Tirofiban (INN, trade name Aggrastat) is an antiplatelet drug. It belongs to a class of antiplatelet named glycoprotein IIb/IIIa inhibitors. Tirofiban is the first drug candidate whose origins can be traced to a pharmacophore-based virtual screening lead.[1][2]
Contents [hide]
1 Medical use
2 Contraindications and precautions
2.1 Cautions
2.2 Adverse Reactions
2.3 Use in pregnancy
2.4 Pediatric use
2.5 Other precautions and laboratory exams
3 Side effects
4 Interactions
5 Pharmacology
6 Physical and chemical properties
7 History
8 References
9 External links
Medical use[edit]
Aggrastat is indicated to reduce the rate of thrombotic cardiovascular events (combined endpoint of death, myocardial infarction, or refractory ischemia/repeat cardiac procedure) in patients with non-ST elevation acute coronary syndrome (NSTE-ACS).[medical citation needed]
Contraindications and precautions[edit]
Tirofiban is contraindicated in patients with:
Known hypersensitivity to any component of Aggrastat.
History of thrombocytopenia with prior exposure to Aggrastat.
Active internal bleeding, or history of bleeding diathesis, major surgical procedure or severe physical trauma within the previous month.
Cautions[edit]
Aggrastat can cause serious bleeding. If bleeding cannot be controlled discontinue Aggrastat.
Thrombocytopenia: Discontinue Aggrastat and heparin.
Adverse Reactions[edit]
Bleeding is the most commonly reported adverse reaction.
Use in pregnancy[edit]
Tirofiban has been demonstrated to cross the placenta in pregnant rats and rabbits. Although the doses employed in these studies were a multiple of those used in human beings no adverse effects on the offspring in both animals have been seen. However, there are no adequate and well controlled studies in pregnant women. Therefore, tirofiban should be used during pregnancy only if clearly indicated.
Nursing mothers: It is not known whether tirofiban is excreted in human milk. However, significant levels of tirofiban are excreted in rat milk. Therefore, nursing should be discontinued during the period of drug administration and the milk discarded. Nursing may resume 24 hours after cessation of treatment with tirofiban.
Pediatric use[edit]
Safety and effectiveness in children have not been established.
Other precautions and laboratory exams[edit]
The activated partial thromboplastin time (aPTT) is .the most reliable coagulation parameter and should be obtained regularly during treatment, particular if a bleeding episode occurs that may be associated with tirofiban therapy. Other important hematological parameters are platelet count, clotting time, hematocrit and hemoglobin. Proper technique regarding artery site access for sheath placement and removal of sheath should be followed. Arterial sheaths should be removed when the patient's activated clotting time is < 180 sec. or 2 to 6 hours following. withdrawal of heparin.
Side effects[edit]
The following side effects were noted under treatment with tirofiban and heparin (and aspirin, if tolerated). Other drugs were used as necessary.
The major adverse effect is bleeding on local sites of clinical intervention and systemically (regarding parts of the body or the whole body system). Major bleeding has occurred in 1.4% of patients and minor bleeding in 10.5%. Transfusions were required to terminate bleeding and to improve bleeding-related anemia in 4.0% of all patients. Geriatric patients have experienced more bleeding episodes than younger, women more than men.
Thrombocytopenia was more often seen in the tirofiban + heparin group (1.5%) than in the heparin control group (0.8%). This adverse effect was usually readily reversible within days.
Positive fecal and urine hemoglobin tests have also been reported.
Post-marketing events have been the occurrence of intracranial bleeding, retroperitoneal bleeding, pulmonary hemorrhage and spinal-epidural hematoma. Fatal bleedings have been reported rarely.
Sometimes, thrombocytopenia was associated with chills, low-grade fever or bleeding complications (see above).
Cases of hypersenitivity including acute anaphylaxis have been seen.
Interactions[edit]
The concomitant application of warfarin or other oral anticoagulants may increase the risk of serious bleeding events. The decision whether maintenance therapy with these drugs should be discontinued during tirofiban treatment has to be made by the responsible clinician.
Pharmacology[edit]
Tirofiban has a rapid onset and short duration of action after proper IV administration. Coagulation parameters turn to normal 4 to 8 hours after the drug is withdrawn.
Physical and chemical properties[edit]
Tirofiban is a synthetic, non-peptide inhibitor acting at glycoprotein (GP) IIb/IIIa receptors in human platelets. It therefore constitutes an anticoagulant, specifically an inhibitor of platelet aggregation.
It is a modified version of an anticoagulant found in the venom of the saw-scaled viper Echis carinatus.[3]
History[edit]
The drug is marketed under the brand name AGGRASTAT in the US by Medicure Pharma and the rest of the world by Correvio International Sàrl.
References[edit]
Jump up ^ Hartzman, G.D.; Egbertson, M.S.; Halczenko, W.; Laswell, W.L.; Duggan, M.E.; Smith, R.L.; Naylor, A.M.; Manno, P.D.; Lynch, R.J.; Zhang, G.; Chang, C. T.-C.; Gould, R.J. (1992). "Non-Peptide Fibrinogen Receptor Antagonists. 1. Discovery and Design of Exosite Inhibitors". Journal of Medicinal Chemistry (American Chemical Society) 35 (24): 4640–4642. doi:10.1021/jm00102a020. PMID 1469694.
Jump up ^ Van Drie, John H. (2007). "Computer-aided drug design: the next 20 years". J. Comput Aided Mol Des (Springer) 21 (10–11): 591–601. doi:10.1007/s10822-007-9142-y. PMID 17989929. Retrieved 2008-06-23.
Jump up ^ "Saw-Scaled Vipers". University of Edinburgh. Retrieved 2008-06-23.
External links[edit]
Tirofiban - Stanford University.
Aggrastat - Food and Drug Administration (FDA) information.
[1] - Aggrastat Product Website- Medicure Pharma.
[hide] v t e
Antithrombotics (thrombolytics, anticoagulants and antiplatelet drugs) (B01)
Antiplatelet drugs
Glycoprotein IIb/IIIa inhibitors
Abciximab Eptifibatide Tirofiban Roxifiban Orbofiban
ADP receptor/P2Y12 inhibitors
Thienopyridines Clopidogrel Prasugrel Ticlopidine Nucleotide/nucleoside analogs Cangrelor Elinogrel Ticagrelor
Prostaglandin analogue (PGI2)
Beraprost Iloprost Prostacyclin Treprostinil
COX inhibitors
Acetylsalicylic acid/Aspirin# Aloxiprin Carbasalate calcium Indobufen Triflusal
Thromboxane inhibitors
Thromboxane synthase inhibitors Dipyridamole (+Aspirin) Picotamide Receptor antagonists Terutroban†
Phosphodiesterase inhibitors
Cilostazol Dipyridamole Triflusal
Other
Cloricromen Ditazole Vorapaxar
Anticoagulants
Vitamin K antagonists
(inhibit II, VII, IX, X)
Coumarins: Acenocoumarol Coumatetralyl Dicoumarol Ethyl biscoumacetate Phenprocoumon Warfarin# 1,3-Indandiones: Clorindione Diphenadione Phenindione Other: Tioclomarol
Factor Xa inhibitors
(with some II inhibition)
Heparin group/
glycosaminoglycans/
(bind antithrombin)
Low molecular weight heparin Bemiparin Certoparin Dalteparin Enoxaparin Nadroparin Parnaparin Reviparin Tinzaparin Oligosaccharides Fondaparinux Idraparinux Heparinoids Danaparoid Dermatan sulfate Sulodexide
Direct Xa inhibitors
Xabans Apixaban Betrixaban Darexaban Edoxaban Otamixaban Rivaroxaban
Direct thrombin (IIa) inhibitors
Bivalent: Hirudin Bivalirudin Desirudin Lepirudin Univalent: Argatroban Dabigatran Melagatran‡ Ximelagatran‡
Other
Antithrombin III Defibrotide Protein C Drotrecogin alfa‡ Ramatroban REG1
Thrombolytic drugs/
fibrinolytics
Plasminogen activators: r-tPA Alteplase Reteplase Tenecteplase UPA Saruplase Urokinase Anistreplase Monteplase Streptokinase# Other serine endopeptidases: Ancrod Brinase Fibrinolysin
Non-medicinal
Citrate EDTA Oxalate
#WHO-EM ‡Withdrawn from market Clinical trials: †Phase III §Never to phase III
Index of cells from bone marrow v t e
Description
Immune system Cells Physiology coagulation proteins granule contents colony-stimulating
Disease
Red blood cell Monocyte and granulocyte Neoplasms and cancer Histiocytosis Symptoms and signs eponymous Blood tests findings
Treatment
Transfusion Drugs thrombosis bleeding other
Contents [hide]
1 Medical use
2 Contraindications and precautions
2.1 Cautions
2.2 Adverse Reactions
2.3 Use in pregnancy
2.4 Pediatric use
2.5 Other precautions and laboratory exams
3 Side effects
4 Interactions
5 Pharmacology
6 Physical and chemical properties
7 History
8 References
9 External links
Medical use[edit]
Aggrastat is indicated to reduce the rate of thrombotic cardiovascular events (combined endpoint of death, myocardial infarction, or refractory ischemia/repeat cardiac procedure) in patients with non-ST elevation acute coronary syndrome (NSTE-ACS).[medical citation needed]
Contraindications and precautions[edit]
Tirofiban is contraindicated in patients with:
Known hypersensitivity to any component of Aggrastat.
History of thrombocytopenia with prior exposure to Aggrastat.
Active internal bleeding, or history of bleeding diathesis, major surgical procedure or severe physical trauma within the previous month.
Cautions[edit]
Aggrastat can cause serious bleeding. If bleeding cannot be controlled discontinue Aggrastat.
Thrombocytopenia: Discontinue Aggrastat and heparin.
Adverse Reactions[edit]
Bleeding is the most commonly reported adverse reaction.
Use in pregnancy[edit]
Tirofiban has been demonstrated to cross the placenta in pregnant rats and rabbits. Although the doses employed in these studies were a multiple of those used in human beings no adverse effects on the offspring in both animals have been seen. However, there are no adequate and well controlled studies in pregnant women. Therefore, tirofiban should be used during pregnancy only if clearly indicated.
Nursing mothers: It is not known whether tirofiban is excreted in human milk. However, significant levels of tirofiban are excreted in rat milk. Therefore, nursing should be discontinued during the period of drug administration and the milk discarded. Nursing may resume 24 hours after cessation of treatment with tirofiban.
Pediatric use[edit]
Safety and effectiveness in children have not been established.
Other precautions and laboratory exams[edit]
The activated partial thromboplastin time (aPTT) is .the most reliable coagulation parameter and should be obtained regularly during treatment, particular if a bleeding episode occurs that may be associated with tirofiban therapy. Other important hematological parameters are platelet count, clotting time, hematocrit and hemoglobin. Proper technique regarding artery site access for sheath placement and removal of sheath should be followed. Arterial sheaths should be removed when the patient's activated clotting time is < 180 sec. or 2 to 6 hours following. withdrawal of heparin.
Side effects[edit]
The following side effects were noted under treatment with tirofiban and heparin (and aspirin, if tolerated). Other drugs were used as necessary.
The major adverse effect is bleeding on local sites of clinical intervention and systemically (regarding parts of the body or the whole body system). Major bleeding has occurred in 1.4% of patients and minor bleeding in 10.5%. Transfusions were required to terminate bleeding and to improve bleeding-related anemia in 4.0% of all patients. Geriatric patients have experienced more bleeding episodes than younger, women more than men.
Thrombocytopenia was more often seen in the tirofiban + heparin group (1.5%) than in the heparin control group (0.8%). This adverse effect was usually readily reversible within days.
Positive fecal and urine hemoglobin tests have also been reported.
Post-marketing events have been the occurrence of intracranial bleeding, retroperitoneal bleeding, pulmonary hemorrhage and spinal-epidural hematoma. Fatal bleedings have been reported rarely.
Sometimes, thrombocytopenia was associated with chills, low-grade fever or bleeding complications (see above).
Cases of hypersenitivity including acute anaphylaxis have been seen.
Interactions[edit]
The concomitant application of warfarin or other oral anticoagulants may increase the risk of serious bleeding events. The decision whether maintenance therapy with these drugs should be discontinued during tirofiban treatment has to be made by the responsible clinician.
Pharmacology[edit]
Tirofiban has a rapid onset and short duration of action after proper IV administration. Coagulation parameters turn to normal 4 to 8 hours after the drug is withdrawn.
Physical and chemical properties[edit]
Tirofiban is a synthetic, non-peptide inhibitor acting at glycoprotein (GP) IIb/IIIa receptors in human platelets. It therefore constitutes an anticoagulant, specifically an inhibitor of platelet aggregation.
It is a modified version of an anticoagulant found in the venom of the saw-scaled viper Echis carinatus.[3]
History[edit]
The drug is marketed under the brand name AGGRASTAT in the US by Medicure Pharma and the rest of the world by Correvio International Sàrl.
References[edit]
Jump up ^ Hartzman, G.D.; Egbertson, M.S.; Halczenko, W.; Laswell, W.L.; Duggan, M.E.; Smith, R.L.; Naylor, A.M.; Manno, P.D.; Lynch, R.J.; Zhang, G.; Chang, C. T.-C.; Gould, R.J. (1992). "Non-Peptide Fibrinogen Receptor Antagonists. 1. Discovery and Design of Exosite Inhibitors". Journal of Medicinal Chemistry (American Chemical Society) 35 (24): 4640–4642. doi:10.1021/jm00102a020. PMID 1469694.
Jump up ^ Van Drie, John H. (2007). "Computer-aided drug design: the next 20 years". J. Comput Aided Mol Des (Springer) 21 (10–11): 591–601. doi:10.1007/s10822-007-9142-y. PMID 17989929. Retrieved 2008-06-23.
Jump up ^ "Saw-Scaled Vipers". University of Edinburgh. Retrieved 2008-06-23.
External links[edit]
Tirofiban - Stanford University.
Aggrastat - Food and Drug Administration (FDA) information.
[1] - Aggrastat Product Website- Medicure Pharma.
[hide] v t e
Antithrombotics (thrombolytics, anticoagulants and antiplatelet drugs) (B01)
Antiplatelet drugs
Glycoprotein IIb/IIIa inhibitors
Abciximab Eptifibatide Tirofiban Roxifiban Orbofiban
ADP receptor/P2Y12 inhibitors
Thienopyridines Clopidogrel Prasugrel Ticlopidine Nucleotide/nucleoside analogs Cangrelor Elinogrel Ticagrelor
Prostaglandin analogue (PGI2)
Beraprost Iloprost Prostacyclin Treprostinil
COX inhibitors
Acetylsalicylic acid/Aspirin# Aloxiprin Carbasalate calcium Indobufen Triflusal
Thromboxane inhibitors
Thromboxane synthase inhibitors Dipyridamole (+Aspirin) Picotamide Receptor antagonists Terutroban†
Phosphodiesterase inhibitors
Cilostazol Dipyridamole Triflusal
Other
Cloricromen Ditazole Vorapaxar
Anticoagulants
Vitamin K antagonists
(inhibit II, VII, IX, X)
Coumarins: Acenocoumarol Coumatetralyl Dicoumarol Ethyl biscoumacetate Phenprocoumon Warfarin# 1,3-Indandiones: Clorindione Diphenadione Phenindione Other: Tioclomarol
Factor Xa inhibitors
(with some II inhibition)
Heparin group/
glycosaminoglycans/
(bind antithrombin)
Low molecular weight heparin Bemiparin Certoparin Dalteparin Enoxaparin Nadroparin Parnaparin Reviparin Tinzaparin Oligosaccharides Fondaparinux Idraparinux Heparinoids Danaparoid Dermatan sulfate Sulodexide
Direct Xa inhibitors
Xabans Apixaban Betrixaban Darexaban Edoxaban Otamixaban Rivaroxaban
Direct thrombin (IIa) inhibitors
Bivalent: Hirudin Bivalirudin Desirudin Lepirudin Univalent: Argatroban Dabigatran Melagatran‡ Ximelagatran‡
Other
Antithrombin III Defibrotide Protein C Drotrecogin alfa‡ Ramatroban REG1
Thrombolytic drugs/
fibrinolytics
Plasminogen activators: r-tPA Alteplase Reteplase Tenecteplase UPA Saruplase Urokinase Anistreplase Monteplase Streptokinase# Other serine endopeptidases: Ancrod Brinase Fibrinolysin
Non-medicinal
Citrate EDTA Oxalate
#WHO-EM ‡Withdrawn from market Clinical trials: †Phase III §Never to phase III
Index of cells from bone marrow v t e
Description
Immune system Cells Physiology coagulation proteins granule contents colony-stimulating
Disease
Red blood cell Monocyte and granulocyte Neoplasms and cancer Histiocytosis Symptoms and signs eponymous Blood tests findings
Treatment
Transfusion Drugs thrombosis bleeding other
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