Diarrhea, Abdominal Pain, and Constipation Pharmacology Flashcards by Sarah Gillen

Agent classes used to tx diarrhea

Prostaglandin inhibitors (bismuth)

Opioid agonists

5-HT3 antagonists

Cl- channel inhibitors

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FDA-issued drug safety communication regarding Loperamide (opioid agonist used for diarrhea)

Cardiac toxicity leading to death

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MOA of Loperamide

Slows peristalsis via direct action on circular and longitudinal muscles in intestinal wall —> allows for fluid/electrolyte reabsorption and increasing bulk/density of feces

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Side effects of loperamide

Dizziness
Fatigue
Drowsiness
Urinary retention (anticholinergic effects)

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What are the opioid agonists used to tx diarrhea?

Loperamide
Diphenoxylate
Eluxadoline

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Diphenoxylate is a category ____ synthetic opiate agonist with which opioid-effects can be seen at very high doses. A small quantity of _____ is added to discourage deliberate abuse/overdose

5; atropine

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MOA and kinetics of diphenoxylate

Believed to exert effect locally and centrally on GI smooth muscle cells; inhibits GI motility and slows excess GI propulsion

Kinetics: active metabolite with long half-life

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SE’s of diphenoxylate

Dizziness
Drowsiness
Urinary retention (d/t atropine)

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MOA of Eluxadoline

Agonist at opioid mu and kappa receptors in GI tract —> slows peristalsis and delays digestion

Antagonist at delta opioid receptors in GI tract —> decreased secretions from stomach, pancreas, and biliary tract

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Indication for Eluxadoline

IBS-D

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Eluxadoline is a C-IV scheduled drug. What are the side effects?

N/V/Abdominal pain

Hepatic/pancreatic toxicity — pancreatitis in high risk patients (those without gallbladder)

CNS-related effects: dizziness, fatigue, sedation, euphoria, impaired cognition

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Contraindications to Eluxadoline

Biliary duct obstruction
Sphincter of Oddi dysfunction
Alcoholism
Hx of pancreatitis
Severe hepatic impairment

Stop therapy if severe constipation develops and lasts 4+ days

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Which 5-HT3 antagonist is indicated for diarrhea? What is its MOA?

Alosetron

MOA: selectively blocks GI-based 5-HT3 receptors —> regulates visceral pain, colonic transit, and GI secretions

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Specific indication for alosetron

Chronic, severe, IBS-D that is not responsive to other conventional therapies (women)

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Side effects of Alosetron

Constipation, dyspepsia, GERD, N/V

Black box warning = Ischemic colitis! — physicians must enroll in prescribing program prior to utilizing this drug

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Contraindications to Alosetron

Hx or active:

GI obstruction, perforation, stricture, adhesions, or toxic megacolon

Diverticulities, Crohns, or UC

Impaired intestinal circulation, thrombophlebitis, or hypercoagulable state

Severe constipation

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What Cl- channel inhibitor is indicated for diarrhea and what is its MOA?

Crofelemer (derived from dark red sap of Croton lechleri tree = botanical pharmaceutical)

MOA: inhibits Cl secretion by blocking CFTR and CaCC channels responsible for regulating fluid secretion by intestinal epithelial cells

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Specific indication for Crofelemer

Non-infectious diarrhea in HIV/AIDS pts on anti-retroviral therapy

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SE’s associated with Crofelemer

Abdominal distention, elevated AST/ALT/bilirubin

Respiratory or urinary infections

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What drug class is utilized in the tx of cramping abdominal pain? What drugs are included?

Antimuscarinic agents:

Hyoscyamine
Dicyclomine
Clidinium/Chlordiazepoxide

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Specific indication and MOA of antimuscarinic therapy in GI patients

Indication: abdominal pain/spasms typically associated with IBS

MOA: competitively inhibit autonomic post-ganglionic cholinergic receptors at multiple sites —> decreased GI motility and spasms (pain)

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Side effects of antimuscarinics used in IBS abdominal pain

Classic anticholinergic-based:

Dry mouth, urinary retention, constipation, drowsiness, mental confusion, blurred vision

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What drug classes are utilized in tx of constipation?

Study These Flashcards

Laxative and cathartic agents
Peripheral opioid antagonists
Guanylate cyclase-C agonists
Selective chloride (C2) channel activators

What 3 drugs are included in the peripheral opioid antagonist family utilized in tx of constipation?

Study These Flashcards

Methylnaltrexone
Naloxegol
Alvimopan

What drug is included in the guanylate cylcase C agonist family utilized in tx of constipation?

Linaclotide

What drug is included in the selective chloride (C2) channel activators family utilized in tx of constipation?

Lubiprostone

MOA of Linaclotide

Selective guanylate cyclase-C (GC-C) Agonist [binds to GC-C on luminal surface of intestinal epithelium and increases intracellular/extracellular concentrations of cGMP; stimulates secretion of chloride/bicarb into intestinal lumen via activation of CFTR ion channel —> increased intestinal fluid and accelerated transit]

Indications for tx with Linaclotide

IBS-C | Chronic idiopathic constipation (CIC)

Side effects of linaclotide

Diarrhea (dehydration, electrolyte imbalance) GERD, dyspepsia, N/V

MOA of lubiprostone

Lubiprostone is a bicyclic fatty acid prostaglandin-E1 derivative that increases intestinal fluid secretion by activating GI-specific Cl- channels (ClC-2) in luminal cells of intestinal epithelium

Indications for tx with Lubiprostone

IBS-C (women) CIC opioid-induced constipation (OIC) [chronic pain, non-cancer/past cancer adults]

Side effects of lubiprostone

Nausea Dyspepsia Dizziness

MOA of methylnaltrexone, naloxegol, and alvimopan

Peripheral mu-opioid receptor antagonists [no common, significant CNS penetration/action or induction of withdrawal/pain symptoms]

Indications for tx with one of the peripheral mu-opioid receptor antagonists [methylnaltrexone, naloxegol, or alvimopan]

Opioid-induced constipation (OIC)

Which of the peripheral mu-opioid receptor antagonists is used for accelerating time to GI recovery following bowel resection surgery with primary anastomosis as a way of preventing postoperative ileus?

Alvimopan

Side effects of the peripheral mu-opioid receptor antagonists

``` Abdominal pain Diarrhea Nausea Flatulence Vomiting ```

Warning associated with alvimopan

Alvimopan carries risk of MI with use; REMS program requires use only in approved institutions for a maximum of 15 doses

Classifications of laxatives and cathartics for tx of constipation

``` Stimulants Osmotics Salines Bulk forming Stool softeners ```

What are the drugs in the stimulants class of laxatives and cathartics?

``` Bisacodyl Castor oil Glycerin Senna Na+ Picosulfate ```

What are the drugs in the osmotics class of laxatives and cathartics?

Lactulose Mg Citrate Polyethylene glycol Sorbitol (glycerin)

What are the drugs in the salines class of laxatives and cathartics?

Mag. Hydroxide | Na+ phosphate

What are the drugs in the bulk forming class of laxatives and cathartics?

``` Dietary fiber Psyllium Methylcellulose Carboxymethylcellulose Calcium polycarbophil ```

What are the drugs in the stool softeners class of laxatives and cathartics?

Docusate | Mineral oil

AEs and drug interactions with bulk-forming or hydrophilic colloidal agents used to tx constipation

Bloating/obstruction — must drink fluids (caution in renal failure) Drug interactions: LOTS — mainly with psyllium and the celluloses (recommendation is to take at a different time than other meds)

Stool softeners are also known as ____ or ____ laxatives

Surfactant; emollient [anionic surfactants soften/lubricate stool via reduction in surface tension as well as increase fluid secretion into GI tract; Mineral oil is hydrocarbon-based (indigestible) and penetrates stool thereby softening it]

Adverse effects of stool softeners

Bloating/flatulence Abdominal cramps Mineral oil can leak past anus in some; aspiration caution in elderly/debilitated/stroke

Which GI stimulant (irritant) also contains magnesium oxide/anhydrous citric acid and thus can be metabolically converted to Mg citrate — an osmotic drug?

Sodium picosulfate

MOA of the GI stimulants

Stimulates peristalsis — irritant to enterocytes, GI smooth muscle —> inflammation Promote water/electrolyte accumulation in GI tract (castor oil is hydrolyzed to ricinoleic acid) Glycerin is a tri-hydroxyl alcohol and functions as an irritant and an osmotic and lubricant agent

Adverse effects of GI stimulants

Abdominal cramping Urine discoloration with senna (yellow-brown/red-pink) Fluid/electrolyte disturbances with long-term use

Drug interactions and cautions with saline agents

Drug interactions: diuretics (electrolyte balance concerns) Cautions: - renal disease (electrolytes) - CHF/HTN (sodium balance)

Osmotic agent that is a disaccharide of galactose and fructose which aids in fluid retention in GI tract

Lactulose

Osmotic agent that is a non-absorbable sugar hydrolyzed to SCFAs — retaining fluid in GI (increased motility)

Sorbitol

Which osmotic agent is also used for severe liver disaease patients (hyperammonemia) because change in pH traps ammonia in the GI tract

Lactulose

AEs of osmotic agents

Electrolyte disturbances — must watch closely! Abdominal pain/distention/flatulence

Which of the osmotic agents is also used for bowel prep prior to GI scopes, radiological procedures, or surgery? What is the MOA?

Polyethylene glycol (PEG-3350) MOA: isotonic solution of long-chain PEGs = not absorbed and retain water in GI tract

Diarrhea, Abdominal Pain, and Constipation Pharmacology Flashcards

(55 cards)