DIARRHEA AND DIARRHEA AND CONSTIPATIONCONSTIPATION

Andrew N. Schmelz, PharmDAndrew N. Schmelz, PharmDPost-Doctoral Teaching FellowPost-Doctoral Teaching Fellow

Dept Pharmacy Practice, Purdue UniversityDept Pharmacy Practice, Purdue Universityanschmel@purdue.eduanschmel@purdue.edu

April 27, 2009April 27, 2009

ObjectivesObjectives

List 4 causes of diarrhea and constipationList 4 causes of diarrhea and constipation Identify the names of drugs commonly Identify the names of drugs commonly

used to treat diarrhea and constipationused to treat diarrhea and constipation Explain the general mechanism of action of Explain the general mechanism of action of

drugs used to treat diarrhea and drugs used to treat diarrhea and constipationconstipation

List major side effects and drug List major side effects and drug interactions with common drugs used to interactions with common drugs used to treat diarrhea and constipationtreat diarrhea and constipation

Explain how diarrhea, constipation, and the Explain how diarrhea, constipation, and the agents to treat these conditions impact the agents to treat these conditions impact the practice of physical therapypractice of physical therapy

DIARRHEADIARRHEA

EpidemiologyEpidemiology

Average person in America has an Average person in America has an episode of diarrhea about 4 times episode of diarrhea about 4 times per year.per year.

Up to 20% of persons receiving Up to 20% of persons receiving antibiotics in the US get diarrheaantibiotics in the US get diarrhea

Approx 272,000,000 episodes per Approx 272,000,000 episodes per year or 517 episodes per minuteyear or 517 episodes per minute

About 707,000 deaths due to About 707,000 deaths due to diarrheal diseases in Africa in 2002 diarrheal diseases in Africa in 2002 vs. 57,000 deaths in the Americas vs. 57,000 deaths in the Americas

IntroductionIntroduction

Clinical DefinitionClinical Definition– An increased frequency of bowel movementsAn increased frequency of bowel movements– Decreased consistency of fecal discharge Decreased consistency of fecal discharge

compared to an individual’s normal bowel compared to an individual’s normal bowel patternpattern

Acute vs. Chronic DiarrheaAcute vs. Chronic Diarrhea 4 Types of Diarrhea:4 Types of Diarrhea:

– SecretorySecretory– OsmoticOsmotic– ExudativeExudative– Altered intestinal transitAltered intestinal transit

EtiologyEtiology

InfectionInfection

DietDiet

MedicationsMedications

Gastrointestinal diseasesGastrointestinal diseases

Infectious CausesInfectious Causes

ViralViral

BacterialBacterial– ShigellaShigella– SalmonellaSalmonella– E. coliE. coli– CampylobacterCampylobacter

SuperinfectionSuperinfection

Dietary CausesDietary Causes

Lactose intoleranceLactose intolerance

Excessive dietary fiberExcessive dietary fiber

Large amounts of salty drinks/foodsLarge amounts of salty drinks/foods

Consumption of poorly soluble Consumption of poorly soluble carbohydratescarbohydrates

Unabsorbed dietary fat Unabsorbed dietary fat

Medication CausesMedication Causes

AntibioticsAntibiotics– Broad spectrumBroad spectrum– AugmentinAugmentin– ErythromycinErythromycin– ClindamycinClindamycin

AntihypertensivAntihypertensiveses– AtenololAtenolol– MethyldopaMethyldopa

ChemotherapyChemotherapy

LaxativesLaxatives NSAIDsNSAIDs AntacidsAntacids MiscMisc

– ColchicineColchicine– DigoxinDigoxin– PotassiumPotassium– QuinidineQuinidine

Diarrhea Treatment OptionsDiarrhea Treatment Options

AdsorbentsAdsorbents AntisecretoryAntisecretory

– Bismuth subsalicylateBismuth subsalicylate– Enzymes (lactase)Enzymes (lactase)

AntimotilityAntimotility– LoperamideLoperamide– DiphenoxylateDiphenoxylate– OpioidsOpioids

Misc AgentsMisc Agents– OctreotideOctreotide

Bismuth SubsalicylateBismuth Subsalicylate

MOAMOA– Inhibits intestinal secretionsInhibits intestinal secretions– Increases stool consistencyIncreases stool consistency– Adsorbs bacteriaAdsorbs bacteria– Antimicrobial propertiesAntimicrobial properties

Adverse EffectsAdverse Effects– NauseaNausea– VomitingVomiting– ConstipationConstipation– Discoloration of feces and tongueDiscoloration of feces and tongue– TinnitusTinnitus

Bismuth SubsalicylateBismuth Subsalicylate

WarningsWarnings– Contains salicylateContains salicylate– Can overdose Can overdose

Drug InteractionsDrug Interactions– Tetracyclines & QuinolonesTetracyclines & Quinolones– MethotrexateMethotrexate– WarfarinWarfarin– Valproic AcidValproic Acid

Usual Dosage:Usual Dosage:– 2 tablets or 30mL q30min to 2 tablets or 30mL q30min to

1 hr up to 8 doses/day1 hr up to 8 doses/day

                 

      

                                                                       

LactobacillusLactobacillus

MOAMOA– Replaces normal intestinal bacteriaReplaces normal intestinal bacteria– Inhibit growth of pathogenic bacteriaInhibit growth of pathogenic bacteria– Enhanced immune responseEnhanced immune response

Adverse EffectsAdverse Effects– FlatulenceFlatulence

Drug InteractionsDrug Interactions– None knownNone known

LactobacillusLactobacillus

WarningsWarnings– Allergy to milk or lactoseAllergy to milk or lactose

ToxicityToxicity– None knownNone known

LoperamideLoperamide

MOA MOA – Inhibits peristalsis via stimulation of Inhibits peristalsis via stimulation of μμ-opiod -opiod

receptor receptor– Antisecretory activityAntisecretory activity

Adverse EffectsAdverse Effects– DizzinessDizziness – – AnorexiaAnorexia– Abdominal painAbdominal pain – – NauseaNausea– Vomiting Vomiting –– FatigueFatigue– Dry mouthDry mouth

LoperamideLoperamide

Drug InteractionsDrug Interactions– None knownNone known

WarningsWarnings– Caution in children < 6 yearsCaution in children < 6 years

Usual Dosage Usual Dosage – 4mg initially then 2mg after each loose 4mg initially then 2mg after each loose

stoolstool– Max dose = 16mg/ 24hrsMax dose = 16mg/ 24hrs

Diphenoxylate & AtropineDiphenoxylate & Atropine

MOAMOA– Inhibits peristalsisInhibits peristalsis

– Results seen in 45-60 minutesResults seen in 45-60 minutes

Drug InteractionsDrug Interactions– Anticholinergic AgentsAnticholinergic Agents

Usual DosageUsual Dosage– 5mg (2 tablets) up to 4 times daily PRN5mg (2 tablets) up to 4 times daily PRN

– Max dose: 20mg/ 24hrsMax dose: 20mg/ 24hrs

Diphenoxylate & AtropineDiphenoxylate & Atropine

Adverse EffectsAdverse Effects

– Nausea Nausea

– VomitingVomiting

– Abdominal painAbdominal pain

– ConstipationConstipation

– Dizziness Dizziness

– DrowsinessDrowsiness

– Headache Headache

– NervousnessNervousness

– MiosisMiosis

– Respiratory Respiratory

depressiondepression

– TachycardiaTachycardia

– Urinary retentionUrinary retention

OctreotideOctreotide

MOAMOA– Blocks release of serotonin and other active Blocks release of serotonin and other active

peptides involved in controlling diarrheapeptides involved in controlling diarrhea– Inhibitory effects on intestinal secretionInhibitory effects on intestinal secretion– Promotes intestinal absorptionPromotes intestinal absorption

Usual DosageUsual Dosage– 50mcg SQ initially then titrate dose based 50mcg SQ initially then titrate dose based

on indication up to 600mcg SQ daily in 2-4 on indication up to 600mcg SQ daily in 2-4 divided dosesdivided doses

OctreotideOctreotide

Adverse EffectsAdverse Effects– Bradycardia (25%)Bradycardia (25%)– Chest PainChest Pain (20%)(20%)– Hyperglycemia Hyperglycemia

(27%)(27%)– Diarrhea Diarrhea (58%)(58%)– Abdominal Abdominal

discomfort discomfort (61%)(61%)– Upper Respiratory Upper Respiratory

infection infection (20%)(20%)– Backache Backache (20%)(20%)

– Flatulence Flatulence (38%)(38%)– Nausea Nausea (61%)(61%)– CholelithiasisCholelithiasis (27%)(27%)– Vomiting Vomiting (21%)(21%)– Injection site pain Injection site pain

(50%)(50%)– DyspneaDyspnea (20%)(20%)– Flu Symptoms Flu Symptoms

(20%)(20%)– Conduction Conduction

abnormalitiesabnormalities (10%)(10%)

Complementary Therapies Complementary Therapies for Diarrheafor Diarrhea

AcerolaAcerola AletrisAletris ChamomileChamomile Chinese Chinese

RhubarbRhubarb MeadowsweetMeadowsweet NutmegNutmeg Oak BarkOak Bark PodophyllumPodophyllum

PulsatillaPulsatilla QuinceQuince TormentilTormentil VeratrumVeratrum Arsenicum Arsenicum

albumalbum Mercurius Mercurius

corrosivescorrosives SulfurSulfur

PRODUCTS USED FOR PRODUCTS USED FOR DIARRHEA DIARRHEA

ANDAND CONSTIPATION CONSTIPATION

Bulk-Forming LaxativesBulk-Forming Laxatives

Examples:Examples:– MetamucilMetamucil®®

– MiralaxMiralax®®

– CitrucelCitrucel®®

MOAMOA– Adds bulk to stoolAdds bulk to stool– Activates peristalsisActivates peristalsis

– Absorbs water – antidiarrhealAbsorbs water – antidiarrheal

Bulk-Forming LaxativesBulk-Forming Laxatives

Adverse EffectsAdverse Effects– FlatulenceFlatulence– Abdominal crampingAbdominal cramping– ObstructionObstruction

Drug InteractionsDrug Interactions– WarfarinWarfarin– DigoxinDigoxin– TetracyclinesTetracyclines– NitrofurantoinNitrofurantoin

Polyethylene GlycolPolyethylene Glycol

MOAMOA– Draws water into stoolDraws water into stool– Increases stool frequency and consistencyIncreases stool frequency and consistency– Results seen in 2 to 4 days Results seen in 2 to 4 days

Usual DosageUsual Dosage– 17gms (1 heaping Tablespoonful)17gms (1 heaping Tablespoonful)

in 8 ounces water dailyin 8 ounces water daily

Polyethylene GlycolPolyethylene Glycol

Adverse EffectsAdverse Effects– Nausea Nausea –– Diarrhea Diarrhea – Abdominal distentionAbdominal distention –– Flatulence Flatulence– Abdominal crampingAbdominal cramping – – ObstructionObstruction– Vomiting Vomiting

Drug InteractionsDrug Interactions– Separate from other meds by at least 1 hourSeparate from other meds by at least 1 hour

CONSTIPATIONCONSTIPATION

EpidemiologyEpidemiology

Most common GI complaint in the USMost common GI complaint in the US Causes ~2 million doctor visits per Causes ~2 million doctor visits per

yearyear Most commonly afflicts women Most commonly afflicts women

(pregnancy), children, and elderly (pregnancy), children, and elderly >65yo>65yo

US has the highest estimated US has the highest estimated prevalence of constipation than any prevalence of constipation than any other country (>4.4 million people)other country (>4.4 million people)

ConstipationConstipation

Clinical DefinitionClinical Definition– <3 stools/week (women)<3 stools/week (women)– <5 stools/week (men)<5 stools/week (men)– ≥≥3 days without a BM3 days without a BM– Straining at defecation >25% of the timeStraining at defecation >25% of the time

Rome CriteriaRome Criteria– Straining at defecation >25% of the timeStraining at defecation >25% of the time– Hard stools >25% of the timeHard stools >25% of the time– Sensation of incomplete bowel evacuation Sensation of incomplete bowel evacuation

>25% of the time>25% of the time– ≤≤2 BMs/week2 BMs/week

EtiologyEtiology

DietaryDietary Sedentary lifestyleSedentary lifestyle PregnancyPregnancy Colorectal disordersColorectal disorders Neurological disordersNeurological disorders Metabolic disordersMetabolic disorders MedicationsMedications

Drug-Induced ConstipationDrug-Induced Constipation

AntacidsAntacids– Aluminum Aluminum – CalciumCalcium

AnticholinergicsAnticholinergics– AntihistaminesAntihistamines– Anti-parkinson’s Anti-parkinson’s – Tricyclic Tricyclic

AntidepressantsAntidepressants

AntidiarrhealsAntidiarrheals CCBsCCBs

Cholestyramine Cholestyramine Sodium Sodium

polystyrene polystyrene sulfonatesulfonate

OpiatesOpiates– MorphineMorphine– OxycodoneOxycodone

Iron Iron NSAIDsNSAIDs DiureticsDiuretics ClonidineClonidine

Laxative AbuseLaxative Abuse

■ Long term useLong term use■ Inability to have a bowel Inability to have a bowel

movement without takingmovement without taking■ Clinical features:Clinical features:

– Severe watery diarrhea frequently occurring Severe watery diarrhea frequently occurring at nightat night

– Abdominal pain, weight loss, nausea, Abdominal pain, weight loss, nausea, vomitingvomiting

– Electrolyte imbalancesElectrolyte imbalances– Steatorrhea, cathartic colon, liver diseaseSteatorrhea, cathartic colon, liver disease

Constipation Treatment Constipation Treatment OptionsOptions

Treat underlying causeTreat underlying cause Nonpharmacologic treatmentNonpharmacologic treatment

– Increase fiber, fluids, and exerciseIncrease fiber, fluids, and exercise– Remove potential offending agentRemove potential offending agent

Drug TherapyDrug Therapy– Stool Softener/Lubricants Stool Softener/Lubricants (Docusate, Mineral Oil)(Docusate, Mineral Oil)– Stimulant Laxatives Stimulant Laxatives (Bisacodyl, Anthraquinones)(Bisacodyl, Anthraquinones)– Osmotic Laxatives Osmotic Laxatives

(Sorbitol, Lactulose, Polyethylene Glycol, (Sorbitol, Lactulose, Polyethylene Glycol, Glycerin)Glycerin)

– Saline Laxatives Saline Laxatives (Magnesium Citrate, MOM)(Magnesium Citrate, MOM)– Misc Agents Misc Agents (Erythromycin)(Erythromycin)

Docusate SodiumDocusate Sodium

MOAMOA– Increases penetration of fluid into stoolIncreases penetration of fluid into stool

– Softens stools to facilitate passageSoftens stools to facilitate passage

Adverse EffectsAdverse Effects– Abdominal crampingAbdominal cramping

– DiarrheaDiarrhea

Usual DosageUsual Dosage– 50 to 360mg / day divided up to 4 times 50 to 360mg / day divided up to 4 times

dailydaily

Mineral OilMineral Oil

MOAMOA– Coats and lubricates stoolsCoats and lubricates stools

– Results seen in 6 – 8 hoursResults seen in 6 – 8 hours

Adverse EffectsAdverse Effects– IncontinenceIncontinence

– Lipid pneumoniaLipid pneumonia

– Impaired absorption of fat-soluble vitaminsImpaired absorption of fat-soluble vitamins

Usual DosageUsual Dosage– 15 to 45mL / day15 to 45mL / day

Mineral OilMineral Oil

Drug InteractionsDrug Interactions– May impair absorption of vitamins A,D,E, May impair absorption of vitamins A,D,E,

and Kand K– Indirectly impair absorption of calcium and Indirectly impair absorption of calcium and

phosphatesphosphates– Do not give with meals (delays gastric Do not give with meals (delays gastric

emptying)emptying)– Avoid use in pregnancyAvoid use in pregnancy– WarfarinWarfarin– Oral contraceptivesOral contraceptives– DigoxinDigoxin– DocusateDocusate

                           

Bisacodyl (Dulcolax)Bisacodyl (Dulcolax)

MOAMOA– Causes peristalsisCauses peristalsis

Adverse EffectsAdverse Effects– Abdominal pain / crampingAbdominal pain / cramping– DiarrheaDiarrhea– HypokalemiaHypokalemia– MalabsorptionMalabsorption

Usual DosageUsual Dosage– 5-15mg (PO) as a single dose 5-15mg (PO) as a single dose – Max dose 30mgMax dose 30mg– 10mg (PR) as a single dose10mg (PR) as a single dose

BisacodylBisacodyl

Drug InteractionsDrug Interactions– AntacidsAntacids– CimetidineCimetidine– FamotidineFamotidine– RanitidineRanitidine– MilkMilk– Proton Pump InhibitorsProton Pump Inhibitors

Senokot (Sennosides)Senokot (Sennosides)

MOAMOA– Increases colonic motilityIncreases colonic motility– Results in 6 – 24 hoursResults in 6 – 24 hours

Adverse EffectsAdverse Effects– Abdominal pain / crampingAbdominal pain / cramping– NauseaNausea– Discoloration of urineDiscoloration of urine

Usual DosageUsual Dosage– 15mg Daily15mg Daily– Max Dose 50mg BIDMax Dose 50mg BID

Castor OilCastor Oil

MOAMOA – Induces peristalsisInduces peristalsis

Adverse EffectsAdverse Effects– HypotensionHypotension– DizzinessDizziness– NauseaNausea– VomitingVomiting– Abdominal pain / crampingAbdominal pain / cramping

Usual DosageUsual Dosage– 15-60mL as a single dose15-60mL as a single dose

SorbitolSorbitol

MOAMOA– Draws water into stoolDraws water into stool– Stimulates evacuationStimulates evacuation

Adverse EffectsAdverse Effects– NauseaNausea– HyperglycemiaHyperglycemia– Electrolyte disturbancesElectrolyte disturbances– Abdominal crampsAbdominal cramps

Usual DosageUsual Dosage– 30-150mL as a single dose30-150mL as a single dose

LactuloseLactulose

MOAMOA– Acidifies fecal contents and softens stool Acidifies fecal contents and softens stool – Causes abdominal distentionCauses abdominal distention– Promotes peristalsisPromotes peristalsis

Adverse EffectsAdverse Effects– Flatulence / DiarrheaFlatulence / Diarrhea– Abdominal distension / crampingAbdominal distension / cramping

Usual DosageUsual Dosage– 10-20gms / day (15-30mL) 10-20gms / day (15-30mL) – Max dose 60mL in 1-2 divided doses Max dose 60mL in 1-2 divided doses

GlycerinGlycerin

MOAMOA– Draws fluid into the rectum to induce a Draws fluid into the rectum to induce a

bowel movementbowel movement– Induces peristalsisInduces peristalsis

Adverse EffectsAdverse Effects– Rectal irritationRectal irritation

Usual DosageUsual Dosage– 1 suppository PR 1-2 times / day PRN1 suppository PR 1-2 times / day PRN– 5-15mL PR daily PRN as an enema5-15mL PR daily PRN as an enema

Saline LaxativesSaline Laxatives

Adverse EffectsAdverse Effects– NauseaNausea– VomitingVomiting– Electrolyte Electrolyte

disturbancesdisturbances– FlatulenceFlatulence

– BloatingBloating– Abdominal Abdominal

crampingcramping– DiuresisDiuresis– DehydrationDehydration

MOAMOA– Increases colonic volumeIncreases colonic volume

– Stimulates intestinal motilityStimulates intestinal motility

– Results in 30 min to 3 hrs (PO) or 5 min (PR)Results in 30 min to 3 hrs (PO) or 5 min (PR)

Saline LaxativesSaline Laxatives

Drug InteractionsDrug Interactions– AspirinAspirin

– AtenololAtenolol

– Bismuth subsalicylateBismuth subsalicylate

– CefpodoximeCefpodoxime

– FluroquinolonesFluroquinolones

– HyoscyamineHyoscyamine

– DigoxinDigoxin

– IronIron

– AzolesAzoles

– SucralfateSucralfate

– TetracyclinesTetracyclines

– TiclopidineTiclopidine

– ZalcitabineZalcitabine

– WarfarinWarfarin

Complementary Therapies for Complementary Therapies for ConstipationConstipation

Aloe veraAloe vera BuckthornBuckthorn ButternutButternut Cascara sagrada Cascara sagrada

barkbark ChicoryChicory DandelionDandelion Dong quaiDong quai FeverfewFeverfew FlaxseedFlaxseed

Fo-tiFo-ti LicoriceLicorice Plantago ovata Plantago ovata

seedseed RhubarbRhubarb Rose hipsRose hips SarsaparillaSarsaparilla Senna leavesSenna leaves SunflowerSunflower Yellow dockYellow dock

IMPLICATIONS FOR IMPLICATIONS FOR PHYSICAL PHYSICAL

THERAPISTSTHERAPISTS

Disease State Disease State ConsiderationsConsiderations

Drugs used do not directly influence Drugs used do not directly influence rehabilitationrehabilitation

Diarrhea and constipation common in Diarrhea and constipation common in nursing home and elderly patientsnursing home and elderly patients

Constipation is a known adverse Constipation is a known adverse effect of pain medicationseffect of pain medications

Frequent use of laxatives in Frequent use of laxatives in hospitalized patientshospitalized patients

Elderly preoccupation with bowel Elderly preoccupation with bowel habitshabits

Social considerationsSocial considerations

Common Adverse Effects of Common Adverse Effects of Diarrhea and ConstipationDiarrhea and Constipation

CrampingCramping

BloatingBloating

FlatulenceFlatulence

DiarrheaDiarrhea

ConstipationConstipation

FatigueFatigue

DehydrationDehydration

Effects on Physical Effects on Physical TherapyTherapy

Positive effectsPositive effects– Very treatable conditionsVery treatable conditions– Medications available OTCMedications available OTC– Most medications = cheapMost medications = cheap– Symptom control - PRNSymptom control - PRN

Areas for concernAreas for concern– EmbarrassmentEmbarrassment– Scheduling of sessionScheduling of session– DehydrationDehydration– ObstructionObstruction

QUESTIONS?QUESTIONS?