AS DRUGS: Gastrointestinal Pharmacology (John Waddington)

Drug name
Side effects
Action
Other
HELICOBACTER PYLORI [Amoxicillin, Clarithromycin and acid suppressant]
HB Treatment: use Triple therapy: Two antibiotics (Amoxicillin and Clarithromycin) and an acid suppressant
.such as Proton pump inhibitor or H2 antagonist
PROTON PUMP INHIBITORS
Uses of Proton Pump inhibitors: Triple therapy for peptic ulcer, gastroesophageal reflux, prophylaxis against
ulcer development.
Omeprazole
Diarrhea, nausea, flatulence
- Irreversible blocking of
H+/K+ Atpase [proton pump]
- prodrug activated in acid pH
H2 RECEPTOR ANTAGONIST [Cimetidine, Ranitidine]
It competitively blocks histamine induced acid release by parietal cells. There is less acid suppression than PPIs
because it only blocks histamine component. Ulcer relapses once treatment stopped.
Cimetidine
- Confusions/drowsiness,
- It inhibits cytochrome p450
Gynaecomastia:
Headaches, rashese, diarrhea
enzymes.
enlargement of breasts in
- Hepatic/renal failure in
- It has antiandrogenic activity.
males.
elderly
Raises prolactin levels
Ranitidine
- Fewer side effects
- little/no inhibition of P450
enzymes and antiandrogenic
activity.
CYTOPROTECTIVE AGENTS [Misoprostol, Sucralfate, Bismuth[
- Cytoprotective agents are used for mucosal barrier fortifying agents. (Encourage mucosal barriers)
Misoprostol
- Diarrhea, uterine
- NSAIDs inhibit COX1 to
- analogue of
contractions, thus,
decrease prostaglandin
Prostaglandin PGE1
contraindicated in pregnancy
formation, thus, promote
ulceration. Therfore, you give
this to high risk NSAID user
Sucralfate
- It binds to ulcer base. It has a
- Its a polymer of
mucosal protecting action
aluminium and sucrose
through stimulation of PG and
bicarbonate
Bismuth
- It binds to ulcer base (inhibits - Colloidal tripotassium
H.pylori).
dicitratobismuthate
- It precipitates at acid ph to
protect mucosa and stimulates
PG and bicarbonate production
ANTACIDS [Aluminium hydroxide, Magnesium hydroxide, Sodium Bicarbonate]
These are weak bases used to neutralize gastric acid. Often used as symptom relief. These are used for non-ulcer
dyspepsia
Aluminum hydroxide
Constipation
Magnesium hydroxide
Diarrhea
Sodium bicarbonate
Alkalosis
STIMULANTS OF GIT MOTILITY [Metoclopramide, Domperidone, Cisapride]
Metoclopramide - Extrapyramidal side effects
- D2 dopamine antagonist
5HT4 receptor-mediated
- It stimulates gastric emptying
Ach release
Domperidone
- Peripheral D2 antagonist
- stimulates gastric emptying.
-increases lower esophageal
sphincter tone and increases
prolactin secretion
Cisapride
- Stimulates Ach release in
myenteric plexus of upper GIT.
- It stimulates gastric emptying.
Increases lower esophageal
sphincter tone

Drug name

Action
Other
ANTIEMETIC DRUGS
[Anticholinergics, Antihistamines, Dopamine receptor antagonist, Serotin receptor antagonist,
Cannabinoid]
Anticholinergics
Anticholinergic side effects - Muscurainic antagonist at
- Little antiemetic effect
vestibular nuclei (VN)
(Hyoscine)
- Motion sickness of short
duration
Antihistamine
Sedation as side effect
- H1 antagonist at VN
- Little antiemetic effect
(Cyclizine)
- Motion sickness
Dopamine receptor - Extrapyramidal side
- D2 antagonist used to depress
- Domperidone also
antagonist
effects to Metoclopramide chemoreceptive trigger zone
simulates GIT motility. It
(Phenothiazines,
(CTZ)
also does not pass BBB
Butyrophenones,
- Decreases vomitting
and increase prolactin
Metoclopramide,
secretion
Domperidone)
Serotin receptor
- Constipation and
- It depress CTZ function and
- 5-HT3 antagonists
antagonist
headache
depress visceral afferents from
- orally or by I.V.
(Ondansetron)
GIT
infusion with cytotoxics
- It decreases vomiting
Cannabinoids
- Drowsiness
- It acts through cannabinoid
- 9tetrahydrocannabinol
(Nabilone)
- Pschological effects
receptor
analogue
-It decreases vomiting due to
drugs stimulating CTZ
INFLAMMATORY BOWEL DISEASE
[Aminosalicylates, Corticosteroids, Immunosppresive agents, Antimicrobials, TNFa Inhibitors
Crohns disease: Transmural inflammation; panenteric (mouth to anus); TNFa
Ulcerative colitis: Mucosal and submucosal inflammation; Rectum (always), colon (variable); immunological
mechanisms
BOTH: diarrhea and bleeding, infectius factors, genetic factors
Aminosalicylates
(Sulfasalazine,
Mesalamine)
Corticosteroids
(Hydrocortisone,
Prednisolone,
Budesonide)
Immunosuppresive
agents
(Azathioprine,
Mercaptopurine,
Cyclosporine)
Antimicrobials
(Metronidazole)
TNFa inhibitors
(Infliximab)

Side effects

- GIT disturbance
- Hypersensitivity Rxns

- Its an anti-inflammatory
agents inhibiting leukotriene/
prostaglandin formation
- Sulfasalazine (prodrug which
gives mesalamine as active)
- typical steroid side effects - It modulations immune system
limit long-term use
- Inhibition of cytokine
production to induce remission
- Purine analogues inhibiting
nucleic acid synthesis for long
term maintenance.
- Azathiprine (Prodrug which
gives Mercaptopurine as active)
- It interrupt bacterial role in
inflammatory process
- Antibodies to inflammatory
effects of TNFa in GUT for
refractory Crohns disease

- 5-aminosalicylates

HC: I.V, topical

PS: orally, topical
BS: orally.
- Cyclosporine (I.V. for
severe, resistant
ulcerative colitis)

- Infliximab (I.V.)

Drug name

Side effects

Action

Other

LAXATIVES
[Dietary Fibre/bulk forming laxatives, Osmotic laxatives, Contact/stimulant laxatives]
- These are the drugs which promote defecation.
Main Characteristics: - They retain water and electrolytes in lumen via hydrophilic/osmotic proterties: by transit
via bulk. - mucosal absorption of H2O and electrolytes: transit via bulk. - intestinal motility: H2O and
electrolyte absorption via direct effect to transit
Dietary Fibre/ Bulk
Adverse effects such as
- Its a fibre rich diet
forming laxatives
decrease absorption of
- stool mass via component
(Bran; methylcellulose,
drugs, intestinal impaction polysaccharides and transit
ispaghula)
and obstruction, (Dry bulk) over 1-7 days
esophageal obstruction.
Osmotic laxatives
- Effects of first three are
- The first three transit over
(Magnesium sulphate,
that little is absorbed
1-3 hours.
magnesium hydroxide,
- Lactulose is osmotically
sodium phosphate)
active disaccharide. It
(Lactulose)
transit over 2-3 days
Contact/stimulant
- they directly stimulate
- Senna: prodrug for
laxatives
myenteric plexus/mucosa. It active anthracine
(Senna)
permeability of mucosal
derivative
(Bisacodyl)
surface. It coordinates
- bisacodyl:
increase in mass movements suppository (inserted
and decrease in
into rectum) and
segmentation. transit over
transit over 15-30 mins
6-8 hours.
ANTIDIARRHOEA AGENTS
Three main approaches:
1) Maintain fluid/electrolyte balance: oral rehydration; NaCl and glucose for infant diarrhea
2) Use of anti-infective agents
3) Use of constipating agents
Absorbent compounds: absorb fluids/toxins (Kaolin, pectin, aluminium hydroxide)
Opiates: muscle tone and propulsive movements. Also, sensory stimulation for defecation
reflex
o Opiate derivatives without CNS effects and dependence liability of morphine:
Diphenoxylate and Loperamide