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NRS 271B > N/V/D/C, IBS & Rota > Flashcards

N/V/D/C, IBS & Rota Flashcards

1
Q

3 stages of N/V

A
  1. Nausea:
    1. subjective feeling
    2. autonomic: pallor, tachycardia diaphoresis, & salivation
  2. Retching:
    1. diaphragm, chest, & abd wall contractions
    2. produce pressure gradient
  3. vomiting
    1. reflexive, forceful, rapid
    2. sustained contractions of abd and thoracic muscles
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2
Q

Triggers of N/V

A
  • Chemoreceptor Trigger Zone (CTZ)
    • located outside BBB → easily stimulated by:
      • uremia, acidosis, circulating toxins (like chemo agents)
    • has many receptors:
      • 5-HT3
      • Neurokinin (NK1) receptors
      • Dopamine (D2) receptors
  • Visceral Vagal Nerve Fibers
    • lots of 5HT3 receptors
      • stimulated by:
        • GI distention
        • mucosal irritation
        • infection
  • Motion Sickness:
    • stimulation of vestibular system
      • lots of histamine (H1) receptors & muscarinic receptors
  • Anticipatory N/V with chemo
    • involves the cortex
    • sights, sounds, smells trigger n/v
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3
Q

Simple vs Complex N/V

A
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4
Q

D2 Antagonists Drug Classes & Names

A
  • Phenothiazines:
    • chlorpromazine
    • Prochlorperazine
    • Promethazine
  • Butyrophenones:
    • Droperidol
    • Haloperidol
  • Benzamides:
    • Metoclopramide
    • Trimethobenzamide
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5
Q

Indications for D2 Blockers

A
  • severe motion sickness
  • vertigo
  • gastritis
  • n/v of pregnancy
  • post-op N/v
  • chemo-induced N/V (CINV)
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6
Q

Phenothiazines

A

Chlorpromazine, Prochlorperazine, Promethazine

D2 antagonists

  • severe motion sickness, vertigo, gastritis, n/v of pregnancy, chemo, or post-op
  • SEs:
    • sedation
    • orthostatic hypotension
    • extrapyramidal symptoms:
      • Dystonia - involuntary muscle contractions
      • Tardive Dyskinesia- permanent involuntary muscle movements
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7
Q

Butyrophenones

A

Haloperidol (Haldol), Droperidol (Inapsine)

D2 antagonists

  • Indications: severe motion sickness, vertigo, gastritis, n/v of pregnancy, chemo, or post-op
  • SEs:
    • sedation
    • agitation, restlessness, arrhythmias
    • BLACK BOX WARNING: QT prolongation
      • CI: male QT > 450ms
        • female QT > 470 ms
      • EKG prior to tx with these meds > 2mg IV
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8
Q

Benzamides

A

metoclopramide, trimethobenzamide

D2 antagonists

  • act both centrally peripherally (in the GI tract)
  • have cholinergic activity
    • increase LES (lower esophageal sphincter) tone
    • promote gastric motility
  • indications: n/v of pregnancy, chemo, or post-op
    • gastroparesis
    • GERD
    • migraine headache
  • SEs:
    • metoclopramide (CROSSES THE BBB)
      • somnolence, reduced mental acuity, anxiety, depression, hyperprolactinemia, gynecomastia, galactorrhea
      • Extrapyramidal side effects
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9
Q

Where is serotonin synthesized and how does it affect GI system?

A
  • synthesizes in CNS and enterochromaffin cells in the gut
  • stimulates the visceral vagal innervation and the chemoreceptor trigger zone (CTZ)
  • 5-HT<u>3</u> receptors: control emesis in the Gut
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10
Q

Serotonin Antagonists for N/V

A
  • Dolasetron: PONV, CINV
  • Granisetron: CINV
    • May be degraded by direct sunlight and pts should cover PATCH with clothing to prevent exposure
  • Ondansetron: PONV, CINV,
  • Palonosetron PONV, CINV
    • longer t½= 40 hours
    • higher receptor binding affinity
  • SEs:
    • headache, prolongation of ecg interval (asymptomatic)
    • constipation, somnolence, diarrhea, fever
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11
Q

Neurokinin-1 Receptors

A
  • found on vagal afferents in the GI tract & brain
  • substance P binds to NK 1 receptors
    • mediate both acute and delayed N/V
  • Aprepitant → for CINV
  • Rolapitant
  • Fosaprepitant
  • Netupitant/palonosetron
  • Fosnetupitant/palonosetron
  • 3a4 inhibitor
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12
Q

Rolapitant

A

NK1 receptor antagonist

  • Indication: CINV
  • PO only
  • SEs: anemia, neutropenia, anorexia, dizziness, UTI, hiccups
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13
Q

Fosaprepitant

A

NK1 Receptor antagonist

  • Indication: CINV
  • IV & PO
  • SEs:
    • neutropenia, bradycardia, HA,
    • Stevens-Johnson syndrome
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14
Q

Corticosteroids for N/V

A
  • dexamethasone and methylprednisolone
  • PONV, CINV, radiation related N/V
  • IV or PO
  • MOA:
    • reduces release of 5-HT
    • reduce permeability of BBB
    • reduction of inflammation
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15
Q

Benzodiazepines for N/V

A

for CINV

  • MOA: prevent input signal from cortex and limbic reaching the vomiting center in brainstem
  • SEs: sedation, amnesia, respiratory depression (i.e. high dose or +EtOH)
  • Lorazepam (Ativan): less addictive
  • Alprazolam (Xanax): CAUTION: addiction/dependence
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16
Q

Types of CINV

A
  • Acute:
    • occurs within 24 hours after chemo tx
  • Delayed:
    • >24 hours after chemo tx
  • Anticipatory:
    • d/t previous experience of poor control of N/V
    • Risk: Poor emetic control, female, young age, low chronic EtOH intake
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17
Q

Regimens for use for CINV: low-high emetogenic risk and acute vs delayed CINV

18
Q

N/V of pregnancy

A
  • Non-pharm:
    • dietary, physical & behavioral
  • Pharm:
    • pyridoxine (vitamin B6) +/- antihistamine (doxylamine)
    • ondansetron (category B)
    • Promethazine
    • Metoclopramide
    • trimethobenzamide
    • Last resort: methylprednisolone → cause oral clefts during 1st trimester
19
Q

6 types of Laxative Drug Classes:

A
  • Laxatives:
    • bulk producers
    • hyperosmotics
    • lubricants
    • stimulants
    • emollients
    • saline
20
Q

Bulk Producing laxatives

A
  • Meds:
    • psyllium
      • semi-soluble
    • methylcellulose
      • water soluble
  • Bulk forming -→ promotes peristalsis
  • need to drink with at least 8 oz of water
  • SEs:
    • flatulence and abd cramps
21
Q

Hyperosmotic Laxatives

A
  • Meds:
    • lactulose
    • sorbitol
    • glycerin
    • PEG (polyethylene glycol) 3350
  • pull fluid into GI tract which promotes movement of bowels
  • SEs:
    • flatulence, abd cramps, bloating
    • Sorbitol PO – check sugars in DM pts
22
Q

Lubricant Laxatives

A

coating the stool → oily film

  • mineral oil (liquid petrolatum)
  • SEs:
    • interfere with fat-soluble vitamin absorption (Vitamins A, D, E, & K)
23
Q

Stimulant Laxatives

A

MOA: acts on nerve plexus of GI muscles which increases motility

Caution: *May develop tolerance* → become dependent to have a bowel movement

Can worsen bowel obstruction or fecal impaction

** good for opioid induced constipation **

  • Anthraquinones:
    • Senna
  • Diphenylmethane:
    • Castor oil
      • no longer used/less frequent → category X, can induce lots of N/V
    • Bisacodyl:
      • do not chew → GI irritation & vomiting (want this to make it to colon and not get released into upper GI tract)
        • high gastric pH → causes premature dissolution of enteric coating → GI cramps and other SEs
        • DDI: antacids (calcium carbonate, magnesium hydroxide[maalox], aluminum hydroxide [mylanta]), PPI, H2 blockers, milk (1-2 hours apart)
24
Q

Emollient Laxatives

A

aka surfactants or stool softeners

  • Meds:
    • docusate
  • MOA: increase surface wetting
  • Don’t use for opioid induced constipation
25
Saline Laxative
Salts of Na+, Mg2+, phosphate * _Meds_: * **magnesium citrate** * _Indications_: * colonoscopy prep Mg and phos → accumulate in renal impairment NaPhos → dehydration, hyperNa+, hyperPhos, acidosis, hypoCa2+ **AVOID in CHF/renal dysfunction**
26
Lubiprostone (amitiza)
Prostaglandin derived medication that activates CIC-2 **chloride channel activator** → increases fluid secretion & motility * _Indications_: * **chronic idiopathic constipation** (CIC) in adults * Opioid-induced constipation * Constipation-predominant IBS * _Contraindications_: * mechanical GI obstruction * Pregnancy → should have neg preg test * _SEs_: * Dyspnea * N/D/V * Abd distention, pain * flatulence
27
Misoprostol (Cytotec)
Prostaglandin E1 analog * _MOA_: inhibits gastric acid secretion * protects GI mucosa * stimulate uterine contractions * _indications_: * chronic constipation * _SEs_: * N/D, HA, dyspepsia, abd pain * hypotension, HTN, (**pay attention to BP**) bronchospasm, teratogenicity, MI * _Contraindications_: * Pregnancy -→ causes spontaneous abortion
28
Cathartic vs Laxatives
* cathartic: accelerate evacuation * Laxatives: ease evacuation
29
Are bulking laxatives indicated for a pt with opioid induced constipation?
No. may worsen constipation and lead to fecal impaction
30
What do prostaglandins do to parietal cells in the GI system?
* increase mucus secretion * increase cell regeneration * increase bicarb release * increase blood flow * decrease H+ secretion
31
Peripheral Opioid Antagonists Meds
* **Methylnaltrexone Bromide** (Relistor) * **Alvimopan** * **Naloxegol** * **Naldemedine** *
32
Methylnaltrexone Bromide (Relistor)
Peripheral Opioid antagonists for constipation * _indication_: opioid induced constipation in advanced illness * _MOA_: selective antagonist of opioid binding at mu-receptor * Does not cross BBB → does not reduce analgesia or cause withdrawal * SEs: * N/D, abd cramping, flatulence, dizziness * hyperhydrosis, hyperthermia, muscle spasm * syncope * _Contraindication_: * GI obstruction
33
Alvimopan (Entereg)
Peripheral Opioid Antagonists for constipation * block opioid binding at mu receptor * Does not cross BBB → does not reduce analgesia or cause withdrawal * _indication_: Ileus (obstruction of GI) post-op * _Contraindications_: * opioid use for more than 7 days prior to alvimopan administration → more sensitive to GI effects * _SEs_: * HypoK+ * dyspepsia * urinary retention * anemia * back pain * increased risk of MI
34
How do you eliminate the toxins in the GI lumen produced by bacteria?
Bile Acid Sequestrants (Cholestyramine)
35
Non-pharmacological treatment of acute diarrhea
* fluid & electrolyte replacement * oral rehydration * pedialyte * rehydralyte * ceralyte * dietary modifications: * increasing bulk in diet * rice * whole wheat & bran
36
Absorbent/Bulk Agents for Diarrhea
* absorbs excess fluid * **calcium polycarbophil** * polyacrylic resin → not absorbed * used for chronic diarrhea * **psyllium and methylcellulose**
37
Antimotility agents for diarrhea
* prolong transit time → reduce fluid loss * **loperamide** (imodium) * **diphenoxylate + Atropine** (lomotil) * atropine = anticholinergic * used to prevent misuse of diphenoxylate → gives the patient SEs * also reduce some of the fluid excretion
38
Antisecretory agents
* **Bismuth subsalicylate** (BSS) * not for salicylate/ASA allergy * used for traveler's diarrhea & non-specific acute diarrhea * **octreotide**: * tx: diarrhea from chemo; HIV, virus; DM; gastric resection; GI * **THE IV FORM/SubQ inj** * _SEs_: * nausea, bloating, injc site rxn, gallstones
39
Naloxegol & Naldemedine
Peripheral Opioid Antagonists for constipation * _MOA_: antagonizes peripheral mu receptors → inhibits opioid induced constipation * _SEs_: Opioid Withdrawal * GI perforation * abd pain; n/v/d, flatulence * DDI: 3A4 substrate = naloxegol
40
Anti-infectives: empiric abx tx for traveler's diarrhea
* **Fluoroquinolones** * cipro or levo * **azithromycin** for resistance * **Rifamixin** * traveler's diarrhea: 200mg PO TID x 3 days with or without food * _SEs_: * HA, flatulence, abd pain, peripheral edema, dizziness
41
Subtypes of IBS
* IBS with predominant constipation * IBS with diarrhea * Mixed IBS * Unclassified IBS * pts who meet diagnostic criteria for IBS but cannot be accurately categorized into one of the other 3 subtypes
42
Types of Meds for IBS
* _Botanicals_: * peppermint oil -relax GI smooth muscle * german chamomile/primrose oil * _antispasmodics:_ * dicyclomine, hyoscyamine, propantheline Br (anticholinergics * Librax * (Clonidine bromide + chlordiazepoxide HCl) * Donnatal * (hyoscyamine+ scopolamine +atropine+ phenobarb) * T_ricyclic Antidepressants:_ * amitriptyline, doxepin * _SSRI_: * paroxetine * _Bulk Forming_: * psyllium * methylcellulose * _Antimotility agents_: * lomotil, imodium (loperamide) * eluxadoline: reduce GI motility, * contraindicated in SEVERE liver failure * _5-HT3 antagonists_: * Alosetron (Lotronex) * \*\*\*only available under certain circumstance\*\*\* * can cause ischemic colitis * _5-HT4 antagonists_: * tegaserod maleate (Zelnorm) * \*\*\*only available as EMERGENCY tx\*\*\* * higher risk of stroke, MI, unstable angina

NRS 271B (10 decks)

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