Drugs for GI Disorders Flashcards
The most common secretory disorder in GI tract is
acid- peptic disease
- peptic ulcer disease
- GERD (50%)
- hypersecretory states (Zollinger ellison syndrome)
Goals of treating acid-peptic disease
Relieve pain, promote healing, prevent recurrence
Anti ulcer drugs act to
neutralize gastric acid, reduce secretion, enhance mucosal defenses
Anti muscarinic drugs for gastric acid secretion
weak inhibitors of acid secretion because they act at one site
-Ach mediator acting on muscarinic receptors
Use with other therapies
Gastrin blockage
-peptide hormones formed by mucosal cells
Stimulates gastric motility, HCL, and pepsin secretion
Acts towards gastrin- cholecystokinin B and is an H2 blocker
H2 antagonists (general)
reduce gastrin secretion by blocking histamine induced inc cAMP and proton pump activation (Gastric acid secretion)
On parietal cell
PPI
-end with -prazole (omeprazole, esomeprazole, etc.)
Benzimidazole cpds irreversibly inhibit parietal cell proton pump, H/K/ATPase
Prodrugs which are inactive at neutral pH- requires acidic environment in canaliculi (don’t give with antacids)
Metabolized in liver
More effective than H2 antagonists or NSAID induced peptic ulcers
AE of PPI
GI effects because no longer having acidic environment to prevent food and microbes from entering small bowel
Diarrhea with prolonged use due to GIT bacterial overgrowth
Activation of PPI
Prodrugs which after passing through stomach, enteric coating dissolve and the pro drug is absorbed in the intestines and then carried to parietal cell, where drug accumulates in secretory canaliculi.
Here, the activated drug binds to sulfyhdryl groups on H/K ATPase
H2 antagonists-
-end with tidine (famotidine > nizatidine = ranitidine > cimetidine)
histamine (H2) receptor antagonists to reduce gastric acid and pepsin secretion (particularly useful at bedtime)- does not inhibit other receptors or channels
inhibit acid secretion for <6 hrs when OTC and inhibits 60-70% for 24 hours when prescription
decline use because of ppi
do not use in combo with ppis because reduce acid secretion in parietal cells so ppi won’t get activated
H2 Antagonist AE
- safe
- not to be given to pregnant women bc they cross placenta and secreted into breast milk
- diarrhea, headaches, bradycardia, fatigue
- confusion and agitation with IV admin in pts who are elderly
Cimetidine
H2 receptor antagonist which causes gynecomastia or impotence in men and galactorrhea in women because endocrine effects (cimetidine inh binding of dihydrotestosterone to androgen receptors)
interferes with cyp 450 pathways
Antacids
- aluminum hydroxide, calcium carbonate, combination aluminum hydroxide and magnesium hydroxide (aluminum will lead to constipation, magnesium will lead to diarrhea, calcium is constipating)
- weak bases that neutralize gastric Hcl
- used as needed to relieve pain in esophagitis, peptic ulcer, and GERD
can cause cation absorption and systemic alkalosis in renal pts
Do not use antacids if you are a
renal pt- can cause cation absorption and systemic alkalosis in renal pts
-Sucralfate (aluminum sucrose sulfate)
- Mucosal protective agent
- protective coating on peptic ulcers
require’s acidic environment to be activated
AE: constipation
few other adverse effects
Misoprostol
Mucosal protective agent
methyl analog of PGE1
Binds to PG receptors on parietal cells to inhibit acid secretion
Used for long term NSAID use because NSAIDs inhibit PG formation, misoprostal will prevent NSAID induced ulcers
AE: diarrhea, abd pain, abortion by stimulating uterine contractions
Bismuth subsalicylate (Pepto Bismol)
mucosal protective agents protective coating of ulcers antibacterial against H pylori -OTC for dyspepsia and acute diarrhea -minimal AE because not absorbed but will darken tongue and stools
H pylori
gram neg bacterium, causes inflammatory gastritis that may lead to peptic ulcers
triple therapy for 10-14 days: calrithromycin, amoxicillin, ppi (allergic to penicillin- use metronidazole)
Laxatives
Used to promote defecation and treat constipation
- often abused by patients with eating disorders
- usually unnecessary as constipation can be resolved by inc water and fiber content, appropriate bowel habits, imrproved physical activity, attention to psychosocial and emotions
Saline laxatives
-Osmotically active
Nonabsorbable salts containing mangesium cations or phosphate anions
-act as osmotic force to hold water inside intestines–> distended intestines–> stimulate peristalsis
-avoid in renal insufficiency, heart disease, electrolyte imbalance, diuretic co treatment
Nondigestible sugars and alcohols
osmotically active laxative
-glycerin acts in rectum as lubricant–> water retention–> stimulate peristalsis
lactulose, sorbitol, mannitol are nonabsorbable sugars–> hydrolyzed to organic acids–> acidify lumen–> draw water in–> increase motility
Polyethylene glycol electrolyte solutions
osmotically active laxative
- poorly absorbed and retain added water by high osmotic pressure
- colonoscopy prep
Stimulant or Irritant Laxatives
Act on enterocytes, enteric neurons, muscle induce low grade intestinal inflammation–> water and electrolytes accumulate–> inc intestinal motility
- Diphylmethane derivatives- bisacodyl (unchewed pill taken at bedtime), phenolphthalein (withdrawn due to carcinogenicity)
- anthraquinones like aloe, cascara sagrada or senna- poorly absorbed in SI and require activation in colon with lax effects later; long term use causes melanomic pigmentation of colonic mucosa and cathartic colon (dilated and ahaustral)
- Ricinoleic acid (castor oil) -local irritant, unpleasant taste, toxic potential
Bulk forming laxatives
dietary supplements add bulk and hold water to intestinal contents
- methylcellulose, lactulose, polycarbophil
- must take with lots of water
Stool softeners
soften stool, facilitate expulsion
- oral or rectal
- mineral oil, glycerin suppositories, docusate sodium
- docusate often prescribed to prevent straining in hospitalized pts or those on opioids
Antidiarrheal
- usually self limiting
- loperamide, diphenoxylate, difenoxin (low efficacy opioids only producing SE of constipation- remove ACh and para tone on GI), bismuth subsacicylate (inh intestinal secretions- manage infxs diarrhea), kaolin/pectin (absorbing cpds and bind potential intestinal toxins), somatostatin/octreotide
Loperamide
- Antidiarrheal drugs
- opioid, inhibits ACh release–> decrease motility, does not cross BBB
- quickly (3-5) hrs for relief of acute, non specific diarrhea (Traveler’s diarrhea) (may exacerbate diarrhea due to criters)
- may result in rebound constipation
-more effective than diphynoxylate
Somatostatin/Octreotide
-inhibits secretin of gastrin, cholesystokinin, glucagon, growth hormone, insulin, secretin, pancreatic polypeptide, VIP, 5-HT
- reduces intestinal fluid and pancreatic secretion
- slows GI motility and inh gall bladder contraction
- reduces portal and splanchnic bloow flow
H1 antagonists
anti-emetics
first gen h1 blockers
prevents motion sickness by producing sedation and antimuscarinic activity
-dimenhydrinate, diphenhydramine, cyclizine, meclizine
Dopamine D2 antagonists
Metoclopramide, trimethobenzamide
anti-emetics
5HT3 antagonists
odansetron, granisetron, dolasetron
used for nausea and vomiting during cancer chemotherapy
NK1 antagonists
aprepitant, fosaprepitant, rolapitant
anti emetic
Phenothiazines
anti-emetic
Chlorpromazine, prochlorperazine
Benzodiazepines
anxiety drugs used for anti-emetics
lorazepam, alprazolam
Marijuana derivatives
Tetrahydrocannabinol (THC) or dronabinol
anti emetic with unknown underlying mechanism
AE: inc SYM activity- laughing, paranoid reactions, thinking abnormalities
Tx of IBS
tricyclic antidepressants-amitriptyline or desipramine
Antispasmodics- anticholinergics (dicylomine, hyoscyamine)
5-HT4 partial agonist- tegaserod (emergency tx only for IBS with constipation), CV events can occur
5HT3 antagonist- alosetron for diarrhea predominant IBS, CV events can occur
opioid agonist- eluxadoline (diarrhea predominant ibs)
Antibiotic- rifaximin- dirrhea predominant IBS (may alter bacterial content of GI tract)
Pancreatic enzyme supplements
For pancreatic insufficiency caused by CF, chronic pancreatitis, resection
-can lead to steatorrhea, vit malabsorption, weight loss
-pancreatin, pancrelipase administered with each meal and snack
can lead to hyperuricosuria and renal stones
Antiobesity drugs
Orlistate- gi lipase inhibitor
Sibutramine- CNS, reduces appetite
RImonabant- CNS (peripheral?), reduces appetite, opposite of weed
