Santanam GI Drugs X2-Melissa Flashcards
Describe the neuronal, hormonal, and paracrine regulation of gastric acid secretion.
Which cells are responsible for secreting gastric acid?
Where in the stomach are these cells located?
Neuronal:
Ach–> M3-R (Gq coupled)–> ^Ca2+/IP3–> ^K+/H+ATPase
Hormonal:
Gastrin–> CCK2-R (Gq coupled)–> ^Ca2+/IP3–> ^K+/H+ATPase
Paracrine:
Histamine–> H2R (Gs coupled)–> ^cAMP–> ^K+/H+ATPase
**Gastric acid secreted by PARIETAL CELLS (body and funds)
What is the role of enterochromaffin cells in regulating gastric acid secretion?
Gastrin + Ach stimulate enterochromaffin cells to produce HISTAMINE–> ^ Parietal cell H+ secretion
List three “defense mechanisms” against acid erosion of the stomach and esophagus:
1) LES
2) Secretion of gastric mucus layer
3) Secretion of gastric bicarb anions
Describe the role of prostaglandins in mediating acid secretion:
Which two prostaglandins are important here?
To which receptor do they bind?
On which cells do they act?
Upon what are these actions contingent?
PGE2 + PGI2–> EP3-R on parietal + gastric epi cells…
1) INHIBIT cAMP (H2) in parietal cells–> DECREASE H+
2) Stimulate gastric epi cells to ^ mucus + ^ HCO3 prodxn
**Note: Effects require adequate mucosal blood flow
What must be done to treat peptic ulcer disease prior to management of acid secretion (2)?
- Irradiate H. pylori (if infected)
- Stop NSAID use (if NSAID induced)
How do antacid work?
Act as weak bases to neutralize gastric acid:
Antiacid + HCL–> H2O + CO2 + Chloride salt
**DO NOT AFFECT ACID PRODUCTION ITSELF
Which antacid is systemic?
What is important about it?
- NaHCO3 (aka Baking soda/Alka seltzer)
Absorbed systemically –> transient metabolic alkalosis
Which antacids are non-systemic (4)?
- CaCO3 (Tums)
- Al (OH)3
- Mg(OH)2
- Mylanta + Gelusil (Al, Mg combos)
These are NOT absorbed systemically and do NOT cause alkalosis
What is simethicone?
surfactant added to antacids; decreases foaming + esophageal reflux
What is one important consideration when prescribing antacids to patient with CHF?
sodium levels
What is one important possible ADR associated with CaCO3 and other Ca2+ containing antacids?
Rebound acid secretion
What are GI ADRs associated with Al and Mg antacids?
What is one metabolic ADR?
What health conditions must you consider when prescribing these antacids?
Al = MINIMUM poops (constipation)
Mg = MEGA poops (diarrhea)
Combo drugs = varying effects
Both Al and Mg bind PO4–> Phosphate salts–> HYPOphosphatemia
Must consider RENAL INSUFFICIENCY (inadequate excretion–> toxicity)
How do antacids affect performance of other drugs (2)?
- ^ gastric pH–> alter bioavailability
(Fe, Ketoconazole, theophylline, ABX)
-Al, Mg alter GI motility–> alter absorption
What is the MOA of H2R antagonists?
When are they especially effective?
List 4 of these drugs.
Cimetidine, Ranitidine, Nizatidine, Famotidine
“IDINE’s”
MOA:
Competitive inhibit H2R–>
1) DECREASE volume/ H+ content gastric juice (60%)
2) DECREASE pepsin
**Especially effective AT NIGHT (NOCTURNAL ACID INHIB–BASAL acid secretion)
List the 4 therapeutic uses for H2R antagonists:
1) Gastric + duodenal ulcers
2) GERD (w/o erosive esophagitis)
3) Zollinger Ellinson Syndrome
4) Acute Stress Ulcers (i.e. following surgery)
Which H2R antagonist interacts with CYP450s?
HOW does it interact with CYP450s?
Cimetidine–CYP450 INHIBITOR
What is the #1 drug class used to treat PUD?
Proton pump inhibitors
What is the MOA for proton pump inhibitors (PPIs)?
List three go these drugs?
Omeprazole, Esomeprazole, Lansoprazole
“PRAZOLE” Drugs
MOA: Prodrugs–activated by stomach acid
IRREVERSIBLE inhib H+/K+ATPase–>
DECREASE BASAL + MEAL STIMULATED ACID prodxn
What are three therapeutic uses for ALL PPI’s
1) PUD (faster sx relief and healing than H2R antagonist)
2) GERD +/- erosive esophagitis
3) Zollinger Ellinson syndrome
Which PPI is approved for use WITH NSAIDS in patients with NSAID asstd gastric ulcers?
Lansoprazole
What is one random weird possible ADR associated with PPI use? What is one POSSIBLE yet unestablished ADR?
Can cause CNS effects (rarely); asstd with gastric cancer in animal models
Which PPIs interact with CYP450s? How?
Omeprazole, Esomeprazole INHIBIT CYP2C19
Which PPIs interact with clopidogril?
How?
Omeprazole, Esomeprazole inhibit conversion of clopidogril to active form–> NO ANTIPLATELET EFFECTS
What is Mesoprostol?
How does it work?
PGE1 analog–>
1) Decrease H+ secretion
2) ^ mucus + ^ HCO3- production
What is the primary therapeutic use for mesoprostol?
Coadmin w NSAIDS to prevent PUD
What are the most common ADRs asstd with Mesoprostol?
When is it contraindicated?
- GI (n/v/d) upset; can ^ IBD asstd. diarrhea
- DO NOT GIVE TO PREGGOS (^ uterine contraction)
What is sucralfate?
How does it work (2)?
Sulfated sucrose polyaluminum
1) Forms polymers (sticky coating gel) @ pH UNDER 4–>
Coats ulcer craters–> protects from further erosion (basically a band-aid for your belly)
2) ^ PGE2 production
**Note that it requires acidic pH to work!!!
What is one ADR associated with sucralfate?
Released Al can cause constipation (minimum poops)
What is the MOA for bismuth compounds (4)?
1) Coats crater ulcers (better healing rate than H2R antag.)
2) ^ mucus + HCO3- production
3) Inhibits pepsin
4) Antibacterial towards H. Pylori
What is the ADR associated with Bismuth compounds that you have to remember because it is weird?
Darkens oral cavity and stool ( due to sulfide reaction w bacterial H2S)
Quick, what the the most important ADR associated with Metaclopramide!?
Tardive dyskinesia or parkinson’s like syndrome from D2 inhibition!!!!!
NEVER FORGET THIS!!!
Ok, now what is the MOA (3) for metaclopromide and what is it used to treat (2)?
Cholinergic agonist; D2 antagonist; Prokinetic in gut–>
1) ^ esophageal clearance
2) ^LES tone
3) ^ gastric emptying
* *Ultimately DECREASE REFLUX…
Therapeutic use:
Mostly for diabetic gastroporeisis; also GERD w/o erosive esophagitis
What is triple therapy for H. pylori infection?
14 days, 2x per day :
PPI + clarithro + (metronidazole OR amoxicillin)
What is quadruple therapy for H. pylori infection?
14 days:
2x / day: PPI
3x / day: metronidazole
4 x / day: Bismuth subsalicylate + tetracycline
OR
2x / day: H2R antagonist
4 x / day: Bismuth subsalicylate + tetracycline + metronidazole
Describe how GERD is treated in stages I-III
1) Treat sporadic GERD with antacids/ lifestyle mod.
2) PPI better than H2RA for frequent sx
3) Chronic and unrelenting gets PPI 2x per day
Which laxatives are luminally active (3)
- Hydrophilic colloids (bulk forming fiber etc)
- Osmotic agents (unabaorbably salts/ sugars)
- Stool wetting agents (surfactants) and emollients (mineral oil)
Which laxatives are nonspecific stimulants/ irritants (3)
- Diphenylmethanes (Bisacodyl)
- Anthraquinones (senna, casara)
- Castor Oil
Work in 6-8 hours (castor oil works faster)
“CADi is an irritating character in Mean Girls”
Which laxatives are pro kinetic agents (2)
- 5HT4 agonists
- Opioid receptor antagonists
What is the difference between laxation and catharsis?
Laxation is a little “laxed”–just poop out the rectal stuff
Catharsis is CATHARTIC (poop out ENTIRE colon contents)
List some natural (3) and synthetic bulk (2) forming laxatives and describe how they work? When should you AVOID them?
Natural: bran, whole grain, psyllium
Synthetic: methylcellulose, calcium polycarbophil
Absorb water to soften stool + ^ bulk; do not take if impacted; work in 1-3 days
List some osmotic laxatives and describe how they work:
- Saline laxatives (Mg and PO4 salts) retain H2O in colon to increase motility
- Lactulose and mannitol = non-absorbable sugars–> hydrolyzed to SHORT CHAIN FAs–> pull H2O into stool–> ^ motility + soften stool
Work in 1-3 hours
What type of laxative is Bisacodyl? How does it work?
Stimulant laxative–> Stimulates H2O and electrolyte secretion into lumen
What are two surfactant laxatives and how do they work?
Docusates + Castor oil–>
1) Decreases stool surface tension–> ^ mixing of FA + Aqueous substance (emulsification)–> ^ easy poops
2) ^ H2O + electrolyte secretion
How does Castor Oil work as a laxative?
Cleaved to RICINOLEIC ACID–> ANIONIC SURFACTANT–> purge in 1-6 hours
How does mineral oil work as a laxative?
What are two potential concerns with use?
Non-absorbed oil lubricant softens stool; works in 2-3 days
- Decrease Vit.ADEK absorption
- Possible lipid pneumonitis if aspirated
What two drugs are used to treat Idiopathic constipation and IBS?
- Lubiprostone
- Linaclotide
Lubiprostone:
MOA? For what is it the DOC?
Metabolite of PGE1–> opens Cl- channels on GI epi–>
^ intestinal electrolyte + fluid secretion–> Accelerates stool transit time
DOC for opioid induced constipaiton
Linaclotide:
MOA? Black box warning?
Activates Guanylate cyclase-C R’s–> ^cGMP–> ^CFTR activity–> ^ intestinal Cl + HCO3 into lumen–> ^ fluid + Accelerate transit time
THIS KILLED BABY MICE: DO NOT GIVE THIS TO PATIENTS UNDER 18 YOA (BLACK BOX)
In whom are laxatives CI?
Appendicitis and other obvious situations; remember that laxatives are often abused and they are also used +/- enema or suppositories before surgery to clean patients out…
What are the most important things to do when treating diarrhea (2)?
- Maintain hydration and electrolyte balance
- Discontinue offending drugs if drug induced
What is the MOA for Opioid antidiarrheals: Loperamide and Diphynoxylate?
What is commonly mixed into preparations of these drugs?
What are they used to treat?
Loperamide and Diphenoxylate are commonly mixed with Atropine (muscarinic antagonism to inhibit abuse)
- u agonists w poor CNS penetration–> decrease motility
- Treats severe travelers’ diarrhea (Loperamide + antimicrobial = DOC)
What is a potential ADR associated with Diphenoxylate + atropine?
CNS effects with HIGH doses (central u receptors)
What are two ways to treat traveler’s diarrhea?
- Loperamide + antimicrobial
- Bismuth (antiinflammatory, anti-secretory, antibacterial)
How does H pylori affect somatostatin secretion?
Decreases D cells–> decreases somatostatin production–> decreases inhibition of gastric acid secretion
What is octreatide?
How is it used to treat GI pathology?
Somatostatin analog–> 100% down regulates GI activity
- Decrease GI endocrine secretion (including intestinal fluid + bicarb)
- Decrease GI motility
Treats diarrhea caused by hormone secreting GI tumors; chemo, AIDS, DM asstd. diarrhea
***Think carcinoid tumor!! Rx gave me this at least 2x
Describe treatment for MILD IBD:
*The pyramid is actually important. I had an Rx question about treating IBD in different stages of severity
- Topical corticosteroids
- ABX
- Glucocorticoid (budensonide)
Describe treatment for MODERATE IBD:
These patients fail initial therapy
- Oral corticosteroids
- Immunomodulators (azothiaprine, 6-mercaptopurine, MTX)
- Anti-TNF Abs
Describe treatment for SEVERE IBD; When do you give Natalizumab or Cyclosporine?
These patients fail moderate therapy
- IV corticosteroids
- Anti-TNF Abs
- Surgery
- *Natalizumab after failing anti-TNF Abs + immunomod.
- *Cyclosporine after failing IV corticosteroids (This was the Rx question)
