Quiz 3

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Quiz 3
2012-02-14 23:28:45
Med Chem

metabolism: drugs
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  1. Warfarin MOA
    anticoagulation; inhibits vitamin K in liver
  2. What enzyme metabolizes warfarin?
  3. What secondary enzyme also metabolizes warfarin (other than CYP)?
    VKORC1 (vitamin K epoxide reductase complex protein 1)
  4. What 3 drugs are great examples of genes affecting response to drugs (pharmacogenomics)?
    • warfarin
    • atomoxetine (strattera for ADHD)
    • irinotecan (anticancer)
  5. Which enzyme metabolizes atomoxetine (strattera)?
  6. Which drug has 15 different alleles in the encoding gene for metabolism?
    atomoxetine (strattera)
  7. What is the the indication of Irinotecan?
  8. What is the indication of atomoxetine?
  9. What is the MOA of Irinotecan?
    topoisomerase inhibitor
  10. What enzyme metabolizes irinotecan?
    UDP-glucuronosyltransferase 1A1
  11. Which drug has a decreased activity in 10% of cancer patients leading to a 5-fold increase in side effects because they do not have the enzyme?
    • irinotecan
    • don't have UDP-glucuronyltransferase 1A1
  12. What anticoag drugs are inhibited by CYP2B6?
    • Ticlopidine
    • Clopidogrel
    • Thiolactone metabolite of Prasugrel
  13. What are some drugs that enhance metabolism (enzyme induction)?
    • phenobarb
    • other barbiturates
    • glutethimide
    • phenylbutazone
    • meprobamate
    • ethanol
    • phenytoin
    • rifampin
    • griseofulvin
    • carbamazepine
  14. What is the indication of Glutethimide?
    piperidine based sedative hypnotic
  15. What sedative hypnotic undergoes selective hydroxylation to create 2 different enantiomers in a mixture?
  16. Which anti-seizure drug is metabolized into 10% 'R' enantiomer and 90% 'S' enantiomer?
  17. Which smooth muscle relaxant/peripheral vasodilator undergoes regioselective metabolism by demethylation?
    Papaverine (Pavabid)?
  18. Papaverine
  19. What is the indication of Papaverine (Pavabid)?
    smooth muscle relaxant used as a peripheral vasodilator
  20. Which two drugs can create metabolites that are active and toxic?
    • Nevirapine (AIDS)
    • Procainamide (anti-arrythmic)
  21. What specific metabolite created from Paroxetine can inactivate CYP2D6?
  22. What drug does the metabolite carbene come from?
    paxil (paroxetine)
  23. How many CYP enzymes does the human genome code for?
    at least 57
  24. What enzyme metabolizes more than 50% of drugs?
  25. Which local anesthetic is de-ethylated (oxidative dealkylation) during the first-pass effect into acetylaldehyde? Also classified as a tertiary aliphatic/alicyclic amine oxidation...
  26. What is the indication of Lidocaine?
    • local anesthetic
    • ventricular arrythmias during acute MI or cardiac sx
    • post-herpatic neuralgia caused by herpes zoster infection
  27. What drug cannot be given oral for ventricular arrythmias and why?
    • Lidocaine
    • b/c first pass effect deactivates the metabolites
  28. What drug has metabolites that can cause neurotoxicity/seizure and must be closely monitored during an IV?
  29. Which drug undergoes a series of metabolic steps prior to urine excretion, can be found in the urine 60-90 days after use, and 6 months after use in hair?
    9THC (marijuana, tetrahydrocannabinol)
  30. Which ant-seizure (anti-epileptic) drug undergoes oxidation via an intermediate arene oxide (epoxide) and a hydride shift?
    Phenytoin (Dilantin)
  31. Which three drugs undergo selective oxidation?
    • Diazepam
    • 17-alpha-ethinylestradiol
    • Bromobenzene
  32. Diazepam
  33. 17-alpha-ethinylestradiol
    oral contraceptive
  34. What is the indication of Diazepam(Valium)?
    • anti-seizure
    • muscle relaxant
  35. ___ is a terrible liver toxin because the epoxide it creates reacts with DNA and RNA? Was used during WWII. Attaches to either water or GSH
  36. Metabolism of this can lead to a carcinogen b/c of the epoxide it creates in the liver?
    benzo[a]pyrene polyaromatic hydrocarbons (charcobroil!)
  37. What is an example of a drug that creates an epoxide that can be isolated from the urine and has even been found in drinking water in CA? In this case, the epoxide metabolite is the ACTIVE drug. Oxidation of C=C olefin.
    Carbamazepine (Tegretol)
  38. Carbamazepine
  39. What is the indication of carbamazepine (tegretol)?
    partial and clonic-tonic seizures (anticonvulsant)
  40. What is another drug that undergoes olefinic oxidation via an intermediate epoxide?
  41. Secobarbitol
  42. What is the indication of secobarbitol?
    short duration anesthetic
  43. What are two drugs that undergo benzylic oxidations?
    • Metoprolol
    • Tolmetin
  44. Metoprolol
  45. Tolmetin
  46. What is the indication of metoprolol?
    beta blocker
  47. What is the indication of tolmetin?
    anti-inflammatory analgesic
  48. What are three drugs that undergo allylic oxidation?
    • Pentazocine (Talwin)
    • Quinidine
    • Hexobarbitol
  49. Pentazocine
  50. What is the indication of Pentazocine (Talwin)
    • narcotic used for pain
    • used for pre- or post op anesthesia
  51. Quinidine
    • Quinidex Extendtabs
    • Quinaglute Dura Tabs
    • Quinalan
    • Cardioquin
  52. What is the indication of quinidine?
  53. Which quinidine brand causes GI upset?
    Quinidex Extendtabs (sulfate salt)
  54. Which form of quinidine cause much less GI upset?
    the sugar salts (compared to the sulfate salt)
  55. What is the indication of glutethimide?
    insomnia (use for 3-7 days)
  56. What are two drugs that are oxidated at an alpha carbon next to carbonyl or an imine?
    • Diazepam
    • Glutethimide
  57. What is Diastat?
    • rectal diazepam gel
    • anticonvulsant
  58. Why would you use Diastat?
    • if you have N/V and you can't keep your oral anticonvulsant down
    • also for anxiety, skeletal muscle relaxant
  59. What drug does the metabolite Oxazepam stem from?
  60. Oxazepam
  61. What is Oxazepam used for?
    • anxiety
    • for detoxing an alcoholic
  62. What are two drugs that undergo aliphatic oxidation?
    • Ibuprofen
    • Chlorpropamide (Diabinese)
  63. What is the indication for Chlorpropamide?
    oral anti-diabetic sulfonylurea
  64. Chlorpropamide
  65. What are two drugs that undergo oxidation at alicyclic carbons?
    • Acetohexamide (dymelor)
    • Minoxidil (Loniten, Rogaine)
  66. What is the indication of Acetohexamide (Dymelor)?
    oral antidiabetic sulfonylurea
  67. What is minoxidil indicated for (two things)?
    • severe unresponsive hypertension (loniten)
    • male pattern baldness (rogaine)
  68. What are 4 examples of tertiary aliphatic and alicyclic amine oxidations?
    • Chlorpromazine (Thorazine)
    • Nicotine
    • Lidocaine
    • Tamoxifen Citrate (Nolvadex)
  69. What is the indication of Chlorpromazine (Thorazine) and Phenothiazine?
    • antiemetic
    • antivertigo
    • antipsychotic
    • tab, cap, supp, syrup, injection
  70. What drug cause the thorazine shuffle?
    • chlorpromazine (thorazine) or phenothiazine
    • it is neurotoxic
  71. What is the the #1 drug for treating breast cancer?
    tamoxifen citrate (nolvadex)
  72. What are 4 examples of oxidations of primary and secondary amines?
    • Propanolol (Inderal)
    • Methylphenidate (Ritalin)
    • Phentermine (Ionamin, Adipex-P, Zantryl, Fastin)
    • (dl)-Amphetamine sulfate
  73. What is propranolol indicated for?
    • beta blocker (non-selective)
    • test anxiety/stage fright
  74. Propanolol
  75. Methylphenidate
  76. What is the indication of Methylphenidate?
    • ADHD
    • narcolepsy
  77. Phentermine HCl
    • Fastin
    • Zantryl
    • Adipex-P
    • Ionamin
  78. What is phentermine indicated for?
    • appetite suppressant
    • managing obesity
    • used to study hardcore
  79. What is (dl)-Amphetamine sulfate indicated for?
    • ADHD
    • narcolepsy
  80. What drug makes metabolites like an imine, an oxime and phenylacetone, which can be found in the urine of meth users?
    (dl)-Amphetamine sulfate
  81. What are two drugs that undergo oxidation of nitrogen heterocycles?
    • Trimethoprim (Trimpex, Proloprim, Bactrim, Septra, Cotrim)
    • Nicotine
  82. What is trimethoprim indicated for?
    • dihydrofolate reductase inhibitor (antibiotic)
    • in combo to make Septra, used for UTIs and pcp (HIV pneumonia)
  83. What 2 drugs undergo oxidation of an amide?
    • Diazepam ---> DesmethylDiazepam
    • Cyclophosphamide (Cytoxan, Neosar)
  84. What is the indication of cyclophosphamide?
    alkylating agent (anticancer)
  85. Which drug has to be a prodrug in order to be active and the metabolite it creates can cause hemorrhagic cystitis? What is the name of the metabolite?
    • Cyclophosphamide= drug
    • Phosphoramide Mustard= active prodrug
    • Metabolite= Acrolein
  86. Which drugs undergo oxidation of a carbon-oxygen system (O-dealkylation)?
    • codeine----> morphine
    • trimethoprim
    • metoprolol
    • prazosin
    • indomethacin
  87. T/F: codeine is active in itself.
  88. What prodrug arises from codeine and is actually the active form of the drug, which some people do not ever get to experience if they are slow metabolizers?
    morphine comes from codeine
  89. Which drug undergoes desulfurization?
    Thiopental (Pentathol)
  90. What is Thiopental indicated for?
    induces anesthesia to get you through stage 1 of anesthesia so you don't vomit
  91. Thiopental
  92. Which drug undergoes sulfur oxidation?
    Thioridazine (Mellaril)
  93. Thioridazine
  94. What is thioridazine indicated for?
    antipsychotic tranquilizer
  95. What is a metabolite of Thioridazine (mellaril) that is not as toxic and is a good antipsychotic?
    Mesoridazine (Serentil)
  96. What is a drug that undergoes oxidative dehalogenation?
    Halothane (Fluothane)
  97. What is halothane indicated for?
    general anesthesia
  98. Halothane
  99. What is the huge problem with Halothane, which is metabolized by oxidative dehalogenation?
    it causes severe liver damage because it creates a fluorocarbon and HCl (10,000 times more acidic than vinegar)
  100. Name a drug that undergoes oxidative aromatization.
    Norgestrel (Progestin)
  101. Name a drug that undergoes stereospecific ketone reduction.
    R (+) Warfarin
  102. What are two drugs that undergo reduction of a nitro or azo compounds?
    • Dantrolene (Dantrium)
    • Sulfasalazine (Azulfidine)
  103. What is Dantrolene indicated for?
    direct acting skeletal muscle relaxant used in spasticity, malignant hyperthermia with seizures
  104. What is sulfasalazine indicated for?
    sulfonamide antibiotic and antiinflammatory used to treat ulcerative colitis and rheumatoid arthritis
  105. Sulfasalazine
  106. Dantrolene
  107. What are two drug that undergo miscellaneous reductions?
    • Disulfiram (Antabuse)
    • Sulindac (Clinoril)
  108. What is disulfiram indicated for?
    chronic alcoholism
  109. What is sulindac indicated for?
  110. Which drug undergoes a reduction in the liver (which is rare) and begins with a sulfoxide prodrug?
    sulindac (Clinoril)
  111. Which drug undergoes ester hydrolysis?
    aspirin (ASA)
  112. What are two other examples of hydrolysis of esters or amides? (reduction section)
    • Clofibrate (Atromid-S)
    • Prazosin (Minipress)
  113. What is the indication of Clofibrate?
  114. Clofibrate
  115. Prazosin
  116. What is the indication of Prazosin?
    • antihypertensive
    • alpha 1 blocker
  117. Which are harder to hydrolyze in the body, amides or esters?
  118. Many prodrugs are _____? Hint: easily hydrolyzed in the body
  119. What is an -enol drug that undergoes oxygen glucuronidase conjugation (phase II)?
    warfarin sodium
  120. Which alcohol hydroxyl drug undergoes glucuronidation?
    Chloramphenicol (Chloromycetin)
  121. What is the indication of Chloramphenicol?
    serious infections, monitor for blood dyscrasias
  122. What is a phenol hydroxyl drug that undergoes glucuronidation?
  123. What is a carboxylate hydroxyl example of glucuronidation?
    Fenoprofen (Nalfon)
  124. Chloramphenicol
  125. Fenoprofen
  126. What is the indication of Fenoprofen?
  127. What is an example of N-hydroxyl glucuronidation?
  128. What is Dapsone indicated for?
    • txt of brown recluse spider bites
    • leprosy
    • pcp (pneumocystitis carinni pneumonia)
  129. What are two drugs that undergo sulfate conjugations (phase II)?
    • Alpha-Methyldopa (Aldomet)
    • Albuterol (Proventil, Ventolin, Airet)
  130. Alpha-methyldopa
  131. Albuterol
    • proventil
    • airet
    • ventolin
  132. What is aldomet indicated for?
  133. What is albuterol indicated for?
    bronchospasms in COPD
  134. What is a drug that is conjugated with glycine?
    Isoniazid (Laniazid, Nydrazid)
  135. Isoniazid
    • Laniazid
    • Nydrazid
  136. What is Isoniazid indicated for?
  137. What are two drugs that undergo Glutathione (GSH) nucleophilic displacement conjugation?
    • Nitroglycerin
    • Azathioprine (Imuran)
  138. What is Nitroglycerin indicated for?
    nitrate vasodilator for treatment and prophylaxis of angina
  139. Azathioprine
  140. What is azathioprine indicated for?
    immunosuppressant used to txt transplantation and rheumatoid arthritis
  141. What drug leads to the active immunosuppressant mercaptopurine?
  142. What are two drugs that undergo GSH Michael Addition phase II conjugation?
    • APAP
    • Ethacrynic Acid (Edecrin)
  143. What is Ethacrynic acid indicated for?
    loop diuretic used to rid edema in CHF, renal and liver diseases= lots of urine produced to rid edema
  144. ethacrynic acid
  145. What toxic metabolite does APAP generate when undergoing phase II Michael addition GSH conjugation?
    • iminoquinone = liver failure
    • *reason why you should not drink alcohol and take APAP with or for hangover
  146. What are two drugs that undergo N-acetylation?
    • Clonazepam (Clonipin)
    • Hydralazine (Apresoline)
  147. What is clonazepam indicated for?
    anticonvulsant benzodiazepine
  148. Clonazepam
  149. Hydralazine
  150. What is hydralazine indicated for?
    antihypertensive vasodilator
  151. Which antihypertensive vasodilator has ~20 metabolites?
    hydralazine (apresoline)
  152. Which drug shows treatment failure because of fast acetylators?
  153. Which drug can have covalent binding in liver cell macromolecules leading to liver damage?
  154. Norepinephrine, dopamine, serotonin, and histamine are all biogenic amines that are inactivated by what 2 methylation molecules?
    • SAM
    • methyltransferase enzymes
  155. Which enzyme is responsible for inactivating dopamine and norepinephrine?
  156. What are two drugs that undergo methylation via COMT?
    • Levodopa (Larodopa, Dopar)
    • Terbutaline (Berthaire, Brethine, Bricanyl): not really though b/c of 1,3 position
  157. What is a resorcinol that is NOT a substrate for COMT because of the 1,3 position of hydroxyls?
  158. What is Terbutaline indicated for?
    sympathomimetic bronchodilator
  159. What position do the hydroxyls have to be to be substrates for COMT?
  160. What drug do you have to co-administer with Levodopa?
  161. Levodopa
    • Larodopa
    • Dopar
  162. Terbutaline
    • Brethine
    • Bricanyl
    • Berthaire
  163. What are 2 drugs that undergo methylation via N-methyl transferase?
    • amantadine (symmetrel)
    • nicotine
  164. Amantadine HCl
  165. What is amantadine indicated for?
    • Parkinson's
    • type A flu virus
  166. What is a drug that undergoes methylation via S-methyl transferase?
  167. What is propylthiouracil indicated for?
    hyperthyroidism by preventing synthesis of T3 and T4
  168. Why is grapefruit juice bad?
    the flavenoids in it inhibit p-glycoproteins in the GI tract = no absorption of drug
  169. Name 5 drugs that have been taken off the market due to DIs causing torsades depointes/QT elongation?
    • Terfenadine (Seldane): antihistamine
    • Mibefradil (Posicor)
    • Astemizole (Hismanal): antihistamine
    • Grepafloxacin (Raxar): antibiotic
    • Cisapride (Propulsid): caused GI problems
  170. Which antibiotic can cause QT elongation problems?
  171. When making an IV solution, what should you NEVER mix phenytoin with?
    • dextrose
    • use NS!
  172. When making an IV, what should you never mix amphotericin with?
  173. When making an IV, what should you NEVER mix with opiates?
  174. What will physically and chemically react with the beta-lactam rings of penicillins, cephalosporins, and monobactams in an IV solution and cause decomposition?
    gentamicin and other basic solution drugs like furosemide
  175. What are some red flag hyperlipidemia drugs?
    • bile acid sequesterants
    • statins
  176. What are some red flag drugs for GERD/ulcers?
    • cimetidine
    • cisapride
    • sucralfate
  177. What is a red flag drug for osteoporosis?
  178. What are some red flag anticonvulsants?
    • carbamazepine
    • phenobarbitol
    • phenytoin
  179. What is a red flag immunosuppressant?
  180. What is a red flag drug for CHF?
  181. What are some red flag drugs for TB?
    • isoniazid
    • rifampin
  182. What is a red flag anticoagulant?
  183. What is a red flag asthma bronchodilator?
  184. What is a red flag herbal product?
    St. John's Wort
  185. What is a red flag drug for UTI?
  186. What are some red flag drugs for HIV/AIDS?
    • reverse transcriptase inhibitors
    • protease inhibitors
    • non-nucleoside reverse transcriptase inhibitors
  187. What is a red flag women's product?
    oral contraceptives
  188. What is a red flag anti-depressant MAOI?
    tranylcypromine (Parnate)
  189. What is a red flag antibiotic?
    erythromycin and other macrolides
  190. What is a red flag manic-depressive drug?
  191. What is a red flag anti-fungal drug?
  192. What are "momma's little helpers"?
    amphetamines and secobarbitol
  193. What drugs are the main substrates for p-glycoprotein, ABC?
    • digoxin
    • fexofenadine
    • vincristine
    • indinavir
    • colchicine
    • topotecan
    • paclitaxel
    • loperamide
  194. What drugs inhibit p-glycoprotein ABC?
    • ritonavir
    • cyclosporine
    • verapamil
    • erythromycin
    • ketoconazole
    • itraconazole
    • quinidine
    • azithromycin
    • valspodar
  195. What drugs induce p-glycoprotein?
    • St. John's Wort
    • rifampin
  196. Which drug is given to cancer patients to get a more effective absorption of anticancer drugs and inhibit p-glycoprotein?
  197. What are some drugs that are substrates for organic cation transporters (OCTs) drug transporters?
    • cimetidine
    • methotrexate
    • zidovudine
  198. What are some drugs that are inhibitors of the OCT transporters?
    • probenicid
    • cefadroxil
    • cefamandole
    • cefazolin
  199. Which (OCT) drug is given with penicillins/cephalosporins to increase their absorption when there is a severe infection?
  200. Which drugs (inhibitors of OCT) can block their own elimination?
  201. What are some known cardiovascular substrates for p-glycoprotein?
    • digoxin
    • diltiazem
    • nicardipine
    • verapamil
    • mostly calcium channel blockers
  202. What are some known antineoplastic substrates for p-gycoprotein?
    • vinblastine
    • vincristine
    • etoposide
    • paclitaxel
  203. What are some known transplant substrates for p-glycoproteins?
    • cyclosporine
    • tacrolimus
  204. What are some steroid substrates for p-glycoprotein?
    • dexamethasone
    • hydrocortisone