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What are the goals of GI drugs in the gut (2)?
- 1. Decrease acidity
- 2. Increase mucosal defense
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What are the 3 receptor sites for parietal cells?
- 1. Histamine (H2)
- 2. Gastrin (CCK-B)
- 3. Acetycholine (M3)
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Which receptor is stimulated sight, smell, taste of food (CNS)?
M3--> Acetylcholine
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Which receptor is stimulated by food, gastric distention?
ACH+G cell--> Gastrin
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Which receptor is most stimulated during postprandial & nocturnal acid secretion?
Histamine
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What are the acid secretion physiology steps? (4)
- 1. Ca+ influx into parietal cell
- 2. cAMP increases and activate protein phosphokinases
- 3. Activation of H/K ATPase pump
- 4. Hydrogen combines w/ CL- from the blood to form HCL
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What is the final common pathway for gastric acid secretion?
Proton pump
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At the proton pump, H+ is transported out the cytoplasm and into _________________?
secretory canalicus
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What are the 5 defensive factors of GI mucosa?
- 1. Mucus secretion
- 2. bicarb secretion
- 3. prostaglandins
- 4. blood flow
- 5. regeneration after cellular injury
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What are 3 caustic agents that lead to GI erosion/ulceration?
- 1. Gastric acid
- 2. Bile
- 3. Pepsin: breaks down protein
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What pH is pepsin irreversibly inactivated?
>7
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What drugs have the action of reducing acidity? (3)
- 1. Antacids
- 2. H2 Receptor Antagonist
- 3. PPI
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What GI drugs have the action of protecting the mucosa?
- 1. Sulcralfate
- 2. Prostaglandin Analogs
- 3. Bismuth compounds
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Antacids function to increase or decrease gastric acidity?
Increase pH
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Antacids react with HCL to form what?
Na + H20 (for partial neutralization)
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T or F. Antacids are useful in heartburn prophylaxis?
False
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Sodium bicarb reacts w/ HCL to form what?
CO2 + NaCL
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What are the side effects of sodium bicarb (Alka Seltzer)? What patients should not take it? (3)
- -S/E--> gastric distention, belching
- -May exacerbate fluid retention in patients w/ HF, HTN, renal insufficiency
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Calcium Carbonate (TUMS) combines w/ HCL to form what?
CO2 + CaCL2
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What are the S/E of Ca+ Carbonate and what risk does it have with dairy products?
- S/E--> belching or metabolic alkalosis
- Risk w/ diary--> hypercalcemia, renal insufficiency, & metabolic acidosis
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What is the S/E of each Aluminum & Magnesium Hydroxide?
- AL salts--> constipation
- Mg salts--> osmotic diarrhea
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What is the effect of taking antacids w/ other drugs?
- -Reduce gastric hydrolysis of drugs
- -Change gastric and/or urinary pH
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What is the MOA of H2RA?
block histamine receptor--> decrease acid secretion
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T or F. H2RA are highly effective o meal stimulated acid secretion?
False: highly effective at inhibiting nocturnal acid secretion (histamine activity), modestly effective at meal stim (gastrin, acetyl, & histamine)
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H2RA inhibit 24hr acid secretion by what percent?
60-70%
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What are the H2RA Dynamics? (5)
- 1. Competitively inhibits H2 receptor
- 2. Suppresses basal/meal stim acid secretion
- 3 Highly selective to H2
- 4. Decrease gastric secretion vol & pepsin concentration
- 5. H2 blockade decreases gastrin/Acetyl. stimulation
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What are adverse effects of H2RA? (4)
- 1. GI discomfort
- 2 CNS effects (h/a, drowsiness, psychosis, hallucinations
- 3. dermatologic (rash)
- 4. hematologic (thrombocytopenia)
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What is the MOA of PPI?
Irreversibly binds to H/K ATPase (proton pump)--> blocking final common acid secretion pathway
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PPI are best at inhibiting nocturnal secretion or basal/meal stim acid secretion?
Inhibit basal & meal stimulated gastric acid secretion ~24hrs, some nocturnal activity w/ newly activating pumps
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Where in the GI are PPI absorbed?
small intestine, transported in serum to acidic canaliculus of parietal cell for protonation to active form
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Converstion of PPI to active form requires what?
actively secreting proton pump
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When should PPIs be taken to be most effective?
30-60min prior to meal on an empty stomach
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What are some adverse effects of PPIs? (4)
- 1. GI discomfort (N/D, pain)
- 2. CNS (H/A, dizziness)
- 3. Increased infection risk (c. diff, pneumonia)
- 4. Rare: skin rash, increase liver enzymes
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How does sulcrafate work?
Forms paste in water/acid soluntions that bind to ulcer or erosion for ~6hrs--> stimulating secretion of mucosal
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What are 4 effects of misoprostol?
- 1. increase mucus & bicarb secretion
- 2. Increase mucosal blood flow
- 3. Bind parietal cells--> reducing histamine
- 4. Stimulate cAMP production
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What are 3 effects of Bismuth compounds?
- 1. Coats ulcers/erosions
- 2. Stimulate prostaglandins, mucus, & bicarb
- 3. Antimicrobial activity against H. Pylori
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What drugs are useful for GERD?
antacids or intermittant H2RA
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What is 1st line therapy for Erosive Esophagitis?
PPI (long term therapy often indicated)
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What med is the DOC for uncomplicated (no H. Pylori) PUD?
PPI
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What is the treatment plan for H. Pylori?
- -PPI is DOC
- -H2RA if intractable infection
- -1/2 dose at night to prevent recurrence
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What is the treatment plan for H. Pylori ulcers?
- Triple therapy:
- -2 ABX + PPI x 14 days
- -PPI x 4-6 weeks
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Why are PPIs effective for H Pylori?
- 1. direct antimicrobial property
- 2. increased pH
-
Which GI med is best for NSAID-induced ulcers?
PPI have better healing than H2RAs
-
What are 5 clinical uses of GI stimulants?
- 1. Selectively stim GI motor function
- 2. ⇑ lower esophageal sphincter tone--> GERD
3. ⇑ gastric emptying--> post-op
4. ⇑ small intestine activity--> post-op ileus
5.⇑ colonic transit--> constipation
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T or F. GI NS regulates motility & secretion autonomously.
True
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What symptoms are caused by stimulation extrinsic afferent nerves?
N/V, abdominal pain
-
What symptoms are caused by stimulation of intrinsic primary afferent nerves?
Perstalsis
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What is the effect of 5-HT3 stimulation?
Vomiting
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What drug is good for inhibiting the 5-HT3 receptor and decreasing nausea?
Ondansetron
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What is the effect of 5-HT4 stimulation?
stimulate motility/peristalsis
-
What drug is an agonist for 5-HT4 and promotes GI motility
metoclopramide
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What is the effect of neostigmine?
- Enhances gastric, small intestine, & colonic empyting
- -good for acute colonic pseudo-obstruction
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What is the effect of Cholinomimetic agents? What are 2 drugs?
- Increase GI function
- -Bethanechol
- -Neostigmine
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What are the side effects of cholimimetic agents?
salivation, N/V/D, bradycardia
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What occurs with D2 stimulation?
D2 dampens cholinergic smooth muscle stim
-
What are the effects of D2 receptor antagonist?
- -Increase esophageal perstalsis
- -Increase lower esophageal sphincter pressure
- -Increase gastric emptying.
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T or F. D2 receptor antagonists have NO effect on the stomach?
False: only works on the stomach NOT the small intestine or colon
-
What are the clinical uses of D2 Receptor Antagonist?
- -GERD
- -Surgery
- -DM gastroparesis
- -Advancing feeding tube
- -chronic dyspepsia
- -Emesis prophylaxis
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What are the adverse effects of D2 Receptor Antagonist? (CNS & EPS)
- Metoclopramide
- -CNS:--> restlessness, drowsiness, insomnia, anxiety, agitation
- -EPS--> dystonia, akathesia, parkinsonian, tardive dyskinesia
-
What is the effect metoclopramide & Domperidone on prolactin?
Increases prolactin levels--> galactorrhea, gynecomastia, impotence, menstrual disorders
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What is the effect of Macrolides on GI activity?
Directly stimulates motilin receptors on GI smooth muslce
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What are 4 indications for laxatives?
- 1. Short term constipation relief
- 2. Prevent straining
- 3. Bowel prep
- 4. Poison/Toxin elimination
-
What are 2 contraindications and 3 adverse effects of laxatives?
- Contraindications: Acute abdominal d/o, UC
- Adverse effects: Diarrhea, abd cramping, fluid/electrolyte imbalance
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What are the effect of builk-forming?
- -Water retained within stool
- -Increased stool mass
- -stimulate peristalsis
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How do stool softeners work?
Reduce surface tension of liquid in stool (grease intestines)
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How do osmotics work?
- -Increase stool liquidity
- -Useful for acute/chronic constipation
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How do stimulants work in the GI tract?
- -Act directly on the intestinal mucosa
- -alter fluid secretion, stimulate peristalsis, increase fluid in stool
-
What are 2 examples of GI stimulants?
Senna & Bisacodyl
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What is an adverse effect of 5-HT4 receptor agonist?
QT prolongation (not available in US)
-
T or F. Opioid agonists do NOT cross BBB?
True
-
What are the effects of opioid agonist? (3)
- 1. Decrease motility
- 2. slow stool passage
- 3. increase time to absorb fluid
-
What are 2 examples of opioid agonists?
- 1. Loperamide
- 2. Diphenoxylate & Atropine (lomotil)
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Name a 5-HT3 receptor antagonist that is approved for women w/ sever diarrheal IBS?
Alosetron (lotronex)
-
Which CL channel activator is approved for women with chronic constipation?
Lubiprostone (Amitza)
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What is the primary use of 5-HT3 Antagonists?
-Prevention of N/V associated with chemo (give 30min prior)
-
What are adverse effects of 5-HT3 Antagonists? (5)
Constipation, diarrhea, H/A, light-headedness, PROLONGED QT (Dolasetron-Anzemet)
-
What drugs is best for delayed chemo induced N/V?
Dexamethasone (enhances effectiveness of 5-HT3 antagonists
-
What is the MOA of Phenothiazines? Name 2 drugs.
Inhibit dopamine receptors in chemoreceptor zone (compazine, phenergan)
-
What drug is considered first line therapy for mild-mod UC?
Aminosalicylates (5ASA)
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