Constipation and IBS Flashcards
What is the definition of constipation?
Described by < 3 bowel movements per week, stool size or consistency, or sensation of incomplete defecation
What are the mechanical causes of constipation?
Colorectal cancer
Colon, rectal or anal stricture
Intestinal pseudo-obstruction
Megacolon
What are the neurologic disease causes of constipation?
Spinal cord lesion
Stroke
Parkinson’s disease
MS
What are the metabolic disturbance causes of constipation?
Hypercalcemia Hypokalemia (severe) Hypomagnesemia Hypothyroidism (severe) Uremia
What medications can cause constipation?
Opioids Anticholinergics Ca Channel blockerws Anticonvulsants Antidepressants Antispasmodics Antihistamines Antiemetics (zofran)
What is acute constipation?
Usually treatable with lifestyle changes (diet, fluid intake, exercise) and OTC treatment
What is chronic constipation?
Often requires Rx treatment if patient does not respond to lifestyle changes and OTC treatment
What is opioid induced bowel dysfunction?
constellation of GI symptoms including N/V, OIC (most common), abdominal cramping, bloating, and abdominal pain
What is OIC?
Opioid induced constipation
What are the nonpharmacological therapies for treatment of constipation?
Increase fiber in diet (25-40g/day) Increase fluid intake (6-8 glasses of water per day) Increase exercise (3-5d/wk)
How does insoluble fiber work?
Insoluble fiber reduces the risk of colon cancer by increasing transit through the colon and decreasing the time carcinogens are in contact with the mucosa. It also dilutes the carcinogenic substance
How does soluble fiber work?
Soluble fiber has been shown to decrease cholesterol by binding to bile acids in the intestines
It also regulates blood glucose by slowing stomach emptying resulting in a steadier rate of carb absorption in the small bowel
What are the saline osmotic laxatives?
Mag Citrate
Mag hydroxide
Mag Sulfate
Sodium phosphate
What is the onset of action for saline osmotic laxatives?
Fast (15min - 3 hours)
What are osmotic laxatives?
Glycerin
Lactulose
PEG
What is the onset of action for glycerin?
Fast (w/in 1 hour)
What is the onset of action for lactulose?
1-2 days (may require multiple doses)
What is the onset of action for PEG?
1-3 days
What are stimulant laxatives?
Bisacodyl
Senna
What is the onset of action for bisacodyl?
6-12 hours (oral) 1 hour (supp.)
What is the onset of action for senna?
6-12 hours
What are the bulk forming laxatives?
Psyllium
Wheat dextrin
Calcium polycarbophil
Methylcellulose
What is the onset of action for bulk-forming laxatives?
12-72 hours
Less effective in drug-induced constipation
What is a stool softener?
Doc sodium
What is the onset of action for doc sodium?
1-6 days
What is a chloride channel activator?
Amitiza
What is Amitiza’s MOA?
Activates chloride channels in colon to draw fluid into colon
What is Amitiza FDA approved for?
CIC in adults
IBS-C
Chronic OID
What is the onset of action for amitiza?
w/in 24 hours
What preg category is amitiza?
C but animal studies suggest the potential for fetal death
Women should have (-) test prior to starting and should use BC while taking
What are common ADRs of Amitiza?
HA
Diarrhea
Nausea
Dyspnea
What is a guanylate cylase-C agonist?
Linzess
Trulane
What is the MOA of Linzess and Trulance?
Increases chloride secretion into intestinal lumen increasing intestinal fluid and decreases transit time (also decreases visceral pain by inhibiting afferent nerve activity)
What is Linzess FDA approved for?
CIC in adults
IBS-C
What is the onset of action for Linzess?
w/in 1-2 days
What is Linzess/Trulance contraindicated for?
Peds up to age 6 (avoid 6-17yo)
What are ADRs for Linzess?
GI (diarrhea, flatulence, ab distension)
HA
What is Trulance FDA approved for?
CIC in adults
What is the onset of action for Trulance?
1-2 days
What are the ADRs for Trulance?
GI (diarrhea, flatulence abdominal distension)
What are the peripheral opioid antagonists?
Methylnaltrexone
Naloxegol
Alvimopan
Naldemedine
What is the MOA of peripheral opioid antagonists?
Blocks opioid binding to the mu, kappa, and gamma receptors in the periphery
- Does not cross BBB
- Does not affect opioid analgesic effects or induce opioid withdrawal
What is methylnaltrexone FDA approved for?
Chronic OIC in both cancer and noncancer pain
What is the onset of action for methylnaltrexone?
30-60 minutes in responding patients
What enzyme metabolizes methylnaltrexone?
Substrate of CYP 2D6 (minor)
What are the ADRs of methylnaltrexone?
GI (ab pain, flatulence, nausea)
What is naloxegol FDA approved for?
Chronic OIC in noncancer pain
What is the OOO for naloxegol?
6-12 hours
How is naloxegol metabolized?
Substrate for CYP 3A4 and P-gp resulting in several drug interactions
What is are the ADRs for naloxegol?
GI (ab pain, diarrhea, flatulence, N/V, HA
What is alvimopan FDA approved for?
Treatment of post-op ileus
What is the OOO of alvimopan?
4-7 hours
What are the ADRs for alvimopan?
Hypokalemia
Dyspepsia
What is naldemedine FDA approved for?
Tx of Chronic OIC in noncancer pain
What is the OOO of naldemedine?
4-24 hours
How is naldemedine metabolized?
Subwstrate of CYP 3A4 (major) and P-gp resulting in potential for several drug interactions
What are the ADRs for naldemedine?
Ab pain
Diarrhea
Nausea
What is a combination peripheral opioid antagonist and opioid agonist?
Targinig ER (Oxycodone/Naloxone)
What is the MOA of Targinig ER?
Naloxone which has a high affinity for opioid receptors in the GI tract, displaces oxycodone from GI tract opioid receptors making oxycodone available for transport to the brain where it exerts its opioid effect. With less opioid binding in the GI tract there will be less opioid inducing constipation
What is Targinig ER FDA approved for?
Treatment of moderate to severe pain requiring daily, around the clock, long term opioid treatment
Can Naloxone cross the BBB?
Yes - while it has very high first pass hepatic metabolism it still crosses the BBB and can reverse the analgesic effects of opioids
What is IBS?
Characterized by altered bowel habits AND abdominal pain for at least 3 months
What are the types of IBS?
IBS-constipation predominant (IBS-C)
IBS-diarrhea dependent (IBS-D)
IBS-mixed constipation/diarrhea
When is IBS prevalent?
3-4th decade
Usually resolves 6-7th decade
What are the physiologic abnormalities in IBS?
Altered GI reactivity (motility, secretion) to luminal (food, distention, inflammation, bacteria) or environmental (psychosocial stress) stimuli, resulting in diarrhea and/or constipation
Hypersensitive GI tract with enhanced visceral perception and pain
Dysregulation of the brain-GI axis
What is encompassed by the brain-GI axis?
Enteric nervous system (including afferent and efferent innervation)
CNS
HPA axis
Serotonin - 80% of all serotonin found in GI tract; increases peristalsis and secretory reflexes
How do we diagnose IBS?
Symptom based criteria since there is no diagnostic test
What are alarm symptoms?
Rectal bleeding Anemia Weight loss Fever FH of colon cancer Onset of sx after age 50 Major change in sx
What do we do if there are alarm sx present?
Rule out other dz
Always test for celiac dz
What are the non-pharma and CAM treatment for IBS?
Exclude dietary triggers Exercise for 30-60min 5 d/wk Psychological treatment (hypnosis, cognitive behavioral therapy, psychotherapy) Acupuncture Chinese, indian, tibetan herbs Peppermint oil - anispasmodic; Melatonin
What are the Pharm tx for IBS?
Treat gut dysmotility AND pain
What is the MOA of antispasmodic agents?
Inhibit muscarinic cholinergic receptors on smooth muscle
What are the ADRs for antispasmodic agents?
Anticholinergic
What are antispasmodic agents?
Hyoscyamine
Dicyclomine
Clindinium chlordiazepoxide
What is the MOA of TCA’s?
Reduce sensitivity of peripheral nerves or to changes that occur in the brain (anticholinergic)
Reduce pain and normalize GI transit time
What is an example of TCAs?
Amitriptyline
When will benefits be seen for TCAs?
w/in 2 weeks - if not seen by 4 weeks DC
How long should TCAs be used to treat IBS?
at least 6 months
When should TCAs not be used for IBS?
IBS-C or mixed d/t the consitpating effects of TCAs
What is the potential MOA of SSRIs on IBS?
Decreases visceral hypersensitivity
What are ADRs of SSRIs?
Zoloft/prozac: diarrhea
Paxil: constipation or diarrhea
Celexa/Lexapro: useful for all IBS
What are SNRIs shown to be effective for in IBS?
Cymbalta and Effexor have been shown to be effective in reducing pain in other chronic conditions, but data is lacking
What do 5-HT3 receptor antagonists treat?
IBS-D for both diarrhea and pain
Which 5-HT3 receptor antagonist is only approved for women with severe IBS-D?
Lotronex
What are two 5-HT3 receptor antagonists used for IBS-D?
Lotronex
Zofran
What is the peripheral mu-opioid receptor agonist?
Viberzi
What is the MOA of Viberzi?
Mixed locally acting, kappa-opioid agonist, and a delta-opioid receptor antagonist (very little oral absorption)
What is Viberzi approved for?
IBS-D to improve diarrhea with ab pain
How is Viberzi metabolzied?
Substrate of several enzymes
Inhibits P-gp
Several potential drug interactions
What are the ADRs for Viberzi?
Nausea
Constipation
Rare pancreatitis (EtOH drinkers)
What antibiotic is used for IBS?
Xifaxan
What is Xifaxan FDA approved for?
IBS-D
What is Xifaxan used off-label for?
Tx of C. diff colitis
What are other FDA indications for Xifaxan?
Traveler’s diarrhea
Hepatic encephalopathy prophylaxis
What are probiotics most useful for?
Bloating
