridazinone Compounds ABT-963 as Selective Cyclooxygenase Inhibitor. J Cell SciTher. 2016;7:243.
- Chang CZ, et al. Parecoxib, A Selective Cyclooxygenase Inhibitor, Attenuates C-Jun N-Terminal Kinase Activation in Experimental Subarachnoid Hemorrhage Induced Early Brain Injury. J NeurolNeurophysiol. 2015;6:294.
- Ishii M, et al. A Cyclooxygenase 2 Gene Polymorphism is a Risk Factor for the Complication of Medication Overuse Headaches in Patients with Migraines. J NeurolDisord. 2015;3:206.
- Srivastava P, et al. Screening and Identification of Salicin Compound from Desmodiumgangeticum and its In vivo Anticancer Activity and Docking Studies with Cyclooxygenase (COX);Proteins from Musmusculus. J Proteomics Bioinform. 2013;6:109-124.
- Ishii M, et al. A Cyclooxygenase 2 Gene Polymorphism is a Risk Factor for the Complication of Medication Overuse Headaches in Patients with Migraines. J NeurolDisord. 2015;3:206.
- Chang CZ, et al. Parecoxib, A Selective Cyclooxygenase Inhibitor, Attenuates C-Jun N-Terminal Kinase Activation in Experimental Subarachnoid Hemorrhage Induced Early Brain Injury. J NeurolNeurophysiol. 2015;6:294.
- Asif M. A Review on Pyridazinone Compounds ABT-963 as Selective Cyclooxygenase Inhibitor. J Cell SciTher. 2016;7:243.
- Sun J, et al. Aspirin Inhibition of α-Granules Release is Associated with Sirt1/AMPK and PI3K/Akt Pathway in Thrombin-Activated Platelets. Cardiovaspathol. 2016;1:111.
- Wei YY, et al. Prevention of Preeclampsia with Aspirin Therapy in the Second Trimester and Pregnancy Outcome: A Meta-analysis. J Health Med Informat. 2016;7:225.
- Mitsui C, et al. P-Selectin is a Key Molecule Underlying the Pathophysiology of Aspirin- Exacerbated Respiratory Disease. ImmunolDisordImmunother. 2016;1:104.
- Kurosawa M, et al. Hypothetical Mechanism of Aspirin-Exacerbated Respiratory Disease Based on Recent Investigations of Gene Polymorphisms in Japanese Patients. J AllergyTher. 2016;7:230.
- Tsai TJ and Hsu PI. Low-Dose Aspirin-Induced Upper Gastrointestinal Injury-Epidemiology, Management and Prevention. J Blood DisordTransfus. 2015;6:327.
- Sarzaeem MM. Low Molecular Weight Heparin and Aspirin Prophylaxis after Total Knee Arthroplasty . J Blood Lymph. 2016;4:e116.
- Michiels JJ, et al. Autosomal Dominant Hereditary Essential Thrombocythemia due to a Gain of Function Mutation in the Thrombopoietin (TPO); and JAK2 Gene as the Cause of Congenital Aspirin-Responsive Sticky Platelet Syndrome: Personal Experiences and Review of the Literature. J HematolThromb Dis. 2014;3:180.
- Patel D, et al. An Alternative Aspirin Desensitization Protocol for Patients with Aspirin-Exacerbated Respiratory Disease. J Allergy Ther. 2015;6:207.
- Mendes GD, et al. Pharmacokinetic Evaluation of Administration of Losartan with Aspirin in Healthy Volunteers. J BioequivAvailab. 2015;7:144-149.