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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 [email protected]@purdue.edu
April 27, 2009April 27, 2009
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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
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DIARRHEADIARRHEA
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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
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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
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EtiologyEtiology
InfectionInfection
DietDiet
MedicationsMedications
Gastrointestinal diseasesGastrointestinal diseases
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Infectious CausesInfectious Causes
ViralViral
BacterialBacterial– ShigellaShigella– SalmonellaSalmonella– E. coliE. coli– CampylobacterCampylobacter
SuperinfectionSuperinfection
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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
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Medication CausesMedication Causes
AntibioticsAntibiotics– Broad spectrumBroad spectrum– AugmentinAugmentin– ErythromycinErythromycin– ClindamycinClindamycin
AntihypertensivAntihypertensiveses– AtenololAtenolol– MethyldopaMethyldopa
ChemotherapyChemotherapy
LaxativesLaxatives NSAIDsNSAIDs AntacidsAntacids MiscMisc
– ColchicineColchicine– DigoxinDigoxin– PotassiumPotassium– QuinidineQuinidine
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Diarrhea Treatment OptionsDiarrhea Treatment Options
AdsorbentsAdsorbents AntisecretoryAntisecretory
– Bismuth subsalicylateBismuth subsalicylate– Enzymes (lactase)Enzymes (lactase)
AntimotilityAntimotility– LoperamideLoperamide– DiphenoxylateDiphenoxylate– OpioidsOpioids
Misc AgentsMisc Agents– OctreotideOctreotide
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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
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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
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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
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LactobacillusLactobacillus
WarningsWarnings– Allergy to milk or lactoseAllergy to milk or lactose
ToxicityToxicity– None knownNone known
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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
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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
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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
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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
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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
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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%)
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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
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PRODUCTS USED FOR PRODUCTS USED FOR DIARRHEA DIARRHEA
ANDAND CONSTIPATION CONSTIPATION
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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
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Bulk-Forming LaxativesBulk-Forming Laxatives
Adverse EffectsAdverse Effects– FlatulenceFlatulence– Abdominal crampingAbdominal cramping– ObstructionObstruction
Drug InteractionsDrug Interactions– WarfarinWarfarin– DigoxinDigoxin– TetracyclinesTetracyclines– NitrofurantoinNitrofurantoin
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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
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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
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CONSTIPATIONCONSTIPATION
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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)
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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
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EtiologyEtiology
DietaryDietary Sedentary lifestyleSedentary lifestyle PregnancyPregnancy Colorectal disordersColorectal disorders Neurological disordersNeurological disorders Metabolic disordersMetabolic disorders MedicationsMedications
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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
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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
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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)
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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
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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
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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
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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
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BisacodylBisacodyl
Drug InteractionsDrug Interactions– AntacidsAntacids– CimetidineCimetidine– FamotidineFamotidine– RanitidineRanitidine– MilkMilk– Proton Pump InhibitorsProton Pump Inhibitors
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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
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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
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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
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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
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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
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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)
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Saline LaxativesSaline Laxatives
Drug InteractionsDrug Interactions– AspirinAspirin
– AtenololAtenolol
– Bismuth subsalicylateBismuth subsalicylate
– CefpodoximeCefpodoxime
– FluroquinolonesFluroquinolones
– HyoscyamineHyoscyamine
– DigoxinDigoxin
– IronIron
– AzolesAzoles
– SucralfateSucralfate
– TetracyclinesTetracyclines
– TiclopidineTiclopidine
– ZalcitabineZalcitabine
– WarfarinWarfarin
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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
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IMPLICATIONS FOR IMPLICATIONS FOR PHYSICAL PHYSICAL
THERAPISTSTHERAPISTS
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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
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Common Adverse Effects of Common Adverse Effects of Diarrhea and ConstipationDiarrhea and Constipation
CrampingCramping
BloatingBloating
FlatulenceFlatulence
DiarrheaDiarrhea
ConstipationConstipation
FatigueFatigue
DehydrationDehydration
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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
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QUESTIONS?QUESTIONS?