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Flashcards in GI pharm - large bowel Deck (56)

What drugs are used for tx of IBD?

- 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


Tx for mild UC - distal and extensive?

- distal: oral/rectal aminosalicylate or rectal corticosteroid
- extensive: oral aminosalicylate


Tx for mild CD?

- oral aminosalicylate with or w/o abx


Tx for moderate UC - distal and extensive?

- distal: oral aminosalicylate and oral/rectal steroids and or an immunosuppressive
- extensive: oral aminosalicyltae, and oral steroids and or immunosuppressive


Tx for moderate CD?

- oral aminosalicylate and oral steroid and/or immunosuppressive


Tx for severe UC - distal and extensive?

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


Tx of severe CD?

- IV corticosteroids with/w/o IV cyclosporine


Tx for remission in UC?

- distal and extensive: oral/rectal aminosalicylate with or w/o oral immunosuppressive


Tx for remission in CD?

- oral aminosalicylate with/w/o oral immunosuppressive


Clinical uses of aminosalicylates?

- 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


Sulfasalzaine (Asulfidine) - Action?

- pregnancy B
- sulfapyridine mesalamine compound
- converted to mesalamine in proximal colon
- tabs admin 4x daily
- CI in sulfa allergy


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

- 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


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

- 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


MOA of aminosalicylates?

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


CIs to aminosalicylates?

- aspirin or salicylate allergy
- G6PD deficiency
- sulfasalazine is CI with hx of sulfa allergy


Dosing of aminosalicylates?

- 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


SEs of sulfasalazine?

- 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


Monitoring sulfasalzine?

- 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


SEs of mesalamine and its compounds?

- 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


Monitoring parameters for mesalamine?

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


Indications for corticosteroids?

- 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


Oral corticosteroids used?

- 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


Topical steroids used for IBD?

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


Abxs used in IBD?

- 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


Immune modifiers used in IBD?

- azathiprione
- 6-mercaptopurine
- methotrexate
- infliximab


Clinical use of azathioprine and 6-mercaptopurine?

- 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


How do azathioprine and 6-mercaptopurine work?

- 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


SEs of azathioprine and 6-mercaptopurine? CI?

- 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


Clinical use of methotrexate?

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


MOA of methotrexate?

- 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


SEs and CI of methotrexate?

- preg: X
- adjust dose for alt renal clearance
- CI in pregnancy and active Liver disease
- SEs:
bone marrow depression - higher dosage
megaloblastic anemia: higher dosage
cirrhosis and liver fibrosis
folic acid deficiency
(usually is well tolerated)


Indications for cyclosporine? Duration of therapy, SEs?

- 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!


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

- 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


TNF inhibitors approved for use in severe refractory CD?

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


Infliximab (remicade) use? Dosing? MOA?

- 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


SEs of TNF inhibitors?

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


BBW of TNF inhibitors?

- reactivation of latent TB
all pts must have PPD prior to use
prophylactic therapy for those with + PPDs


When should you begin steroids in IBD tx?

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


Pharm therapy for IBS?

- antispasmodic agents
- antidiarrheal agents
- anticonstipation agents
- psychotropic agents
- serotonin receptor agonists and antagonists
- nonabsorbable abxs
- probiotics


Pharm therapy for constipation predominant IBS?

- increase fluids, fiber
- TCAs or SSRIs
- peppermint oil
- osmotic laxatives
- lubiprostone


pharm therapy for pain predominant IBS?

- antispasmodics (anticholinergics)
- TCAs (low dose)
- peppermint oil


Pharm therapy for diarrhea predominant IBS?

- fiber (sometimes controversial in sx tx of IBS)
- loperamide
- cholestramine
- TCAs


Antispasmodics used in IBS?

- 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)


MOA of antispasmodics?

- 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


Caution and CIs of antispasmotics?

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


1st and 2nd line antistpasmodics?

- 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


Anticonstipation agents used in IBS?

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


MOA of lubiprostone? Use? SEs?

- 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


MOA of linaclotide (linzess)?

- 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


Psychotropic agents used in IBS?

- 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


Use of TCAs? CIs?

-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

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


How do SSRIs help IBS?

- may lead to improvement in overall sense of wellbeing but have little impact on abdominal pain or bowel sxs


Alosetron (lotronex)? What is it, CIs?

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


Indications for Alosetron?

- 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!


Nonabsorbable abx used in IBS?

- rifaximin (xifaxan)
- refractory sxs, esp bloating
- not FDA approved


Probiotics for IBS?

- bifodobacterium infantis has shown modest improvement in sxs in small studies