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INTERPRETATION OF LAB TESTS with a Pharmaceutical Focus

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    INTERPRETATION OF LAB TESTS with a Pharmaceutical Focus INTERPRETATION OF LAB TESTS with a Pharmaceutical Focus Presentation Transcript

    • INTERPRETATION OF LAB TESTS with a Pharmaceutical Focus
      Barb Bancroft, RN, MSN, PNP
      Chicago, IL
      www.barbbancroft.com
      BBancr9271@aol.com
      AUGUST 5, 2010
    • 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
    • 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)
    • 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)
    • 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)
    • Serum protein electrophoresis
      List the plasma proteins
      1) albumin
      2) globulins
      3) fibrinogen
      Is there a difference between plasma proteins and serum proteins?
    • 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
    • What conditions increase the risk of clotting?
      Venous catheters
      Heart failure/Atrial fibrillation
      Immobilization
      Trauma
      Surgery
      Pregnancy and postpartum
      Prolonged travel (economy class syndrome—air travel)
      Heparin-induced thrombocytopenia
      Estrogen therapy (?)
    • 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?
    • 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?
    • 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
    • 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)
    • Quantitative and qualitative platelet dysfunction
      Platelet counts and bleeding times—quantitative and qualitative measurements
      WHAT IS PLATELET TYPE BLEEDING?
      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
    • Platelet-type bleeding
      Acute DIC -- Severe thrombocytopenia due to meningococcemia
    • Platelet type bleeding –thrombocytopenia; chronic DIC
      Secondary to malignancy
    • The most common drugs that cause thrombocytopenia
      heparin
      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
    • 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
    • Glycoprotein IIb/IIIa receptor inhibitors
      Abciximab (ReoPro)
      Eptifibatide (Integrillin)
      Tirofiban (Aggrastat)
      gpIIb/IIIa is a molecule necessary for platelet aggregation
    • 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
    • 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
    • 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
    • Serum Proteins
      Albumin
      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
    • Serum Protein Electrophoresis—based on molecular weight and overall charge (positive or negative)
      + -
      Well in the gel
      Electrical current running through gel
    • Serum electrophoresis
      albumin
      globulins
      β
      α1
      α2
      Γ
    • 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%
    • 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
    • What else boosts HDLs?
      Exercise
    • What else boosts HDLs?
      Estrogen
      Premenopausal women have fabulously high HDLs—one of the major reasons the heart is protected prior to menopause
    • 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
    • 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…
      OR…
    • 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
    • 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
    • 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)
    • 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)
    • Risk factors for increased LDLs
      Diet high in trans and saturated fats
      Smoking
      High iron levels
      High insulin levels
      Couch potato
      Fat around the middle
    • LDL reduction
      Exercise? Eat right?
      Foods; fiber; almonds; plant stanols
      Reduce red meat, sat fats and trans fats
    • 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%
    • 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
    • Drugs that influence LDL-cholesterol
      Increase LDLs: Progestins, androgens, cyclosporines, tacrolimus, thiazide diuretics, setraline, atypical antipsychotics
      Decrease LDLs: estrogens/estradiol
    • VLDL (very low density lipoproteins)--triglycerides
      Dietary causes? Copious amounts of refined sugars, high fructose corn oil, and alcohol (?)
      Genetics
      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
    • 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
    • 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
    • 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%
    • Drugs that increase triglycerides
      Alcohol
      Estrogens
      Androgens, testosterone
      Glucocorticoids
      Cyclosporine
      Tacrolimus
      Thiazidediurectics
      Beta-blockers
      Sertraline (Zoloft) possibly
      Protease inhibitors
      Valproic acid
      Isotretinoin
      (progestins decrease TGs)
    • WBC and DIFFERENTIAL
      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)
    • 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)
    • 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
    • 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
    • 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)
    • 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
    • Clinical conditions with an increased WBC and “shift-to-the-left”
      GABHS
      Pyelonephritis
      Acute appendicitis
      Surgical site infection with MRSA
    • 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
    • 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
    • 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
    • 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
    • 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
    • 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
    • NEUTROPHILS…normal function
      Margination, pavementing, migration, engulfment, and degranulation
      Yum.
    • 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!
    • STRESS!
      Stress and the WBC
      Screaming kids
      24-hours post-op
      Last trimester of pregnancy
      No bands
    • 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
    • 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)
    • In addition to losing the inches around the waistline, what else can reduce hs-CRP?
      Exercise
      Omega-3 fatty acids
      Nuts
      The Mediterranean diet is anti-inflammatory
      DRUGS
      JUPITER STUDY (2008) and rosuvastatin (Crestor) and most likely all statins (Ridker)
      Pioglitazone (Actos)
      Aspirin and potentially other anti-inflammatory drugs
    • 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
    • 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
    • Gulp, chew, process, spit, kick…
      “ON”
      T4 cell
      IL-2
      IL-1 release
      B s, Ts
      WBCs
      TNF-a
      IFN-gamma
      CD4
      CD4
      macrophage
      With CD4 receptor
      T4 or helper T cell
    • 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
    • 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
    • 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)
    • 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)
    • IL-1 release…
      Increases melatonin production and makes you sleepy
    • IL-1 release…
      Lowers pain threshold—everything hurts
      Your hair hurts
      Your teeth hurt
      Your skin hurts
      Your tummy hurts
      You’re miserable…
    • 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
    • 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
    • RBC’s-- drugs and anemia
      Barb Bancroft, RN, MSN, PNP
      www.barbbancroft.com
      BBancr9271@aol.com
    • 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?
    • 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
    • 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
    • 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…
    • 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)
    • Iron
      FACT: you need iron produce RBCs
      You need iron to grow vertically, not…
    • You need iron to grow a baby…
      And you need LOTS of it!
    • 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
      GI/GU?
      Cooking with an iron skillet?
    • 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
    • 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)
    • 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
    • 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
    • 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)
    • 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
      H2 receptors
      H2 blockers work here
    • 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?
    • 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:
    • 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
    • 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
    • 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)
    • 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?
    • 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?
    • 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?
    • 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
    • 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
    • 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
      Hematocrit
      females—39-50 (0.39-0.50)
      males—35-47 (0.35-0.47)
      What is anemia defined as?
    • 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
    • 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…
    • 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
    • And don’t forget your occult fecal blood tests…every year
      Blood in the stool is a primary sign of colon cancer
    • 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?
    • Gastrectomy patients
      Chronic atrophic gastritis
      Chronic malabsorption
      Alcoholics
      Competition for B12 (tapeworms)
      Strict vegetarianism
    • Drugs that cause megaloblastic anemia
      Acyclovir
      ASA
      Anticonvulsants
      Azathioprine (Imuran)
      Colchicine
      INH
      Metformin
      MTX
      Neomycin
      Proton Pump inhibitors
    • Normocytic anemia
      RBCs 3,000,000
      MCV normal
      The anemia of chronic disease—CKD, hypothyroidism, chronic inflammation (TB), cancer (unless a bleed is involved)
    • Liver function tests, serum enzymes and drugs…
    • Liver function tests (LFTs)
      Hepatocellular integrity (SGOT, SGPT)—also known as AST, ALT
      Hepatobiliary integrity--Bile formation and flow (bilirubin, GGT, alkaline phosphatase)
    • 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
    • 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
    • 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
    • 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)
    • 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
    • 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)
    • 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.
    • 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)
    • 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
    • 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)
    • 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
    • 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
    • Causes of non-alcoholic fatty liver disease
      Obesity
      Diabetes
      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
    • 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
    • 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
    • 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
    • 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)
    • 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
    • Pancreatic enzymes
      What are the 2 major causes of elevated pancreatic enzymes?
      Booze and gall stones cause 70% of cases
      Perforated peptic ulcer
      Peritonitis
      Ruptured ectopic pregnancy
      Mumps orchitis (why do they call them “orchids”?
    • Drugs and acute pancreatitis (partial list)
      Sulfasalazine (Azulfidine) and other sulfas
      Furosemide, Thiazides
      Azathioprine (Imuran)
      Gliptans
      Exanatide (Byetta)
      Chemotherapy—L- asparaginase
      HAART drugs
      Sulindac (Clinoril)
      Acetaminophen
      Alphamethyldopa
      Cannibis
      Azothiaprine
      Benazapril
      Bezafibrate
      Cimetidine
      Clozapine
      Codeine
      Corticosteroids
    • 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)
    • 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)
    • 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
    • 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
    • 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
    • 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
    • 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
      (Naughton)
    • DRUGS AND THE KIDNEY
    • Gross anatomy
      Renal capsule
      Renal cortex (glomeruli)
      Renal medulla (tubules)
      renal papillae
      the renal interstitium (columns)
      renal pelvis (pyelo)/calyces
      Pyelonephritis vs. glomerulonephritis
    • 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?
    • 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),
    • 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)
    • 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
    • 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
    • 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
    • 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
    • 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
    • “Angie” and the healthy kidney…
      Afferent arteriole
      (vasodilated via
      (prostaglandins)
      Blood entering
      glomerulus
      Glomerulus->filter
      Efferent arteriole
      (vasoconstricted via
      (angiotensin 2)
      Blood exiting
      glomerulus
      PG
      filter
      AT2
      Toilet
    • 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)
    • 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)
      irbesartan—Avapro
      olmesartan—Benicar
      eprosartan--Teveten
    • The Diabetic Kidney…hyperglycemia/HTN (the deadly duo)
      Afferent arteriole
      (  vasodilation by
      (  prostaglandins)
      Blood entering
      glomerulus
      Glomerulus->filter
      Efferent arteriole
      (  vasoconstriction via
      (  angiotensin 2)
      Blood exiting
      glomerulus
      Microalbuminuria (between 30 mg—300 mg of alb/g creatinine—10-fold > risk of RD & CKD)
    • 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
    • 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)
    • 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;
    • 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
    • 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
    • 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
    • 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
    • YOU TRY TO PRY THOSE PRUNES OUT OF THAT ARTHRITIC DEATH GRIP!
    • Whew. Finito. Thanks.
      Barb Bancroft, RN, MSN, PNP
      www.barbbancroft.com
      BBancr9271@aol.com
    • 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.
    • 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.
    • 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.
    • 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
    • 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)
    • 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)
    • 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
      Or
      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.
    • 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)
    • 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)
    • 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)
    • 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)
    • Drugs that may decrease levothyroxine’s effect
      Amiodarone, antacids, colestyramine, calcium supplements, ciprofloxacin, iron, phenobarbital, phenytoin, raloxifene, rifampinritonavir, sertraline, sucralfate (Medical Letter August 2009)
    • 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)
    • 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
    • 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)
    • 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)
    • 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)
    • 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.
    • 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