Walters-Laxatives

Front 1

list and describe the dietary fiber and bulk forming laxatives

Back 1

1. PSYLLIUM-consists of seed husks from the herb plantago; also used to ↓ LDL cholesterol by to binding bile acids
2. METHYLCELLULOSE
3. POLYCARBOPHIL-nonabsorbed polyacrylic resin that absorbs H2O; is a Ca2+ salt, so avoid if taking tetracycline (will chelate)

Front 2

describe the MOA and side effects of dietary fiber and bulk forming laxatives

Back 2

MOA: absorb H2O and ions thus softening the stool and increasing its bulk; increase in bulk causes intestinal distention that stimulates peristalsis (better for prevention than acute constipation)
note-take w/ H2O in divided doses to avoid impaction--> obstruction, choking or asphyxiation
Side effects:
1. Do not use if obstructive bowel disease, strictures or Crohn’s disease (could cause perforation)
2. significantly decrease Rx absorption either by adsorption or by reducing transit time secondary to ↑ peristalsis

Front 3

describe the saline laxatives

Back 3

MOA:
1. create osmotic force that traps fluid in intestinal lumen (H2O follows solute)--> softens stool and distends intestine--> peristalsis
2. Mg2+ stimulates CCK release--> increases intestinal secretions & motility
1. MAGNESIUM HYDROXIDE
2. MAGNESIUM CITRATE
CAUTION: Chronic use--> HYPERMAGNESEMIA--> muscle weakness, respiratory paralysis, EKG changes, sedation & confusion due to competition w/ Ca2+ by Mg2+
3. Na Phosphate/Biphosphate-hyperphosphatemia--> hypocalcemia
Class side effect-dehydration

Front 4

list the osmotic laxatives

Back 4

1. LACTULOSE
2. GLYCERIN (suppositories)-contains Na+ stearate that causes local irritation; can also burn & cause slight hemorrhaging of rectal mucosa
3. POLYETHYLENE GLYCOL-ELECTROLYTE SOLUTION-taken prior to a colonoscopy to clean out the GI tract; isotonic solution of NaSO4, NaHCO3, NaCl & KCl in polyethylene glycol (PEG)

Front 5

describe lactulose

Back 5

MOA:
1. metabolized to galactose + fructose by colonic bacteria--> metabolized to lactate, acetate & formate that contribute to the osmotic effect
2. ↓ luminal pH which stimulates GI secretions & motility
OTHER USE: treat hepatic encephalopathy associated with severe liver disease w/ an accumulation of NH3
MOA: ↓ in pH caused by lactulose ionizes NH3--> NH4+ which becomes trapped in the gut and excreted (Ion-Trapping)
SIDE-EFFECTS:
1. flatulence & cramping
2. Diarrhea--> dehydration--> hypernatremia & hypokalemia (dehydration stimulates aldosterone release)

Front 6

describe BISACODYL

Back 6

stimulant laxative
MOA:
a) stimulates mucosa & myenteric neurons--> peristalsis
b) inhibits Na+-K+-ATPase--> salt/H2O accumulation in lumen
c) ↑s synthesis of PGs & cAMP--> ↑ fluid/electrolyte secretion
Uses:
1. OTC laxative
2. bowel evacuation for diagnostic tests
Side effects:
1. abdominal cramps
2. Chronic use-->loss of normal bowel function, electrolyte disturbances, malabsorption & weight loss
3. Years of misuse--> cathartic colon (atony & dilation) with loss of haustra resembling ulcerative colitis

Front 7

describe surfactants

Back 7

anionic soaps that soften stool & prevent straining
MOA:
1. ↓ surface tension between intestinal H2O & the feces--> ↑ mixing of GI contents
2. stimulate intestinal fluid & electrolyte secretion
Use: weak laxatives intended to keep things running smoothly more than to treat acute constipation
1. DOCUSATE Na+ (avoid if CHF or hypertension)
2. DOCUSATE Ca2+
Side effects: ↑ absorption of other Rxs--> increased Rx toxicity

Front 8

describe LUBIPROSTONE

Back 8

metabolite of PGE1 used for chronic idiopathic constipation
MOA: activates Cl- channel in the apical membrane of the intestines--> ↑ secretions & motility
Side effects:
1. headache
2. nausea

Front 9

describe the MOA, side effects, and contraindications of opioids

Back 9

MOA:
1. Hyperpolarize myenteric & submucosal neurons--> ↓ ACh release--> decreases peristalsis by longitudinal smooth muscles
2. Direct effect on smooth muscles to ↑ resting tone causing spasms instead of organized contractions that propel the contents forward
3. Contraction of circular smooth muscles to ↑ segmentation and thus impede progression of contents
4. Inhibit release of VIP--> ↓ salt & H2O secretion by the mucosa
NET EFFECT: Slows transit; increased contact time between the luminal fluid & epithelial cells--> increases fluid reabsorption & thus ↑ viscosity of intestinal contents
Side-effects:
1. constipation
2. high doses--> CNS effects & anticholinergic effects of atropine
Contraindications:
1. infectious diarrhea b/c they inhibit expulsion of offending microbes
2. inflammatory bowel diseases (ulcerative colitis)--> excessive dilation of colon from retention of fecal matter--> TOXIC MEGACOLON--> ↑ risk of bowel perforation

Front 10

list and describe the opioid agents

Back 10

1. DIPHENOXYLATE + ATROPINE (added to discourage abuse)
CAUTION: Limited use in children due to increased penetration across immature blood brain barrier--> CNS depression
2. DIFENOXIN-active metabolite of diphenoxylate
3. LOPERAMIDE-decreased risk of abuse (no atropine needed)

Front 11

describe BISMUTH SUBSALICYLATE (Pepto-Bismol)

Back 11

indicated for infectious & inflammatory diarrhea
hydrolyzed in the stomach to
a) BISMUTH OXYCHLORIDE (bactericidal)
b) SALICYLATE (antisecretory & antiinflammatory)
Side effects:
1. can turn tongue & stool black (not blood in stool)
2. avoid use in kids after smallpox or influenza b/c of association of salicylates with Reye's syndrome

Front 12

list drugs given for diarrhea in inflammatory bowel disease and AIDS

Back 12

1. SULFASALAZINE
2. MESALAMINE-marketed w/out sulfapyridine thus eliminating certain side effects; enteric coated and releases 5-ASA only at a pH > 7 (terminal ileum and colon)
3. OLSALAZINE
FDA: ↑ risk of bleeding when used w/ salicylates or low molecular weight heparin after neuraxial anesthesia; ↑ risk of myelosuppression when used w/ cancer drugs 6-mercaptopurine or thioguanine
4. BALSALAZIDE
5. OCTREOTIDE

Front 13

describe SULFASALAZINE

Back 13

5-aminosalicylic acid (5-ASA) linked by an azo bond to sulfapyridine (azo link prevents absorption in the stomach & small intestine); remains in the GI tract where the azo bond is cleaved by colonic bacteria to 5-ASA and sulfapyridine
MOA:
1. 5-ASA (mesalamine)
a. inhibits COX and lipoxygenase (inhibition of lipoxygenase contributes to the antidiarrheal effect)
b. Acts through PPARγ to inhibit transcription of genes coding for NF-κB
2. Sulfapyradine-no major therapeutic effects
Side effects:
1. sulfapyradine is absorbed systemically and is responsible for most of the systemic side effects:
a. nausea
b. fever
c. arthralgias
d. rashes
e. agranulocytosis
2. Sulfasalazine ↓ folate absorption (might need to supplement)

Front 14

describe OCTREOTIDE

Back 14

synthetic analog of somatostatin given SC often following surgical drainage procedures
MOA:
1. inhibits secretion of VIP
2. inhibits contractility of longitudinal smooth muscles
Side effects:
FDA warning:
a. depot formulation used in treating acromegaly can inhibit gallbladder contractility & ↓ bile secretion--> sludge (pseudolithiasis) characterized by nausea, anorexia, epigastric distress and colic
b. alters balance between insulin, glucagon & GH--> hyper- or hypoglycemia
c. suppresses secretion of TSH--> hypothyroidism

Front 15

describe the miscellaneous drugs used for treating diarrhea

Back 15

1. RIFAXIMIN-nonabsorbed antibiotic for TRAVELER'S DIARRHEA (E. coli); no systemic side effects
2. CLONIDINE-antihypertensive medication whose side effects include constipation by stimulating α2A heteroreceptors on myenteric and submucosal cholinergic neurons; subsequent ↓ in ACh release causes intestinal smooth muscle to relax--> inhibiting peristalsis -> ↑ time for Na+ and H2O reabsorption
3. CALCIUM CHANNEL BLOCKERS-cause constipation as an unwanted side effect

Front 16

describe SIMETHICONE

Back 16

OTC medication that decreases the surface tension between gas bubbles allowing them to coalesce; in doing so, some gas gradually escapes

Front 17

describe 5-HT3 antagonists

Back 17

end in 'setron'
1. ALOSETRON
FDA Black Box Warning-Serious GI side effects, including ischemic colitis and complications of constipation, have led to hospitalizations, transfusions, surgery & death!
USE: Only in women w/ severe diarrhea-predominant irritable bowel syndrome who haven’t responded to other therapy
2. DOLASETRON
uses:
a. IV low dose for postoperative nausea & vomiting
b.orally in higher doses for chemotherapy induced nausea and vomiting
Side effects: higher doses ↑ the risk of Torsades (prolongs the Q-T & P-R intervals and the QRS complex)
3. GRANISETRON
4. ONDANSETRON
Side effects:
a. headaches
b. ↑ the risk of prolonging the Q-T interval--> Torsades
5. PALONOSETRON-nausea & vomiting w/ cancer chemotherapy
note-these agents work best when used w/ DEXAMETHASONE

Front 18

describe the mixed D2/5HT3 antagonists

Back 18

1. METOCLOPRAMIDE-used for chemotherapy- & radiation-induced vomiting & for nausea w/ pregnancy
MOAs:
a. PROKINETIC agent that increases ACh release--> stimulating coordinated GI motility & gastric emptying
b. blocks DA D2 receptors--> ↑ ACh release--> ↑ GI motility
c. acts in the upper GI tract to ↑ lower esophageal sphincter tone & stimulates antral & small intestine contractions
PROKINETIC USES:
a. esophageal reflux
b. increase passage of barium contrast media
c. facilitate GI intubation
Side effects:
a. tardive dyskinesia-from blocking DA D2 receptors in the basal ganglia
b. most common cause of Rx-induced movement disorders!
2. TRIMETHOBENZAMIDE-for chemotherapy- & radiation-induced emesis

Front 19

describe D2 antagonists

Back 19

A. PHENOTHIAZINES:
Side effects:
i. Orthostatic-hypotension (α-block)
ii. sedation
note-tolerance usually develops to these effects
ends in 'azine'
1. CHLORPROMAZINE
2. PERPHENAZINE
3. PROCHLORPERAZINE-causes a high incidence of dystonias
4. PROMETHAZINE-has high antihistaminic activity
B) DROPERIDOL: BUTYROPHENONE used for nausea & vomitring due to general anesthetics or chemotherapy
CAUTION: prolongs Q-T interval--> Torsades

Front 20

describe antihistamines

Back 20

used for nausea & vomiting due to MOTION SICKNESS
1. DIPHENHYDRAMINE (Benadryl)
2. DIMENHYDRINATE (Dramamine)-contains equimolar amounts of diphenhydramine + chlorotheophylline (antiemetic activity is due to diphenhydramine)
3. MECLIZINE (Dramamine Less Drowsy Formula)-dimenhydrinate replaced w/ meclizine

Front 21

describe ANTICHOLINERGIC SCOPOLAMINE

Back 21

best used in treating motion sickness
side-effects:
1. sedation
2. dry mouth
3. blurred vision

Front 22

describe cannabinoids

Back 22

1. DRONABINOL-synthetic Δ9-THC
Side effects:
a. dysphoria
b. hallucinations
c. sedation
d. ↓ seizure threshold
note-generally reserved for refractory cases
2. NABILONE-synthetic cannabinoid agonist at the CB1 receptor; long acting and is thus given twice daily for nausea and vomiting due to cancer chemotherapy in patients that do not respond to other therapy

Front 23

describe benzodiazepines and aprepitant

Back 23

1. BENZODIAZEPINES-↓anxiety & enhance the antiemetic effects of other Rxs
2. APREPITANT-centrally acting antagonist of Substance P NK1 receptors
used for chemotherapy-induced nausea & vomiting in combination w/ other Rxs
Side effect: ↓ plasma levels of oral contraceptives so be careful if you don’t want to become pregnant!