GI: PUD, GERD Flashcards
what dz are we talking about for “acid-peptic dz”
GERD
Gastric/duodenal ulcers
non-ulcer dyspepsia
stress related gastritis
causes of PUD
- infection w/ gram- HP **
- use of NSAIDs **
- increase HCL secretion
- inadequate mucosal defense against gastric acid
list the tx approaches for PUD
- eradicate HP (ABX)
- reduce secretion of gastric acid (PPIs, H2 recp)
- Provide agents that protect gastric mucosa from damage (prostaglandins, antimuscarinics, antacids, mucosal protective agents)
pneumonic for tx PUD
Acid.. decrease it
Protect…gastric mucosa
Eradicate HP if tests +
6 agents used for PUD
H2 rec antags PPI Antacids Prostaglandins Mucosal protectors anti-microbials
List the H2 receptor antagonists
*ending?
-tidine
Cimetidine
Famotidine
nizatidine
ranitidine
what stimulates gastric acid secretion? (3)
ACH
histamine
Gastrin
MOA for H2 blockers
- competitively block binding of histamine to the H2 receptor (NOT H1****)–>reduces H+ being secreted into stomach
- inhibit basal, food stimulated and nocturnal secretion of gastric acid
explain what happens after ACH histamine and gastrin bind to stomach receptors
- stimulation of H+/K+-ATP proton pump–>secretes H+ in exchange for K+–>goes into the stomach lumen
Percent that H2’s reduce gastric acid
70%
direct and indirect pathways for H2 rec antags
DIRECT: ACH, gastrin and histamine stimulate parietal cell–trigger release of H+ into stomach lumen
INDIRECT: ACH and gastrin also stimulate enterochromaffin-like cells (ECL)–>result in secretion of histamine–>then histmaine also acts on parietal cell
indications for H2 receptor antags
PUD (w/o HP)
stress ulcers
GERD
Pharmkinetics for H2 receptor antags
- abs
- excretion
- T1/2
- peak time
well absorbed
peaks in 1-3 hours
short half life
excreted by kidneys
time of day to take H2 antags
at night or in fasting state
NSAID induced ulcers–PPI or H2 blockers work best? why
PPI
*helps heal and prevent future ulcers better than H2
high or low tolerance for H2 recep blockers
High **
so it is common for s/s to return after a few days of tx
Cimetidine:
-drug to drug rxns high or low? and why
HIGH since it is CYP450 isoenzyme inhibitor
what drugs interact heavily with Cimetidine (10)
INCREASES levels of:
- warfarin
- TCAs
- Lidocaine
- CCBs
- quinidine
- oral sulfonylureas
- phenytoin
- theophylline
- benzos
- BBs (metroprolol and prorp)
Famotidine routes of admin
IV or PO
which H2 blocker was removed by FDA in 2020 and why
Ranitidine
*low levels of nitrosamine impurity was found
Nizatadine also removed by FDA
H2 rec antags and ketoconazole
WHY?
Concomittant use can reduce effectiveness of ketoconazole
*for ketoconazole to work— it needs to be in an acidic envi and H2 blockers reduce the acidic envir
Absorption of H2 rec blockers is reduced or increased by __% when given with ____?
REDUCED
10-20%
Antacids
do H2 blockers go into Breast milk?
yes
do H2 blockers cross placenta?
yes
SE of Cimetidine
endocrine SE due to its antiandrogen effects:
- gynecomastia
- impotence
- Galactorrhea
CNS:
-confusion, AMS (usually with older or after IV admin) MORE so than Famotidine
inhibits CYP450 so it interfers with a lot of drugs***
which H2 rec blocker is assoc with causing the most SE?
Cimetidine
how long does it take for tolerance to develop with cimetidine?
days
PPIs list of drugs
*ending?
-prazole **
Esomeprazole Iansoprazole Omeprazole Dexlansoprazole Pantoprazole Rabeprazole
what class of drugs is Aripiprazole and Brexpiprazole
Antipsychotics and NOT PPIs**
MOA for PPIs
bind to H+/K+ ATPase proton pump and suppress H+ secretion into the gastric lumen
- *Irreversible**
- *membrane bound proton pump is the final step in acid secretion**
PPIs affect on basal and stimulated acid secretion
Stops BOTH !
explain chemical composiiton of the PPIs
- prodrugs
* have enteric coating that is acid-resistant so they are not degraded in the gastric acid
when is the enteric coating of the PPIs degraded? aka where are they absorbed
in the duodenum aka an alkaline environment
*absorbed and transported to the parietal cell
what do the active forms of PPI bind to after being asborbed?
bind to the H+/K+ ATPase enzyme IRREVERSIBLY–stops the acid production for about 18 hours until new enzyme is resynthesized
how long does the effects of PPI generally last for?
18 hours—then new ATPase enzyme is synthesized
indications for PPIs (6)
- GERD
- erosive esophagitis
- active duodenal ulcer
- pathologic hypersecretory conditions (Zollinger-Ellison)
- prophylaxsis use to prevent NSAID induced ulcers and stress induced ulcers
- reduce risk of bleeding from ulcers caused by ASA
- combined with ABXs for tx of HP
*duration of action and first time dosing effects for PPI
limited effect with the first dose BUT bc of irreversible binding, they have a PROLONGED effect over time
best to give PPIs with full or empty stomach
fasting state
most effective route of admin for PPIs
PO
when to administer PPI
30 to 60 mis before breakfast or largest meal of the day
why do PPIs have a long duration of action?
beause of the COVALENT irreversible binding to the H+/K+ ATPase enzyme
Metabolism for PPIs
*drug-drug interactions: which ones?
P450 enzyme
- Clopidogrel effectiveness decrease if administerd with Omeprazole and Esomeprazole
- warfarin, diazepma, phenytoin
- methotrexate toxicity*
increase in _____ with >1 year of use of PPIs
fractures
SE of PPIs (9)
- increase risk of fx (bc of Ca2+ absoprtion issues)
- B12 deficiency
- increase risk of C. Diff and enteric infections
- diarrhea
- affects Ca2+ and B12 and magnesium absorption
- hypomagnesia
- incr risk of pneumonia
- HA
- nausea
Esomeprazole has a plasma half-life of a few hours yet suppresses acid secretion for 24 to 48 hours. The reason for this paradox is____?
acid suppression continues unitl new H+/K+ ATPase molecules are synthesized
antacids
*describe chemical composition
weak bases
what happens when antacids react with gastric acid
form water and salt–>diminishes gastric acidity
list the antacids
Aluminum hydroxide
Mag hydroxide
Ca Carbonate (tums)
Mag Trisilicate
at what ph is pepsin deactivated
pH > 4
what is pepsin
proteolytic enzyme
MOA of antacids
They are weak bases**
- react with gastric acid to form salt and water
- since they raise pH, they also inactivate pepsin
take antacids on full or empty stomach
FULL aka take antacids AFTER meal
- delayed gastric emptying with a full stomach
- so allows more time for the antacids to work–>prolong the duration of action
why is sodium bicarbonate not recommended as an antacid?
because it produces transient metabolic alkalosis–>producing a high sodium load
therapeutic uses for antacids
*what are they not used for?
- symptomatic relief of PUD (but not to treat PUD)
- heartburn
- GERD
NOT USED: tx of PUD
SE of aluminum hydroxide
constipation
SE of magneisum hydroxide
diarrhea
which antacid causes:
- diarrhea
- constipation
- mag hydroxide
2. aluminum hydroxide
which antacids are combined in OTC preparations and WHY
Aluminum and mag hydroxide beause their SE of costipation and diarrhea cancel eachother out
antacids + renal impaired patients can lead to?
accumulation of Mg, Al, Ca (cations)
–>milk Alkali Syndrome
lab findings for milk alkali syndrome
hypercalcemia
alkalosis
renal injury
Prostaglandin-E
- where/what produces it
- function?
prod: by gastric mucosa
Funct: inhibits secretion of acid and stimulates secretion of mucus and bicarb
***cytoprotective effect
deficiency of prostaglandin can lead to___
Peptic ulcers
list the prostaglandin drugs
Misoprostol
Misoprostol
- drug class
- MOA
- indications and contras
- SE
Class: Prostaglandin E1 analog
MOA: inhibits secretion of gastric acid and stimulates secretion of bicarb and mucous
Indications: prevention of NSAID induced gastric ulcers
*good for prophylactic use
Contra: pregnancy bc it can stim contractions and cause miscarriages
SE:
- MC= diarrhea (dose-related)
- cramping
- abdominal pain
which drug class is preferred for prevention of NSAID induced ulcers Prostaglandin analogs or PPIs?
PPIs
what drug classes are known to be cytoprotective ?
- prostaglandin analogs
2. mucosal protective agents
define cytoprotective
agents stimulate mucus production and enhance blood flow throughout the lining of the gastrointestinal tract. These agents also work by forming a coating that protects the ulcerated tissue
Sucralfate
- drug class
- Drug composition
- MOA
- indications and not used for?
- contraindications
- drug-drug rxns?
- SEs
- Class: Mucosal Protective Agents
- Drug Composition: Aluminum Hydroxide + Sulfated Sucrose
- MOA:
1. Binds to ions in normal + damaged mucosa–>creating a physical barrier (gel like substance)
2. Protects ulcer from pepsin and acid– allowing ulcer to heal
3. DOES NOT affect gastric acid or pepsin secretion - indications:
1. GERD in pregnancy
- NOT USED IN: PUD due to PPIs being superior
Contras: none
- requires acidic environment for activation DO NOT use with PPIs, H2 antags or antacids
- can bind to other drugs and interfere with their absoprtions
SE: very well tollerated
MOA for the class of drugs: Mucosal Protective Agents
*MOA: cytoprotective: enhance mucosal protection mechanisms, prevent mucosal injury, reduce inflammation, and heal existing ulcers
List the mucosal protective agents
Bismuth Subsalicylate and Bismuth Subcitrate
Sucralfate
Bismuth Subsalicylate and Bismuth Subcitrate
- Drug class
- MOA
- indication
- SEs
Drug class: Mucosal protective Agent
MOA:
- supresses HP via its antimicrobial actions
- inhibits pepsin
- may increase mucus secretion–to promote ulcer healing via interacting with glycoproteins in necrotic tissue and coats/protects ulcer
- No effects on inhibiting or neutralizing acid
Indications:
*part of quad tx for HP eradication
SE:
- black stool
- can raise levels of salicylates–>possible toxicity
which is superior for GERD and PUD: PPIs or H2
PPIs
PPIs are superior to H2 rec antags for tx of?
acid suppresion in PTs with GERD and PUD
which drug class can patient’s develop a tolerance for?
H2 rec antagonists
*why their use is limited
HP is effectively eradicated via?
COMBO of
1. acid-suppressing drugs
2. multiple ABX
10-14 days
which patients need ABX?
HP infections and PTs with PUD (both duodenal and gastric)
List the drugs in the two regimens for tx of PUD with +HP infection
*percent eradication for each
FIRST LINE: QUAD THERAPY 91%: bismuth subsalicylate + metronidazole + tetracycline + PPI x14 days
OR
TRIPLE THERAPY 80%: Clarithromycin + amoxicillin (or metronidazole if PCN allg) + PPI X14 days
if someone if allergic to Penicllin, which ABX can you give instead
*replace _____ with____?
replace amoxicillin for metronidazole in triple therapy
