Pharm 23 Objectives Flashcards
Describe the physiology of the protective gastric mucosal layer
secreted by gastric mucosal cells, protective layer.
blood flow vitally maintains mucosal barrier
tight junctions –> relatively impermeable to acid
Describe the physiology of the protective gastric epithelium
Epithelial regeneration - rapid cell turnover
The epithelium of the mouth and stomach –> most frequently replaced cells in the body
Prostaglandins effects on gastric acidity
Inhibit gastric acid secretion by the parietal cell
Enhance mucosal defense mechanisms (bicarb)
Misoprostol MOA
Synthetic PGE1 analog
Inhibits basal and nocturnal gastric acid secretion via direct action on parietal cell
Stimulates mucosal protectant effect
What pregnancy category does Misoprostol fall under?
Category X
can cause miscarriage, uterine contraction, and teratogenic.
Indication for Misoprostol?
Indicated for NSAID induced gastric ulcer prophylaxis
ASES of Misoprostol?
Diarrhea, dose-dependent abdominal pain, headache, flatulence, n/v
List and compare measures to prevent GI ulcers in patients who take NSAIDs long term
Find an alternative to systemic NSAIDs
Add Misoprostol or PPI to and NSAID (reduce risk for GI bleed)
Choose a COX-2 selective NSAID
Reduce direct irritation of the GI mucosa (ie. DR tabs and prodrugs)
What is the role of gastrin that stimulates parietal cell acid secretion?
Released in response to stomach distension and Ach
Increases intracellular calcium levels in parietal cells
Acids in the stomach is a negative feedback on gastrin release
What is the role of pepsin that stimulates parietal cell acid secretion?
Most active at pH 2.0
Becomes progressively less active at higher pH
Irreversibly inactive at pH of 8
What is the role of acetylcholine that stimulates parietal cell acid secretion?
Released in response to amino acids in foods and stomach distention
Increase intracellular calcium levels in parietal cells
The most potent stimulator of pepsinogen secretion from chief cells
What is the role of Histamine that stimulates parietal cell acid secretion?
Release of histamine is stimulated by Ach and gastrin
The most potent stimulator of gastric acid secretin
Receptor = Gs protein linked —> increase cAMP
What is the role of H+/K+-ATPase that stimulates parietal cell acid secretion?
Stimulated via protein kinases
MOA of antacids
Increases pH
Inactivated pepsin (at least temporarily)
Bind bile salts
Adverse effects of antacids?
Diarrhea, constipation, acid-base disruption and excessive sodium intake, drug interactions that can result in treatment failures:
- mostly chelation issues, which prevents absorption of both drug and mineral
Clinical use/effectiveness of antacids?
Rapid onset and short duration of action
Rapid relief
OTC and inexpensive
Molecular formula of calcium carbonate
CaCO3
Molecular formula of magnesium hydroxide
Mg(OH)2
Molecular formula of sodium bicarbonate?
NaHCO3
Mg(OH)2 is frequently added to what?
Calcium or aluminum to be constipation neutral
H2 receptor antagonist (H2RA) drug names?
Ranitidine
Famotidine
H2 receptor antagonist (H2RA) efficacy?
Strongest stimulator of parietal cell
Reduce total volume of gastric juice –> decreasing pepsin secretion
1st line for GERD
H2 receptor antagonist (H2RA) FDA indications?
Duodenal ulcer disease
Erosive esophagitis
Gastric hypersecretion
Gastric ulcer
GERD
H. pylori gastrointestinal tract infection, Indigestion
Zollinger-Ellison syndrome
Night time symptoms
H2 receptor antagonist (H2RA) pharmacokinetics?
First mass metabolism –> reduces bioavailability 30-60%
Do cross the BB
Are excreted in breast milk
H2 receptor antagonist (H2RA) onset of action?
Peak [ ] in serum in 1-3 hrs
H2 receptor antagonist (H2RA) drug interactions?
Cimetidine - gynecomastia, heart rate changes (brady (MC) or tachy)
Nizatidine - insomnia, somnolence, anemia
H2 receptor antagonist (H2RA) common ASEs?
Headache Diarrhea N/V Constipation Vertigo/dizziness Fatigue Confusion
H2 receptor antagonist (H2RA) severe ASEs?
Organ impairment/toxicity:
- hepatic, cardiac, pancreatic, renal
H+/K+ ATPase (PPI) efficacy?
More effective and longer lasting effects than H2RAs/antacids.
Suppress daytime, nocturnal, and meal stimulated acid secretion
H+/K+ ATPase (PPI) FDA indications?
Erosive esophagitis
GERD
Duodenal ulcer
H. Pylori
H+/K+ ATPase (PPI) pharmacokinetics?
Short half lives
metabolize by the liver by CYP2C19 and CYP3A4 to inactive metabolites
H+/K+ ATPase (PPI) onset of action?
0.6 - 1.9 hrs
H+/K+ ATPase (PPI) drug interactions?
Ketoconazole
Amphetamines
Citalopram
Clopidogrel
PPI + ketoconazole causes?
May impair the GI absorption of ketoconazole leading to loss of therapeutic effect.
(drink coke if need to take the two together)
PPI + Amphetamines causes?
Increases the absorption of amphetamine
PPI + citalopram causes?
Citalopram tox: serotonin syndrome, QT prolongation.
PPI + clopidogrel causes?
PPI may decrease serum [ ] of the active metabolites of clopidogrel.
H+/K+ ATPase (PPI) ASEs?
“GI” side effects
HA
Hypomagnesemia (long term use)
Gastric atophy
Iron and B12 deficiencies
Hypersensitivity rxn: immunologic, dermatologic, hematologic, hepatic manifestation.
H+/K+ ATPase (PPI) appropriate duration?
2 wks, 4wks, up to 8-12 wks
- lowest effective dose for the shortest duration possible.
What is hypergastrinemia caused by a PPI?
High gastrin [ ] in the blood.
- cellular and hormonal changes that increase gastric acid secretion capacity.
Sucralfate MOA?
Reacts with HCl
Adherent, paste-like substance, an acid buffer
Binds electrostatically to proteins on ulcer surface (protective barrier)
Sucralfate proper dosing?
1 gram QID on empty stomach for 4 weeks
Acid neutralizers should not be taken within one-half hour before or after administration
Avoid H2RAs, fluroquinolones, tetracyclines, or digoxin within 2 hours before administration
Sucralfate ASEs?
Potential aluminum toxicity with long term use, esp. in patient with kidney dysfunction
Hypophosphatemia
Flatulence
HA
Safe and effective therapeutic treatment of PUD w/ H pylori?
MC = the PPI-based 3-Drug Regimen - first choice if local resistance is low.
3 Drugs = 1 Acid Reducer + 2 Antibiotics
- Amoxicillin, clarithromycin, lansoprazole
- Amoxicillin, clarithromycin, omeprazole
Pts w/ penicillin allergy: used metronidazole over amox.
Safe and effective therapeutic treatment of PUD w/ dyspesia?
Acid suppression: Antacids, H2RAs, PPIs
Safe and effective therapeutic treatment of PUD w/ GERD phase 1?
phase 1:
- OTC antacids, H2RA, or PPI x2 wks
Define what a “prokinetic” drug would do?
increases GI transit rates
Describe the relative lack of availability of “prokinetic” agents within the U.S.
Reported CV deaths
Metoclopramide MOA
Promotes motility in upper GI tract, sensitizes tissues to ACh action w/o stimulation of gastric secretions.
Decreases the flow in the esophageal varices causing a reduction in variceal pressure
Dopamine (D2) central and peripheral receptor inhibition w/o antipsychotic or tranquilizing activity
Weak 5-HT3 receptor antagonism
Metoclopramide clinical use
GERD
Relief of symptoms in adults with acute and recurrent diabetic gastroparesis
Chemotherapy-induced or postoperative nausea/vomiting
MAX 12 wks
Metoclopramide ASEs
Tardive dyskinesia (BB warning)
Headache, somnolence, fatigue, N/V
Production of serotonin?
Tryptophan - 5-HTP (5-hydroxytryptophan)
—>
5-HT (5-hydroxytryptamine)
= serotonin
Distribution of serotonin?
95% in GI tract of the 95%:
- 90% is in Enterochromaffin cells
- 10% is in Enteric neurons
Metabolism of serotonin through pineal gland?
Serotonin (5-HT) ---> pineal gland ---> melatonin ---> 6-sulfaoxymelatonin
Metabolism of serotonin through MAO?
Serotonin (5-HT) ---> MAO ---> 5-hydroxyindolacetic acid
Location of serotonin receptors?
Gut has 7 types of receptors
- Gut: increase tone and facilitate peristalsis
- CNS
- PNS
- Lungs- bronchoconstriction
- Enteric nerves: bady, hypoTN, nausea.
List the drugs that agonize the 5- HT4 receptor?
Tegaserod
Prucalopride
Describe gastrointestinal therapeutic applications of drugs that act on the agonize the 5- HT4 receptor?
Speeds GI transit
Stimulates peristalsis
Improves BM frequency
Soften stool
List the drugs that antagonize the 5- HT3 receptor?
Alosetron
Ondsanserton
Cilansetron
Describe gastrointestinal therapeutic applications of drugs that act on the antagonize the 5- HT3 receptor?
Nausea/vomiting
Irritable-bowel (diarrhea predominant)
Safe and effective therapeutic treatment of PUD w/ GERD phase 2?
- Rx H2RA (6-12wks)
- Rx PPI (4-8wks) or prokinetic agent if motility disorder.
List the 5 primary antiemetic drugs classes
- 5-HT3 antagonist
- Dopamine 2 antagonist
- Substance P/Neurokinin-1 antagonist
- Antimuscarinics
- 1st gen antihistamines
5-HT3 antagonist most appropriate clinical uses?
Nausea
Vomiting
IBS
Dopamine 2 antagonist most appropriate clinical uses?
Psychiatric disorders
Substance P/Neurokinin-1 antagonist most appropriate clinical uses?
Vasodilation
Inflammation
Pain
Mood
Vomiting
Antimuscarinics most appropriate clinical uses?
Motion sickness (scopolamine patch)
1st gen antihistamines most appropriate clinical uses?
Motion sickness
Anxiety for flights
5-HT3 antagonist ASEs?
HA
Constipation
Fever
Diarrhea
Prolonged QT interval
Cardiac arrhythmias
Dopamine 2 antagonist ASEs?
Extrapyramidal sxs
QT Prolongation
NMS
Substance P/Neurokinin-1 antagonist ASEs?
Steven johnson syndrome
Diarrhea
Constipation
Antimuscarinics ASEs?
Dry mouth and skin
Blurred vision
Hot flashes
1st gen antihistamines ASEs?
Sedation
Fatigue
Dizziness
Anticholinergic side effects (dry mouth, tachy, blurred vision)
What drug is used for motion sickness and temporarily as a sleep aid?
First generation antihistamines
ie. Dimenhydrinate (Dramamine), promethazine.
Name the drug under the class: substance p/neurokinin 1 receptor antagonists?
Aprepitant
