N/V/D/C, IBS & Rota Flashcards
3 stages of N/V
- Nausea:
- subjective feeling
- autonomic: pallor, tachycardia diaphoresis, & salivation
- Retching:
- diaphragm, chest, & abd wall contractions
- produce pressure gradient
- vomiting
- reflexive, forceful, rapid
- sustained contractions of abd and thoracic muscles
Triggers of N/V
-
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
- located outside BBB → easily stimulated by:
-
Visceral Vagal Nerve Fibers
- lots of 5HT3 receptors
- stimulated by:
- GI distention
- mucosal irritation
- infection
- stimulated by:
- lots of 5HT3 receptors
-
Motion Sickness:
- stimulation of vestibular system
- lots of histamine (H1) receptors & muscarinic receptors
- stimulation of vestibular system
-
Anticipatory N/V with chemo
- involves the cortex
- sights, sounds, smells trigger n/v
Simple vs Complex N/V
D2 Antagonists Drug Classes & Names
-
Phenothiazines:
- chlorpromazine
- Prochlorperazine
- Promethazine
-
Butyrophenones:
- Droperidol
- Haloperidol
-
Benzamides:
- Metoclopramide
- Trimethobenzamide
Indications for D2 Blockers
- severe motion sickness
- vertigo
- gastritis
- n/v of pregnancy
- post-op N/v
- chemo-induced N/V (CINV)
Phenothiazines
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
Butyrophenones
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
- CI: male QT > 450ms
Benzamides
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
- metoclopramide (CROSSES THE BBB)
Where is serotonin synthesized and how does it affect GI system?
- 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
Serotonin Antagonists for N/V
- 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
Neurokinin-1 Receptors
- 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
Rolapitant
NK1 receptor antagonist
- Indication: CINV
- PO only
- SEs: anemia, neutropenia, anorexia, dizziness, UTI, hiccups
Fosaprepitant
NK1 Receptor antagonist
- Indication: CINV
- IV & PO
-
SEs:
- neutropenia, bradycardia, HA,
- Stevens-Johnson syndrome
Corticosteroids for N/V
- 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
Benzodiazepines for N/V
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
Types of CINV
- 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
Regimens for use for CINV: low-high emetogenic risk and acute vs delayed CINV
N/V of pregnancy
-
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
6 types of Laxative Drug Classes:
- Laxatives:
- bulk producers
- hyperosmotics
- lubricants
- stimulants
- emollients
- saline
Bulk Producing laxatives
-
Meds:
-
psyllium
- semi-soluble
-
methylcellulose
- water soluble
-
psyllium
- Bulk forming -→ promotes peristalsis
- need to drink with at least 8 oz of water
-
SEs:
- flatulence and abd cramps
Hyperosmotic Laxatives
-
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
Lubricant Laxatives
coating the stool → oily film
- mineral oil (liquid petrolatum)
-
SEs:
- interfere with fat-soluble vitamin absorption (Vitamins A, D, E, & K)
Stimulant Laxatives
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)
- do not chew → GI irritation & vomiting (want this to make it to colon and not get released into upper GI tract)
-
Castor oil
Emollient Laxatives
aka surfactants or stool softeners
-
Meds:
- docusate
- MOA: increase surface wetting
- Don’t use for opioid induced constipation
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
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
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
Cathartic vs Laxatives
- cathartic: accelerate evacuation
- Laxatives: ease evacuation
Are bulking laxatives indicated for a pt with opioid induced constipation?
No. may worsen constipation and lead to fecal impaction
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
Peripheral Opioid Antagonists Meds
- Methylnaltrexone Bromide (Relistor)
- Alvimopan
- Naloxegol
-
Naldemedine
*
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
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
How do you eliminate the toxins in the GI lumen produced by bacteria?
Bile Acid Sequestrants (Cholestyramine)
Non-pharmacological treatment of acute diarrhea
- fluid & electrolyte replacement
- oral rehydration
- pedialyte
- rehydralyte
- ceralyte
- dietary modifications:
- increasing bulk in diet
- rice
- whole wheat & bran
- increasing bulk in diet
Absorbent/Bulk Agents for Diarrhea
- absorbs excess fluid
-
calcium polycarbophil
- polyacrylic resin → not absorbed
- used for chronic diarrhea
- psyllium and methylcellulose
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
- atropine = anticholinergic
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
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
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
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
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
- ***only available as EMERGENCY tx***
- tegaserod maleate (Zelnorm)