1.
What causes clot formation?
Correct Answer
E. All of the above.
Explanation
Estrogen therapy increases the synthesis of clotting factors and can cause ischemic strokes. Protein C and S help keep clot formation in balance.
2.
After tissue injury, place the following events in the correct order. A. von Willebrand factors attracts plateletsB. Platelets secrete ADP - attracts more plateletsC. Collage is exposed, activating plateletsD. Platelets secrete serotonin and thromboxane A2 - vasoconstriction
Correct Answer
B. C, A, D, B
Explanation
Collagen is exposed after tissue injury, which activates platelets. von Willebrand factor is then released, attracting platelets to the site of injury. Platelets secrete serotonin and thromboxane A2, causing vasoconstriction. Finally, platelets secrete ADP, which attracts more platelets to the site of injury. Therefore, the correct order is C, A, D, B.
3.
What are the steps in fibrin formation?
Correct Answer
D. A and B
Explanation
"Tissue factor" or thromboplastin is released from endothelial wall - starts the extrinsic pathway ("tissue factor pathway" - a factor from outside the vascular system is required.
Contact of blood with collagen starts the intrinsic pathway of blood ("contact activation pathway") - all clotting factors required to start the pathway are present within the vascular system.
4.
Proteins C and S are dependent on which vitamin for synthesis?
Correct Answer
D. Vitamin K
Explanation
Proteins C and S are dependent on Vitamin K for synthesis. Vitamin K is essential for the production of blood clotting proteins, including proteins C and S. These proteins play a crucial role in regulating blood clotting and preventing excessive clot formation. Without sufficient Vitamin K, the synthesis of proteins C and S would be impaired, leading to an increased risk of abnormal blood clotting. Therefore, Vitamin K is necessary for the proper functioning of proteins C and S in the body.
5.
What might cause a deficiency in Prothrombin (factor II) or in Stuart-Prower factor (factor X)?
Correct Answer
E. A and C
Explanation
A deficiency in Prothrombin (factor II) or in Stuart-Prower factor (factor X) can be caused by liver disease and vitamin K deficiency. Liver disease can impair the liver's ability to produce these clotting factors, leading to a deficiency. Vitamin K is essential for the production of these factors, so a deficiency in vitamin K can also result in a deficiency of Prothrombin and Stuart-Prower factor. Therefore, both liver disease and vitamin K deficiency can contribute to a deficiency in these clotting factors.
6.
Why can't Heparin be administered orally?
Correct Answer
D. A and B
Explanation
It is large and negatively charged and cannot cross the membrane to be absorbed.
7.
What does heparin inhibit?
Correct Answer
E. A and C
Explanation
Heparin acts as an anticoagulant by way of antithrombin (a protease inhibitor) - antithrombin inhibits factors Xa, thrombin (IIa), and IXa, XIa, and XIIa. Heparin therefore inhibits conversion of prothrombin to thrombin (via inhibition of Xa) and fibrinogen to fibrin (via inhibition of IIa).
8.
Heparin also has a:
Correct Answer
C. Lipid clearing activity.
Explanation
Heparin releases a clearing factor (a lipoprotein lipase) - this lipase hydrolyzes triglycerides in chylomicrons.
9.
How can heparin be administered?
Correct Answer
F. A and B
Explanation
Cannot be administered orally - large and negative. Cannot be administered IM - hematoma. Only IV and SQ.
10.
Heparin is metabolized in the:
Correct Answer
A. Liver
Explanation
Heparinase in liver.
11.
Heparin metabolites are excreted in the:
Correct Answer
B. Kidneys
Explanation
Heparin metabolites are excreted in the kidneys. The kidneys play a vital role in the excretion of waste products and metabolites from the body. Heparin, a medication used as an anticoagulant, undergoes metabolism in the liver and is then excreted primarily through the kidneys. The kidneys filter the blood and remove waste products, including heparin metabolites, through urine. Therefore, the correct answer is kidneys.
12.
Is heparin ok in pregnancy?
Correct Answer
A. Yes.
Explanation
Heparin is the drug of choice for pregnant women because it does not cross the placental membrane.
13.
Heparin's adverse effects include:
Correct Answer
G. All of the above.
Explanation
Hypersensitivity is due to animal origin. Osteoporosis and alopecia are only seen in long-term use - 2-3 months. Hemorrhage is the major concern. Thrombocytopenia = hepairin induced (HIT) platelet aggregation - heparin antibody develops 7-14 days after start of treatment. Thromboembolism is induced by HIT.
14.
Which drugs is used in the treatment of heparin toxicity?
Correct Answer
D. Protamine
Explanation
Protamine is a small, positively charged molecule that binds with heparin. Dosages is based on the level of heparin - must be dosed to titrate 1:1 with heparin, taking into account the different half lives of the drugs. Adverse effects of protamine are anticoagulation (acts as an anticoagulant if administered without heparin) and anaphylactic shock (derived from fish sperm).
15.
Low molecular weight heparins include which of the following:
Correct Answer
F. A, D, and E.
Explanation
The correct answer is A, D, and E. Low molecular weight heparins (LMWHs) are a type of anticoagulant medication. Enoxaparin (Lovenox), dalteparin (Fragmin), and tinzaparin (Innohep) are all examples of LMWHs. Warfarin and coumadin, on the other hand, are not LMWHs.
16.
What is the mechanism of action of LMWH and why is it different than heparin?
Correct Answer
B. It inactivates Xa but has little inactivation at IIa (thrombin) via antithrombin because chains are too short for thrombin binding.
Explanation
LMWH (Low Molecular Weight Heparin) inactivates Xa (Factor Xa) but has little inactivation at IIa (thrombin) via antithrombin because the chains of LMWH are shorter compared to heparin. Thrombin has a higher molecular weight and requires longer chains to bind effectively. Therefore, LMWH primarily targets and inhibits Xa, which is involved in the formation of blood clots, while having minimal effect on thrombin. This is different from heparin, which can inhibit both Xa and IIa.
17.
What are the benefits of LMWHs?
Correct Answer
E. All of the above.
Explanation
LMWHs are cleared renally. Less interactions with platelets means less risk of HIT! (Still can't use in patients who have had HIT.) Additional benefits include little monitoring (don't have to be in the hospital), self-administration SQ.
18.
Which of the following is a synthetic pentasaccharide identical to the antithrombin binding region of heparin?
Correct Answer
D. Fondaparinux
Explanation
Fondaparinux (Arixtra) is a LMW Heparin Derivative that does not originate from unfractionated heparin. It is a synthetic pentasaccharide identical to the antithrombin binding region of heparin.
19.
What factor is inhibited by Fondaparinux (Arixtra) in conjunction with antithrombin?
Correct Answer
D. Xa
Explanation
Fondaparinux (Arixtra) inhibits factor Xa in conjunction with antithrombin. Factor Xa is a key enzyme in the coagulation cascade that plays a crucial role in the formation of blood clots. By inhibiting factor Xa, Fondaparinux prevents the formation of blood clots and reduces the risk of thromboembolic events.
20.
Which drug is an irreversible direct thrombin inhibitor that is used in place of heparin when HIT is an issue?
Correct Answer
C. Lepirudin (Refludan)
Explanation
Dosing by IV and is expensive - renal elimination so use caustion in renally compromised patients.
21.
Which drug is a direct reversible thrombin inhibitor used to treat thrombosis in HIT?
Correct Answer
A. Argatroban (Acova)
Explanation
Synthetic drivative of arginine - direct reversible thrombin inhibitor by blocking the catalytic site - treats thrombosis in HIT - IV administration - metabolized by the LIVER so don't have to worry about renally compromised patients.
22.
Which drug is a direct thrombin reversible inhibitor given in combination with aspirin to prevent clot formation with unstable angina undergoing coronary angioplasty?
Correct Answer
D. Bivalirudin (Angiomax)
Explanation
Synthetic derivative - IV administration - renal elimination so must use caution in renally compromised patients.
23.
Which drug is a direct thrombin almost irreversible inhibitor used for DVT prevention in hip replacements?
Correct Answer
A. Desirudin (Iparavask)
Explanation
Newest of the group - direct thrombin almost irreversible inhibitor - can be used in HIT patients - SQ so more useful - renal elimination, use caution.
24.
Which drug acts by competitive inhibition of vitamin K reductase?
Correct Answer
B. Warfarin
Explanation
Warfarin acts thru competitive inhibition of vitamin K reductase - blocks the synthesis of factors II, VII, IX, X, and protein C and S - results in lack of gamma carboxylation of the factors (gamma carboxylation allows calcium to bind, which is necessary for activation and platelet binding).
25.
How much time is required for peak anticoagulant effect of Warfarin?
Correct Answer
D. 3 days
Explanation
Warfarin takes out the synthesis of inactivated factors but you need to wait for the body to get rid of the activated factors before seeing the effects of warfarin. Activated IIa has the longest half life, at 60 hours.
26.
Does Warfarin or Heparin have a longer half-life?
Correct Answer
A. Warfarin
Explanation
Warfarin has a 35 hour half-life! It is well absorbed by the oral route and is 99% bound to plasma proteins (albumin).
27.
What adverse effect can be seen in the fetus when the mother takes Warfarin, especially in the first trimest?
Correct Answer
D. Bone defects.
Explanation
Fetal bone defects are due to lack of gamma carboxylation of osteocalcein.
28.
Which drugs act as synergists for Warfarin?
Correct Answer
F. A, C, and D
Explanation
Acetylsalicylic acid - platelets - reduce platelet aggregation - displacement of warfarin from albumin (get more unbound, active aspirin and more free warfarin too). Acetaminophen - high dose and long term - inhibits warfarin degradation - competition for CYP1A2 and 3A4. Antibiotics - (broad spectrum) gut flora - bacteria in the stomach synthesize vitamin K - reducing the amount of vitamin K produced means there is less for warfarin to compete with so it is able to work better. Antibiotics - sulfonamides - compete in plasma albumin binding.
29.
Which drugs act as synergists for Warfarin?
Correct Answer
F. A, B, and C.
Explanation
Thyroid - increased metabolism of clotting factors so there are less clotting factors around. Miconazole - is able to cross the membrane and affect warfarin enzymes - inhibits CYP450 - increased warfarin levels. Gemfibrozil - competes for plasma proteins.
30.
Which of the following are Warfarin antagonists?
Correct Answer
F. All of the above.
Explanation
Barbiturates increase metabolism by inducing degradation enzymes. Rifampin increases metabolism by inducing CYP450 enzymes. Vitamin K competes for binding (role of foods). Estrogens increase factors VII and X which increases the synthesis of coagulation factors. Estrogens also decrease the synthesis of antithrombin. Cholestyramine - binds fat soluble vitamins and so eliminates warfarin if given concurrently
31.
What is the treatment for Warfarin toxicity?
Correct Answer
E. A and B
Explanation
Phytonadione (K1) can be given orally, IV, or SC and it competes with warfarin. Transfusion of fresh frozen plasma provides a lot of fresh clotting factors.
32.
Is bound plasmin or circulating plasmin better?
Correct Answer
A. Bound plasmin.
Explanation
We want plasmin associated with the clot (bound) - systemic lysis can occur when plasmin is present in circulating plasma - it will destroy clotting factors in addition to clots!
33.
Which drug is a protein from group C, beta hemolytic streptococci that induces a lytic state?
Correct Answer
B. Streptokinase
Explanation
Streptokinase forms a non-enzymatic complex with circulating plasminogen which catalyzes thrombolytic reactions - used IV and infused directly into coronary arteries *(less than 6 hours for MI)*
34.
Which drug is antigenic?
Correct Answer
B. Streptokinase
Explanation
If patient has had a previous strep infection or has been given streptokinase before, the patient will have antibodies to streptokinase that will cause an allergic reaction or neutralization of streptokinase).
35.
Which of these drugs is a tissue-type plasminogen activator (t-PA) and is basically the clone of what we produce in our bodies?
Correct Answer
A. Alteplase (Activase)
Explanation
activates plasminogen bound to platelets and endothelial cells (relatively clot specific) - not very antigenic (unless allergic to E. coli) - inhibited by t-PA inhibitor - short half-life of 5-10 minutes - long infusion of 90 min. infusion - higher intracranial bleeding risk but no hypotension (which can be an issue with streptokinase).
36.
What are the advantages of the new derivatives of alteplase (reteplase and tenecteplase)?
Correct Answer
C. All of the above
Explanation
Increased half-life because the plasminogen activator inhibitor doesn't degrade these as quickly. Only specific approved indications.
37.
Which of the following is a derivative of tPA that is only approved for acute MI?
Correct Answer
D. Reteplase
Explanation
Reteplase is clot specific but less so than alteplase - not very antigenic - 13-16 min. half-life - 2 separate 2 minute IV bolus separated by 30 min. - bleeding risk.
38.
Which drug has the highest fibrin selectivity and only a 5 second IV bolus injection?
Correct Answer
B. Tenecteplase (Tnkase)
Explanation
Only 3 AAs different from alteplase - 20-24 minute half-life - more resistant to t-PA circulating inhibitors - highest fibrin selectivity - wont have as many issues with extraneous plasminogen formation.
39.
In what order are the following drugs clot specific? (From most clot specific to least.)1. Tenectaplase2. Reteplase3. Alteplase
Correct Answer
C. 1, 3, 2
Explanation
This is also the order for activating thrombin - tenectaplase the least and reteplase the most.
40.
Which of the following drugs inhibits platelet aggregation?
Correct Answer
C. Acetylsalicylic acid (Aspirin)
Explanation
Mechanim of action: irreversible inhibition of cyclooxygenase (COX-1 and COX-2). COX-1 is ubiquitously present in all cells - inhibiting COX-1 inhibits the synthesis of thromboxanes which inhibits platelet aggregation. COX-2 is not present on platelets.
41.
What disorder(s) can be caused by aspirin?
Correct Answer
D. All of the above
Explanation
Gout - low doses of aspirin increase uric acid levels - competes for excretion of uric acid. Salicylism - aspirin is an acid - use sodium bicarb to treat - excrete in anionic form.
42.
Which adenosine diphosphate receptor antagonist does not work any better than aspirin but is recommended for those patients allergic to aspirin?
Correct Answer
A. Clopidogrel (Plavix)
Explanation
Clopidogrel (Plavix) is indicated in thrombosis and coronary artery disease - side effects include a low risk of TTP (thrombotic thrombocytopenia purpura), bleeding, hypersensitivity, abdominal pain, constipation - resistance to clopidogrel (Plavix) can be seen if the patient has a defect in CYP450 enzymes - prodrug doesn't get converted to active form.
43.
Which adenosine diphosphate receptor antagonist is similar to clopidogrel but has fewer thrombotic events but increased risk of major bleeding?
Correct Answer
A. Prasugrel (Effient)
Explanation
indicated in arterial thromboembolism prophylaxis
44.
Which of the following are Super Aspirins?
Correct Answer
D. All of the above
Explanation
abciximab (Reopro) = murine-human chimeric antibodies. eptifibatide (Integrelin) = synthetic peptide form. tirofiban (Aggrastat) = synthetic peptide forms.
45.
What type of anticoagulant acts as a platelet glycoprotein IIb/IIIa receptor antagonist?
Correct Answer
D. Super Aspirins
Explanation
Acts as reversible antagonists of glycoprotein IIb/IIIa - the receptor on the platelet for adhesive proteins such as fibrinogen and von Willebrand factor. Maximally inhibit the final common pathway involved in platelet adhesion, activation, and aggregation.
46.
What are the indications for platelet glycoprotein IIb/IIIa receptor antagonists (Super Aspirins)?
Correct Answer
F. B and D
Explanation
Drugs are infused - rapid acting - and rapidly reversed after stopping infusion - major side effect: bleeding.
47.
Which (2) drug'(s) mechanism of action is proposed interference with platelet function by increasing the cellular concentration of cyclic AMP, by decreasing phosphodiesterase activity, or raising adenosine levels?
Correct Answer
F. B and C
Explanation
Inhibits platelet activation by increasing cellular cyclic AMP by inhibiting a phosphodiesterase that degrades cAMP.
48.
What is the major difference between cilostazol (Pletal) and dipyridamole?
Correct Answer
D. Dipyridamole must be given with aspirin to be effective.
Explanation
Dipyridamole and aspirin formulation (Aggrenox) is recommended for use with prosthetic heart valves in combination with aspirin. Technically A would be true too but is not the most important difference between the two. More platelet inhibition is seen with cilostazol than with aspirin or dipyridamole.
49.
What disorder is cilostazol strongly contraindicated in?
Correct Answer
D. Congestive heart failure.
Explanation
(I'm not sure why, but according to my notes, emphasis was placed on the importance of this point...)
50.
What drug would likely be prescribed for a patient with atherosclerosis in the legs (intermittent claudication) causing pain, cramping, and weakness in calf muscles when walking?
Correct Answer
C. Cilostazol
Explanation
Cilostazol would likely be prescribed for a patient with atherosclerosis in the legs causing intermittent claudication. Cilostazol is a medication that helps improve blood flow by dilating the blood vessels and reducing platelet aggregation. It is specifically indicated for the treatment of intermittent claudication, which is characterized by pain, cramping, and weakness in the calf muscles during physical activity such as walking. Aspirin, Dipyridamole, and Niacin may have other uses, but Cilostazol is the most appropriate choice for this particular condition.