Hem & Onc - Pharm (Heme Drugs) Flashcards
Pg. 398-401 in First Aid 2014 or Pg. 367-369 in First Aid 2013 Sections include: -Heparin -Argatroban, bivalirudin -Warfarin (Coumadin) -Direct factor Xa inhibitors -Heparin vs. warfarin -Thrombolytics -Aspirin (ASA) -ADP receptor inhibitors -Cilostazol, dipyridamole -GP IIb/IIIa inhibitors
What is the mechanism of heparin? What coagulation factors does it effect, and in what way?
Cofactor for the activation of antithrombin; (1) Thrombin - decrease (2) Factor Xa - Decrease
What is important to remember about the half-life of heparin?
Short half-life
What are important things to remember about the clinical use of heparin?
(1) IMMEDIATE ANTICOAGULATION - PE, acute coronary syndrome, MI, DVT (2) Used during pregnancy (does not cross placenta) (3) Follow w/ PTT
What toxicities/side effects should you associate with heparin?
(1) Bleeding (2) Thrombocytopenia (HIT) (3) Osteoporosis (4) Drug-drug interactions
What is used as an antidote for heparin, and how does it work?
Protamine sulfate; Positively charged molecule binds negatively charged heparin
What are examples of low molecular weight heparins?
Enoxaparin, dalteparin;
List 6 major ways that low molecular weight heparins compare/contrast to heparin.
(1) Act more on factor Xa (2) Better bioavailability (3) 2-4 times longer half-life (4) Can be administered subcutaneously (5) Do not require laboratory monitoring (6) Not easily reversible
What is HIT? What is its mechanism? What symptoms/signs result?
Heparin-induced thrombocytopenia; Development of IgG antibodies against heparin bound to platelet factor 4 (PF4). Antibody-heparin-PF4 complex activates platelets –> thrombosis & thrombocytopenia
Argatroban and bivalrudin are derivates of what chemical? What purpose does this chemical of origin serve? What mechanism do they all share?
Derivates of hirudin = the anticoagulant used by leeches; Inhibit thrombin
How is bivalirudin used clinically? What is another example of a drug used like bivalirudin?
Used as an alternative to heparin for anticoagulating patients with HIT; Argatroban
What is another name for Warfarin?
Coumadin
What is the mechanism of Warfarin?
Interferes with normal synthesis and gamma-carboxylation of vitamin-K dependent clotting factors II, VII, IX, and X and proteins C and S
What metabolizes Warfarin?
Cytochrome P-450 pathway
What coagulation pathway does Warfarin effect? What is used to monitor it?
Extrinsic pathway; PT (increased); Think: “the EX-PresidenT went to war.”
What is important to remember about the half life of Warfarin?
Long
What are important things to remember about the clinical use of warfarin?
(1) CHRONIC ANTICOAGULATION (after STEMI [FYI - ST elevation myocardial infarction], venous thromboembolism prophylaxis, & prevention of stroke in atrial fibrillation) (2) NOT used in pregnant women (because warfarin, unlike heparin, can cross the placenta) (3) Follow with PT/INR values
What are the toxicities/side effects associated with warfarin?
(1) Bleeding (2) Teratogenic (3) Skin/tissue necrosis (4) Drug-drug interactions
How is Warfarin reversed? How is rapid reversal of severe warfarin overdose achieved?
Vitamin K; Fresh frozen plasma
Compare/contrast the structure of Heparin and Warfarin.
HEPARIN - large anionic, acidic polymer; WARFARIN - small lipid-soluble molecule
Compare/contrast the route of administration of Heparin and Warfarin.
HEPARIN - parenteral (IV, SC); WARFARIN - Oral
Compare/contrast the site of action of Heparin and Warfarin.
HEPARIN - blood; WARFARIN - liver
Compare/contrast the onset of action of Heparin and Warfarin.
HEPARIN - Rapid (seconds); WARFARIN - Slow (limited by half-lives of normal clotting factors)
Compare/contrast the mechanism of action of Heparin and Warfarin.
HEPARIN - Activates antithrombin, which decreases action of IIa (thrombin) and factor Xa; WARFARIN - Impairs the synthesis of vitamin K-dependent clotting factors II, VII, IX, and X (vitamin K antagonist)
Compare/contrast the duration of action of Heparin and Warfarin.
HEPARIN - Acute (hours); WARFARIN - Chronic (days)
Does Heparin and/or Warfarin inhibit coagulation in vitro?
HEPARIN - Yes; WARFARIN - No
What is the treatment of active overdose for Heparin versus Warfarin?
HEPARIN - Protamine sulfate; WARFARIN - IV vitamin K and fresh frozen plasma
Compare/contrast the monitoring for Heparin and Warfarin.
HEPARIN - PTT (intrinsic pathway); WARFARIN - PT/INR (extrinsic pathway)
Does Heparin and/or Warfarin cross the placenta?
HEPARIN - No; WARFARIN - Yes (teratogenic)
What are examples of thrombolytics?
(1) Alteplase (tPA) (2) Reteplase (rPA) (3) Tenecteplase (TNK-tPA)
What is the mechanism of thrombolytics? What effect do they have on PT, PTT, and platelet count?
Directly or indirectly aid conversion of plasminogen to plasmin, which cleaves thrombin and fibrin clots; Increased PT, Increased PTT, no change in platelet count
What are thrombolytics used for clinically?
(1) Early MI (2) Early ischemic stroke (3) Direct thrombolysis of severe pulmonary embolism
What are the toxicities/side effects/contraindications associated with thrombolytics?
Bleeding, Contraindicated in patients with active bleeding, history of intracranial bleeding, recent surgery, known bleeding diatheses, or severe hypertension
How is thrombolytic toxicity treated, and what is the general mechanism of this treatment? What else can be used, and what exactly is it used for?
Treat toxicity with aminocaproic acid, an inhibitor of fibrinolysis; Fresh frozen plasma and cryoprecipitate can also be used to correct factor deficiencies.
What is the mechanism of aspirin (ASA)? How long does it effects last, and why?
Irreversibly inhibits cyclooxygenase (both COX-1 and COX-2) enzyme by covalent acetylation; Last until new platelets are produced, because (drugged) platelets cannot synthesize new enzyme
What lab measurements/changes should you associate with aspirin?
(1) Increased bleeding time (2) Decreased TXA2 (3) Decreased prostaglandins (4) No change in PT (5) No change in PTT
How is aspirin used clinically?
(1) Antipyretic (2) Analgesic (3) Anti-inflammatory (4) Antiplatelet (decreased aggregation)
What are the 2 major toxicities associated with aspirin?
(1) Gastric ulceration (2) Tinnitus CNVIII
What can result from chronic use of aspirin?
(1) Renal failure (2) Interstitial nephritis (3) Upper GI bleeding
What can aspirin cause in children with viral infection?
Reye’s syndrome (FYI - a potentially fatal disease that has numerous detrimental effects to many organs, especially the brain and liver, as well as causing a lower than usual level of blood sugar)
What pH disturbance(s) does aspirin overdose cause?
Overdose causes respiratory alkalosis initially, which is then superimposed by metabolic acidosis
What are examples of ADP receptor inhibitors?
(1) Clopidogrel (2) ticlopidine (3) Prasugrel (4) Ticagrelor
What is the mechanism of ADP receptor inhibitors?
(1) Inhibit platelet aggregation by irreversibly blocking ADP receptors (2) Inhibit fibrinogen binding by preventing glycoprotein IIb/IIIa from binding to fibrinogen
How are ADP receptors used clinically?
(1) Acute coronary syndrome (2) Coronary stenting (3) Decrease incidence/recurrence of thrombotic stroke
Which of the ADP receptor inhibitors is associated with a particular toxicity? What is the toxicity? What other toxicity may be seen with ADP receptor inhibitors?
Ticlopidine; Neutropenia; TTP/HUS may be seen
What is a drug that shares the same mechanism as cilostazol? What kinds of drugs are these, and what are their mechanisms/effects)?
Dipyridamole; Phosphodiesterase II inhibitors; (1) Increase cAMP in platelets, thus inhibiting platelet aggregation (2) Vasodilators
How are Cilostazol and dipyridamole used clinically?
(1) Intermittent claudication (2) Coronary vasodilation (3) Prevention of stroke or TIAs (transient ischemic attacks) (combined with aspirin) (4) Angina prophylaxis
What are toxicities/side effects associated with cilostazol and dipyridamole?
(1) Nausea (2) Headache (3) Facial flushing (4) Hypotension (5) Abdominal pain
What are examples of GP IIb/IIIa inhibitors?
(1) Abciximab (2) Eptifibatide (3) Tirofiban
What is the mechanism of GP IIb/IIIa inhibitors and its effect?
Bind to the glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation
What is abciximab? What effect does it have? How is it made?
GpIIb/IIIa inhibitor - binds glycoprotein receptor IIb/IIIa on activated platelets, preventing aggregation; Made from monoclonal antibody Fab fragments
How are GpIIb/IIIa inhibitors used clinically?
(1) Acute coronary syndromes (2) Percutaneous transluminal coronary angioplasty
What are the toxicities/side effects associated with GpIIb/IIIa inhibitors?
(1) Bleeding (2) Thrombocytopenia
What kind of drug is Apixaban? What is another drug in this same class?
Direct factor Xa inhibitors; Apixaban, Rivaroxaban
What is the mechanism of Apixaban and rivaroxaban?
Direct factor Xa inhibitors = bind and directly inhibit the activity of factor Xa.
What are the clinical uses for direct factor Xa inhibitors (apixaban, rivaroxaban)?
Treatment and prophylaxis of DVT and PE (rivaroxaban), stroke prophylaxis in patients with atrial fibrillation. Oral agents do not usually require coagulation monitoring.
What toxicity is associated with direct factor Xa inhibitors (apixaban, rivaroxaban)? What is the availability of interventions regarding this toxicity?
Bleeding (no specific reversal agent available).
As it relates to direct factor Xa inhibitors, what is important to know about coagulation monitoring?
Oral agents do not usually require coagulation monitoring
Which direct factor Xa inhibitor is particularly used in the treatment and prophylaxis of DVT and PE?
Treatment and prophylaxis of DVT and PE (rivaroxaban)
