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
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
- photosensitivity, oligospermia
- skin discoloration
- decreased folate levels (need to take folate supplement)
- severe: SJS, crystalluria, pancreatitis, hepatitis, bone marrow suppression
- 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?
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
- fever, rash
- 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
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
- 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
Pharm therapy for constipation predominant IBS?
- increase fluids, fiber
- TCAs or SSRIs
- peppermint oil
- osmotic laxatives
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)
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
severe UC where bowel movements have stopped
myasthenia gravis, COPD
infants less than 6 mo
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:
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?
- have anti-ach effects, works good in diarrhea iBS
- 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
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
- 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