Drugs Affecting the Gastrointestinal Tract and Antiemetic Drugs

Question 1

Amoxicillin (AMOXIL, TRIMOX); “Bismuth compounds (PEPTO-BISMOL, KAOPECTATE)”; Clarithromycin (BIAXIN); Metronidazole (FLAGYL); Tetracycline (Sumycin)

Answer 1

Pharmacodynamics: Antimicrobial agent;
Indications for use: Used to treat gastric ulcers (duodenal as well) caused by H.pylori leading to rapid healing and low recurrence.
Clinical information: given as triple therapy (PPIs + Amoxicillin (Metronidazole if allergic) + Clarithromycin) alternatively there is quadruple therapy (pepto-bismol + metranidazole + tetracycline + PPI).
N.B Bismuth compounds can be used as an agent to modify fluid and electrolyte transport.

Question 2

Cimetidine (TAGAMET); “Famotidine (PEPCID)”; Nizatidine (AXID); Ranitidine (ZANTAC)

Answer 2

Pharmacodynamics: H2 - histamine receptor blockers (reversible competitive antagonist);
Indications for use: used to treat peptic ulcers (if-NSAID induced then PPIs should be used), acute stress ulcers (temporary), gastroesophageal reflux disease;
Clinical information: also inhibits basal, food stimulated and nocturnal stimulation; the use of these has been diminished due to PPIs.

Question 3

Dexlansoprazole (DEXILANT); Esomeprazole (NEXIUM); Lansoprazole (PREVACID); “Omeprazole (PRILOSEC)”; Pantoprazole (PROTONIX); Rabeprazole (ACIPHEX)

Answer 3

Pharmacodynamics: Proton pump inhibitors (PPIs) bind directly H+/K+ ATPase (lasts for 18 hours);
Indications for use: Used in treatment of GERD, prophylaxis in conjunction with NSAIDS to prevent ulcerations of the stomach, erosive esophagitis, active ulcers and diseases such as Zollinger - Ellison (gastrin producing tumor) and used in treatment of H.pylori ulcers.

Question 4

“Misoprostol (CYTOTEC)”

Answer 4

Pharmacodynamics: Prostoglandin E inhibits gastric secretion and promotes secretion of mucus and bicarbonate;
Indications for use: Used to treat peptic ulcers caused by deficiency in prostoglandin E, should be given as prophylaxis for people who take NSAIDs;
Contraindication: pregnancy (can cause premature uterine contractions).

Question 5

Dicyclomine (BENTYL)

Answer 5

Pharmacodynamics: Antimuscarinic agents;

Indications for use:

Question 6

“Aluminium hydroxide (ALTERNAGEL)”; “Calcium carbonate (TUMS)”; “Magnesium hydroxide (MILK OF MAGNESIA)”; Sodium bicarbonate

Answer 6

Pharmacodynamics: Antacids weak bases that react with gastric acid to form water and reduce pepsin activity by inactivating it in alkaline conditions;
Indications for use: used to control symptoms of peptic ulcers and treat GERD;
Contraindication: in renal patients due to absorption of cations;
Side effects: Aluminium causes constipation and magnesium causes diarrhoea.

Question 7

“Bismuth subsalicylate (PEPTO-BISMOL)”; Sucralfate (CARAFATE)

Answer 7

Pharmacodynamics: Mucosal protective agents;
Indications for use: Sucralfate used in treatment of peptic ulcer as aluminium and sucrose bind to proteins on necrotic tissue and form a protective gel;
Bismuth part of quadruple therapy to treat peptic ulcers inhibits pepsin, increases mucus secretion, interacts with glycoproteins forming a protective coating on the mucosa;
Contraindication: Sucrasulfate requires acid to should not be given with PPIs, H2 antagonists and antacids.

Question 8

Prochlorperazine (COMPAZINE)

Answer 8

Pharmacodynamics: Phenothiazines block dopamine receptors;

Indications for use: used to control chemotherapy-induced nausea and vomiting.

Question 9

Granisetron (KYTRIL); Palonosetron (ALOXI); “Ondansetron (ZOFRAN)”; Dolasetron (ANZEMET) (last two no longer used due to prolonging of QTc interval)

Answer 9

Pharmacodynamics: 5-HT3 serotonin receptor blockers (antagonists) in the periphery and the CTZ long duration and high efficacy;
Indications for use: used to control chemotherapy-induced and post operative nausea and vomiting;
Contraindications: ondansetron requires a dose adjustment in hepatically impaired patients.

Question 10

“Metocloperamide (REGLAN)”

Answer 10

Pharmacodynammics: Substituted benzamides leading to inhibition of dopamine in the CTZ ;
Indications for use: used to control chemotherapy-induced (cisplatin) nausea and vomiting;
Side effects: Can cause extrapyrimidal effects so should not be used long term or for GERD.

Question 11

Droperidol; Haloperidol (HALDOL)

Answer 11

Pharmacodynamics: Butyrophenones block dopamine receptors;
Indications for use: used to control chemotherapy-induced (cisplatin) nausea and vomiting;
Side - effects: prolongs QTc interval.

Question 12

Alprazolam (XANAX); Lorazepam (ATIVAN)

Answer 12

Pharmacodynamics: Benzodiazepines GABA-A agonists mostly due to sedative, anxiolytic and amnesic properties (prophylaxis);
Indications for use: used to control chemotherapy-induced nausea and vomiting;
Contraindications: alcohol (CNS depression).

Question 13

Dexamethasone (DECADRON); Methylprednisolone (MEDRIOL)

Answer 13

Pharmacodynamics: corticosteroids (blockade of prostoglandins?);
Indications for use: used to control chemotherapy-induced nausea and vomiting.

Question 14

Aprepitant (EMEND)

Answer 14

Pharmacodynamics: Substance p/neurokinin-1 receptor blocker targets neurokinin receptor and blocks action of substance P;
Indications for use: used to control chemotherapy-induced nausea and vomiting;
Clinical information: Given along side dexamethasone and 5-HT3 antagonists;
Contraindications: metabolised by CYP3A4 so effects metabolism of warfarin and oral contraceptives.

Question 15

How do H2 receptor antagonists regulate gastric acid secretion?

Answer 15

Secretion is stimulated by histamine as well as gastrin and ACh. Receptor binding –> activates protein kinase –> stimulates H+/K+ ATPase PP –> exchange of H+ and K+ into the stomach. Blocking of H2 reduces secretion.

Question 16

What are the side effects of H2 receptor antagonists?

Answer 16

Mostly well tolerated. Cimetidine has endocrine effects (nonsteroidal anti-androgen) leading to gynocomastia and galactorrhea (release of prolactin), CNS effects (confusion and altered mental state in the elderly), inhibits CYP450 and the metabolism of warfarin, phenytoin and clopidogrel. All reduce the effect of drugs such as ketoconzole that require acid for absorption.

Question 17

Diphenoxylate + atropine (LOMOTIL); “Loperamide (IMODIUM A-D)”

Answer 17

Pharmacodynamics: anti-motility agents have opioid like action on gut blocking pre-synaptic opioid receptors in the enteric NS decreasing peristalsis by reducing release of ACh;
Indications for use: Used in treatment of diarrhoea;
Side - effect: can cause toxic megacolon.

Question 18

“Aluminium hydroxide” (ALTERNAGEL); Methylcellulose (CITRUCEL)

Answer 18

Pharmacodynamics: adsorb intestinal toxins and microorganisms and protecting the intestinal mucosa - methyl cellulose is also a bulk laxative;
Indications for use: treatment of diarrhoea;
Contraindication: interfere with the absorption of other drugs.

Question 19

“Bisacodyl (CORRECTOL, DULCOLAX)”; Castor oil; “Senna (SENOKOT)”

Answer 19

Pharmacodynamics: irritants and stimulants - anthraquinone glycosides causing electrolyte and water secretion into bowels, bisacodyl acts on nerve fibres in the mucosa of the colon and castor oil’s product (ricinoleic acid) irritates the stomach producing peristalsis;
Indications for use: Used as laxatives;
Contraindications: can cause uterine contractions so should not be used in pregnancy.

Question 20

Psyllium (METAMUCIL, FIBERALL)

Answer 20

Pharmacodynamics: Bulk laxative - hydrophilic colloids form gels in large intestine causing fluid retention and distention increasing peristalsis;
Indications for use: Used as a laxative;
Contraindications: Potentially can cause an obstruction so should not be given to those who are immobile.

Question 21

“Magnesium citrate (CITROMA); Magnsium hydroxide (MILK OF MAGNESIA)”; Polyethylene glycol / “Sodium picosulfate” (used for gastric lavage before surgery) (MIRALAX, GOLYTELY, MOVIPREP, NULYTELY, TRILYTE); Lactulose

Answer 21

Pharmacodynamics: Saline and osmotic laxative - hold water via osmosis (increased salt or sugar concentration within the lumen) causing peristalsis;
Indications for use: Laxative (PEG specifically used for colonic lavage and causes less cramping and gas), lactulose used to treat hepatic encephalopathy as it reduces ammonia levels.

Question 22

Docusate (COLACE, DOCU-SOFT)

Answer 22

Pharmacodynamics: stool softener - surface active agents –> emulsified with stool to produce softer feces;
Indications for use: prophylactic laxative;
Contraindications: should not be taken with mineral oil as it will be absorbed.

Question 23

Glycerin suppositories, Mineral oil

Answer 23

Pharmacodynamics: lubricant;
Indications for use: laxative;
Clinical information: mineral oil should be taken upright to avoid aspiration and lipoid pneumonia.

Question 24

Lubiprostone (AMITIZA)

Answer 24

Pharmacodynamics: Chloride channel activators increasing fluid secretion into the intestinal lumen;
Indications for use: laxative for chronic constipation as no tolerance, dependency, electrolyte imbalance or chronic constipation;
No contraindications as metabolism occurs in stomach and jejunum.

Question 25

Why should PPIs and H2-antagonists not be taken together?

Answer 25

H2 - antagonists deactivate PPs that PPIs require to function.

Question 26

What are the adverse side effects of PPIs?

Answer 26

May decrease the effectiveness of clopidogrel as inhibits CYP2C19; increased risk of fracture; prolonged acid suppression –> B12 deficiency; impairs absorption of “calcium carbonate” so citrate given instead as doesn’t require acid; diarrhoea, hypomagnesemia, pneumonia.

Question 27

What are the side - effects of antacids?

Answer 27

Diarrhoea and nausea.

Question 28

How do chemotherapeutic agents increase 5-HT and why does this lead to emesis?

Answer 28

They damage the GI tract and release 5-HT from enterochromaffin cells in small intestine activating 5-HT3 receptors on the vagus and splanchnic afferent fibres carrying sensory signals to the medulla and inducing emesis.

Question 29

What are the major side effects of laxatives?

Answer 29

They can cause dehydration with prolonged use as well as dependence.

Question 30

“Aprotinin”

Answer 30

Pharmacodynamics: Competitive inhibitor of kallikrein inhibiting factor XIIa slowing fibrinolysis;
Indications for use: reduces bleeding during complex surgeries.

Question 31

“Ursodeoxycholic acid”

Answer 31

Pharmacodynamics: Dissolves cholesterol and has an anti-inflammatory effect increasing restitution of wounds in the colon;
Indication for use: reduces gallstone formation, treatment of primary biliary cirrhosis, improve bile flow in cystic fibrosis.

Question 32

“Ademethionine”

Answer 32

Used to treat osteoarthritic pain, however an adverse effect is dyspepsia.