Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Common learning issues Test 2 OMS I spring 2014 MOSBYS Acetylcholine Receptor Antibody (AChR Ab) • For diagnosis of myasthenia gravis (MG) and monitoring of patient response to immunosuppressive therapy • Presence of AChR Ab is diagnostic for MG, but levels do not correspond to disease severity. Monitoring of levels is useful for measuring progress of immunosuppressive therapy. • Cannot diagnose congenital MG (b/c non-immune pathology) • 3 different types of AChR Ab test for MG: • AChR – binding Ab - most commonly used • AChR – modulating Ab – most sensitive • AChR – blocking Ab – least sensitive ; best for quantifying Before 1 year of MG illness , these tests often are not positive and radioimmunoassay should be used instead Increased levels: MG , ocular MG , thymoma Interfering factors: ALS therapies and muscle relaxant drugs can cause false postives; immunosuppressive drugs treating subclinical MG can suppress AChR Ab formation Complement Assay • Indication: Used to diagnose angioedema or (in PBL case) to diagnose systemic lupus erythematosus (SLE), also used to diagnose various nephritis conditions • Test measures amount of C3 and C4 complement present in units / mL after a blood sample is exposed to antigen and 50% of RBCs are lysed • Increased levels: rheumatic fever, acute MI, ulcerative colitis, inflammatory illness, cancer Decreased levels: Hereditary angioedema (congenital lack of C1 inhibitor causes overuse of complement protein and exhaustion), severe liver disease (synthesis site of complement), autoimmune disease (SLE in particular), serum sickness, renal transplant rejection , protein malnutrition, anemia, infection, glomerulonephritis Blood Cortisol • Performed on pts who are suspected to have hyper or hypo-functioning adrenal glands Test Explanation • CRH is made in the hypothalamus-> stimulates ACTH in the anterior pituitary-> stimulates the adrenal cortex to produce cortisol • Cortisol, a glucocorticoid, produces negative feedback on CRH/ACTH • Affects fat, protein, and carbohydrate metabolism and has a profound effect on blood glucose levels • Stimulates gluconeogenesis • Inhibits insulin’s effects (aka reduces glucose transport into cells) Cortisol levels vary during the day (diurnal variation) and are highest between 6-8 am** Blood collected at 8am and 4pm (levels at 4pm=1/3-2/3 of 8am value) • Sometimes the earliest sign of adrenal hyperfunction (Cushing’s syndrome) is the loss of diurnal variation, even when cortisol levels are not elevated • High lvls of cortisol=Cushing’s syndrome; Low levels=Addison’s dz Blood Cortisol • Increased levels: pregnancy, stress • Drugs causing increased levels: amphetamines, cortisone, estrogen, OCPs, spironolactone • Drugs causing decreased levels: Androgens, aminoglutethimide, betamethasone/exogenous steroids, danazol, lithium, levodopa, metyrapone, phenytoin Blood glucose • Direct measure of blood glucose used mainly for diabetic patients • Test explanation: • Glucose levels are low in the fasting state which causes glucagon release by pancreatic alpha islet cells • Glucagon breaks glycogen down to glucose in the liver • If fasting persists, proteins and fatty acids are broken down under glucagon stimulation • Glucose levels are elevated after a meal causing a release of insulin from pancreatic beta cells • Insulin causes upregulation of insulin receptors and glucose uptake into mainly muscle, liver and adipose tissue. [Note: Glucose uptake into the brain is not regulated by insulin] • ACTH, adrenocorticosteroids, epinephrine, growth, and thyroxine affect glucose • Must be evaluated for the time of day • True glucose elevation is usually DM • Hypoglycemia is inadvertent insulin overdose in patients with brittle diabetes • Must monitor frequently in diabetes patients • Finger stick blood glucose are performed before meals and at bedtime • Interfering factors: • Increased levels: Stress (trauma, general anesthesia, infection, burns, MI), caffeine, pregnancy, IV dextrose, antidepressants, beta blockers, corticosteroids, dextrothyroxine, diazoxide, diuretics, epinephrine, estrogens, glucagon, isoniazid, lithium, phenothiazines, phenytoin, salicylate, and triameterene • Decreased levels: acetaminophen, alcohol, alpha glucosidase inhibitors, anabolic steroids, biguanides, clofibrate, disopyramide, gemfibrozil, incretin mimetics, insulin, MAOi, meglitinides, pentamidine, propanolol, sulfonylurea, and thiazolidinediones Glucose, postprandial • The 2 hour test is a measurement of the amount of glucose in the patient’s blood 2 hours after a meal is ingested (postprandial) • Test explanation: • The meal acts as a glucose challenge to the body’s metabolism • Insulin is normally secreted after a meal in response to the high blood glucose, in diabetes patients the glucose is usually still elevated 2 hours later • If the levels are between 140-200 then a glucose tolerance test must be obtained • If the levels are greater than 200 then a diagnosis of DM is made • 1 hour test detects gestational diabetes • The detection of gestational diabetes prevents excessive fetal growth and birth trauma, fetal death, neonatal morbidity, called O’Sullivan test • O’ Sullivan test gives a 50 g oral glucose dose and tests 1 hour later 24-28 weeks gestation; a 3 hour test is ordered for levels above 140 • Interfering factors • Increasing factors: smoking during testing, stress (via catecholamine secretion), eating a snack or candy • Falsely decreased if the person cannot eat the entire test meal or vomits Glucose, Postprandial – Increased and Decreased Levels • Increased: • Diabetes mellitus, gestational DM, malnutrition (b/c of decreased glucose tolerance), hyperthyroidism, acute stress, Cushing syndrome (b/c of increased cortisol), pheochromocytoma, chronic renal failure (b/c kidney fails to metabolize glucagon), glucagonoma, diuretic therapy, acromegaly (b/c GH stimulates glucagon release), liver disease (b/c liver metabolizes most glucose) • Decreased: • Insulinoma , hypothyroidism , hypopituitarism , Addison disease (b/c diminished cortisol) , insulin overdose , malabsorbtion/maldigestion (b/c glucose is not absorbed) Glucose tolerance test • Assists in the diagnosis of DM and the evaluation of patients with hyperglycemia • Test explanation: • Criteria to diagnose diabetes: [KNOW] • Sufficient clinical symptoms ( polydipsia, polyuria, ketonuria, weight loss) plus random blood glucose > 200 • Elevated Fasting Blood Glucose on more than one occasion • 2 hours after meal glucose > 200 • Used when diabetes is expected (retinopathy, neuropathy, renal disease) but criteria for diagnosis can’t be met without GT • May be used for the following • • • • • • Family history of diabetes Patients who are massively obese History of recurrent infections Delayed healing of wounds Women who have stillbirths or large babies Transient glycosuria or hyperglycemia during pregnancy, or following MI, surgery or stress • The ability to tolerate glucose load is evaluated through serum and urine glucose levels at 30 minutes, 1, 2, 3, and 4 hours • Normally there is a rapid insulin response that peaks in 30- 60 minutes and returns to normal in 3 hours, glucose shouldn’t spill into urine Glucose tolerance test • Indication: diagnosis of DM or gestational diabetes or evaluation of hypoglycemia • Test explanation: • For diabetes mellitus: • • Used when diabetes is suspected because of diabetes spectrum symptoms (e.g. retinopathy) but confirmation is required 75g glucose load is administered with serum glucose readings at .5 , 1 , 2 , 3 , or even more hours • Glucose exceeding 200 at two hours is sufficient for diagnosis of DM, indicative of a lack of insulin response. Glucose will spill over into the urine of diabetic patients. • For gestational Diabetes: • A 50 g dose administered between 24 and 28 weeks gestation. (O’Sullivan Test). Cushing’s , pheocromocytoma, acromegaly, aldosteronism, or hyperthyroidism may all also cause glucose intolerance • Chronic renal failure, acute pancreatitis, myxedema, type IV lipoproteinemia, infection or cirrhosis cause abnormal GT test • Contraindications • • Serious concurrent infections or endocrine disorders (glucose intolerance) Patients who vomit all or part of the meal • Interfering factors • • • Increasing factors: smoking, eating, stress, exercise Fasting or reduced caloric intake before test can cause intolerance Drugs that cause intolerance: antihypertensives, antiinflammatories, aspirin, beta blockers, furosemide, nicotine, oral contraceptives, phenothiazines, psychiatric drugs, steroids, and thiazides GT – increased and decreased factors • Increased: • DM , acute stress , cushing syndrome , pheochromocytoma , chronic renal failure , glucagonoma , acute pancreatitis , diuretic therapy , corticosteroid therapy , acromegaly , myxedema , gastrectomy Glycosylated hemoglobin • Used to monitor diabetes treatment because it provides accurate long-term index of patient’s average blood glucose level • Normal non-diabetic: 4-6% • ADA target for diabetic: 7% • Test explanation: • HbA1C is a hemoglobin subtype that combines strongly with glucose via a glycosylation reaction • The amount of GHb (glycohemoglobin) depends on the most of glucose available in the bloodstream over the 120 day life an RBC, • Provides a 100-120 day approximation of blood glucose levels (b/c normal RBC lifespan is 120days) and is not effected by short term spikes or timing of blood draw • Serum glycalated protein tests shows provide evaluation of more recently elevated blood glucose because the are degraded faster than RBC (e.g. glycated albumin or fructosamine) Glycosylated hemoglobin Good for determining: • • • • • • • Evaluation of the success of diabetic treatment and patient compliance Comparing and contrasting the success of past and new forms of diabetic therapy Determining duration of hyperglycemia Providing sensitive estimate of glucose imbalance in patients with mild diabetes Individualizing diabetic control Providing a sense of reward for many patients Evaluating the diabetic patient whose glucose levels change significantly from day to day (brittle diabetes) • Mean plasma glucose = (35.6 x GHb) – 77.3 • Interfering factors • Hemoglobinopathies affect results because quantity of hemoglobin A varies • False elevation: when RBC life span is lengthened because the HBA1 has longer period for glycosylation • Abnormal low levels of proteins may falsely indicate normal glycalated fructosamine levels despite reality of high glucose • Ascorbic acid may cause false lows of glycated fructosamine • Also elevated in: splenectomy (b/c RBC survival is prolonged) and pregnancy (indicating gestational diabetes or prediabetes) Growth Hormone pp. • Indication: • identify adolescent GH deficiency or document patients with gigantism or acromegaly. Can also be used to evaluate pituitary hypofunction. • Explanation: • Secreted by acidophils of anterior pituitary to mediate somatomedin release. In childhood, insufficiency results in non-growth while excess results in gigantism. • GH should be drawn 60-90 minutes after deep sleep to attempt to draw when GH levels are at maximum. Exercise also stimulates GH release. • Increased levels: • Gigantism, acromegaly, anorexia nervosa (b/c starvation stimulates GH secretion), stress, surgery, hypoglycemia, starvation, deep sleep, exercise • Decreased levels: • GH deficiency, pituitary insufficiency, dwarfism, hyperglycemia, failure to thrive, delayed sexual maturity Somatomedin C (aka insulin like growth factor-1, IGF-1) • Used to screen: • Patients with growth hormone deficiency, Pituitary insufficiency, acromegaly. • Levels depend on GH levels • Somatomedins stimulate somatostatin and should feedback to decrease pituitary. • Test explanation: • GHRH (from hypothalamus) -> GH (from anterior pituitary) -> Somatomedin C/IGF-1 (mostly from liver) • GH secretion varies widely throughout the day. • Insulin-like growth factor-1 (IGF-1) provides a more accurate reflection for the mean plasma concentration of GH for acromegaly. • Not used to ddx GH deficiency (additional testing needed) • A person with normal IGF-1 almost never has acromegaly. IGF-1 • Increased: • • • • • • • • Gigantism Acromegaly Stress Major surgery Hypoglycemia Starvation Deep-sleep state Exercise • Decreased: • GH deficiency (but more tests to ddx) • Pituitary insufficiency • Dwarfism • Laron type dwarfism (GH receptor insensitivity) • Hyperglycemia • Hypothryoidism • Liver disease Magnesium • Most magnesium is intracellular; about ½ is in bone • Most magnesium is bound to an ATP molecule and is important in phosphorylation of ATP • Important in enzymatic and metabolic processes as well as organ function (neuromuscular and cardiac tissue in particular) • Low magnesium levels may increase cardiac irritability and aggravate cardiac arrhythmias • Hypermagnesemia slows neuromuscular conduction and is demonstrated by cardiac conduction slowing (widened PR and QT intervals, wide QRS), diminished DTR and respiratory depression Magnesium • Intracellular levels of ions, in order: K> Mg> Ca • Because charges must be maintained, a total body reduction in any one of these causes extracellular ions to shift into the cell, creating a comparable blood reduction in all 3 Mg increases intestinal absorption of calcium (hypocalcemia can respond to Mg replacement) • Magnesium deficiency occurs in the malnourished, like in postop pts • Alcohol use increases Mg loss in urine • Mild hypomagnesemia is found in DM, hypoparathyroidism, hyperthyroidism, hyperaldosteronism • Toxemia of pregnancy is associated w/ reduced magnesium levels • Signs of magnesium depletion: neuromuscular (weakness, irritability, tetany), EKG changes, delirium, convulsions • Signs of increased Mg levels: lethargy, N/V, slurred speech • Increased Mg levels assoc w/ ingestion of Mg-containing antacids • Because Mg is excreted by the kidney, chronic renal dz causes increased Mg levels • Because Mg is intracellular, hemolysis of the blood sample will cause falsely elevated values • Drug interactions can cause changes in Mg levels** Vitamin B12 (540-541) • Identify the cause of megaloblastic anemia and evaluate malnourished patients • Test explanation: • B12 needed for the conversion of folate to its active form • • • • • Necessary for synthesis of nucleic acids and amino acids RBC are megoblastic in B12 deficiency so they cannot conform to the size of small capillaries, consequently fracture and hemolyse causing shortened RBC life span and anemia Giant, hypersegmented neutrophils and large nucleated platelets are also seen May take 6-18 months to be seen (Large liver store) Meat, eggs, and dairy are main source of B12 • Causes: • No Intrinsic factor (needed for B12 absorption (results in pernicious anemia)) • Lack of gastric acid to separate B12 from its binding protein • Diseases of ileum (where B12 is absorbed) • • • • • Serum B12 measures recent B12 ingestion Prolonged deficiency is best measured by MMA (urinary methylmalonic acid) Elevated serum MMA and urinary excretion of MMA directly measure B12 activity The active form of B12 converts L-methylmalonyl CoA to succinyl CoA so without active B 12 larger quantities of MMA is seen in urine • Urine MMA test is more accurate. uMMA : creatinine test is more accurate because it indicates tissue - cellular B12 deficiency Interfering factors • Chloral hydrate increases B12 • Drugs that decrease: alcohol, aminoglycosidesm aminosalicylic acid, anticonvulsants, colchicine, oral contraceptives Increased and Decreased B12 • Increased: • • • • Leukemia polycythemia vera liver dysfunction myeloproloferative disease Decreased Levels: • pernicious anemia • malabsorbtive syndromes (Chron’s dz) • intestinal worms (D. Latum) • atrophic gastritis, • Zollinger-Ellison (tumor secreting gastrin) • gastrectomy • ileum resection • Achlorydia (lack of stomach acid) • pregnancy, • vit C deficiency • folic acid deficiency Nerve Conduction Studies (Electroneurography) • Identifies peripheral nerve injury in patients with localized or diffuse weakness, to differentiate primary peripheral nerve disease from muscular injury, and to document the severity of injury in legal cases • Normal findings: show no peripheral nerve injury or disease • Monitors nerve injury and response to treatment Nerve Conduction Studies • Test explanation: • Allows the detection and location of peripheral nerve injury or disease • Initiate an electrical impulse at one site (proximal) of a nerve and record the time required for that impulse to travel to a second site (distal) of the same nerve • The conduction velocity can be determined • Done in conjunction with EMG • Normal values vary from nerve to nerve and among individuals • Compare conduction velocity of the suspected side with the contralateral nerve conduction velocity • Normal conduction velocity is 50-60 m/sec • Greater than normal values are not pathologic • Muscular factor can be evaluated by measuring latency (time required for stimulation of distal end to cause muscular contraction) • Conduction velocity = (distance (m))/ (total latency – distal latency) • Distal latency = time from distal nerve stimulation to muscle contraction • Pathologies (slowing): • Traumatic transection or contusion of a nerve will usually cause maximal slowing of conduction • Neuropathies, both local and general, cause slowing • Primary muscle disorders can cause a slow conduction because conduction may require muscle contraction • Interfering factors • Patients in severe pain Urine glucose • Monitors the effectiveness of therapy for DM; if present, reflects degree of glucose elevation in blood • Test explanation • May indicate DM or other glucose intolerance disorders • Normally blood glucose is filtered from blood by glomeruli and all the glucose is reabsorbed in proximal tubules • Blood glucose exceeds capability of renal threshold to reabsorb and it spills into the urine. Occurs at about 180 mg / dL . • Glucosuria may occur immediately after a high carb meal or in patients on IV dextrose or due to stress or injury • Glucosuria can indicate diseases that affect renal tubule or genetic defects in metabolism and excretion of glucose • In these disorders renal threshold for glucose is low so normal blood glucose cannot be reabsorbed • GT test in these patients are usually normal • Interfering factors • • • • Sugars can cause false positive b/c they reduce copper in test strip Drugs that cause false positive: ASA, aminosalicylic acid, ascorbic acid, cephalothin, chloral hydrate, nitrofurantoin, streptomycin, and sulfonamides False negative: ascorbic acid (clinistix test), levodopa, and phenazopyridine Drugs that increase urine glucose: ASA, cephalosporins, chloral hydrate, chloramphenicol, dextrothyroxine, diazoxide, diuretics, estrogen, glucose infusions, isoniazid, levedopa, lithium, nafcillin, nalidixic acid, and nicotinic acid DRUGS TO KNOW Drug Uses Side effects Contraindications Therapeutic considerations levothyroxine Hormone, T4, for hypothyroidism, myxedema coma Replaces missing hormone Hyperthyroidism, osteopenia, pseudotumor cerebri, seizure, myocardial infarction Acute MI, uncorrected adrenal cortical insufficiency Untreated thyrotoxicosis Cholestyramine and sodium polystyrene sulfonate decrease absorption of synthetic thyroid hormone Rifampin and phenytoin increase metabolism T4 desirable because of its longer half life Hydrocortisone • Corticosteroid • Replacement therapy for primary and secondary adrenal insufficiency • Reduces inflammation Cushing syndrome, reduces bone density with chronic use Fungal infection Cisplatin Pg 696 Class: Directly modify DNA structure Mech: Platinum compound that cross-links intrastrand guanine bases Indications: • Genitourinary and lung cancer • • • • • • Severe bone marrow depression • Renal or hearing impairment Nephrotoxicity Myelosuppression Peripheral neuropathy Ototoxicity Electrolyte imbalance • Can be injected intraperitoneally for treatment of ovarian cancer • Co-administration of amifostine can limit nephrotoxicity Drug Uses Side effects Lomustine Mech: Alkylating agent Myelosupression, Nausea, toxic to liver and kidney Not in book Contraindica tions Therapeutic considerations It is very lipid soluble; “mustiness” are used for brain CA because unlike many chemo drugs they cross the blood-brain barrier easily Class: Mustard gas, nitrosurea Indications: Brain Cancer Ezetimibe Mech: Decreases cholesterol transport from micelles into enterocyte inhibiting NPC1L1 Indications: Primary hypercholesterolemia Familial hypercholesterolemia sitosterolemia Vincristine Mech: Binds tubulin subunits and prevents microtubule polymerization Indications: Leukemia, hodgkin’s disease, nonhodgkins lymphoma, rhadomyosarcoma, Elevated liver function tests, myopathy, dyspepsia, arthralgia, myalgia, headache Active liver disease, persistently elevated liver function tests when co-administered with statin Modest LDL reduction, small effect on HDL and Tgs Inhibition of hepatic cholesterol absorption causes compensatory increases in synthesis partially off setting; prevented by giving statin Rapidly absorbed Levels are increased by cyclosporines and fibrates Peripheral neuropathy, myopathy, myelosuppression Alopecia, GI disturbancees, diplopia Charcot-Marie Tooth syndrome Intrathecal use Peripheral neuropathy is dose limiting Drug Uses Side effects Contraindications Therapeutic considerations Octreotide Pg 503 CLASS: somatostatin analogue Mech: inhibits GH release Indications: Acromegaly Flushing and diarrhea from carcinoid tumors Carcinoid crisis Diahrrea from vasoactive intestinal peptide – secreting tumors TSH producing adenomas • • • Class: IMPDH inhibitor (rate limiting step of guanosine formation) • Myelosuppresion , neutropenia , increased risk of infection , lymphoma Mycophenolate mofetil Pg 803 Indications: • Solid organ transplant • Lupus • Rheumatoid arthritis • pemphigus Arrhythmias , bradycardia , hypoglycemia , gallstone formation Hypersensitivity to drug • • Hypersensitivity to drug Also used to control GI bleeds Available in monthly formation Useful for treatment of autoimmune disorders because highly selective for lymphocytes Administered in case 3 prior to surgical thymus removal to reduce size of thymus Drug Uses Vasopressin Class: ADH analogue (analogues of vasopressin): Mech: Acts at collecting ducts of kidneys on V2 receptors. Results in concentration of urine and decrease in thirst. Desmopressin Pg 474 Terlipressin (investigational) Pg 344 Indications: Neurogenic DI Aziathioprine Pg 503 Class: inhibits IMPDH to interfere with purine metabolism Indications: • Lymphoblastic leukemia , acute myelogenous leukemia , Crohn’s, RA, and IBD Side effects Therapeutic considerations ADH is a neurohypophysial hormone. Functions to retain water and constrict blood vessels Only effective in Neurogenic Diabetes insipidus • Myelosuppression, hepatotoxicity, pancretitis, infection, gastritis • pregnancy • Metabolized by xanthine oxidase, thus Allopurinol increases toxicity by limiting degradation • Also used for immunosuppression Drug Uses Side effects Contraindications Therapeutic 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 • • • • • • • • • • • • • • • • Prednisone Pg 503 Class: Glucocorticoid receptor agonist Mech: mimic cortisol function function by acting as agonists at glucocorticoid receptor Indications: • Inflammatory conditions • 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 • Same as above Systemic fungal infection • • • • Same as above 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 18x more potent than cortisol • Same as above • 4-5 x as potent as cortisol Drug Uses Side effects Contraindicatio ns Therapeutic considerations Edrophonium p. 128 AchEsterase inhibitor Seizure, bronchospasm, cardiac arrhythmia, bradycardia, cardiac arrest, hypotension, salivation, lacrimation, diaphoresis, vomiting, miosis GI or GU obstruction Short half life (2-10 minutes) Same as above Same as above Diagnosis of myasthenia gravis Pyridostigmine p. 128 AchEsterase Inhibitor Treatment of myasthenia gravis Another choline ester or depolarizing NM blocker therapy Cardiovascular therapy For chronic treatment of MG because of its longer half life Drug Uses Side Effects Contraindications Therapeutic Considerations Glyburide (2nd generation sulfonurea) Type 2 DM Hypoglycemia DKA Orally available, metabolized by liver Rash, diarrhea, nausea, dizziness Mechanism-Sulfonylureas and meglitinides inhibit the B-cell K+ ATP channel at the SURl subunit, thereby stimulating insulin release from pancreatic f3 -cells and increasing circulating insulin to levels sufficient to overcome insulin resistance Major adverse effect=hypoglycemia; use cautiously in pts unable to recognize or respond to hypoglycemia (pts on Bblockers or elderly/incapacitated) Can cause wt gain –better in non-obese pts 1st generation agents bind w/ lower affinity to SUR 1 Channel and require higher doses than second gen Insulin Prandial bolus: Regulal, lispro, aspart, glulysine Basal long-acting: NPH, Glargine, Detemir Mechanism-The classic anabolic hormone, insulin promotes carbohydrate metabolism and facilitates glucose, amino acid, and triglyceride uptake and storage in liver, cardiac and skeletal muscle, and adipose tissue DM Hypoglycemia Injection site rxn, lipodystrophy Hypoglycemia Not orally available, delivered parenterally, subcutaneous route most common. Rapid Acting Insulins: Lispro, Aspart, Glulysine: injected minutes before a meal Regular Insulin: Short acting, injected 30 minutes before a meal NPH: intermediate acting; contains protamine, prolonging time required for absorption; administered twice a day Glargine and Detemir: long, acting, steady release without a peak, injected 1*/day Drug Uses Side Effects Contraindications Therapeutic Considerations Metformin (insulin sensitizer/biguanide) Type 2 DM (drug of choice) Lactic Acidosis GI distress is transient, minimize w/ slow titration Mechanism-Activates AMP-dependent protein kinase (AMPK) to block synthesis of fatty acids and to inhibit hepatic gluconeogenesis and glycogenolysis; increases insulin receptor activity and metabolic responsiveness in liver and skeletal muscle PCOS (off-label) Heart failure Alcohol Abuse Hepatic dz Repiratory dz Renal impairment Metabolic Acidosis Diarrhea, dyspepsia, flatulence, N/V, cobalamin deficiency Lactic Acidosis is not common (but a very high yield side effect!); typically occurs in pts w/ conditions that predispose to metabolic acidosis Does not induce hypoglycemia Lowers serum lipids and decreases wt