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6. HDS GI Repro > Antiemetics, Laxatives, Antidiarrheals > Flashcards

Antiemetics, Laxatives, Antidiarrheals Flashcards

1
Q

Nausea/Vomiting

Associated Conditions

A
  • Drug treatments
    • Chemotherapy
    • Pain
    • Anesthesia
  • Motion sickness
  • Pregnancy
  • GI disease
  • Advanced cancer
  • Migraine
  • Bulimia
  • Psychological stress
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2
Q

Nausea

Physiology

A
  • Emetic center (medulla) inputs:
    1. Higher centers
      • ⊕ by memories and fear
    2. Solitary nucleus
      • ⊕ by 5-HT, dopamine, ACh (mAChR), and histamine
    3. Cerebellum
      • ⊕ by ACh (mAChR) and histamine from inner ear
    4. Chemo-receptor trigger zone (area postrema)
      • ⊕ by 5-HT, dopamine, ACh (mAChR)
        • ⊕ by blood-borne emetics
  • Local irritants ⇒ ⊕ GI tract ⇒ 5-HT ⇒ ⊕ chemo-receptor trigger zone or solitary nucleus
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3
Q

Antihistamine

Antiemetics

A

⊗ Histamine H1 receptors

Most have significant anti-muscarinic activity

Used almost exclusively for motion sickness

  • Cyclizine and Meclizine
    • Used exclusively for motion sickness (OTC)
  • Promethazine [Phenergan] (weak anti-D2 activity) and diphenhydramine
    • May be more effective for nausea
  • CNS adverse effects: sedation, confusion, dizziness, tinnitus, incoordination, tremors
  • Antimuscarinic adverse effects: urinary retention, blurred vision, exacerbation of narrow angle glaucoma
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4
Q

Anticholinergic

Antiemetics

A

Scopolamine

(PO or transdermal patch)

  • Indications:
    • 1° for motion sickness
    • May be used for post-operative N/V
    • No role in chemotherapy induced nausea
  • Adverse effects: dry mouth, urinary retention, blurred vision, exacerbation of narrow angle glaucoma
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5
Q

Dopamine Receptor Antagonists

Antiemetics

A

Prochlorperazine [Compazine] and Metoclopramide [Reglan]

⊗ D2 receptors in chemo receptor trigger zone

  • Prochlorperazine
    • Antihistamine and anticholinergic properties
    • Adverse effects: sedation, dystonia, extrapyramidal symptoms, impaired thermoregulation
  • Metoclopramide
    • ⊗ 5-HT3 receptors
    • ⊕ 5-HT4 receptors
    • Sensitizes muscarinic receptors
    • Prokinetic agent ⇒ causes coordinated contractions that enhance transit
      • Can be used to aid in drug absorption when tx migraines
    • 1° use to tx N/V ass. w/ GI dysmotility syndromes
    • Anti-dopaminergic effects ⇒ tardive dyskinesia
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6
Q

Serotonin Receptor Antagonists

Antiemetics

A

Ondansetron

  • ⊗ 5-HT3 receptors @ both peripheral sites in GI tract and central sites (solitary nucleus and area postrema)
    • Periphery: 5-HT from ECL cells of small intestine in response to chemotherapeutic agents that ⊕ vagal afferents
    • Central: 5-HT recpetors in solitary nucleus and area postrema
  • Persistent drug effects after ↓ [drug] ⇒ qDay dosing
  • Extensively hepatic metabolized by cyp450 enzymes ⇒ ∆ dose w/ hepatic function
  • Adverse effects: constipation, diarrhea, headache, lightheadedness, minor EKG changes, QT prolongation
  • Used for chemotherapy, upper abd irradiation, hyperemesis of pregnancy
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7
Q

Cannabinoids

Antiemetics

A

Dronabinol

  • ⊕ CB1 cannabinoid receptor
  • MOA unknown
  • Metabolites detectable for weeks
  • CNS effects: sympathomimetic activity, marijuana-like highs, paranoid reactions
  • Abstinence syndrome when terminating use
  • Use with caution in pts w/ hx of drug abuse
  • Used in cancer chemotherapy when other agents ineffective
  • Stimulates appetite
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8
Q

Glucocorticoids

Antiemetics

A

Used in the tx of nausea in pts w/ widespread cancer

May suppress peritumoral inflammation and prostaglandin production

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9
Q

Benzodiazepines

Antiemetics

A
  • Usually used in combo w/ other agents
    • Not very effective when used alone
  • Tx nausea related to psych conditions
  • Sedative, amnesic and anti-anxiety properties can reduce anticipatory N/V
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10
Q

Substance P Antagonist

Antiemetics

A
  • Substance P
    • Tachykinin family
    • Present in vagal afferents → ⊕ solitary tract nucleus
  • Aprepitant
    • Highly bound to plasma proteins
    • Metabolized by cyp450 ⇒ ∆ dose w/ drugs like dexamethasone (also metabolized cyp450)
    • Used in combo w/ other tx and for delayed nausea
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11
Q

Antiemetics

Common Uses

A
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12
Q

Post-Operative Nausea

A
  • Assess risk: type of surgery, female sex, hx of nausea, non-smoking status, long duration, use of post-op opioids
  • Low risk: no prophylaxis, rescue w/ 5-HT antagonist
  • Moderate risk: Prophylaxis w/ 1-2 agents from different classes (use propofol)
  • Highest risk: Prophylaxis w/ 2 agents from different classes (use propofol)
  • Rescue with an agent from a different class
  • Propofol has the lowest risk of nausea
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13
Q

Chemotherapy Induced Nausea

A
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14
Q

Constipation

A
  • Definitions:
    • Inability to have stools frequently
    • Incomplete evacuation of the rectum
    • Stools that are too firm or too difficult to pass
  • Associated sx: flatulence, bloating, abd pain
  • Middle-aged or elderly pts ⇒ look for obstructing colonic lesion / evaluate cause
  • Otherwise healthy pt ⇒ dietary change and exercise > laxatives
    • Risk for laxative dependence
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15
Q

Bulk Forming Laxatives

A

Indigestible polysaccharides or cellulose derivatives

  • Swell upon contact w/ water ⇒ bulky gel
    • Distends the colon
    • Promotes peristalsis
  • For long-term management: soft stools within 24-48 hours
  • Two bulk laxatives:
    • Insoluble fiber (bran)
      • AE: abd pain, flatulence, bloating
    • Soluble fiber (psyllium, methylcellulose)
      • AE: abd pain
  • Need to drink enough water to prevent SBO
  • If GI strictures already present, can precipitate obstruction
  • May ↓ serum lipids by binding cholesterol excreted by the bile
  • Titrate dose to avoid gas and cramping
  • ↑ Dietary fiber ⇒ ∆ dose so total = 15 grams of fiber/day
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16
Q

Stool Softeners

A

Surfactants & Emollients

Ex. Docusate sodium [Colace] given PO or rectally

  • Allows water and lipids to penetrate ⇒ emulsify the stool
  • May also cause water secretion into the intestine and colon ⇒ facilitates this process
  • Indications:
    • Hospitalized pts s/p MI or surgery
      • Need to avoid straining at defecation but activity and fluid intake restricted
    • Pt receiving opioids s/p surgery
    • Chronic constipation in pts w/ fluid-restriction or unable to consume enough fiber
      • Lose their effectiveness w/ time
17
Q

Lubricants

A

Oil based products

Coat the bowel ⇒ ↓ colonic absorption of water ⇒ allows easier passage of stools

  • Mineral oil
    • Prevents fecal impaction in young children and debilitated adults
    • Mixed w/ juices (more palatable)
    • Taken in upright position ⇒ avoid aspiration & lipid pneumonitis
    • Long-term use can impair absorption of fat-soluble vitamins
    • Not preferred
  • Glycerin suppositories also considered to lubricants
18
Q

Stimulant Laxatives

A

⊕ Intestinal motility

  • Exact MOA unclear
    • Direct ⊕ enteric NS?
    • ⊕ Fluid secretion in small intestine and colon?
  • PO admin ⇒ takes 6-8 hours
  • Rectal admin ⇒ takes 1-2 hours
  • AE: abd cramps, diarrhea
  • Chronic use may lead to perceived need for laxatives
  • Potential to be abused because they work quickly
  • Sometimes used long-term in pts who are neurologically impaired or bed-bound
  • Senna
    • Component of Senekot and Ex-Lax
    • Chronic use ⇒ ± brown pigmentation of the colon (melanosis coli)
  • Bisacodyl
    • Useful in chronic constipation
    • Admin w/ agents that ↑ stomach pH (ex. PPIs and antacids) ⇒ premature dissolution of enteric coated tablets in the stomach ⇒ irritation and pain
19
Q

Osmotic Laxatives

A
  • Poorly absorbed by intestine and colon ⇒ net water movement into GI tract ⇒ bowel distention ⇒ ↑ intestinal motility
  • AE:
    • Abd cramps and diarrhea
      • Except for low-dose polyethylene glycol ⇒ milder actions
    • Sx of dehydration may develop
20
Q

Low-dose

Polyethylene Glycol

A

Miralax, Glycolax

17 grams in a cup of liquid

  • Osmotic laxative
  • Causes less cramping and gas than other laxatives in this class
  • Onset of action is 2-4 days
  • Useful for chronic constipation
21
Q

Magnesium Hydroxide

(Milk of Magnesia)

A
  • Nonabsorbable salt
  • Osmotic laxative
  • Onset of action is 30 min to 3 hours
  • Can cause hypermagnesia in pts w/ renal insufficiency
  • May be abused because it works quickly
22
Q

Lactulose

A
  • Nonabsorbable disaccharide sugar
  • Osmotic laxative
  • Degraded by colonic bacteria into various acids ⇒ ↑ osmotic pressure
  • Onset of action is 2-4 days
  • Poorly tolerated d/t palatability
  • Higher concentrations ⇒ prevent hepatic encephalopathy in pts w/ liver disease
    • ↓ Colonic pH ⇒ ⊗ diffusion of ammonia from colon → blood ⇒ ↓ blood ammonia levels
23
Q

Purgatives

A
  • Used for bowel evacuation
  • Usu. prep for colonoscopy
  • Protocol involves consumption of large amounts of liquid & osmotically active agents
  • Rapid movement of water into distal small bowel and colon ⇒ high volume of liquid stool
  • Can cause abd cramps
24
Q

Balanced Polyethylene Glycol Solution

A
  • Purgative
  • Ingested rapidly over a short period (2-4 liters over 2-4 hours)
  • Solution designed so that no significant intravascular fluids or electrolyte shifts occur
  • Useful on all classes of pts
25
Q

Magnesium Citrate

A
  • Purgative
  • Liquid that tastes bad
  • Consumed w/ large amounts of liquid
  • AE: hypermagnesemia, respiratory depression, and electrolyte disorders
26
Q

Sodium Phosphate

A
  • Purgative
  • Available as a liquid or pill
  • Necessary to consume large amounts of liquid
  • AE: hyperphosphatemia, hypocalcemia, hypernatremia, hypokalemia
    • In susceptible pts ⇒ cardiac arrhythmias or acute renal failure d/t tubular deposition of calcium phosphate
  • Contraindications: frail, elderly, renal insufficiency, cardiac disease
27
Q

Chloride Channel Activators

A

Ubiprostone and Linaclotide

  • ⊕ Chloride channel in small intestine ⇒ Cl- rich secretion in the intestine ⇒ ⊕ intestinal motility
  • Works within 24 hours
  • Indications:
    • Chronic constipation
    • IBS w/ constipation component
28
Q

Methylnaltrexone

A

Peripheral opioid antagonist

Approved for opoid-induced constipation in pts receiving palliative care w/ opioids who have not responded to other agents

29
Q

Antidiarrheal Agents

A
  • Opioid Agonists
    • Diphenoxylate (Lomotil)
      • Used combo w/ atropine
      • Low dose Atropine prevents abuse & OD
      • Acts by slowing intestinal contractions
    • Loperamide (Imodium)
      • ⊕ Peripheral mu receptors only
      • Often used for IBS and short bowel syndrome
  • Bismuth Subsalicylate
    • Found in Pepto Bismol and Kaopectate
    • ? Efficacy in diarrhea

6. HDS GI Repro (30 decks)

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