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Common learning issues. MOSBY’S Cholesterol (166 – 170) Normal Findings: Adult: <200 mg/dL Child: 120-200 mg/dL Newborn: 53-135 mg/dL -Needed for production.

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Presentation on theme: "Common learning issues. MOSBY’S Cholesterol (166 – 170) Normal Findings: Adult: <200 mg/dL Child: 120-200 mg/dL Newborn: 53-135 mg/dL -Needed for production."— Presentation transcript:

1 Common learning issues


3 Cholesterol (166 – 170) Normal Findings: Adult: <200 mg/dL Child: 120-200 mg/dL Newborn: 53-135 mg/dL -Needed for production of steroids, sex hormones, bile acids, and cellular membranes -The main lipid associated with arteriosclerotic disease -Metabolized by the liver -75% bound inside LDL and 25% is in HDL - Main component of LDL (minimal in HDL and VLDL) - Testing is typically part of a lipid profile (by itself is not an accurate predictor of heart disease) - Individual cholesterol levels can vary daily by 15% -Positional changes affect levels (15% decrease seen in lateral recumbent position, often seen in hospitalized patients) -Repeat tests should be done for abnormal values and an average will be established -Used to predict risk of CHD within the Framingham Coronary Prediction algorithm (determines overall risk of ischemic event) Increased levels: liver disease, pregnancy, oorophorectomy, postmenopausal status, familial hyperlipidemias or hypercholesterolemias, hypothyroidism, uncontrolled diabetes mellitus, nephrotic syndrome, xanthomatosis, hypertension, atherosclerosis, biliary cirrhosis, stress Drugs that increase levels: adrenocorticotropic hormone, anabolic steroids, beta-adrenergic blocking agents, corticosteroids, cyclosporine, epinephrine, oral contraceptives, phenytoin, sulfonamides, thiazide diuretics, and vit D Decreased levels: liver disease, malabsorption, malnutrition, acute myocardial infarction (6-8 weeks following), advanced cancer, hyperthyroidism, cholesterol-lowering medication, pernicious anemia, hemolytic anemia, sepsis, stress, Drugs that decrease levels: allopurinol, androgens, bile salt-binding agents, captopril, chlorpropamide, clofibrate, colchicine, colestipol, erythromycin, isoniazid, liothyronine, MAO inhibitors, niacin, nitrates, and statins

4 C – Reactive Protein (197 – 199) Average: 1.0 - 3.0 mg/dL Normal <10 mg/L Low <1.0 mg/L High >10 mg/L -Nonspecific protein produced primarily by the liver during an acute inflammatory process and other diseases -Positive test result indicates the presence, but not the cause of disease -Synthesis is initiated by antigen-immune complexes, bacteria, fungi, and trauma -Used to diagnose bacterial infectious disease and inflammatory disorders, such as acute rheumatic fever and rheumatoid arthritis -Will disappear with recovery or use of anti-inflammatory agents, salicylates, or steroids -In an acute MI, CRP will peak 18-72 hours after CK-MB, and failure to normalize may indicate ongoing heart damage (levels will not be elevated in angina) -CRP levels may be a good predictor of cardiovascular events, especially in conjunction with a lipid profile -more sensitive and rapidly responding than ESR; would also normalize faster than ESR with recovery Increased levels: bacterial infection (UTI, TB, postoperative wound), risk of ischemic events, inflammatory reactions (acute rheumatic fever, Reiter syndrome, Crohn disease), collagen vascular disease (vasculitis, lupus erythrematosus), tissue infarction (acute MI, pulmonary infarction), cigarette smoking, estrogens, progesterones Decreased levels: moderate alcohol consumption, weight loss, increased activity or endurance exercise, fibrates, niacin, and statins

5 Erythrocyte Sedimentation Rate (234 – 236) Westergren Method Male: up to 15mm/hr Female: up to 20mm/hr Child: up to 10mm/hr Newborn: 0-2mm/hr - Measurement of the rate at which the RBCs settle in saline solution or plasma over a specified time -nonspecific (not diagnostic), -detects illnesses associated with acute and chronic infection, inflammation, advanced neoplasm, and tissue necrosis or infarction -the above illnesses increase the protein (mostly fibrinogen) content of plasma causing the RBCs to stack on one another and be weighted down in solution faster (increased ESR) -a fairly reliable indicator of the course of the disease and can be used to monitor disease therapy -can occasionally be useful in differentiating diseases (ex. pt with chest pain will have increased ESR for MI, but normal for angina) -Limitations: nonspecific, sometimes not elevated in active disease, many factors play into the results -ESR elevation may be late to appear in early disease (compared with other markers or indicators), but may also remain longer -Artificial results can occur if sample is allowed to stand for >3hrs Increased ESR: pregnancy, menstruation, B12 or iron deficient anemias, diseases associated with elevated proteins (macroglobulinemia), chronic renal failure, malignant diseases, bacterial infection, inflammatory diseases, necrotic diseases, Drugs that increase ESR: dextran, methyldopa, oral contraceptives, penicillamine, procainamide, theophylline, and vit A Decreased ESR: sickle cell anemia, spherocytosis, diseases associated with decreased proteins (hypofibrinogenemia), polycythemia (increased cells will inhibit sedimentation rate) Drugs that decrease ESR: aspirin, cortisone, and quinone

6 Lipoproteins (incomplete 356 – 360) Lipoproteins- accurate predictor of heart disease -Proteins in the blood whose main purpose is to transport cholesterol, triglycerides, and other insoluble fats -Used as markers to indicate the levels of lipids

7 Serum Osmolality (391 – 392) Adult: 285-295 mOsm/kg H2O Child: 275-290 mOsm/kg H2O Critical Value: 320 mOsm/kg H2O -Test used to learn about fluid status and electrolyte imbalance -Measure the concentration of dissolved particles in blood -Increased water and/or decreased particles will cause decreased osmolality -Decreased water and/or increased particles will cause increased osmolality -A high osmolality will stimulate ADH release to increase H2O reabsorption in the kidney (result in more concentrated urine and less concentrated serum) -Osmolol Gap: this represents the difference between what the osmolality should be based on calculations of serum sodium, glucose, and BUN (the 3 most important solutes in the blood) and what the osmolality actually is measured. -A large gap indicates that solutes such as organic acids (ketones), sugars, or ethanol by products are suspected to be present -Plays an important role in toxicology and workups for coma patients (grand mal seizures can occur between 400 -420 mOsm/ kg H2O) Increased levels: hypernatremia, hyperglycemia, hyperosmolar nonketotic hyperglycemia, ketosis, azotemia, dehydration, mannitol therapy, ingestion of ethanol, methanol, or ethylene glycol, uremia, diabetes insipidus, renal tubular necrosis, severe pyelonephritis Decreased levels: overhydration, SIADH, paraneoplastic syndromes associated with carcinoma Adult: 285-295 mOsm/kg H2O Child: 275-290 mOsm/kg H2O Critical Value: 320 mOsm/kg H2O

8 Plasma renin assay (463 – 467 ) Adult/Ederly: Upright position, sodium depleted (sodium restricted diet) Age 20-39 yrs: 2.9-24 ng/ mL/ hr >40 yrs: 2.9- 10.8 ng/mL/hr Upright position, sodium replaced (normal sodium diet) Age 20-39 yrs: 0.1-4.3 ng/mL/hr >40 yrs: 0.1-3 ng/mL/hr -Renin is an enzyme released by the kidney in response to hyperkalemia, sodium depletion, decreased renal blood perfusion, or hypovolemia -Renin is activated in the renin-angiotensin system to eventually produce angiotensin II (powerful vasoconstrictor that also stimulates aldosterone production) -Angiotensin and aldosterone increase the blood volume, blood pressure, and serum sodium -Renin is not actually measured; the test actually measures the rate of angiotensin I generation per unit time through a radioimmunoassay -a determination of the PRA and a measurement of the plasma aldosterone levels are used in the differential diagnoses of primary vs secondary hyperaldosteronism -Renal vein assays are performed to diagnose renovascular hypertension (HTN as a result of high renin from a diseased or hypoperfused kidney) - Renal vein assays will produce a renal vein renin level 1.4 times or greater than that of the unaffected kidney (levels of the same value or a smaller difference indicate the HTN is not of a renovascular cause) -Renin Stimulation Test: used to distinguish primary from secondary hyperaldosteronism PRA is obtained from the recumbent position of pt on a low salt diet PRA is then repeated with pt standing erect If renin levels increase, it is secondary hyperaldosteronism- decreased renal perfusion while standing will cause increase in renin production If levels remain the same, the cause is primary -Captopril Test: Pts with renovascular HTN will have greater drops in blood pressure and increases in PRA after administration of an ACE inhibitor than those with essential HTN (take baseline measurements, administer captopril, and reasses PRA at 60 mins) -Renin levels are higher in the morning and when taken from a patient in the upright position for 2 hrs prior (this should be when and how the sample is collected) due to the decrease in renal perfusion which stimulates renin production -Decreased levels are seen in the recumbent position Increased levels: pregnancy, reduced salt intake, essential HTN, Malignant HTN, Renovascular HTN, Chronic Renal failure, Salt-losing GI disease (vomiting or diarrhea), Addison disease, Renin- producing renal tumor, Bartter syndrome Cirrhosis, Hyperkalemia, Hemorrhage Drugs that increase levels: ACE inhibitors, antihypertensives, diuretics, estrogens, oral contraceptives, and vasodilators Decreased levels: Primary hyperaldosteronism, steroid therapy, congenital adrenal hyperplasia, ingestion of large amounts of licorice Drugs that decrease levels: beta blockers, clonidine, potassium, and reserpine

9 Blood Sodium (479 – 482) Blood Sodium Adult/Ederly: 136-145 mEq/L or 136-145 mmol/L Children, Infant, and Newborn: roughly 134-150 mmol/L Critical: 160 mEq/L -Major cation of the extracellular space (values as above; intracellular value of only 5 mEq/L) -Aldosterone causes conservation of sodium through reabsorption in the kidneys -Natriuretic hormone is stimulated by high sodium levels and decreases renal absorption -ADH controls the reasborption of sodium at the distal tubules of the kidney -the 1st symptom of hyponatremia is weakness and may then progress to confusion, lethargy, stupor, or even coma -Hypernatremia includes symptoms of dry mucous membranes, thirst, agitation, restlessness, hyperreflexia, mania, and convulsions -recent trauma, surgery, or shock may cause increased levels because renal blood flow is decreased Causes of Hypernatremia: increased sodium intake, decreased sodium loss (Cushing syndrome, Hyperaldosteronism), excessive free body water loss (excessive sweating, thermal burns, diabetes insipidus, osmotic diuresis) Drugs that may increase levels: anabolic steroids, antibiotics, carbenicillin, clonidine, corticosteroids, cough medicine, estrogens, laxatives, methyldopa, and oral contraceptives Cause of Hyponatremia: decreased sodium intake, increased sodium loss (Addison disease, diarrhea, vomiting, or nasogastric aspiration, intraluminal bowel loss, diuretic administration, chronic renal insufficiency), increased free body water (excessive oral or IV H2O intake, hyperglycemia, congestive heart failure, peripheral edema, ascites, intraluminal bowel loss, oversecretion of ADH) - Treatment of Hyponatremia: water restriction Drugs that may decrease levels: ACE inhibitors, captopril, carbamazapine, diuretics, haloperidol, heparin, NSAIDs, sodium free IV fluids, sulfonylureas, triamterene, tricyclic antidepressants, and vasopressin

10 Triglycerides (521 – 522) Adult: Male 40-160 mg/dL Female 35-135 mg/dL Critical: >400 mg/dL -Produced in the liver using fatty acids and glycerol -Transported by VLDL and LDL -When levels are high, triglycerides are deposited in fatty tissues -Constitute most of the fat of the body -Measured as part of a lipid profile Increased levels: ingestion of fatty meals, alcohol, pregnancy, glycogen storage disease, apoprotein CII deficiency, hyperlipidemias, hypothyroidism, high carb diet, nephrotic syndrome, chronic renal failure Drugs that may increase levels: cholestyramine, estrogens, and oral contraceptives Decreased levels: malabsorption, malnutrition, abetalipoproteinemia, hyperthyroidism Drugs that may decrease levels: ascorbic acid, asparaginase, clofibrate, colestipol, fibrates, and statins

11 Electroencephalography (573-577) -EEG is a graphic recording of the electrical activity of the brain -Performed to identify and evaluate patients with seizures, detection of pathologic conditions of the brain cortex (tumors, infarction), evaluate trauma or drug intoxication, and determination of brain death -In epileptic states the seizure activity is characterized by rapid, spiky waves on the graph -Can be used to monitor blood flow during surgery as an early detection of ischemia -Electrocorticography (ECoG) is a form of EEG in which the electrodes are placed directly on the exposed surface of the brain (this is the "gold standard" for defining epileptogenic zones) - A less invasive technique for localizing pathology or defining sites of epileptic activity is the magnetoencephalography (MEG) -MEG measures the magnetic fields produced by brain electrical activity using a sensitive device called a superconducting quantum interference device (SQID) -Sleep may need to be shortened the night before -16 or more electrodes are applied to the scalp with electrode paste in a specified pattern over both sides of the head, covering the prefrontal, frontal, temporal, parietal, and occipital areas -The procedure take 45 minutes to 2 hours -A sleep EEG can be performed after oral administration of a sedative or hypnotic Factors that may affect test results: hypoglycemia, caffeine, body and eye movements during the exam, lights, drugs (sedatives) Clinical Significance: Seizure disorders, Brain tumor, Brain abscess, Intracranial hemorrhage, Cerebral infarct, Cerebral death, Encephalitis, Narcolepsy, Metabolic encephalopathy

12 Evoked Potentials (589-593) Normal: No neural conduction delay -Indicated in patients with a suspected sensory deficit, but are unable to indicate or are unreliable in indicating recognition of a stimulus (such as infants, comatose pts, or those unable to communicate) -EP studies focus on changes and responses in brain waves that are evoked from stimulation of a sensory pathway -While the EEG measures spontaneous activity, the sensory EP study measures minute voltage changes produced in response to a specific stimulus, such as light pattern, an audible click, or a shock -EP studies measure and assess the entire sensory pathway from the peripheral sensory organ to the brain cortex -Clinical abnormalities are detected by an increase in latency, which is a delay between the stimulus and wave response -Visual-evoked response (VER)occurs in the occipital area and is usually stimulated by a strobe light flash, reversible checkerboard pattern, or retinal stimuli -90% of MS patients show abnormal latencies in VERs -Auditory brainstem evoked potentials (ABEPs) are typically stimulated by clicking sounds to evaluate the temporal lobe and central auditory pathways of the brainstem -One of the most successful applications of ABEPs has been screening low birth weight newborns for hearing disorders -Somatosensory evoked potentials (SERs) are initiated by sensory stimulus to an area of the body to evaluate patients with spinal cord injuries and to monitor spinal cord functioning during spinal surgery -A main benefit of EPs is their objectivity because voluntary patient response is not necessary Prolonged latency for VERs: Parkinson disease, demyelinating disease, optic nerve damage, ocular disease, blindness, optic tract disease, occipital lobe tumor, CVA, absence of binocularity, visual field defects Prolonged latency for ABEPs: demyelinating diseases, acoustic neuroma, CVA, auditory nerve damage, deafness Abnormal latency for SERs: spinal cord injury, cervical disk disease, spinal cord demyelinating disease, peripheral nerve injury, parietal cortical tumor

13 Lumbar Puncture and CSF Examination (682-690) Indications: Assist in diagnoses of primary or metastatic brain or spinal cord neoplasm, cerebral hemorrhage, meningitis, encephalitis, degenerative brain disease, autoimmune diseases of the CNS, neurosyphilis, and demyelinating disorders. Also used to measure the pressure of the subarachnoid space, to reduce intracranial pressure in those with normal pressure hydrocephalus with pseudotumor cerebri, or to inject therapeutic or diagnostic agents. Contraindications: Increased intracranial pressure (LP may induce cerebral or cerebellar herniation), degenerative vertebral joint disease, infection near LP site, anticoagulation drugs (may cause epidural hematoma) *If blockage in CSF circulation is suspected, a Queckenstedt-Stookey test is performed through occlusion of the jugular vein. Within 10 seconds, the CSF pressure should increase 15-40 cm H2O and then return to normal after release of pressure. A sluggish rise or fall of CSF pressure suggests partial blockage and no rise suggests a complete obstruction Pressure -Pressure is measured through the attachment of a sterile manometer to the LP needle at the beginning and end of the procedure (a significant difference btwn the two is could indicate a spinal cord obstruction such as a tumor or hydrocephalus) -A pressure of 20 cm H2O or greater is considered abnormal and indicative of increased intracranial pressure -Because the cranial venous sinuses are connected to the jugular veins, obstruction of the veins or of the superior vena cava will increase intracranial pressure -Decreased pressure is associated with hypovolemia, chronic leakage of CSF, or a nasal sinus fracture with a dura tear -If high opening pressures are noted, normal volumes of CSF should not be removed to prevent risk of cerebellar herniation Color -Normal is clear and colorless -Xanthochromia means an abnormal color (usually refers to a yellow tinge) -Color differences occur in hyperbilirubinemia, hyercarotenemia, melanoma, or elevated protein -Cloudy appearance may indicate increased WBCs or protein -Red tinge indicates blood (may be present from the LP needle) -Blood in the CSF will clot in a traumatic puncture, but not in a subarachnoid hemorrhage Cells -WBCs and RBCs should not be present in normal CSF (except for a few lymphocytes) -Polymorphonuclear leukocytes is indicative of bacterial meningitis or cerebral abscess -Mononuclear leukocytes indicate viral or tubercular meningitis or encephalitis -Leukemia or tumors may increase WBCs -WBCs may appear in the CSF due to a "traumatic tap", but more than 1 WBC per 500 RBCs is considered pathologic and may indicate meningitis -Pleocytosis is used to describe turbidity of CSF because of an increased number of cells in the fluid

14 Lumbar Puncture and CSF Examination (682-690) Culture -Organisms in the CSF can be cultured and identified -A gram stain can also be used, which allows appropriate antibiotic therapy before the results of the culture return -The most common cause of meningitis is Haemophilus influenzae in children and Neisseria and Steptococcus in adults Protein -Normally little protein is found in the CSF as the large molecules cannot cross the BBB -Proportion of albumin to globulin is higher than in blood plasma because of the small size of the albumin -Because albumin is not made in the CNS, increased levels of these proteins indicate increased permeability of the BBB -The permeability can be altered by infectious or inflammatory disease processes such as meningitis, encephalitis, or myelitis -CNS tumors may also produce and secrete protein -CSF protein electrophoresis is important is diagnoses -An increase in CSF immunoglobin G and the detection of oligoclonal gamma globulin bands are highly suggestive of inflammatory and autoimmune diseases, especially MS Glucose -Glucose levels are decreased when bacteria, inflammatory cells, or tumor cells are present -A blood sample is usually drawn prior to the spinal tap (compare CSF glucose to blood glucose. Significant if CSF lvls are 2/3 that of blood lvls) Chloride -Not normally tested in CSF, but can be requested -Levels can be decreased in patients with meningeal infections, tubercular meningitis, and conditions of low blood chloride -Increased levels are not neurologically significant; it correlates with blood levels Lactic Dehydrogenase -Elevated levels are associated with infection or inflammation -Source of LDH may be the neutrophils fighting the invading bacteria -Nerve tissue in the CNS is also high in LDH, meaning that diseases directly affecting the brain or spinal cord are correlated with high levels Lactic Acid -Elevated levels indicate anaerobic metabolism associated with decreased oxygenation of the brain -Lactic acid cannot cross the BBB, therefore the blood levels do not affect the CSF level -Levels are increased in bacterial and fungal meningitis, but not viral -Also elevated levels are seen in patients with mitochondrial diseases that affect the CNS

15 Lumbar Puncture and CSF Examination (682-690) Cytology -Examination of cells in the CSF can determine if they are malignant (Ex. tumor cells) Tumor Markers -Carcinoembryonic antigen, alphafetoprotein, or human chorionic gonadotropin may indicate metastatic tumor Serology of Syphilis -Latent syphilis is detected with serologic testing of the CSF including: The Wassermann test The Venereal Disease Research Laboratory (VDRL) The flourescent treponemal antibody (FTA) test- most sensitive and specific Glutamine -Made by increased levels of ammonia, which are commonly associated with liver failure -May detect and evaluate hepatic encephalopathy and hepatic coma -Also increased in patients with Reye syndrome C-Reactive Protein -nonspecific, acute-phase reactant used in the diagnosis of bacterial infections and inflammatory disorders -Failure to find elevated levels of CRP in CSF is strong evidence against bacterial meningitis -Valuable in distinguishing bacterial meningitis from viral or tuberculosis meningitis, febrile convulsions, and other CNS disorders Potential Complications -Persistant CSF leak -Introduction of bacteria into the CSF -Herniation of the brain -Inadvertent puncture of the spinal cord -Puncture of the aorta or vena cava -Transient back pain -Pain or paresthesia of the legs -Transient postural headache Patient is usually placed in the lateral decubitus (fetal) position

16 Sweat electrolytes (711-713) Children: sodium: 90) chloride: 60) -sensitive and specific test used to diagnose Cystic Fibrosis -does not measure the severity of the disease -test is indicated in children with recurrent respiratory tract infections, chronic cough, early onset asthma, malabsorption issues, late passage of meconuim stool, or failure to thrive -CF patients will have increased sodium and chloride contents in their sweat -Sweat, induced by electrical current (pilocarpine iontophoresis), is collected, and the sodium and chloride contents are measured -In normal individuals, sweat produced at the bottom of a sweat duct is rich in sodium and chloride, but as it moves through the duct, the chloride (followed by sodium) is transported through the lining cells out of the sweat. This leaves behind water. -In CF patients, the epithelial lining cells in the sweat ducts fail to take up the electrolytes, leaving a high sodium and chloride content -a small electrical current is felt during this test, but no pain or discomfort should be felt -the positive electrode is saturated with pilocarpine hydrochloride, a drug that induces sweating -the negative electrode is saturated with a bicarbonate solution -the electrical current flows for 5-12 mins -then paper disks with a paraffin airtight seal are placed over the test site to 1 hr -a screening test to detect chloride levels is done by pressing paper containing silver nitrate against the child's hand for several seconds. A positive test occurs when the child leaves a white powder, "heavy" handprint on the paper -dehydration may affect results Test MUST be done multiple times to be useful as a diagnostic tool

17 Urine Osmolality (980-981) Urine Osmolality 12-14 hr fluid restriction: >850 mOsm/ kg H2O Random specimen: 50-1200 mOsm/ kg H2O (depending on fluid intake) -This test is an accurate determination of the kidney's concentration capabilities -Also used to evaluate ADH abnormalities and fluid and electrolyte balance -Measures the number of dissolved particles in the urine -Most commonly measured by determining the freezing point -Osmolality is more accurate and measured over a wider range than specific gravity -More exact measurement of urine concentration than specific gravity, because specific gravity depends on the weight and density of particles, temperature, and requires correction for presence of glucose or protein -osmolality is more easily interpreted when the serum osmolality is simultaneously measured with a normal ratio of urine to serum osmolality of 1:3 Increased levels: SIADH, shock, hepatic cirrhosis, CHF, paraneoplastic syndromes associated with carcinoma Decreased levels: Diabetes insipidus, excess fluid intake, renal tubular necrosis, severe pyelonephritis,


19 DrugUsesSide effectsContraindicationsTherapeutic considerations Albuterol Pg 834 Class: Selective Beta2- adrenergic agonist Mech: agonist at beta adrenergic receptors on airway smooth muscle; act on G s to cause smooth muscle relaxation Indications: Asthma COPD Tachyarrhythmia Palpitations Restlessness Dizziness Headache Tremor hypersensitivity Cardiac effects lessened compared to non-selective adrenergic agonists Atorvastatin Pg 330 Class: Inhibitor of cholesterol synthesis (Statin) Mech: inhibits HMG-CoA reductase Indications: Hypercholesterolemia Familial hypercholesterolemia Coronary atherosclerosis Prophylaxis for coronary aterosclerosis Myopathy-increased risk Rhabdomyolysis Hepatotoxicity Abdominal pain (constipation, diarrhea, nausea) Headache Active liver disease Pregnancy and lactation Up to 60% dec. in LDL 10% HDL increase 40% Triglyceride dec. Drug of choice for lowering LDL, one of the most potent Metabolism by P450 3A4 Combo with bile acid sequestrant yields lower LDL Co-admin with Niacin-> inc. risk of myopathy Co-admin with gemfibrozil can induce rhabdomyolysis

20 DrugUsesSide effectsContraindicationsTherapeutic considerations Captopril Pg 349 Class: ACE inhibitor Mech: decreases conversion of AT I to AT II decreasing arteriolar vasoconstriction, aldosterone synth, renal proximal tubule NaCl reabsorp. and ADH release. Also inhibit degradation of the vasodilator, Bradykinin Indications: Hypertension Heart failure Diabetic Nephropathy Myocardial Infarction Angioedema (more frequent in black patients) Agranulocytosis Neutropenia Cough Edema Hypotension Rash Gynecomastia hyperkalemia History of angioedema Bilateral renal artery stenosis Renal failure pregnancy Given as active drug and processed to active metabolite Cough and angioedema caused by bradykinin action Hyperkalemia risk increased when used with potassium- sparing diuretics First-dose hypotension more common in patients with bilateral renal stenosis Furosemide Pg 351 Class: Loop diuretic Mech: reversibly and competitively inhibit Na+/K+/Cl- co-transporter in apical membrane of thick ascending limb Indication: Hypertension Acute pulmonary edema Edema from heart failure, hepatic cirrhosis, or renal dysfunction Hypercalcemia Hyperkalemia Hypotension Pancreatitis leukopenia Volume contraction alkalosis Hypokalemia Hyperuricemia Hypomagnesemia Hyperglycemia Glycouria Co-admin with aminoglycosides increases ototoxicity and nephrotoxictiy Sulfonamide derivative Front-line therapy for listed indications Can counteract hypercalcemic and hyperkalemic states

21 DrugUsesSide effectsContraindicationsTherapeutic considerations Nifedipine Pg 369 Class : Calcium channel blocker; Dihydropyridine Mech: block voltage-gated L-type Ca++ channels and prevent the influx of Ca++ that promotes actin-myosin cross-bridge formation Indication: Hypertension Exertional/unstable Angina Coronary spasm Hypertrophic cardiomyopathy Pre-eclampsia Increased angina Rare MI Palpitations Edema Flushing Constipation, heartburn Dizziness Preexisting hypotension Very fast onset can cause hypotensive episode with reflex tachycardia which causes worsening ischemia Arteriolar dilation greater than venous High vascular-to- cardiac selectivity Binds to “N” binding site of Ca++ channel Clonidine Pg 144 Class: alpha2 adrenergic agonist Mech: selectively activate central alpha2-adrenergic auto-receptors to inhibit sympathetic outflow from CNS Indication: Hypertension Opioid withdrawal Cancer pain Bradycardia Hypotension Heart failure Hepatotoxicity (side effects related to depressed sympathetics and increased vagal response) Not listed Used for HTN and symptoms of opioid withdrawal

22 DrugUsesSide effectsContraindicationsTherapeutic considerations Potassium Chloride Class: Supplement Indications: Treatment for Hypokalemia (stated by faculty as the only thing we needed to know about this drug for this unit) Not in our pharm book Cisplatin Pg 696 Class: Directly modify DNA structure Mech: Platinum compound that cross-links intrastrand guanine bases Indications: Genitourinary and lung cancer Nephrotoxicity Myelosuppression Peripheral neuropathy Ototoxicity Electrolyte imbalance Severe bone marrow depression Renal or hearing impairment Can be injected intraperitoneally for treatment of ovarian cancer Co-administration of amifostine can limit nephrotoxicity Etoposide aka VP-16 Pg 691 & 697 Class: Antineoplastic agent: Topoisomerase inhibitor Mech: bind topoisomerase II and DNA, trapping the complex in its cleavable state Indications: Lung cancer Testicular cancer Leukemia Heart failure Myelosuppression Alopecia (hair loss) Rash GI disturbance hypersensitivity Class breakdown: Antineoplastic-> topoisomerase inhibitors-> epipodophyllotoxin Action is specific to late S and G phases of cell cycle

23 DrugUsesSide effectsContraindicationsTherapeutic considerations Avonex Refib aka: Interferon Beta-1a Pg 903 Class: Protein used to augment an existing pathways (Group Ib) Mech: Unknown; Anti-viral and immune regulator Indication: Multiple Sclerosis Not listed Recombinant Interferon Beta Reduce frequency of relapses in MS Betaseron aka: Interferon beta-1b Pg 903 Class: Protein used to augment an existing pathways (Group Ib) Mech: Unknown; antiviral and immunoregulator Indications: Multiple Sclerosis Not listed Recombinant Interferon Beta Reduce frequency of relapses in MS Copaxone aka Glatiramer acetate Not in our pharm book Indications: Multiple Sclerosis Not in our pharm book Reduce frequency of relapses in MS injection

24 DrugUsesSide effectsContraindicationsTherapeutic considerations Dexamethasone Pg 503 Class: Glucocorticoid receptor agonist Mech: Mimic cortisol function by acting as agonists at glucocorticoid receptor Indications: Inflammatory conditions in many different organs Autoimmune diseases Immunosupression Cataracts Hyperglycemia Hypercortisolism Depression Euphoria Osteoporosis Growth retardation in kids Muscle atrophy Impaired wound healing Hypertension Fluid retention Inhaled may cause oropharyngeal candidiasis and dysphonia Topical causes skin atrophy Systemic fungal infection Doesn’t correct underlying etiology just limits inflammation Should be tapered when given chronically to avoid withdrawal and acute adrenal insufficiency Intranasal and inhaled greatly reduce systemic adverse effects 5-6x more potent than cortisol Prednisone Pg 503 Class: Glucocorticoid receptor agonist Mech: mimic cortisol function function by acting as agonists at glucocorticoid receptor Indications: Inflammatory conditions Autoimmune diseases Same as above Equally as potent as cortisol

25 DrugUsesSide effectsContraindicationsTherapeutic considerations Phenytoin aka: Dilantin Pg 236 Class: Sodium channel inhibitor Mech: inhibit electrical neurotransmission by use- dependent block of neuronal voltage-gated Na+ channel Indication: Focal and tonic-clonic seizures, status epilepticus, nonepileptic seizures Neuralgia Ventricular arrhythmias Ataxia Nystagmus Inncoordination Confusion Hirsutism Agranulocytosis Leukopenia Pancytopenia Megaloblastic anemia Hepatitis Stevens-Johnson syndrome Toxic epidermal necrolysis Hydantoin hypersensitivity Sinus bradycardia SA node block 2 nd or 3 rd degress AV block Stockes-Adams syndrome Interacts with many drugs due to P450 2C9/10 and P450 2C19 metabolism Phenytoin levels are increased by cimetidine, felbamate, isoniazid Phenytoin decreases levels of warfarin, carbamazepine, cyclosporine, levodopa, lamotrigine, doxycycline, oral contraceptives, methadone, and quinidine At high doses, phenytoin saturates the P450 system so that small dose changes cause large serum concentration changes Ciprofloxacin pg596 Class: Quinolones: inhibitor of topoisomerase Mech: inhibit bacterial type II topoisomerases; causing dissociate of Top II (DNA gyrase) from cleaved DNA, leading to double stranded breaksand cell death Indication: Gram (-) infections Common Upper Resp Infections UTI GI infections Cartilage damage Tendon rupture Periph. Neuropathy Increased Intracranial pressure Seizure Severe hypersensitivity reaction Rash GI disturbance (Nausea/ Vomiting, diarrhea) Co-admin with tizanidine Hypersensitivity Resistance: thru chromosonal mutations in genes that encode type II tops, or thru alterations in expression of membrane porins and efflux pumps that determine drug lvls in bacteria Bacteriostatic at low conc. Bactericidal at high conc.

26 DrugUsesSide effectsContraindicationsTherapeutic considerations Trimethoprim Pg 579 “Bactrim” = Trimethoprim /Sulfametho xazole Class: Antimicrobial dihydrofolate reductase inhibitor Mech: folate analogue; competitively binds microbial DHFR to prevent regeneration of tetrahydrofolate from dihydrofolate Indications: Urinary Tract Infection Stevens-Johnson syndrome Leukopenia Megaloblastic anemia Rash pruritus Megaloblastic anemia due to folate deficiency Used with medication below to limit resistance development Excreted unchanged into urine Sulfamethoxazol e Pg 579 “Bactrim” = Trimethoprim/ Sulfamethox azole Class: Antimircrobial dihydropteroate synthase inhibitor Mech: PABA analogue that competitively inhibit microbial dihydropteroate synthase and thereby prevent the synthesis of folic acid Indications: Pneumocystis carinii pneumonia Shigellosis Traveler’s diarrhea UTI Granuloma inguinale Acute otitis media Kernicterus in newborns Brain damage in newborns Crystalluria Stevens-Johnson syndrome Agranulocytosis Aplastic anemia Hepatic failure GI disturbance rash Infants less than 2 months old Pregnant women at term Breastfeeding Megaloblastic anemia due to folate deficiency Co-administration with PABA Used with medication above to limit resistance development Indications listed are those Sulfamethoxazole/Trim ethoprim used together Compete with bilirubin for binding sites on serum albumin and can cause kernicterus in newborns; can also cause brain damage

27 DrugUsesSide effectsContraindicationsTherapeutic considerations Vancomycin pg614 Class: Inhibitor of murein polymer synthesis Mech: Bind to D-Ala-D-Ala terminus of the murein monomer and inhibit PGT preventing addition of murein units to the growing chain Indication: MRSA (IV admin) Serious skin infections involving staph or strep (IV admin) C. Difficile enterocolitis(oral) Neutropenia Ototoxicity Nephrotoxicity Anaphylaxis “Red-man syndrome” (flushing and erythroderma) Drug fever Hypersensitivity rash Co-admin with Gentamycin Solutions containing dextrose in patients with known corn allergy Increased nephrotox with aminoglycosides “red-man syndrome” can be avoided by slowing infusion rate or preadministering antihistamines Resistance: arises thru acquisition of DNA encoding enzymes that catalyze formation of D-Ala-D-lactate Used for Gram (+) rods and cocci Gram(-) rods are resistant Methicillin Pg 615 Class: Penicillins: inhibitors of polymer cross-linking Mech: Beta-Lactams inhibit transpeptidase by forming a covalent (“dead-end”) acyl enzyme intermediate Indication: Skin and soft tissue infections or systemic infection with B- lactamase- producing methicillin-senstive S. aureus All side effects listed are for the other drugs in this class Hypersensitivity to penicillins Beta-lactamase resistant (staphlococcal) Narrow-spectrum antibacterial activity Gram (+) only Is a hydrophobic substance Penicillins have a 5- membered ring attached to the beta- lactam ring

28 DrugUsesSide effectsContraindicationsTherapeutic considerations Ceftriaxone Pg 616 Class: Cephalosporin: inhibitor of polymer cross- linking Mech: Beta-Lactams inhibit transpeptidase by forming a covalent (“dead-end”) acyl enzyme intermediate Indication: N. gonorrhoeae Borrelia burgdorferi H. Influenzae Most Enterobacteriaceae Lower resp infections Community-acquired meningitis Culture negative endocarditis Cholestatic hepatitis (rare) Pseudomembranous enterocolitis Leukopenia Thrombocytopenia Hepatotoxicity Nausea Vomiting Diarrhea rash Hypersensitivity to cephalosporins Rarely cross-react with penicillins Can give to patients with penicillin allergy unless their reaction was anaphylaxis 3 rd generatioin cephalosporin Highest CNS penetration of this class Resistant to many beta- lactamases Highly active against Enterobacteriaceae Less active against Gram (+) than are 1 st - generation cephalosporins Active against S. pneumonea Cephalosporins have a 6-membered ring attached to the beta- lactam ring


30 Marcus Gunn Pupil (pg 244) Cause: Afferent pupillary defect from damage to optic nerve. Observed during swinging light test. Light in unaffected eye: Both direct and consensual pupil dilation present. Light in affected eye: Partial dilation of both pupils. The afferent stimulus to the affected eye is reduced, thus the efferent signals to both pupils will also be reduced and a net dilation will occur, but less than that compared to the unaffected eye response.

31 Cranial Nerves (pg 659)

32 Air and Bone Conduction (pg 226-27) Tests used for distinguishing conductive from sensorineural hearing loss. NEED: Quiet room and tuning fork (preferably 512 Hz or possibly 1024 Hz; these fall within range of human speech). Weber Test: Tests for Lateralization Place base of lightly vibrating tuning fork firmly on top of pt’s head or on mid-forehead. Ask pt where they hear it; one side or both? Normal: Sound heard midline or equally in both ears. If nothing is heard, try again pressing the fork more firmly on head. Because pt’s with normal hearing may lateralize, this test should be restricted to those with hearing loss. Unilateral Conductive Hearing Loss: Sound is louder in impaired ear. Unilateral Sensorineural Hearing Loss: Sound is louder in good ear. Rinne Test: Comparing air conduction (AC) and bone conduction (BC). BC: Place base of lightly vibrating fork on Mastoid Process, behind the ear and lvl with the canal. AC: When the pt can no longer hear the sound, quickly place the fork close to the ear canal (U part of fork pointed toward ear) and ask if the sound can be heard again. Normal: Sound heard longer through air than bone (AC > BC) Conductive Hearing Loss: Sound through bone is as long or longer than air (BC = AC or BC > AC) Sensorineural Hearing Loss: Sound is heard longer through air (AC > BC). Yes, this is the same as a normal finding.

33 Mietzner guide to bacterial tests Directly from his powerpoint

34 Catalase Test Detects the presence of catalase, and enzyme the converts hydrogen peroxide to water and oxygen. The liberated oxygen causing bubbles. 4/16/2013 Differentiates -Streptococci (-) from Staphylococci (+) -Clostridia (-) from Bacillus (+)

35 Catalase Test 4/16/2013 Rod Gram Positive Cocci Staphylococcus Catalase Test Positive Negative Clostridia Negative Bacillus Streptococcus

36 COAGGULASE Test Detects the presence of coagulase. This enzyme acts with a plasma factor to convert fibrinogen to a fibrin clot Used to differentiate Staphylococcus aureus (pos) from Staphylococcus epidermidis (neg) 4/16/2013

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