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Large Bowel Pharm Flashcards

1
Q

Treatment of Ulcerative Colitis and Crohn’s Disease

5 drugs

A
  1. Aminosalicylates
  2. Corticosteroids
  3. Antibiotics
  4. Immunosuppresive agents
  5. Biological Agents
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2
Q

Drugs that are used for treatment are based on?

4

A
  1. Severity of disease
  2. Ulcerative colitis
  3. Crohn’s disease location of lesions
  4. Exacerbation vs. maintenance therapy
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3
Q

Drugs used for treatment of inflammatory bowel disease

  1. Aminosalicylates
    - used how? 2
  2. Corticosteroids
    - Used how?
    - Should not be used for what?
A
    • Mild to moderate UC and CD exacerbations
    • Maintenance of remission
    • Treatment of UC and CD acute exacerbations
    • Should not be used chronically to maintain remission
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4
Q

Drugs used for treatment of inflammatory bowel disease

  1. Antibiotics
    - Used for?
  2. Immunosuppresive agents
    - Used for?
A
  1. Acute exacerbations and maintenance of remission

2. To maintain remission

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5
Q

Drugs used for treatment of inflammatory bowel disease
1. IV cyclosporine
used for?
2. Immune modifiers used for?

A
  1. Severe active steroid refractory UC

2. Maintain remission in steroid refractory UC and CD

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6
Q 
Treatment Options for Crohn’s and Ulcerative Colitis:
Describe treatment of Distal UC
1. Mild 
2. Moderate
3. Severe
4. Remission
A

Severity of Disease
Distal UC

  1. Mild
    Oral/rectal aminosalicylate or rectal corticosteroid
  2. Moderate
    Oral Aminosalicylate and oral/rectal steroids and/or immunosuppressive
  3. Severe
    IV corticosteroids with/without IV cyclosporine
  4. Remission
    Oral/rectal aminosalicylate with/without oral immunosuppressive
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7
Q 
Treatment Options for Crohn’s and Ulcerative Colitis:
Describe treatment of Extensive UC?
1. Mild 
2. Moderate
3. Severe
4. Remission
A

Extensive UC
1. Mild- Oral Aminosalicylate

  1. Moderate- Oral Aminosalicylate and oral steroids and/or immunosuppressive
  2. Severe- IV corticosteroids with/without IV cyclosporine
  3. Remission- Oral/rectal aminosalicylate with/without oral immunosuppressive
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8
Q 
Treatment Options for Crohn’s and Ulcerative Colitis:
Describe treatment of CD?
1. Mild 
2. Moderate
3. Severe
4. Remission
A

CD
1. MIld- Oral Aminosalicylate with/without antibiotics

  1. Moderate- Oral Aminosalicylate and oral steroid and/or immunosuppressive
  2. Severe- IV corticosteroids with/without IV cyclosporine
  3. Remission- Oral Aminosalicylate with/without oral immunosuppressive
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9
Q

What are the Aminosalicylates?

4

A
  1. Sulfasalazine (Azulfidine)
  2. Mesalamine (Asacol, Pentasa)
  3. Olsalazine (Dipentum)
  4. Basalazide (Colazal)
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10
Q

Aminosalicylates clinical uses

2

A
  1. Induce and maintain remission in UC
  2. Efficacy in Crohn’s is not well established, but often used as 1st line tx of Crohn’s involving the colon or distal ileum.
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11
Q

Aminosalicylates forms of administration?

3

A
  1. PO
  2. Enema
  3. Suppository
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12
Q

Aminosalicylates: Sulfasalazine (Asulfidine)

  1. Preg cat?
  2. Converted to what in the proximal colon?
  3. Take how many times daily?
  4. Contraindication?
A
  1. Pregnancy cat. B (Sulfapyridine-mesalamine compound)
  2. Converted to mesalamine in the proximal colon
  3. Tablets administered 4 times daily
  4. Contraindicated in sulfa allergy
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13
Q

Aminosalicylates: Mesalamine (Asacol, Pentasa)

  1. Preg cat?
  2. Poorly absorbed in the GI tract so works primarily like a topical agent with what kind of effects?
  3. Describe the four ways of administration?
A
  1. B
  2. limited systemic SE and drug interactions
  3. -Oral tablets (Asacol)
    released in the distal ileum and colon

-Oral capsules (Pentasa)
released in the proximal small intestine and throughout the colon

-Enema
Can reach distal and sigmoid colon, administered at bedtime
Rectal suppositories

-Primarily used for UC proctitis

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14
Q

Aminosalicylates: Basalazide (Colazal)

  1. Preg cat?
  2. Converted to mesalanine where?

Olsalazine (Dipentum)

  1. Preg cat?
  2. Converted to mesalanine where?

These 2 drugs are not used as much as the others due to the increased cost but no added efficacy
Both are poorly absorbed in the GI tract so work primarily like a topical agent with limited systemic SE and drug interactions

A

Basalazide (Colazal)

  1. Pregnancy cat. B
  2. Converted to mesalamine in the proximal colon

Olsalazine (Dipentum)

  1. Pregnancy cat. C
  2. Converted to mesalamine in the proximal colon
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15
Q

MOA Aminosalicylates

3

A
  1. Blocks prostaglandin production
  2. Perhaps interferes with production of inflammatory cytokines
  3. May inhibit natural killer cells, lymphocytes and macrophages

Exact mechanism unknown

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16
Q

Contraindications to Aminosalicylates

3

A
  1. Aspirin or other salicylate allergy
  2. Glucose-6-phosphate dehydrogenase deficiency
  3. Sulfasalazine is contraindicated with a history of sulfa allergy
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17
Q

Dosing of Aminosalicylates?

  1. What must we dose at?
  2. SE increase with what?
A
  1. Must be used at max doses for maximum therapeutic benefit
  2. Side effects increase as the dose increases
    - Dosing varies from once daily to four times daily depending on the formulation
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18
Q

Side effects of sulfasalazine 5

Severe rxns? 5

What do we need to supplement with?

A
  1. Worst side effect profile of all the aminosalicylates
  2. Nausea, Vomiting
  3. Photosensitivity, oligospermia
  4. Skin discoloration
  5. Decreased folate levels

Severe:

  1. Steven-Johnson syndrome,
  2. crystalluria,
  3. pancreatitis,
  4. hepatitis,
  5. bone marrow suppression

Need to take a folic acid supplement

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19
Q

What do we need to monitor with Sulfasalazine and how often? 2

Periodically what else? 2

A
  1. CBC with differential,
  2. LFTs prior to therapy then every other week for 3 months, then every month for 3 months, then quarterly

Periodic renal and LFTs

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20
Q

Side effects of mesalamine & it’s compounds

Mesalamine 4

Olsalazine 1

Balsalazide 1

Rarely these can be associated with what?

A

Mesalamine

  1. Headache,
  2. malaise,
  3. abdominal pain and
  4. diarrhea

Olsalazine
1. Similar to mesalamine but has more severe secretory diarrhea

Balsalazide
Similar to mesalamine
1. If capsules opened and sprinkled in food may cause staining of the teeth

Rarely can be associated with renal impairment

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21
Q

Mesalamine
No specific recommendations on how frequent to monitor these labs
-Which ones? 3

A
  1. Renal function prior to and during therapy
  2. CBC
  3. Hepatic function
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22
Q

Corticosteroids

  1. Used for what?
  2. Short term side effects? 6
  3. Long term side effects? 5
A 
1. Used for acute exacerbations
Not used for maintaining remission
2. Short term side effects
-Increased glucose levels, 
-increased appetite,
- insominia, anxiety,
- tremors, 
-increased fluid retention, 
-increased blood pressure

Long term side effects

  • Decreased bone mineral density,
  • fat redistribution,
  • ulcers from decreased prostaglandin production,
  • hypertriglyceridemia,
  • hirsutism
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23
Q

Prednisone (Deltasone) and Prednisolone (Prelone) are most commonly used oral medications

  1. Initial dose? then what?
  2. IV formulas? 2
A
  1. 40-60mg/d initially
    Taper with patients response
  2. IV – Hydrocortisone (Solu-Cortef) and Methylprednisolone (Solumedrol)
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24
Q
  1. Budesonide (Entocort) is what?

- It is used how for treatment?

A

Budesonide (Entocort)

  1. Controlled release with limited systemic absorption
    - Has been used as the treatment of choice in patients with mild to moderate CD in combo with 5-ASA or as mono therapy
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25
Q

What are the topical steriods?
3

What is this used to treat?

A
  1. Cortenema,
  2. Cortifoam,
  3. Anusol-HC suppositories
    - Hydrocortisone enemas, foam or suppositories
  4. For IBD involving the rectum/sigmoid colon
    Sometimes referred to as topical
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26
Q

Antibiotics are generally used for the treatment of what?

A
  1. Used generally for treatment of Crohn’s disease that does not respond to 5-ASAs after 3-4 weeks or if the patient is intolerant to 5-ASAs

Efficacy in Ulcerative colitis has not been established

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27
Q

What antibiotics are used in the treatment of Crohn’s?

2

A
  1. Cipro

2. Metronidazole (Flagyl)

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28
Q
  1. Why do we use cipro for crohns?

2. May take up to how long for remission?

A
  1. May have some immunosuppressive properties

2. May take up to 6 weeks for remission

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29
Q
  1. HOw should we administer Flagyl?
  2. May have what kind of properties?
  3. May take how long to respond to therapy?
  4. Duration of therapy may be up to how long?
A
  1. Start at a higher dose and decrease after response is noted
  2. Likely also has some immunosuppressive properties
  3. May take 1-2 months for response to therapy
  4. Duration of therapy may be up to 12 months
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30
Q

What are the Immune modifiers?

4

A
  1. Azathioprine
  2. 6-mercaptopurine
  3. Methotrexate
  4. Infliximab
31
Q

Clinical use of Azathioprine and 6-mercaptopurine

  1. Uses?
  2. Specific diseases?
  3. ______months of treatment induces remission in 50-60% of patients with active disease?
  4. _____% maintain remission?
  5. Use may allow you to do what?
A
  1. Induction and maintenance of remission
  2. UC and Crohn’s
  3. 3-6 months
  4. 80% maintain remission
  5. Use may allow reduction of steroid therapy
32
Q

Immune Modifiers

  1. Is an active metabolite of what?
  2. Describe its half life?
  3. Prolonged kinetics results in a what?
  4. Preg cat?
A
  1. Active metabolite of azathioprine
  2. Short half life but active metabolite with long half life of 3-13 days
  3. Prolonged kinetics results in a median delay of 17 weeks before onset of therapeutic benefit from oral medication.
  4. Preg Cat. D (although recent publications suggest it may be continued safely during pregnancy)
33
Q

Azathioprine and 6-mercaptopurine MOA

2

A
  1. Inhibition of purine neucleotide metabolism and DNA synthesis and repair, resulting in inhibition of cell division and proliferation.
  2. May decrease proliferation of immune cells leading to lower autoimmune activity
34
Q

Azathioprine and 6-mercaptopurine side effects
8

Monitor what? 2

A
  1. Side effects are mostly dose related
  2. Nausea, vomiting, diarrhea
  3. Fever, rash
  4. Pancreatitis
  5. Bone marrow suppression (leukopenia)
  6. Hepatic toxicity
  7. Arthralgias, malaise
  8. Drug toxicity with use of concurrent use of Allopurinol

Monitoring:
Routine
1. CBC and
2. liver function tests

35
Q

Azathioprine and 6-mercaptopurine

  1. COntraindicated in who?
  2. Decrease dose for CrCl of what?
A
  1. Contraindicated in pregnancy or active liver disease

2. Decrease dose for CrCl less than 50

36
Q

Methotrexate
clinical uses? 2

Can be given how? 3

A

Clinical Use:

  1. Induction and maintenance of remission in patients with Crohn’s disease
  2. Effects in UC are uncertain

Can be given PO, SQ or IM

37
Q

Methotrexate
MOA?
2

A
  1. Inhibits metabolism of folic acid
    - -Shares structural homology with interleukin-1, thus interferes with its inflammatory actions
  2. May stimulate apoptosis and death of activated T lymphocytes
38
Q

Methotrexate

  1. Preg cat?
  2. Adjust dose for who?
  3. Contraindicated in who? 2
A
  1. Preg Cat. X
  2. Adjust dose for altered renal clearance
  3. Contraindicated in
    - pregnancy and
    - active liver disease
39
Q

Methotrexate SE?

9

A
  1. Alopecia
  2. Muscositis
  3. Bone marrow depression – higher dosage
  4. Megaloblastic anemia – higher dosage
  5. Cirrhosis and liver fibrosis
  6. Pneumonitis
  7. Folic acid deficiency
  8. Rash
  9. Nausea and diarrhea
40
Q

Cyclosporine

  1. Used for what?
  2. Improvement should be seen in who?
  3. Duration of therapy?
  4. Given how?
  5. SE? 3
A
  1. Used for the acute treatment of severe, steroid refractory exacerbations of UC in hospitalized patients
  2. Improvement should be seen in 2-3 days
  3. Duration of therapy 7-10 days
  4. Given IV
  5. Side effects
    - Nephrotoxicity,
    - hypomagnesemia,
    - hypertension
41
Q

Anti-tumor necrosis factor agents
TNF Inhibitors
1. Leads to symptomatic improvement in 2/3 of patients with what kind of dz?

  1. Leads to disease remission in 1/3 of patients with what kind of dz?
  2. Used when pts arent responding to what? 3
A
  1. moderately severe or fistulizing Crohn’s
  2. moderately severe or fistulizing Crohn’s
  3. Used when patients are not responding to
    - steroids,
    - 6-mercaptopurine or
    - methotrexate
42
Q

TNF inhibitors approved for use in severe refractory CD. What are the drugs? 3

A
  1. Infliximab (Remicade)
  2. Adalimumab (Humira)
    3 .Certolizumab Pegol (Cimzia)
43
Q

Infliximab (Remicade)

is also indicated in what?

A

Also indicated for maintaining remission in CD and treating UC

44
Q 
Anti-tumor necrosis factor agents
TNF Inhibitors
Infliximab (Remicade)  
1. Preg cat?
2. Administered how?
3. Describe the dosing? 2
A
  1. Preg. Cat B
  2. Administered via IV infusion
  3. Given 5mg/kg dose intially, at two weeks and at 6 weeks.
    Then maintenance every 6-12 weeks
45
Q 
Anti-tumor necrosis factor agents
TNF Inhibitors
Infliximab (Remicade)  
MOA?
3
A
  1. Dysregulation of the TH1 T cell response present in IBD.
  2. Antibody to human TNF-alpha
  3. Neutralizes membrane bound TNF
46
Q

Anti-tumor necrosis factor agents
TNF Inhibitors
SE?
4

A 
Infusion reaction (>10% of patients)
>10% of patients
1. Fever, chills
2. Pruritis, urticaria
3. Chest pain, dyspnea
4. Hemodynamic instability

Prophylactic Tylenol and Benadryl

47
Q

Anti-tumor necrosis factor agents
TNF Inhibitors:
1. Infusion reaction more common with which infusions?

  1. Prophylactic treatment? 2
A
  1. Infusion reaction more common with 2nd and subsequent infusions other than the 1st.
  2. Prophylactic Tylenol and Benadryl
48
Q

Anti-tumor necrosis factor agents
-TNF Inhibitors: Delayed infusion reaction: (5 % of patients)? 4

  • occurs how soon after treatment?
  • Treat with?
A
  1. Myalgia, arthralgia
  2. Fever
  3. Rash, urticaria
  4. Facial, hand and lip edema
  5. Occurs 1-2 weeks after infusion
  6. Treat with antihistamines or corticosteroids
49
Q

Anti-tumor necrosis factor agents
TNF Inhibitors
1. BBW?

  1. What do we need to test for?
A
  1. Side effects: Black box warning
    Reactivation of latent TB
  2. All patients must have PPD prior to use
    Prophylactic therapy for those with + PPD’s
50
Q
  1. Start with an what for most cases except severe?
  2. Choose the formula for delivery based on the extent of what?
  3. Use of combo oral and rectal 5-ASA have better efficacy when?
  4. Move onto what if no response in 3-4 weeks or
  5. start with _______ if more severe cases?
  6. Antibiotics are beneficial in what only and can be used 2nd line after failure of 5-ASA.
A
  1. aminosalicylate like mesalamine
  2. GI tissue involved
  3. better efficacy than either agent alone. Use together
  4. corticosteroids
  5. steroids, (rectal steroids very effective in UC)
  6. CD
51
Q

Pharmacologic therapy for IBS

7

A
  1. Antispasmodic agents
  2. Antidiarrheal agents
  3. Anticonstipation agents
  4. Psychotropic agents
  5. Serotonin receptor agonists and antagonists
  6. Nonabsorbable antibiotics
  7. Probiotics
52
Q

IBS Pharmacotherapy
Based on predominant complaint
Constipation?
5

A

Constipation

  1. Increase fluids, fiber
  2. TCAs or SSRIs
  3. Peppermint oil
  4. Osmotic laxatives
  5. Lubiprostone
53
Q

IBS Pharmacotherapy
Based on predominant complaint
Pain?

4

A

Pain

  1. Antispasmodics (Anticholinergics)
  2. TCA’s (Tricyclic antidepressants) (low dose)
  3. SSRI (Selective serotonin reuptake inhibitors)
  4. Peppermint oil
54
Q

IBS Pharmacotherapy
Based on predominant complaint
Diarrhea?
6

A
  1. Fiber (sometimes controversial in the symptomatic treatment of IBS)
  2. Loperamide
  3. Cholestramine
  4. TCA’s
  5. Lotronex
  6. SSRI’s
55
Q

Antispasmodics
2

Work primarily through what receptors?

A
  1. Anticholinergics
  2. Belladonna alkaloids
  • Work primarily thru cholinergic receptors
  • Provide relief through antispasmotic action
56
Q

Antisposmodics

  1. What are the anticholinergics? 2
  2. What are the Belladonna alkaloids? 2

Preg cat?

A

Anticholinergics

  1. Hyoscyamine (Levbid, Levsin SL)
  2. Dicyclomine (Bentyl)

Belladonna alkaloids

  1. Donnatol
  2. Clidinium (Librax)

C

57
Q

MOA of Antispasmodics

2

A
  1. Block action of acetylcholine at parasympathetic sites in secretory glands, smooth muscle and CNS
  2. Inhibit muscarinic cholinergic receptors in the enteric plexus and on smooth muscle

Plain and simple, these reduce contraction of the bowel

58
Q

Pharmacotherapy of antispasmotics

  1. What kind of SE?
  2. Caution in what pts? 4
  3. Contraindications? 8
A
  1. Watch for anticholinergic side effects
  2. Caution in the
    - elderly,
    - BPH,
    - HTN,
    - hyperthyroidism
  3. Contraindications:
    - Peptic ulcer
    - Arrhythmias
    - Congestive heart failure
    - Severe ulcerative colitis where bowel movements have stopped
    - Glaucoma
    - Myasthenia gravis , COPD
    - Infants less than 6 months of age
    - Nursing Mothers
59
Q

1st and 2nd line antispasmodics

  1. Used for treatment of what? 3
  2. First line agent?
  3. Second line agent?
  4. Can be used how?
A
  1. Treatment of
    - postprandial abdominal pain,
    - gas, bloating,
    - fecal urgency
  2. Dicyclomine (Bentyl) 1st line agent
    Short half life = less cholinergic side effects
  3. Hyoscyamine Sulfate (Levbid, Levsin SL) 2nd line agent Longer half life
    Sublingual, oral, or oral sustained release (Q 12 hours)
  4. Can be used on a prn basis and with anticipation of stressors
60
Q

Antispasmodics summary

  1. Causes relaxation of what?
  2. MOA?
  3. Most commonly used types? 2
  4. SE?
A
  1. Smooth muscle relaxation of the GI tract
  2. MOA: Block acetylcholine at muscarinic cholinergic receptors
  3. Most commonly used: Bentyl and Levbid
  4. Anticholinergic side effects
61
Q

Anticonstipation agents

3

A
  1. Miralax (polyethylene glycol)
    - Osmotic laxative
  2. Increased intestinal chloride and fluid secretion
    - Lubiprostone (Amitiza)
    - Linaclotide (Linzess)
62
Q

Chloride Channel Activator: Lubiprostone (Amitiza)

  1. MOA?
  2. Approved only for who?
  3. Use only when?
  4. SE?4
  5. Long term use?
A
  1. MOA: Locally acting calcium channel activator that increases intestinal fluid secretion
  2. Approved only for women with constipation dominant IBS
  3. Use only if persistent constipation after trial of other treatments
  4. SE:
    - most common nausea,
    - diarrhea,
    - abdominal pain,
    - abdominal distention
  5. Long term safety has not been established
63
Q

Linaclotide (Linzess)

  1. MOA?
  2. Interactions?
  3. Administration?
A
  1. MOA: Binds to GC-C receptor on luminal surface of the intestinal epithelium ultimated affects the chloride and bicarbonate levels in the intestine and increases intestinal fluid and causes accellerated intestinal transit.
  2. Interactions: none
  3. Admininstration: once daily in the AM after eating
64
Q

Psychotropic agents used in IBS

  1. TCAs? 3
  2. SSRI? 5
A
  1. TCA’s
    - Amitryptyline (Elavil)
    - Desipramine (Norpramin)
    - Imipramine (Tofranil)
  2. SSRI
    - Escitalopram (Lexapro)
    - Citalopram (Celexa)
    - Sertraline (Zoloft)
    - Paroxetine (Paxil)
    - Fluoxetine (Prozac)
65
Q 
Tricyclic Antidepressants (TCA’s)
MOA 3

Preg cat?

A
  1. Visceral analgesic effect by increasing pain threshold in the gut
  2. Prolongs oral-cecal transit time
  3. Increases global well being

Cat C

66
Q

What are the TCAs?

3

A
  1. Imipramine (Tofranil) Preg. Cat C
  2. Amitriptyline (Elavil) Preg. Cat C
  3. Desipramine (Norpramin) Preg.
67
Q

TCA contraindications?

3

A

Contraindications:

  1. Narrow angle glaucoma
  2. Recent MI
  3. MAOI’s or Fluoxetine (Prozac) in patients who took them in the previous 2 weeks
68
Q

SSRIs may help with what?

A

May lead to improvement in overall sense of well being but have little impact on abdominal pain or bowel symptoms.

69
Q

Alosetron (Lotronex)

is what kind of drug?

A

5-HT3 receptor inhibitor

70
Q

Alosetron (Lotronex): Contraindications: Hx of… ?

7

A
  1. chronic/severe constipation or sequelae from thereof
  2. Ileus, obstruction, stricture, toxic megacolon
  3. GI perforation, adhesions
  4. Ischemic colitis, impaired intestinal circulation
  5. Crohn’s or UC
  6. Diverticulitis/diverticulosis
  7. Hx of thrombophlebitis/hypercoagulable state
71
Q
  1. Alosetron (Lotronex)
    who is this indicated for?
  2. Why was it initially pulled from the market?
A
  1. Indicated only for women with severe diarrhea-predominant IBS who have not responded adequately to conventional therapy.
  2. because of serious life-threatening, gastrointestinal side effects including ischemic colitis and serious complications of constipation
72
Q

Before receiving the initial prescription for LOTRONEX what must happen? 2

A
  1. the patient must read and sign the Patient-Physician Agreement for Alosetron
  2. Prescribers need to enroll in the Prometheus Prescribing Program for alosetron
73
Q
  1. Nonabsorbable antibiotics
    used for what?
  2. What is the antibiotic in this category?
A
  1. Refractory symptoms, esp. bloating
  2. Rifaximin (Xifaxan)
    Not FDA approved
74
Q

What probiotic has been used for IBS?

A

Bifodobacterium infantis has shown modest improvement in symptoms in small studies

Gastroenterology (20 decks)

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