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  1. Angina
    •Chronic Stable

    • –Increase
    • in activity, emotions, large meal, cold

    • –Stops
    • with rest

    •Variant Angina-Prinzmetal’s

    • –Coronary
    • vasospasm

    •Unstable Angina (ACS)

    –Medical emergency

    • –Occurs at rest, new onset or
    • intensification of existing stable angina
  2. healthy vs not so healthy heart
    Image Upload 1
  3. Stable (exertional)
    •Underlying cause-CAD

    • –Fatty
    • plague deposits in arteriole walls

    •Treatment Goal: reduce O2 demand

    • –reduce
    • frequency and intensity of attacks

    • –decrease
    • risk of infarct and extending


    • –Dilate
    • veins and decrease preload

    •Beta blockers

    • –Decrease
    • rate and force of contraction

    • •Ca+
    • channel blockers

    • –Dilate
    • arteriole-decrease afterload

    • –Verapamil
    • and diltiazem
    • afterload, rate and contractility
  4. Prinzmetal-Vasospasm
    • •Unknown mechanism causes coronary
    • vasospasm

    • •Treatment Goal: reduce frequency and
    • intensity of attacks (increasing O2 supply)

    • •Nitrates & Ca+
    • channel blockers

    –Relaxing coronary artery spasm

    •Treatment is symptomatic only
  5. Unstable Angina


    •platelet aggregation

    •transient coronary thrombi or emboli
  6. Nitroglycerin
    •Acts directly on vascular smooth muscle

    • –Primarily on veins, modest dilation of
    • arteriole

    • –Decreases preload and (slightly)
    • afterload

    –Rapid Inactivation by liver

    •Half life-5-7 mins

    –Adverse effects:

    –Drug interactions

    • •Sildenafil/Viagra-life threatening
    • hypotension

    –Tolerance with high dose therapy
  7. Nitroglycerin
    Highly lipid soluble multiple routes
    •Sublingual-direct from oral mucosa

    –.4 mg SL 5 minute intervals-X3-only

    •Sustained release oral-prophylaxis only

    • –Isosorbide/Imdur
    • (no first pass)

    • •Transdermal- off
    • at night to avoid tolerance

    –Ointment:1 inch/15mgs patch: .1-.8mg/hr

    •IV infusion-short term only

    • –5 ug/min
    • up 50 ug/min
  8. Anginal Prophylaxis
    •Not used for acute events

    • •Ca+
    • Channel Blockers

    • –Verapamil/Calan,
    • diltiazem/cardizem,
    • (nifedipine)

    • –Arteriole
    • dilation

    • –Relax
    • coronary vasospasm

    •Beta Blockers

    • –Slow
    • HR, increase coronary arterial flow time

    • –Mild
    • reduction in arterial pressure (mech
    • unknown)
  9. Ranolazine/Ranexa
    • •Reduces accumulation of Na+ and Ca+
    • in myocardial cells

    • •Helps myocardium use energy more
    • efficiently?

    •Adverse effects-dysrhythmias, HTN, GI

    •Reserved for refractory cases
  10. Anginal Drug Selection
    Image Upload 2
  11. Anticoagulation

    –Platelet activation

    •Platelets exposed to damaged vessel

    • formation of plug

    –Fibrin reinforces the platelet plug

    • –Plasmin breaks down the clot after
    • healing of injury occurs

    • •Prevent clots & prevent increasing
    • the size of a clot
  12. Coagulation
    Image Upload 3
  13. Anticoagulants

    –inactivates thrombin and factor Xa

    • –fibrin production reduced, clotting
    • suppressed

    –bovine lungs and porcine intestines

    –Short half life 1.5 hours

    –Used for PE, Embolic stroke, MI, DIC
  14. Heparin  (polarity)
    - Highly polar
  15. Anticoagulants

    (all about hep)

    • –Monitor aPTT
    • (22-34 sec) 1.5 – 2X

    • –Risk for bleeding. Antidote: Protamine
    • Sulfate

    –HIT-heparin induced thrombocytopenia

    •1-3% with 4 days heparin therapy

    • •Antibodies activate platelets and damage
    • endothelium

    •Decreased platelets and new thromboses


    –IV intermittent therapy

    • •Not done often because of fluctuating
    • drug levels

    –IV continuous therapy

    •Given by weight and managed by protocol

    •Q6h after dose given or change made

    –Low Dose Therapy

    • •To prevent DVT
    • •Low Molecular Weight Heparins

    •Fractionated-use part of the long chains

    •Don’t affect aPTT

    • –only factor Xa
    • (not thrombin)

    •Can be done at home

    •Less HIT

    •Administered SC

    • •Enoxaparin/lovenox,
    • dalteparin/fragmin
  16. Anticoagulants
    •Oral: Warfarin/Coumadin

    •Vitamin K antagonist

    • –Affects
    • production of VII, IX, X, & prothrombin

    • •require
    • K

    • –Monitor
    • prothrombin
    • time (PT)

    • •Q
    • week and once a month when stable


    • •2-3
    • is therapeutic (3-4.5 for heart valves)

    • –Risk
    • for bleeding

    • –Many
    • drug  & food interactions
  17. Anticoagulants (INR ...)
    •International Normalized Ratio

    –Lab tests compare PT to a control

    • –Controls are different so labs report
    • different values for same specimen.

    • –INR is determined by multiplying PT value
    • by a correction/calibrating factor specific to the preparations employed for
    • the test

    • –INR of 2-3 is appropriate for most
    • conditions
  18. Direct Thrombin Inhibitors
    •Used IV during PCI


    •Used PO and Sub Q

    • –Dabigatren/pradaxa-approved
    • for stroke 2010

    • –Non-valvular
    • at-fib-clot prevention

    • •Major bleed occurred less with lower
    • doses of pradaxa

    • –Thromboemolism
    • tx

    •Same effects

    • •GI side effects caused pradaxa
    • discontinuation
  19. antiplatelet

    Image Upload 4
  20. Anti-platelet
    •Prevention of aggregation

    • •Prevention of thromboses
    • in arteries
  21. •ASA-acetylsalicylic acid–
    Inhibits COX2…produces TXA2(irreversible)–TXA2 causes platelet aggregation andarterial constriction•Primary prevention of MI and stroke•Adverse effect-GI bleeding
  22. •ADP receptor antagonist
    –Irreversibleblockage of plt ADP
  23. •Ticlopidine/Ticlid
    –Hematologiceffects: TTP and Neutropenia
  24. •Clopidogrel/Plavix
    • –Lessside effects
    • •Prevention of ischemic stroke and MI
  25. •Prasugrel/Effient
    –Lessthromboses,more major bleeding
  26. •Glycoprotein IIb/IIIa receptor antagonists
    –Reversible blocking of GPIIb/IIIareceptor to prevent aggregation–In combination with ASA and heparin•Given IV short term for ACS and PCI only–Very expensive •Abciximab/ReoPro,Eptifibatide/Integrillin,–Tirofiban/Aggrastat
  27. •Dipyridamole/Persantin
    –Used only for prevention of thromboemolism following heart valve replacement combined with coumadin
  28. –Aggrenox-persantincombined with ASA
    •Reduced incidence of stroke
  29. •Cilostazol/Pletal
    –Platelet inhibitor and vasodilator forintermittent claudication=Grapefruit juice!
  30. Thrombolytics
    •Remove thrombi that have formed

    •Convert plasminogen to plasmin

    –Plasmin degrades the fibrin cap

    •Indications: Acute MI, DVT, Massive PE,

    –Ischemic stroke

    •Risk of bleeding

    • •Protocols and guidelines for
    • administration
  31. Thrombolytics-contraindications
    •Active Bleeding

    •Aortic Dissection

    •Intracranial Bleeding

    •Cerebral Vascular Disease

    •Cerebral Neoplasm

    •Acute Pericarditis
  32. Thrombolytics

    • –Allergic reactions (from streptococci
    • cultures)

    •Alteplase (tPA)

    –Short half-life



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