1.
What is the average lifespan of a platelet?
Correct Answer
C. 5-10 days
Explanation
The answer is 5-10 days for the lifespan of platelets. This has implications for the use of irreversible anti platelet medications, which will have effects even when discontinued due to the time necessary for platelet regeneration. A normal platelet count is 150,000 to 400,000 per microLiter, which can be abbreviated as "150" to "400." Platelets are normally smooth, but have glycoproteins that can assist in the aggregation and formation of a clot.
2.
Is Ticagrelor (Brilinta) reversible?
Correct Answer
A. Yes
Explanation
Ticagrelor is unique among the antiplatelets in that it is reversible. It is also a non-thienopyridine, and must be used with low-dose aspirin.
3.
Which of the following is NOT an indication of aspirin?
Correct Answer
F. All of the above are indications of aspirin
Explanation
Please note that aspirin can be used for primary prophylaxis in appropriate individuals.
4.
Clopidogrel (Plavix) has interactions primarily with which of the following CYP isozymes?
Correct Answer
D. CYP 2C19 inhibitors
Explanation
The inhibition of CYP 2C19 by drugs such as omeprazole, a PPI (proton pump inhibitor), will lead to less conversion of clopidogrel (a prodrug) to its active metabolite, and less antiplatelet activity. If a PPI is required, pantoprazole is the drug of choice due to less inhibition of CYP 2C19.
5.
Ticagrelor (Brilinta) has interactions primarily with which CYP isozyme?
Correct Answer
E. A and B
Explanation
Ticagrelor has interactions with both CYP 3A4 inhibitors and inducers; thus, it may have several clinically significant drug-drug interactions. As a result, the maximum doses of simvastatin and lovastatin are 40 mg to prevent the incidence of rhabdomyolysis.
6.
Which of the following are indications of cilostazol (Pletal)? Check all that apply.
Correct Answer
B. Intermittent claudication (peripHeral arterial disease)
Explanation
Cilostazol (Pletal) has a unique niche in being useful for the treatment of intermittent claudication symptoms due to peripheral arterial disease (PAD). This is its only FDA-labeled indication. Of note, avoid cilostazol in heart failure patients.
7.
Which of the following are indications of aspirin/dipyridamole (Aggrenox)? Check all that apply
Correct Answer
C. Recurrent stroke propHylaxis
Explanation
This is a niche role for aspirin/dipyridamole (Aggrenox) and its only FDA-labeled indication.
8.
What are glycoprotein IIb/IIIa inhibitors used for?
Correct Answer
A. Invasive management during a PCI
Explanation
By inhibiting the final common pathway for platelet aggregation at greater than 80% of receptor occupancy, these extremely potent agents are used during a PCI to prevent clotting. Basically, the platelets cannot hold hands and form the clot, so the patient is spared further clotting.
9.
Which of the following glycoprotein IIb/III inhibitors are reversible? Check all that may apply.
Correct Answer
A. Abciximab (Reopro)
Explanation
The gold standard of glycoprotein IIb/IIIa inhibitors, abciximab (Reopro) is reversible by overwhelming the agent with platelets. The other agents (eptifibatide and tirofiban) are not reversible, have renal dosing, and are shorter-acting.
10.
Which enzyme does warfarin act upon to exert its pharmacological effect?
Correct Answer
Vitamin K Oxide Reductase
VKORC1
Explanation
Warfarin inhibits the enzyme "Vitamin K Oxide Reductase", which normally takes oxidized Vitamin K and reduces it in order for the reduced form to assist in the conversion of a prothrombin precursor to prothrombin. Less prothrombin means less thrombin, and less thrombin means less conversion of fibrinogen to fibrin. Warfarin inhibits the synthesis of the vitamin K dependent clotting factors (2, 7, 9, 10) and the ANTICOAGULANT proteins C and S. Since the anticoagulant proteins are inhibited first (shortest half lives), starting warfarin without a heparin or LMWH bridge can INCREASE the risk of clotting.
11.
Warfarin is bound to which plasma protein?
Correct Answer
A. Albumin
Explanation
Acidic and neutral drugs bind to albumin, which is basic. Basic drugs bind to alpha-1 acid glycoprotein. Oxygen binds to hemoglobin. Warfarin binds to albumin at greater than 95%. These are facts. Thus, if a patient has another drug on board that displaces warfarin from albumin, there will be more free warfarin and more anticoagulation. Something to consider.
12.
Which of the following can affect the INR for a patient on warfarin? Check all that apply.
Correct Answer(s)
A. DemograpHics
B. Vitamin K intake
C. Hepatic function
D. Drug interactions
Explanation
With vitamin K intake, always educate your patients to maintain a CONSISTENT intake of vitamin K. More vitamin K will lead to more clotting, but the patient can still eat their leafy green vegetables, since their increased intake was factored into their maintenance dosing.
13.
For which indications should the goal INR be 2.0-3.0?
Correct Answer(s)
A. PropHylaxis of VTE
B. Treatment of VTE (DVT/PE)
C. PropHylaxis of stroke/systemic embolism
D. Mechanical aortic valve
F. Bioprosthetic aortic valve
G. Bioprosthetic mitral valve
Explanation
Mechanical valves have greater risks of developing clots, and mitral valves have greater risks of clots due to the lower pressure compared to in the aorta. Therefore, the mechanical mitral valve requires a goal of 2.5-3.5. If a patient has both mechanical mitral and aortic valves, use the goal of 2.5-3.5.
14.
The heparin or LMWH bridge with warfarin should be continued until the INR is greater than 2.0 for how many consecutive days?
Correct Answer(s)
2
two
Explanation
The heparin/LMWH bridge is necessary due to the depletion of proteins C and S, which are anticoagulant proteins, before the other Vitamin K dependent clotting factors (2, 7, 9, 10). Thus, warfarin without the bridge could lead to a clot with initial therapy.
15.
True or False: Unfractionated heparin can dissolve clots
Correct Answer
B. False
Explanation
Heparin can only prevent further clotting; it cannot dissolve a clot. You will need a clot-buster, aka a fibrinolytic such as tPA (alteplase/Activase) to break up an active clot. This is due to heparin's mechanism of action, which has an indirect effect on thrombin via antithrombin; thrombin eventually converts fibrinogen to fibrin, which solidifies a clot. By stopping thrombin, you can stop more fibrin from solidifying the clot, but heparin cannot get into and bust up a clot.
16.
Check all of the advantages of direct thrombin inhibitors.
Correct Answer(s)
A. Do not require cofactor (antithrombin)
B. Bind clot-bound thrombin
C. Predictable effects of anticoagulation
D. Decreased bleeding compared to heparin
Explanation
A key point here is that direct thrombin inhibitors can get into clots and exert an effect on thrombin. In general, the direct thrombin inhibitors bivalirudin and argatroban are a good alternative to heparin or a glycoprotein IIb/IIIa inhibitor for PCI management.
17.
True or false: fondaparinux (Arixtra) requires antithrombin to inhibit Factor Xa
Correct Answer
A. True
Explanation
This is true; fondaparinux requires antithrombin in order to inhibit Factor Xa; this inhibition results in less conversion of prothrombin to thrombin and less conversion of fibrinogen to fibrin.
18.
Which of the following plays a role in the dosing of fondaparinux? Check all that apply.
Correct Answer(s)
A. Weight
B. Indication
C. Renal function
Explanation
Weight is used to determine the dose for treatment of VTE; for prophylaxis dosing, a weight less than 50kg results in the contraindication of fondaparinux. Indication (prophylaxis vs treatment) determines the dosing choices, which are then based on weight for treatment. Renal function is not used to determine dosing, but plays a role in that a CrCl of less than 30ml/min results in the contraindication of fondaparinux. As far as I know, prior use of fondaparinux does not affect its use.
19.
Which of the following affect the dosing of apixaban (Eliquis)?
Correct Answer(s)
A. Age
B. Body weight
C. Serum creatinine
D. CYP 3A4 or P-gp inhibitors
Explanation
While the usual dose of apixaban for non-valvular atrial fibrillation is 5 mg PO BID, if the patient has 2 of the following (age > 80, body weight 1.5mg/dL), then the dose should be 2.5 mg PO BID. If a patient is on a CYP 3A4 or P-gp inhibitor, then the dose should be 2.5 mg PO BID. If the patient is on the CYP 3A4/P-gp inhibitor and is eligible for the 2.5mg PO BID dosing due to their age, weight, or serum creatinine, then the patient cannot take apixaban.
20.
True or false: fibrinolytics only work on fibrin to bust a clot.
Correct Answer
B. False
Explanation
Fibrinolytics are also know as tissue plasminogen activators, and as such they activate plasminogen to plasmin, which then breaks up fibrin, but also breaks down fibrinogen, thus preventing more fibrin from forming. However, tPA is more specific for clot-bound fibrin than for fibrinogen. Breaking down too much circulating fibrinogen could lead to systemic fibrinolysis, which would not be good.
21.
True or false: streptokinase is a direct tissue plasminogen activator?
Correct Answer
B. False
Explanation
Streptokinase is less specific than tPA for clot-bound fibrin, and thus binds equally to circulating and the clot-bound plasminogen, resulting in more systemic bleeding. Therefore, tPA is preferred over streptokinase for dissolving coronary and cerebral vascular thrombi. Fun fact: streptokinase is derived from streptococci (the bacteria), so patients with a recent strep infection will need a higher dose!
22.
To change the INR due to therapy with warfarin by 1.0, change the WEEKLY dose by how much?
Correct Answer
B. 10-15%
Explanation
While there are many nomograms and tools for dosing warfarin, this is a rule of thumb for adjusting warfarin doses.