Chapter 66: Other GI Drugs

Antiemetics

Serotonin Receptor Antagonists

• most effective drugs for N/V suppression
  • for CA causes
  • radiation
  • anethesia
  • viral gastritis
  • pregnancy

Ondansetron

• prolongs QT interval
  • increases risk of torsades des pointes
• use with caution if
  • electrolyte disturbances present
  • HF
  • bradydysrythmias
  • other effecting QT drugs

Glucocorticoids

• most Common drugs=
  • Methylprednisolone (solumedrol)
  • Dexamethasone (decadron)
• no serious side effects

Substance P/Neurokinin-1 Antagonists

• Aprepitant
  • Actions and Use
    • unique MOA, can enhance action of used with other drugs
    • prolonged duration of action
    • useful for acute and prophylactic use in CINV¹
  • Drug Interactions
    • Complex interactions d/t being a inhibitor, substrate, and inducer of CYP₃A₄
    • Can also induce CPY₂D₆

Dopamine Antagonists

• Phenothiazines
  • Side effects:
    • extrapyramidal reactions²
    • anticholinergic effects
    • hypotension
    • sedation
  • Promethizine (Phengren)
    • widely used in children
    • side effects
      • resp. depression
      • local tissue injury
        • d/t extraversion
          • abscess, necrosis, gangrene
        • intramuscular dosing is safer

Promethazine Black Box Warning

Severe respiratory depression, do not use in children below 2, use with caution in older children

Droperidol Black Box Waring

risk of fatal dysrhythmias d/t QT prolongation, check EKG before prescribing

Cannabinoids

• Dronabinol (marinol)
• Nabilone (Cesamet)
• Therapeutic Uses
  • Suppress CINV
  • Stimulate appetite in AIDS patients

Adverse Effects

• temporal disentegration
• dissociation
• depersonalization
• dysphoria
• tachycardia
• hypotension
• Abuse Potential
• Contraindications:
  • Psychiatric Disorders
  • cardiovascular disease
  • Sedative or EtOh use

Chemotherapy-Induced Nausea and Vomiting

Three types of emesis:

• 1. Anticipatory
• 1. Acute: within minutes or hours
• 1. Delayed: a day or more
• Antiemetics are more effective at preventing CINV than resolving it.
• Adminster before chemotherapy
• Oral therapy preferred
  • Oral and IV equally effective

Nausea and Vomiting of Pregnancy

• First line therapy: doxylamine and vitamin B₂
  • No adverse effect on fetus
• Last resort: Methylprednisolone after 10 weeks gestation
  • cleft lip in earlier use
• Avoid Metoclopramide, dronabinnol, and droperidol during breastfeeding
• Avoid Benzos, scopolamine, and metoclopramide in older adults

Drugs for Motion Sickness

Scopolamine

• most effective drug for motion sickess
• Side effects
  • dry mouth
  • blurred vison
  • drowsiness
  • urinary retention
  • constipstion
  • disorientation

Antihistamines

• less effective than Scopalamine
• avoid in elderly
• Side Effects
  • sedation
  • dry mouth
  • blurred vison
  • drowsiness
  • urinary retention
  • constipstion

Antidiarrheal Agents

• Two groups
  • specific: treat underlying cause
  • non-specific: act within bowel to suppress symptoms

Nonspecific Antidiarrheal Agents

Opioids

• Most effective anti diarrheal agent
• MOA
  • suppress GI Motility
  • decreases fluid secretin in intestine
  • increases fluid absorption in intestiens
  • At therapeutic doses, typical opioid effects do not occur
  • Irritable Bowel Disease -> Toxic Mega Colon
• ‌Diphenoxylate
  • only opioid used for diarrhea
  • dosage is mixed between Diphenoxylate and Atropine (to discourage abuse)

Management of Infectious Diarrhea

General Considerations

• Bacteria or Protozoan infection
• usually self limited, with specific treatment not required
• Unnecessary use of Abx can lead to an asymptomatic carrier state
• Specific Infections
  • Salmonella
  • Shigella
  • Campylobacter
  • Clostridium

Traveler’s Diarrhea

• Loperamide preferred, but can prolong infection d/t delaying expulsion of E. coli infection

Clostridium difficile–Associated Diarrhea

• gram + anaerobic baccilus
• symtoms d/t bacterial toxin
• Mild or severe symptoms
  • toxic megacolon
  • pseudomembranous colitis
  • colon perforation
  • sepsis
  • death

Drugs for Irritable Bowel Syndrome

Non Specific Drugs

• Four drug classes
  • antispasmodics (Hycosamine, dicyclomine)
  • bulk forming agents (psyllium, polycarbophil)
  • anti-diarrheal (loperamide)
  • tricyclic anti-depressants
• Recent knowledge is that TCAs are the only drug more effective than placebo
• Symptoms can also be relived with antibiotics(ie SIBO³) or acid supreesants
  • Rifaximin (well tolerated, poor systemic absorption)
• Probiotics - ‌Bifidobacterium infantis
• Acid Supressants
  • Proton Pump Inhibitors (Lansoprazole, Pantoprazole)
  • H₂ Receptor Blockers (Famotidine, Ranitidine)

Inflammatory Bowel Syndrome-Specific Drugs

• Alosetron (primary drug)
• eluxadoline - IBS-D
• Lubiprostone - IBS-C
• Linactolide - IBS-C
• Tegaserod (can cause cardiovascular events)