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Pharm - AntiCoag etc

Saba - Basic Sciences - Semester 4 - Pharm - Blk3 - Lect03

QuestionAnswer
Prevention of hemorrhage D/t trauma - Mechanisms for Prevention (2) This is prevented by Vasospasm, and formation of an arterial thrombus (platelet plug & fibrin clot)
Prevention of hemorrhage D/t trauma - Mechanisms for Prevention - Arterial thrombus This biological structure, formed upon stimulation, is rich in platelets trapped in fibrin meshwork
Prevention of hemorrhage D/t trauma - Mechanisms for Prevention - Arterial thrombus - Formation -Stimuli Both platelet aggregation, fibrin secretion and blood coagulation are required for the formation of this, and are stimulated by atherosclerotic regions, which release certain factor inducing these conditions.
Prevention of hemorrhage D/t trauma - Mechanisms for Prevention - Arterial thrombus - Formation -Stimuli - Factors for Platelet Aggregation (4) Activated platelets bound to collagen of the damaged cell endothelia release thromboxane A2 to form this, along with ADP, serotonin, and PAF, by increasing calcium levels
Prevention of hemorrhage D/t trauma - Mechanisms for Prevention - Arterial thrombus - Formation -Stimuli - Calcium Increasing levels of this r/i release of platelet granules, activatn of TXA2 synthesis from arachadonic acid, and activation of GPIIbIIIa rc (expressoin induced by ADP binding) so that platelets can bind to each other and tp fibrinogen, to activate it
Prevention of hemorrhage D/t trauma - Mechanisms for Prevention - Arterial thrombus - Formation -Assd Conditions The formation of this is associated with acute MI's, cerebral infarcts, etc.
Rx for BV Occlusion - Types (3) Antiplatelet, fibrinolytic and anticoagulant drugs are all used for this purpose.
Rx for BV Occlusion - Antiplatelet Drugs – Synonym This class of drug is also known as antithrombotics
Rx for BV Occlusion - Antiplatelet Drugs – Drug List (6) Aspirin, Ticlopidin, Clopidogrel, Prasugrel, Dipyradimole, Glycoprotein IIb/IIIa Receptor Inhibitors (Abciximab, Eptifibatidate, Tirofiban) are members of this class of drugs
Rx for BV Occlusion - Antiplatelet Drugs – Aspirin - Effects This drug is an NSAID, with analgesic, antipyretic, anti-inflammatory and anti-platelet aggregation effects
Rx for BV Occlusion - Antiplatelet Drugs - Aspirin – Method of Action This drug irreversibly inhibits Cyclooxygenase-1, inhibitin prostaglandin synthesis (PGH2>TXA2). At low doses (80-160 mg/day), it selectively irreversibly inhibits the Thromboxane A2 synthesis and hence prevents platelet aggregation.
Rx for BV Occlusion - Antiplatelet Drugs - Aspirin – Indications (4) This drug is indicated in the prevention of arterial thrombi in IHD and Stroke px, and in prophylaxis of TIA, MIs & angina
Rx for BV Occlusion - Antiplatelet Drugs - Aspirin – Adverse Effects (3) The adverse effects of this drug are Bleeding, gastric irritation & ulcers
Rx for BV Occlusion - Antiplatelet Drugs - Ticlopidine – Method of Action This drug interferes with binding of ADP to its receptors on platelets, inhibiting the activation of GP IIb/IIIa receptors required for platelets to bind to fibrinogen and to each other.
Rx for BV Occlusion - Antiplatelet Drugs - Ticlopidine – Indications (3) This drug is indicated as an alternative to Aspirin in TIAs, post-MI, and in unstable angina cases
Rx for BV Occlusion - Antiplatelet Drugs - Ticlopidine – Adverse Effects (6) Adverse effects of this drug include Neutropenia, Thrombocytic pupura, Rash, Nausea, Dyspepsia & Diarrhea (20%) – seldom used for these reasons
Rx for BV Occlusion - Antiplatelet Drugs - Clopidogrel – Pharmacokinetics This antiplatelet drug requires activation via the CYP450 enzyme isoform CYP2C19. D/A: 7-10 days
Rx for BV Occlusion - Antiplatelet Drugs - Clopidogrel – Method of Action This drug inhibits ADP-induced expression of platelet glycoprotein receptors, thereby reducing fibrinogen binding and platelet aggregation.
Rx for BV Occlusion - Antiplatelet Drugs - Clopidogrel – Drug Interactions PPI (Omeprazole) being a CYP219 inhibitor may interfere with activation of this drug that usually has less side effects than Ticlopidine
Rx for BV Occlusion - Antiplatelet Drugs - Clopidogrel – Side Effect Profile While comparable to Ticlopidine, this drugs has less side effects
Rx for BV Occlusion - Antiplatelet Drugs - Clopidogrel – Indications This drug has similar indications to Ticlopidine, serving as an alternative to aspirin in TIA's, post-MI's and unstable angina. However it is seldom used today d/t toxicity.
Rx for BV Occlusion - Antiplatelet Drugs - Prasugrel - Pharmacokinetics While similar to clopidogrel, this antiplatelet drug does not require CYP450 activation
Rx for BV Occlusion - Antiplatelet Drugs - Prasugrel - Indications This drug is used for acute coronary syndrome in combo w/ aspirin.
Rx for BV Occlusion - Antiplatelet Drugs - Prasugrel - Adverse Effects This antiplatelet drug may cause bleeding (mj or mn)
Rx for BV Occlusion - Antiplatelet Drugs - Prasugrel - Contraindications This antiplatelet drug is c/I in px w TIA/stroke history
Rx for BV Occlusion - Antiplatelet Drugs - Prasugrel - Mechanism of Action This drug has a simliar moA as clopidogrel, in that it inhibits ADP-induced expression of platelet glycoprotein receptors and thereby reducing fibrinogen binding and platelet aggregation
Rx for BV Occlusion - Antiplatelet Drugs – Dipyridamole - Pharmacological Effects Coronary vasodilator w/ weak antiplatelet activity by inhibiting uptake of ADP. Also increases intracellular cAMP (TXA2 syntehsis decreased), potentiates PGI2 synthesis & decreases platelet adhesion
Rx for BV Occlusion - Antiplatelet Drugs – Dipyridamole - Mechanism of Action This drug inhibits ADP-induced expression of platelet glycopr- rcs and thereby (-) fibrinogen binding and platelet aggr.. Also (+) intrac'r cAMP by inhibiting phosphodiesterase enzyme (- TXA2 synthesis), potentiates PGI2 synthesis ((-) platelet adhesion)
Rx for BV Occlusion - Antiplatelet Drugs – Dipyridamole – Indications This drug is indicated in the Prophylaxis in angina pectoris, usually w aspirin, and adminstered in combo w/ Warfarin for prosthetic heart valves
Rx for BV Occlusion - Antiplatelet Drugs – Glycoprotein IIb/IIIa Receptor Inhibitors – Types This type of Antiplatelet Drug includes Abciximab, Eptifibatide, Tirofiban
Rx for BV Occlusion - Antiplatelet Drugs – Glycoprotein IIb/IIIa Receptor Inhibitors – Indications (3) This type of antiplatelet Drug is indicated in px undergoing percutaneous coronary intervention, w unstable angina, and for post-MI
Rx for BV Occlusion - Antiplatelet Drugs – Glycoprotein IIb/IIIa Receptor Inhibitors – Abciximab This is a mAB against glycoprotein IIb/IIIa receptors on the platelets
Rx for BV Occlusion - Antiplatelet Drugs – Glycoprotein IIb/IIIa Receptor Inhibitors – Abciximab - Pharmacokinetics This antiplatelet drug is given through IV administration (along with heparin or aspirin)
Rx for BV Occlusion - Antiplatelet Drugs – Glycoprotein IIb/IIIa Receptor Inhibitors – Abciximab - Mechanism of Action This drug prevents the binding of fibrinogen and other adhesive molecules (such as von Willebrand factor).
Rx for BV Occlusion - Antiplatelet Drugs – Glycoprotein IIb/IIIa Receptor Inhibitors – Abciximab – Indications (3) This antiplatelet drug is indicated during percutaneous transluminal coronary angiography/angioplasty, postangioplasty and in acute coronary syndromes
Rx for BV Occlusion - Antiplatelet Drugs – Glycoprotein IIb/IIIa Receptor Inhibitors – Adverse Reactions (4) Adverse effects of this antiplatelet drug includes Bleeding, Thrombocytopenia, Hypotension, Bradycardia
Rx for BV Occlusion - Fibrinolytic Drugs – Synonym Thrombolytics is a synonym for this type of drug
Rx for BV Occlusion - Fibrinolytic Drugs – Mechanism of Action This drug converts plasminogen to plasmin, which degrades fibrin and fibrinogen, leaing to clot dissolution
Rx for BV Occlusion - Fibrinolytic Drugs – Indications (5) This drug is indicated for Short-term management of coronary thromboses (MI), Pulmonary thromboembolism, DVT & stroke (carotid/cerebral infarcts). MJ factor in effectiveness is early adminstration - >60% decrease in mortality post-MI if used within 3 hrs.
Rx for BV Occlusion - Fibrinolytic Drugs – Drug List (4) Drugs of this category include 1) Streptokinase, 2) Recombinant Tissue-Plasminogen Activators (tPA), 3) Urokinase, 4) Anistreplase (streptokinase and plasminogen together).
Rx for BV Occlusion - Fibrinolytic Drugs – tPA – Drug Names This fibrolytic drug type includes Alteplase and Reteplase
Rx for BV Occlusion - Fibrinolytic Drugs – tPA – Actions This fibrinolytics Selectively activates plasminogen bound to fibrin (clot-specific).
Rx for BV Occlusion - Fibrinolytic Drugs – tPA – Adverse Effects This fibrinolytic has lesser hemorrhagic episodes than Streptokinase & no allergy problems.
Rx for BV Occlusion - Fibrinolytic Drugs – Streptokinase - Structure Enzyme obtained from Group C beta-hemolytic streptococci.
Rx for BV Occlusion - Fibrinolytic Drugs – Streptokinase - Pharmacokinetic Profile This fibrinolytic has a longer half-life than altepase (tPA)
Rx for BV Occlusion - Fibrinolytic Drugs – Streptokinase - Phamacological Effects This drug acts on bound and free plasminogen (not clot specific), and also depletes fibrinogen, Factor V & Factor VIII.
Rx for BV Occlusion - Fibrinolytic Drugs – Streptokinase -Adverse Effects This fibrinolytic is antigenic and can cause hypersentivity reaction so a second dose should not be given.
Rx for BV Occlusion - Fibrinolytic Drugs – Adverse Reactions Adverse effects of this drug category include Intracerebral hemorrhage & hypersensitivity rxns (Streptokinase).
Rx for BV Occlusion - Fibrinolytic Drugs – Uses in Acute MI Reserved when angioplasty is not an option or until the patient can be taken to a facility that performs percutaneous coronary interventions.
Rx for BV Occlusion - Fibrinolytic Drugs – Statistics unsuccessful in about 20% of infarcted arteries and 15 % of the arteries that are opened will later close again. Clot dissolution & reperfusion occur with a higher frequency when therapy is initiated early after clot formation.
Rx for BV Occlusion - Fibrinolytic Drugs – Contraindications (6) This category of drugs is c/I in 1) Peptic ulcer, 2) Healing wounds, 3) Recent surgery (surgery within 10 days), 4) H/O cerebrovascular accidents, 6) Pregnancy, 7) Metastatic cancer
Rx for BV Occlusion - Fibrinolytic Drugs – Antidote (2) Adverse reaction to this drug can be treated with Aminocaproic Acid (competitve blocker of plasminogen activator) & Tranexamic Acid (antifibrinolytic)
Rx for BV Occlusion - Blood Coagulation Requirements – 100mL blood 1) 0.2 mg Factor VIII, 2) 2 mg Factor X, 3) 15 mg prothrombin, 4) 250 mg fibrinogen
Rx for BV Occlusion - Anticoagulation – Mechanisms of Action and Classes (2) This category of drugs either inhibits the action of coagulation factors (parental form) OR interferes with the synthesis of the coagulation factors (the oral vitamin K antagonists)
Rx for BV Occlusion - Anticoagulants - Parenteral – Drug List (3) This category of drugs include Heparin, Direct Thrombin Inhibitors, Danaparoid
Rx for BV Occlusion - Anticoagulants- Parenteral– Heparin This anticoagulant is A mixture of sulfated polysachharides with a MW of 15-20,000 Da obtained from porcine intestine & bovine lung. It can be fractionated or unfractionated.
Rx for BV Occlusion - Anticoagulants- Parenteral – Heparin – Unfractionated -Method of Action This anticoagulant works by catalyzing binding of antithrombin-III (AT-III), a Ser protease inhibitor, to factors IIa, IXa, Xa, XIa, & XIIa, resulting in their rapid inactivation (particularly thrombin (Iia) and factor Xa
Rx for BV Occlusion - Anticoagulants - Parenteral – Heparin - Unfractionated - Pharmacokinetics This anticoag isn't absorbed from gut & m/b admin'd IV or SC. Should not be admin'd in muscle - can cause bleeding. Activity measured by pTT (usually 1.5-2.5 x longer)some px req. (+) dose of heparin for (+) aPTT.(d/t (+) clearance or antithrombin def)
Rx for BV Occlusion - Anticoagulants - Parenteral– Heparin - Fractionated - LMWH (3) This category of anticoagulants include Enoxeparin, Dalteparin, Tinzaparin
Rx for BV Occlusion - Anticoagulants - Parenteral – Heparin - Fractionated - LMWH - Action This category of anticoagulants Selectively targets inactivation of Factor Xa (less effect on thrombin (IIa)
Rx for BV Occlusion - Anticoagulants- Parenteral – Heparin - Fractionated – LMWH – Pharmacokinetics Predictable PK & plasma levels. No need to monitor aPTT. Given SC they have better bioavailability longer half life than UFH. Effects are more predictable and less frequent dosing is required.
Rx for BV Occlusion - Anticoagulants- Parenteral – Heparin - Fractionated – LMWH – Effects This anticoagulant form shows Less thrombocytopenia & enhanced activity against factor Xa than its unfractionated counterpart.
Rx for BV Occlusion - Anticoagulants - Parenteral – Heparin – Indications (8) This anticoagulant is indicated in Acute thromboembolic disoders, preventing clotting during surgery, Acute fibrillation to prevent embolization, unstable angina & MI, prevent DVT & Pulmonary embolism, DIC, Blood transfusions, dialysis.
Rx for BV Occlusion - Anticoagulants - Parenteral - Heparin – Adverse Reactions - (7) Adverse effects of this drug include 1) Hemorrhage – monitor aPTT. 2) Thrombocytopenia (HIT)* - more with UFH. 3) OP. 4) Hypoaldosteronism ((-) aldosterone: HyperK). 5) Hypersensitivity. 6) Alopecia. 7) Tolerance d/t clearance or antithrombin deficiency.
Rx for BV Occlusion - Anticoagulants - Parenteral– Heparin – Adverse Reactions – Heparin Induced Thrombocytopenia This adverse reaction is a systemic hypercoagulable state where IgG antibodies are formed & induce platelet aggregation, thrombosis & thromboembolis. Can be life threatening.
Rx for BV Occlusion - Anticoagulants- Parenteral– Heparin – Adverse Reactions – Heparin Induced Thrombocytopenia – Treatment Treatement of this condition involves discontinuation of heparin & replacement by direct thrombin inhibitor (Argatroban) or Fondaparinux.
Rx for BV Occlusion - Anticoagulants- Parenteral– Heparin – Antidote An antidote for this anticoagulant is Protamine Sulfate
Rx for BV Occlusion - Anticoagulants - Parenteral – Heparin – Contraindications (4) Bleeding, Dissecting aortic aneurysm, recent surgery, hypersensitivity. [[Ok to use in pregnancy]]
Rx for BV Occlusion - Anticoagulants – Parenteral - Direct Thrombin Inhibitors – Drug List (7) This category of anticoagulants include Hirudin, Desirudin, Lepirudin, Bivalirudin, Argatroban, Fondaparinux, Daniproid
Rx for BV Occlusion - Anticoagulants – Parenteral - Direct Thrombin Inhibitors – Hirudin This drug is a Natural anticoag obtained from leech. Administed by IV infusion, used in patients with HIT.
Rx for BV Occlusion - Anticoagulants – Parenteral - Direct Thrombin Inhibitors – Desirudin This drug is a hirudin analog used to prevent venous thrombembolism after hip arthroplasty. Can cause severe allergic rxn.
Rx for BV Occlusion - Anticoagulants – Parenteral -Direct Thrombin Inhibitors – Lepirudin This drug is a Recombinant derivative of Hirudin used in patients with Heparin induced Thrombosis/Thrombocytopenia. IV infusion.
Rx for BV Occlusion - Anticoagulants – Parenteral -Direct Thrombin Inhibitors – Bivalirudin this anticoagulant has afast onset, short-acting IV infusion. Thrombin (IIa) specific drug used for Percutaneous Coronary Angioplasty (PCA) w/ Aspirin
Rx for BV Occlusion - Anticoagulants – Parenteral -Direct Thrombin Inhibitors – Argatroban This anticoagulant is used in patients with HIT. Heavily dependent on liver function & must monitor aPTT.
Rx for BV Occlusion - Anticoagulants – Parenteral -Direct Thrombin Inhibitors – Fondaparinux This drug is an Inhibitor of Factor Xa. Low chance of causing HIT. No thrombin inactivation.
Rx for BV Occlusion - Anticoagulants – Parenteral -Direct Thrombin Inhibitors – Danaparoid This anticoagulant is a Mixture of non-heparin GAGs isolated from porcine intestinal mucosa: Heparan, Dermatan, Chondroitin. Anti-Factor Xa & Anti-thrombin activity.
Rx for BV Occlusion - Anticoagulants – Oral – Types This drug class includes vitamin k antagonists and direct thrombin inhibtors
Rx for BV Occlusion - Anticoagulants – Oral – Vitamin K Antagonists (2) This class of drugs includes Warfarin & Dicumarol
Rx for BV Occlusion - Anticoagulants – Oral – Vitamin K Antagonists – Warfarin - Pharmacological Effects This anticoagulant Inhibits clot formation by the inhibition of hepatic SYNTHESIS of Vitamin-K dependent clotting factors: II, VII, IX, X
Rx for BV Occlusion - Anticoagulants – Oral – Vitamin K Antagonists – Warfarin – Method of Action This drug Blocks reduction of Vit K by inhibiting Vit K epoxide reductase enzyme which inhibits γ - carboxylation of clotting factors reqrd for activn. Effects take 3-5 days as (-) circulatg factors. need parental anticoag in "window period" for rapid tx
Rx for BV Occlusion - Anticoagulants – Oral – Vitamin K Antagonists – Warfarin – Pharmacokinetics This anticoagulant is Completely absorbed by oral administration and 98% is plasma protein bound. Metabolized by CYP450. Monitor PT (International Normalized Ratio – INR). PT(obs):PT(control) = 2-3.
Rx for BV Occlusion - Anticoagulants – Oral – Vitamin K Antagonists – Warfarin – Adverse Reactions Adverse reactions of this anticoagulant include 1) Bleeding, 2) Fetal hemorrhage & teratogenicity (bone dysmorphogenesis - Fetal warfarin syndrome & 3) Dermal vascular thrombosis + Skin necrosis (due to lack of protein C).
Rx for BV Occlusion - Anticoagulants – Oral – Vitamin K Antagonists – Warfarin – Adverse Reactions - Protein C Deficiency This condition marked by transient hypercoagulability can be induced w administration of this drug b/c Protein C & Factor VII have shortest half-lives, and extrinsic path and protein C system get activated
Rx for BV Occlusion - Anticoagulants – Oral – Vitamin K Antagonists – Warfarin – Contraindications This drug is c/I in 1) Bleeding, 2) Pregnancys (fetal warfarin syndrome), 3) Recent surgery, 4) Hypersensitivity
Rx for BV Occlusion - Anticoagulants – Oral – Vitamin K Antagonists – Warfarin – Drug Interactions This drug interactions with 1) Cholestyramine 2) Apsirin, Sulfonamide, Phenytoin, 3) Barb, carbamzeipine, rifapin 4) (Cimetidine, Macrolides, Azoles
Rx for BV Occlusion - Anticoagulants – Oral – Vitamin K Antagonists – Warfarin – Drug Interactions - Cholestyramine This drug decreases oral absorption of warfarin
Rx for BV Occlusion - Anticoagulants – Oral – Vitamin K Antagonists – Warfarin – Drug Interactions - Aspirin, Sulfonaminde and Phenytoin These drugs increase the anticoagulation effects of warfarin by displacing warfarin from albumin binding sites. Can result in hemorrhage
Rx for BV Occlusion - Anticoagulants – Oral – Vitamin K Antagonists – Warfarin – Drug Interactions - Barbituates, Carbamazepine, Rifampin These drugs are enzyme inducers and decrease anticoag activity of warfarin
Rx for BV Occlusion - Anticoagulants – Oral – Vitamin K Antagonists – Warfarin – Drug Interactions - Cimetidine, Macrolides and Azoles These drugs are enzyme inhibitors that increase the activity of warfarin
Rx for BV Occlusion - Anticoagulants – Oral – Vitamin K Antagonists – Warfarin – Indications This drug is indicated in long-term therapy to prevent DVTs, Thrombosis & embolis for post-MI, atrial fibrillation & prosthetic heart valve patients.
Rx for BV Occlusion - Anticoagulants – Oral – Direct Thrombin Inhibitor – Digabatrin - indications (3) This anticoagulant is as effective as warfarin for atrial fibrillation & acute venous thromboembolism, or oral agent for HIT.
Rx for BV Occlusion - Anticoagulants – Oral – Direct Thrombin Inhibitor – Digabatrin - Limitation The limitation of this drug is that it's Anticoagulant effect is irreversible – may need emergency surgery for bleeding.
Rx for BV Occlusion - Anticoagulants – Oral – Direct Factor Xa Inhibitor – Rivaroxaban - Indications (2) This drug is used prophylactically after knee or hip replacement, and to prevent stroke & systemic embolism in non-valvular atrial fibrillation
Rx for BV Occlusion - Anticoagulants – Oral – Direct Factor Xa Inhibitor – Apixaban This Factor Xa inhibitor drug is under investigation.
Created by: mprentic12