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GI pharm - large bowel Flashcards

1
Q

What drugs are used for tx of IBD?

A
  • aminosalicylates: mild to moderate UC and CD exacerbations, and maintenance of remission
  • corticosteroids: Tx of UC and CD acute exacerbations, shouldn’t be used chronically to maintain remission
  • Immunosuppressive agents: to maintain remission
  • IV cyclosporine: severe active steroid refractory UC
  • abx: acute exacerbations and maintenance of remission
  • immune modifiers: maintain remission in steroid refractory UC and CD
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2
Q

Tx for mild UC - distal and extensive?

A
  • distal: oral/rectal aminosalicylate or rectal corticosteroid
  • extensive: oral aminosalicylate
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3
Q

Tx for mild CD?

A
  • oral aminosalicylate with or w/o abx
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4
Q

Tx for moderate UC - distal and extensive?

A
  • distal: oral aminosalicylate and oral/rectal steroids and or an immunosuppressive
  • extensive: oral aminosalicyltae, and oral steroids and or immunosuppressive
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5
Q

Tx for moderate CD?

A
  • oral aminosalicylate and oral steroid and/or immunosuppressive
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6
Q

Tx for severe UC - distal and extensive?

A
  • distal: IV corticosteroids with or w/o IV cyclosporine

- extensive: IV corticosteroids with/w/o IV cyclosporine

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7
Q

Tx of severe CD?

A
  • IV corticosteroids with/w/o IV cyclosporine
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8
Q

Tx for remission in UC?

A
  • distal and extensive: oral/rectal aminosalicylate with or w/o oral immunosuppressive
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9
Q

Tx for remission in CD?

A
  • oral aminosalicylate with/w/o oral immunosuppressive
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10
Q

Clinical uses of aminosalicylates?

A
  • induce and maintain remission in UC
  • efficacy in crohn’s not well est., but often used as 1st line tx of Crohns involving the colon or distal ileum
  • PO
  • enema
  • supp
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11
Q

Sulfasalzaine (Asulfidine) - Action?
Dosing?
CI?

A
  • pregnancy B
  • sulfapyridine mesalamine compound
  • converted to mesalamine in proximal colon
  • tabs admin 4x daily
  • CI in sulfa allergy
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12
Q

Mesalamine (Asacol, pentasa) - Action? Diff routes?

A
  • preg cat B
  • poorly absorbed in GI tract so works primarily like a topical agent with limited systemic SE and drug interactions
  • oral tabs (asacol)
  • oral capsules (pentasa)
  • enema: can reach distal and sigmoid colon, admin at bedtime
  • rectal supps: primarily used for UC proctitis
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13
Q

Use of Basalizide (colazal) and olsalazine (dipentum)?

A
  • not used as much as other two due to increased cost but no added efficacy
  • both poorly absorbed in GI tract so work primarily like a topical agent with limited SE and drug interactions
  • Basalazide: preg B, converted to mesalamine in proximal colon
  • olsalazine: preg C, converted to mesalamine in proximal colon
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14
Q

MOA of aminosalicylates?

A
  • exact mechanism is unknown
  • blocks prostaglandin production
  • perhaps interferes with production of inflammatory cytokines
  • may inhibit natural killer cells, lymphocytes and macrophages
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15
Q

CIs to aminosalicylates?

A
  • aspirin or salicylate allergy
  • G6PD deficiency
  • sulfasalazine is CI with hx of sulfa allergy
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16
Q

Dosing of aminosalicylates?

A
  • must be used at max doses for max therapeutic benefit
  • dosing varies from once daily to 4x daily depending on formulation
  • SEs increase as dose increases
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17
Q

SEs of sulfasalazine?

A
  • worst SE profile of all aminosalicylates
  • N/V
  • photosensitivity, oligospermia
  • skin discoloration
  • decreased folate levels (need to take folate supplement)
  • severe: SJS, crystalluria, pancreatitis, hepatitis, bone marrow suppression
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18
Q

Monitoring sulfasalzine?

A
  • CBC with diff, LFTs prior to therapy then q other week for 3 months, then q month for 3 months then quarterly
  • periodic renal and LFTs
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19
Q

SEs of mesalamine and its compounds?

A
  • rarely assoc with renal impairment
  • mesalamine: HA, malaise, abdominal pain, and diarrhea
  • olsalazine: similar to mesalamine but more severe secretory diarrhea
  • balsalazide: similar to mesalamine - if capsules opened and sprinkled in food may cause staining of teeth
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20
Q

Monitoring parameters for mesalamine?

A
  • no specific recommendations on how frequent to monitor labs
    -renal fxn prior to and during therapy
  • CBC
  • hepatic fxn
    (want to get baseline tests)
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21
Q

Indications for corticosteroids?

SEs?

A
  • used for acute exacerbations
  • not used for maintaining remission
  • short term SEs:
    increased glucose levels, increased appetite, insomnia, anxiety, tremors, increased fluid retention, increased BP
  • long term: decreased bone mineral density, fat redistribution, ulcers from decreased prostaglandin production, hypertriglyceridemia, hirsutism
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22
Q

Oral corticosteroids used?

A
  • prednisone and prednisolone most commonly used oral meds:
    40-60 mg/day initially
    taper with pts response
    IV - hydrocortsione and methylprednisolone
  • budesonide (entocort): controlled release with limited systemic absorption, has been used as tx of choice in pts with mold to moderate CD in combo with 5-ASA or as monotherapy
  • stays in gut, has poor bioavailabilty
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23
Q

Topical steroids used for IBD?

A
  • cortenema, cortifoam, anusol-HC suppositories
  • hydrocortisone enemas, foam, or supps
  • for IBD involving the rectum/sigmoid colon
  • sometimes referred to as topical
24
Q

Abxs used in IBD?

A
  • ciprofloxacin: quinolone, may have some immunosuppressive properties, may take up to 6 wks for remission
  • metronidazole: start at higher dose and decrease after response is noted, likely also has some immunosuppressive properties, may take 1-2 months for response to therapy, duration of therapy may be up to 12 months
  • used generally for tx of CD that doesn’t respond to 5-ASAs after 3-4 wks or if pt is intolerant to 5-ASAs
  • used as 2nd or 3rd line in CD, used if intolerant to 5-ASA
  • efficacy in UC hasn’t been established
25
Q

Immune modifiers used in IBD?

A
  • azathiprione
  • 6-mercaptopurine
  • methotrexate
  • infliximab
26
Q

Clinical use of azathioprine and 6-mercaptopurine?

A
  • induction and maintenance of remission
  • UC and CD
  • 3-6 months of tx induces remission in 50-60% of pts with active disease
  • 80% maintain remission
  • use may allow reduction of steroid therapy
27
Q

How do azathioprine and 6-mercaptopurine work?

A
  • 6-mercaptopurine is an active metabolite of azathioprine
  • short half life but active metabolite with long half life of 3-13 days
  • prolonged kinetics results in median delay of 17 wks b/f onset of therapeutic benefit from oral med
  • Preg D ( some studies suggest it may be cont safely throughout pregnancy)
  • inhibition of purine neucleotide metabolism and DNA synthesis and repair, resuting in inhibition of cell division and proliferation
  • may decrease proliferation of immune cells leading to lower autoimmune activity
28
Q

SEs of azathioprine and 6-mercaptopurine? CI?

A
  • SEs are mostly dose related
  • N/V/D
  • fever, rash
  • pancreatitis
  • bone marrow suppression: leukopenia
  • hepatic toxicity
  • arthralgias, malaise
  • drug toxicity with concurrent use of allopurinol
  • monitor: Routine CBC and LFTs

CI: in pregnancy or active liver disease
- decrease dose for CrCl lower than 50

29
Q

Clinical use of methotrexate?

A
  • induction and maintenance of remission in pts with CD
  • effects in UC are uncertain
  • can be give PO, SQ, or IM
30
Q

MOA of methotrexate?

A
  • inhibits metabolism of folic acid (need folic supplement)
  • shares structural homology with interleukin-1, thus intereferes with its inflammatory actions
  • may stimulate apoptosis and death of activated T lymphocytes
31
Q

SEs and CI of methotrexate?

A
  • preg: X
  • adjust dose for alt renal clearance
  • CI in pregnancy and active Liver disease
  • SEs:
    alopecia
    muscositis
    bone marrow depression - higher dosage
    megaloblastic anemia: higher dosage
    cirrhosis and liver fibrosis
    pneumonitis
    folic acid deficiency
    rash
    Nausea/diarrhea
    (usually is well tolerated)
32
Q

Indications for cyclosporine? Duration of therapy, SEs?

A
  • used for acute tx of severe, steroid refractory exacerbations of UC in hosp pts
  • improvement should be seen in 2-3 days
  • duration of therapy 7-10 days
  • given IV
  • SEs: nephrotoxicity, hypomagnesemia, HTN
  • This is a really powerful drug!
33
Q

Clincial use of anti-tumor necrosis factor agents (TNF inhibitors)?

A
  • leads to sx improvement in 2/3 of pts with moderately severe or fistulizing crohns
  • leads to disease remission in 1/3 pts with moderately severe or fistulizing crowns
  • used when pts are not responding to steroids, 6-mercaptopurine or methotrexate
34
Q

TNF inhibitors approved for use in severe refractory CD?

A
  • infliximab (remicade): also indicated for maintaining remission in CD and tx UC
  • adalimumab (humira)
  • certolizumab pegol (cimzia)
35
Q

Infliximab (remicade) use? Dosing? MOA?

A
  • preg B
  • admin via IV infusion
  • given 5 mg/kg dose initially, at 2 and 6 weeks
  • then maintenance q 6-12 wks
  • MOA: dysregulation of TH1 T cell response present in IBD, ab to human TNF-alpha, neutralizes membrane bound TNF
36
Q

SEs of TNF inhibitors?

A

infusion reaction (more than 10% of pts):

  • fever, chills,
  • pruritus, urticaria
  • chest pain, dyspnea
  • hemodynamic instability
  • infusion reaction more common with 2nd and subsequent infusions other than the first
  • prophylactic tylenol and benadryl

delayed infusion rxn (5% of pts):

  • occurs 1-2 wks after infusion
  • myalgia, arthralgia
  • fever
  • rash, urticaria
  • facial, hand and lip edema
  • tx with antihistamines or corticosteroids
37
Q

BBW of TNF inhibitors?

A
  • reactivation of latent TB
    all pts must have PPD prior to use
    prophylactic therapy for those with + PPDs
38
Q

When should you begin steroids in IBD tx?

A
  • if no response in 3-4 weeks, or its a severe case (rectal steroids are very effective in UC)
39
Q

Pharm therapy for IBS?

A
  • antispasmodic agents
  • antidiarrheal agents
  • anticonstipation agents
  • psychotropic agents
  • serotonin receptor agonists and antagonists
  • nonabsorbable abxs
  • probiotics
40
Q

Pharm therapy for constipation predominant IBS?

A
  • increase fluids, fiber
  • TCAs or SSRIs
  • peppermint oil
  • osmotic laxatives
  • lubiprostone
41
Q

pharm therapy for pain predominant IBS?

A
  • antispasmodics (anticholinergics)
  • TCAs (low dose)
  • SSRI
  • peppermint oil
42
Q

Pharm therapy for diarrhea predominant IBS?

A
  • fiber (sometimes controversial in sx tx of IBS)
  • loperamide
  • cholestramine
  • TCAs
  • lotronex
  • SSRIs
43
Q

Antispasmodics used in IBS?

A
  • anticholinergics: hyoscyamine (levbid, Levsin SL), dicyclomine (bentyl)
  • belladonna alkaloids: donnatol, clidinium (librax)
  • provide relief through antispasmodic action, work primarily through cholinergic receptors:
    Dicyclomine preg C
    hyoscyamine preg C
    (decreasing smooth muscle activity in gut)
44
Q

MOA of antispasmodics?

A
  • block action of acetylcholine at parasympathetic sites in secretory glands, smooth muscle and CNS
  • inhibit muscarinic cholinergic receptors in enteric plexus and on smooth muscle
  • reduce contraction of the bowel
    • have to use with caution in elderly b/c of anticholinergic effects
  • works best in diarrhea IBS
45
Q

Caution and CIs of antispasmotics?

A
  • watch for anticholinergic SEs
  • caution in elderly, BPH, HTN, hyperthyroidism
  • CIs:
    peptic ulcer
    arrhythmias
    CHF
    severe UC where bowel movements have stopped
    glaucoma
    myasthenia gravis, COPD
    infants less than 6 mo
    nursing mothers
46
Q

1st and 2nd line antistpasmodics?

A
  • tx of postprandial abdominal pain, gas, bloating, fecal urgency
  • dicylcomine (bentyl): 1st line - short half life- so less cholinergic side effects
  • hyoscyamine sulfate (levbid): 2nd line, longer half life, sublingual, oral or oral sustained release (q 12 hrs)
  • can be used on prn basis and with anticipation of stressors
47
Q

Anticonstipation agents used in IBS?

A
  • miralax (polyethylene glycol): osmotic laxative
  • increased intestinal chloride and fluid secretion:
    lubiprostone (amitiza)
    linaclotide (linzess)
    these cause a fluid shift into the colon
48
Q

MOA of lubiprostone? Use? SEs?

A
  • chloride channel activator, loccally acting chloride channel activator that increases intestinal fluid secretion
  • approved only for women with constipation dominant IBs
  • use only if persistent constipation after trial of other txs
  • SEs: most common nausea, diarrhea, abdominal pain, abdominal dissension
  • long term safety hasn’t been established
49
Q

MOA of linaclotide (linzess)?

A
  • binds to GC-C receptor on luminal surface of intestinal epithelium ultimately affects chloride and bicarb levels in the intestine and increases intestinal fluid and causes accelerated intestinal transit
  • interactions: none
  • administration: once daily in AM after eating
50
Q

Psychotropic agents used in IBS?

A 
- TCAs:
amitryptyline (elavil)
desipramine (norpramin)
imipramine (tofranil)
- have anti-ach effects, works good in diarrhea iBS
- SSRIs:
escitalopram (lexapro)
citalopram (celexa)
sertraline (zoloft)
paroxetine (paxil)
fluoxetine (prozac)
  • tell pt that these will help sxs b/c decrease stress in general
51
Q

Use of TCAs? CIs?

A

-visceral analgesic effect by increasing pain threshold in the gut
- prolongs oral-cecal transit time
- increases global well being:
imipramine preg C
amitriptyline preg C
desipramine preg C

CIs:
narrow angle glaucoma
recent MI
MAOIs or fluoxetine (prozac) in pts who took them in previous 2 weeks

52
Q

How do SSRIs help IBS?

A
  • may lead to improvement in overall sense of wellbeing but have little impact on abdominal pain or bowel sxs
53
Q

Alosetron (lotronex)? What is it, CIs?

A

5-HT3 receptor inhibitor - used for diarrhea predominant IBS

  • CIs: hx of
  • chronic/severe constipation or sequelae from thereof
  • ileus, obstruction, stricture, toxic megacolon
  • GI perf, adhesions
  • ischemic colitis, impaired intestinal circulation
  • crohns or UC
  • diverticulitis/diverticulosis
  • hx of thrombophlebitis/hypercoagulable state
54
Q

Indications for Alosetron?

A
  • indicated only for women with severe diarrhea predominant IBS who haven’t responded adequately to conventional therapy
  • cauased serious life threatening, GI side effects including ischemic colitis, and serious complications of constipation
  • came back on the market, not pt has to read and sign pt-physician agreement for alosetron
  • prescribers need to enroll in prometheus prescribing program for alosetron
  • never give to pts without diarrhea!
55
Q

Nonabsorbable abx used in IBS?

A
  • rifaximin (xifaxan)
  • refractory sxs, esp bloating
  • not FDA approved
56
Q

Probiotics for IBS?

A
  • bifodobacterium infantis has shown modest improvement in sxs in small studies

GI (21 decks)

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