Flashcards in Drugs that alter bleeding Deck (64):
What patients use medications that alter bleeding?
- At-risk cardiac groups
○ (stroke, MI, AF, artificial heart valves)
- Cardiac stents
- Orthopedic surgical patients
Name the patient risk groups for platelet related fatalities
1. Aging population is surviving chronic cardiac disease
2. At-risk cardiac groups
3. Increased placement of cardiac stents
4. Outliving prosthetic replacements
What are the leading causes of re-hospitalization following joint replacement surgery?
- Deep Vein Thrombosis
- Pulmonary Embolism
**Reason why recommendation to use blood thinners immediately following major orthopedic surgery
Name the 3 types of acute coronary syndromes
1. Unstable angina
- No permanent damage to heart muscle
2. Non-ST-elevated MI
- Incomplete blockage of a coronary artery
- Small amount of heart muscle damaged
3. ST-elevated MI
- Completely blockage of a coronary artery
- Muscle damaged, large heart attack
Purpose of Anti-platelet drugs
reduce risk of stroke and other adverse thromboembolic events
Anti-platelet drugs have stroke reduction benefits when taken with what other medication?
Two types of stents:
- Drug-eluting stents
Which drug is the most comprehensively studied and least expensive of all antiplatelet medications?
Describe affects of aspirin
Causes irreversible platelet aggregation
T or F, there is a definitive need to discontinue the use of aspirin prior to a dental appointment for treatment
False, there is no need! Risk for patient having a stroke is greater than patient having an uncontrollable bleeding problem during treatment
T or F, sudden discontinuation of aspirin increases mortality risk
- also have a 3-fold higher risk for an adverse cardiac event
- Risk was a factor of 89 for those with a stent placed
What drug therapy is required to help ensure that stents remain patent and free from thrombosis?
- Short-term and long-term dual antiplatelet therapy with aspirin and a thienopyridine is required
- Cause irreversible effects on platelets
Name the Anti-platelet drugs
1. Ticlopidine (Ticlid) (canadien)
2. Clopidogrel (Plavix)
3. Prasugrel (Effient)
4. Ticagrelor (Brilinta)
What is amino acid is required to form clots?
What is the action of Plavix?
- Inhibition of the cellular availability of adenosine and adenosine uptake
- Prevents the binding of ADP to collagen receptors which prevents platelet aggregation
3 recommendations from advisory statement about premature discontinuation of dual antiplatelet therapy
1. Those concerned with peri/postprocedural bleeding must be aware of catastrophic risks of premature discontinuation
2. Elective procedures should be deferred until therapy of thienopyridine is complete
3. Essentially if the thienopyridine has to be halted for certain reasons, do not discontinue use of aspirin
Platelet Glycoprotein IIb/IIIa receptor Antagonists do what?
- Used with aspirin and heparin to treat acute coronary syndromes via IV infusion (unstable angina)
- They are also administered at time of placement of PCI
Explain the biochemical/physiological action of platelet glycoprotein Iib/IIIa receptor antagonists
1. Inhibit final common pathway for platelet adhesion, activation and aggregation
2. Inhibits binding of fibrinogen, von Willebrand factor and other adhesive molecules.
- Platelets are unable to bind to collagen on damaged vessel wall.
General mechanisms of action for Antiplatelet drugs
1. Decrease production of thromboxane A2 by inhibiting COX
2. Antagonism of glycoprotein Iib/IIIa receptor
3. Inhibiting the activation of GP Iib/IIIa by ADP
4. Inhibiting cyclic nucleotide phosphodiesterase
T or F, NSAIDS cause irreversible effects on platelets
T or F, Ibuprofen can interfere with the anti-platelet effect of low dose aspirin
True. Makes it less effect
FDA advisory statement for ibuprofen use with aspirin
Does the ibuprofen at least 30 minutes or longer after aspirin ingestion or more than 8 hours before aspirin to avoid attenuation of aspirin's effect
What other drugs may an interaction with NSAID cardiac drugs decrease effect?
- Beta blockers
- ACE inhibitors
- Diuretics: Thiazides and Diuretic
Name the 4 different families of Anticoagulants
1. Coumarin derivatives/Vitamin K antagonist
4. Low Molecular Weight Heparin
Indications of Heparin:
- Prevention and treatment of thromboembolic disorders
- Anticoagulant for Dialysis procedures
How quickly does Heparin onset?
Immediately. Patients being admitted into hospital are given heparin and warfarin but heparin produces initial effect
Adverse reactions to Heparin
1. Bleeding in gut, brain and GI tract
2. Syngergistic effect with oral anticoagulants, NSAIDS, alcohol
3. Histamine release is possible if heparin is administered too rapidly = extensive bleeding can result
4. Antidote to heparin = Protamine
Use of Low Molecular Weight Heparins
- Prevention of DVT with or without PE
- Reduce risk for PE
- Acute unstable angina
Mechanism of action for Low Molecular Weight Heparins
Inhibit factor Xa and Iia (thrombin)
Name the preparations for Low Molecular Weight Heparins
1. Dalteparin (Fragmin)
2. Enoxaparin (Lovenox)
3. Tinzaparin (Innohep)
What is Warfarin?
An oral anticoagulant
Mechanism of action for Warfarin
Interferes with liver synthesis of vitamin-K dependent clotting factors
What clotting factors does Wafarin interfer with?
Factors II, VII, IX, X and proteins C and S
How is warfarin administered in relation to heparin?
1 to 2 day overlap period with heparin following warfarin administration
Indications for warfarin
- Prophylaxis and treatment of TE disorders and embolic complications that arise from atrial fibrillation or cardiac valve replacement
- Adjunct to reduce risk of systemic embolism after MI
Describe where warfarin is metabolized and by what structures?
in the liver by p450 enzymes
What drugs will decrease level of warfarin?
drugs that induce liver metabolism will decrease levels of warfarin
What is the therapeutic index for warfarin?
Low therapeutic index: very narrow window of safety = easy to alter the level of anticoagulation
Give a specific name of drug that will induce liver metabolism and decrease levels of warfarin
- Classic board exam example
Describe the things that might upset a patient's level of anticoagulation from warfarin
3. Diarrhea or vomiting
4. Use of many drugs, including antibiotics
5. Change in diet (leafy vegetables increase vitamin K intake = promotes clotting)
4 dental considerations with anticoagulants
1. Warfarin use has been associated with increased gingival bleeding and mouth ulcers
2. May need physical consultation to determine whether to discontinue drug prior to invasive surgical procedures
3. No need to discontinue warfarin prior to routine dental procedures
4. Verify prothrombin time prior to initiating txmt
Name the 3 bleeding tests
1. Bleeding time test (1 to 6 minutes)
2. Prothrombin time (10-13 seconds)
3. Activated Partial Prothrombin Time (25 to 35 seconds)
Which bleeding test is used to measure the effects of heparin?
Activated partial prothrombin time (aPTT)
- heparin will increase aPTT to 50 to 70 seconds from 25 to 35.
What is the International Normalized Ratio (INR)?
Used to measure the effect of warfarin
- Calibrated/standardized prothrombin test
Give the INR equation
INR = PT (patient) / PT (control)
What is the therapeutic range of INR for venous thrombosis, pulmonary embolism, systemic embolism and atrial fibrillation?
INR = 2.0 - 3.0
What is the therapeutic range of INR for mechanical prosthetic heart valves
INR = 2.5 - 3.5
T or F, It is ok to provide dental treatment when INR falls between 2.0 to 5.0
False, 2.0 to 3.5
What is a significant dental drug interaction with Warfarin?
- Combination causes enhanced anticoagulation
The odds of having a high INR did what when a patient tok both acetaminophen and warfarin together?
The odds of having an INR > 6.0 increased 10 fold above those not taking acetaminophen
T or F, always check compatibility with other drugs prior to issuing a prescription to warfarin
*******Warfarin causes the greatest number of drug interactions
What is dabigatran (Pradaxa)?
FDA approved October 2010
- Thrombin inhibitor
What does it mean to say that dabigatran is a prodrug?
It lacks anticoagulant activity until it is converted in vivo to active dabigatran
How does dabigatran work?
inhibits coagulation by preventing thrombin-mediated effects, including cleavage of fibrinogen to fibrin monomers, activation of factors V, VIII, XI, and XIII
Indications for dabigatran
- Prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation
- canada: postoperative thromboprophylaxis after total hip or knee replacement
What are the advantages and disadvantages in comparison to warfarin of dabigatran?
Advantages: no monthly monitoring; fewer drug-drug and drug-diet interactions
Disadvantages: very expensive; twice daily dosing
Adverse effects of dabigatran?
What is the antidote to dabigatran?
- protamine and vitamin K do NOT reverse anticoagulant effects
- May be removed with dialysis (60% removed over 2-3 hours
Name the direct thrombin inhibitors
What do Factor Xa Inhibitors do?
Prevent/reduce ischemia with unstable angina
- Prevent DVT following hip replacement
- Prevent/treat thromboembolism
- treatment of heparin-induced thrombocytopenia
Factor XA inhibitor mechanism of action
Factor Xa, as part of the prothrombinase complex, catalyzes the conversion of prothrombin to thrombin. Thrombin both activates platelets and catalyzes the conversion of fibrinogen to fibrin
Name the Factor Xa Inhibitors
Which of the factor Xa inhibitors is the best documented alternative to warfarin and aspirin for stroke prevention in the broad population with AF