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42 Cards in this Set
- Front
- Back
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What is inflammatory bowel disease (IBD)?
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Group of diseases primarily affecting small and large intestines
All characterized by chronic inflammation - Ulcerative Colitis (UC) and Crohn's Disease (CD) |
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Describe UC and CD.
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UC - more commonly confined to colon but can span other areas; characterized by chronic yet superficial inflammatory process
CD - can affect small and large intestines; inflammation can be focal yet also affect all layers of mucosa; can result in abscesses and fistulas |
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What are the clinical symptoms of IBD?
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Secretory diarrhea/malabsorption
Abdominal pain/cramping Mucosal inflammation/irritation/ulcerations Bleeding Exudation with protein-losing enteropathy |
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What are the goals of therapy for IBD?
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Reduce/eliminate painful/disabling symptoms
Induce remission (maintain flare-free) Prevent relapse (maintain flare-free) |
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What are the agents for UC?
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5-ASA
Corticosteroids TNF-alpha inhibitors |
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What are the agents for CD?
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5-ASA (used off label)
Corticosteroids TNF-alpha inhibitors Alpha-4 integrin inhibitors |
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Which drugs are 5-aminosalicyclic acid products (5-ASA)?
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Sulfasalazine (sulfapyridine + 5-ASA)
Mesalamine (single 5-ASA) Olsalazine Balsalazide |
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What is the MOA of 5-ASA?
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Inhibition of PG and LT production via arachidonic acid pathway (COX and LIPOX)
Reduction in PMN and macrophage chemotaxis May also inhibit activation of NFkB - nuclear transcription factor that regulates transcription of genes for pro-inflammatory proteins |
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What are the side effects of 5-ASA products?
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Sulfasalazine: fever/fatigue, headache, N/V/D, epigastric distress
Less systemic side effects with pure 5-ASA products Contraindicated in ASA- and sulfonamide- allergic pts |
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What is the topical action of 5-ASA?
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Oral: varies by agent, may be released in distal/terminal ileum, colon, or throughout GI tract
Rectal enemas: may reach splenic flexure, do not frequently concentrate in rectum Rectal suppositories: reach upper rectum (15-20 cm beyond anal verge) |
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What are the uses of 5-ASA agents?
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Treatment of mild-to-moderate active UC
Maintenance of remission of UC 5-ASA family good for treating and keeping in remission for mild to moderate disease; can't treat severe |
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What is the MOA of glucocorticosteroids?
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Readily cross cell membranes binding to specific cytoplasmic receptors
Binding induces response by modifying transcription and ultimately protein synthesis to achieve the steroid's intended action, including: inhibition of leukocyte infiltration at site of inflammation, interference in function of mediators of inflammatory response, suppression of humoral immune responses |
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What are the side effects of glucocorticosteroids?
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Increase glucose, BP and lipid profile
GI distress Fluid retention/edema/swelling of face & extremities Increased appetite/fat distribution Insomnia/jitterness/nervousness/anxiety/psychoses Bone defects |
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What are the indications and dosing for glucocorticosteroids?
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Severe UC and CD uncontrolled by other meds
Not for maintenance of remission unless absolutely required Dosing: oral/IV/rectal, use for shortest duration possible! |
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Which drugs are TNF-alpha inhibitors?
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Adalimumab - indicated for UC and CD
Infliximab - indicated for UC and CD Certolizumab - indicated for CD only |
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What are the biological activities attributed to TNF-alpha?
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Induction of pro-inflammatory cytokines and acute phase reactants
Enhancement of leukocyte migration by increasing endothelial layer permeability and expression of adhesion molecules by endothelial cells and leukocytes Activation of neutrophil and eosinophil functional activity |
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When are TNF-alpha inhibitors indicated?
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*All agents indicated for moderate-to-severe treatment resistant CD - induction of remission and maintenance of remission (steroid-sparing effect)
*Adalimumab and Infliximab also indicated for moderate-to-severe UC |
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What are the side effects of TNF-alpha inhibitors?
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Infections - Black Box Warning
GI-related (N/V/D/dyspepsia) Headache/arthralgias/fatigue Liver toxiciy Serum-sickness/hypersensitivity |
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*What is the dosing of TNF-alpha inhibitors?
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Adalimumab - administered SQ every other week (after decreasing loading doses for treatment 1 & 2 (2 wks apart)
Infliximab - administered IV as a 2 hr infusion every other month (after loading doses every other week x 2 and final loading dose a month later) Certolizumab - administered SQ every 4 weeks (after loading doses every other week x 2) |
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Which drug is an alpha-4 integrin inhibitor?
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Natalizumab - indicated for CD only
A recombinant, humanized IgG4 monoclonal antibody |
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What are the biological activities attributed to integrins?
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Assist in aiding migration and adhesion of cells from vasculature into inflamed tissues
Leukocytes found in inflamed tissues of patients with IBD |
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What are the indications of alpha-4 integrin inhibitor?
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*Indication: moderate-to-severe treatment resistant CD- induction and maintenance of remission (don't take concomitantly with immune modulators)
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What is the dosing and side effects of alpha-4 integrin inhibitor?
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Administered IV as 1hr infusion every 4 weeks
Side effects: infections, GI-related, headache/arthralgias/fatigue, depression, hypersensitivity Black Box Warning: progressive multifocal leukoencephalopathy |
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What is irritable bowel syndrome (IBS)?
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Complex of symptoms
Individual symptoms with limited accuracy in diagnosis Abdominal pain Diarrhea or constipation (or both) "Alarm features" - rectal bleeding, weight loss, iron-deficient anemia, nocturnal symptoms, family history of colorectal cancer, IBD and celiac sprue |
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What are the agents for IBS?
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Antimuscarinic agents
Bulk-forming and laxative agents Anti-diarrheals Serotonin (5HT3) antagonists Guanylate cyclase-C agonist Selective chloride (C2) channel activators |
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Which drugs are antimuscarinics and what are they used for?
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Hyosscyamine
Dicyclomine Clidium bromide/chlordiazepoxide For spasms and abdominal pain |
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What is the MOA of antimuscarinics?
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Competitive inhibitors at autonomic, post-ganglionic cholinergic receptors (GI/pulmonary/urinary, exocrine glands, heart, eye)
Results in decreased GI motility and spasms |
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What are the side effects for antimuscarinics?
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Anticholinergic-based: dry mouth, urinary retention, constipation, drowsiness, mental confusion, blurred vision
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Which drugs are the anti-diarrheals?
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Loperamide
Diphenoxylate |
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What is the MOA of loperamide?
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Interferes with peristalsis by 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 |
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What is the MOA of diphenoxylate?
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Appears to exert its effect locally and centrally on smooth muscle cells of GI tract; inhibits GI motility and slows excess GI propulsion
Chemically related to opioids, with opioid actions only at higher doses |
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What are the side effects of loperamide and diphenoxylate?
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Anti-cholinergic:
Constipation Dizziness Drowsiness Urinary retention |
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Which drug is the 5HT3 antagonist?
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Alosetron (for diarrhea)
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What is the MOA of alosetron?
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Selectively blocks GI-based 5HT3 receptors
Antagonism at 5HT3 receptors in GI tract modulate regulation of visceral pain, colonic transit, and GI secretions |
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What are he indications of alosetron?
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Only in women with severe IBS-D not benefited from previous traditional medications
No refills without follow-up exam by prescriber Physicians must enroll in prescribing program Pts and physicians must sign risk-benefit statement and agree to adhere to therapy plans Additional self-training and testing by physicians to learn to appropriately diagnose IBS is required |
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What are the side effects of alosetron?
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Black Box Warning: ischemic colitis and death
GI complaints (constipation, dyspepsia, GERD, N/V) Colitis Rash/arrhythmias/electrolyte disturbances |
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Which drug is a guanylate cyclase-C agonist?
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Linaclotide
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What is the MOA of linaclotide?
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Binds to GC-C on luminal surface of intestinal epithelium
Increases intracellular/extracellular concentrations of cyclic guanosine monophosphate (cGMP) Stimulates secretion of Cl/bicarb into lumen, through activation of CFTR ion channel, resulting in increased intestinal fluid and accelerated transit |
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What are the indications, side effects, and dosing of linaclotide?
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Indications: IBS-C, chronic idiopathic constipation (CIC)
Side effects: diarrhea, GERD/dyspepsia/N/V, headache/fatigue Dosing: oral once daily; contraindicated < 6 years of age |
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Which drug is a chloride channel (C-2) activator?
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Lubiprostone
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What is the MOA and indications for Lubiprostone?
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Increases intestinal fluid secretion by activating specific C-2 Cl channels in luminal cells of intestinal epithelium
Indications: IBS-C (women), CIC |
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What are the side effects and dosing of lubiprostone?
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Side effects: nausea, dyspepsia, dizziness
Dosing: oral twice daily |
