53 ENDOCRINOLOGY PHARMACOLOGY What is the Mechanism of Action of Insulin? What are the Indications for Insulin? What is the Adverse Effect of Insulin? What are the Rapid Acting Insulin drugs? What is the Short Acting Insulin drug? What is the Intermediate Acting Insulin drug? What are the Long Acting Insulin drugs? What is the Mechanism of Action of Sulfonylureas? Pushes K+ into the cell, Liver: Increases Glucose storage as Glycogen, Increases Triglyceride Synthesis. Muscle: Increases protein and glycogen synthesis. Adipose Tissue: Improves Triglyceride storage by activating Lipoprotein Lipase, Decrease circulating Free Fatty Acids DM Type 1; DM Type 2; Hyperkalemia; Stress induced Hyperglycemia; Gestational Diabetes Hypoglycemia Aspart, Lispro and Glulisine Regular Insulin NPH and Lente Ultratente, Glargine, Protamine, Zinc, and Detemir Closes K+ channel in the pancreatic Beta cell membrane, Reduces K+ efflux & increases Ca (2+) influx, and cell depolarize to increase secretion of insulinENDOCRINOLOGY PHARMACOLOGY What are the Indications for Sulfonylureas? What is the Adverse Effect of Sulfonylureas? Function of what cells is necessary for the action of Sulfonylureas? What is the first generation Sulfonylureas? What is the Adverse Effect for first generation Sulfonylureas? What is the second generation Sulfonylureas? What is the Mechanism of Action of Biguanides? What are the Indications for Biguanides? What is the Adverse Effect of Biguanides? What are the Biguanides drugs? NIDDM (Type 2) Hypoglycemia, Gl disturbances, Muscle weakness, mental confusion, Sulfur allergy Requires some islet cell function so drugs use less in Type 1 DM Chlorpropamide and Tolbutamide Disulfiram like effects Glyburide, Glimepiride, and Glipizide Decrease Gluconeogenesis, Increase Glycolysis, and Increase peripheral Glucose uptake. (Insulin sensitivity) First line therapy in Type 2 0M. Lactic Acidosis (Contra indicated in Renal Failure). Stop use in patients undergoing studies using Contrast Metformin55 ENDOCRINOLOGY PHARMACOLOGY What is the Mechanism of Action of Glitazones/Thiazolidinedione’s? What are the Indications for Glitazones/Thiazolidinedione’s? What is the Adverse Effect of Glitazones/Thiazolidinedione’s? What are the Glitazones/Thiazolidinedione’s drugs? What is the Mechanism of Action of Alpha-Glucosidase Inhibitors? What are the Indications for Alpha-Glucosidase Inhibitors? What is the Adverse Effect of Alpha-Glucosidase Inhibitors? What are the Alpha-Glucosidase Inhibitors? Increases Insulin sensitivity in peripheral tissues. Transaction modulation by Peroxisome Proliferator Activated Receptor ‘Gamma in Nucleus NIDDM. (Type 2) ‘Weight gain, edema, hepatotoxicity, Increases LDL and triglycerides, CHF and Contraindicated Pioglitazone and Rosiglitazone Inhibits intestinal brush border Alpha-Glucosidases, Delays sugar hydrolysis and Glucose absorption from the gut, Decreases postprandial hyperglycemia NIDDM. (Type 2) Gl disturbances and may reduce absorption of Iron, no use with kidney problems Acarbose and MiglitolENDOCRINOLOGY PHARMACOLOGY What is the mechanism of action of DPP-4 inhibitors? What is the indication of DPP-A inhibitors? What is the adverse effect of DPP-4? What are the DPP-4 inhibitors? What is the adverse effect of sodium-glucose cotransporter 2 (SGLT 2)? What is the indication for sodium glucose cotrasporter 2 (SGLT 2)? What is the adverse effect of sodium-glucose cotransporter 2? What are the sodium-glucose cotransporter 2? What is the Mechanism of Action of Mimetics? What is the Indication for Mimetics? What are the Adverse Effects of Mimetics? What are the Mimetic drugs? Inhibits the enzyme that deactivates GLP-1 (decreased glucagon) NIDDM (Type 2) Urinary and respiratory infections Linagliptin, Saxagliptin, Sitagliptin Block reabsorption of glucose in the Pct Type 2 diabetes UTI, glucosuria, dehydration and weight loss Canagliflozin, Depagliflozi Empaglifiozin Decreases Glucagon NIDDM. (Type 2) Hypoglycemic, Nausea and Diarrhea Pramlintide57 ENDOCRINOLOGY PHARMACOLOGY What is the Mechanism of Action of GLP-1 Analogs (glucagon like peptides)? What is the Indication for GLP-1 Analogs (glucagon like peptides)? What are the Adverse Effects of GLP-1 Analogs? What are the GLP-1 Analog drug? What is the Mechanism of Action of a Growth Hormone? What are the Indications for GH? What is the Mechanism of Action of Octreotide (Synthetic analog of Somatostatin)? What are the Indications for Octreotide? What are the Indications for Oxytocin? What is the Mechanism of Action Desmopressin (DDAVP)/ADH? What are the Indications for Desmopressin (DDAVP)/ADH? Increase Insulin and Decrease Glucagon release NIDDM. (Type 2) Nausea, Vomiting and Pancreatitis Exenatide and Liraglutide Stimulates liver production of insulin-like growth factors and gastric emptying GH deficiency in children, Turner syndrome, and Burn victims Decreases release of GH, Gastrin, CCK, Carcinoid, VIP, Glucagon and Insulin, ‘Acromegaly; Glucagonoma; Insulinoma; Carcinoid syndrome Induces labor and Controls uterine hemorrhage Recruits water channels to Luminal Membrane in collecting duct Antidiuresis and Central (pituitary) D1ENDOCRINOLOGY PHARMACOLOGY What are the Adverse Effects of Desmopressin (DDAVP)/ADH? What is the Mechanism of Action of Propylthiouracil and Methimazole? What is the Indication for Propylthiouracil and Methimazole? What are the Adverse Effects of Propylthiouracil and Methimazole? What is the Mechanism of Action of Levothyroxine (T4)/Triiodothyronine (13)? What are the Indications for Levothyroxine (T4)/Triiodethyronine (T3)? What are the Adverse Effects of Levothyroxine (T4)/Triiodothyronine (T3)? What is the Mechanism of Action of Demeclocycline? What is the Indication for Demeclocycline? What are the Adverse Effects of Demeclocycline? ‘Over hydration and allergic reaction Inhibits peroxidase enzyme in Thyroid and Decreases synthesis of Thyroid Hormones Hyperthyroidism Agranulocytosis, skin rash and Aplastic Aner ‘Thyroxine replacement Hypothyroidism and Myxedema Tachycardia, heat intolerance, tremors and Arrhythmias ADH antagonist SIADH Nephrogenic D1, Photosensitivity and Abnormalities of Bone and Teeth59 ENDOCRINOLOGY PHARMACOLOGY What is the Mechanism of Action of Cinacalcet? What are the indications for Cinacalcet? What are the Adverse Effects of Cinacalcet? What is the Mechanism of Action of Sevelamer? ications for Sevelamer? What are the Adverse Effects of Sevelamer? What is the Mechanism of Action of Glucocorticoids? What are the Indications for Glucocorti What are the Adverse Effects of Glucocorticoids? What are the Glucocorticoid drugs? Sensitize Ca¥? receptor in the parathyroid gland Primary hyperparathyroidism or renal failure Hypocalcemia Phosphate binder that prevents the PO,” absorption in the Gl tract KD Glupset Decrease production of Leukotrienes and prostaglandins by inhibiting phospholipase A2 and expression of COX-2 Addison's disease; inflammation; immune suppression; asthma latrogenic Cushing's syndrome. (Adrenal insufficiency when drug stopped after chronic use) Hydrocortisone, Triamcinolone, Dexamethasone, Prednisone Beclomethasone61 GASTROINTESTINAL What Gl disease has a Corkscrew on X-Ray? What Gl disease has an Apple Core on X-Ray? What Gl disease has a Stacked Coin on X-Ray? What Gl disease has a Thumb Print on X-Ray? What Gi disease has an Abrupt Cut Off on X-Ray? What Gi disease has Barium Clumping on X-Ray? What Gl disease has a Bird's Beak on X-Ray? What Gl disease has a String Sign on X-Ray? What Gl diseases are the causes of solid and liquid Dysphagia? What Gl diseases are the causes of liquid Dysphagia? What is Barrett's Esophagus? What are Esophageal Varices? Esophageal spasm and Volvus Colorectal Cancer Intussusception Toxic Megacolon Volvulus Celiac Sprue Achalasia Pyloric Stenosis and Crohn's Disease ‘Schatzki's Rings, Stricture, Cancer Scleroderma and Achalasia Metaplasia of the lower esophagus Increased risk of Adenocarcinoma Due to Portal HTN, vomit large amounts of blood when they rupture62 GASTROINTESTINAL What is Mallory-Weiss? What is Boerhaave Syndrome? What is Achalasia? What is irschprungs Disease? What is Zenker's Diverticulum? What ie 2 Traction Diverticulum? What is Plummer-Vinson Syndrome? What is Schatzki’s Ring? Tearing of the lower esophageal sphincter (LES), associated with chronic vomiting, cough up a little blood and possible visual varices Transmural Tearing of the Esophagus. Left Sided most ‘common, Pneumonia/Pain/Effusion Increased LES Pressure (no ‘Auerbach’s Plexus), Bird's Beak on X- Ray and also seen in Chagas Disease Failure of innervation to the rectum (No Auerbach's Plexus), lack of Meconium passage in the newborn, Neural crest cell migration problem ‘Cough up undigested food from above the UES, Halitosis, motor dysfunction problem ‘Out pouch between the UES and LES Esophageal webbing at the upper Esophageal Sphincter (UES), spoon nails from iron deficiency anemia Esophageal webs in the lower Esophagus Dysphagia (mucosal tissue)63 GASTROINTESTINAL What is a Tracheoesophageal (TE) Fistula (H-Type)? What is an Esophageal Atresia with a TE Fistula (C-type)? What is Duodenal Atre: What is Pyloric Stenosis? How does Choanal Atresia Present? How does Tetrology of Fallot (TOF) present differently from Choanal Atresia? What makes Scleroderma Unique? What makes Esophageal Spasms Unique? What makes Achalasia unique? What Gi disease has a RUQ Olive Mass? ‘Chokes with each feeding and is Congenital Baby vomits with first feeding, large gastric bubble and distended abdomen (failure of apotosis) Dilious vomiting with fist feeding, double bubble sign on x-ray, associated with Downs Syndrome Non-Bilious projectile vomiting (3-4 week old) and RUQ Olive Mass on palpation Baby turns blue with feeding, pinks up when breast or bottle is removed (blocked nasal passages) TOF Babies...Turns blue with crying and has No feeding issues Can have a decreased LES pressure or increased LES pressure Increased Peristalsis, Decreased Peristalsis and increased LES pressure Pyloric StenosisGASTROINTESTINAL What Gl disease has a RLQ Sausage mass? Intussusception What is a Bezoar? Mass of non-digestible product (Le. Hair) causing an occlusion at the pylorus What is Type A gastritis? Upper Gl bleed, autoimmune (anti- parietal cell antibodies), Atrophic / Achlorhydria and increased risk for adenocarcinoma (body & fundus region of the stomach) What is Type B gastritis? Upper Gl bleed, associated wi eating spicy foods, loss of bari protection and H. Pylori infec (antrum of stomach) What is a Duodenal Ulcer? Pain 20-30 minutes after eating, relieved with food, caused by H. Pylori infection 80-90% of the time and weight gain What is a Gastric Ulcer? Loss of protective barrier, pain during the meal, associated with NSAIDs, H. Pylori infection and weight loss What is a Sliding Hiatal Hernia? Fundus of the stomach herniates through the Esophageal Hiatus into the Thorax What is a Rolling Hiatal Hernia? Bowel protruded through a defect in the Diaphragm. This can strangulate the bowel and can cause Atelectasis,What is Menetrier's Disease? What defines constipation? What defines Diarrhea? What is Osmotic Diarrhea? What is Secretory Diarrhea? What is Inflammatory Diarthea? What is Celiac Sprue? What is Tropical Sprue? What is Mesenteric Ischemia? 65 GASTROINTESTINAL Loss of protein through the rugal folds. Causes generalized edema. CMV association in children and H Pylorus in Adults Less than 3 bowel movements per week >200 grams of stool per day High osmolality in the bowel pulling water into the lumen Water pushed from cells into the gastric lumen (increased cAMP) Diarrhea with blood and pus Found in the Jejunum Wheat allergy Villous atrophy Anti-gluten/gliadin antibodies Found in the distal ilium Caused by bacterial o viral, amoeba or parasitic infection Villous atrophy ‘Abdominal pain out of proportion to physical exam,GASTROINTESTINAL What bugs cause Bloody Diarrhea? What is Primary Biliary Cirrhosis? What is Primary Sclerosing Cholangitis? What is Ascending Cholangitis? What are the physical signs of Alcoholic Cirrhosis? What ie Hepatorenal Syndrome? What is Cholangitis? What is Cholecystitis? What is Cholelithiasis? What is Choledocholithiasis? "CASES": Campylobacter, Amoeba (Entamoeba Histolytica), Shigella, E.coli and Salmonella Anti-Mitochondrial antibody Bile ducts are destroyed Xanthelasmas present and Pruritus ‘Anti-smooth muscle antibody (20% - 50%), bile ducts are scarred from inflammation, there is beading and ‘onion skinning, it’s associated with Ulcerative Colitis and P-ANCIA (80%) Common bile duct infection due to stones Spider Angioma, Palmar Erythema, Gynecomastia and Dupuytren's Contracture Build up liver toxine that cause renal failure Inflamed bile duct Inflammation of the gallbladder Formation of gallstones Gallstone obstructs the bile ducto7 GASTROINTESTINAL What is Cholestasis? What is Conjugated Bilirubin? What is Unconjugated Bilirubin? What is the most common type of Gallstone? What type of Gallstone can be seen on X-Ray? What is a Xanthoma? What is a Xanthelasma? What can high Cholesterol Cause? What can high Triglycerides Cause? What is Type 1 Hyperlipidemia? What is Type 2A Hyperlipidemia? What is Type 28 Hyperlipidemia? Obstructed bile duct high alkaline phosphatase (if in the ‘common bile duct) Water soluble and direct Bilirubin Fat soluble and indirect Bilirubin Cholesterol stone (not see on X-Ray) Calcium Bilirubinate stone Cholesterol build up (common at the elbow or Achilles tendon) Triglyceride build up and is seen under the eyes (Xanthoma subtype) Atherosclerosis Pancreatitis Defective Liver Lipoprotein Lipase (chylomicrons are elevated) Defective LDL-Clathrin Pit or B-100 (LDL are elevated) Deficiency of adipose receptors and LDL receptors (Increased LDL and VLDL levels)GASTROINTESTINAL What is Type 3 Hyperlipidemia? What is Type 4 Hyperlipidemia? What is Type 5 Hyperlipidemia? What do Chylomicrons do? What does VLDL do? What does IDL do? What does LDL do? Where is VLDL made? What are the breakdown products of VLDL? What is the treatment for hypercholesterolemia? What is the only statin to undergo renal excretion? Defective ApoE (Elevated IDL) Defective Adipose Lipoprotein Lipase, elevated VLDL Defective enzyme and receptor (C-lI) levated VLDL and Chylomicrons Associated with diabetes mellitus ‘They take Triglycerides (TG) from GI to liver and endothelium It takes TG's from liver to adipose It takes TG's from adipose to tissue It carries Cholesterol (only one to do this) Liver IDL and LOL Statins PravastatinGASTROINTESTINAL What blood level should be monitored in patients taking statins? What is the Mechanism of Action of Statins? What is Crigler-Najjar Type I? What is ilbert's Syndrome? What is Rotor's? What is Dubin-Johnson? What is Cullen's Sign? Liver enzymes every 3 months and Serum Cr Inhibit HMG CoA reductase Unconjugated bilirubin buildup Newborn or Infants No UDP-GT Phenobarbital yields no change Stress induced elevated Unconjugated Bilirubin Increased load saturates Glucurenyl Transferase Defective Bilirubin storage and Elevated Conjugated Bilirubin Defective Bilirubin storage BLACK LIVER Increased conjugated bilirubin Bruising around the umbilicus Caused by hemorrhagic pancreatitis (late sign)70 GASTROINTESTINAL What is Turner's Sign? What tests are used for following Pancreatitis? What will Ranson's criteria tell you and what will you see at 48 hours? What is Carcinoid Syndrome (Triad)? What is Peutz Jegher Syndrome? What produces Currant Jelly Sputum? What produces Currant Jelly Stool? What is Turcot's Syndrome? Bleed into Flanks and caused by Hemorrhagic Pancreatitis (early signs) Amylase (sensitive) breaks down Carbohydrates and Lipase (specific) breaks down Triglycerides Prognosis of Pancreatitis patients BUN >Smg/dl (decreased RBF) Calcium <8mg/dL. (saponification) HCT drops >10% (bleeding into pancreas), sequester >6 liters of fluid (3rd Spacing), Oxygen pO2<60mmHg (fluid/protein leak leads to ARDS), base deficit >4mEq/L (diarrhea due to no pancreatic enzymes) Diarrhea, flushing and wheezing Hyper-pigmented lower lip, patients will have dark gums and vagina, and ‘small bowel polyps Klebsiella Intussusception Familial Polyposis with Brain Tumorsn GASTROINTESTINAL What is Gardener's Syndrome? What is Familial Palyposis? What is Ulcerative Colitis? What is Crohn's Disease? What is Intussusception? How does Diverticulosis Present? How does Diverticulitis present? How does Spastic Colon present? How does Irritable Bowel Syndrome (IBS) present? Familial Polyposis with Bone Tumors 100% risk of Colon Cancer, APC gene defect and annual Colonoscopy starting at 5 years of age Starts at the rectum and ascends, Causes continuous lesion mucosa land submucosa, 1%/year risk for CA (10yr = 1056) IBD with Pseudopolyps, Hematochezia, Lead Pipe Colon and Toxic Megacolon Transmural, Cobblestones, Melena, Creeping Fat, Fistulas, Causes skip lesion. Currant Jelly Stool, Stacked Coin Enema, sausage shaped mass and knees to chest for comfort Grose blood Pain in LLQ no visible blood and may cause peritonitis, Intermittent severe cramps Alternating diarrhea / constipation History of stress No abnormalities on colonoscopyR GASTROINTESTINAL What is Pseudomembranous Colitis? What is Whipple's Disease? What color is stool with an Upper GI Bleed? What color is stool with a Lower Gl Bleed? What adds color to Stool? What gives urine its yellow color? What is the common side effect of the ERCP procedure? What is Charcot's Triad? What is Reynold's Pentad? Overgrowth of Clostridium Difficile Due to normal flora being killed off from long term antibiotic use ‘Tropheryma Whipplei (T. Whipplei) destroy the Gl tract Causing Malabsorption/Arthralgia, PAS (+) Black (Dark Red) (Melena) Bright Red Blood (Hematochezia) Stercobilinogen being oxidized to stercobilin Urobilinogen being oxidized to urobilin Pancreatitis from blocking the pancreatic duct during the procedure Jaundice, Fever (usually with rigors) and RUQ Pain Jaundice, Fever (usually with rigors), RUQ Pain, Hypotension and change in mental statusB GASTROINTESTINAL What separates unconjugated bilirubin from albumin? What does Sudan Black Stain test for? What are the risk factors for Primary Liver Cancer? What are the risk factors for Esophageal / Gastric CA? What are the bacteria associated with Colon Cancer? What Hepatitis B labs indicate an acute recent infection? What hepatitis B labs indicate recent immunization within >2/S2wks? What hepatitis B labs indicate immunization >2/52 weeks? What hepatitis 8 labs indicate previous infection and now immunity? What hepatitis 8 labs indicate infectious state? What hepatitis B labs indicate non-infectious state? ‘Sulfur (no Sulfur Rx in pregnancy) Steatorthea (fat malabsorption), patient seen with chronic pale, greasy, malodorous diarrhea and no evidence of infection Hepatitis B & C, Aflatoxin, Alcohol, ‘Smoking and Hemochromatosis, ‘Smoking, alcohol and nitrates Clostridium Melanogosepticus and Streptococcus Bovis HBcAg+, HBsAgs, (HBcAb+/-) HBsAge HBsAbt HBcAb+, HBsAb+, HBsAg- HBeAgt HBeAg-a GASTROINTESTINAL What hepatitis B labs indicate a chronic carrier state? What hepatitis 8 labs indicate that the patient is in the window period? What are the bugs that cause gastroenteritis, within & hours of eating the preformed toxin? HBsAge, (>6 months), HBsAb (+/-) HBeAbs, HBcAb+, HBSAg- Staph Aureus (potato salad) Clostridium Perfringens (holiday turkey/ham) Bacillus Cereus (fried rice syndrome)5 GASTROINTESTINAL PHARMACOLOGY What is the mechanism of action of H2 blockers? What are the indications for H2 blockers? What are the adverse effects of H2 blockers? What are the H2 blockers? What is the mechanism of action of Proton Pump Inhibitors (PPI)? What are the indications for Proton Pump Inhibitors? What are some Proton Pump Inhibitors (PPI)? What is the Mechanism of Action Misoprostol? What are the Indications for Misoprostol? Reversible block of histamine H2 receptors to decrease H+ secretion by parietal cells Peptic ulcer, gastritis and esophageal reflux Prolactin release: Gynecomastia, decreased libido, impotence in males Cimetidine inhibits P450 Cimetidine, Ranitidine, Famot and Nizatidine Irceversibly inhibit H+/K+ ATPase in stomach parietal cells Decreases proton secretion by parietal cells Peptic ulcer, gastritis, mid- ‘ezophageal Reflux and Zollinger- Ellison syndrome Omeprazole, Lansoprazole PGE1 analog, increase production and secretion of gastric mucous barrier, decreased acid production Prevents NSAID-induced peptic ulcers, maintenance of a Patent Ductus Arteriosus, induce Labor76 GASTROINTESTINAL PHARMACOLOGY What are the Adverse Effects of Misoprostol? What is the Mechanism of Action Octreotide? What are the Indications for Octreotide? What are the Adverse Effects of Octreotide? What is the Mechanism of Action Bismuth, and Sucralfate? What is Bismuth, and Sucralfate used for? What is the Mechanism of Action infliximab? What are the Indications for Infliximab? What are the Adverse Effects of infliximab? Diarrhea; Contraindicated in women of childbearing potential abortion inducing drug Long-acting somatostatin analog Acute variceal bleeds, acromegaly, ViPoma, carcinoid tumors Nausea, cramps, steatorrhea Bind to ulcer base, providing physical protection allows bicarbonate ion secretion to reestablish pH gradient in the mucous layer Increase ulcer healing, traveler's diarrhea Monoclonal antibody to TNF Crohn's Disease, Rheumatoid arthritis Respiratory infection (including reactivation of latent TB) fever, hypotensionGASTROINTESTINAL PHARMACOLOGY What is the Mechanism of Action Sulfasalazine? What are the Indications for Sulfasalazine? What are the Adverse Effects of Sulfasalazine? What is the Mechanism of Action Ondansetron? What are the Indications for Ondansetron? What are the Adverse Effects of Ondansetron? What is the Mechanism of Action Osmotic Laxatives? What is the Indication for Osmotic Laxatives? A.combination of sulfapyridine (antibacterial) and 5-aminosalicylic acid (anti-inflammatory) activated by colonic bacteria Ulcerative colitis, Crohn's disease Malaise, nausea, Sulfonamide toxicity, reversible Oligospermia 5-HT3 antagonist, powerful central acting antiemetic Control vomiting in patients undergoing chemo therapy and postoperatively Headache, constipation, dizziness Provide osmotic load to draw water out Lactulose treats Hepatic encephalopathy: gut flora degrades, itinto metabolites (lactic acid and acetic acid) that promote Nitrogen excretion as NH4+ Constipation