DPT IV Exam 3 (brittain)

constipation

difficult or infrequent passage of stool

associated with straining or a feeling of incomplete defecation

quantitative constipation

fewer than 3 bowel movements per week

no real normal frequency

qualitative constipation

stool size and consistency

chronic constipation

≥ 6 months

signs and symptoms of constipation

infrequent bowel movements (<3 per week)

stools that are hard, small, or dry

difficulty or pain of defecation

feeling of abdominal discomfort or bloating, incomplete evacuation, etc.

alarm signs and symptoms of constipation

hematochezia

melena

family history of colon cancer

family history of inflammatory bowel disease

anemia

weight loss

anorexia

nausea and vomiting

severe, persistent constipation that is refractory to treatment

new onset or worsening constipation in elderly without evidence of primary cause

physical examination for constipation

rectal exam

digital examination of rectum

laboratory and other diagnostic tests for constipation

no routine recommendations for lab testing

in patients with s/s specific of organic dysorder, specific testing may be preformed

in patients w/ alarm s/s may may preform:

protoscopy

sigmoidoscopy

colonoscopy

barium enema

what factors may contribute to abrupt symptoms of constipation?

in adults

malignancy

in infants

neurologic

in the elderly

higher number of daily meds, chronic comorbidities, etc.

what may contribute to constipation?

dietary influences

laxative regimens

concurrent medical conditions

concurrent medications

if a patient has constipation and hypothyroidism, how can it be corrected?

thyroid replacement therapy

if a patient has constipation and GI malignancy, how can it be corrected?

surgical resection

if a patient has drug-induced constipation, how can it be corrected?

consider use of another agent

if not, general measures to prevent constipation

opioid-induced constipation

nonpharmacologic therapy for constipation

dietary modifications

surgery

biofeedback

electric stimulation

how much daily fiber is recommended?

20-30g daily

use dietary changes of fiber supplementation

when initiating dietary modifications for constipation, how should you about it?

initiate for 1 month

fruit, veggies, and cereals are high in fiber

early: abdominal distension/flatulence

gradually increase fiber intake

increase fluid intake as well

may notice effects on bowel function as early as 3-5 days (but may require longer period of time)

high fiber foods

100% bran cereal

↓

cooked artichoke hearts

↓

almonds

↓

lentils

↓

raspberries

↓

banana

↓

apple w/skin

↓

orange

↓

prunes, dried

surgery as a non-pharmacologic therapy for constipation

resection or revision

colonic malignancies or GI obstruction

biofeedback as a non-pharmacologic therapy for constipation

pelvic floor training with biofeedback therapy

4-6 hour sessions

success rate of 65-80% sustained up to 1 year

electrical stimulation as a non-pharmacologic therapy for constipation

sacral nerve stimulation (severe refractory chronic constipation)

general treatment algorithm for patients with:

opioid-induced constipation for >4 weeks

osmotic or stimulant laxative

OR

lubiprostone or opioid receptor antagonists (methylnatrexone, naloxegol, naldemedine)

general treatment algorithm for patients with:

acute constipation for (<3 to 6 months)

add osmotic laxative (ex. PEG) if no relief, trial 2-4 weeks

OR

add stimulant laxative (ex. bisacodyl) if no BM in or no relief

general treatment algorithm for patients with:

chronic constipation for (>6 months)

trial of intestinal secretagogue (ex. lubiprostone, linaclotide, plecanatide)

pharmacologic therapy for constipation

laxatives

calcium channel activators

gyanylate cyclase c agonist

opioid receptor antagonists

serotonin 5-HT4 receptor agonists

probiotics

which laxatives soften the feces in 1-3 days?

polyethylene glycol

methylcellulose

docusate

lactulose

which laxatives provide soft or semifluid stool in 6-12 hours?

senna

bisacodyl (oral)

which laxatives provide evacuation in 1-6 hours?

bisacodyl (rectal)

sodium phosphates

magnesium hydroxide

magnesium citrate

polyethylene glycol - electrolyte preparations

bulk-forming agents

products

psyllium, methylcellulose, polycarbophil

MOA

similar to dietary fiber, increase water content of stool to increase stool bulk and weight

time to action

within 3 days

adverse effects

flatulence, abdominal bloating/distention

counseling

drink lots of fluids with use

emollient laxatives

products

docusate

MOA

"stool softeners"

surfactant agents by increasing water, fatty materials, and electrolyte secretion in small/large bowel

time to action

within 1-3 days

adverse effects

may increase absorption of agents administered concurrently, fecal soiling

true or false: emollient laxatives are used for treatment, not prevention

false

what are the osmotic laxatives?

lactulose and sorbitol

polyethylene glycol

magnesium salts

glycerin

lactulose

MOA

nonabsorbable disaccharide metabolized by colonic bacteria promoting osmotic effect to retain fluid in colon, increases colonic peristalsis

time to action

within 2-3 days

adverse effects

flatulence, nausea, abdominal discomfort/bloating, electrolyte imbalances

other

sorbitol is similar in action and effectiveness but may be a cheaper option for patients

polyethylene glycol

MOA

lower doses to treat constipation, no systemic absorption or metabolism of colonic bacteria, water retention in stool

time to action

within 1-3 days

adverse effects

nausea, vomiting, flatulence, abdominal cramping

other

higher doses for bowel evacuation/"prep" (also comes with electrolytes)

magnesium salts (hydroxide, phosphate, citrate) & sodium phosphate

MOA

osmotic retention of fluid causing colonic distension and increased peristalsis

time to action

within 1-6 hours

adverse effects

may cause fluid and electrolyte imbalances (magnesium and sodium accumulation*)

other

frequently used as bowel prep for diagnostic procedures

glycerin (rectal)

MOA

osmotic action within rectum

time to action

< 30 minutes

adverse effects

rectal irritation

other

considered safe, acceptable for intermittent use, useful in children

stimulant laxatives

products

bisacodyl, senna

MOA

stimulate mucosal nerve plexus of colon, increase intestinal fluid secretion

time to action

within 8-12 hours

adverse effects

severe cramping, electrolyte imbalances (chronic use)

other

not recommended first-line, useful for those who fail other therapies, however, may be needed in severe chronic constipation

long-term use is controversial. do they cause damage to the enteric nervous system?

what are the intestinal secretagogues used for constipation?

the calcium channel activators and guanylate cyclase C agonists

lubiprostone

MOA

calcium channel activator, increases fluid secretion and accelerates GI transit time

time to action

within 24-48 hours

adverse effects

N/V/D

FDA-approved for

chronic idiopathic constipation; IBS-C

what are the guanylate cyclase C agonists used for constipation?

linaclotide (Linzess) and plecanatide (Trulance)

linaclotide

MOA

activates guanylate cyclase C receptor on intestinal epithelium, increasing intestinal fluid secretion and quickens intestinal motility

time to action

???

adverse effects

diarrhea, flatulence, abdominal pain

FDA-approved for

chronic idiopathic constipation; IBS-C

plecanatide

MOA

activates guanylate cyclase C receptor on intestinal epithelium, increasing intestinal fluid secretion and quickens intestinal motility

time to action

???

adverse effects

diarrhea

FDA-approved for

chronic idiopathic constipation; IBS-C

what are the opioid receptor antagonists used for constipation?

alvimopan (Entereg®)

methylnaltrexone (Relistor®)

naloxegol (Movantik®)

naldemedine (Symproic®)

alvimopan

MOA

antagonism of binding of opioid agonists to mu opioid receptors - GI periphery not BBB

use

short-term hospitalized patients to accelerate recovery of bowl function after bowel resection

other

only available through special use program (ENTEREG access support and education) - hospitals required to register and meet requirements first

methylnaltrexone

MOA

mu-receptor antagonist - GI periphery

use

OIC in patients with advanced diseases receiving palliative care or when response to laxative therapy has not been sufficient

other

available orally or subQ (weight-based and fixed dosing based on dosage form)

naloxegol

MOA

antagonizes mu-receptor, pegylated to reduce passage through BBB

use

OIC in adult patients with noncancer pain

other

25 mg once daily 1 hour before or 2 hours after eating, reduce dose by 50% for CrCl < 60 ml/min

naldemedine

MOA

peripherally acting opioid antagonist

use

OIC in adult patients with noncancer pain

dose

no dose adjustments for renal/hepatic impairment.

other

CI in patients with severe hepatic impairment

prucalopride

MOA

promotes neurotransmission of enteric neurons stimulating peristaltic reflex, intestinal secretions and GI motility

use

chronic idiopathic constipation

caution

elderly or those with renal dysfunction

signs and symptoms of IBS

s/s

lower abdominal pain, abdominal bloating/distension, extreme urgency, passage of mucus, depression/anxiety

other symptoms

urinary sxs, fatigue, dyspareunia

other concurrent conditions

fibromylagia, functional dyspepsia, chronic fatigue syndrome

reduced quality of life

IBS-C

constipation predominant

<3 stools/week, straining, incomplete evacuation

IBS-D

diarrhea predominant

diarrheal signs and symptoms, > 3 stools/day

what is the treatment of IBS dependent on?

the predominant symptoms and severity

lifestyle modifications of IBS

dietary restrictions

higher fiber diet

physical activity

relaxation techniques

pharmacologic treatments for IBS

as needed for symptom managment

underlying neurohormonal imbalance

treatment algorithm for IBS-C

increase dietary fiber and intake

↓

add bulk-forming laxatives

↓

secretagogues

↓

add serotonin-4 agonist (ex. tegaserod)

↓

add psychotherapeutic behavior modifications, including stress reduction, and consider antidepressants for associated pain symptoms

treatment algorithm for IBS-D

lactose-free, caffeine-free diet and counsel patient on other diarrhea-inducing foods and drugs to avoid

↓

rifaximin or eluxadoline

↓

add serotonin-3 antagonist (ex. alosetron)

↓

add psychotherapeutic behavior modifications, including stress reduction, and consider antidepressants for associated pain symptoms

treatment for constipation predominant IBS

stress management

increase dietary fiber and fluid intake

add bulk-forming laxatives

add drug therapy

add psychotherapeutic behavior modifications

drug therapies for IBS-C

linaclotide, plecanatide, lubiprostone, tegaserod

psychotherapeutic behavior modifications for IBS-C

stress reduction

antidepressants for associated pain syndromes

how should you increase dietary fiber and fluid intake?

start with 1 tbsp of fiber (dietary bran) with one meal daily

gradually increase to include fiber 2-3 meals a day until desired outcome is achieved (provides bulkier, easily passed stool)

if intolerant to bran/other options: use psyllium, PEG laxatives, other laxatives (low dose, least amount of time), linaclotide, plecanatide, lubirprostone*

tegaserod (Zelnorm)

5HT-4 partial agonist

short-term, intermittent treatment of IBS-C in women (< 55 y/o)

restricted access program: increase in ischemic events (MI, CVA, unstable angina) in patients with pre-existing CVD and/or CV risk factors

adverse effects: diarrhea

withdrawn from US market

treatment for IBS-D

stress management

lactose-free, caffeine-free diet (including avoidance of other diarrhea-inducing foods, drugs, and artifical sweeteners)

add drug therapy

add pscyhotherapeutic behavior modifications

what drug therapies can be used for IBS-D?

loperamide

alosetron

rifaximin

eluxadoline

what psychotherapeutic behavior modifications can occur for IBS-D?

stress reduction

antidepressants for associated pain syndromes

what does a lactose-free, caffeine-free diet consist of in those with IBS-D?

avoidance of other diarrhea-inducing food and drugs

artificial sweeteners (sorbitol, fructose, mannitol) irritate the gut = laxative effect

lactose intolerance?

herbal medicines/teas (senna)

risk of elimination diets

loperamide (Imodium)

MOA: decreases intestinal transit, enhances water and electrolyte absorption, & strengthens rectal sphincter tone

avoid in constipaton

alosetron (Lotronex®)

indication: women with IBS-D longer than 6 months not relieved by convential therapy

only available through FDA restricted use program due to severe GI adverse effects: constipation, ischemic colitis

rifaximin (Xifaxan®)

indication: treatment of IBS-D in adults, traveler's diarrhea (reserve for patients who have failed other therapies)

benefit for improvement in abdominal pain, stool consistency and bloating

sustained effects up to 10 weeks following 2 week course of therapy. Recurrences may be treated up to 2 times

eluxadoline (Viberzi®)

mu opioid agonist

treatment of IBS-D in adults (those with gallbladder who do not consume 3+ alcoholic beverages per day)

benefit for improvement in abdominal pain & stool consistency

adverse effect: CNS depression

potential for drug abuse and psychological dependence

tricyclic antidepressants for diarrhea

amitriptyline, doxepin, imipramine

indication: treatment of IBS-D with moderate-severe

adverse effects: CNS depression

how are some treatments for IBS associated with pain?

antispasmodic agents

conflicting data

low dose antidepressant therapy

pain associated with eating

produces analgesia and may relieve depressive sxs

anticholinergics before meals

helpful with overactive postprandial gastrocolonic response

true or false: tricyclic antidepressants should be avoided in patients with pain and constipation

true

crohn's disease

malaise/fever

common

rectal bleeding

common

abd. tenderness

common

abd. mass

common

abd. pain

common

abd. wall & internal fistulas

common

distribution

discontinuous

aphthous or linear ulcers

common

rectal involvement

rare

ulcerative colitis

malaise/fever

uncommon

rectal bleeding

common

abd. tenderness

may be present

abd. mass

absent

abd. pain

unusual

abd. wall & internal fistulas

absent

distribution

continuous

aphthous or linear ulcers

rare

rectal involvement

common

characteristics of ulcerative colitis

confined to rectum and colon

affects mucosal and submucosal layers

symptoms: diarrhea and bleeding

complications: hemorrhoids, anal fissures, perirectal abscesses, toxic megacolon, colonic perforation, massive colonic hemorrhage, colorectal carcinoma

intermittent bouts of illness after varying intervals of remission with symptoms

mild UC

< 4 stools per day, with or without blood, no systemic disturbances, normal ESR

moderate UC

> 4 stools per day but with minimal systemic disturbances

severe UC

> 6 stools per day with blood, evidence of systemic disturbances

fulminant UC

> 10 stools per day with continuous bleeding, toxicity, abdominal tenderness, requirement for transfusion, colonic dilation

what does severe UC include?

profuse bloody diarrhea with high fever, leukocytosis and hypoalbuminemia, dehydration (tachycardia, hypotension)

characteristics of CD

onset of complaints to initial diagnosis (~3 years)

diarrhea and abdominal pain

hematochezia occurs in 1/2 of patients with colonic involvement

signs & symptoms: malaise and fever, abdominal pain, frequent bowel movements, fistula, weight loss, malnutrition, arthritis

mild-moderate CD

ambulatory

no evidence of dehydration, systemic toxicity, loss of weight, abdominal tenderness/mass/obstruction

moderate-severe CD

fail to respond to treatment for mild/moderate

those with fever, weight loss, abdominal pain/tenderness, vomiting, intestinal obstruction, anemia

severe-fulminant CD

persistent symptoms, evidence of systemic toxicity despite treatment, rebound tenderness, intestinal obstruction, abscess

•Serum c-reaction protein (CRP)

remission in UC

1 year with medical therapy

remission in CD

1 year

is IBD curative?

no, resolve symptoms

pharmacologic therapy for IBD

aminosalicyclic acids (ASAs)

corticosteroids

immunomodulators

antimicrobials

TNF-alpha inhibitors

leukocyte adhesion/migration inhibitors

interleukin inhibitors

sulfasalazine vs mesalamine

mesalamine better tolerated and can be administered alone

topical > oral

adverse effects occur more commonly in sulfasalazine

side effects of the ASAs

n/v/d, anorexia, headache, arthralgia

true or false: the side effects associated with ASAs are most common with initiation of therapy and decrease as therapy is continued

true

what supplementation does sulfasalazine require?

folic acid

there is reduced folic acid absorption with this medication

corticosteroids for IBD

budesonide or prednisone

suppress acute inflammation

typically used for acute symptoms in both UC and CD

not recommended for maintenance therapy

true or false: corticosteroids are recommended for maintenance therapy

false

what agents are steroid-sparing?

azathioprin or 6-MCP

methotrexate

ADRs of corticosteroids

hiigher doses over longer period of time

hyperglycemia, HTN, osteoporosis, acne, fluid retention, electrolyte disturbances, myopathies, muscle wasting, increased appetite, psychosis, infection, adrenocortical suppression

how can you minimize the side effects of corticosteroids?

alternate-day dosing

what can the abrupt discontinuation of corticosteroids cause?

adrenal insufficiency

budesonide in IBD

lower bioavailability

lower potential for adverse effects

immunomodulators used in IBD

thiopurines

azathioprine

mercaptopurine

methotrexate

cyclosporine

tacrolimus

azathioprine & mercaptopurine in IBD

used for long-term treatment in UC and CD

reserved for patients who fail ASAs or are dependent on corticosteroids

used in conjunction with mesalamine derivatives, corticosteroids, TNF-alpha antagonists

long-term use (weeks-1 year) to see benefit