Lecture One (GI intro)-Exam 1 Flashcards
What are medications that increase Gastric pH? (3)
- Antacids
- Histamine 2 blockers
- Proton pump inhibitors
Stomach acid pathophysiology
* What does mucous and mucous neck cells do?
* What does parietal cells do?
Mucous and mucous neck cells:
* Produce thick mucous that helps protects the surface of the stomach
Parietal cells:
* Produce hydrochloric acid (HCl) that produces low pH environment
Stomach acid pathophysiology
* What do chief cells do?
* What does enterochromaffin like cells do?
* What does G-cells do?
Chief cells:
* Produce pepsinogen – protein digestion
* Lipase – fat digestion
Enterochromaffin-like cells:
* Produces histamine
G-cells:
* Produce gastrin – regulates gastric activity
Stomach acid pathophysiology
* What does the food stimulate? What does that result in?
Food stimulates the vagus nerve to release acetylcholine (Ach) resulting in:
* Direct stimulation of parietal cells via muscarinic (M3) receptor
* Indirect stimulation of parietal cells via stimulation of ECL and G-cells
Stomach acid pathophysiology: parietal cells via stimulation of
* WHat does ECL cells and G cells release and bind to?
ECL cell
* Releases histamine – binds to histamine H2 receptor
G-cell
* Releases gastrin – binds to CCK-B receptors
- ECL – enterochromaffin-like cell
- CCK-B –cholecystokinin B
Stomach acid pathophysiology
* H2 receptor activation cause?
* What does M3 and CCK-B activation cause?
- H2 receptor activation -> increases cAMP
- M3 and CCK-B activation -> increases intracellular calcium
Stomach acid pathophysiology
* Pathways converge to ultimately activate what?
* What happens to Cl- and H+? what does those form?
- Pathways converge to ultimately activate H+/K+ proton pump
- Actively pumps H+ out of cell
- Cl- passively transported out
- Form hydrochloric acid in the stomach lumen – ideal for digestion
Antacids
* What does it not do?
* what does it do?
* Recommended for what?
* What products?
- DO NOT decrease acid secretion
- DO directly neutralize HCl
- Recommended for intermittent use
- Multiple combination products
Antacids
* Reacts with what? What does that form?
* What increaes and decreases?
React with HCl to form salt and water
* Increases gastric pH
* Decreases conversion of pepsinogen to pepsin
* May increase LES pressure
Focus on sodium bicarb
Antacids
* What are the multiple drug interaction causes? (3)
- Alteration in gastric pH
- Adsorbing medications
- Physically blocking absorption
Antacids
* What do you need to do for medications that can interact?
* What are there significant itneractions with? (6)
- Separate administration of antacids and interacting medications: Take 1 hour before or two hours after antacids
- Significant interactions with: Tetracyclines, ferrous sulfate, sulfonylureas, quinolones, ketoconazole, voriconazole
Alginic acid (Gaviscon)
* Does not do what?
* Does do what?
* Viscous solution that does what?
* Generally used in conjunction with what?
- DOES NOT decrease gastric pH greatly or increase LES pressure
- DOES float on the surface of stomach contents
- Viscous solution that coats and protects the esophagus when refluxed
- Generally used in conjunction with other antacids (e.g., calcium carbonate)
H2 receptor antagonists
* What does it do? What are the results of that? (3)
Competitively, reversibly block H2 receptors
* Decrease activation of proton pump
* Decrease production of nighttime and food-induced acid secretion
* Acid secretion reduction > 90%
H2 receptor antagonists
* What are the indications? (4)
- Peptic ulcer disease (PUD)
- Ulcer prophylaxis
- GERD
- Zollinger-Ellison disease
H2 receptor antagonist
* What are the unique characteritics of Clinetidine?
* What are the SE of H2RAs?
* Dose reduction?
* Monitor for what?
* May cause what?
Proton pump inhibitors
* What is the MOA?
* What are examples?
Irreversibly binds and inhibit parietal cell proton pumps
Proton pump inhibitors
* more effective than what? How?
* What is the onset?
* What is the duration of activity?
* Decreases drug absorption how?
- More effective than H2 antagonists via Decrease acid secretion > 99%
- Onset: 3-4 days for full effect
- Duration of activity: 2-5 days
- Decreases drug absorption by increasing gastric pH
Proton pump inhibitors
* What does omeprazole inhibit?
Inhibits CY3A4 and 2C19
PPIs
Check what levels?
PPI doses
* What are the doages forms?
- IV
- Tablets
- Capsules
- Powder packs
- Dissolvable tablets
cytoprotectants: misoprostol
* Wwhat is the MOA? (think about what is stimulates, increases, decreases and improves)
Cytoprotectants: Misoprostol
* What are the indications? (2)
- Protectant NSAID-induced ulcers or patients at high risk of ulcers
- Short-term use for gastric or duodenal ulcers
Cytoprotectants: Misprostol
* What are the SE? (3) what is the CI? (1)
Adverse effects (dose related):
* Nausea
* Diarrhea
* Abdominal cramping
CI: pregnancy (induce abortions)
Cytoprotectants: Sucralfate
* What is the drug made out of?
* What is the MOA?
Aluminum hydroxide + sulfated sucrose molecules
Acidic environment
* Disassociate into aluminum salt and sucrose sulfate
* Negatively charged sucrose sulfate binds to positively charged proteins in base of gastric erosion and in the mucosal membrane
Cytoprotectants: Sucralfate
* What are the overall effects? (3)
Physical barrier – promotes healing
* Increases bicarbonate secretion
* Increases mucous viscosity and thickness
Sucralfate:
* What are the SE?(6)
- Consitipation
- HA
- dizziness
- Dry mouth
- Hyperglycemia
- Multiple drug interactions
Cytoprotectants: Sucralfate
* What are the indications? (5)
- Duodenal ulcers
- Dyspepsia
- Epithelial wounds
- Mucositis
- Radiation proctitis
Vomiting reflex
* Located where?
* What does it contain?
* What happens with stimulation?
Located in medulla oblingata
* Contains muscarinic receptors
* Stimulation = triggers vomiting reflex
Vomiting reflex
* What are the Four primary stimulators of VC?
- Chemoreceptor trigger zone (CTZ)
- Vestibular system (VS)
- GI mechanoreceptors
- Higher brain centers
Vomiting pathophysiology: Chemcoreceptor trigger zone
* Located where?
* Outside what?
* Triggered by what?
* Stimulates what?
* What are the receptors?
Receptors: Chem D(2)oN(K1)’t (5)HiT(3)
Vestibulat system:
* What is it important for?
* Problems communicated via what?
* Stimulations of what?
* What are the receptors?
Higher brain centers (cerebrum)
* Response to what?
* Direct stimulation of what?
- Response to emotional, pain, smell, sight
- Direct stimulation of vomiting center muscarinic receptors
Gastrointestinal center
* What is resleased?
* Stimulates what? (2)
* What are the receptors?
What are the Select Nausea and vomiting etiologies? (10)
- Increased intracranial pressure
- Vestibular dysfunction
- Dyspepsia
- Gastroparesis
- Infections
- Medications / chemicals
- Pregnancy
- Pain
- Psychiatric disorder
“I Vow Doctors Get Instant Medical Pregnancy Pain Patches”
Antihistamines / anticholinergic agents
Antihistamines / anticholinergic agents
5Ht3 / NK-1 receptor antagonists
5Ht3 / NK-1 receptor antagonists
Miscellaneous antiemetics
Laxatives:
* produce what?
* What are the different mechanisms? (5)
Produce bowel movements and relieve constipation
Many different mechanisms
* Osmotic
* Bulk forming
* Stimulant
* Irritant
* Lubricant
Osmotic laxatives
* increases what? (2)
* Pull water where?
* Triggers what?
- Increases solute load in intestine
- Pulls water into GI lumen
- Increases stool volume and stretches bowel
- Triggers defecation reflex
Laxatives: bulk laxatives
* Insoluble what?
* Takes up what?
* Intestinal wall _
* Stimulation of what?
* Induce what?
- Insoluble methylcellulose fibers
- Take up water in the large intestine forming a large mass
- Intestinal wall distension
- Stimulation of mechanoreceptors
- Induce contraction and relaxation of intestinal smooth muscle
Irritant and stimulant laxatives
* Prevent what?
* Promote what?
* Irriate what?
- Prevent water reabsorption in the colon and / or
- Promote water secretion from the intestinal mucosa
- Irritate nerve fibers of the intestinal mucosa
- Stimulate defecation
Laxatives
* What is generally first line?
* What is second line?
* What is imporant about PEG 3350 AKA Miralax? (2)
Bulk laxatives generally first line
Osmotic laxatives second line if no response to bulk laxatives
PEG 3350 AKA Miralax
* More effective than lactulose
* Safe for infants
Laxatives
* Magnesium salts (MOM) – caution with what?
* Sodium salts – many what?
* Bisacodyl / senna – severe what?
* What is not effective for treatment?
- Magnesium salts (MOM) – caution with renal failure
- Sodium salts – many electrolyte abnormalities
- Bisacodyl / senna – severe cramping and melanosis coli
- Stool softeners not effective for treatment
Def know the onset of action
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What are secretagogues reserved for?
Prescription products reserved for patients with refractory, chronic constipation
* Last line
secretagogues
secretagogues
Bowel prep regimens
* What is first line?
* What are the two options?
* What can you add?
- First-line includes polyethylene glycol preparations
- Golytely vs Miralax
- ± Lubiprostone / bisacodyl
Bowel prep regimens
* What is more effective? what is it limited by?
* Specific regimens depend on what?
* Fluids when?
- Split regimens may be more effective->Limited by procedure timing
- Specific regimens depend on comorbidities
- Fluids only day -1; nothing red, orange, purple
Melanosis coli
* Secondary to what?
* Active form in colon causes what?
* What is it?
* Resolves how and when?
- Secondary to chronic senna use
- Active form in colon causes cell apoptosis and death of cells lining the colon
- Dark pigmentation of cells
- Resolves spontaneously if laxatives stopped-> Could take up to 1 year for full resolution
Antispasmodics
* What is the MOA of action? (think about what it blocks, decrease and reduce)
- Blocks acetylcholine from binding to muscarinic receptors
* M3 receptor in smooth muscle - Blocks histamine and bradykinin receptors
- Decreases GIT peristalsis and secretions from stomach to colon
- Reduces spasms
Antispasmodics
Antispasmodics
Prokinetics: metoclopramide
* What is the MOA?
- Inhibits D2, apomorphine, and 5HT3 receptors
- Increases LES pressure and gastric contractions
- Mild antiemetic
Prokinetics: Macrolide antibiotics
* What are the examples? (2) What does it cause? (2)
* What are the interactions?
Erythromycin / azithromycin
* Increase high amplitude gastric contractions
* May cause tachyphylaxis
Interactions
* Avoid concomitant administration with magnesium or aluminum-containing antacids
Macrolide antibiotics:
* What are the ADRs? (5)
- GI: nausea, vomiting, diarrhea (erythromycin > clarithromycin > azithromycin)
- Prolongation of QT – interval
- Hepatotoxicity
- Drug interactions CYP3A4 (erythromycin, clarithromycin)
- Hearing loss (erythromycin)
Antidiarrheals:
* Decrease what?
* Increase what?
* Recommended for what?
- Decreased diarrhea frequency
- Increase consistency of bowel movements
- Recommended for self-limiting diarrhea
Antidiarrheals
* Do not use what?
* Caution with who?
* used in conjuction with what?
- Do not use > 2 days without medical supervision
- Caution with elderly
- Used in conjunction with rehydration/refeeding
What is the MOA?
Fill in for the SE and Cautions
Pancrelipase
* Exogenous digestive hormones and enzymes required for what?
* Ingested with what?
- Exogenous digestive hormones and enzymes required for normal digestion
- Ingested with meals and snacks to improve digestion and absorption; decrease abdominal pain
Pancrelipase:
* What are the indications? (6)
- Exocrine pancreatic insufficiency
- Pancreatitis
- Pancreatic surgery
- Cystic fibrosis
- Steatorrhea – post gastrectomy syndrome
- Pancreatic cancer
Pancrelipase: Porcine lipase, amylase, and protease
* Lipase –
* Amylase –
* Proteases –
- Lipase – hydrolysis and degradation of fats
- Amylase – hydrolysis and digestion of starches
- Proteases – breakdown proteins and amino acids
Pancrelipase:
* What is the site of action?
* Minimal what?
* What is the dose?
- Site of action: duodenum
- Minimal systemic absorption
- Based on lipase component
- 500 to 2500 units/kg/dose with each meal
- 50% dose per snack
Pancrelipase
* What are the SE?
* What is monitoring? (4)
Adverse effects – minimal
Monitoring
* Abdominal symptoms
* Weight / growth
* Stool character
* Blood glucose
