Laxatives (for Constipation)

Question 1

General MOA for Luminally Active Agents, Nonspecific Stimulants/Irritants, and Chloride secretion activator

Answer 1

Luminally Active Agents: Simulating peristalsis by intraluminal filling

Nonspecific Stimulants/Irritants:
- direct effect on enterocytes, enteric neurons
and GI smooth muscle
- Probably induce low-grade inflammation in small and
large bowel –> stimulate the secretory cells –>
accumulation of water and electrolytes –> increases motility

Chloride secretion activator
- Prostanoid acid
- MOA: Stimulation of EP4 receptors –> activation of
Cl- Channels –> increase Cl-rich fluid secretion
–> increase motility
-Use: Chronic Constriction, IBS-C
Effect: <24hr
AES: Nausea
CIs: Pregnancy

Question 2

Bulk-forming agents

Answer 2

Type: Luminally Active Agents

MOA: water absorption –> forms bulky emollient gel
–> peristalsis
- Soften feces: 1-3days

Ex: Psyllium Preparations, Methylcellulose, Calcium polycarbophil

SIG: Drink lots of fluid

Question 3

Osmotic agents

Answer 3

Type: Luminally active agents

MOA: – Nonabsorbable osmotic agents –> increase secretion of water –> softening stool and promoting defecation
– Watery evacuation, 1-3 hours

Ex:
Saline Laxatives (e.g. Mg citrate, Mg(OH)2, Na2PO4)
* Mg –> Avoid in patients with renal insufficiency
–> Hypermagnesemia
Lactulose, Sorbitol
PEG (cleaning before procedures)

SIG: Drinks lots of fluid

Question 4

Stool wetting agents and emollients

Answer 4

MOA: Soften fecal material and allow water to penetrate

Drugs:
Docusate salts (effect: 24-72 hr)
- Lower surface tension –> allow mixing of aqueous and fatty substances –> stool softening –> easier defecation

Mineral oil (effect: 6-8 h)
- PO
- AES: interferes with absorption of fat-soluble substances
- Aspiration –> Severe Lipid-pnuemonitis

Question 5

Bisacodyl

Answer 5

Type: Nonspecific stimulants/irritants

• Prodrug: activated via hydrolysis in bowel

Effect:
- PO: 6 - 12hr
- Supp: 30 - 60 min

AES: Abdominal Pain

Question 6

Anthraquinone laxatives

Answer 6

Type: Nonspecific stimulants/irritants

Plant Derived: aloe, cascara, senna

Prodrug: activated in colon

MOA: irritate oral mucosa

Effect: 6-12hr

AES: long term use
- melanotic pigmentation of colon –> melanosis coli

Question 7

Castor oil

Answer 7

Type: Nonspecific stimulants/irritants

Castor bean: source of ricin (toxic) and oil

Prodrug: requires hydrolysis

Effect: 1 -3 hr
AES: Unpleasant taste, abdominal pain

Question 8

Lubiprostone

Answer 8

• Prostanoid Acid

Type: Chloride secretion activator

MOA: Stimulation of EP4 receptors on GI epithelial cells –> activation of Cl- Channels –> increase Cl-rich fluid secretion –> increase motility

Use: Chronic Constriction, IBS-C

Effect: <24hr

AES: Nausea

CIs: Pregnancy

Question 9

Linaclotide, plecanatide

Answer 9

MOA: Guanylate cyclase-C (GCC) agonist –> increase intracellular cGMP –> increase fluid/ electrolyte secretion –> increase motility

Use: Chronic idiopathic constipation (lina and pleca) and IBS-C (lina)

AES: GI effects: Diarrhea, abdominal pain

CIs: Children, infants, neonates (BBW)
- Risk of serious dehydration in pediatric patients