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GI Week 2 > Anti-ulcer Drugs > Flashcards

Anti-ulcer Drugs Flashcards

1
Q

What are the three general usues for the anti-ulcer drugs?

A
  1. peptic acid disease (ulcers)
  2. GERD and NERD
  3. Hypersecretory states
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2
Q

What are the two most common causes of peptic acid disease?

A

H pylori infection and NSAID toxicity

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3
Q

What are some hypersecretory states you can use these drugs for?

A
  1. hyperacidity
  2. dyspepsia
  3. stress ulcers
  4. gastronoma (Zollinger-Ellison)
  5. Systemic mastocytosis
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4
Q

What are the 6 management objectives for treating peptic ulcer disease?

A
  1. health the lesion
  2. stop the pain
  3. avoid recurrence
  4. avoid complications
  5. avoid the necessity for maintenance dosing
  6. prevent development of H pylori resistance
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5
Q

What are the three general treatment strategies?1

A
  1. Kill the H pylori with ABx
  2. Relieve the pain by decreasing the effects of H+
  3. replace prostaglandins if the ulcer is caused by NSAID use
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6
Q

What are the 4 ways you can decrease the effects of H+?

A
  1. decrease stimulation of acid formation (anticholinergics or H2 blockers)
  2. decrease acid secretion (PPI)
  3. Buffer the acid (antacid)
  4. Protect the surface
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7
Q

What is the number one class of drugs for relieving the pain?

A

PPIs

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8
Q

What are the 5 antimicrobials used for H pylori infections?

A 
amoxicillin
clarithromycin
metronidazole
rifabutin
tetracycline
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9
Q

What are the two general ways an antimicrobial can get to the H pylori?

A

Either directly in the stomach lumen or by movement across the stomach epithelial cells to get into the lumen

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10
Q

What’s a hugely important characteristic of an antibiotic if it’s going to work againt H pylori?

A

needs to be acid stable

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11
Q

What are the main factors that influence the choice of specific antimicrobial agents for treatment of H pylori?

A
  1. H pylori susceptibility to agent
  2. pharmacokinetics - distribution (where does it get in the stomach(
  3. drug resistance
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12
Q

What penicillin do we use for H pylori and why?

A

Amoxicillin

The group 1 penicillins and penicillinase-resistant penicillins don’t work against gram negatives

Group 4 anti-pseudomonals like piperacillin aren’t orally effective in the gut

Ampicillin isn’t acid stable

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13
Q

Can you substitute ampicilin for amoxicillin?

A

Nope - they’re both aminopenicillins, but ampicillin isn’t acid stable enough

plus, amoxicillin can reach more than twice the blood levels with the same oral dose

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14
Q

What’s the mechanism of action for amoxicillin?

A

bactericidal beta lactam cell wall inhibitor

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15
Q

What’s the main toxicity for amoxicillin?

A

hypersensitivity reactions

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16
Q

What macrolide can be used for H pylori?

A

Clarithromycin.

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17
Q

Why is clarithromycin the best macrolide?

A

first of all, erythromycin isn’t acid stable

second, azithromycin just isn’t as effective against H pylori (demonstrated with Clarithromycin having a lower MIC50)

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18
Q

What’s the mechanism of action for clarithromycin?

A

bacteriostatic 50S rRNA protein synthesis inhibitor

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19
Q

WHat are the major toxicities of clarithromycin?

A

GI irritation

drug interactions via inhibition of cyp 3A4

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20
Q

Which tetracycline antibiotic is used for H pylori

A

tetracycline itself

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21
Q

Why is tetracycline better than the others like doxycycline and minocycline?

A

Because it isn’t completely absorbed, which means some stays in the stomach lumen (which is a good thing in this case)

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22
Q

What instructions should you give to patients about how to take tetracycline for H pylori?

A

Tell them to take with food so that emptying is delayed and it stays in the stomach loner

DON’T take it with antacids because they will chelate it and decrease effectiveness

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23
Q

What’s the mechanism of action for tetracycline?

A

bacteriostatis 30s rRNA subunit protein synthesis inhibitor

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24
Q

What are the toxicities for tetracycline?

A

GI irritation
photosensitivity
discoloraiton of growing teeth (don’t give to pregnant women and chidlren)

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25
Q

Why do we use rifabutin and not rifampin? THey’re both rifamycin ABx….

A

Rifabutin is more effective than the others in this class

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26
Q

What’s the mechanism of action for rifabutin?

A

bacteriocial - inhibits bacterial RNA polymerase

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27
Q

What are the toxicities for rifabutin?

A

hypersensitivity reactions and fever
hepatotoxicity
CYP p450- induction
turns fluids orange/red

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28
Q

What’s the newer formulation of metronidazole that’s getting to be more common because there are fewer dosing requirements?

A

tinidazole

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29
Q

How does metronidazole/tinidazole work

A

mechanism somewhat unknown - probably DNA damage

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30
Q

Why are we using metronidazole/tinidazole less often now?

A

35-60% of strains are resistance

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31
Q

What are the side effects of metronidazole/tinidazole?

A

GI discomfort, CNS toxicity, disulfiram-like reaction, maybe teratogenic inhibition of cyp 2C9

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32
Q

What are the two considerations for metronidazole’s inhibition of cyp 2C9 in the context of peptic ulcer disease?

A
  1. potentiate warfarin, which is bad for a bleeding ulcer
  2. one good thing is that it will reduce the clearance of H2 blockers which increases the effect. Also increases side effects though
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33
Q

What are the two ways that bismuth subsalicylate helps with peptic ulcer disease?

A
  1. antimicrobial action (disrupts cell wall, prevent adhesion, urease inhibition?)
  2. protection of the surface (coating it and stimulating seretion of mucus, PGE2 and bicarb)
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34
Q

The active ingredient is the bismuth, but where does it work?

A

in the stomach, not in the lower GI

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35
Q

What are the side effects of bismuth subsalicylate?

A

Bismuth will turn the tongue and stools black

Salicylate is the bigger issue for side effects though: vomiting, tinnitus, confusion, hyperthermia, respiratory alkalosis early and metabolic acidosis late

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36
Q

What are the two main issues for antimicrobial treatment failure?

A

resistance

compliance - have to take a ton of pills for weeks

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37
Q

Describe the rates of resistance tot he various antimicrobials?

A

35-65% resistant to metronidazole

5% res. to clarithromycin, but maybe higher

rare to tetracycline, amoxicillin and rifabutin

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38
Q

What class of drugs were used historically, but not anymore because they slow gastric emptying and prolong the exposure of the ulcer to acid?

A

muscarinic receptor antagonists

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39
Q

What are the two muscarinic receptor antagonists we should know?

A

atropine

pirenzipine

40
Q

What receptors do atropine and pirenzipine block?

A

atropine blocks M1 and M3

Pirenzipine is selective for M1

41
Q

What are the side effects for the antimuscarinics are therapeutic dose?

A 
ABCD's....
anorexia
blurry vision
constipation, confusion
dry mouth
sedation, stasis of urine
42
Q

What are the overdose effects for the antimuscarinics?

A

hallucinations and confusion
tachycardia
hot, dry skin

43
Q

What are the 4 H2 receptor antagonists we need to know?

A

dimetidine
famotidine
nixatidine
ranitidine

44
Q

How do the H2 receptor antagonists work?

A

highly selective for H2 - they block histamine-induced gastric acid secretion (including what’s produced during sleep)

they also lower intracellular cAMP which affects the basal and nocturnal secretion due to other agents - like meal-time secretion

45
Q

Do the H2 blockers have relatively long or short half lives?

A

relatively short - only 1-4 hours OTC and 10 hrs for Rx strength

46
Q

H2 blocker metabolism? excretion?

A

extensive hepatic metabolism and renal excretion

47
Q

Which H2 blocker is the most potent?

A

famotidine - also requires the lowest dose so it’s the best tolerated

48
Q

What are the side effects for the H2 blockers? When given to healthy patients…

A

really no significant side effects when given orally to healthy patients

rapid IV infusion can cause bradycardia and hypotension, so just give it slowly

not sure what happens in pregnancy, so advise against it

49
Q

What are the drug-drug interactions for the H2 blockers though?

A
  1. decreased ethanol metabolism (esp in women) so don’t drink with these!
  2. compete for tubular secretion in the kidneys with weak bases - like metronidazole!
50
Q

What’s the special potential side effect for cimetidine seen in 3% of patients?

A

can cause decreased binding of DHT to androgen receptor, decreased estrogen metabolism and increased prolactin, so causes gynecomastia in males and galactorrhea in females

inhibits cyp p450 so increases other drug effects

51
Q

What suffix do the PPIs end in”

A

prazole

52
Q

What are the PPIs we need to know?

A

esomeptrazole/omeprazole
lansoprazole
pantoprazole
rabeprazole

53
Q

How do esomeprazole and omeprazole differ?

A

they don’t really…
omeprazole is the racemic mixture and esomeprazole is just the S isomer (metabolized more slowly and theoretically provides a therapeutic advantage - not really though)

54
Q

How do the PPIs work?

A

they are the most effective agents for reducing acidity because they irreversibly block the final common pathway in acid secretion — the H/K ATPase found in the parietal cell

55
Q

How are the PPIs absorbed? Why is this important?

A

they’re absorbed in the small intestine but they’re acid labile, which means they need a coating to be able to pass through the stomach to get to the small intestine

56
Q

Why are PPIs selective for what we want?

A

once the prodrug reaches circulation, it just circulates around and then concentrates in acidified ccompartments like the canaliculi where they’re protonated to the active form. So they’re only active in acidic environments

57
Q

How is the timing of the PPIs critical?

A
  1. you need to give during the fasting state so that stomach motility will be low and the pills won’t be crushed!

ISSUE: This means they would be effectve at a time when the H/K pumps aren’t even on - worthless

  1. Means you need to take them 30 mintues before eating so the drugs get activated int he parietal cells right when the pumps turn on
58
Q

Why are the PPIs only dosed once a day?

A

they have a relatively short half life, but they’re irreverisble inhibitors so it takes about 18 hours for new pumps to generate

thus, take them 30 mintues before breakfast and then they last the whole day

59
Q

Full inhibition of all the H/K pumps takes how many days? What does this mean for dosing?

A

3-4 days

this means you start out with a high dose and then taper as symptoms get under controll

60
Q

Can you give the PPIs IV?

A

yes for all but omeprazole

61
Q

What are the side effects of the PPIs?

A

No significant side effects! Which is why they can be given OTC…

some people get HA, diarrhea and nausea

62
Q

What’s the issue when you stop taking the PPIs though?

A

there’s significant rebound hypersecretion

63
Q

What are the concerns for long-term blocking of acid production in the stomach?

A
  1. decreased absorption of Ca (hip fx), Zn, B12 and iron (anemia)
  2. increased risk for infections - esp respiratory and enteric
  3. Maybe ECL hyperplasia?
64
Q

Why would you get ECL hyperplasia and hypergastronemia after long-term PPI use?

A

normally decreased pH will trigger somatostatin release which inhibits gastrin, but if you block acid production with a PPI, you don’t get the signal for somatostatin, so gastrin keeps being secreted, which may trigger ECL hyperplasia

65
Q

True or false: PPIs are also highly effective in treating non-ulcer-related dyspepsia.

A

False! - only 10-20% better than placebo for this despite marketing claims to the contraty

66
Q

What are some examples of bases that are used to bugger stomach acid? Antacids….

A

Aluminum hydroxide
calcium carbonate
magnesium hydroxide
sodium bicarbonate

67
Q

Of the 4 antacids we know, which are systemically absorbed? Is this bad or good?

A

Calcium carbonate and sodium bicarbonate are systemically absorbed

this is bad because it doesn’t stay where you need it to

68
Q

What’s the sort of benefit to having an antacid that rapidly dissociates?

A

benefit is that you have faster onset, but this also means you have short duration

69
Q

Which antacids have fast dissociation and thus rapid onset?

A

CaCO3 and NaHCO3 again

70
Q

Many of the side effects of the antacids have to do with the effects of their cations or products. What is the side effect of CaCO3 and NaHCO3?

A

they both dissociate to products including CO2, so you get gas and burping

71
Q

What’s the product effect of aluminum hydroxide?

A

it’s constipating

72
Q

WHat’s the product effect of magnesium hydroxide?

A

osmotic diarrhea

73
Q

How can you avoid the product effects for Magnesium hydroxide and aluminum hydroxide?

A

just give them together and the effects will balance out

74
Q

What’s the serious but rare side effect of aluminum hydroxyde?

A

decreased PO4 absorption leading to increased Ca2+ loss and osteomalacia

75
Q

What’s the serious but rare side effect for magnesium hydroxide?

A

renal insuffiency leading to hyper-magnesemia and CNS and cardio toxicity

76
Q

What are the serious but rare side effects for caclium carbonate?

A

mild systemic alkalosis

hypercalcemia with imparied renal function if taken with diary products

77
Q

What are the serious but rare side effects for sodium bicarbonate?

A

severe metabolic alkalosis
hypercalcemia
alkalinizes urine
absorption of NaCl causes fluid retention in CHF, HTN or renal insuf.

78
Q

What are the 4 general ways that the antacids can REALLY affect other drugs?

A
  1. increase gastric pH (altering drug absorption)
  2. will bind drugs and decrease absorption
  3. bulky, so delay gastric emptying
  4. Systemic absorption leading to alkaline urine and altering elimination of drugs
79
Q

What antibiotic in particular cannot be given with the antacids?

A

tetracycline - documented proof that it decreases efficacy

80
Q

What does simethicone do?

A

it is an anti-foaming agent that will decrease gas pain but also affect absorption

81
Q

True or false: antacids can’t prevent ulcer recurrence

A

true

82
Q

What’s ultimately the best drug for both treatment of symptoms and prevention of uclers?

A

PPIs

83
Q

When everything else fails, what strategy should you take?

A

protect the surface of the ulcer

84
Q

How can you protect the ulcer surface?

A

sucralfate (Al(OH)3) and sulpahted sucrose

it’s not an antacid, but it will bind to the basement membrane and blocks the acid from it

85
Q

In what patients is sucralfate helpful?

A

those with stress-induced uclers in the ICU

86
Q

Why can’t you give sucralfate with a PPI or H2 blockers?

A

it absolutely requires an acidic environment to be converted to a paste for the bandaid effect

87
Q

What are the side effects of sucralfate?

A

constipation and will bind to other drugs

88
Q

What prostaglandin do we give for NSAID-induced ulcers?

A

misoprostol - synthetic methyl PGE1

89
Q

WHat’s the pathophys of an NSAID-induced ulcer?

A

you inhibit production of PGE1, so you lose the inhibition on acid production and also lose the ativation of mucus and bicarb secretion, so you get an ulcer

90
Q

One way to avoid NSAID ulcer sis to give a combo of NSAID and misoprostol. How does this work?

A

it works because PGE1 is less involved with inflammation which the NSAIDS are concerned with

Is has a short half life compared to the NSAIDS, but long enough to maintain appropriate acid/bicarb balance

91
Q

What are the side effects of misoprostol?

A

MANY - compliance an issue

diarrhea, severe cramping (stimulates uterine contractions), nausea. so in 10-20% of patient it makes their GI symptoms worse

92
Q

What’s the current triple therapy for peptic ulcer disease related to H pylori?

A

PPI and clarithromycin for 5 days followed by amoxicillin OR tinidazole for 5 days

93
Q

What’s the quadruple therapy used more commonly?

A

PPI + tetracycline + metronidazole + bismuth subsalicylate for 14 days

94
Q

What’s the quadruple therapy of last resport?

A

PPI + Amoxicillin + Rifabutin + Ciprofloxacin for 10 days

95
Q

Describe how gastric absorption of weak acids is affected by pH?

A

the unionized form crosses easier….

so absorption will increase at low pH (bc more unionized form) and decrease at high pH (bc more ionized form)

opposite is true for bases

96
Q

Describe how excretion of weak acids if affected by pH?

A

the ionized form will be trapped in the lumen and excreted, so..

excretion of weak acid will decrease at low pH because more will be in the unionized form and will be reabsorbed. More will be excreted at high pH because more will be in the ionized form that gets trapped in the lumen

opposite is true for bases

GI Week 2 (11 decks)

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