Gastrointesinal(GIT)
Pharmacology
CONSTIPATION
Difficulty or infrequent passage of stool,
hardness of stool, or a feeling of incomplete
evacuation
TYPES OF CONSTIPATION
ACUTE:
Bowel obstruction, Drug related
CHRONIC:
colonic tumors, metabolic disorders,
CNS disorders,
LAXATIVES(purgatives)
LAXATIVES
Purgatives – drugs which increase movement and
speed up the passage of food through the small
intestines (intestinal transit time-ITT)
LAXATIVES
intestinal transit time is ↑ by :
↑ vol. of non-absorbable solid residue
↑ water content
altering faecal consistency
↑ motility and secretions
LAXATIVES
4 types:
- Bulk
- Osmotic
- Stimulant
- Surfactant
LAXATIVES
1. BULK LAXATIVES:
BRAN,
PSYLLIUM,
METHYLCELLULOSE(citrucel),
CALCIUM POLYCARBOPHIL
BULK LAXATIVES
MOA: unprocessed fibres/polysaccharides polymers
that remained in the GIT as they are not broken down
by the normal process of digestion in the upper GIT
Absorbing water and promoting bacterial growth; on
swelling they distend to the colon and increase
peristaltic motility. Softening of feces occurs
ONSET: 12-72h
BULK LAXATIVES
Bulk laxatives require water intake
oesophageal and intestinal obstruction if not taken
with enough water.
Long term use=dehydration and electrolyte
disturbances
S/E: allergic reactions (low incidence), flatulence
LAXATIVES
2. OSMOTIC LAXATIVES:
MAGNESIUM SULPHATE(Epsom salts)
MAGNESIUM HYDROXIDE(milk of magnesia)
LACTULOSE(miralax)
MOA:
• Poorly absorbed drugs which increases the bowel
volume of the small and large intestine by osmosis.
This results in increased motility that causes
distention which leads to purgation.
• Watery feces produced
ONSET: 8-12 hrs (2-3 days) for lactulose and 6-8h for
Mg(OH)
LAXATIVES
OSMOTIC LAXATIVES cont’d
Lactulose
• Semi-synthetic derivative of fructose and galactose
• Acted on by bacteria to produce fructose and
galactose which ferment to form lactic and acetic
acids → osmotic laxatives
• Onset: 8-12 hrs (2-3 days)
LAXATIVES
OSMOTIC LAXATIVES cont’d
• For emptying the GIT prior surgery, radiology,
colonoscopy
• should be taken with adequate water to avoid
dehydration
• Lactulose is reserved for chronic constipation
S/E:
Minimal: flatulence, abdominal cramps
Long term use may result in dehydration and
electrolyte disturbances
LAXATIVES
3. STIMULANT LAXATIVES
CASTOR OIL (recinoleic acid)
BISACODYL(dulcolax)
ANTHRAQUINONE DERIVATIVES:
CASCARA (buckhorn tree)
SENNA (plantains)
LAXATIVES
STIMULANT LAXATIVES
MOA:
Direct stimulation of nerves in the enteric nervous system
to result in increased water and electrolyte secretion from
mucosa, also increase peristaltic activity.
CASTOR OIL
In small intestines- hydrolysed by pancreatic lipase to
active compound, recinoleic acid.
Soft to semi-fluid faeces produced
Onset: 2-6h for Castor oil and 15 mins for Bisacodyl
LAXATIVES
ANTHRAQUINONE DERIVATIVES
(Eg. Senna and Cascara)
* Removed from US market
• Acted on by bacteria to produce their active
forms(emodin)
• Soft/Semi fluid stool
LAXATIVES
SIDE EFFECTS OF ANTHRAQUINONES
• Minimal systemic S/E -due to limited absorption
from GIT (absorbed amount excreted via urine)
• Abdominal cramping.
• Atonic colon
• Long term use may result in melanosis of the colon=
increase risk of cancer
• Urine discoloration, electrolyte imbalance
LAXATIVES
4. SURFACTANT LAXATIVES- FECAL SOFTENERS
DOCUSATE (Dioctyl sodium sulfosuccinate)
GYLCERIN
MINERAL OIL
MOA: emulsify stool, making it softer, making passage
easier.
ONSET: 1-3 days
S/E: Oil leakage at anal sphincter . Long-term use
interfere with absorption of fat- soluble vitamins
ANTIDIARRHEAL AGENTS
• In diarrhea:
- ↑motility of the GIT
- ↑ secretion
- ↓in the absorption of fluid
→ loss of electrolytes (Na+) and H2O
• Can be associated with various complications- from
discomfort to medical emergency (due to electrolyte
imbalance and hypovolemia)
CAUSES OF DIARRHEA
Acute Diarrhea Chronic Diarrhea
Bacteria Tumors
Viral Diabetes
Drug-induced Addison’s disease
hyperthyroidism Inflammatory bowel disease
Nutritional Irritable bowel syndrome
Protozoal
ANTIDIARRHEAL AGENTS
1. Drugs to replace fluid and electrolyte balance
ORAL REHYDRATION SALTS (eg. Pedialyte®)
Usually the only therapy needed for acute
diarrhoea (body defense mechanism)
Eg: WHO formulation
NaCl 3.5 g/L
KCl 1.5 g/L
NaCitrate 2.9 g/L
Glucose 20 g/L
ANTIDIARRHEAL AGENTS
2. Drugs to decrease motility
a. ANTIMUSCARINIC DRUGS:
ATROPINE, HYOSCINE
DICYCLOMINE
MOA: Block muscarinic receptors (m3), thus inhibiting
parasympathetic activity
ANTIDIARRHOEAL DRUGS
Dicyclomine (most pop)
a specific anticholinergic(antimuscarinic) effect
Direct smooth muscle relaxant effect
Decrease gastric acid secretion
Oral Route
ANTIDIARRHEAL AGENTS
2. Drugs to decrease motility
b. OPIATE-LIKE DRUGS:
DIPHENOXYLATE (Lomotil),
LOPERAMIDE(Imodium)
MOA: Stimulate µ opiate receptors in the myenteric
plexus to reduce Ach release and therefore decrease
peristaltic activity. Also reduces pain
ANTIDIARRHEAL AGENTS
Opiates
• Greater potency than morphine: Diphenoxylate (2 x)
Loperamide (40-50 x)
• Limited entry into CNS, therefore activity only on
peripheral opiate receptors
• Side effects: nausea drowsiness
dizziness paralytic ileum
w
ANTIDIARRHEAL AGENTS
3. Drug that reduce GIT secretions
BISMUTH SUBSILICYLATE (Pepto-bismol®) ,
MOA: converted by HCl to salicylic acid and bismuth
oxynitrate. Bismuth absorbs bacterial toxins.
• For travellers’ (infection) diarrhea.
• Salicylate content = anti-inflammatory action
ANTIDIARRHEAL AGENTS
4. Drugs to increase stool bulk
KAOLIN, PECTIN, Psyllium, Polycarbophil
Kaolin is a natural hydrated aluminium silicate.
Pectin consists of purified carbohydrate extracted
from citrus fruit or apple .
MOA: produce bulking of the stool.
ANTIDIARRHEAL AGENTS
5. Anti-infective drugs
Usually if diarrhoea is viral- no antiviral required due
to self-limiting nature
Bacterial infections, eg. Salmonella –Tetracycline
Shegella – Ampicillin
Campylobacter- Erythromycin
Q&A
1. In the gastric acid secretion cascade, which cell is
responsible for histamine secretion?
a. Chief cells
b. Parietal cells
c. G cells
d. ECL cells
Q&A
2. Which H2 receptor antagonist when given may
result in impotence?
a. Ranitidine
b. Cimetidine
c. Famotidine
d. Nizatidine
Q&A
3. Which agent used in the symptomatic relief of peptic
ulcer disease is contraindicated in pregnancy
a.Sucralfate
b.Bismuth Subsalicylate
c.Misoprostol
d.Dicyclomine
Q&A
4. Which salt containing antacid is a poor choice in the
management of acid secretion?
a. Ca2+
b. Mg2+
c. Na+
d. Al3+
