Spring 2015 exam 1 OMSI CLIs

Mosby’s

AmmoniaElevated Values: cause encephalopathy and coma; values are usually taken from venous samples even though arterial values are more reliable• Supports Dx of severe liver dz (fulminant hepatitis, cirrhosis);

follow-up of hepatic encephalopathy• Byproduct of protein catabolism, made by gut bacteria• Under normal circumstances, goes through the Urea cycle in the liver

and on to be excreted in the kidneys-> cannot be catabolized in severe hepatocellular dysfx/portal htn

• Congenital defects in the urea cycle• Impaired renal function• Hemolysis (RBCs have 3 x the amount of ammonia as plasma)• GI bleeding• Muscular exertion, cigarette smoking, tourniquet

Decreased levels in essential/malignant htn and hyperornithinemia . We clinically only care about high levels.

Note: humans don’t have urease

Recognize that BUN is related to ammonia levels

Serum amylase p. 60-62 • Amylase is an enzyme produced in the pancreas and by the salivary glands that converts starches,

glycogens, and related polysaccharides into simple and easily digested sugar.

• The test is primarily used, in conjunction with a lipase test, to help diagnose and monitor acute pancreatitis and other pancreatic disorders.

Ordered frequently to:• Detect and monitor the clinical course of pancreatitis • When a patient presents with acute abdominal pain

• Test explanation• Sensitive but not most specific for pancreatitis

• Amylase is normally secreted from pancreatic acinar cells into pancreatic duct and into duodenum• Aids in the digestion of carbs

• Damage to acinar or obstruction of duct by carcinoma or gallstones causes outpouring into intrapancreatic lymph and free peritoneum

• Abnormal levels rise within 12 hours of the onset of the disease• It is rapidly excreted by kidneys• Persistence = pathology• Non-pancreatic diseases that can elevate:

• Can be elevated for bowel perforation, penetrating peptic ulcer, duodenal obstruction, salivary gland infection, ectopic pregnancies, severe diabetic ketoacidosis

• Patients with chronic pancreatic necrosis due to tumor or massive hemorrhage may cause low amylase levels

Serum amylase• Interfering factors

• Serum lipidemia factitiously decreases amylase• IV dextrose lowers amylase• Aminosalicylic acid, aspirin, azathioprine, corticosteroids, dexamethasone, ethyl alcohol, glucocorticoids, iodine

containing contrast medium, loop diuretics, methyldopa, narcotic analgesics, oral contraceptives, prednisone

• Increased levels• Acute pancreatitis, chronic relapsing pancreatitis, penetrating

peptic ulcer into the pancreas• GI disease• Acute cholecystitis• Parotiditis (mumps)• Ruptured ectopic pregnancy• Renal failure• Diabetic ketoacidosis• Pulmonary infarction• After endoscopic retrograde pancreatography

Antinuclear antibody (ANA) p. 90-92

• Used to diagnose systemic lupus erthematosus (SLE) and other autoimmune disease• Drug-induced SLE• Scleroderma• Rheumatoid Arthritis• Sjogren syndrome• Dermatomyotosis• Polyarteritis

• ANA is a group of protein antibodies that react against cellular nuclear material

• Normal findings negative at 1:40 dilution. • Used to rule out SLE, negative results probably not SLE.

Erythrocyte sedimentation rate (ESR) p. 234-235

• Non-specific test used to detect illnesses associated with acute and chronic infection, inflammation, advanced neoplasm, and tissue necrosis or infarction

• Routine test for patient with vague symptoms• ESR lags behind other indicators early in an infection. May stay elevated

longer in the convalescent stage of a disease or infection. • Especially helpful for inflammatory autoimmune disease• Measure rate at which RBC settle in saline solution or plasma per unity

time• RBC will settle faster with illness due to increased plasma proteins

(fibrogen)• Westergren Method• Male up to 15 mm/hr• Female up to 20 mm/hr• Child up to 10 mm/hr• New born 0-2 mm/hr

GGT p. 259-260• Sensitive to hepatobiliary disease, also an indicator of heavy and chronic

alcohol use• Test explanation

• Enzyme participates in the transfer of amino acids and peptides across the cell membrane

• Highest concentrations found in liver and biliary tract• Smaller concentrations found in kidney, spleen, heart, intestine, brain, and

prostate gland• Detect liver cell dysfunction highly accurate in indicating even slightest degree of

cholestasis• Detects biliary obstruction, cholangitis, or cholecystitis• Parallels elevation of ALP but more sensitive• Not increased in bone disease• Elevated in 75% of patients that chronically drink• Elevated with MI

• Interfering factors• May decrease late in pregnancy• Drugs that increase: alcohol, phenobarbitol, and phenytoin• Drugs that decrease: clofibrate and oral contraceptives

Gliadin antibodiesAnti-gliadin IgA/IgG; Anti-endomysium IgA; Anti-tissue transglutaminase IgA p. 263-265 • Endomysial IgA, gliadin IgA, tissue transglutaminase TG-ab• Diagnose celiac disease and sprue by identifying ab to gliadin

and gluten in affected patients• Crohn, colitis, and severe lactose intolerance may increase

levels• Test explanation

Gliadin and Gluten are found in wheat products. Patients cannot tolerate ingestion of gliadin and gluten which are

toxic to intestinal mucosa• Patients experience severe malabsorptive symptoms• Gliadin and gluten cause direct mucosal damage and Ig appear

in gut mucosa and in serum

Lactose tolerance test *assigned pages wrong

(332-334?)

• Used to diagnose lactose intolerance caused by lactase insufficiency, intestinal malabsorption, maldigestion, or bacterial overgrowth in small intestine. In enterogenous diarrhea (lactose broken down but not absorbed due to damaged gut)

• Test explanation:• Glucose plasma will not rise after the ingestion and the small bowel is

flooded with a high lactose load• Bacterial catabolism occurs in the intestine creates flatus and

hydrogen• Symptoms include flatulence, abdominal cramping, bloating, diarrhea,

and failure to thrive in infants• Lactose load is given and if lactase is absent then the serum glucose

will not rise• Given glucose tolerance test to isolate lack of lactase• Hydrogen Breath test in which expelled air is analyzed for hydrogen

content (goes up) for when bacteria are exposed to undigested food

ProteinIndications: monitor disease course w/ cancer (lymphoma, myeloma); intestinal/renal protein wasting states, immune disorders, liver dysfx, impaired nutrition, edema• Proteins are the most significant component contributing to

osmotic pressure in the vascular space, minimizing extravasation of fluid.

• Albumin makes up 60% of total protein; its major effect is to maintain colloid osmotic pressure and transports drugs, hormones, and enzymes

• Because albumin is synthesized in the liver, protein levels will be severely decreased in liver dysfunction-> but the ½ life of albumin is 12-18 days, so this may not be apparent immediately

Protein• Globulins are the building blocks of antibodies, and are not as important in maintaining

osmotic pressure• A1 globulin = a1 antytripsin*; • A2 globulins = haptoglobins, ceruloplasmin, prothrombin, and cholinesterse**; increased in

nephrotic syndrome and inflammatory conditions; decreased in hemolysis, Wilson’s dz, hyperthyroidism, and liver dysfx

• B1 globulins = lipoproteins, transferrin, plasminogen; increased in hypercholesterolemia and iron-deficiency anemia

• B2 globulins = fibrinogen• Gamma globulins = immune globulins; increased in multiple myeloma and Waldenstrom

macroglobulenemia, chronic inflammatory conditions, other malignancies (Hodgkin’s dz, lymphoma, leukemia, cirrhosis, infections); decreased in genetic conditions and immunodeficiencies

People w/ decreased proteins: malnourished, burn pts, protein losing enteropathies (nephrotic syndrome), pregnancy, inherited dzSelective lack of albumin: collagen vascular dz (albumin is a small molecule), chronic liver dz-> total protein may be normal, but the normal albumin > globolun ratio of >1 is offIncreased total proteins: multiple myeloma; factious elevations can happen in dehydration; inflammatory dz

Proteins• Electrophoresis separates various components of blood via electrical

charge• Normally patterns specific to immunoglobulins is polyclonal; a monoclonal

spike indicating overproduction of one immunoglobulin-: suspect allergy or a neoplasm like multiple myeloma

*See Table 2-41 for detailsUrine electrophoreses: detection of renal protein-losing nephopathies. BENCE JONES = MULTIPLE MYELOMA; pts have a monoclonal spike in Beta or Gamma globulin zoneLipoid nephrosis causes selective albumin leaks

While there are multiple methods of electrophoresis, the common one is immunoflication electrophoresis (IFE)• Monospecific antibody is placed in contact w/ the gel after protein

separation• Protein-antibody complexes are specifically stained for visualization;

the pts pattern is compared to references

Rheumatoid factor (RF) p. 471-472• Negative <60 units/mL• Used in the diagnosis of RA• RA: • morning stiffness for 6 weeks• pain in at least one joint• swelling in at least 1 joint• symmetric bilateral joint swelling,• presence of subcutaneous nodules• radiographic changes

• Abnormal IgG made in synovial joints, act as “antigens” • IgG and IgM along with Fc attack abnormal IgG• Immune complexes are activated and joint destruction begins

RF• Tests mainly for identification of IgM (Reactive IgM and

sometimes IgG and IgA make up Rheumatoid Factor)• Approximately 80% of pts with RA have positive RF titers• Must be found in greater than 1:80 dilution• SLE may also give false positive (dilution usually less than 1:80)• Other autoimmune dzs, tuberculosis, chronic hepatitis, infectious

mononucleosis and subacute bacterial endocarditis may give false reading

• Does not disappear in remission, ANA does• False negatives 20% of time, so negative test not used to rule

out RA.

Free Thyroxine Index p 512-513• Evaluate thyroid function• Corrects for changes in thyroid hormone binding serum proteins that can affect T4• Diagnose hypothyroidism and hyperthyroidism esp. in patients with abnormal thyroxin-binding

globulin or evaluation during pregnancy (TBGs go up).• Measures the amount of free thyroxine T4 which is only 1% unbound goes into cells and is activated • Not affected by thyroxin-binding globulin (TBG ) abnormalities so it correlates more closely to

hormonal status than total T4 and T3 • If TBG is increased, the T3 uptake decreases and corrects for the increased T4 association TBG

proteins.• If TBG is normal and T4 is elevated, FT4 will be elevated indicating true hyperthyroidism• Low FT4 indicates hypothyroidismIncreased levels:

• primary hyperthyroidism, • acute thyroiditis, • factitious hyperthyroidism, • struma ovarii (germ cell ovarian cancer producing thyroid hormone)

Decreased: • hypothyroidism,• pituitary insufficiency,• Hypothalamic failure• iodine insufficiency

Total Thyroxine p. 15-516• Diagnose thyroid function and to monitor replacement and suppressive therapy• Measures T4, both free and protein bound

• T4 is 90% of secreted hormone from thyroid. • Nearly all T3 and T4 are bound by serum proteins (eg TBG, albumin)• TRH (hypothalamus) -> TSH (Pituitary) -> Thyroid hormones

• TSH stimulates thyroid to secrete thyroid hormone • High levels of hormone inhibit TRH

• High levels indicate hyperthyroid, low is hypothyroid• TBG affects results (When T4 is bound it is not metabolically active, so

increased binding causes increased secretion of hormones, without metabolic abnormalities)

• Interfering factors:• increased after iodinated contrast x-ray, pregnancy causes increased levels, amphetamines, clofibrate, estrogens, heroin,

iodinated contrast media, iodine, methadone, and oral contraceptives increase• Decrease levels:

• anabolic steroids, androgens, anti-inflammatory drugs, antithyroid drugs, barbituates, furosemide, nonsteroidal lithium phenytoin, propranolol, propylthiouracil

Total Thyroxine

High:• Primary Hyperthyroidism• Acute thyroiditis,• Familial dysalbuminemic

hyperthyroxemia*• factitious hyperthyroidism,• Struma ovarii, • TBG increase *

*= difference from Free T4 test

Low:• Hypothyroidism• pituitary insufficiency• hypothalamic failure• protein malnutrition and

other protein depleted states*• iodine insufficiency• non-thyroid illness

Uric Acid, blood p. 536-537• Used to evaluate gout or recurrent urinary calculus (Kidney

stones).• Test explanation: • Uric acid is a waste product of purine catabolism, made primarily

by liver. • 75% of uric acid is excreted by the kidneys, 25% by intestinal tract• Uric acid is poorly soluble and with elevations (hyperuricemia)

crystals can from in kidney’s or ureters or synovium of joints (esp. distal lower extremity (Gout). Soft tissue deposition are called tophi.

• Causes of hyperurcemia can be overproduction (eg tumor lysis syndrome in chemotherapy, enzyme deficiencies) or decreased excretion (e.g. kidney failure). Many cases are idiopathic

• Hyperuricemia is defined as a plasma uric acid level greater than 6.8 mg/dL

Uric AcidIncreased• Increased production

• Increased ingestion of purines (foods such as liver, breads, kidney, anchovies)

• Genetic inborn error in purine metabolism• Metastatic cancer• Multiple myeloma• Leukemias• Cancer Chemotherapy• Hemolysis• Rhabdomyolysis

• Decreased excretion• Idiopathic• Chronic renal disease• Acidosis• Hypothyroidism• Alcoholism• Shock or chronic blood volume depletion

states

Decreased• Wilsons disease• Faconi syndrome• Lead poisoning• Yellow atrophy of the liver

Vitamin D• Used in the assessment of postmenopausal women to ensure they

have adequate levels to absorb dietary calcium• Fat Soluble Vitamin (A,D, E, K)• Vit D2= ergocalciferol*; vit D3= Ergocalciferol-> from sunlight• 7-dehydrocholesterol reacts w/ UVB light -> vit D3• Adequate levels of vit D3 can be achieved in 10-15 mins, 2+

times/week• Melanin is a light filter in the skin, so dark skinned people need

more time in the sun to get as much vit D• Vit D2/3 is converted in the liver to 25-hydroxyvitD, then in the

kidney to 1,25 dihydroxyvit D; it is then bound to proteins and circulates in the plasma

• Hormonally active form binds to the Vit D receptor in the nucleus, acting as a txn factor to increase the expression of genes like TRVP6 and calbindin, encouraging Ca2+ absorption in the intesting

Vitamin D• Vit D activation in intestine, bone, kidney and parathyroid gland is important

for Ca and phosphorous dietary absorption• Vit D inhibits PTH secretion• Enhances immune responses (phagocytosis etc)Deficiencies: • inadequate sunlight, malabsorption (Cystic fibrosis, etc), Liver/Kidney dysfx,

hereditary metabolic d/o-> leads to defective mineralization-> Rickets in kids and Osteomalacia in adults

Other deficiency problems• Vit D is also thought to be involved in apoptosis-vit D deficiency is observed in

cancers (colon, breast, pancreas)• +BP, cardiovascular risk• Immunity-> VDR expressed in monocytes, T/B cells

Optimal levels are 30 ng/Dl-> , higher requirements for darker skinned people and the elderly (7-dehydrocholesterol converting activity reversed in the elderly); breast milk does not have vit D; obese people have a harder time getting vit D into the blood stream

Vit D • Toxicity: nonspecific (vomiting, poor appetite, confusion,

rhythm abnormalities); associated w/ hypercalcemia• Increased risk of kidney stones

Drugs that decrease Vit D: steroids, orlistat, cholestyramineDrugs that increase Vit D: barbituates, phenytoin (inhibit hepatic metabolism)

Increased levels: Williams syndrome*, excessive dietary supplements, sarcoidosis Decreased levels: Rickets/Osteomalacia, Osteoporosis, Malapsorption, Renal dz, Liver Dz, X-linked hypophosphatemic rickets, Inflammatory dz, inadequate diet/sun

Electroencephalography• Indications: identify/evaluate pts with seizures; can detect other

conditions involving brain cortex; confirmatory test for brain death; evaluation of trauma

• Graphic recording of the electrical activity of the brain• Seizures: the focus is characterized by rapid, spiking waves• Cerebral lesions: abnormally slow EEG waves• Monitors electrophysiological effects of blood flow during surgical

procedures (example: carotid endarterectomy)• EcoG (electrocroticography): performed during craniotomy; electrodes

are placed directly on the brain to record activity from the cerebral cortex• Gold standard for defining epileptogenic zones before surgical procedures.

• MEG (Magnetoencephalography): noninvasive imaging, measures manetic fields produced by the brain using a SQUID (superconducting quantum interference device); help surgeons localize pathology/identify seizure loci and plan surgical procedures (aka avoiding critical areas)

Electroencephalography• Interfering factors: hypoglycemia, caffeine, body/eye movements, lights,

sedatives• Abnormal results (except when indicated, most of these show slowing of the

EEG): Seizures (increased activity), brain tumor, abscess, intracranial hemorrhage, infarct, brain death, encephalitis, narcolepsy (sleep waves seen during waking hours), metabolic encephalopathy

• Criteria for Brain Death (Box 3-4)• Absence of hypothermia (T> 32.2 C-you’re not dead until you’re warm and dead)• Absence of neuromuscular blockade administration• Ruled out drug/metabolic coma• No response to noxious/painful stimuliConfirmatory tests• Cerebral flow shows no flow to the brain• Isoelectric EEG (repeat in 6h)• No attempt at respiration w/ PCO2 >50 mmHg• Fixed pupils• Absent corneal reflex

Arthrocentesis p 673-674

• Normal findings: • Synovial fluid – clear and straw colored with few WBCs, no crystals, and

good mucin clot

• Indications: • Ddx joint infection, arthritis, crystal-induced arthritis (gout and

pseudogout), synovitis, or neoplasms involving the joint• Monitor chronic arthritic dzs, inject steroids • Can be performed on any major joint (examples: knee, shoulder,

hip, elbow, wrist or ankle)• Adding acetic acid to aspirated joint fluid, should clot• Poor clot quality in in presence of inflammatory disease.• If bleeding has occurred into the joint, it may clot spontaneously,

but this is abnormal.

Arthrocentesis p 673-674• Septic Arthritis:

• Resulting from either penetrating trauma or blood-borne infection (during bacteremia) • Joint is usually red, warm, swollen, and painful

• Reduced glucose, increased WBCs, increased Protein, Increased lactate. • Gram stain and culture

• Osteoarthritis:• Non gouty crystals or other degenerative changes can cause chronic and acute flare up.

• Synovitis:• Inflammatory or infectious

• Neoplasm:• Protein levels elevated, microcopy may reveal malignant cells

• Joint effusion:• Fluid in the joint, fluid analyzed to determine source of swelling

• Systemic lupus erythematous, Rheumatoid Arthritis:• Autoimmune or collagen-vascular dzs can be ass with immunogenic arthritis

• Reduced complement level, increased WBCs, increased protein

• Gout, pseudogout:• Cystral-induced arthritis with urate crystals or calcium pyrophosphate crystals are deposited into joint-

surrounding structures and joint surface cartilage. • Inflammation (up WBCs in synovial fluid)

• Trauma:• Joint effusion or bleeding into joint may occur

Quantitative fecal/stool fat p. 893-895• Confirm diagnosis of steatorrhea, when patient has large, greasy, and foul-smelling

stools• Total output of fecal fat per 24 hours in a 3-day stool collection provides the most

reliable measurements.• Abnormally high fat content confirms diagnosis• Fat retention coefficient is used in infants and children. Coefficient should be at least

95%.

Increases in fecal fat:• Cystic Fibrosis: • Children with CF have obstructed pancreatic ducts so they cannot be expelled into the

intestine • Any condition that causes malabsorption (sprue, Crohn, Whipple, gallstones,

tumor, duct obstructions)• Short gut: causes higher fecal fat• Enemas and laxatives may increase fat• Barium and fiber laxatives decrease • Increased: CF, malabsorption due to celiac, sprue, whipple, crohn or radiation

enteritis, short gut

Stool for occult blood p. 898-901• Screening for colorectal cancer• Test explanation

• Tumors of the intestine grow into the lumen and are subjected to repeat trauma by the fecal stream

• The friable neovascular tumor ulcerates and bleeds• Guaiac chemistry (most common) performed on the stool to detect blood

peroxidase-like activity of hgb, which catalyzes reaction of peroxide and a chromogen forming ortholidine, producing a blue color.

• OB can be detected by immunochemical methods called fecal immunochemical test (FIT) or immunochemical fecal occult blood test, these are not affected by red meats or plants like Guaiac, but may fail to recognize upper GI blood

• DNA stool sample test is twice as sensitive as guaiac for colorectal precancerous, benign or malignant tumors because some polyps don’t shed blood

• Benign, malignant GI tumors, ulcers, inflammatory bowel disease, arteriovenous malformations, diverticulosis, hematobilia all cause OB

• Also Hemorrhoids and swallowed blood result in OB

Stool hemoccult• Interfering factors

• Bleeding gums following dental procedure or disease• Animal hemoglobin of ingested animal meat• Peroxidase rich vegetables (turnips, horseradish, artichokes, mushrooms, radishes, broccoli, bean

sprouts, cauliflower, oranges, bananas, cantaloupes, grapes)• Anticoags, aspirin, colchicine, iron, nonsteroidal antiarthritics, and steroids• drugs that instigate peroxidation reaction Boric acid, bromides, colchicine, iodine, iron, rauwolfia• Vitamin C inhibits peroxidation reaction causing false negatives

• Results and significance: Can detect occult blood with as little as 5mL lost per day• GI tumor and polyps• Peptic disease (esophagitis, gastritis, and ulceration)• Varices (from portal hypertension)• IBD (Ulcerative colitis, Crohn disease)• Ischemic bowel disease• GI trauma or surgery• Hemorrhoids and other anorectal problems

Urine amylase p. 953-954• Normal value up to 5000 somogyi units• Used to assist in making the diagnosis of pancreatitis although other

nonpancreatic diseases can cause elevated urine amylase levels• Levels rise later than blood amylase levels• Several days after the onset of disease serum may be normal but

urine levels are significantly elevated, useful for detecting pancreatitis late in the disease course

• Test explanation:• Kidneys clear amylase, disorders that affect pancreas cause increased

amylase levels in urine• Serum levels rise transiently after resolution of acute phase of disease,

urine levels remain elevated 5-7 days after onset• Not specific for disorders: parotiditis, cholecystitis, perforated bowel,

peptic ulcer, ectopic pregnancy and renal disease• See Serum amylase for test result significance

Barium enemaDetect:• Malignant tumor – evident as filling defect “apple core” appearance.• Polyps – round filling defects, however stool can create same effect• Diverticula – outpouchings. Diverticulitis is inflammation of these defects in the wall and may show narrowing

• Inflammatory bowel disease - evident as narrowing of colon• Ulcerative colitis – may produce cobblestone-like patterns a result of inflammation surrounding the colon (do not

confuse with cobblestone appearance inside lumen seen in Crohn!). Loss of hustra. “Lead pipe appearance “.

• Crohn disease- areas devoid of contrast are classic finding. Rectum is usually involved in crohn, but spared in Ulcerative colitis. Fistulas may be evident. “String sign “ = tubular narrowing due to spasm or stricture.

• Colonic stenosis secondary to ischemia – “non-apple core” like narrowing • Perforated colon – leakage of contrast. Most common cause is cancer or diverticulitis (avoid use if perforation is

suspected)• Colonic fistula– leakage to another organ (example : urinary bladder)• Appendicitis- lack of filling, 30%-60% of normal appendixes do not fill. • Extrinsic compression of colon from extracolonic tumor or absecess – convexity• Malrotation of gut- congenital abnormality cecum usually in RLQ, appears in LUQ• Colon Volvulus – cut off of flow• Intussusception – flow of barium stops at the tip of the intussuceptum. • Hernia – seen inside gut lumen outside abdomen

• Do not use if there is a risk of perforation of the bowels.

Bone Densitometry p 1055-1057• Findings:

• Normal = <1 SD below normal• Osteopenia = 1.0-2.5 SD below normal• Osteoporosis = >2.5 SD below normal

• DEXA = Dual Emission X-ray Absorptiometry• Dual photons used in x-ray spectrum, can measure density of bones• [THIS WAS A BONUS QUESTION LAST YEAR]

• Important causes of reduced bone density• Postmenopausal women, esp. with early menopause• Hyperparathyroidism• Chronic renal insufficiency (vitamin D is activated in kidney and phosphate levels regulated)• GI malabsorption (Vit D is fat soluble, calcium not absorbed)• Anorexia• Certain cancers• Corticosteroid use longer than 3 months• Certain endocrinopathies (eg Cushing syndrome)• Chronic Heparin therapy• Chronic immobility

Drugs

Drug Uses Side effects Contraindications Therapeutic considerations

Alendronate Class: BisphosphonateMech: Decreases bone reabsorption by osteoclasts; blocks a step in the mevalonate pathway

Indications: • Osteoporosis

prevention and treatment

• Paget’s disease

• Jaw osteonecrosis in cancer patients

• Cessation of bone remodeling

• Gastroesophageal pain, ulceration

• Delayed gastric emptying

• Inability to sit up for 30 minutes after taking drug

• Hypocalcemia

Oral formulations require staying up right, to prevent esophageal reflux.

• Extended skeletal effects,

• unclear how to define overdose

• IV dose corrects hypercalcemia in days

• all secreted by kidney

Calcitonin (Salmon)

Mech: binds to and activates a G-protein coupled receptor on osteoclasts to decrease resorptive activityIndications:• Hypercalcemia• Paget’s disease• Postmenopausal

osteoporosis

• Flushing• Nausea• Diarrhea• Tachyphylaxis

• Hypersensitivity • Nasal spray or subcutaneous

• Subcutaneous lowers blood calcium over hours

Raloxifene Class: Selective estrogen receptor modulator (SERMs)Mech: Estrogen receptor agonist in bone, estrogen receptor antagonist against endometrium and breastIndication: • Osteoporosis prevention

and treatment

• Retinal vascular occlusion

• Venous thromboembolism

• Pulmonary embolism• Hot flashes• Leg cramps

• Pregnancy• History or presence of

venous thromboembolism

• Decreases breast cancer incidence

• (Currently used for Prevention; risk reduction of invasive breast cancer in postmenopausal women at high risk for invasive breast cancer . )

Drug Uses Side effects Contraindications Therapeutic considerations

Enalapril Class: ACE InhibitorsMech: Decreases conversion of angiotensin (AT) I to AT II, which decreases vasoconstriction of arterioles, aldosterone synthesis, renal proximal tubule NaCl reabsorption, and ADH release; also inhibits degradation of bradykinin, which increases vasodilationIndications:• Hypertension• heart failure• diabetic nephropathy• post - MI

• Angioedema (more frequent in black patients)

• Agranulocytosis• Neutropenia• Cough,• Edema• Hypotension• Rash• Gynecomastia• Hyperkalemia• Proteinuria

• History of angioedema

• Bilateral renal artery stenosis

• Renal failure• Pregnancy (Cat X)

Co-admin with allopurinol may predispose to hypersensitivity rxn including Steven Johnson syndrome

• Ester prodrug activated in plasma

• Bradykinin causes cough and edema; angioedema can be potentially life-threatening

• Delays progression of cardiac contractile dysfunction in HF and after MI; delay diabetic neuropathy (Mortality benefits = EVERYONE GETS IT unless contraindicated)

Amlodipine (Dihydropyridine)

Class: Calcium channel blockerMech: calcium channel blocker Indication:• Exertional angina• Unstable angina• Coronary spasm• Hypertension• Hypertrophic

cardiomyopathy• Pre-eclampsia

• Increased angina,• Rare MI• Palpitations• Peripheral edema• Flushing• Constipation• Heartburn• Dizziness

• Preexisting hypotension

• Arteriolar dilation greater than venous

• High vascular to cardiac selectivity (see Verapamil for comparison)

• Less depression of myocardial contractility, minimal effects on nodal conduction

• Higher bioavailability, longer time to peak plasma concentration, and slower hepatic metabolism

Drug Uses Side effects Contraindications Therapeutic considerations

Naproxen Propionic acid (NSAID) Mech: See Ibuprofin

mild to moderate pain, fever, osteoarthritis, RA, dysmenorrhea, gout

pseudoporphyria, See Ibuprofen • Longer half life,• 20x more potent

than ibuprofen, • causes fewer GI

adverse affects

Ketorolac(Brand = Toradol)

Acetic acid (NSAID)

Severe pain

See Ibuprofen

See Ibuprofen See Ibuprofen Analgesia in postsurgical patients, used for no more than 3-5 days

FeSO4 Iron supplement for anemia due to blood loss and iron insufficiency

Stomach upset or pain, constipation, diarrhea, nausea or vomiting

Diabetes, infants, may upset ulcers, not to be take with thalassemias, may irritate IBS

(Clinical pearl: May cause dark stools, of note clinically when someone has a suspected GI bleed. Stools will not have positive Occult blood test, if dark from only iron supplement)

Drug Uses Side effects Contraindications Therapeutic considerations

Donepezil Class: Acetylcholinesterase Inhibitor

Mech: Increases ACh by blocking breakdown in synapse

Mild to moderate Alzheimer’s/Dementia

Diarrhea, nausea, vomiting, cramps, anorexia, vivid dreams

= symptoms of hyperactive parasympathetics

Treatment associated liver function test abnormalities

Modest symptomatic benefitsACHe inhibitors

Dementia may be linked to low levels of Acetylcholine.

Pantoprazole Proton pump inhibitor

Same as omeprazole

Same as omeprazole Same as omeprazole

Given as IV

-erosive esophagitis-bleeding ulcer

Omeprazole Proton pump inhibitor: decrease acid secretion by irreversibly inhibiting H+/K+ ATPase on parietal cells

Peptic ulcer disease, GERD, erosive esophagitis, gastic acid hypersecretionh. Pylori GI tract infection

Pancreatitis, hepatotoxicity, interstitial nephritis, may affect effects of clopidigrel increased risk of hip, wrist and spine fracture, hospital acquired pneumonia, and enteric infections including clostridium difficile, salmonella, E. coli, headache, rash, GI discomfort, diarrhea, anorexia, asthenia, back pain

hypersensitivity Proton pump inhibitors metabolized in liver by CYP2C19 and CYP3A4 drug interaction with ketoconazle or itraconazle due to acid environment needed to absorb azole drugs

Drug Uses Side effects Contraindications Therapeutic considerations

Aluminum hydroxide

Symptomatic relief of dyspepsia associated with peptic ulcer disease, GERD or hiatal hernia

Phosphate depletion (severe weakness, malaise anorexia), constipation, osteomalacia in patients with renal failure

hypersensitivity All antacids can potentially increase or decrease the rate or extent of absorption of concurrently administered oral drugs by changing transit time or by binding the drug

Magnesium hydroxide

Symptomatic relief of dyspepsia associated with peptic ulcer disease, GERD or hiatal hernia

Also used to treat constipation

Diarrhea, hypermagnesemia in patients with renal failure

Hypersensitivity Same as above

Drug Uses Side effects Contraindications Therapeutic considerations

Levothyroxine Thyroid Hormone, T4, for hypothyroidism, myxedema comaReplaces missing hormone

Hyperthyroidism, osteopenia, pseudotumor cerebri, seizure, myocardial infarction

Acute MI, uncorrected adrenal cortical insufficiencyUntreated thyrotoxicosis

Cholestyramine and sodium polystyrene sulfonate decrease absorption of synthetic thyroid hormoneRifampin and phenytoin increase metabolism

T4 is the more desirable hormone to replace because of its longer half life (compared to T3).

Hydrocortisone • Corticosteroid • Replacement therapy

for primary and secondary adrenal insufficiency

• Reduces inflammation

Cushing syndrome (iatrogenic) , reduces bone density with chronic use

Abrupt discontinuation can cause adrenal insufficiency

Fungal infection Systemic steroids given for getter than 5-7 days require tapering the dosage to avoid adrenal insufficiency.

Hyperglycemia is common in diabetics due to the counter regulatory hormonal action of steroids.

Verapamil (Phenylalkylamine)

Class: Calcium channel blockerMech: block voltage-gated L-type calcium channels & prevent influx of calcium that promotes actin-myosin cross-bridge formationIndications: • Prinzmetal or variant

angina or chronic stable angina

• Hypertension• A fib or flutter, paroxysmal

SVT

• Rare cardiac arrhythmia• AV block• Bradyarrhythmia• Exacerbation of heart failure• Peripheral edema• Syncope• Gingival hyperplasia• Dizziness

• IV is contraindicated in patients with ventricular tachycardia and patients receiving IV beta blockers

• Sick sinus syndrome or 2nd or 3rd AV block

• SVT associated with bypass tract

• Left ventricular failure• Hypotension• Acute MI

• Low ratio of vascular to cardiac selectivity

• Depresses both SA and AV node conduction velocity

• Raises serum carbamazepine levels which may cause toxicity

• Avoid using with beta blockers

• Greater suppressive effect on cardiac contractility

Drug Uses Side effects Contraindications Therapeutic considerations

Acetaminophen Class: NSAIDMech Weak inhibitor of peripheral cyclooxygenases; predominant effect may be inhibition of cyclooxygenase-3 (COX-3) in the CNS

Indications: FeverMild to moderate pain

Hepatotoxicity, nephrotoxicity (rare)Rash, hypothermia

Hypersensitivity to acetaminophen

• Although acetaminophen has analgesic and antipyretic effects similar to aspirin, the anti -inflammatory effect of acetaminophen is insignificant because of its weak inhibition of peripheral cyclooxygenases

• Acetaminophen overdose is a leading cause of hepatic failure

• Antidote for acetaminophen overdose is N-acetylcysteine

Ibuprofen Class: Propionic acids: (NSAID)Mech: Inhibit cyclooxygenase-l (COX-I) and cyclooxygenase-2 (COX-2), decreasing the biosynthesis of downstream eicosanoids and thereby limiting the inflammatory responseIndications: • Mild to moderate pain• Fever• Osteoarthritis, rheumatoid

arthritis• Dysmenorrhea• Gout

Gastrointestinal hemorrhage, ulceration, perforation;nephrotoxicity; Stevens-Johnson syndrome;Gastrointestinal disturbance, tinnitus

Gastrointestinal or intracranialbleedingCoagulation defectsAsthma, urticaria, or allergic-typereactions after taking NSAIDS,due to risk of severe, even fatal,anaphylactic reactionsSignificant renal insufficiency

N-AcetylcystineMech: Supplies cysteine to replenish glutathioneIndications: • Acetominophen Overdose

ANTIDOTE FOR ACETOMINAPHEN OD

Drug Uses Side effects Contraindications Therapeutic considerations

Celecoxib

Only COX-2 inhibitor still on market!

Class: COX-2 inhibitor (NSAID)Mech: Selectively inhibits COX-2 Indications: • Osteoarthritis, rheumatoid• arthritis in adults, and• ankylosing spondylitis• Primary dysmenorrhea• Acute pain in adults• Familial adenomatous

polyposis

Myocardial infarction, ischemic stroke, heart failure;gastrointestinal bleeding, ulceration, perforation;renal papillary necrosis; exacerbation of asthmaGastrointestinal disturbance, peripheral edema

Hypersensitivity to sulfonamidesHypersensitivity to celecoxibAsthma, urticaria, or allergic-typereactions after taking NSAIDs,due to risk of severe, even fatal,anaphylactic reactionsPain associated with coronaryartery bypass graft surgery

• Decreases efficacy of ACE inhibitors

• Incidence of gastropathy and nephropathy may be less than that associated with NSAIDs, but may still be significant

• Valdecoxib and rofecoxib recently withdrawn from U.S. market due to possible increase in cardiovascular mortality

Etomidate Class: carboxylated imidazole Mech appears to facilitate GABA-minergic neurotransmission by increasing the number of available GABA receptors, possibly by displacing endogenous inhibitors of GABA binding Indications: IV anesthesia intubation

Can cause adrenal insufficiency, can cause seizure activity

Labor / Imminent Delivery

Septic shock

Very short acting.

Loperamide

OTC- Imodium

Class: Opioid agonistMech: activates u-recptor in GI tract, specifically in the myenteric plexus, reduces muscle tone and decreases peristalsis

Indications: • Diarrhea

• dry mouth• dizziness• drowsiness• vomiting• stomach pain, discomfort,

or distention (enlargement)• constipation• fatigueanticholenergic effects (turns off parasympathetics)

Under two years of age

Paralytic ileus

Also has Anticholinergic effects.

Opioid that only acts in the GI tract (no effect on pain)

Drug Uses Side effects Contraindications Therapeutic considerations

Ranitidine

(Brand name = Zantac)

Class: H2 RECEPTOR ANTAGONISTS (antihistamine antacid)Mech: Decreases acid secretion by inhibiting histamine binding to H2 receptors on parietal cellsIndications: • Peptic ulcer disease• Gastroesophageal reflux

disease (GERD)• Erosive esophagitis• Gastric acid

hypersecretion

Necrotizing enterocolitis in fetus or newborn,pancreatitisHeadache, dizziness, arthralgia, myalgia,constipation, diarrhea

Hypersensitivity • Ranitidine can be given IV to treat hypersecretory conditions or to treat patients who are not able to tolerate the oral formulation

• Has few side effects, or drug interactions than Cimetidine . It is also more potent.

• Unlike H1 blockers, sedition is not common.

Succinylcholine Class: Nicotinic receptor agonistMech: Stimulate opening of nicotinic ACh receptor channel and produce depolarization of the cell membrane; succinylcholine persists at the neuroeffector junction and activates the nicotinic receptor channels continuously,which results in inactivation of voltage-gated sodium channels so that they cannot open to support further action potentials (sometimes called "depolarizing blockade‘)Indications: • Induction of

neuromuscular blockade in surgery

• Intubation

Bradyarrhythmia, cardiac arrest, cardiac arrhythmia, malignant hyperthermia, rhabdomyolysis, respiratory depression Skeletal muscle myopathies Muscle rigidity, myalgia, raised intraocular pressure

Personal or family history of malignant hyperthermia

Skeletal muscle myopathy

Upper motor neuron injury

Extensive denervation of skeletal muscle

Short duration of action makes succinylcholinein surgery drug of choice for paralysis during intubation

Causes transient fasciculations