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INTERPRETATION OF LAB TESTS with a Pharmaceutical Focus

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  • 1. INTERPRETATION OF LAB TESTS with a Pharmaceutical Focus
    Barb Bancroft, RN, MSN, PNP
    Chicago, IL
    AUGUST 5, 2010
  • 2. Rule number one …
    Know your own lab’s normal values
    The reference values are affected by many variables, including patient population and laboratory methods used
  • 3. Rule #2--READ the package insert for suggested testing intervals
    This is specifically a CYA (Cover your “donkey”) procedure for prescribing purposes
    Every drug and every pharmaceutical company has different testing intervals—it would be wise to know them
    Examples: Amiodarone (Cordarone)—liver function tests (LFTs) at baseline and every six months (if the LFTs are greater than 3x the ULN, or doubles in a patient with elevated baseline LFTs, decrease the dose or d/c the drug)
  • 4. Another example:
    Spironolactone (Aldactone) and eplerenone (Inspra)—check potassium and renal function (serum creatinine) at baseline, three and seven days after initiation, monthly for three months, then quarterly; restart monitoring cycle if ACE or ARB is added or their dose is increased;
    Do not start if serum creatinine is greater than 2.5 mg/dL (221 mmol/L) in men or greater than 2 mg/dL (176.8 mmol/L) in women (for spironolactone ≥ 200 mmol/L per Canadian Cardiovascular Society)
    Reduce dose or d/c if serum potassium > 5.5 mEq/L (same as mmol/L in Canada)
  • 5. Is genotyping necessary with certain drugs?
    Carbamazepine—baseline HLA-B*1502 testing in Asians—severe skin reactions can occur
    High prevalence (15%) in Hong Kong, Thailand, Malaysia, and parts of the Philippines, followed by Taiwan (10%), North China (4%), and Japan and Korea (1%). In South Asians, including Indians, risk is 2-4% (Novartis Pharmaceuticals Corporation—Product information. February 2009)
  • 6. Serum protein electrophoresis
    List the plasma proteins
    1) albumin
    2) globulins
    3) fibrinogen
    Is there a difference between plasma proteins and serum proteins?
  • 7. Yes. The removal of fibrinogen
    So, the serum proteins are albumin and the “globulins”.
    Fibrinogen—(1.4-4.0 mg/dL or 140 to 400g/L)
    Hyperfibrinogenemia (greater than 4.0 g/dL or 400 g/dL) increases the risk of clotting
  • 8. What conditions increase the risk of clotting?
    Venous catheters
    Heart failure/Atrial fibrillation
    Pregnancy and postpartum
    Prolonged travel (economy class syndrome—air travel)
    Heparin-induced thrombocytopenia
    Estrogen therapy (?)
  • 9. What about the estrogen controversy?
    Estrogen excess increases fibrinogen
    COC’s? The “old days” vs. today
    HT? (hormone therapy—E + P—po, not patch or gel or any other topical route)
    How about your own ovaries, ie, endogenous estrogen?
  • 10. What else increases fibrinogen?
    Smoking increases fibrinogen
    So how about smoking and estrogen, eg, oral contraceptives or HT in the PMF? (use patch)
    Smoking accelerates aging
    Aging and fibrinogen—increases by 1% per year after age 30
    How many 30 –year-olds are on warfarin/Coumadin?
  • 11. Biological rhythms and clotting
    DVT (venous clot or redclot) may take a few hours or a few weeks to form depending on the circumstances; attached to the deep veins of the legs and pelvis; breaks off in early a.m. due to standing up and moving around; takes 30 minutes to travel to the lungs—Up at 7 a.m.? Pulmonary embolism at 7:30 a.m.
    Coumadin/Heparin inhibit clotting factors (red clots)
    If the pulmonary embolism is huge, tissue plasminogen activator (Activase/alteplase or reteplase/Retavase; streptokinase) may be infused
    Incidence varies based on AGE(0.2 cases/100,000 in kids under 15 ; 700 cases per 100,000 in patients over 85
  • 12. Coagulation profile
    Platelet counts and platelet aggregation/clumping (how well platelets aggregate as measured by the bleeding time—3 to 6 minutes)
    PT (prothrombin time)—11.3 to 13.3 seconds
    INR is used to measure PT in patients on Coumadin (2-3)
    aPTT—22.1 to 34 seconds (stable aPTT on heparin is 60 to 84 seconds)
  • 13. Quantitative and qualitative platelet dysfunction
    Platelet counts and bleeding times—quantitative and qualitative measurements
    Normal platelet count--150,000 to 450,000;
    Platelet counts above 100,000 do well w/ hemostasis;
    50,000 to 100000 may show increased bruising;
    platelet counts less than 50,000 need monitoring;
    spontaneous hemorrhage under 10,000
  • 14. Platelet-type bleeding
    Acute DIC -- Severe thrombocytopenia due to meningococcemia
  • 15. Platelet type bleeding –thrombocytopenia; chronic DIC
    Secondary to malignancy
  • 16. The most common drugs that cause thrombocytopenia
    sulfa drugs, piperacillin, linezolid, rifampin
    quinine and quinidine
    cimetidine (Tagamet)
    valproic acid(Depakene, Depakote)—check platelet count and coagulation tests baseline, periodically, and prior to planned surgery
    Don’t forget ETOH abuse also causes thrombocytopenia
  • 17. ASA , NSAIDS and clopidogrel (Plavix) cause qualitative platelet dysfunction
    Cause a qualitative dysfunction NOT quantitative (numbers are normal, bleeding time is prolonged)
    ASA and NSAIDs inhibit the enzyme cyclooxygenase (COX), which in turn prevents the formation of thromboxane A2 and prostaglandins
    Clopidogrel (Plavix) blocks platelet aggregation by inhibiting the ADP receptor
  • 18. Glycoprotein IIb/IIIa receptor inhibitors
    Abciximab (ReoPro)
    Eptifibatide (Integrillin)
    Tirofiban (Aggrastat)
    gpIIb/IIIa is a molecule necessary for platelet aggregation
  • 19. Aspirin’s effect on platelets is irreversible and lasts 7 to 10 days; d/c aspirin 7 days prior to major surgery
    d/c NSAIDs (short-acting) 24 hours prior to surgery; long-acting 7 days prior to surgery
  • 20. Alternative therapies and platelet aggregation
    If it starts with a G it inhibits platelet aggregation—gingko, garlic, glucosamine, ginseng, ginger, grapeseed extract
    SJW does too as does feverfew (used for migraines)
    Fish oil can decrease the ability of platelets to aggregate especially if the patient is taking other G’s + ASA and/or NSAIDS and/or Plavix
    d/c feverfew, garlic, ginger, and ginseng 7 days prior to surgery; gingko 36 hours prior to surgery
  • 21. Arterial clots
    Liver produces clotting factors (II, VII, IX, X), cholesterol, glucose, and inflammatory mediators overnight
    Spits them all out in the a.m.
    MI (arterial clot or white clot)—inflammation is the operative word
    inflammatory mediators are highest in the morning; triggers an unstable plaque in one of the coronary arteries to rupture; platelets are stickiest in the early a.m. due to the highest blood sugar of the day; platelet plug forms, triggers clotting cascade; takes 2-3 hours to form; up at 7? MI between 9 and 10 a.m.
    ASA inhibits platelet aggregation and decreases inflammation
    Chest pain? Chew a 325 mg ASA
  • 22. Serum Proteins
    Globulin’s ‘
    Add the two together and you have the total serum protein test or TSP
    Albumin comprises 2/3 of the total serum proteins; globulins 1/3—this is called the A/G ratio
    Generally used as screening tests altho’ the albumin level can be used to determine nutritional status and/ or prognosis in liver disease
    A better test that gives you more bang for your buck is the serum protein electrophoresis
  • 23. Serum Protein Electrophoresis—based on molecular weight and overall charge (positive or negative)
    + -
    Well in the gel
    Electrical current running through gel
  • 24. Serum electrophoresis
  • 25. The globulins…
    The alpha 1 globulins—there are a few alpha-1 globulins; however, we’ll only discuss the most clinically important for today’s lecture and for YOUR health
    High-density lipoprotein—the good guy
    What do they do? HDL’s clear excess cholesterol from the blood; HDL’s are also potent “anti-oxidants” and prevent LDL from oxidizing; the HDLs are also potent “anti-inflammatory” lipoproteins; keep levels above 40 mg/dL (1.04 mmol/L) and above 60 mg/dL (≥ 1.55 mmol/L) would be ideal
    For every 5 mg/dL (0.13 mmol/L) decrease in HDL below the mean, the risk of CHD increases by 25%
  • 26. So if HDLs are good for you, how can we boost HDLs without drugs?
    Eat right— garlic (crush it, let it sit for 10 minutes, eat it raw or lightly sauteé it for less than 6 minutes), beans, omega-3 fatty acids, fiber, almonds (and other nuts), plant stanols (Take Control, Benechol, Smart Balance, Yoplait Yogurt, Minute Maid Heart Wise OJ)
    Decrease saturated and trans fats
  • 27. What else boosts HDLs?
  • 28. What else boosts HDLs?
    Premenopausal women have fabulously high HDLs—one of the major reasons the heart is protected prior to menopause
  • 29. Booze to boost HDLs… a little dab‘ll do ya’…
    This is a yes…
    5 oz of wine of any color—This amount->
    Guys, you can have 2 glasses
    How much of the hard stuff? 1-2 ounces for women; 2-3 ounces for men
    How about a brewski? 12 ounces for women, 24 ounces for men
  • 30. So, what’s my motto?
    Bike a mile, guzzle a brewski, and pop a Premarin…OR…
    Have a delicious glass of Chardonnay with a lovely salmon dinner with my Mom…
  • 31. Increasing HDLs with pharmacologic agents
    Say YES to drugs…
    Niacin/Niaspan boosts HDL the most—up to 25%
    Drugs— the “statin” sisters (prescribed to lower LDL)– rosuvastatin/Crestor) gives you the most bang for your buck in raising HDLs (boosts HDLs by 12-14% vs. ~6% for the other statins)
    Metformin (Glucophage) increases HDLs
    Pioglitazone (Actos) increases HDLs
  • 32. Other drugs that influence HDL levels
    Increase HDL--glucocorticoids, cyclosporine, tacrolimus
    Decrease HDL—androgens/testosterone, progestins, thiazide diuretics, beta-blockers, valproate and related drugs, isotretinoin
  • 33. Beta globulins—the bad guys
    LDLs (low density lipoproteins)—directly deposit into the walls of the arteries via the process of oxidation
    The higher the LDLs, the greater the risk for atherosclerosis
    Familial hypercholesterolemia—heterozygous vs. homozygous (Quebec)
  • 34. Guidelines for LDLs
    A patient with CAD or a risk equivalent (diabetes), the LDL should be ~70 mg/dL (2.2 mmol/L or even lower, perhaps 1.8 mmol/L)
    For the rest of us with other risk factors—100 mg/dL (<2.85 mmol/L)
    Unless you’re perfect…--130 mg/dL (<3.37 mmol/L)
    Size of the LDL particles…small and dense vs. large and loose (diabetics tend to have small and dense due to high triglycerides)
  • 35. Risk factors for increased LDLs
    Diet high in trans and saturated fats
    High iron levels
    High insulin levels
    Couch potato
    Fat around the middle
  • 36. LDL reduction
    Exercise? Eat right?
    Foods; fiber; almonds; plant stanols
    Reduce red meat, sat fats and trans fats
  • 37. How about drugs to reduce LDL? Say YES to the “statin” sisters…
    Say yes to the “statin” sisters—lova (Mevacor), atorva (Lipitor), prava (Pravachol), simva (Zocor), fluva (Lescol), rosuva (Crestor), and the newest statin “sister” is pitavastatin (Livalo)
    Statin dose chosen should reduce the LDL by 30-40%
  • 38. Statin doses
    Instead of starting with the lowest doses, begin with a dose that drops the LDL-C by 30-40%
    Rosuvastatin/Crestor—5-10 mg = 39-45% LDL reduction
    Fluvastatin/Lescol—40-80 mg = 25-31% reduction
    Atorvastatin/Lipitor – 10 mg = 39% reduction
    Pravastatin/Pravachol– 40 mg = 34% reduction
    Simvastatin/Zocor– 20-40 mg = 35-41% reduction
    Lovastatin/Mevacor– 40 mg = 31% reduction
  • 39. Drugs that influence LDL-cholesterol
    Increase LDLs: Progestins, androgens, cyclosporines, tacrolimus, thiazide diuretics, setraline, atypical antipsychotics
    Decrease LDLs: estrogens/estradiol
  • 40. VLDL (very low density lipoproteins)--triglycerides
    Dietary causes? Copious amounts of refined sugars, high fructose corn oil, and alcohol (?)
    Ideal is less than 150 mg/dL (1.70 mmol/L)
    Borderline high is 150-199 (1.70-2.25 mmol/L)
    TG are a major risk factor for peripheral neuropathy in the diabetic
    TG and fatty liver disease
  • 41. Drugs? Fish oil for TG reduction?
    Niacin/Niaspan (see slides at the end of handout for titrating Niacin)
    Gemfibrozil (Lopid)
    How much fish oil?
    For fish oil? READ the label –1000 mg of combined EPA and DHA per day for maintenance; cardiologist may prescribe more
  • 42. Lovaza—prescription omega-3s
    Or the cardiologist may prescribe a form of fish oil which provides ALL YOU NEED in one pill
    LOVAZA (old name, Omacor); used for very high triglyceride levels; 4 g/day is the dose
  • 43. Pharmacological management of hypertriglyceridemia
    Triglyceride levels greater than 1000-1500 mg/dL (11.3 to 16.9 mmol) require treatment with fibrates to reduce the risk of acute pancreatitis
    “fibrates”--(TriCor, Lipofen, Triglide, and Lipidil in U.S. and Bezalip in Canada)
    Lifestyle modifications—weight loss results in a mild-to-moderate decrease (about 22%) and an increase in HDL (about 9%), largely because of an increase in HDL2, about 43%)
    The level of small, dense LDL particles may decrease by as much as 40%
  • 44. Drugs that increase triglycerides
    Androgens, testosterone
    Sertraline (Zoloft) possibly
    Protease inhibitors
    Valproic acid
    (progestins decrease TGs)
    5 types of mature WBC’s and one immature WBC circulate in the “cold, cruel world” known as peripheral blood
    Normal range 5,000 to 10,000 (3500-12000)
  • 46. The differential…
    Neutrophils (polys, PMN, segs)(57-63%) of the total white count; acute inflammation, acute bacterial infections, acute necrosis (1.51-7.07)
    Bands (0-4%) (0.00-.51)—precursor to the neutrophil
    Too many? Neutrophilia.
    Too few? Neutropenia (usually preceded by two words— “life threatening…”
    Lymphocytes (30%)-first responder to viruses; cells of the immune system (0.65-2.8)
  • 47. The differential, continued…
    Monocytes (4%)—macrophages in tissues; cells of chronic inflammation; antigen processing cell (APC) (0.00-0.51);
    Eosinophils (3%)—cells that respond to parasites and allergies (0.00-0.42) (Carlotta)
    Basophils (less than 1%)—who cares? Contain histamine (0.00-0.16) (basophilia—CML, PV)
    *all the cells with the last name “phil” are collectively called granulocytes—hence, the term agranulocytosis means a decrease of all three; but in clinical practice agranulocytosis means neutropenia
  • 48. Neutrophils
    Phagocytic functions-- their only job in the world is to EAT until they die
    Cell of acute inflammation
    First responder to bacterial invasion (strep, staph, E. Coli, H. flu, meningococcus, Pseudomonas, C. difficile)
    Loves acute necrotic tissue (gangrene, MI, appendicitis)
    Fastest dividing cell in adult bone marrow
  • 49. How do neutrophils grow up (the process of differentiation)?
    Stem cells
    Myeloblast (BM=bone marrow)
    Promyeloctye (BM)
    Myelocyte (BM)
    Metamyelocyte (juvenile) (BM)
    Band neutrophil (BM and PB=peripheral blood)
    Segmented neutrophil (BM and PB)
  • 50. Differentiation and the “shift to the left”
    During the time of acute need, the bone marrow is functioning overtime…massive production results in a partial loss of quality control concerning the immaturity of the cells that are released into the peripheral blood
    WBC and diff will show an increased number of neutrophils and bands and maybe even a metamyelocyte or two—
    shift toward immaturity— “more immature forms”
    Shift-to-the-left—increased number of bands
    What is the usual number of bands? 0-4%
    Bands and SIRS—the systemic inflammatory response syndrome—greater than 10% bands
  • 51. Clinical conditions with an increased WBC and “shift-to-the-left”
    Acute appendicitis
    Surgical site infection with MRSA
  • 52. The Absolute Neutrophil Count (ANC)
    Neutropenia is defined as an absolute neutrophil count (ANC) <500/mm3 or an ANC of <1,000/mm3 with an expected decline.
    Serious bacterial infectious risk increases directly with the following: (1) severity of neutropenia (ANC < 100 cells/mm3 imposes a greater risk than ANC < 500 cells/mm3), (2) rate of ANC decline (rapidly falling rate imposes a greater risk than chronic neutropenia or aplastic anemia), and (3) duration of neutropenia
    % segs + %bands x total WBC
    57% segs + 3% bands x 10,000 = 6,000
  • 53. Clinical cases…
    46 y.o. female receiving chemotherapy for breast cancer—total WBC is 2,000
    Is she neutropenic? Don’t know…Is she leukopenic? Yes
    Segs = 57%, bands = 3%; ANC is 60% of 2000 = 1200
    She is NOT neutropenic
  • 54. Clinical cases…
    52 y.o. female receiving chemotherapy for colon cancer—total WBC is 2,000
    Is she neutropenic? Don’t know…Is she leukopenic? Yes
    Segs = 37%, bands = 3%; ANC is 40% of 2000 = 800
    She isneutropenic
  • 55. Neupogen or Neulasta
    TO THE RESCUE: Filgrastim (G-CSF-- granulocyte colony stimulating factor), Neupogen, and pegfilgrastim (with polyethylene glycol ), Neulasta—stimulates neutrophil maturation and differentiation in the bone marrow to reduce febrile neutropenia in chemo patients—for non-myeloid malignancies
  • 56. Drugs and neutropenia
    Chemotherapy (all patients)
    Cimetidine (Tagamet), ranitidine (Zantac)
    Captopril (Capoten), enalapril (Vasotec), amiodarone, quinidine
    Zidovudine (Retrovir)
    Clozapine (Clozaril)
    Antibiotics including metronidazole (Flagyl),gentamicin, clindamycin, imipenem, PCNs, tetracyclines
    Azothiaprine (Imuran)
    PTU and methimazole
  • 57. Anti-convulsants that cause neutropenia
    Carbamazepine (Tegretol)—baseline, monthly for 2 or 3 months, then at least every-other-year
    Felbamate (Felbatol)—anticonvulsant; baseline, frequently during therapy, and for a significant time after discontinuation (dangerous drug, use only if nothing else works)—if it doesn’t cause neutropenia, it will kill your liver
    Phenytoin (Dilantin) can also cause neutropenia
  • 58. NEUTROPHILS…normal function
    Margination, pavementing, migration, engulfment, and degranulation
  • 59. Prednisone and the neutrophil
    Inhibits migration and degranulation, hence its anti-inflammatory properties
    Prednisone also increases blood sugar by stimulating glycogenolysis in the liver
    Hyperglycemia inhibits the function of neutrophils
    Diabetes– Blood glucose greater than 180 mg/dL (9.99 mmol/L) inhibits neutrophil migration (normal blood glucose is 74-110 mg/dL or 4.1-6.1 mmol/L)
    Elderly with decreased migration of neutrophils, increases infection susceptibility
    Fever increases the migration of neutrophils—is fever good for you? YES!
  • 60. STRESS!
    Stress and the WBC
    Screaming kids
    24-hours post-op
    Last trimester of pregnancy
    No bands
  • 61. Inflammation—lab tests
    C-reactive protein -- < 1 mg/dL or < 10 mg/L; the CRP is an acute phase reacting protein; rapid, marked increases occur with inflammation, infection, trauma, tissue necrosis, malignancies, and autoimmune diseases
    Increases quickly and dramatically in response to stimuli, and decrease substantially with resolution of the disorder
    May serve as a “marker” to determine how adequate the treatment regimen is—ex. Antibiotics for osteomyelitis—follow the CRP to gage clinical response
    Not a “diagnostic” marker, but used as a “prognostic” marker
  • 62. High sensitivity or hs-CRP reflects low levels of inflammation in the vascular system and cardiac risk
    Patients with chronic vasculitis have an increased risk of cardiovascular events—lupus, rheumatoid arthritis
    Use of hs-CRP + lipid values together are more accurate at predicting risk than lipid studies alone
    Inflammatory mediators, IL-6 and TNF-α are produced within unstable plaques as well as from adipocytes in abdominal fat, which in turn increases hs-CRP production by the liver
    The bigger the waistline the greater the hs-CRP and the greater the risk for cardiovascular disease
    (Ridker PM et al. N Engl J of Med 2000; 342:836-43)
  • 63. In addition to losing the inches around the waistline, what else can reduce hs-CRP?
    Omega-3 fatty acids
    The Mediterranean diet is anti-inflammatory
    JUPITER STUDY (2008) and rosuvastatin (Crestor) and most likely all statins (Ridker)
    Pioglitazone (Actos)
    Aspirin and potentially other anti-inflammatory drugs
  • 64. Monocyte/Macrophage
    Monocyte in blood, macrophage in tissue (Kupffer cell in liver, microglial cell in brain, histiocyte in connective tissue)
    Phagocytes that respond much slower than the seg (2-4 days vs. 5-10 minutes for the seg)
    Eats for months
    Cell of chronic inflammation
  • 65. The macrophage—the link between inflammation and immunity
    The macrophage is the antigen processing and presenting cell (APC)
    It engulfs the pathogen
    Chews it up
    Processes it and presents it to the helper T cell (T4 cell) of the immune system
    VITAL link in the functioning of the immune system
  • 66. Gulp, chew, process, spit, kick…
    T4 cell
    IL-1 release
    B s, Ts
    With CD4 receptor
    T4 or helper T cell
  • 67. How do drugs influence this immune response
    Prednisone inhibits IL-1 (interleukin-1) release—immunosuppressive
    Methotrexate induces lymphocyte apoptosis
    Hydroxychloroquine (Plaquenil)—inhibits antigen processing by changing the pH of the macrophage
    Cyclosporine inhibits IL-2—used to reduce tissue transplant rejection
    Etanercept (Enbrel) binds with excess TNF-a molecules—anti-inflammatory
    Azathioprine (Imuran)—blocks proliferation of lymphocytes
  • 68. Monoclonal antibodies (the “li” group)
    Adalimumab (Humira), infliximab (Remicade), golimumab (Simponi), and certolizumabpegol (Cimzia) block TNF-a
    Daclizumab (Zenapax)—blocks IL-2 on activated T cells to prevent organ transplant rejection
    Basiliximab (Simulect)—prevent organ transplant rejection via same mechanism as daclizumab
  • 69. What else does IL-1 do?
    Increases temperature set point by increasing the production and release of prostaglandins in the hypothalamus
    Acetaminophen and aspirin work in the hypothalamus to inhibit prostaglandin production (central inhibition)
  • 70. IL-1 release…
    Increases serotonin release from brainstem—vomiting
    Increases serotonin release from the duodenum—nausea
    Duodenum—the organ of nausea
    You are sick to your duodenum
    “setrons” block serotonin release from the brainstem and duodenum
    Granisetron, (Kytril), ondansetron (Zofran), doasetron (Anzamet)
  • 71. IL-1 release…
    Increases melatonin production and makes you sleepy
  • 72. IL-1 release…
    Lowers pain threshold—everything hurts
    Your hair hurts
    Your teeth hurt
    Your skin hurts
    Your tummy hurts
    You’re miserable…
  • 73. Amphoterrible B/Amphotericin B for systemic fungal infections
    Triggers release of IL-1 from macrophages
    MISERY with fever, chills, rigors, nausea, vomiting, and nephrotoxicity
    Newer liposomal preparations of amphotericin (AmBisome, Abelcet, and Amphotec) are associated with fewer side effects
  • 74. Other WBCs and drugs
    Eosinophilia – elevated eosinophils usually means allergies or parasites
    Certain drugs can also elevate eosinophils as a part of an allergic phenomenon to the drug; drug allergies can also trigger a fever and rash
  • 75. RBC’s-- drugs and anemia
    Barb Bancroft, RN, MSN, PNP
  • 76. What do you need to make happy, healthy red blood cells?
    One is good parents (genes and hemoglobinopathies), and you can’t do anything about that
    Hemoglobin electrophoresis
    What else do you need?
  • 77. Healthy Kidneys…
    Erythropoietin production and hypoxia
    Renal failure and anemia (one of the first signs of early renal failure is mild anemia)
    No kidneys? No problem…synthetic erythropoietin is available
    Erythropoiesis-stimulating agents (ESAs)—the “poietins”
    Epoetinalfa (Epogen) in 1989
    Darbepoetin (Aranesp) in 2000
  • 78. Erythropoiesis stimulating agents—ESAs
    Epoetin-alfa (Procrit) and darbopoietin (Aranesp)—target to low side of the hemoglobin range; higher range = more deaths, hospitalizations, HF, stroke in non-dialysis kidney failure pts. (Dharmaraja TS)
    To minimize risks, use the lowest dose to maintain Hb between 10-12 g/dL
  • 79. Healthy thyroid--Hypothyroidism…low metabolic rate
    Decreased metabolism decreases the production of red blood cells
    Ladies, get those thyroid glands checked! 10:1 female to male ratio
    Starting testing at age 35-45…
  • 80. Drugs and the thyroid
    Amiodarone—mixed bag--check TSH at baseline and every six months; may cause hyperthyroidism (10%) OR hypothyroidism (22%)
    Oxcarbazepine (Trileptal): consider evaluation of thyroid hormone status (frequency not specified)—may decrease total and/or free T4 (thyroxine) levels
    Lithium—TSH and T4 at baseline and yearly; Lithium can cause hypothyroidism
    Check TSH if the patient is on a statin and muscle aches and pains occur (hypothyroidism predisposes to myopathy)
  • 81. Iron
    FACT: you need iron produce RBCs
    You need iron to grow vertically, not…
  • 82. You need iron to grow a baby…
    And you need LOTS of it!
  • 83. Fact: You lose iron when you bleed
    Women have 20% less blood than men and premenopausal women lose blood once a month; hence, lower iron stores
    Cooking with an iron skillet?
  • 84. Geriatrics and iron
    Elderly and iron absorption
    Decreased acid in stomach decreases iron absorption; PPIs for GERD?
    If iron supplements are necessary, use vitamin C with supplements to help absorb the iron
    Use calcium citrate in low acid situations, not calcium carbonate
    PMF—??iron supplements?
    Not unless you’re symptomatic with iron deficiency
  • 85. Iron storage
    Serum ferritin
    adults –M = 20-250 ng/mL or mcg/L
    F = 10-120 ng/mL or mcg/L
    Iron overload with >400 ng/mL in M and >200 ng/mL in females; consider hemochromatosis
    Iron deficiency with levels < 10 ng/mL (mcg/L)
  • 86. Treating iron deficiency anemia
    Feosol Carbonyl Iron tablets or Feosol Ferrous Sulfate Tablets
    Hemoglobin concentration usually increases by 1.0 g/dL weekly; continue treatment until anemia is corrected and the serum ferritin concentration is greater than 50 ng/mL.Microcytosis, if present, typically resolves several months after iron stores are replete. Completion of therapy in patients without continuing blood loss typically requires several months
    Oral iron therapy often fails in patients who take antacids, H2 Blockers, PPIs, or calcium supplements
  • 87. B12 …
    2,000 to 5,000 mcg of B12 is stored in the liver for 5-7 years;
    Use about 1 mcg per day for making RBCs, keeping the myelin in our central and peripheral nervous system healthy, and making serotonin in our “happy” centers
    Takes 5-7 years of no B12 intake to deplete
  • 88. High-risk patients for B12 deficiency
    Over 55
    Lack of intrinsic factor (IF); autoimmune gastritis; gastrectomy patients
    No animal protein in the diet; vegetarians; Tea and Toasters; alcoholics
    Liver failure
    Malabsorption—Crohn’sdisease, celiac disease; gastric by-pass surgery
    Metformin (glucophage);
    Proton Pump Inhibitors—inhibit the pump that pumps HCL acid AND Intrinsic factor; Intrinsic factor binds B12 and takes it to the ileum for absorption
    (Am J CliniNutr (2007);86:1384)
  • 89. The “prazoles”—Proton Pump Inhibitors
    MOA—Inhibition of the proton pump at the lumenal surface of the stomach…especiallyafter a meal
    H+, Intrinsic Factor-B12
    PPIs work here
    Lumenal surface
    Parietal cell
    Basilar surface
    H2 receptors
    H2 blockers work here
  • 90. Clinical conditions associated with B12 deficiency
    Big, immature RBCs—called megaloblastic anemia
    Cognitive dysfunction—#1 cause of nutritional dementia
    Peripheral neuropathy (one of three top causes in elderly)
    Depression (B12 is a co-factor in the production of serotonin)
    So you have NO energy, you’re demented, can’t feel your feet and depressed…JEEZZZZ…how important is B12?
  • 91. B12 replacement
    How can we replace B12? 4 ways…how much?
    With B12 dementia—B12 injections 1000mcg every other day for 2 weeks, then once a week for 6 weeks, then monthly
    With peripheral neuropathy—B12 injections
    Oral, nasal, or sublingual B12 in all others—1000 micrograms/day
    4 S’s…shoot it, swallow it, snort it or suck it…
    Can you overdose on B12?
    No, the one dreaded side effect however is:
  • 92. You need Folic acid (B9) to make happy, healthy RBCs
    Dr. George Herbert
    40 days and 40 nights to deplete bone marrow stores
    Maintenance of healthy RBCs--anemia
    Maturation of the neural tube (first 28 days)--NTDs
    Take folic acid 400 mcg (0.4 mg) BEFORE you get pregnant + eat
    Green leafys and citrus fruits
  • 93. Drugs that block folic acid synthesis that are taken longer than 40 days and 40 nights…
    TMP/SFX (Bactrim, Septra)
    Rheumatrex (Methotrexate)
    Phenytoin (Dilantin)
    Oral contraceptives
    Supplement with folic acid
  • 94. How do RBCs grow up? The process of differentiation and maturation…
    Stem cell (BM)(bone marrow)
    Erythroblast (BM)(nucleated)
    Pronormoblast (BM) (nucleated)
    Normoblast (BM) (nucleated)
    Reticulocyte (BM and PB)(no nucleus)
    Erythrocyte (PB)
    (process takes 7-12 days)
  • 95. The reticulocyte count
    The reticulocyte count…0.5-1.5% of total RBC count; takes 7-12 days to make and release a “retic” from the bone marrow
    Is this patient “reticking”?
    In other words, is this patient actively making RBCs?
  • 96. Making retics, but destroying them
    High retic count…RBC’s are being destroyed in the peripheral blood (hemolysis) and the bone marrow is working overtime to produce more
    Hemolytic anemias
    27-year-old African American female with anemia
    RBC=3,000,000 (normal range = 4.5-6 million)
    Retic count 35% (normal range = 0.5-1.5%)
    What should you think about?
  • 97. Hemolytic anemias
    Hereditary--Sickle cell? Thalassemia? G6PD deficiency
    Autoimmune hemolytic anemia (lupus)
    Is she pregnant? HELLP syndrome (hemolysis, elevated liver enzymes, low platelets)
    Coomb’s test—what is it used for?
  • 98. Drug/medication exposure and anemias
    Penicillin, cephalosporin, procainamide, quinidine, quinine, sulfonamide—drug-induced hemolytic anemia
    Dapsone, naphthalene, and fava beans – oxidant-induced hemolysis (G6PD deficient patients)
    Cancer chemo (recent use) (bone marrow aplasia;hypoplasia, oxidant damage, fluid retention/dilutional anemia, megaloblastic anemia
  • 99. Underproduction anemia
    Low retic count
    Usually due to a deficiency of a nutrient
    Iron, B12, folic acid
    Cancer chemo (past use)(bone marrow hypoplasia), myelodysplasia, acute myeloid leukemia
    Chloramphenicol, gold salts, sulfonamides, anti-inflammatory drugs—bone marrow aplasia, hypoplasia
  • 100. Some numbers…
    Total RBC count—4.2-5.6 (M) million and 3.8-5.3 (F) million
    Hemoglobin adult females (11-15.5 g/dl) (110-155 g/L)
    males (13-17.3)(130-173 g/L
    females—39-50 (0.39-0.50)
    males—35-47 (0.35-0.47)
    What is anemia defined as?
  • 101. Anemia
    Anemia is defined by the WHO as a hemoglobin level less than 12 g/dL for women and less than 13 g/dL for men.
    Prevalence of anemia in the over 65 group is ~10.6%, and the prevalence increases with age to more than 20% in the over 85+ group
  • 102. RBC indices…(morphology)
    **MCV (mean cell volume) – 90 (83-97) fL;
    microcytic, normocytic, macrocytic
    MCH (mean cell hemoglobin) – 29 (27-31) pg (27-35); hypochromic, normochromic, polychromic
    MCHC (mean cell hemoglobin concentration)—34 (32-36) g/dL
    How do we define anemias? Based on morphology, the MCV is the most important test…
  • 103. Microcytic anemia
    RBC 3,000,000
    MCV 65 (normal 83-97)
    9/10 with iron deficiency anemia
    Where’s the bleed? Female? Male? Exercise? NSAIDS?
    Growing kid?
    Tea drinking?
    Two other causes of microcytic anemia—lead poisoning, Thalassemia
    You need to correct the iron deficiency in patients on erthropoiesis stimulating agents in order for the patient to benefit from using these drugs
  • 104. And don’t forget your occult fecal blood tests…every year
    Blood in the stool is a primary sign of colon cancer
  • 105. Macrocytic anemia
    RBC 3,000,000
    MCV greater than 100 fL
    MCV between 100 and 120—think booze
    MCV greater than 120—think B12 or Folic acid deficiency
    Who’s at risk?
  • 106. Gastrectomy patients
    Chronic atrophic gastritis
    Chronic malabsorption
    Competition for B12 (tapeworms)
    Strict vegetarianism
  • 107. Drugs that cause megaloblastic anemia
    Azathioprine (Imuran)
    Proton Pump inhibitors
  • 108. Normocytic anemia
    RBCs 3,000,000
    MCV normal
    The anemia of chronic disease—CKD, hypothyroidism, chronic inflammation (TB), cancer (unless a bleed is involved)
  • 109. Liver function tests, serum enzymes and drugs…
  • 110. Liver function tests (LFTs)
    Hepatocellular integrity (SGOT, SGPT)—also known as AST, ALT
    Hepatobiliary integrity--Bile formation and flow (bilirubin, GGT, alkaline phosphatase)
  • 111. Hepatocellular enzymes
    AST (SGOT) is NON-specific…in other words, it is found in many tissues and therefore not specific as a liver enzyme
    ALT (SGPT) is found almost exclusively in liver cells and is therefore highly specific for the liver
    If a “healthy” person demonstrates an elevated ALT, a thorough history is warranted with special questions such as hepatitis exposure, hepatotoxin exposure, and drugeffects
  • 112. Hepatocellularenzymes
    If enzymes are not terribly elevated (less than 2x normal—(some hepatologists say up to 3x normal), have the patient stop all drugs that are NOT necessary and recheck the enzyme levels in 2 weeks before doing a multi-million dollar work-up
  • 113. Hepatotoxin exposure and drug effects
    Chemicals (cleaning chemicals such as CCl4 ), vinyl chloride
    Occupational hazards—dry cleaners, painters, chemists
    Vitamin A toxicity
    Hundreds, if not thousands, of drugs can elevate liver enzymes and cause drug-induced-liver-injury
  • 114. Drug induced liver injury (DILI)—who’s at risk?
    Children are more prone to DILI w/ salicylates and valproic acid
    Obesity increases the risk of liver injury due to halothane and methotrexate (Rheumatrex dose pack, Trexall)
    Acetaminophen-induced liver injury is more likely in persons who are fasting or malnourished, as well as those who chronically abuse ETOH (more than 3 adult beverages per day)
  • 115. Acetaminophen overdose
    The minimum toxic single dose in healthy adults is between 7.5 and 10 grams and ≥ 150 mg/kg in children.
    Variability among patients re: toxic dose is most likely due to a genetic variation
  • 116. Drug-induced liver injury—who’s at risk?
    Women are more likely to experience DILI caused by diclofenac*, isoniazid, or nitrofurantoin, while azathioprine (Azasan, Imuran) is a more likely cause in men
    The incidence of liver injury varies among the NSAIDs and appears to be the most common with diclonfenac (1-5 cases per 100,000) and sulindac (Clinoril)
  • 117. What should be done?
    Discontinue the drug if all non-drug causes of liver injury have been investigated and ruled out
    What are the nondrug causes? Hepatitis A-E, biliary disease, biliary obstruction, alcohol abuse autoimmune hepatitis or cholangitis, bacterial infections that can mimic acute hepatitis (Camplobacter, Salmonella, andListeria) and Wilson’s disease.
  • 118. But what if it’s the only drug that works for that specific condition?
    Continue treatment with the drug if the ALT is less than 5x the ULN, as long as the patient remains asymptomatic and the serum bilirubin remains within normal limits (Scott)
  • 119. Positive criteria that implicates a drug
    Drug levels elevated
    Allergic manifestations (peripheral eosinophilia, rash, fever)—occur in about 23% of the patients
    Latency period of 1 month or less
    Rapid development of symptoms upon rechallenge (not that you would do this to prove your point…it would have to be an inadvertent challenge)
    Liver biopsy—with eosinophilic infiltration, granulomas
  • 120. Acetaminophen (Tylenol) and the liver
    Acetaminophen is in over 300 OTC products
    Drippy, coughy, hacky, sneezy, wheezy, headachy, achy, sleepy, ouchy products
    Prescription products—with the last name “cet”—Darvocet, Percocet
    Acetaminophen overdose is the most frequent cause of acute liver failure in the U.S. population, accounting for 39% of cases (Ostapowicz)
  • 121. AST/ALT ratio
    AST 8-20 U/L (0.43-1.28 μKat/L—adult males; 11-26 U/L (0.19-0.44 μKat/L—adult females)
    ALT 10-40 U/L (0.17-0.68 μKat/L—adult males; 7-35 U/L (0.12-0.60)
    The normal AST/ALT ratio should be 1
  • 122. If the AST/ALT ratio is greater than 1…
    Consider ETOH…
    AST is especially sensitive to alcohol
    If alcohol damages liver cells, the AST will increase higher than the ALT
    Ratio in alcohol- induced hepatitis is usually 3:1 to 8:1*
    Also consider any other cause of a fatty liver (see next slide for the causes of non-alcoholic fatty liver disease)
    *It is rare for the AST level to be more than 8 times the normal value in patients with alcohol abuse
  • 123. Causes of non-alcoholic fatty liver disease
    The above two have traditionally been the “only” causes of NAFLD, but there are more…
    Males greater than females
    Drugs—prednisone, MTX, synthetic estrogens, amiodarone (Cordarone, Pacerone), tamoxifen, nifedipine, and diltiazem
    Heavy exposure to organic solvents
    Long-term IV feeding
    Rare genetic diseases
  • 124. AST/ALT ratio of less than 1
    If less than 1 consider drugs other than those that cause fatty liver disease, viruses, autoimmune hepatitis, hemochromatosis, Wilson’s disease, alpha-1 antitrypsin deficiency
    Always check the TSH—may see mild increase in liverenzymes with hypothyroidism
    Eating lots of fast foods can also increase liver enzymes
  • 125. Extremely high levels of hepatocellular enzymes
    Marked elevation of ALT and AST is typical of severe acute viral hepatitis, toxic or drug-induced hepatic necrosis, and shock or ischemia to the liver
    The finding of extremely high levels (greater than 2000 to 3000 U/L) should always raise concern for acetaminophen OD, use of excessive therapeutic doses of acetaminophen by an alcoholic patient, or shock and/or ischemia to the liver
  • 126. Alkaline Phosphatase (ALP, or AP)
    35-105 U/L
    Think Biliary and Bone
    Any disturbance in the synthesis, secretion, or excretion of bile leads to the accumulation of bile acids in the liver increasing the synthesis of ALP
    Sensitive indicator of cholestasis—estrogen can cause cholestasis
    Infiltrative processes such as liver metastasis
  • 127. Alkaline Phosphatase (ALP, or AP)
    Alkaline phosphatase is produced in the osteoblasts to build bone
    Increased with growth spurts—1st year and adolescence
    Pagets disease—hypermetabolism of bone
    Osteogenic sarcoma
    Metastatic disease to bone (breast, prostate)
  • 128. Pancreatic enzymes
    Amylase 3 – 100 (U/L) and lipase 1.3 – 6 (U/L)
    Amylase also found in the parotid gland (mumps)
    With pancreatitis, amylase and lipase rise rapidly within 2 to 6 hours, reaching a maximum in 12 to 30 hours
    Serum lipase remains elevated for 8 to 14 days; serum amylase usually reaches baseline after 2 to 3 days; urinary amylase remains elevated for 8 days
  • 129. Pancreatic enzymes
    What are the 2 major causes of elevated pancreatic enzymes?
    Booze and gall stones cause 70% of cases
    Perforated peptic ulcer
    Ruptured ectopic pregnancy
    Mumps orchitis (why do they call them “orchids”?
  • 130. Drugs and acute pancreatitis (partial list)
    Sulfasalazine (Azulfidine) and other sulfas
    Furosemide, Thiazides
    Azathioprine (Imuran)
    Exanatide (Byetta)
    Chemotherapy—L- asparaginase
    HAART drugs
    Sulindac (Clinoril)
  • 131. CreatineKinase—Total CK—55-170 units/L (male); 30-135 units/L (female)
    Found in high-energy tissues including:
    Isoenzymes for specific tissues—1 (BB),2 (MB), 3 (MM)
    Skeletal muscle (98% CK-3, CK-MM; 2% is CK-MB)
    Cardiac muscle (40% CK-2, CK-MB; 60% CK-MM)
    Brain (CK-1, CK-BB) (also large intestine, CK-BB)
  • 132. Rhabdo “skeletal” myo “muscle” lysis
    Myopathy is defined as any muscle symptom—pain, tenderness, or weakness—accompanied by a creatinekinase concentration greater than ten times the ULN (also called myositis)
    Severe myopathy with muscle breakdown and myoglobin release into the circulation, which can cause brown discoloration of urine and risk of renal failure
    Rhabdomyolysis is usually diagnosed when the CK concentration is greater than 40 times the ULN or there is evidence of end organ damage (acute renal failure or worsened renal function)
  • 133. Rhabdomyolysis
    Statins get all of the press, but in reality over 150 drugs and toxins (including alcohol) have been known to cause rhabdomyolysis
    Who are the statin sisters? Lova/Mevacor, prava/Pravachol, simva/Zocor, fluva/Lescol, atorva/Lipitor, rosuva/Crestor, and pitavastatin (Livalo)
    cerivastatin/Baycol was removed from the market because she caused more cases of rhabdomyolysis than all of the other statins combined— ”ceriva” was associated with a 7-fold increase in myopathy compared to atrovastatin
  • 134. Rhabdomyolysis
    Patients on statins who are at highest risk? Concomitant use of gemfibrozil (Lopid), over 80, hypothyroidism, renal impairment, higher doses)
    Overall risk of myopathy with monotherapystatin use is 4- 1 per 100,000 person-years of follow-up, with the risk of rhabdomyolysis about one-third of this (3 to 4 per 100,000 person-years)(Armitage)
    Renal failure develops in up to 50% (Naughton)
    Check renal function
  • 135. Amiodarone (Cordarone, Pacerone) and simvastatin (Zocor)
    High risk of rhabdomyolysis with the above combination
    Amiodarone inhibits CYP3A4 which increases concentrations of drugs metabolized by this enzyme—lova, simva, and to a lesser extent atorvastatin
    Don’t prescribe more than 20 mg of simvastatin or 40 mg of lovastatin per day with amiodarone
  • 136. Recommendations to Healthcare Professionals Regarding the Muscle and Statin Safety
    Whenever muscle symptoms or an increased CK level is encountered in a patient receiving statin therapy, health professionals should attempt to rule out other etiologies—increased physical activity, trauma, falls, accidents, seizure, shaking chills, hypothyroidism, infections, carbon monoxide poisoning, polymyositis, dermatomyositis, alcohol abuse, and drug abuse (cocaine, amphetamines, heroin, or PCP) (McKenney JM)
    Vitamin D deficiency causes muscle aches and pains
    ED drugs cause muscle aches and pains
    Exercise causes muscle aches and pains
  • 137. One last note on rhabdomyolysis
    Many drugs of abuse have been reported to cause rhabdo
    Cocaine, heroin, ketamine (Ketalar), methadone, and methamphetamine
    Drugs and alcohol are causative factors in up to 81 percent of the cases of rhabdomyolysis
  • 139. Gross anatomy
    Renal capsule
    Renal cortex (glomeruli)
    Renal medulla (tubules)
    renal papillae
    the renal interstitium (columns)
    renal pelvis (pyelo)/calyces
    Pyelonephritis vs. glomerulonephritis
  • 140. The kidney as an innocent bystander
    Drugs that cause tubular cell toxicity—ie. Acute tubular necrosis with drugs such as cisplatinin (Platinol), aminoglycosides, amphotericin B, antiretrovirals, contrast dye, foscarnet (Foscavir), and zoeldronate (Zometa)
    What’s the good news about acute tubular necrosis?
  • 141. The kidney as an innocent bystander
    Drugs can cause inflammatory changes in the glomerulus, renal tubular cells, and the surrounding interstitium, leading to fibrosis and renal scarring
    Glomerulonepthritis—ampicillin and penicillin, apresoline, interferon-alfa (Intron A), lithium, NSAIDs, PTU, pamidronate (Aredia),
  • 142. The kidney as an innocent bystander
    Acute interstitial nephritis—idiosyncratic non-dose-dependent—allopurinol (Zyloprim), beta lactam antibiotics, quinolones, rifampin, sulfonamides, and vancomycin, acyclovir (Zovirax) and indinavir (Crixivan), thiazide and loop diuretics, NSAIDs, phenytoin (Dilantin), PPIs (especially omeprazole, pantoprazole (Protonix) and lansoprazole (Prevacid) and ranitidine (Zantac)
  • 143. The kidney as an innocent bystander
    Chronic interstitial nephritis—acetaminophen, aspirin and NSAIDS when used in high doses for more than two years (greater than 1 gram per day)
    Cyclosporine, tacrolimus, Chinese herbals containing aristocholic acid, and lithium
  • 144. Serum creatinine
    Female: 0.5 – 1.1 mg/dl or 44-97 μmolL
    Male: 0.6 -1.2 mg/dl or 53-106 μmol/L
    Measures the amount of creatinine in the blood which is made via creatine (breakdown of muscle); excreted mainly by the kidneys and therefore is directly proportional to renal excretory function
    Metformin (glucophage)—contraindicated when serum creatinine is higher than 1.5 mg/dL in men and 1.4 mg dL in women
  • 145. Serum creatinine
    Trimethoprim-sulfamethoxazole and cimetidine can decrease the secretion of creatinine and falsely elevate serum creatinine
    Cefoxitin increases serum creatinine by interfering with the assay
    BUN does NOT change
  • 146. The kidney as an innocent bystander…
    Altered intraglomerular dynamics—intraglomerular pressure is maintained by the action of angitotensin II – mediated vasoconstriction of the efferent arteriole
    Renal perfusion depends on circulating prostaglandins to vasodilate the afferent arterioles
  • 147. Drugs and the kidney
    Drugs, such as cyclosporine (Neoral) or tacrolimus (Prograf) cause dose-dependent vasoconstriction of the afferent arterioles, leading to renal impairment in high-risk patients
    Drugs with anti-prostaglandin activity (NSAIDs) or those with anti-angiotensin-II activity (ACE inhibitors or ARBs) can interfere with the kidney’s ability to autoregulateglomerular pressure and decrease GFR
  • 148. “Angie” and the healthy kidney…
    Afferent arteriole
    (vasodilated via
    Blood entering
    Efferent arteriole
    (vasoconstricted via
    (angiotensin 2)
    Blood exiting
  • 149. Proteinuria—a manifestation of kidney disease
    Activation of the renin-angiotensin-aldosterone system exacerbates proteinuria
    Glomerular capillary hypertension leads to an increase in glomerular permeability and excessive protein filtration
    Although proteinuria is considered a marker of renal disease risk, it also contributes to kidney damage. Proteins present in the urine are toxic to the tubules and can result in tubulointerstitial inflammation and scarring (Brewster UC and Perazella MA)
  • 150. Drugs that block the renin-angiotensin-aldosterone system and reduce proteinuria
    Captopril (Capoten)
    Enalapril (Vasotec)
    Lisinopril (Prinivil, Zestril)
    Perindopril (Aceon)
    Moxepril (Univasc)
    Benazepril (Lotensin)
    Quinapril (Accupril)
    Trandolapril (Mavik)
    Ramipril (Altace)
    losartan (Cozaar),
    valsartan (Diovan), candesartan (Atacand), telmisartan (Micardis)
  • 151. The Diabetic Kidney…hyperglycemia/HTN (the deadly duo)
    Afferent arteriole
    (  vasodilation by
    (  prostaglandins)
    Blood entering
    Efferent arteriole
    (  vasoconstriction via
    (  angiotensin 2)
    Blood exiting
    Microalbuminuria (between 30 mg—300 mg of alb/g creatinine—10-fold > risk of RD & CKD)
  • 152. Why is microalbuminuria a “bad” thing?
    There is a 4-fold increase in acute coronary syndromes in Type 1 DM greater than 35 years old;
    When microalbuminuria is present the risk is increased by a factor of 140!
    The presence of albuminuria suggests that large vessel walls are more permeable to lipoproteins or damage from the local release of growth factors
    PRILS and SARTANS can decrease the decline in renal function by 50% or MORE in the diabetic kidney
  • 153. K+ levels and ACE inhibitors
    Use cautiously in patients with creatinine levels > 3 mg/dL, or potassium levels greater than 5.5 mEq/L (> 5.0 mEq/L in diabetics)
    Check K+ level no later than one week after starting spironolactone (low risk patients check at 7 days; moderate and high risk patients check at 4 and 10 days, after a dose increase or if diuretic doses are increased)
  • 154. K+ and serum creatinine
    Potassium levels?
    5-5.5 recheck in 7 days
    5.6 to 6.0 stop ACE and check in 7 days
    6.1-6.5 stop ACE and treat hyperkalemia; diet restriction; oral diuretics including loops or metolazone (the most K+ wasting); oral NaHCO3
    Greater than 6.5 stop ACE and check urgently (may need to head to the ER for ECG
    Greater than 8? Hospitalize; ECG changes with peaked T waves, prolonged PR interval, loss of P waves, widened QRS;
  • 155. Potassium potassiumpotassium
    K+ sparing diuretics and K+ supplements should be d/c’d unless there is continuing hypokalemia
    Diuretics should be withheld for 2-3 days before commencing therapy if possible, to reduce risk of first-dose hypotension
    NSAIDs should be avoided if possible during the initiation phase
    The effects of ACE inhibition on blood pressure are potentiated by restriction of salt intake
  • 156. Serum creatinine and ACE inhibitors
    Creatinine—a rise of greater than 20-30% is considered to be significant; smaller rises are common and are to be expected in many patients
  • 157. Spironolactone, eplerenone, and drospirenone and K+ levels
    Yasmin (drospirenone and ethinylestradiol) marketed to treat PCOS because of its progestin component (drospirenone) is an analog of spironolactone, an anti-androgenic agent for hirsutism
    can cause hyperkalemia
    Used in gals with PCOS who also might be on an ACE inhibitor because of the associated hypertension and type 2 diabetes with PCOS
  • 158. Last but not least, discontinue foods with high potassium…
    Banana (1m) 422 mg
    Potatoes (with skin) 540 mg
    French fries (1med) 924 mg
    Halibut (3 oz) 490 mg
    Spinach (1c) 839 mg
    Pasta sauce (1c) 940 mg
    Oranges 1 m 237 mg
    Prunes (elderly) 10 615 mg
  • 160. Whew. Finito. Thanks.
    Barb Bancroft, RN, MSN, PNP
  • 161. Bibliography
    Aronow WS. Hypercholesterolemia: The evidence supports the use of statins. Geriatrics 2003; 58 (8): 1832.
    Armitage J The safety of statins in clinical practice. The Lancet 2007;370:1781-90)
    Bakerman S. ABCs of Interpretive Laboratory Data 2002; Scottsdale, AZ
    Barron A, Falsetti D. Polycystic Ovary Syndrome in Adolescents. ADVANCE for Nurse Practitioners, 2008 (March);49-54.
    Brent GA. Grave’s Disease. N Engl J Med 2008; 358(24):2594-2605.
    Brewster UC, Perazella MA. The Renin-Angiotensin-Aldosterone System and the Kidney: Effects on Kidney Disease The Am J of Med 2004;116:263-72.
  • 162. Bibliography
    Charles EC, et al. Evaluation of cases of severe statin-related transaminitis with a large health maintenance organization. www.mdconsult.com (accessed 4/30/07)
    Dharmarajan TS and Widjaja D. Erythropoiesis-stimulating agents in anemia. Geriatrics, 2008 (June);63(6):13-18.
    Flora KD, Keeffe EB. Significance of mildly elevated liver tests on screening biochemistry profiles. J Insur Med 1990:22:206-210.
    Goldstein P. Assessment and Treatment of hypoglycemia in elders: cautions and recommendations. MEDSURG Nursing; July/August 2009; 18(4):215-224.
  • 163. Bibliography
    Gupta S, de Lemos JA. Use and misuse of cardiac troponins in clinical practice. Progress in cardiovascular diseases 2007 (September/October); 50(2):151-65
    Medical Letter. Acetaminophen Safety (2002); vol. 51(1316)
    McKenney JM, et al. Final conclusions and recommendations of the National Lipid Association Statin Safety Assessment Task Force. Am J Cardio. 2006;97(suppl):88C-94C)
    Naughton CA. Drug-Induced Nephrotoxicity. Am Fam Phys 2008;78(6):743-50.
    Ostapowicz G, et al. Results of a prospective study of acute liver failure at 17 tertiary care centers in the US. Ann Intern Med. 2002;137(12):947-954.
  • 164. Perez ME, Graham MG. Strategies for bridge anticoagulation therapy. Patient Care 2007 (October):7-14
    Ridker PM et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive . N Engl J Med 2008;359:2195-207.
    Williams Textbook of Endocrinology (11th ed. Philadelphia, Pa: WB Saunders;2007)
    Wu A. Tietz Clinical Guide to Laboratory Tests. Fourth edition. 2006. WB Saunders, Co
  • 165. Niacin titration schedule to minimize side effects
    Niaspan (niacin extended-release)
    weeks 1-4 500 mg @ hs
    weeks 5-8 1000 mg @ hs
    If needed: weeks 9-12 1500 mg @ hs (as two 750 mg tablets or three 500 mg tablets)
    weeks 13 and on: 2000 mg hs (as two 1000 mg tablets or four 500 mg tablets)
    Do not alternate between two 750 mg and three 500 mg tablets—not interchangeable)
  • 166. Niacin titration schedule
    Niacin immediate-release (IR)--Niacor (also called crystalline niacin and can be purchased OTC or by prescription)
    250 once daily following dinner. Increase dose every 4 to 7 days, divided two or three times daily, until the desired HDL and/or triglyceride goal is met, or a total daily dose of 1,500 mg to 2,000 mg, divided two or three times daily. After two months, may increase by 500 mg every two to four weeks to 1000 mg three times daily. Maximum total daily dose is 6000 mg (note: NCEP III lists maximum as 4500 mg)
    Prescribers Letter, 2010.
    P.S. tell patients to NOT use long-acting (Slo-Niacin) products or the “no-flush” Niacin—first one is toxic, second type is ineffective)
  • 167. Niacin Titration Schedule
    Niacin IR—maximum daily dose 4,500 mg
    Week 1: 100 mg w/ bkfst and dinner
    Increase by 100 mg/week to week 5
    Niacin IR—maximum daily dose 4,500 mg
    Week 1: 100 mg TID w/ food
    Week 2: 200 “
    Week 3: 250 mg TID w/ food
    Week 4: 500 mg TID w/ food
    Week 8: reassess lipids and if needed, increase to 750 mg TID with food
    Week 10: as above and increase to 1000 mg TID w/food.
  • 168. Drugs and platelet aggregation
    Heparin -- heparin-induced thrombocytopenia—type I and type II
    Patients with a hx of type II HIT should not receive either UFH or LMWH (Use direct thrombin inhibitors or fondaparinux (Arixtra)
    DTIs are structurally different from heparin and do not cross-react with HIT antibodies
    (Perez ME, Graham MG)
  • 169. Thyrotropin (TSH) 0.4 – 4.5. mIU/L; 0.6 – 4.5 μU/dL
    Primary hypothyroidism is usually the result of Hashimoto’s thyroiditis, thyroidectomy for hyperthyroidism, goiter or cancer, or radioactive iodine therapy for hyperthyroidism
    May take 2-3 weeks before the resolution of symptoms and but steady-state free T4 (FT4) concentrations (0.8-2 ng/dL)(12-21 pmol/L) and optimal TSH levels (0.4-4.5 mIU/L may not be achieved for 6-8 weeks)
    Treat to what level? The general rule of thumb is to maintain the level between 1.0 and 2.0-2.5 mU/L, but make sure you pay attention to the patient’s overall state of health (Williams)
  • 170. Check the thyroid!
    Thyroid replacement. The dose to initiate thyroid replacement should be the patient’s weight in kilograms (pounds divided by 2.2) x 1.6 = mcg dose. Then titer the dose to keep the patient’s TSH less than 3. If the patient says…“I am feeling fabulous…” check the TSH level and keep it at that level. Brilliant. (Michigan NP group discussion—2007, Lansing NP meeting)
  • 171. Monitoring patients on thyroid replacement
    TSH at baseline, every six to eight weeks until normal, then every six to 12 months
    TSH six weeks to three months (eight to 12 weeks per labeling) after change in dose or product
    Also check if clinically indicated, or if there is a change in patient health
    Patients over 50 years of age with cardiac disease: monitoring interval four to six weeks
    Adults less than 50 years of age with severe hypothyroidism: monitoring interval two to four weeks (Prescriber’s Letter, Detail Document #260704)
  • 172. Drugs that may decrease levothyroxine’s effect
    Amiodarone, antacids, colestyramine, calcium supplements, ciprofloxacin, iron, phenobarbital, phenytoin, raloxifene, rifampinritonavir, sertraline, sucralfate (Medical Letter August 2009)
  • 173. Drugs and hypoglycemia
    Secretagogues—sulfonylureas are associated with hypoglycemic events by enhancing insulin secretion from pancreatic beta cells; older the patient, the higher the risk
    In the U.S. glylburide (Micronase, Diabeta) has been associated with the highest number of serious hypoglycemic episodes (Goldstein P)
  • 174. Statin doses
    Instead of starting with the lowest doses, begin with a dose that drops the LDL-C by 30-40%
    30-40% reduction—Atorvastatin 10 mg-20 mg; simvastatin 40 mg; lovastatin 20 mg + ezetimibe 10 mg; pravastatin 20 mg + ezetimibe 10 mg
    40-50% reduction—Atorvastatin 20 mg-40 mg; simvastatin 80 mg; rosuvastatin 5 mg; simvastatin 10-20 + 10 mg ezetimibe; pravastatin or lovastatin 40 mg + 10 mg ezetimibe
    50-60% reduction—rosuvastatin 10-20; atorvastatin 80 mg; Atorvastatin 20 mg + ezetimibe 10 mg; simvastatin 40-80 mg + ezetimibe 10 mg
  • 175. Clopidogrel (Plavix)
    Inhibits ADP-induced platelet aggregation via the glycoprotein IIb IIIa complex
    Irreversible action
    Reduces CV events in established CVD patients—75 mg daily
    Give to patients with ACS (unstable angina and NSTEMI patients)—300 mg loading dose and then 75 mg daily with 75-325 mg of ASA
    ASA and Plavix for unstable angina or a new stent—combo for 9 months for unstable angina and 12 months after a stent (Lancet 2004:364:331)
    Adding aspirin to clopidogrel after stroke doesn’t improve endpoints but doubles the risk of life-threatening bleeding episodes (Lancet 2004; 364:331-337)
  • 176. Hyperthyroid drugs and the liver
    PTU causes severe allergy-mediated hepatic failure in 0.1 –0.2% of patients; about 30% will have transient elevations in AST/ALTs
    Liver failure has occurred in 1 in 2000 to 1 in 4000 children treated with PTU; no reports of liver failure with methimazole
    Methimazoleinfrequently causes liver dysfunction including cholestatic jaundice (elevated bilirubin, alkaline phosphatase, GGT)
  • 177. Thyroid drugs and neutropenia
    The thionamides—the antithyroid drugs, methimazole (thiamazole in some countries) and propylthiouracil (PTU) –
    Agranulocytosis (neutropenia) occurs in ~0.1 to 0.4% of patients, generally within the first 3 months of Rx. But, it can occur anytime
    More frequent in elderly and with re-introduction of the drug in a patient who previously used it uneventfully
    Dose-response with methimazole; doses over 30 mg daily have highest risk
    Not so with PTU—any dose can cause a reaction
    discontinue drug and have a WBC drawn if a fever or other evidence of infection develops (Brent GA and Med Letter 2009/August)
  • 178. Caution: Ayervedic medicines, heavy metals, and anemia + more
    A study in JAMA (August 2008;300:915) found that 21 percent of 193 traditional Indian Ayurvedic medicines bought on the Internet from U.S. or Indian sources contained high amounts of lead, mercury, or arsenic. One sample of a preparation called E Kangvir Ras had 26,000 parts per million of lead. This compares with a U.S. legal limit of 2 ppm in pharmaceutically produced calcium tablets for the elderly. A subset of preparations called Rasa Shastra are prepared with heavy metals such as mercury and arsenic.
  • 179. As an FYI…
    Patient with triglycerides above 250 mg/dL (2.81 mmol/L) and an HDL less than 40 mg/dL (1.04 mmol/L)—THINK either …
    1) Type 2 Diabetes (check the fasting blood sugar or Hemoglobin A1C), OR…
    2) Hypothyroidism (TSH) (0.4-4.5 μU/mL or mU/L) for 21-54 y.o.; 0.5-8.9 μU/mL or mU/L for 55-87);
    incidence is 10:1 female/male;
    **One in seven people with high cholesterol has underlying hypothyroidism; seventy percent of hypothyroid patients have high TC and TG