GET IT! LAST ONE. E1: BLEEDING DRUGS Flashcards by Austin Shackelford

Who uses these drugs??? (3)

1.At risk cardiac Pts 2.Cardiac Stents 3.Orthopedic surgincal pt’s

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Holy cow: More than half the people who died in the U.S. in 2009 were killed by _______ (______ and ______)

platelets: stroke and MI

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More than _______(freaking A!) knee and hip replacement surgeries annually in US…Procedures associated with increased risk for ________.

800,000……DEEP VEIN THROMBOSIS

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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

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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)

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_______ drugs are used to reduce risk of stroke and other adverse thromboembolic events….Stroke reduction benefits improve when used in combination with ______!

Antiplatelet… aspirin!

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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

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What is the most comprehensively studied and least expensive of all anti platelet medications???

ACE-TYL-SALI-CYCLIC ACID-ASPIRIN

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Acetylsalicyclic Acid causes _________ platelet aggregation and effects last for life of the platelet = _____ days

irreversible…7-10 days

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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

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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.

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Stopping Aspirin before Tx: Risk was amplified by a factor of ____ in patients who had undergone STENTING.

89X!!!

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What are the 2 main indications of anti=platelet drugs?

1.reducing stroke and MI 2.support outcomes post PCI (percutaneous coronary intervention)

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SAY WHAAAAAT????More than _______ people get a stent each year

2 million

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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

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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

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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.

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Platelet Glycoprotein IIb/IIIa Receptor Antagonists ahahahahaha are also called:

FIBRINOGEN RECEPTOR INHIBITORS

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Platelet Glycoprotein IIb/IIIa Receptor Antagonists: inhibit the final common pathway for platelet ______, _______ and _______ (3 a’s)

adhesion, activation and aggregation

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Platelet Glycoprotein IIb/IIIa Receptor Antagonists: inhibits the binding of ________, __________ factor and other adhesive molecules

fibrinogen, von Willebrand factor

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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

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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

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NSAIDS also cause ________ effects on platelets

REVERSABLE

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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!

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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?

1. Prevention of Stroke and Systemic Embolism 2.Post op knee/hip replacement

DA-BI-GAT-RAN vs warfarin: ADVANTAGES (2)

1. No monthly monitoring 2.fewer drug-drug interactions

DA-BI-GAT-RAN vs warfarin: DISADVANTAGES (2)

1. 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