GI Pharmacology Flashcards
1
Q
What are the different GI disorders?
A
Gastroesophageal Reflux Disease (GERD)
Peptic Ulcer Disease (PUD)
Duodenal Ulcer
Nausea
Emesis
IBS
Diarrhea
Constipation
2
Q
Gastric Mucosal Barrier
A
- The alkaline-rich mucus produced by mucosa cells in the pyloric region that protects the epithelium of the stomach and duodenum from harsh acid conditions of the lumen
- These cells are stimulated by mechanical and chemical irritation and parasympathetic inputs.
- This protective mucus barrier can be damaged by bacterial and viral infection, certain drugs, and aspirin
3
Q
GERD
A
- Backflow of stomach acid into the esophagus, which can cause scarring
- Usual symptom of heartburn (burning sensation behind the breastbone; MI is often mistaken for GERD)
- severe symptoms=difficulty swallowing and chest pain
- complications include esophageal erosions, esophageal ulcer and esophageal stricture (narrowing)
- ~10% pts, normal esophageal lining is replaced with Barrett’s epithelium (aka Barrett’s esophagus) and has been linked to cancer
- Precipitants include: fatty food, alcohol, caffiene, smoking, obesity, and pregnancy
—this is usually a chronic/relapsing course
4
Q
Peptic Ulcer Disease
A
- Can be benign or malignant
- Benign: normal gastric acid production, but the mucosal barrier is weak
- Malignant: Excessive secretion of gastric acid that overwhelms the mucosal barrier
5
Q
Treatments for GERD and PUD
A
- Antacids
- H2 Receptor Blockers
- Mucosal Protective Agents
- Proton Pump Inhibitors
- Anti-cholinergics
- Prostaglandin Analogs
- Anti-microbial Agents
6
Q
Antacids
A
Systemic antacid: Sodium bicarbonate
Nonsystemic antacids: Aluminum Hydroxide+Mg Hydroxide (Maalox and Mylanta)
- Maalox and Mylanta are contraindicated in pts with impaired renal function and Mg may cause diarrhea
- Calcium carbonate (Tums): Ca may cause constipation
7
Q
H2 Receptor Blockers
A
- Cimetidine
- Famotidine
- Ranitidine
- Nizatidine
- Inhibit secretion of gastric acid through competitive inhibition of Histamine H2 receptors
- Prevention and Tx of PUD, Esophagitis, GI bleeding, stress ulcers, and Zollinger-Ellison Syndrome
- May alter the effects of other drugs through interactions with CYP450 (especially cimetidine)
- Very few side effects (except for cimetidine which inhibits metabolism of estrogen which can cause breast tissue growth in men when taken long term)
- Suppresses 24 hour gastric secretion by 70%
8
Q
Proton Pump Inhibitors (PPIs)
A
- Omeprazole
- Esomeprazole
- Rebeprazole
- Lansoprazole
- Pantoprazole
- Strong inhibitors of gastric acid secretion through irreversible inhibition of proton pump
- Prevents release or pumping of gastric acid (24 hr action)
- Indicated in PUD, Gastritis, GERD, & Zollinger-Ellison syndrome
- Faster relief and healing than H2 receptor blockers
- Decreases acid secretion by up to 95% for up to 48 hours -4-8 week course of treatment
9
Q
Mucosal protecting agents
A
Sucralfate (carafate)
- -used to prevent and Tx PUD
- -requires an acidic pH to activate
- -forms a sticky polymer in the acidic environment & adheres to the ulcer site forming a barrier
Chelated Bismuth
- -protects the ulcer crater and allows healing -some activity against H. pylori
- -should not be used repeatedly or for more than 2 months at a time
- -can cause black stools and constipation
10
Q
Anti-H. pylori therapy
A
>85% PUD caused by H. pylori Antibiotic Ulcer Therapy: Used in Combinations
- Bismuth: Disrupts bacterial cell wall
- Clarithromycin: Inhibits protein synthesis
- Amoxicillin: Disrupts cell wall
- Tetracycline: Inhibits protein synthesis
- Metronidazone: Used often due to bacterial resistance to amoxicillin and tetracycline, or due to intolerance
11
Q
Anti-H. pylori therapy
A
Triple Therapy is a 7 day treatment 80-85% effective
-Proton pump inhibitor + amoxicillin/tetracycline + metronidazone/clarithomycin
Quadruple Therapy is a 3 day treatment and as efficacious as triple therapy
-Add Bismuth to triple therapy
12
Q
Prostaglandins
A
Misoprostol
- PGE1 analog
- Stimulates GI pathway leading to a decrease in gastric acid release
- For treatment of NSAID induced injury
- Side effects include diarrhea, pain, and cramps (30%)
**Do not give to women of childbearing years unless a reliable method of birth control can be DOCUMENTED
**Can cause birth defects, and premature birth
13
Q
Anticholinergics
A
Pirenzipine
- Muscarinic M1 Ach receptor antagonist
- Blocks gastric acid secretions
- About as effective as H2 blockers
- Rarely used, primarily as adjunct therapy
- Anticholinergic side effects (anorexia, blurry vision, constipation, dry mouth, sedation)
14
Q
Inflammatory Bowel Disease
A
Ulcerative Colitis
- A diffuse mucosal inflammation limited to the colon
- Bloody diarrhea, colicky pain, urgency, tenesmus (feel like you have to use the bathroom even though bowels are empty) Crohn’s Disease
- Patchy transmural inflammation
- May affect any part of the GI tract
- Causes abdominal pain, diarrhea, weight loss, intestinal obstruction
15
Q
Treatment for Inflammatory Bowel Disease
A
Goal of treatment is to resolve the acute episodes and prolong remission
- Aminosalicylates - for mild symptoms
- Corticosteroids - for moderate symptoms
- Thiopurines - for active and chronic symptoms
- Methotrexate - for active and chronic symptoms
- Cyclosporin - for active and chronic symptoms refractory to corticorsteroids- (significant side effects)
- Infliximab - antibody infusion
16
Q
Constipation
A
- Usually effectively treated with dietary modification
- Only if this fails should laxatives be used
- Laxative abuse is #1 cause of constipation
Therapy:
- -Bulking agents
- -Osmotic laxatives
- -Stimulant drugs
- -Stool softeners
17
Q
Bulk laxatives
A
- Increase in bowel content volume triggers stretch receptors in the intestinal wall
- Causes reflex contraction (peristalsis) that propels the stool forward
Psyillium
Bran
Methylcellulose
- -insoluble and non-absorbable
- -non digestible
- -must be taken with lots of water or it will make constipation worse
18
Q
Saline and Osmotic Laxatives
A
- Effective in 1-3hrs
- used to purge the intestine (i.e. surgery or poisoning)
- Fluid is drawn into the bowel by osmotic force, increasing volume and triggering peristalsis
19
Q
Saline and Osmotic Laxatives
A
Nondigestible sugars and alcohols:
- -Lactulose (broken down by bacteria to acetic and lactic acid, which causes the osmotic effect)
Salts:
- -Milk of Magnesia (Mg(OH)2)
- -Epsom Salt (MgSO4)
- -Glauber’s Salt (Na2SO4)
- -Sodium Phosphates (used as enema)
- -Sodium Citrate (used as enema) Polyethylene glycol
20
Q
Stool Softeners-Emollients
A
Docusate sodium (surfactant and stimulant)
Liquid parafin (oral solution)
Glycerin suppositories
21
Q
Irritant/Stimulant Laxatives
A
- Increase intestinal motility
- Irritate the GI mucosa and pull water into the lumen
- Indicated for severe constipation where more rapid effect is required (6-8hrs)
Therapy:
- Castor oil-from the castor bean
- Senna-plant derivative
- Bisacodyl
- Lubiprostone-PGE1 derivative that stimulates chloride channels and produces Cl rich secretions
22
Q
Laxative Abuse
A
- Most common form of constipation
- A longer interval is needed to refill colon after use and is misinterpreted as constipation=repeated use
- Enteral loss of water and salts causes release of aldosterone
- This stimulates reabsorp. in the intestine and increases renal excretion of K
- Double loss of K=hypokalemia which reduces peristalsis & is misinterpreted as constipation which leads to repeated laxative use
23
Q
Diarrhea
A
- Caused by Toxins
- Caused by microorganisms: Shigella, salmonella, E.coli, campylobacter, c.diff
- Caused by antibiotic associated colitis
Indications for treatment
- -Last longer than 2-3 days
- -severe diarrhea in elderly or small children
- -chronic inflammatory disease
- -when a specific cause has been determined
24
Q
Anti-Diarrheal Agents
A
Anti-motility Agents Reduce peristalsis by stimulating opioid receptors in the bowel
Allow time for more water to be absorbed by the gut
- Morphine
- Codeine
- Diphenoxylate
- Loperamide:
- -40-50x more potent than morphine
- -Poor CNS penetration
- -Increases transit time and sphincter tone
- -Antisecretory against cholera & some E.coli toxin
- -T½ 11 hours, dose: 4 mg followed by 2mg doses (16mg/d max)
- -Overdose: paralytic ileus, CNS depression
- -Caution in IBD (toxic megacolon)
Contraindications for antidiarrheals
- -Toxic Materials
- -Microorganisms (salmonella, E.coli)
- -Antibiotic associated
25
Clostridium difficile
The major cause of diarrhea and colitis in patients exposed to antibiotics
Fecal - oral route of transmission
Three steps to infection:
* -Alteration of normal fecal flora
* -Colonic colonization of C. difficile
* -Growth and production of toxins Infection can lead to formation of colitis and toxic megacolon
Pharmacological Treatment:
* -Discontinue offending antibiotic
* -Metronidazole (contraindicated in patients with liver or renal impairment)
* -Vancomycin (contraindicated in patients with renal impairment)
26
Antiflatulants
-Used to relieve the painful symptoms associated with gas
Simethicone (a detergent):
- Alters elasticity of mucus-coated bubbles, causing them to break
- Large bubbles -\> smaller bubbles, and less pain -Used often, but limited data regarding effectiveness
27
Emesis
Occurs via activation of three main areas in the brain
* -Cortex (see something repulsive)
* -Vestibular apparatus (motion sickness)
* -Chemoreceptor Trigger Zone (feeds into the vomiting center in the brain)
Ingesting a toxin also causes emesis
28
Syrup of Ipecac Emetic
- Prepared from the root of the ipecacuanha plant
- Induces emesis
- Side effects include drowsiness, diarrhea, and stomach ache
Acceptable for use when:
* -There is no contraindication to the use of ipecac
* -There is risk of serious toxicity to the victim
* -No alternative therapy is available or effective to decrease gastrointestinal absorption (e.g., activated charcoal)
* -There will be a delay of greater than 1 hour before the patient will arrive at an emergency medical facility and ipecac syrup can be administered within 30-90 minutes of the ingestion
* -Ipecac syrup administration will not adversely affect more definitive treatment that might be provided at a hospital
29
Antiemetic Therapeutics M1 receptor antagonist
Muscarinic (M1) receptor antagonist
-Scopolamine (skin behind the ear is best place for patch b/c skin is thinnest there)
Side Effects:
* -dry mouth
* -dizziness
* -restlessness
* -dilated pupils
* -delirium at high doses
* -allergic reaction
Contraindications:
* -kidney or liver disease
* -enlarged prostate
* -difficulty in urination/bladder problems
* -heart disease -glaucoma
30
Antiemetic Therapeutics Histamine H1/Dopamine D2 receptor antagonist
Phenothiazines
Promethazine (Phenergan)
Prochlorperazine (Compazine)
Side Effects:
* -These drugs are neuroleptics (typical antipsychotics)
* -Blurred vision
* -Dry mouth
* -Dizziness
* -Restlessness
* -Seizures
* -Extrapyramidal effects - Tardive dyskinesia (long term treatment)
Contraindications:
* -Allergy to phenthiazines
* -Glaucoma
* -Liver disease
* -Prostate / bladder problems
31
Antiemetic Therapeutics Serotonin 5-HT3 receptor antagonist
Excellent for chemotherapy induced nausea and vomiting
- Ondansetron (Zofran)
- Granisetron
Side Effects:
* -Very few common side effects
* - usually well tolerated
* -Headache
* -Constipation
Rarely:
* -Hiccups
* -Itchiness
* -Transient blindness
