Pharmacology Week 2 Flashcards
Classes of Treatment for IBD & IBS
Aminosalicylates Corticosteroids Antibiotics Immunosuppressive agents Biological agents
Characteristics to determine which treatment should be used
Severity of disease
UC
Crohn’s lesions locations
Exacerbations vs. maintenance
Drugs used for Treatment of IBD
Aminosalicylates Corticosteroids Immunosuppresive agents IV cyclosporine Antibiotics Immune modifiers
When do you use aminosalicylates in the treatment of IBD?
Mild to moderate UC & CD exacerbations
Maintenance of remission
When do you use corticosteroids in the treatment of IBD?
Treatment of UC & CD exacerbations
When do you use immunosuppressive meds in the treatment of IBD?
Maintain remission
When do you use IV cyclosporine in the treatment of IBD?
Severe active refractory UC
When do you use antibiotics in the treatment of IBD?
Acute exacerbations
Maintenance of remission
When do you use immune modifiers in the treatment of IBD?
Maintain remission in steroid refractory UC & CD
Examples of Aminosalicylates
Sulfasalazine (Azulfidine)
Mesalamine (Asacol, Pentasa)
Olsalazine (Dipentum)
Basalazide (Colazal)
Clinical Uses for Aminosalicylates
Induce/maintain remission in UC
Routes of Administration of Aminosalicylates
PO
Enema
Suppository
Suflasalazine (Asulfidine)
Preg. B
Converted to mesalamine in the proximal colon
Contraindications of Sulfasalazine (Asulfidine)
Sulfa allergy
Mesalamine (Asacol, Pentasa)
Preg B
Works like a topical agent due to being poorly absorbed
Drug Release of Asacol Oral Tablets
Distal ileum & colon
Drug Release of Pentasa Oral Capsules
Proximal small intestine and throughout the colon
Routes of Administration of Melalamine
Oral tablets (Asacol)
Oral capsules (Pentasa)
Enema
Rectal suppositories
Where can a mesalamine enema reach?
Distal/sigmoid colon
When are melamine rectal suppositories primarily used?
UC proctitis
Why are the aminosalicylates banalized (Colazal) and olsalazine (Dipentum) not used frequently?
Increased cost
No extra efficacy
MOA of Aminosalicylates
Blocks prostaglandin production
Interferes with production of inflammatory cytokines
Inhibit NK cells, lymphocytes & macrophages
Contraindications of Aminosalicylates
Aspirin/salicylate allergy
G6PD deficiency
SE of Sulfasalazine
N/V Photosensitivity Oligospermia Skin discoloration Decreased folate levels SJS Crystalluria Pancreatitis Hepatitis Bone marrow suppression
Labs to monitor with Sulfasalazine
CBC with diff
LFTs
SE of Mesalamine
Headache
Malaise
Abdominal pain
Diarrhea
SE of Olsalazine
Headache
Malaise
Abdominal pain
Severe secretory diarrhea
SE of Balsalazide
Headache Malaise Abdominal Pain Diarrhea Staining of teeth (capsule opened & sprinkled on food)
Monitoring of Mesalamine
Renal function
CBC
Hepatic function
Short Term SE of Steroids
Hyperglycemia Increased appetite Insomnia Anxiety Tremors Increased fluid retention Increased BP
Long Term SE of Steroids
Decreased bone mineral density Fat redistribution Ulcers from decreased prostaglandin production Hypertriglyceridemia Hirsutism
Examples of Oral Corticosteroids
Prednisone (Deltasone)
Prednisolone (Prelone)
Budesonide (Entocort)
What is the treatment of choice in patients with mild to moderate CD?
Budesonide (entocort)
Examples of Topical Corticosteroids
Cortenema
Cortifoam
Anusol-HC suppositories
Antibiotics used in IBD
Ciprofloxacin
Metronidazole
Duration of Ciprofloxacin Therapy in Crohn’s Disease
Up to 6 weeks
Duration of Metronidazole (Flagyl) in Crohn’s Disease
1-2 months for response
Up to 12 months total
Examples of Immune Modifiers
Azathioprine
6-mercaptopurine
Methotrexate
Infliximab
Clinical Use of Azathioprine & 6-Mercaptopurine
Induction/maintenance of remission
UC & Crohn’s
Allow reduction of steroids
Pregnancy Category of Azathioprine & 6-Mercaptopurine
Preg D
MOA of Azathioprine & 6-Mercaptopurine
Inhibition of purine nucleotide metabolism & DNA synthesis & repair
Inhibition of cell division/proliferation
SE of Azathioprine & 6-Mercaptopurine
N/V Diarrhea Fever, rash pancreatitis Bone marrow suppression Hepatic toxicity Arthralgias Malaise Drug toxicity
Routine labs for monitoring Azathioprine & 6-Mercaptopurine
CBC
LFTs
Dose changes and contraindications of Azathioprine & 6-Mercaptopurine
Contraindicated in pregnancy or active liver disease
Decreased dose of CrCl
Clinical Use of Methotrexate
Induction & maintenance of remission in patients with Crohn’s disease
MOA of Methotrexate
Inhibits metabolism of folic acid
Interferes with interleukin-1 inflammatory actions
Stimulate apoptosis of activated T lymphocytes
Issues with Methotrexate
Preg X
Adjust dose for altered renal clearance
Contraindicated in pregnancy and liver disease
SE of Methotrexate
Alopecia Muscositis Bone marrow depression megaloblastic anemia Cirrhosis & liver fibrosis Pneumonitis Folic acid deficiency Rash Nausea Diarrhea
Indications for Cyclosporine
Acute treatment of severe, steroid refractory exacerbations of UC in hospitalized patients
SE of Cyclosporine
Nephrotoxicity
Hypomagnesemia
HTN
Clinical Use for TNF Inhibitors
Symptomatic improvement in 2/3 patients with moderately severe Crohn’s
Disease remission in 1/3 patients with moderately severe or fistulizing Crohn’s
Not responding to steroids, 6-mercaptopurine or methotrexate
Examples of TNF Inhibitors
Infliximab (Remicade)
Adalimumab (Humira)
Certolizumab Pegol (Cimzia)
MOA of Infliximab (Remicade)
Dysregulation of the TH1 cell response present in IBD
Antibody to human TNF-alpha
Neutralizes membrane bound TNF
Pregnancy Category of Infliximab (Remicade)
B
SE of Immediate Infusion Reaction to Infliximab (Remicade)
Fever, chills
Pruritis, urticaria
Chest pain, dyspnea
Hemodynamic instability
SE of Delayed Infusion Reaction to Infliximab (Remicade)
Myalgia, arthralgia
Fever
Rash, urticaria
Facial, hand, & lip edema
How to treat immediate infusion reaction to Infliximab (Remicade)
Prophylactic Tylenol & Benadryl
How to treat delayed infusion reaction to Infliximab (Remicade)
Antihistamines
Corticosteroids
Black Box Warning of TNF Inhibitors
Reactivation of latent TB
Treatment of Mild Distal UC
Oral/rectal aminosalicylate
Rectal corticosteroid
Treatment of Mild Extensive UC
Oral aminosalicylate
Treatment of Mild CD
Oral aminosalicylate
Antibiotics
Treatment of Moderate Distal UC
Oral aminosalicylate
Oral/rectal steroids and/or immunosuppressive
Treatment of Moderate Extensive UC
Oral aminosalicylate
Oral steroids and/or immunosuppressive
Treatment of Moderate CD
Oral aminosalicylate
Oral steroid and/or immunosuppressive
Treatment of Severe Distal UC
IV corticosteroids
IV cyclosporine
Treatment of Severe Extensive UC
IV corticosteroids
IV cyclosporine
Treatment of Severe CD
IV corticosteroids
IV cyclosporine
Treatment of Remission of Distal UC
Oral/rectal aminosalicylate
Oral immunosuppressive
Treatment of Remission of Extensive UC
Oral/rectal aminosalicylate
Oral immunosuppressive
Treatment of Remission of CD
Oral aminosalicylate
Oral immunosuppressive
Pharmacologic Therapy for IBS
Antispasmodic agents Antidiarrheal agents Anticonstipation agents Psychotropic agents Serotonin receptor agonists & antagonists Nonabsorbable antibiotics Probiotics
Pharmacotherapy for Constipation in IBS
Increase fluids, fiber TCAs or SSRIs Peppermint oil Osmotic laxatives Lubiprostone
Pharmacotherapy for Pain in IBS
Antispasmodics- anticholinergics
TCAs
SSRIs
Peppermint oil
Pharmacotherapy for Diarrhea in IBS
Fiber Loperamide Cholestramine TCAs Lotronex SSRIs
Types of Antispasmodics
Anticholinergics
Belladonna alkaloids
Examples of Anticholinergic Antispasmodics
Hyoscyamine (Levbid, Levsin SL)
Dicyclomine (Bentyl)
Examples of Belladonna Alkaloid Antispasmodics
Donnatol
Clidinium (Librax
Pregnancy Category of Dicyclomine (Bentyl) and Hyoscyamine (Levsin, Levbid)
Pregnancy C
Pregnancy C
MOA of Antispasmodics
Block acetylcholine at muscarinic cholinergic receptors
Cautions of Antispasmodics
Anticholinergic SE Elderly BPH HTN Hyperthyroidism
Contraindications for Antispasmodics
Peptic ulcer Arrhythmias CHF Sever UC Glaucoma Myasthenia gravis COPD Infants
First line Antispasmodic
Dicyclomine (Bentyl)
Second-line Antispasmodic
Hyoscyamine Sulfate (Levbid, Levsin SL)
What does antispasmodics treat in IBS?
Postprandial abdominal pain
Gas
Bloating
Fecal urgency
Anticonstipation Agents in IBS
Miralax (polyethylene glycol)
Lubiprostone (Amitiza)
Linaclotide (Linzess)
Which anti-constipation medication is an osmotic laxative?
Miralax (Polyethylene glycol)
Which anti-constipation medications increase intestinal chloride & fluid secretion?
Lubiprostone (Amitiza)
Linaclotide (Linzess)
MOA of Lubiprostone (Amitiza)
Locally acting calcium channel activator that increases intestinal fluid secretion
SE of Lubiprostone (Amitiza)
Nausea
Diarrhea
Abdominal pain
Abdominal distention
MOA of LInaclotide (Linzess)
Binds to GC-C receptor on luminal surface of the intestinal epithelium
Affects the chloride and bicarbonate levels in the intestine
Increases intestinal fluid & causes accelerated intestinal transit
Examples of TCA’s for Treatment of IBS
Amitryptyline (Elavil)
Desipramine (Norpramin)
Imipramine (Tofranil)
Examples of SSRI’s for Treatment of IBS
Escitalopram (Lexapro) Citalopram (Celexa) Sertraline (Zoloft) Paroxetine (Paxil) Fluoxetine (Prozac)
MOA of TCA’s
Increasing pain threshold in the gut
Prolongs oral0cecal transit time
Pregnancy Category of Imipramine, Amitriptyline, Desipramine
Pregnancy C
Pregnancy C
Pregnancy C
Contraindications for TCA’s
Narrow angle glaucoma
Recent MI
MAOI’s or Fluoxetine (Prozac)
Reason of SSRI’s in treatment of IBS
Lead to improvement in overall sense of well being
Little impact on abdominal pain or bowel symptoms
Contraindications of Alosetron (Lotronex)
Hx of chronic/severe constipation or sequelae from thereof
Hx of ileus, obstruction, stricture, toxic megacolon
Hx of GI perforation, adhesions
Hx of ischemic colitis, impaired intestinal circulation
Hx of Crohn’s or UC
Hx of Diverticulitis or diverticulosis
Hx of thrombophlebitis or a hypercoagulable state
Non-absorbable Antibiotics
Rifaximin (Xifaxan)
Refractory symptoms
Probiotics that has shown modest improvement in symptoms in small studies
Bifodobacterium infantis
