Presentation on theme: "Treatment of constipation and diarrhea"— Presentation transcript:
1Treatment of constipation and diarrhea LectureTreatment of constipation and diarrhea
2ConstipationDefinition: Chronic constipation is a disorder characterized by unsatisfactory defecation that results from infrequent stools, difficult stool passage, or both over a time period of at least 12 weeks
3Causes of constipation 1. In most cases of chronic constipation, no specific cause is found (chronic idiopathic constipation)2. Lifestyle Factors a) Inadequate fluid intake b) Decreased food intake c) Inappropriate bowel habits d) Immobility3. MedicationsEndocrine and Metabolic disorders a) Hypothyroidism b) Hypercalcemiac) Hypokalemiad) Pheochromocytoma
4Causes of constipation Neurologic a) Parkinson's disease b) Multiple sclerosis c) Spinal lesions d) Damage to sacral parasympathetic nerves e) Autonomic neuropathy (Diabetes mellitus6. Psychological a) Depression b) Eating disorders (e.g., anorexia nervosa)7. GI disorders:a) Irritable bowel syndromeb) Diverticulitisc) Hemorrhoids and anal fissuresd) Tumorse) Herniaf) Hirschsprung’s disease.8. Pregnancy
5Drugs causing constipation NSAIDs (inhibit prostaglandin synthesis)Opiates: Orally administered opiates have greater inhibitory effect than parenterally administered agentsAnticholinergicsAntihistaminesAntiparkinsonian agents (e.g., benztropine or trihexyphenidyl)PhenothiazinesTricyclic antidepressantsAntacids containing calcium carbonate or aluminum hydroxideBarium sulfateCalcium channel blockersClonidineDiuretics (nonpotassium-sparing)Ganglionic blockersIron preparationsMuscle blockers (D -tubocurarine, succinylcholine)
6Mechanism of drug-induced constipation Drugs with anticholinergic action (e.g. first generation antihistaminic drugs, tricyclic antidepressants, benztropine, phenothiazines,..):GIT motility is under parasympathetic (cholinergic) control. Parasympathetic stimulation → ↑motilityDrugs with anti-cholinergic effect (whether it is their main action or a side effect) →↓motility → constipation
7Mechanism of drug-induced constipation 2. Opioids: Opioids cause constipation by: A) Increasing the smooth muscle tone, suppressing forward peristalsis, raising sphincter tone at the ileo-cecal valve and anal sphincter. This delays passage of feces through the GIT → increase in absorption of electrolytes and water in the small intestine and colon → constipation B) Reducing sensitivity to rectal distension.
8Mechanism of drug-induced constipation Electrolyte disturbance as hypokalemia or hypercalcemiaLaxative abuse (leads to atonic intestine)
9Treatment of constipation General measures:Increase the amount of fiber consumed daily fruits, vegetables, bran and cereals).Definition: Fiber is that part of food that resists enzymatic digestionEffect of fiber: Fiber reaches the colon unchanged.Colonic bacteria → Fermentation →Short-chain fatty acids (→ prokinetic effect)Increased bacterial mass (→ increased stool bulk).Fiber that is not fermented → osmotic effect →increases stool bulk.Increasing fluid intake.Regulation of bowel habitsRegular exercise.Treatment of the causeFor drug causes of constipation, a non constipating alternatives should be used. If no alternatives exist, lower the dose.
10Treatment of constipation If general measures alone are inadequate or not applicable (e.g., because of old age), they may be supplemented with bulk-forming agents, osmotic laxatives or stimulant laxatives.When stimulant laxatives are used, they should be administered at the lowest effective dosage and for the shortest period of time to avoid abuse
11Definitions Laxatives Cathartics Drugs that help evacuation of formed fecal material from the rectumDrugs that help evacuation of unformed, usually watery fecal material from the entire colon.
12Drug treatment of constipation (laxatives) General indications:Fecal impactionConstipation associated with illness, surgery, pregnancy or poor dietDrug-induced constipationConditions where bowel strain is undesirablePreparation for surgery or investigations involving the GIT (e.g. sigmoidoscopy)
13Classification of laxatives Bulk-forming laxativesStimulant laxativesOsmotic laxativesEmollient laxatives (fecal softeners)Lubricants
141- Bulk-forming agents (active after 12-36h) Drugs: (taken as granules, powders or tablets)MethylcelluloseBranPsylliumMechanism of action of bulk-forming agents:They increase stool bulk and water content (make stools bulky (→ stimulate peristalsis) and soft → easy to pass) (similar to natural fiber)
15Bulk-forming agents (cont.) (active after 12-36h) Indications:They are the first-line treatment of constipationConditions where dietary intake of fibers can not be increasedPrecautions:Adequate fluid intake to avoid intestinal obstructionAdverse effects of bulk-forming laxatives:Abdominal distension (due to fermentation).Intestinal obstruction when not consumed with sufficient fluidContraindications:Atony of the colonIntestinal obstructionFecal impaction (should be corrected before administration of fiber)Immobility
162. Stimulant (irritant) laxatives Dosage forms::BisacodylOral and rectal suppositorySodium picosulfateOralSenna and CascaraCastor oil
17Mechanism of action and classification of stimulant (irritant) laxatives They are given in an inactive form → hydrolyzed in the GIT into active forms → GIT irritation → modify permeability of the mucosal cells → ↑ fluid and electrolyte secretion in the GIT → distension → evacuation of soft (or liquid) bulky stools. They probably cause direct stimulation of the enteric nerves.According to the site of GIT irritation they are classified into:Small bowel irritant (hydrolysed in the small intestine by the action of lipases): castor oilLarge bowel irritants (hydrolyzed by colonic bacteria):Bisacodyl and Sodium picosulfateSenna and Cascara
18Stimulant (irritant) laxatives (cont.) Indications of large bowel irritants:Bisacodyl and Sodium picosulfateSenna and CascaraPrevention of straining at stool following surgery, myocardial infarction or strokePainful diseases of the anus, e.g., fissure or hemorrhoids.
19Stimulant (irritant) laxatives (cont.) 1. Bisacodyl and sodium picosulfate:Dosage forms:Oral (the laxative effects after a dose occurs after 6 – 12 hours; taken at bedtime, it will produce its effect the next morning)Rectal suppository (for bisacodyl only – the laxative effect occurs within 30 to 60 min.)Indications: (also for cascara and senna)Should not be used for more than 10 consecutive days (due to the possibility of developing atonic colon)Preparation before diagnostic procedures involving the GIT
20Stimulant laxatives (cont) Bisacodyl and sodium picosulfate (cont)Adverse effects:Abdominal cramps after each doseOver dosage → catharsis and fluid and electrolyte disturbances.Can damage mucosa and cause inflammation in the colon.Atonic colon (following years of use)Contraindications:Intestinal obstruction
21Stimulant laxatives (cont.) 2. Cascara and SennaDosage forms:Oral (the laxative effects after a dose occurs after 6 – 12 hours; taken at bedtime, it will produce its effect the next morning)Adverse effects of long-term use;Abdominal cramps after each doseOver dosage → catharsis and fluid and electrolyte disturbances.Pigmentation of the colonic mucosa (melanosis coli). (4 – 9 months of use)Atonic colon (years of use)Contraindications:Breast feeding (active compounds are absorbed to a variable degree from the colon and excreted in breast milk)Intestinal obstruction
22Stimulant laxatives (cont.) 3. Castor Oil:Dosage form:Oral in a liquid form (laxative effect occurs after 1 – 3h)Adverse effects:Unpleasant tasteDamage to intestinal epithelium and enteric neuronsUses:Strong purgative → evacuation of the bowel before surgery and diagnostic proceduresContraindications:Intestinal obstruction
233- Osmotic laxatives1. Saline laxatives (have cathartic action in large doses)Magnesium salts (sulfate, hydroxide or citrate)Sodium phosphateMechanism of action:Poorly absorbed → water retention (osmotic effect) →soft bulky stools → ↑peristalsis → relief of constipationMagnesium-containing laxatives may stimulate the release of cholecystokinin, which leads to intraluminal fluid and electrolyte accumulation and to increased intestinal motilityUses:Enema (causes bowel evacuation after 30 min)Oral forms (cause bowel evacuation after 2-5h)Both forms are used for intestinal evacuation before abdominal radiological procedures, sigmoidoscopy or surgery (cathartics)
25Osmotic laxatives (cont.) 2. Non-digestible sugars and alcoholsLactulose (disaccharide of galactose and fructose that resists intestinal disaccharidase activity)Sorbitol (monosaccharide)Mechanism of action:Lactulose → metabolized by colonic bacteria into short chain fatty acids → osmotic effect → stimulate propulsive activityAdverse effects:Abdominal distentionDiarrhea
26Osmotic laxatives (cont.) Uses:Lactulose: (24-48h)Used for treatment of hepatic encephalopathy (↓ blood ammonia by lowering fecal pH →↓growth of ammonia-producing bacteria and conversion of ammonia in the colon to ammonium ion).Constipation in the elderly patientAlternative for acute constipationSorbitol:Chronic constipation
27Osmotic laxatives (cont.) 3. Polyethylene Glycol-Electrolyte Solutions.Mechanism of action:Poorly absorbed, and retained in the lumen of the gut → osmotic effect → increase water content of stools.Uses:Cathartic: high volume of aqueous polyethylene glycol - isotonic electrolyte solution (4 liters), used for colonic cleansing for radiological, surgical, and endoscopic procedures . The isotonic electrolyte solution avoids transfer of ions across the intestinal wall. The osmotic activity of the PEG molecules retains the added water .Laxative: small oral doses of polyethylene glycol used for the short-term treatment of occasional constipation in difficult cases (2 weeks or less). This preparation does not contain electrolytes, so larger volumes may represent a risk for ionic shifts. Onset of effect: 2- 4 days
28Osmotic laxatives (cont.) 4. GlycerinDosage form:Suppository (laxative effect > 30 min.)Mechanism of action:Osmotic effect in the rectum.Adverse effects:Occasional rectal irritation.Uses:Intermittent constipation in children.
294- Fecal softeners/emollient laxatives Docusate salts (sodium or calcium) (weak laxatives)Mechanism of action:Reduces surface tension of stools → increases penetration of fluids into feces → soft bulky stoolsStimulate intestinal fluid and electrolyte secretion (by altering mucosal permeability)Dosage forms:Oral form (active within 1-3 d)Rectal form has a rapid onset of action but is contraindicated in hemorrhoids and anal fissure.Uses:Used in hospitalized patients following myocardial infarction or surgery, when straining at defecation should be avoided but activity and fluid intake may be restricted.They have little role in the management of chronic constipation, except when the patient is fluid-restricted or incapable of increasing his or her dietary fiber or activity.
30Fecal softeners/emollient laxatives (cont.) 2. Mineral oil:Mechanism of action:Indigestible and with minimal absorption. Coat stool and allow easier passage.Inhibit colonic absorption of water → increasing stool weight and decrease stool transit time.Dosage forms:Oral or rectal. Laxative effect is noted after 2 or 3 days of oral use.Indications:Similar to docusates: to maintain a soft stool and avoid straining for relatively short periods of time (a few days to 2 weeks),
31Fecal softeners/emollient laxatives (cont.) Mineral oil:Adverse effects:May be absorbed systemically → foreign-body reaction in lymphoid tissue.May be aspirated (in debilitated or recumbent patients) → lipoid pneumoniaDecreases absorption of fat-soluble vitamins (A, D, E, and K)When given orally, mineral oil may leak from the anal sphincter.
32New agents Lubiprostone Mechanism of action: Opening of chloride channels locally in the GI luminal epithelium, which stimulates chloride-rich intestinal fluid secretion and shortens GI transit timeUses:Chronic idiopathic constipation in adultsAdverse effects:HeadacheDiarrhea, and nausea, as a result of delayed gastric emptying.
34Laxative abuse syndrome Mechanism:1. With the use of strong purgatives, the colon may be so thoroughly evacuated that a bowel movement may not occur normally until a few days later. This delay reinforces the need for more laxative. Eventually the patient may require daily laxatives to maintain bowel function.
36DiarrheaDefinition:diarrhea is an increased frequency and decreased consistency of fecal discharge as compared to an individual’s normal bowel pattern.Classification:Acute <14 dPersistent >14 dChronic > 30 d
37Causes of diarrheaInfectious (viral or bacterial)Non infectious
38Pathophysiologic mechanisms of diarrhea Type of diarrheaA stimulating substance (e.g. a laxatives or a bacterial toxin) changes active ion transport in the intestine by either decreased sodium absorption or increased chloride secretionSecretory diarrheaChange in intestinal motility (e.g by overgrowth of bacteria)Altered intestinal motilityIncrease in intestinal luminal osmolarity due to poorly absorbed substancesOsmotic diarrheaIncrease in tissue hydrostatic pressure due to inflammatory diseases of the GITExudative adiarrhea
41Treatment of diarrhea Non-pharmacologic therapy: Dietary management: Discontinue consumption of solid foods and dairy products for 24 h (valuable in osmotic diarrhea)For patients who are experiencing nausea and/or vomiting, a mild, digestible, low-residue diet should be administered for 24 hours.If vomiting is present and uncontrollable with antiemetics, nothing is taken by mouth. As bowel movements decrease, a bland diet is begun.Rehydration and maintenance of water and electrolytes
42Treatment of dehydration Increase fluid intake (fruit juice – contain glucose and potassium)Oral rehydration solution (ORS). The WHO formula contains glucose, sodium, potassium, chloride and bicarbonate in an isotonic fluid.Glucose concentrations between 80 – 120 mmol/L are needed to optimize sodium absorption in the small intestine. Glucose concentration > 160 mmol/L will cause osmotic diarrhea.Sodium concentration = 75 mmol/L (higher concentrations may cause hypernatremia)Dose in mild/moderate diarrhea for adults: 2L/first 24 h followed by 200 ml per each loose stool
43Antidiarrheal agents Indications of antidiarrheal agents: Patients with mild to moderate acute diarrheaControl chronic diarrhea caused by IBS or IBDContraindications:Patients with bloody diarrhea, fever or systemic toxicity (risk of worsening of the underlying condition)Discontinued in patients whose diarrhea is worsening despite therapy
44Treatment of diarrhea Pharmacologic therapy: Drugs used for the treatment of diarrhea includeAntimotility agentsAdsorbentsAntisecretory compoundsAntibioticsEnzymesIntestinal microflora.
45Antimotility agents (opioids) Opioids agonists:Action in the GIT (mediated by binding to opioid receptors)Increase segmentation and a decrease propulsive movement → ↑ intestinal transit time → ↑ absorption of water and electrolyte → feces become more solidAntisecretory↑ tone of the internal anal sphincter↓ response to the stimulus of a full rectum (by their central action)
46Antimotility agents (cont) Mechanism of opioid action: Inhibition of presynaptic cholinergic nerves in the submucosal and myenteric plexuses
47Opioiods - Diphenoxylate Opioid agonist that has no analgesic properties in standard doses. Higher doses have central opioid actions. Used in combination with a subtherapeutic dose of atropine (to prevent abuse)Contraindications:Children below 2 y (toxicity at lower doses than adults)Obstructive jaundiceDrug interactions:Potentiate the effects of CNS depressantsCo-administration with MAO inhibitors→ hypertensive crisesAdverse effects:Caused by the atropine in the preparation and include anorexia, nausea, pruritus, dizziness, and numbness of the extremities.Prolonged use of high doses may cause dependence
48Opioids - LoperamideOpioid agonist that does not cross the blood-brain barrier and has no analgesic properties and no potential for addiction Adverse effects: Abdominal pain and distention, constipation, dry mouth, hypersensitivity, and nausea and vomiting.
49Adsorbents1. Kaolin and Pectin: Kaolin (hydrated magnesium aluminum silicate), often combined with pectin (indigestible carbohydrate). Mechanism of action: Adsorb bacterial toxins and fluid Indications: Acute diarrhea (given after each loose bowel movement) Adverse effects: Not absorbed and has no adverse effects.
50Adsorbents (cont) 2. Bismuth subsalicylate: Insoluble complex of bismuth and salicylateMechanism of action:Bismuth: antimicrobialSalicylate: antisecretoryAdverse effects: blackening of tongue and stools
51Octreotide (somatostatin analogue) Mechanism of the anti-diarrheal action:1. It inhibits the secretion of many GIT hormones, including gastrin, cholecystokinin, glucagon, insulin, secretin, pancreatic polypeptide, vasoactive intestinal peptide, and 5-HT3.2. It reduces intestinal fluid secretion and pancreatic secretion.3. It slows gastrointestinal motility and inhibits gallbladder contraction.4. It induces direct contraction of vascular smooth muscle, leading to a reduction of portal and splanchnic blood flow.
52Octreotide (somatostatin analogue) Indications in diarrhea:Secretory diarrhea due to carcinoid tumor2. Diarrhea due to vagotomy3. Diarrhea caused by short bowel syndrome or AIDS.4. Octreotide has been used in low doses to stimulate small bowel motility in patients with small bowel bacterial overgrowth or intestinal pseudoobstruction secondary to scleroderma.
53Octreotide (somatostatin analogue) Adverse effects:Steatorrhea leading to fat-soluble vitamin deficiency (due to impaired pancreatic secretion)Nausea, abdominal pain, flatulence, and diarrhea due to alterations in gastrointestinal motilityGall bladder sludge, gall stones or cholecystitis due to inhibition of gallbladder motilityHyperglycemiaProlonged treatment may result in hypothyroidism. Octreotide also canBradycardia.
54Antimicrobials Indications: Patients with +ve stool culture Patients presented with dysenteryPatients with suspected exposure to bacterial infection → Quinolones (as ciprofloxacin)