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Block 10; Week 5-M > GI pharm-Harvey > Flashcards

Flashcards in GI pharm-Harvey Deck (81)
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1

What are some important peptic acid diseases?

GERD
Peptic ulcer disease

2

WHat are the defensive forces in peptic ulcer disease?

mucus
bicarb
mucosal blood flow
apical surface membrane transport
epithelial regenerative capacity
elaboration of prostaglandins

3

What are some things that can predispose or worsen peptic ulcer disease?

H. pylori infection
NSAID
aspirin
cigarettes
alcohol
gastric hyperacidity
duodenal gastric reflux

4

What are the 5 treatment categories for peptic acid diseases?

antacids
H2 histamine receptor antagonists
proton pump inhibitors
mucosal protective agents
antibiotics

5

What are some antacids used in peptic acid diseases? What is their MOA?

magnesium hydroxide
aluminum hydroxide
calcium carbonate
sodium bicarbonate
MOA: weak bases that neutralize stomach acid

6

What are the drawbacks to each type of antacid?

**all require frequent dosing
magnesium hydroxide--can cause diarrhea
aluminum hydroxide--can cause constipation
calcium carbonate & sodium bicarb--can cause bloating, metabolic alkalosis, milk alkali syndrome

7

What are some H2 histamine receptor antagonists used in peptic acid disease?

cimetidine
ranitidine
famotidine
nizatidine

MOA: blocks H2 histamine receptors on parietal cells.
**parietal cells secrete gastric acid

8

Which things do mucous neck cells secrete in the gastric glands of the stomach?

mucus
bicarb

9

What do parietal cells in gastric glands of the stomach secrete? What prompts this secretion?

Gastric acid-->activates pepsin
INtrinsic factor-->complexes w/ vit b12
stimulus: ach, gastrin, histamine

10

What do the enterochromaffin cells of the gastric glands of the stomach secrete? What prompts this secretion? Results?

secrete histamine-->increases gastric acid secretion
**stimulus is ach or gastrin

11

What do chief cells in gastric glands of the stomach secrete? Stimulus?

pepsin--digests proteins
gastric lipase--digests fats
**stimulus for release: ach, acid, secretin

12

What do the D cells in the gastric glands of the stomach secrete? Stimulus & fcn?

somatostatin-->inhibits gastric acid secretion
stimulus: acid

13

What do the G cells in the gastric glands of the stomach secrete? Stimulus & fcn?

gastrin-->stimulates gastric acid secretion
stimulus: peptides, AA, Ach

14

How does the antrum & fundus interact in the stomach?

ANTRUM: dietary peptides stimulate the G cell to release gastrin into bloodstream.
luminal acid stimulates D cells to release somatostatin that inhibits G cells.
Vagus nerve releases ACh that inhibits D cells & activates G cells.
FUNDUS: More Ach stimulation of parietal cells & enterochromaffin cells. Gastrin in bloodstream activates enterochromaffin cells to release histamine.
Histamine, Ach, gastrin act on parietal cells to release luminal acid.

15

What are some possible side effects of H2 receptor antagonists, specifically cimetidine?

interfere with hepatic metabolism of other drugs
can cause confusion, hallucinations, and agitation at high doses, especially in the elderly
block androgen receptors causing gynecomastia or impotence in men

16

How are H2 receptor antagonists metabolized & excreted?

liver & kidney

17

When is cimetidine most effective?

more effective for inhibiting nocturnal H+ secretion than meal stimulated H+ secretion.

18

What is the advantage of H2 receptor antagonists?

longer duration of action than antacids
replaced by PPI

19

What are some PPIs? What is their MOA?

omeprazole
esomeprazole
lansoprazole
pantoprazole
rabeprazole
MOA: structurally similar to H2 receptor antagonists
inhibit H+/K+ ATPase (proton pump) specific to gut

20

What are the side effects of PPIs?

can interfere with metabolism of some drugs
reduce absorption of vitamin B12, iron, calcium
increase incidence of respiratory infections
increased gastrin levels (rebound acid production)

21

How are PPIs metabolized?

via hepatic metabolism
have first pass metabolism--short half life (1.5 hours)

22

Describe how PPIs work in detail.

weak bases that are acid labile, so they are enteric coated & are prodrugs that are activated at site of action
@ parietal cells they irreversibly inhibit the proton pump & last for 24 hours

23

What are some examples of mucosal protection agents for peptic acid diseases?

sucralfate
misoprostol
bismuth subsalicylate

24

What is the MOA of sucralfate?

sucrose-sulfated aluminum hydroxide complex
forms viscous paste that selectively binds ulcers
stimulates prostaglandin and bicarbonate secretion

25

What are some therapeutic considerations w/ sucralfate for peptic acid diseases?

< 3% absorbed
used to avoid pH reduction (H2 blockers, PPIs)
may cause constipation
may impair drug absorption

26

What is the MOA of misoprostol?

analog of prostaglandin E1 (PGE1)
activates E3 prostaglandin receptors on parietal and non-parietal epithelial cells
inhibits H2 receptor stimulated H+ production
stimulates mucus and bicarbonate secretion
enhances mucosal blood flow

27

What are some therapeutic considerations when prescribing misoprostol?

readily absorbed orally
half-life < 30 min – requires frequent dosing
diarrhea, cramping, abdominal pain in 10-20% of patients

28

What is the MOA of bismuth subsalicylate?

coats ulcers creating protective layer
direct antimicrobial effects (including H. pylori)
absorbs enterotoxins

29

What are some therapeutic considerations when prescribing bismuth subsalicylate?

causes blackening of stools
can cause constipation
GOOD FOR:
traveler's diarrhea
very safe!
in H. pylori treatment combos

30

What is the quadruple therapy to great H. Pylori associated ulcers?

PPI
clarithromycin
amoxicillin or metronidazole
bismuth subsalicylate

31

What are the 2 types of gastric motility disorders?

hypomotility: constipation
hypermotility: diarrhea

32

What are the 5 treatment categories for hypo motility?

laxatives
cholinomimetics
D2 dopamine receptor antagonists
serotonin 5-HT4 receptor agonists
opioid receptor antagonists

33

What are the different types of laxatives?

bulk forming (psyllium, methylcellulose)
stool softeners (docusate, mineral oil, glycerin supp.)
osmotics (magnesium hydroxide, magnesium citrate, sodium phosphate)
stimulants (phenolphthalein, senna, bisacodyl)

34

What is an example of a cholinomimetic? MOA?

neostigmine
acetylcholinesterase inhibition
enhances Ach activation of gut smooth muscle muscarinic receptors

35

What is neostigmine used for? What are the negative side effects?

**used in the hospital for acute colonic pseudo-obstruction & a single dose evacuates!
SE: salivation, N/V/D, bradycardia (lots of parasympathetic response)

36

Give examples of D2 receptor antagonists used to treat hypo motility. What are their MOA?

metoclopramide
domperidone
MOA: blocks D2 receptor mediated inhibition of cholinergic smooth muscle contraction

37

Aside from hypo motility, what else are D2 receptor antagonists used for?

increasing gastric emptying in gastroparesis
diabetes
w/ H2 blocker & PPI for GERD
antiemetic

38

What are some side effects to keep in mind w/ prescribing D2 receptor antagonists for Hypomotility?

increases esophageal peristalsis & lower esophageal sphincter pressure
restlessness, drowsiness, insomnia, anxiety, agitation
galactorrhea, gynecomastia, impotence, menstrual disorders b/c of increased prolactin

39

What is an example of 5-HT4 receptor agonists that are used for treating hypo motility? What is the MOA?

tegaserod
MOA: partial agonist @ 5-HT4 receptors
acts presynaptically @ primary afferent neurons stimulating release of Ach & increasing smooth muscle contraction in the GI tract.

40

What are some therapeutic considerations when prescribing tegaserod?

good for idiopathic constipation or constipation from IBS

41

What are examples of opioid receptor antagonists? MOA?

methylnaltrexone
alvimopan
MOA: opioid receptors usu inhibit Ach release from enteric neurons. these meds block that! Allowing Ach release.

42

Therapeutic considerations when prescribing methylnaltrexone or alvimopan?

great for treating constipation in pts being treated w/ opioid analgesics
doesn't cross BBB though!

43

What are the treatment categories for hypermotility/diarrhea?

opioid agonists
colloidal bismuth
bile salt binding resins
somatostatin analogs

44

What are some examples of opioid agents used to treat hyper motility? MOA?

loperamide
diphenoxylate
MOA:
activates presynaptic opioid receptors, inhibiting Ach release
**increases colonic transit time & fecal water absorption

45

What are the therapeutic considerations for prescribing loperamide?

no analgesic effects b/c doesn't cross BBB
reduces potential for abuse or dependence

46

What are therapeutic considerations for prescribing diphenoxylate?

these preparations also contain atropine

47

What are some examples of colloidal bismuth drugs used to treat hyper motility? MOA?

bismuth subsalicylate
bismuth subcitrate potassium
MOA: can absorb bacterial enterotoxins

48

What are some examples of bile binding resins used to treat hyper motility? MOA?

cholestyramine
colestipol
colesevelam
MOA: absorbs bile salts that cause colonic secretory diarrhea

49

What are bile binding resins used to treat? SE?

disease of the terminal ileum (crohn's) bc it results in malabsorption of bile salts
SE: bloating, flatulence, constipation

50

WHat is an example of a somatostatin analog? MOA?

octreotide
MOA: activates somatostatin receptors in gut
inhibits gastrin production
reduces intestinal fluid secretion

51

Therapeutic considerations in prescribing somatostatin analogs for hypermotility?

short half-life (3 min)
administered subcutaneously
used to treat secretory diarrhea associated with GI neuroendocrine tumors
can inhibit pancreatic secretions leading to steatorrhea and fat soluble vitamin deficiency

52

what is IBS?

Recurring idiopathic condition associated with abdominal discomfort (pain, bloating, cramps), diarrhea and/or constipation.

53

What are the 3 treatment categories for IBS?

anticholinergics
serotonin 5-HT3 receptor antagonists
serotonin 5-HT4 receptor agonists

54

Give an anticholinergic agent used to treat IBS & its MOA.

dicyclomine
MOA: blocks muscarinic cholinergic receptors in gut, reducing secretions & motility

55

What are the therapeutic considerations with prescribing dicyclomine for IBS?

used for the treatment of diarrhea-predominant IBS
not particularly effective
higher doses cause significant anticholinergic side effects (dry mouth, blurred vision, urinary retention)

56

GIve an example of a serotonin 5-HT3 receptor antagonist used to treat IBS & its MOA.

alosetron
MOA: blocks 5-HT3 receptors on extrinsic primary afferent neurons

57

What are some important therapeutic considerations for prescribing alosetron?

diarrhea-predominant IBS
**SE: pretty bad constipation

58

Give an example of a serotonin 5-HT4 receptor agonist used to treat IBS. MOA?

tegaserod
MOA: partial agonist at 5-HT4 receptor
**stimulates release of Ach, GI smooth muscle contraction

59

What are the therapeutic considerations when prescribing tegaserod?

used to treat constipation-predominant IBS

60

What are the treatment types for nausea?

serotonin 5-HT3 receptor antagonists
neurokinin NK1 receptor antagonists
phenothiazines & butyrophenones
antihistamines/anticholinergics
cannabanoids

61

Give an example of a 5-HT3 receptor antagonist used to treat nausea & its MOA.

ondansetron
MOA: blocks 5-HT3 receptors peripherally & centrally (vomiting center & chemoreceptor trigger zone)

62

What are the therapeutic considerations for prescribing ondansetron for nausea?

postop nausea & chemo
not good for other types of nausea

63

Give an example of a neurokinin NK1 receptor antagonist used to treat nausea & its MOA.

aprepitant
MOA: blocks central neurokinin NK1 receptors in the vomiting center & chemoreceptor trigger zone

64

What are the therapeutic considerations for prescribing aprepitant?

used for nausea w/ chemo & taken w/ corticosteroids

65

What are some phenothiazines & butyrophenones used to treat nausea & what is their MOA?

prochlorperazine
promethazine
droperidol
MOA:
blocks D2 dopamine receptors in the chemoreceptor trigger zone
blocks M1 muscarinic receptors in the vomiting center

66

What are some therapeutic considerations when prescribing phenothiazines & butyrophenones?

used to treat chemotherapy and postoperative nausea
also used to treat vertigo
may cause extrapyramidal effects (movement disorders

67

What are some antihistamines/anticholinergics used to treat nausea? MOA? NOTE: these are good for motion sickness.

scopolamina
diphenhydramine
MOA:
scop--blocks M1 muscarinic receptor in the vestibular system
diphen--blocks H1 histamine receptors in the vomiting center

68

Give an example of a canabanoid & when it is used to treat nausea.

dronabinol
for chemo nausea

69

Describe the symptoms & process of ulcerative colitis.

diffuse mucosal inflammation of the colon
bloody diarrhea, pain, tenesmus

70

Describe the symptoms & process of crohn's disease.

patchy transmural inflammation affecting any part of the GI tract
immune response possibly directed against bacteria that attacks the GI tract
pain, vomiting, diarrhea, weight loss, intestinal obstruction

71

Give the 4 categories of treatments for inflammatory bowel disease.

aminosalicylates
glucocorticoids
antimetabolites
tumor necrosis factor (TNF) antagonists

72

Give some drugs that are considered aminosalicylates & their MOA.

sulfasalazine
mesalamine
MOA:
5-ASA is the active compound
inhibits COX & lipoxygenase pathways
**inhibits inflammatory cytokines

73

What are aminosalicylates used to treat exactly?

mild-moderate UC
crohn's

74

Give some examples of glucocorticoids used to treat IBD & their MOA.

prednisone, prednisolone, budesonide, hydrocortisone (enema)
MOA: inhibits inflammatory cytokines (like TNFalpha) & chemokines
inhibits COX-2 dependent production of prostaglandins & leukotrienes

75

When are glucocorticoids used in IBD?

Moderate-->severe UC
crohn's

76

Give some anti-metabolites & their MOA in treatment of IBD.

methotrexate
azathioprine
6-mercaptopurine
MOA: suppresses immune system
**interferes w/ IL-1
**increases release of adenosine
**stimulates apoptosis of activated T cells
**helps with maintenance of remission

77

Give some examples of tumor necrosis factor antagonists used to treat IBD & their MOA.

infliximab
adalimumab
certolizumab
MOA: antibodies against the pro inflammatory cytokine TNFalpha

78

When do you use TNF antagonists in IBD?

moderate-severe Crohn's disease that doesn't respond to other meds.

79

Give the meds used for mild & responsive IBD.

budesonide (ileitis)
topical corticosteroids (proctitis)
antibiotics
5-ASA

80

Give the meds used for moderate IBD.

TNF antagonists
oral corticosteroids
methotrexate
azathioprine/6-mercaptopurine

81

Give the meds used for severe/refractory IBD.

surgery
natalizumab
cyclosporine
TNF antagonists
IV corticosteroids