Seagers Diarrhea/Constipation Flashcards
Loperamide
Chemically-related to opioids but does not exhibit analgesic/opiate-like effects, or appear to produce physical dependence
Loperamide: MOA
MOA of Loperamide: Interferes with peristalsis (slows transit time)
Direct action on circular and longitudinal muscles of intestinal wall, slowing motility
Also may directly inhibit fluid and electrolyte secretion and/or increase water absorption
Loperamide: Side effects
dizziness, drowsiness & urinary retention (anticholinergic)
Diphenoxylate (Lomotil): what it is
synthetic opiate agonist (chemically-similar to meperidine) [C-V]
Diphenoxylate (Lomotil): how it works
Opioid-effects only seen at very high doses (constipation)
Diphenoxylate (Lomotil): why it was starred by seagers
Small quantity of atropine added to discourage deliberate abuse/over-dosage
MOA of Diphenoxylate:
Believed to exert effect locally & centrally on GI smooth muscle cells; inhibits GI motility and slows excess GI propulsion
Eluxadoline (Viberzi) (C-IV): MOA of Eluxadoline
Agonist at opioid mu & kappa receptors in GI
tract (slows peristalsis/delays digestion)
Antagonist at delta opioid receptors in GI
stomach, pancreas & biliary tract secretions decreased
Eluxadoline (Viberzi) (C-IV): Indication:
Indication:
Irritable Bowel Syndrome, Diarrhea- predominant subtype (IBS-D)
Eluxadoline (Viberzi) (C-IV): Side effects:
Hepatic/Pancreatic toxicity (increased enzymes)
Pancreatitis hi-risk in pts. w/o a gallbladder – Deaths have occurred
CNS-related (dizziness/fatigue/sedation/euphoria/impaired cognition)
Eluxadoline (Viberzi) (C-IV): Contraindications
biliary duct obstruction
sphincter of Oddi dysfunction
alcoholism history of pancreatitis
severe hepatic impairment
Alosetron: MOA
Selectively blocks GI-based 5HT3 recepto
Antagonism in GI modulate regulation of visceral pain, colonic transit & GI secretions
Alosetron: indication
Chronic, severe IBS-D not responsive to other conventional therapies (women)
Alosetron: SE
Constipation+Ischemic Colitis
Ischemic Colitis
side effect of alosetron
No refills without a follow-up exam by the prescriber
Physicians must enroll in prescribing program
Patients and physicians must sign a risk-benefit statement and agree to adhere to therapy plans
Additional self-training and testing by physicians to learn to appropriately diagnose IBS required
Cl- Channel Inhibitors-Diarrhea
Crofelemer (Mytesi), derived from dark red sap of Croton lechleri tree (botanical pharmaceutical).
Crofelemer (Mytesi): MOA
Cl- Channel Inhibitors-Diarrhea
Inhibits chloride ion secretion by blocking cAMP-stimulated CFTR (cystic fibrosis transmembrane regulator) & calcium-activated (CaCC) chloride channels
channels regulate fluid secretion by intestinal epithelial cells
Crofelemer (Mytesi): indication
Non-infectious diarrhea in HIV/AIDS
pts. on anti-retroviral therapy
Crofelemer (Mytesi): SEs
GI-related
Abdominal distention, elevated AST/ALT/Bilirubin
Upper-Respiratory Infections
Antimuscarinics: abdominal pain drugs
Hyoscyamine Dicyclomine Clidinium/Chlordiazepoxide
Antimuscarinics: MOA
Competitively-inhibit autonomic, post-ganglionic cholinergic receptors (multiple sites)
Antimuscarinics (for Abd. Pain/Spasms): Results, indications
decreased GI motility and spasms (pain), Abdominal pain/spasms, esp. when associated with IBS
Laxative & Cathartic Agents
Opioid Antagonists: Methylnaltrexone, Naloxegol
Guanylate Cyclase-C Agonists: Linaclotide
Selective Chloride (C2) Channel Activators: Lubiprostone
Constipation Type Drug
Linaclotide
Linaclotide: MOA
Binds to GC-C on luminal surface of intestinal epithelium.
Increases intracellular/extracellular concentrations of cGMP
Stimulates secretion of chloride/bicarbonate into intestinal lumen via activation of cystic fibrosis transmembrane conductance regulator (CFTR) ion channel
Results in increased intestinal fluid and accelerated transit
Linaclotide: indications
Irritable Bowel Syndrome-Constipation predominant subtype (IBS-C)
Chronic Idiopathic Constipation (CIC)
Linaclotide: SE
GI-Related: GERD/Dyspepsia/N/V
Lubiprostone MOA:
a bicyclic fatty acid, prostaglandin E1 (PGE-1) derivative
increases intestinal fluid secretion by activating GI specific chloride channels (ClC-2) in luminal cells of intestinal epithelium
Lubiprostone: indications
Irritable Bowel Syndrome-Constipation predominant subtype (IBS-C) (women)
Chronic Idiopathic Constipation (CIC)
Opioid-Induced Constipation (OIC) (non-cancer adults)
Lubiprostone: SE
Nausea, dyspepsia, dizziness
Methylnaltrexone & Naloxegol: MOA
peripheral mu-opioid receptor antagonists
No common, significant CNS penetrations/actions or induction of withdrawal/pain symptoms
Methylnaltrexone & Naloxegol: indications
Opioid-Induced Constipation (OIC)
Stimulants
Bisacodyl Castor Oil Glycerin Senna Na+ Picosulfate
Osmotics
Lactulose
Mag citrate
Polyethylene glycol (PEG)
Sorbitol (Glycerin)
Salines
Mag. hydroxide
Na+ phosphate
Bulk Forming
Dietary (Fiber/Bran) Fruits/Grains/Cereal) Psyllium Methylcellulose/ Carboxymethylcellulose Calcium polycarbophil
Stool Softeners
Docusate, Mineral Oil
Bulk-forming/Hydrophilic Colloidal Agents
Dietary Fiber/Bran, Psyllium, Metamucil, Genfiber, others…
