GET IT! LAST ONE. E1: BLEEDING DRUGS Flashcards
Who uses these drugs??? (3)
1.At risk cardiac Pts 2.Cardiac Stents 3.Orthopedic surgincal pt’s
Holy cow: More than half the people who died in the U.S. in 2009 were killed by _______ (______ and ______)
platelets: stroke and MI
More than _______(freaking A!) knee and hip replacement surgeries annually in US…Procedures associated with increased risk for ________.
800,000……DEEP VEIN THROMBOSIS
Recommend use of blood thinners immediately following major orthopedic replacement surgery and extended use post-discharge….At least ____ days post knee replacement….Up to 35 days post hip replacement
10 days knee….35 days hip
What are the 3 types of acute coronary syndromes?
1.unsable angina 2.NON-ST-elevatedMI (small heart attack-small blockage, small damage) 3.ST-elevated MI (big heart attack, complete blockage)
_______ drugs are used to reduce risk of stroke and other adverse thromboembolic events….Stroke reduction benefits improve when used in combination with ______!
Antiplatelet… aspirin!
What is the fancy name for a stent? What are the two types? (IMPORTANT! you will Tx these Pt’s differently!!)
PerCutaneous Coronary Intervention (PCI) 1.Bare-Metal 2. Drug-Eluting stents
What is the most comprehensively studied and least expensive of all anti platelet medications???
ACE-TYL-SALI-CYCLIC ACID-ASPIRIN
Acetylsalicyclic Acid causes _________ platelet aggregation and effects last for life of the platelet = _____ days
irreversible…7-10 days
Hey GUESS WHAT?!?! No need to discontinue low dose _____ therapy prior to dental treatment!!! Risk to patient for having a stroke is GREATER than the risk for the patient having an uncontrollable bleeding incident or bleeding to death in the dental chair!!!
aspirin
A meta-analysis reviewing data from over 50,000 patients showed that aspirin non- adherence/withdrawal was associated with a ___X higher risk for major adverse cardiac events.
3X
Stopping Aspirin before Tx: Risk was amplified by a factor of ____ in patients who had undergone STENTING.
89X!!!
What are the 2 main indications of anti=platelet drugs?
1.reducing stroke and MI 2.support outcomes post PCI (percutaneous coronary intervention)
SAY WHAAAAAT????More than _______ people get a stent each year
2 million
Short-term and long-term dual antiplatelet therapy with aspirin and a _________ is required to help ensure that stents remain patent and free from thrombosis…these drugs cause ________ effects on platelets
thienopyridine…. irreversible
INTERESTING MECHANISM OF ACTION: clo-pid-ogrel (PLAVIX) A ________ that decreases platelet aggregation with collagen…Requires _________ to form the clot…Desired effect is caused by the inhibition of the cellular availability of ________ and __________ uptake….prevents the binding of ADP to ________ receptors which prevents platelet aggregation
thienopyridine… adenosine (3x)…..collagen
What are the 3 recommendations about peri/post operational bleeding?
1.Consult the Cardiologist 2.Stent Type: No Tx 12 mo post Drug-Eluding Stent and 1 mo post bare-metal stent 3.Stay on thienopyridine/aspirin. If pt needs to be off thio, stay on aspirin.
Platelet Glycoprotein IIb/IIIa Receptor Antagonists ahahahahaha are also called:
FIBRINOGEN RECEPTOR INHIBITORS
Platelet Glycoprotein IIb/IIIa Receptor Antagonists: inhibit the final common pathway for platelet ______, _______ and _______ (3 a’s)
adhesion, activation and aggregation
Platelet Glycoprotein IIb/IIIa Receptor Antagonists: inhibits the binding of ________, __________ factor and other adhesive molecules
fibrinogen, von Willebrand factor
What are the three Platelet Glycoprotein IIb/IIIa Receptor Antagonists (fibrinogen receptor inhibitors)?
- ABC-ixi-mab 2.EP-tifi-bat-ide 3.Tri-of-iBAN
What are the 4 MECHANISMS of action for AntiPlatelet drugs?
1.Cox inhibitor blocking thromboxane AII 2.Block GlycoProtein IIb/IIIa receptor 3.inhibit ADP from activating the GPIIb/IIIa 4.inhibit Cyclic Nucleotide PhosphoDiesterAse
NSAIDS also cause ________ effects on platelets
REVERSABLE
THINK THIS IS IMPORTANT????? IBUPROFEN has a very short half-life (__-__ hours)….Withhold for ___-___ half-lives PRIOR to invasive dental surgical procedures (about _____ prior to treatment)….Cause _______ as a side effect….Especially _________!
(2-4 hours)..with hold for 4-6 half lives (16-24 hours)..1 day…BLEEDING….GI bleeding!
NSAIDS!!!!Use caution with ______ retention. Avoid use in ________.
fluid….heart failure
NSAIDS!!!!! Concurrent administration of IBUPROFEN, and potentially other nonselective NSAIDs, may interfere with _______’s cardioprotective effect!!!
aspirin’s
“_________can interfere with the anti- platelet effect of low dose aspirin (81 mg per day), potentially rendering aspirin less effective when used for cardioprotection and stroke prevention.”
IBUPROFEN
Healthcare professionals (ME) should ADVISE PATIENTS regarding the appropriate concomitant use of ibuprofen and _______.”
aspirin
With OCCASIONAL use of ibuprofen, there is likely to be _______ risk from any attenuation of the antiplatelet effect of low dose aspirin, because of the long-lasting effect of aspirin on platelets.
MINIMAL
FREAKING IMPORTANT: Dose the ibuprofen at least _____ minutes or longer AFTER aspirin ingestion, or more than ___ hours BEFORE aspirin ingestion to avoid attenuation of aspirin’s effect
30min before OR 8 hours after!!!!
Other nonselective OTC NSAIDs should be viewed as having the potential to interfere with the ________ effect of low-dose aspirin unless proven otherwise!!!!!
antiplatelet
**NSAIDS decrease the effectiveness of which 3 antiHTN meds??????
1.Beta Blockers 2.ACE inhibitors 3.Diuretics (thiazides & others)
What is the NATUALLY-produced antiCOAGULANT (anti-thrombin)????
HEPARIN
What is the indication for Heparin?
Prevention and Tx of thrombioembolic disorders
Heparin produces ________ anticoagulation effect
IMMEDIATE
Patient admitted to hospital (stroke/mi) is started on _______ and _______: ________ produces INITIAL effect
heparin and warfarin…..HEPARIN intitial
UhOH: Adverse Rxns to Heparin: Bleeding in _____, _____, ______
gut, brain, GI Tract
UhOH: Adverse Rxns to Heparin: Synergistic effect with oral _________….(coumadin), NSAIDS, alcohol
anticoagulants
UhOH: Adverse Rxns to Heparin: _______ release is possible if heparin is administered too RAPIDLY = extensive ________ can result
Histamine…. BLEEDING
UhOH: Adverse Rxns to Heparin: WHAT IS THE ANTIDOTE TO HEPARIN?????
Antidote to heparin = PRO-TAM-INE
What do Low molecular weight Heparins do?
inhibit factor Xa and IIa(thrombin)
What are the 3 Low Molecular Weight Heparins?
1.DALT-ep-arin 2.ENOX-ap-arin 3.TINZ-ap-arin
Warfarin interferes with liver synthesis of _______ dependent clotting factors…wait. WHICH ONES ARE THOSE??? :) (6)
vitamin-K…..II, VII, IX, X, Protein C, Protein S
How long does warfarin (coumadin) take to have an effect?
takes 4 to 5 days after initial administration
to see effect
___ to ___ day overlap period with heparin following warfarin administration
1 to 2 day
What are the 3 main indications for warfarin?
1.A Fib 2.Valve replacement 3.post MI
warfarin is metabolized in ____ by ____ enzymes
liver…P450
Drugs that induce __________ will DECREASE level of warfarin ( dose will need to be INCREASED to maintain the desired effect)
liver metabolism
______ is a NOTORIOUS inducer of warfarin metabolism.
Phenytoin
Low __________: very NARROW window of safety = easy to alter the level of anticoagulation—-eg.Changes in diet, fever, antibiotics, GI disorder/flu can all alter warfarin levels
therapeutic index
Freaking DIET can alter warfarin levels: ESPECIALLY new healthy eaters of ________ that have Vit K!
green leafy vegetables
WHEELHOUSE!!! Dental Consideration with Anticoagulants-warfarin use has been associated with what 2 oral conditions?
increased gingival bleeding and mouth ulcers
WHEELHOUSE!!! Dental Consideration with Anticoagulants–a __________ may be required to determine whether the patient needs to discontinue the drug prior to invasive surgical procedures
physician consultation…psh what do they know?! :)
WHEELHOUSE!!! Dental Consideration with Anticoagulants– No need to ______ warfarin prior to routine dental procedures…Risk to patient outweighs risk for _______ complications
discontinue…. bleeding
WHEELHOUSE!!! Dental Consideration with Anticoagulants- verify _________ prior to initiating txmt!!!!!
prothrombin time
Prothrombin Time (PT) = 10 to 13 seconds…Evaluates ______ pathway (II, VII, X, V)
extrinsic
________________ (aPTT) = 25 to 35 seconds; used to measure the effects of heparin, which increases aPTT to 50 to 70 seconds…Evaluates _______ pathway (XII, XI, IX, VIII, X, V)
Activated Partial Prothrombin Time…. intrinsic
Which test measures Heparin? Which test measures warfarin?
Heparin-Activated Partial Prothrombin Time…Warfarin-International Normalized Ratio
INR = PT (_____) / PT (_____)
INR = PT (Patient) / PT (control)
INR = ____-____ therapeutic range for venous thrombosis, pulmonary embolism, systemic embolism, atrial fibrillation
2.0 - 3.0
INR = ___-____ therapeutic range for mechanical prosthetic heart valves
INR = 2.5 - 3.5 therapeutic range for mechanical prosthetic heart valves
WHEELHOUSE!!! OK to provide dental treatment when INR falls between ____ to ____
OK to provide dental treatment when INR falls between 2.0 to 3.5
SIGNIFicant Dental Drug Interaction with Warfarin!!! _______ (_______) and warfarin (Coumadin) causes enhanced _________
acetaminophen (Tylenol)…. anticoagulation
In patients who reported taking the equivalent of at least 4 regular strength (325 mg) acetaminophen for longer than a week, the odds of having an INR > 6.0 (toxic overdose level) increased __X above those not taking acetaminophen.
10X…holy bleeding batman!
KEY MESSAGES: _______ causes the greatest number of drug interactions
warfarin
Prior to performing oral surgery, WHEN do we order INR???
SAME DAY of procedure
What is the thrombin inhibitor that was FDA approved in Oct 2010? Its a PRODRUG that lacks anticoagulant activity but is converted in vivo to active form
DA-BI-GAT-RAN (pra-dax-a)
DA-BI-GAT-RAN is a specific, _______, direct thrombin inhibitor that inhibits both FREE and FIBRIN-BOUND _______
reversible…thrombin
DA-BI-GAT-RAN inhibits coagulation by preventing thrombin-mediated effects, including cleavage of fibrinogen to fibrin monomers, activation of factors __,__,___, and ____.
V, VIII, XI, and XIII (5,8,11,13)
What are the 2 indications for DA-BI-GAT-RAN?
- Prevention of Stroke and Systemic Embolism 2.Post op knee/hip replacement
DA-BI-GAT-RAN vs warfarin: ADVANTAGES (2)
- No monthly monitoring 2.fewer drug-drug interactions
DA-BI-GAT-RAN vs warfarin: DISADVANTAGES (2)
- very expensive 2.twice daily dosing
BOOM!!! DA-BI-GAT-RAN vs warfarin:in studies, patients who took Pradaxa had fewer ______ than those taking warfarin
strokes
What are the two adverse effects of DA-BI-GAT-RAN?
bleeding, GI effects
Does DA-BI-GAT-RAN have an antidote? How can we get it out of the system?
NOPE…dialysis can remove 60% of it in 2-3 hours
Direct Antithrombins (Thrombin Inhibitors; Factor Xa Inhibitors)- Prevent/reduce ______ with unstable angina…Prevent _____ following hip replacement…..Prevent/treat thromboembolism…Treatment of ______-induced thrombocytopenia (HIT)
ischemia…DVT…Heparin
Direct Antithrombins (Thrombin Inhibitors; Factor Xa Inhibitors)-Factor Xa catalyzes the conversion of ________ to ________. Thrombin both activates _______ and catalyzes the conversion of _______ to _______.
prothrombin to thrombin….platelets…..fibrinogen to fibrin
Direct Antithrombins (Thrombin Inhibitors; Factor Xa Inhibitors)- Time to put on the big boy pants. WHAT ARE THE three Xa inhibitors (anti-coagulants)?
1.API-XA-BAN 2.FOND-A-PAR-IN-UX 3.RIVA-ROX-A-BAN
Cool! What do you give for a Direct Antithrombin (Thrombin Inhibitor; Factor Xa Inhibitor) OVERDOSE?
activated CHARCOAL
Clot-Busting Drugs are used within _____ of adverse embolic event
hours
Clot-Busting Drugs:_______- Serine protease released from endothelial cells; binds to fibrin and activates plasminogen
tPA (tissue plaminogen activator)= IV drug
Clot-Busting Drugs: tPA- _______ = recombinant form given in 2 shots
RE-TA-VASE
Clot-Busting Drugs: tPA- ANTIDOTE for tPA = Epsilon AminoCaproic Acid (Amicar) = treat hemophilia and cerebral aneurysm bleeds
Epsilon AminoCaproic Acid (AMICAR)
Clot-Busting Drugs: ________ Enters the clot and changes conformation of incorporated plasminogen so that drug can break down fibrin…VERY EXPENSIVE, but effective for heart attacks…Successive exposure causes antibody production = triggers ________ upon repeated exposure :(
streptokinase (Streptase)… anaphylaxis
Clot-Busting Drugs: _______ - converts inactive plasminogen to active form of plasmin which circulates and dissolves fibrin
urokinase