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GI II Final > Diarrhea, Abdominal Pain, and Constipation Pharmacology > Flashcards

Diarrhea, Abdominal Pain, and Constipation Pharmacology Flashcards

1
Q

Agent classes used to tx diarrhea

A

Prostaglandin inhibitors (bismuth)

Opioid agonists

5-HT3 antagonists

Cl- channel inhibitors

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2
Q

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

A

Cardiac toxicity leading to death

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3
Q

MOA of Loperamide

A

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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4
Q

Side effects of loperamide

A

Dizziness
Fatigue
Drowsiness
Urinary retention (anticholinergic effects)

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5
Q

What are the opioid agonists used to tx diarrhea?

A

Loperamide
Diphenoxylate
Eluxadoline

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6
Q

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

A

5; atropine

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7
Q

MOA and kinetics of diphenoxylate

A

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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8
Q

SE’s of diphenoxylate

A

Dizziness
Drowsiness
Urinary retention (d/t atropine)

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9
Q

MOA of Eluxadoline

A

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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10
Q

Indication for Eluxadoline

A

IBS-D

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11
Q

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

A

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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12
Q

Contraindications to Eluxadoline

A 
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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13
Q

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

A

Alosetron

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

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14
Q

Specific indication for alosetron

A

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

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15
Q

Side effects of Alosetron

A

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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16
Q

Contraindications to Alosetron

A

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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17
Q

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

A

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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18
Q

Specific indication for Crofelemer

A

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

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19
Q

SE’s associated with Crofelemer

A

Abdominal distention, elevated AST/ALT/bilirubin

Respiratory or urinary infections

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20
Q

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

A

Antimuscarinic agents:

Hyoscyamine
Dicyclomine
Clidinium/Chlordiazepoxide

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21
Q

Specific indication and MOA of antimuscarinic therapy in GI patients

A

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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22
Q

Side effects of antimuscarinics used in IBS abdominal pain

A

Classic anticholinergic-based:

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

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23
Q

What drug classes are utilized in tx of constipation?

A

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

24
Q

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

A

Methylnaltrexone
Naloxegol
Alvimopan

25
Q

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

A

Linaclotide

26
Q

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

A

Lubiprostone

27
Q

MOA of Linaclotide

A

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]

28
Q

Indications for tx with Linaclotide

A

IBS-C

Chronic idiopathic constipation (CIC)

29
Q

Side effects of linaclotide

A

Diarrhea (dehydration, electrolyte imbalance)

GERD, dyspepsia, N/V

30
Q

MOA of lubiprostone

A

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

31
Q

Indications for tx with Lubiprostone

A

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

32
Q

Side effects of lubiprostone

A

Nausea
Dyspepsia
Dizziness

33
Q

MOA of methylnaltrexone, naloxegol, and alvimopan

A

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

34
Q

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

A

Opioid-induced constipation (OIC)

35
Q

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?

A

Alvimopan

36
Q

Side effects of the peripheral mu-opioid receptor antagonists

A 
Abdominal pain
Diarrhea
Nausea
Flatulence
Vomiting
37
Q

Warning associated with alvimopan

A

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

38
Q

Classifications of laxatives and cathartics for tx of constipation

A 
Stimulants
Osmotics
Salines
Bulk forming
Stool softeners
39
Q

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

A 
Bisacodyl
Castor oil
Glycerin
Senna
Na+ Picosulfate
40
Q

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

A

Lactulose
Mg Citrate
Polyethylene glycol
Sorbitol (glycerin)

41
Q

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

A

Mag. Hydroxide

Na+ phosphate

42
Q

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

A 
Dietary fiber
Psyllium
Methylcellulose
Carboxymethylcellulose
Calcium polycarbophil
43
Q

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

A

Docusate

Mineral oil

44
Q

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

A

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)

45
Q

Stool softeners are also known as ____ or ____ laxatives

A

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]

46
Q

Adverse effects of stool softeners

A

Bloating/flatulence
Abdominal cramps

Mineral oil can leak past anus in some; aspiration caution in elderly/debilitated/stroke

47
Q

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

A

Sodium picosulfate

48
Q

MOA of the GI stimulants

A

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

49
Q

Adverse effects of GI stimulants

A

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

50
Q

Drug interactions and cautions with saline agents

A

Drug interactions: diuretics (electrolyte balance concerns)

Cautions:

  • renal disease (electrolytes)
  • CHF/HTN (sodium balance)
51
Q

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

A

Lactulose

52
Q

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

A

Sorbitol

53
Q

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

A

Lactulose

54
Q

AEs of osmotic agents

A

Electrolyte disturbances — must watch closely!

Abdominal pain/distention/flatulence

55
Q

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

A

Polyethylene glycol (PEG-3350)

MOA: isotonic solution of long-chain PEGs = not absorbed and retain water in GI tract

GI II Final (8 decks)

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