PHRD5985 Pharmacotherapy Lecture 5 - Drug-Induced NVD, Constipation, IBD

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PHRD5985 Pharmacotherapy Lecture 5 - Drug-Induced NVD, Constipation, IBD
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2014-02-05 06:49:53
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pharmacotherapy
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  1. location of the VC (vomiting center)
    medulla oblongata
  2. major NT targets for prevention/treatment of N/V (4)
    • 1) 5HT3
    • 2) D2
    • 3) cholinergic
    • 4) histamine
  3. drug-induced causes of N/V (7)
    • 1) chemotherapy
    • 2) opiates
    • 3) abx
    • 4) NSAIDs
    • 5) digoxin
    • 6) estrogens, progesterone
    • 7) DA agonists
  4. drug class of prochlorperazine & promethazine
    phenothiazines
  5. MOA of phenothiazines
    • block dopamine, M1 (ACh), & -adrenergic Rs in brain
    • depresses brainstem reticular system
  6. which phenothiazine can be used to prevent motion sickness?
    promethazine (blocks H1 Rs)
  7. drug class of ondansetron, granisetron, dolasetron, palonosetron
    5HT3 R antagonists

    (-setron looks like serotonin)
  8. MOA of 5HT3RAs
    block presynaptic 5HT3 Rs on sensory vagal fibers in gut wall
  9. advantage of odansetron over granisetron
    fast orally disintegrating tablet for faster relief & better if vomiting
  10. which is better for pregnant women - phenothiazines or 5HT3RAs?
    5HT3RAs - Pregnancy Category B
  11. MOA of metoclopramide
    • blocks DA Rs in CTZ
    • increases LES tone
    • aids gastric emptying
  12. which is better for pregnant women - metoclopramid, trimethobenzamide, or droperidol?
    metoclopramide - Pregnancy Category B
  13. drugs for prevention of motion sickness (2)
    • 1) scopalamine transdermal patch
    • 2) promethazine
  14. MOA of scopalamine
    acts in CNS by blocking cholinergic (ACh) transmission from vestibular nuclei to higher centers in the CNS, and from reticular formation to VC
  15. how to use scopalamine patch
    apply 4hrs prior to activity, and then every 72hrs as needed to prevent motion sickness
  16. 4 types of diarrhea
    • 1) secretory (bacteria)
    • 2) osmotic (laxatives, sugar, ions)
    • 3) exudative/inflammatory
    • 4) altered intestinal motility (motor)
  17. drug-induced causes of diarrhea (11)
    • 1) abx
    • 2) chemotherapy
    • 3) -glucosidase inhibitors
    • 4) antacids w/ Mg
    • 5) colchicine
    • 6) laxatives
    • 7) metformin
    • 8) metoclopramide
    • 9) NSAIDs
    • 10) orlistat
    • 11) sorbitol
  18. drug class of diphenoxylate/atropine (Lomotil), loperamide
    antidiarrheal
  19. MOA of antidiarrheals
    -opioid receptor agonist -> reduce intestinal motility
  20. which antidiarrheal works both locally AND centrally on opioid receptors?
    diphenoxylate/atropine (Lomotil)

    (loperamide only locally)
  21. safer antidiarrheal
    loperamide - Pregnancy Category B, no DDIs
  22. antidiarrheal contraindicated in UC
    loperamide
  23. drugs to treat OIC (opioid induced constipation) (2)
    • 1) methylnaltrexone (Relistor)
    • 2) Lubiprostone (Amitiza)
  24. antidiarrheal w/ abuse potential
    Lomotil (can cross BBB & have euphoric effects)
  25. MOA of methylnaltrexone (Relistor)
    peripheral -opioid R antagonist
  26. MOA of lubiprostone (Amitiza)
    chloride channel activator -> enhances chloride-rich intestinal fluid secretion & improves fecal transit
  27. safer OIC treatment in pregnant women
    methylnaltrexone (Relistor) -> pregnancy category B
  28. OIC treatment appropriate for renally impaired pt
    lubiprostone (Amitiza)
  29. OIC treatment appropriate for hepatically impaired patient
    methylnaltrexone (Relistor)
  30. IBS drug approved only for treatment in women
    lubiprostone (Amitiza)
  31. drugs used for IBS-C treatment (3)
    • 1) linaclotide (Linzess)
    • 2) lubiprostone (Amitiza, ONLY WOMEN)
    • 3) Tegaserod (Zelnorm)
  32. MOA of linaclotide (Linzess)
    guanylate cyclase agonist - stimulates secretion of chloride & bicarbonate into intestinal lumen
  33. MOA of tegaserod (Zelnorm)
    5HT4 partial agonist - stimulates peristalsis & reduces visceral pain
  34. drug used for IBS-D treatment
    alosetron (Lotronex)
  35. MOA of alosetron (Lotronex)
    selective 5HT3 antagonist -> blocks activation of ligand-gated cation channels & delays transit & secretion
  36. 2 antispasmodic drugs
    • 1) dicyclomine (Bentyl)
    • 2) hyoscyamine (Levsin)
  37. MOA of dicyclomine (Bentyl)
    antispasmodic/anticholinergic agent alleviates smooth muscle spasm of GI tract
  38. MOA of hyoscyamine (Levsin)
    belladonna alkaloid that inhibits action of ACh on smooth muscle
  39. antispasmodic that is safe for children
    hyoscyamine (Levsin)
  40. antispasmodic that is safe for pregnant women
    dicyclomine (Bentyl) - Pregnancy Category B
  41. 1st line treatment for IBS-C
    bulk-forming laxatives
  42. 1st line treatment for IBS-D
    diet change, loperamide/Lomotil
  43. droperidol (antiemetic) formulation
    injection
  44. methylnaltrexone (OIC tx) formulation
    SC injection
  45. lubiprostone (Amitiza; OIC tx) formulation
    capsule
  46. linaclotide (Linzess; IBS-C tx) formulation
    capsule
  47. alosetron (Lotronex; IBS-D tx) formulation
    tablet
  48. 2 drugs mentioned in this lecture as only being injectable
    • 1) droperidol
    • 2) lubiprostone
  49. only drugs mentioned in this lecture as being available as a suppository
    • prochlorperazine, promethazine 
    • -> phenothiazines
  50. special population to avoid prochlorperazine
    patients w/ Parkinson's disease
  51. contraindication with 5HT3 RAs
    concomitant use w/ apomorphine
  52. key point about alosetron (Lotronex; IBS-D tx)
    it is not approved in children and males

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