Exam 1

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Exam 1
2012-09-18 22:58:18
Med Chem

Med Chem II Exam 1 (GI and Heart Packet 1)
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  1. Where is carbonic anhydrase located?
    • in the intracellular membrane and luminal brush membrane in the proximal convoluted tubule
    • also in the eye
  2. What does carbonic anhydrase do?
    converts water and carbon dioxide to hydrogen and bicarbonate in the proximal convoluted tubule
  3. Where do carbonic anhydrase inhibitors act?
    proximal convoluted tubule
  4. What are some side effects of carbonic anhydrase inhibitors?
    • hypokalemia
    • metabolic acidosis
    • 20% decrease in GFR
    • alkalinization of the urine
    • urinary calcium salt calculi formation
    • sulfa allergy
  5. Name the 3 carbonic anhydrase inhibitors.
    • Acetazolamide (Diamox, Dazamide)
    • Methazolamide (GlucaTabs, Naptazane)
    • Dichlorphenamide (Daranide)
  6. Which carbonic anhydrase inhibitor is indicated for acute elevation sickness, epilepsy, glaucoma, CHF edema?
  7. What is the main indication for the carbonic anhydrase inhibitors?
  8. What can happen after 1 week of therapy with a carbonic anhydrase inhibitor?
    resistance develops to the diuresis
  9. Does massive sodium excretion occur with use of carbonic anhydrase inhibitors?
    no, because of highly efficient reabsorption mechanisms downstream
  10. Which H2RA acidifies the urine?
  11. What does OATS pump out?
    • anions 
    • (anything negatively charged)
    • carboxylates or sulfonamides
    • organic acids
  12. What does OCTS pump out?
    • cations
    • (anything positively charged)
    • amines
    • organic bases
  13. Name 6 osmotic diuretics.
    • Glycerin (Osmoglyn)
    • Isosorbide (Ismotic)
    • Mannitol (Osmitrol)
    • Urea (Ureaphil)
    • 1:1 Complex (Pamabrom)
    • Ammonium Chloride in combo with caffeine 
  14. What is pyrilamine maleate?
    antihistamine sedative that is combined with APAP in Pamabrom for women
  15. Name an osmotic diuretic that acidifies the urine.
    Ammonium chloride
  16. Where in the kidney do osmotic diuretics act?
    proximal convoluted tubule
  17. What is the MOA of osmotic diuretics?
    • excretion into the lumen to alter the osmotic pressure, thereby, pulling water INTO the lumen for excretion 
    • (highly water soluble agents)
  18. This osmotic diuretic is indicated for acute renal failure, cerebral edema, elevated intraocular pressure?
  19. This osmotic diuretic is indicated for cerebral edema and elevated intraocular pressure?
  20. What are all of the osmotic diuretics generally indicated for?
    eyeball explosion (elevated intraocular pressure)
  21. What are glycerin and isosorbide indicated for?
    elevated intraocular pressure
  22. Name the OTC osmotic diuretic agents.
    • 1:1 complex of APAP with Pamabrom (Women's Tylenol Menstrual Relief, Maximum Strength Aqua Ban)
    • Pamabrom + APAP + Pyrilamine maleate (Midol Maximum Strength Menstrual Formula, Maximum Strength Multi-Symptom Pamprin)
    • Pamabrom + Magnesium salicylate + APAP (Maximum Cramp Relief Pamprin)
    • Ammonium Chloride + Caffeine
  23. Which drug is 40 times more potent than furosemide?
  24. Where do the loop diuretics act?
    thick ascending loop of Henle
  25. Name the two 5-2-3 high ceiling/loop diuretics.
    • Furosemide (lasix)
    • Bumetanide (bumex)
  26. Which drugs can be used off-label to treat end stage cancer when plasma calcium levels might be really high?
    loop diuretics like furosemide and bumetanide
  27. What are the 5-2-3 loop diuretics indicated for?
    • edema caused by CHF and hepatic cirrhosis
    • renal disease
    • acute pulmonary edema
    • hypertension (only oral dosage form)
    • symptomatic hypercalcemia
  28. What is the MOA of 5-2-3 loop diuretics?
    • inhibit the Na-K-Cl-carrier system primarily in the Loop of Henle
    • some trace of activity in the proximal and distal tubules
  29. These drugs are weak acids and therefore are excreted in the proximal tubule via OATS?
    5-2-3 loop diuretics (furosemide and bumetanide)
  30. T/F: 5-2-3 loop diuretics are extensively albumin bound  and therefore diuresis takes 2-3 days if the drug is given orally.
  31. When given in submaximal doses for HTN, which one has less frequency of hypokalemia? Thiazides or loops?
    Loops = less hypokalemia because of shorter duration of action
  32. What are some side effects of the 5-2-3 loop diuretics?
    • hypokalemia (use caution w/ glycosides like dig)
    • excess fluid and electrolyte loss (reduced GFR and loss of efficacy)
    • increased resorption of drugs normally excreted by proximal tubule (lithium and uric acid (gouty attack))
    • otoxicity (because of loss of K+)
    • N/V
    • myalgia
    • hyperglycemia
    • sulfa hypersensitivity
  33. Name the 4-3 loop diuretic. 
    Torsemide (Demadex)
  34. Which loop diuretic is metabolized by the CYP system and therefore has a lot of DIs?
    torsemide (demadex)
  35. This loop diuretic has the same indication and MOA as furosemide and bumetanide?
  36. This loop diuretic is 99% protein bound?
  37. This loop diuretic has side effects like ototoxicity, dizziness, muscle cramps, fatigue, nausea, and ORTHOSTATIC HYPOTENSION?
  38. What is the only loop diuretic that does not have a sulfa group?
    Edecrin (ethacrynic acid)
  39. Name the phenoxyacetic acid loop diuretic. 
    Edecrin (ethacrynic acid)
  40. This is the loop diuretic of choice if you have a sulfa allergy?
  41. This loop is indicated for ascites due to malignancy, idiopathic edema, lymphedema, pediatric congenital heart disease and nephrotic syndrome?
  42. T/F: All three classes of the loop diuretics have the same MOA.
  43. This loop is excreted 66% via OATS as unaltered drug and cysteine and glutathione conjugates and 33% goes into the bile?
  44. Name some drugs that interact with loop diuretics.
    • aminoglycosides
    • cardiac glycosides
    • lithium
    • salicylates
    • NSAIDs
    • anticoagulants
    • clofibrate
    • beta blockers
    • thiazide diuretics
  45. Should you take loop diuretics with or without food?
    without food for max absorption
  46. Describe GERD.
    • injury to the lumen of the esophagus by regurgitation of gastric or gastroduodenal contents (H+, pepsin, bile acids, pancreatic enzymes)
    • poor clearance of stomach contents and defective sphincter function
    • aka heartburn
  47. Name some drugs that lower esophageal sphincter tone.
    • calcium channel blockers
    • nitrates
    • theophylline
    • anticholinergics
    • narcotics
    • beta agonists
    • estrogen 
    • progesterone
  48. Name 3 direct irritants on the GI tract.
    • NSAIDs
    • Potassium supplements
    • bisphosphonates
  49. When might you suspect that a child has GERD?
    • if they:
    • cough at night
    • complain of abdominal pain
    • refuse to eat
    • have a bad taste in their mouth
  50. How do you treat GERD?
    • stop alcohol
    • stop tobacco
    • avoid certain foods 
    • eat 4-6 hours before bed
    • drugs like antacids, PPIs, H2RAs
  51. What are some symptoms of severe GERD?
    • erosion
    • continual pain
    • stricture/spasm--Barrett's esophagus--adenocarcinoma risk is greatly increased
  52. What are some symptoms of atypical GERD?
    • chest pain
    • hoarseness
    • throat tightness
    • asthma
    • chronic cough
    • hiccups
    • lingual dental erosion
    • recurrent otitis in kids
  53. What are some symptoms of common GERD?
    • heartburn
    • hyper-salivation
    • belching
    • vomiting
    • regurgitation
  54. Name the 3 steps of ulcers healing.
    • Exfoliation
    • Restitution
    • Recovery
  55. What type of bacteria is H. pylori?
    gram (-) rod
  56. What causes peptic ulcers? Bacteria or stress?
  57. How prevalent is the H. pylori infection that causes ulcers?
    50% have it worldwide and it increases with age
  58. How does H. pylori cause peptic ulcers (in basic terms)?
    it colonizes the mucus of the gastric epithelium
  59. Who proved that H. pylori was the cause of peptic ulcers and not stress?
    Barry Marshall and J. Warren
  60. Specifically, how does H. pylori create an ulcer?
    • H. pylori adheres to GI epithelial cells via a lipid raft-associated protein called HpA adhesion protein 
    • translocation of the CagA protein of H. pylori into the host cells
  61. T/F: H. pylori has been associated with gastric cancer.
  62. How do you determine if H. pylori is the true cause of an ulcer?
    • H. pylori produces a urease enzyme that cleaves urea to carbon dioxide and ammonia
    • the ammonia allows the bacteria to penetrate the protective mucus layer in the GIT
    • patient eats isotopically labeled Carbon13 or radioactive Carbon14 urea
    • if patient has infection, the bacteria will cleave the labelled urea and patient will either have carbon dioxide on their breath, or bicarbonate in their blood plasma
    • (use a mass spec to measure increase in Carbon13 isotopic label)
  63. What test is the gold standard for diagnosing H. pylori?
    urea test
  64. T/F: resistance to anti-microbials is high with H. pylori and that necessitates the use of multiple drugs.
  65. Which anti-microbials can you use to treat an H. pylori infection?
    • amoxicillin
    • clarithromycin
    • tetracycline
    • metronidazole
    • tinidazole
    • rifabutin
  66. Which anti-microbial drug could H. pylori develop a resistance to via the nitroreductase mutant?
  67. What are some combo products used to eliminate H. pylori infection?
    • Bismuth subsalicylate+ Metronidazole + TCN HCl (Helidac)
    • Lansoprazole
    • Omeprazole and other PPIs (H+ pump inhibitors)
    • Nizatidine and other H2RAs
    • Ranitidine bismuth citrate (Tritec)
    • Lansoprazole + amoxicillin + clarithromycin (Prevpac)
    • Omeprazole + sodium bicarbonate + magnesium hydroxide (Zegerid)
    • Biskalcitrate bismuth + metronidazole + tetracycline (Pylera)
  68. Pylera
    • bismuth
    • metronidazole
    • tetracycline
  69. Zegerid
    • omeprazole
    • sodium bicarbonate
    • magnesium hydroxide
  70. Prevpac
    • lansoprazole
    • amoxicillin
    • clarithromycin
  71. Tritec
    • ranitidine
    • bismuth citrate
  72. What is the MOA of H2 histamine antagonists?
    reversible competition at H2 receptors in gastric parietal cells
  73. What are the 2 major pathways of metabolism/inactivation of histamine?
    • 1. ring methylation by histamine N-methyl transferase
    • 2. oxidative deamination by MAO
  74. Where is histamine excreted?
    in the urine
  75. T/F: histamine is widely distributed (but unevenly) in all mammalian tissues.
  76. Where can you find histamine, specifically?
    • mast cells
    • blood
    • basophils
  77. What endogenous chemical in the body has 3 subtypes and is a member of the superfamily of G-protein coupled receptors?
  78. H1
  79. H2
  80. H3
    CNS and peripheral
  81. How do prostaglandins interact with histamine?
    • prostaglandins counter the histamine adenylate cyclase pathway
    • prostaglandins are cytoprotective (NSAIDs knock them out)
    • prostaglandins increase mucus and bicarbonate production
  82. _____ is a hydrophillic molecule whose active form is the monocation and is synthesized from the amino acid histidine by L-histidine carboxylase? It also contains nitrogens...
  83. Which one can a tolerance be developed to? H2 antagonists or PPIs?
    H2 antagonists
  84. Which H2 blocker does not undergo extensive first pass effect?
  85. What are the biological functions of histamine?
    • allergic responses
    • gastric acid secretion (powerful)
    • neurotransmitter functions in the CNS
    • vasodilation
    • increased capillary permeability
    • constriction of large vessels and bronchial tissue
    • increases HR, but decreases BP due to baroreceptor responses
    • T-lymphocyte proliferation
  86. This chemical has no positive charge at physiological pH and has electron withdrawing groups on the guanidine or guanidine-like group which decreases the basicity of the nitrogens in the molecule. What chemical is it?
  87. Name the 4 H2 blockers mentioned in class.
    • Tagamet (cimetidine)
    • Zantac (ranitidine)
    • Axid (nizatidine)
    • Pepcid (famotidine)
  88. What is the ultimate mediator of acid secretion?
    H+K+ATPase proton pump
  89. Why are PPIs so much better at treating GERD?
    because they inhibit the proton pump (H+K+ATPase) system which is far more superior than blocking H2 receptors
  90. This H2 blocker is a CYP450 INHIBITOR therefore has many drug interactions and should be the last choice?
    Tagamet (cimetidine)
  91. This H2 blocker can cause gynecomastia, drug fever, neutropenia, and depression? It also acidifies the urine...
  92. What are the 2 OTC H2 blockers that are indicated for sour stomach, heartburn and acid indigestion?
    • Pepcid and Tagamet
    • (I thought Zantac was too...)
  93. Which H2 blocker may cause an increase in transaminases?
    Axid (nizatidine)
  94. T/F: Ranitidine, famotidine, and nizatidine all inhibit CYP450 enzymes.
    false; only cimetidine does
  95. Which H2 blocker is 90% bioavailable (the highest of all of em)?
    Axid (Nizatidine)
  96. Where are the H+K+ATPase proton pumps located?
    • exclusively in the apical membranes of the parietal cells 
    • they are transmembrane proteins
  97. These have little to no effect on gastric juice production, secretion of pepsin, Intrinsic Factor, and GI motility?
  98. T/F: you do not need to stagger doses of antacids and H2 blockers.
    false; you do to maximize bioavailability
  99. Duexis
    • Ibuprofen + Famotidine
    • for arthritis
  100. T/F: all PPIs are acid unstable.
  101. If you have renal failure, would you use digitoxin or digoxin?
  102. If you have hepatic failure, would you use digitoxin or digoxin?
  103. These should not be chewed and are in enteric coated tab form or capsule form?
  104. Which one has a narrower therapeutic index and is more toxic? Digoxin or Digitoxin?
    Digoxin, but it is the one that is still on the market
  105. Which one is 100% renally excreted? Digoxin or Digitoxin?
  106. What do you give in a digoxin OD?
  107. What do you die from in an OD of digoxin?
    cardiac arrhythmia
  108. What are the two most common side effects of PPIs?
    headache and diarrhea
  109. Which ones are more highly protein bound- PPIs or H2 blockers?
    PPIs are highly protein bound (95-98%)
  110. What is the consequence of PPIs being highly protein bound?
    prolonged duration of action (24-72 hours)
  111. How are PPIs metabolized?
    • hepatically 
    • rapid
  112. What is the MOA of PPIs?
    within the parietal cells (at an acidic pH) they undergo an intramolecular rearrangement which generates a sulfenamide that covalently reacts with thiol functional groups forming a disulfide on the extracellular luminal domain of the pump protein
  113. T/F: PPIs are prodrugs.
  114. In order to get full inhibition of the proton pump, how many molecules of the PPI do you need?
  115. T/F: PPIs are permanent inhibitors of the proton pump system.
  116. T/F: PPI action can be overridden after a few days.
  117. How long does it take for the protein/membrane turnover to occur after a PPI has inhibited the system?
    3-5 days
  118. Where do PPIs act?
    • not in the stomach!!!
    • in the parietal cells
  119. What is hypochlorhydria?
    poor absorption of calcium salts which leads to malabsorption
  120. What can cause hypochlorhydria?
    taking a PPI without a meal
  121. What do PPIs do to bone?
    they decrease bone resorption of calcium by inhibiting osteoclastic vacuolar H+K+ATPase
  122. High dose PPI use for ____ long can significantly increase your risk for _____?
    • 1 year
    • hip fracture
  123. T/F: women have a higher risk of hip fracture while taking a PPI than men
  124. If you are taking a PPI, what should you supplement with?
    • calcium supplements
    • dairy products
    • if insoluble calcium salts, take with a meal
  125. Omeprazole
  126. Rabeprazole
  127. Pantoprazole
  128. Lansoprazole
  129. Esomeprazole
  130. What enzyme metabolizes the R enantiomer of omeprazole?
  131. What enzyme metabolizes the S enantiomer of omeprazole?
  132. This drug is the S enantiomer of omeprazole? And what enzyme metabolizes it?
    • esomeprazole
    • 3A4
  133. Which one would you recommend for an Asian? Prilosec or Nexium?
    Nexium because it is metabolized by 3A4, not 2C19 (Asians have trouble with 2C19)
  134. Asians show prolonged plasma levels of which drug?
  135. T/F: if patient has hepatic disease, you should decrease the dose of omeprazole.
    false; don't need to because it is urinally and fecally excreted
  136. T/F: protonix can be taken with antacids, with food, or without food
  137. This PPI is indicated for the maintenance of healing of GERD?
  138. Kids aged 1-11 years old can take which PPI?
  139. This drug is the pure enantiomeric form of Prevacid?
  140. Dexlansoprazole
  141. This PPI can decrease levels of the AIDS drug atazanvir by more than 70%?
  142. This PPI is not a CYP inhibitor, but is metabolized by 3A4 and 2C19?
  143. Consider dosage adjustment or use caution with which PPIs if hepatic impaired?
    • aciphex
    • protonix
    • prevacid
  144. T/F: you can take PPIs if you are pregnant.
  145. T/F: PPIs can cause hypomagnesemia.
  146. What 2C19 metabolized cardiac drug displays significant interactions with omeprazole?
  147. What are some important pearls to watch for if recommending an antacid?
    • be aware of sodium content in hypertensive patients
    • do not abuse antacids = rebound hyperacidity
    • use extreme caution with aluminum and magnesium products in renal failure patients
  148. Basaljel
    aluminum carbonate
  149. Riopan, Iosopan
  150. Amphojel, Alu-Cap, Dialume
    aluminum hydroxide
  151. MOM
    magnesium hydroxide
  152. CitrapH
    sodium citrate
  153. Do not take antacids 30 minutes before or after which drug?
  154. 90% of this drug is excreted in the feces and most of it is not absorbed?
  155. What is sucralfate indicated for?
    active duodenal ulcer
  156. What is the MOA of sucralfate?
    under acidic pH, the aluminum is split off, which produces a sulfated sucrose which forms a complex with proteinaceous exudate protecting the ulcer against acid, pepsin, and bile salts
  157. Sucralfate
  158. Cytotec
  159. This drug is indicated for the prevention of ASA and NSAID induced gastric ulcers?
  160. What is the MOA of cytotec?
    • it is a synthetic prostaglandin analog with anti-secretory and mucosal protective properties 
    • increases bicarbonate and mucus production
    • it counters histamine and increases adenylate cyclase activity
  161. this drug is absolutely contraindicated in pregnant women due to abortifacient properties?