Term
| 1. Compare and contrast the mechanism of action of aspirin ticlopidine/clopidogrel? |
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Definition
Aspirin inhibits the cyclooxygenase enzyme leading to decreased production of prostaglandins including thromboxane A2. This prostaglandin causes platelets to change shape, release granules, and aggregate
Ticlopidine and clopidogrel inhibit ADP-induced platelet aggregation. They prevent binding of adenosine diphosphate (ADP) to its platelet receptor. Thus, ADP-mediated activation of the glycoprotein GPIIb/IIIa complex is impaired. Because the glycoprotein GPIIb/IIIa complex is the major receptor for fibrinogen, impaired activation of the GPIIb/IIIa complex prevents fibrinogen binding to platelets which ultimately inhibits platelet aggregation |
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Term
| 2. What are the most common adverse effects of aspirin? |
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Definition
GI adverse effects including gastric erosion, peptic ulcers; Bleeding can occur secondary to direct irritation of the gastric mucosa as well as due to inhibition of platelet aggregation and potentially thrombocytopenia (GI adverse effects are dose-related)
Renal adverse effects such as nephrotoxicity are related to inhibition of prostaglandins that maintain renal perfusion
CV adverse effects include fluid retention and edema
Derm. adverse effects include hypersensitivity reactions, rash, bruising |
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Term
| 4. How do low-molecular weight heparins differ from unfractionated heparin? |
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Definition
| Unfractionated heparin has a less predictable anticoagulant response due to decreased and variable bioavailability (due to tissue and protein binding). Therefore, frequent monitoring of PTT and dosage adjustments are necessary with unfractionated heparin (except when used for DVT prophylaxis). Low molecular weight heparins have greater anti-factor Xa activity compared to unfractionated heparin which equally effects factor Xa and IIa. LMWHs do not significantly affect platelet activity, prothrombin time (PT) or partial thromboplastin time (PTT). LMWH have a decreased risk of bleeding. |
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Term
| 3. What are the differences between clopidogrel and ticlopidine? |
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Definition
| Clopidogrel has a shorter onset of action and less potential for hematologic and GI adverse effects (ticlopidine requires q2week monitoring of CBC while clopidogrel does not) |
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Term
| 5. Describe the mechanism of action of warfarin? |
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Definition
| Inhibits synthesis of the vitamin-K dependent clotting factors II, VII, IX, and X |
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Term
| 6. How do foods such as spinach and greens affect the activity of warfarin? |
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Definition
The vitamin K contained in these foods antagonizes the activity of warfarin.
Patients are generally instructed to keep their intake of vitamin-K containing foods consist on a day to day basis to minimize fluctuations in the INR.
The following link provides useful information on the vitamin-K content of various foods. http://www.coumadin.com/consumer/INT_VitaminK1.asp |
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Term
| 7. What laboratory test is used to monitor warfarin therapy? |
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Definition
Prothrombin time (PT) and International normalized ratio (INR)
The INR was developed to take into account inter-laboratory differences in assays used to monitor PT |
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Term
| 8. Which of the class of antihyperlipidemic agents exerts its effects primarily on triglycerides? |
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Definition
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Term
| 9. The HMG-CoA reductase inhibitors (statins) exert their effect primarily on which type of cholesterol? |
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Definition
| Mainly LDL; will see some decreases in triglycerides and increases in HDL |
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Term
| 10. Which of the class of antihyperlipidemic agents is considered safest for use in children and pregnant women? |
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Definition
Bile acid sequestrants are preferred since they are not absorbed systemically
However caution is recommended in pregnancy since they may impair the absorption of fat soluble vitamins (ie. ADEK). Statins are pregnancy category X and should not be used in pregnancy. All other classes are category C. |
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Term
| 11. Describe the advantages and disadvantages of the use of niacin in the treatment of hyperlipidemia. |
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Definition
Advantages include: it is well absorbed orally, non-CYP mediated metabolism leading to less drug interactions, decreases triglycerides by 20-50%.
Disadvantages include: adverse effects of flushing (most common) and GI effects, also must be used with caution with statin therapy due to the increased risk of Myopathy with the combination of the two medications. |
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Term
| 12. Which statins are least likely to interact with agents that inhibit the CYP3A enzyme system? |
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Definition
Pravastatin, fluvastatin, rosuvastatin-least likely
Atorvastatin-intermediate (undergoes some 3A4 metabolism so need to be careful with 3A4 inhibitors; for example with the HIV protease inhibitors, we do not start with more than 10 mg and max out at 20 mg (usual max dose without a 3A4 inhibitor on board is 80 mg)
Simvastatin and lovastatin are contraindicated with many CYP3A4 inhibitors since the levels of these statins will be substantially increased leading to increased risk for toxicity |
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Term
| 13. What laboratory tests would you routinely monitor after starting a patient on a HMG-CoA reductase inhibitor? |
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Definition
| LFTs should be checked before the initiation of therapy and after dose changes. After stable on effective dose, then monitor LFT’s every 3-6 months thereafter. |
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Term
| 14. What is the role of ezetimibe (Zetia) in the treatment of hyperlipidemia? |
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Definition
| This medication is used in the treatment of Hypercholesterolemia as monotherapy or combined with a statin. If combined, it increases its effectiveness in lowering LDLs and increases HDLs |
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Term
15. JB is a 52 year old female who recently had a fasting lipid panel obtained by her primary care provider. Her PMH includes hypertension (she is on HCTZ) and allergic rhinitis. Her BP today is 112/76. Her family history includes father died age 50 from colon cancer, mom died from MI at age 59. She currently smokes cigarettes 1.5 ppd.
Total-C: 253 mg/dL LDL-C 185 mg/dL HDL-C 35 mg/dL Trigs: 165 mg/dL |
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Definition
A. How would you classify the patient’s total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides according to the ATP III Classification?
Total: High, LDL: High, HDL: Low, Triglycerides: borderline high |
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Term
| A. How would you classify the patient’s total cholesterol, LDL cholesterol, HDL cholesterol, and triglycerides according to the ATP III Classification? |
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Definition
| Total: High, LDL: High, HDL: Low, Triglycerides: borderline high |
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Term
| B. How many major risk factors does the patient have? |
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Definition
| 4: Hypertension, smoking, low HDL, family history of premature CHD |
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Term
| C. What is the patient’s 10 year risk of developing CHD? |
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Definition
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Term
| D. What is the LDL goal of therapy for this patient? |
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Definition
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Term
| E. How would you manage this patient’s hyperlipidemia? |
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Definition
Initiate 3 month trial of TLC; then add drug if needed
Statins, bile acid sequestrants, niacin are options for LDL lowering
Since patient’s triglycerides are also elevated, would probably avoid bile acid sequestrants since these can increase triglycerides |
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Term
| F. What would you recommend to raise the patient’s HDL? |
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Definition
| Stop smoking, increase physical activity, weight reduction (if obese) 16. |
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Term
| 1. When evaluating a patient for anemia, which lab values would you consider? |
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Definition
CBC-including the following:
HCT percent of red blood cells in plasma
HGB is made up of iron containing heme and protein (globulin)-The oxygen-combining ability of the blood is in direct proportion to the hemoglobin concentration
MCV is defined as the size of the RBC. The type of anemia is based on the size of the red blood cell (macrocytic, normocytic or microcytic)-if this is elevated consider B12 and folate deficiency
MCHC is the portion of the cell taken up by hemoglobin. Cells are defined as hyperchromic, normochromic, and hyperchromic depending on how much hemoglobin is present.
Reticulocyte count: Immature RBC, percentage of RBCs. Low levels can indicate a failure in production of RBCs in aplastic anemia, bone marrow disorders or suppression, anemia of chronic disease, liver disease, and hypothyroidism. Elevated levels indicate hemolysis of some sort such as blood loss or sickle cell anemia, s/p splenectomy or a positive treatment to iron, B12 or folate administration. |
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Term
| Microcytic hypochromic anemia (MCHC low, MCV low) |
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Definition
Iron deficiency
Thalassemia
Sideroblastic anemia
Lead poisoning
Anemia of chronic disease (rare) |
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Term
| Normochromic macrocytic anemia (MCHC normal, MCV high) |
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Definition
Vitamin B12 deficiency
Folate deficiency
Liver disease
Hypothyroidism |
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Term
| Normocytic anemia (normal MCV to decreased MCV, MCHC norm to decreased) |
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Definition
Bone marrow involvement
Aplastic anemia
Leukemia
Reticulocytosis
Secondary to underlying disease
Liver disease, cirrhosis
Acute bleeding
Anemia of chronic disease |
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Term
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Definition
o thrombotic thrombocytopenic purpura (TTP)
o disseminated intravascular coagulation (DIC),
Sickle cell anemia |
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Term
| 3. Which medications decrease the absorption of iron and increase the absorption of iron? |
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Definition
Drugs that reduce iron absorption:
Milk and dairy products
H2 blockers
PPIs
Antacids |
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Term
| Drugs that increase iron absorption |
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Definition
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Term
| 4. What are the most common adverse effects of iron formulations? |
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Definition
| GI irritation is the most common adverse effect. Darkening of stool may also occur. With liquid preparations, darkening of teeth common as well. |
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Term
| 5. Where is erythropoietin produced and what is its purpose? |
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Definition
| 90% of erythropoietin is produced in the kidney. Erythropoietin is a glycoprotein that regulates the production of red blood cells by stimulating the division and differentiation of committed erythroid progenitor cells in the bone marrow. |
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Term
| 6. What are the differences between epoetin alfa and darbepoetin alfa? |
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Definition
| Darbepoetin alpha has a longer half-life. |
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Term
| 7. List adverse effects that can occur with the erythropoiesis stimulating proteins. |
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Definition
CV (more common with chronic renal failure): HTN, cardiac arrhythmias, cardiac arrest, chest pain, CHF, acute MI, stroke, TIAs
Vascular complications-PE, venous thrombosis
Seizures-2.5% of patients on dialysis, usually within first 90 days and associated with sudden rise in blood pressure, rare with other indications
Non-fatal MI, vascular access thrombosis, thromboembolism more common in dialysis patients with hematocrit target of 42% compared to 30%
Increased incidence of deep venous thrombosis in orthopedic surgery patients with pre-treatment hemoglobin > 13 mg/dL
Flu-like symptoms (arthralgias/myalgias, fever, weakness)-during initiation of therapy, usually disappear after 2-12 hours
GI: nausea, vomiting, abdominal pain, diarrhea or constipation
Iron deficiency-evaluate iron stores (transferrin saturation, serum ferritin) before and during therapy with these agents
Red blood cell aplasia (secondary to neutralizing antibodies, “antierythropoietin antibodies”), rare and more common with products marketed outside of US, not yet documented with darbepoetin
Thrombophlebitis with IV administration, injection site reactions with SQ administration (usually minor)
Bone pain |
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