Ch.35a: Gastrointestinal Pharmacology (Hill) Flashcards
3 strategies to prevent gastric ulceration
1) buffer acid
2) inhibit receptors (i.e. histamine, gastrin, ACh, PG)
3) inhibit H:K ATPase in parietal cell
Groups of agents that prevent gastric ulceration
- antacids
- H2 inhibitors
- H:K ATPase (proton pump) inhibitors (PPI)
- mucosal protectants (chelating and complexing agents)
- prostaglandin analogs (misoprostol)
- prokinetics (cisapride)
disadvantages of antacids
- requires frequent administration
- divalent cations inhibit enrofloxacin absorption**
name 2 H2 inhibitors. Which interfere with P450 in the liver? Which is a prokinetic?
1) ranitidine - interferes with P450, is a prokinetic**
2) famotidine
Name 3 PPI
omeprazole
pantoprazole
lansoprazole
when should PPI be given?
before a meal, BID because they work best on open, active pumps
omeprazole features of note
- a PPI
- given ORALLY
- less expensive than other PPIs
- best for keeping gastric pH normalized
pantoprazole features of note
- a PPI
- given IV, so can be used on anorexic patients**
Lansoprazole features of note
- a PPI
- formulated with HCO3 as oral liquid for small dogs
Sucralfate features of note
- a mucosal coating chelating and complexing agent**
- a prodrug converted by acid that coats stomach lesions + an Al antacid
- Al antacid component inhibits enrofloxacin absorption
which is longer acting: famotidine or ranitidine?**
famotidine. Also more expensive
Name 4 antagonists of parietal cell acid secretion**
1) gastrin antagonists
2) prostaglandin AGONISTS
3) H2 antagonists
4) muscarinic antagonists
Name a prostaglandin analog
misoprostol
Misprostol features of note
- a prostaglandin analog
- low dose: stimulates blood flow (blood flow is a key mech. of controlling ulceration in the stomach!!)
- high dose: antacid
- prevents ulcers from aspirin
- does NOT prevent hemorrhage from pred.
- can induce labor/abortion
- used to tx NSAID overdose
- very expensive
aspirin inhibits/stimulates prostaglandin production
inhibits
Name 3 classes of drugs that promote (induce) vomiting
dopamine agonists (apomorphine) alpha-2 agonists (xylazine) gastric irritants (hydrogen peroxide)
2 part model for vomiting composed of:
1) chemoreceptor trigger zone (CRTZ) in dorsal medulla
2) vomiting center in reticular formation
Best way to induce vomiting in DOGS***
apomorphine (DA agonist) applied to conjunctiva. (Cats don’t have DA receptors!)
Best way to induce vomiting in CATS***
xylazine (alpha-2 agonist)
apomorphine MOA
DA agonist; acts through CRTZ
Drugs/classes of drugs that reduce vomiting (7)**
1) M1 inhibitors (scopolamine, pirenzipine)
2) H1 inhibitors (diphenhydramine)
3) Alpha-2 antagonists/Phenothiazines (Chlorpromazine, Prochlorperazine, Acepromazine)
4) DA antagonists (Metoclopramide)
5) 5HT3 antagonists (Ondansetron)
6) Neurokinin receptor antagonists (Maropitant)
7) Antimuscarinics (Centrine)
Where do most antiemetics act?
CRTZ
Name 2 classes of drugs for motion sickness/reduce vomiting
M1 (Ach receptor) inhibitors (scopolamine, pirenzipine) H1 inhibitors (diphenhydramine)
Name 3 alpha-2 antagonists/Phenothiazines and their effects
All 3 reduce BP, antiemetics
1) chlorpromazine
2) prochlorperazine
3) Acepromazine: also anti-motion sickness
Where do M1 inhibitors act?
vestibular apparatus and CRTZ
Where do H1 inhibitors act?
vestibular apparatus
name a dopamine antagonist
metoclopramide
features of metoclopramide
- DA agonist
- antiemetic
- crosses BBB
- may cause extrapyramidal effects (tremor)
- a PROKINETIC (promotes gastric emptying)
Name a 5HT3 (serotonin) receptor antagonist. Characteristics?
ondansetron:
- antiemetic
- may slow colonic transit
- expensive
Name a neurokinin (NK1) receptor antagonist. Chars.?
Maropitant (“Cerenia”):
- antiemetic (acts on vomiting center and CRTZ)
- can be used in combo with 5HT3 antagonists, but has many drug interactions
- approved for motion sickness
Which antiemetics used in dogs but not cats?**
H1 inhibitors
DA antagonists (Metoclopramide)
Maropitant (“Cerenia”) not licensed in cats, but still used
name an antimuscarinic. Chars.?
Centrine:
- weak antiemetic
- reduces SI motility and gastric emptying (paralyzes the gut)
- block prokinetics
- NOT recommended to use
Name 6 PROKINETICS (promoters of GI motility)***
metoclopramide** cisapride** 5HT4 agonists** Bethanacol** Ranitidine** Erythromycin Thoracic epidural analgesia for post-op ileus Octreotide
Cisapride features of note
- prokinetic
- serotoninergic agent (mixed 5HT3 antagonist/5HT4 agonist)
- promotes Ach release in SI
- causes fatal dysrhythmia in humans
Bethanacol features of note
- prokinetic
- limited use due to SLUD
Ranitidine MOA as a prokinetic
inhibits acetylcholinesterase and blocks H2
SLUD =
salivation, lacrimation, urination, defecation
2 types of motility in the stomach
1) FED: rapid contractions against closed pylorus to churn up food
2) UNFED: housekeeping clearing action about every 100 mins. when stomach is empty. Stimulated by Migrating Myoelectrical Complex (MMC)
2 types of contractility in the bowel
propulsive and mixing
Prokinetics general MOA
act on enteric nerves to increase cholinergic neurotransmission. They increase strength of propulsive contractions, improve antroduodenal coordination, and smooth m. tone.
Octreotide features of note
- an antiemetic
- a somatostatin analog
- must be given frequently
- expensive, not used frequently
Name 3 types of antidiarrheals
1) morphine agonists (loperamide, diphenoxalate)
2) inhibitors of SI secretion (bismuth subsalicylate)
3) absorbents (kaolin, activated charcoal)
Name 2 morphine agonist antidiarrheals
Loperamide, Diphenoxalate
Loperamide features of note***
- morphine agonist (antidiarrheal)
- slows transit and aids absorption
- does NOT cross BBB, doesn’t cause sedation
- is like a cork!
Diphenoxalate features of note**
-morphine agonist (antidiarrheal)
-slows transit and aids absorption
slightly crosses BBB, can cause some sedation
-also inhibits secretion
Name an inhibitor of SI secretion. MOA?
bismuth subsalicylate ("Pepto Bismol"):
inhibits PG and cAMPName 2 absorbent antidiarrheals
Kaolin, Activated Charchoal
Q: what antibiotic should you give for acute GI disease?***
NONE! (avoid if possible because will destabilize intestinal flora)
What kind of bacteria are in upper intestine?**
G+ and -
What kind of bacteria are in lower intestine?**
G- and anaerobes
advantage of enrofloxacin. When should you use it?**
Doesn’t disrupt anaerobes
-use for Salmonella, acute pancreatitis, Boxer Colitis
What abx should be used for clostridial colitis?
metronidazole
tylosin
vancomycin
What tx should be used for Helicobacter?
combination of PPI (omeprazole) and abx
tx for Small Intestinal Dysbiosis/SI Bacterial Overgrowth***
tetracycline
metronidazole
tylosin
Name anti-inflammatory and immunosuppressive agents
1) Prednisone/Prednisolone
2) Dexamethason
3) Budesonide
4) Azathioprine
5) Cyclosporine
6) Leflunamide
7) Sulfasalazine (an aminosalicylate)
8) Olsalazine (an aminosalicylate)
9) Bismuth subsalicylate
Sulfasalazine MOA
- anti-inflamm/immunosuppressive
- acts like aspirin
- inhibits prostaglandin prod.
- a pro-drug
Name 2 osmotic agents that act as laxatives
magnesium sulfate
Colyte
Name 6 laxatives and their MOA
magnesium sulfate (osmotic agent)
colyte (osmotic agent)
psyllium (bulk forming osmotic agent-soluble fiber)
lactulose (bulk forming osmotic agent-insoluble fiber)
mineral oil (lubricant)
petrolatum (lubricant)
Name 5 agents that treat round worms
Benzimidazoles (i.e. Panacur)
Pyrantel (strongid)
Ivermectin
Emodepside (Profender)
What treats tapeworm?
Praziquantel (Droncit)
Which agents treat whipworms?**
Fenbendazole (Panacur) Febantel (in Drontal Plus) Moxidectin (in Advantage Multi) Milbemycin (interceptor, Trifexis) Emodepside (Profender)
Probiotics
Population determined by food supply and environment, so must use every day or immediately eliminated. Ex:
- Lactobacillus in yogurt
- Bacillus cereus
- Enterococcus faecium (in Purina)*
- Bifidobacterium animalis (in Iams)*
- Saccharomyces
Prebiotics examples
- oligo-saccharides: FOS, soy
- poly-saccharides in soluble fiber: pectins, gums
- mixed soluble and insoluble fibers: beet pulp
