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Pharmacology II > Inflammatory Bowel Disease > Flashcards

Inflammatory Bowel Disease Flashcards

1
Q

What are the distinguishing factors of ulcerative colitis?

A

Mucosal inflammatory condition
Confined to the rectum and colon
Continuous pattern of involvement

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2
Q

What are distinguishing factors of Crohn’s disease?

A

Transmural inflammation of GI tract (throughout the full thickness of the bowel wall
Can affect any segment of the GI tract
Skip pattern involvement
strictures, fistulas, and ulcers

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3
Q

What are the two conditions that cause IBD?

A

Ulcerative colitis and Crohns Disease

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4
Q

What are the sx of ulcerative colitits?

A

Bloody diarrhea and abdominal pain = cardinal sx

Severe cases: fever, anorexia, weight loss

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5
Q

What is the course for ulcerative colitis?

A

Chronic, recurrent, unpredictable
65-75% exacerbations and remissions
INCREASED RISK OF CANCER IS UC >7-10 YEARS

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6
Q

What are the extraintestinal manifestations of ulcerative colitis?

A

erythema nodosum, arthritis, pyoderma gangrenosum, uveitis, chronic active hepatitis, cirrhosis, sclerosing cholangitis, oral aphthous ulcerations

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7
Q

What are the sx of Crohn’s Disease?

A

DIARRHEA AND ABDOMINAL PAIN= cardinal sx

Weight loss, vomiting, fever, perianal discomfort, bleeding= common complaints

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8
Q

What are the extraintestinal manifestations associated with Crohn’s disease?

A

Extraintestinal manifestations: erythema nodosum, arthritis, pyoderma gangrenosum, uveitis, ankylosing spondylitis, oral aphthous ulcerations, cholelithiasis, nephrolithiasis

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9
Q

What are the infectious causes of IBD?

A

Viruses
Bacteria
Mycobacteria
Chlamydia

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10
Q

What are the genetic causes of IBD?

A

1st degree relatives have 4-20s risk of IBS
Metabolic defect
Connective tissue disorder

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11
Q

What are the environmental causes of IBD?

A

Diet

Smoking

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12
Q

What are the immune defect causes of IBD?

A

Altered host susceptibility

Immune mediated mucosal damage

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13
Q

What are the psychological causes of IBD

A

Stress
Emotional/physical trauma
Occupational

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14
Q

What are the infectious factors of IBD?

A

–Increase in pathogenic bacteria
Bacteroides
Escherichia coli

–Decreased beneficial bacteria
Bifidobacterium
Lactobacillus species

–Clinical controversy
Mycobacterium avium subspecies paratuberculosis (MAP)

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15
Q

What are the immunological factors of IBD?

A
  • CD patients have generalized impaired immune response
  • Trauma of skin or intestine
  • Decreased blood flow to site in pts with CD vs. non-CD pts
  • Decreased neutrophils and IL-8 accumulation at injury site (part of the healing process, starting to heal and clot)
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16
Q

What are the environmental factors of IBD?

A

Luminal bacteria
Aberrant immune response to enteric flora

Diet
Dietary antigens contribute to inflammation

Smoking
Protective for (Negative correlation) UC
More aggressive disease (Increase in flares) in CD

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17
Q

What are the drugs to avoid with IBD?

A

Opiates
Reduce GI Motility

NSAIDS
Worsen IBS by disrupting mucosal barrier

Antidiarrheals
Loperamide, Diphenoxylate/Atropine
Risk of Precipitating Toxic Megalocolon

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18
Q

What are the goals of therapy for IBD?

A

Resolve acute inflammatory process
Resolve complications (fistulas, abscess)
Alleviate systemic manifestations
Maintain remission

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19
Q

What are the general principles of treatment of IBD?

A

Disease Location
Severity–Mild, Moderate, Severe
Complications–Fistulas, Toxic megacolon
Patient Response–Prior symptomatic response, tolerance
Therapy sequential– Treat acute disease, Maintain remission

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20
Q

What are the Non-pharmacologic managements for UC?

A

Psychological support

Nutritional measures

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21
Q

What are the nutritional measures for non-pharmacologic management of UC?

A

NO DIET IMPROVES OR EXACERBATES UC
Reduce dietary fiber during exacerbation
Folic acid (1mg/day) when leafy veggies restricted or sulfasalazine being used
Oral iron if anemia or considerable rectal bleeding
Metamucil 1-2 times/day for mild diarrhea during remissions

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22
Q

What can be used to treat mild-moderate ulcerative colitis?

A 
Sulfasalazine  
OR
Mesalamine    
OR
Aminosalicylate at dose equivalent to mesalamine 
OR 
if Distal Disease
Mesalamine Enema/Suppository
Corticosteroid Enema

Remission
Reduce dose by half
OR
With enema/ suppository: Reduce frequency to q 1-2days

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23
Q

What should you replace when you prescribe a patient sulfasalazine for UC?

A

Folic acid

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24
Q

What can be used to treat moderate to severe UC?

A

Sulfasalazine OR Mesalamine
Plus Prednisone

Remission:
Taper prednisone, then reduce sulfasalazine or mesalamine after 1-2 months to approximately half

Refractory
Add Azathioprine or Mercaptopurine (6-MP) OR
Consider Infliximab (antibody) if no response

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25
Q

What can be used to treat severe or fulminant ulcerative colitis?

A

Hydrocortisone

Remission: Change to prednisone add sulfasalazine or mesalamine

If no response in 5-7 days:
Cyclosporine IV
If no response, patient candidate for colectomy

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26
Q

When is surgery necessary in UC?

A

High-grade dysplasia, suspected cure

Pts w/ severe disease required high-dose steroids that can’t be tapered after 6-12 months

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27
Q

Can surgical resection in ulcerative colitis cure?

A

Yes

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28
Q

What is used for ulcerative colitis maintenance?

A

Aminosalicylates and/or AZA or 6-MP

Alternative Infliximab

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29
Q

What are the non-pharmacologic managements of Crohns disease?

A

Psychological support

Nutritional meausres

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30
Q

What are the nutritional measures that are used as non-pharmacologic management of Crohns disease?

A

Limit fiber with cramping and diarrhea
Decrease fat intake when steatorrhea
Multivitamin with minerals daily

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31
Q

What do you treat mild-moderate Crohns thats in the ileocolic or colonic area with?

A

Sulfasalazine
or
Oral mesalamine

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32
Q

What do you treat mild-moderate Crohns thats in the perianal area with?

A 
Sulfasalazine 
or
Oral mesalamine 
and/or
Metronidazole
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33
Q

What do you treat mild-moderate Crohns thats in the small bowel with?

A 
Oral mesalamine 
or
Metronidazole 
or
Budesonide
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34
Q

What do you treat moderate to severe Crohn’s with?

A

Mild-moderate protocol
Add prednisone
or

If refractory and fistulizing disease
Add infliximab

Inadequate response
Adalimumab
Natalizumab
Certolizumab
Once pt responds to therapy
Taper prednisone after 2-3 weeks
Add AZA, 6-MP or MTX  (methotrixate)
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35
Q

Do you need to taper prednisone?

A

Yes

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36
Q

How do you treat severe-fulminant crohns?

A

Hydrocortisone IV
If no response in 5-7 days
Cyclosporin IV
Assess need for surgical resection

37
Q

What is the maintenance therapy for Crohns disease?

A

No role for long term corticosteroids

Azathioprine/6-MP
1st line for maintenance

Azathioprine/6-MP or mesalamine also effective after surgical resection to prevent recurrence

Infliximab 5mg/kg IV q wk x 6, then q 8 weeks

Methotrexate 25mg IM up to 16 weeks followed by 15mg IM weekly

38
Q

What is the maintenance therapy for severe-fulminant disease?

A 
Severe-fulminant disease
Hospitalization--Surgical interventions, Supportive care
Parenteral corticosteroids
IV cyclosporin, tacrolimus
Infliximab
39
Q

What are the drugs used to treat IBD?

A

Aminosalicylates:
Sulfasalazine
Mesalamine

Corticosteroids
Immunomodulators:
Azathioprine
6-MP

Methotrexate (MTX)

Cyclosporin

Antibiotics

Monoclonal Antibodies
Infliximab (Remicade)
Adalimab (Humira)
Natalizumab (Tysabri)

40
Q

What are the aminosalicylate drugs?

A

Sulfasalazine

Mesalamine

41
Q

Sulfasalazine (Azulfidine)-MOA

A

Aminosalicylate

Metabolized by intestinal bacteria to to the active component 5-aminosalicylate (5-ASA) and sulfapyridine (mesalamine)

42
Q

Sulfasalazine (Azulfidine)- use

A

Most commonly used for inducing and maintaining remission

Response can take 2-3 weeks

43
Q

Sulfasalazine (Azulfidine)- contraindications

A

SALICYLATE HYPERSENSITIVITY

Renal impairment- monitor SCr

44
Q

Sulfasalazine (Azulfidine)- side effects

A

NOT WELL TOLERATED
N/V, heartburn, anorexia
HA
HYPERSENSITIVITY RXNS (RASH, FEVER)- DO NOT USE IN PTS W/ SULFA ALLERGY
BLOOD DISORDERS (ANEMIA, THROMBOCYTOPENIA, GRANULOCYTOPENIA)
CAN IMPAIR FOLIC ACID ABSORPTION
IDIOSUNCRATIC RXNS (HEPATOCELLULAR INJURY, AGRANULOCYTOSIS, LUPUS-LIKE SYNDROME)
LOW SPERM COUNTS

45
Q

Mesalamine (Asacol, Rowasa, Pentasa, Canasa)- MOA

A

Aminosalicylate
Unclear various effects on inflammatory process
Formulations vary and target different parts of the colon
Mesalamine or suppositories for rectosigmoid disease
Delayed release formulations of mesalamine for Crohn’s ileitis
Response is slow

46
Q

Mesalamine (Asacol, Rowasa, Pentasa, Canasa)- side effects

A

Local itching and mild rectal irritation with topical enemas

Idiosyncratic rxns: pleuropericarditis, pancreatitis, nephrotic syndrome

47
Q

What are the corticosteroids?

A

Prednisone, Budesonide, Prednisolone, Hydrocortisone, Methyprednisolone (available in a syrup)

48
Q

Corticosteroids- MOA

A

Anti-inflammatory effects
Improves Symptoms
Improves disease severity

49
Q

Corticosteroids-ROA

A

PO
IV- hospitalization for parenteral
Topical: suppositories, foams, enemas (effective in distal colonic inflammation)

50
Q

How are corticosteroids used in crohns disease?

A

Budesonide for mild-moderate ileal or right sided disease

For moderate-severe disease or patients unresponsive to aminosalicylates or budesonide
Oral steroids

For severe or fulminant disease or unable to tolerate PO
IV steroids

51
Q

How are corticosteroids used for ulcerative colitis?

A

IV hydrocortisone or methylprednisolone may prevent need for colectomy in some patients
Steroids should be tried before surgery in most patients
Methylprednisolone preferred for reduced mineralcorticoid effect

52
Q

Corticosteroids- tapering

A

Induction of response takes 7-14 days
Taper by 5mg/wk prednisone or equivalent
Budesonide taper: 9mg6mg3mg
Inability to taper is indication for amtimetabolite and/or infliximab therapy
Parenteral steroid indicated in pts failing to respond to 7-14 days of high dose oral prednisone or equivalent

53
Q

When do is tapering needed for corticosteroids and by how much should predinisone or equivalent be taperd weekly?

A

Anytime over 7 days the patient will need to be tapered

5 mg/wk

54
Q

Corticosteroids- monitoring for complications

A

Glucose intolerance/ metabolic abnormalities
Hyperkalemia
Hyponatremia
glucose

Greater risk for adrenal insufficiency and infections
N/V
Postural hypotension

Long-term therapy (>3mo)
Bone density
Annual eye exam

55
Q

What are the immunosuppressives?

A

6-Mercaptopurine (6-MP)

Azathioprine (Imuran)

56
Q

What is azathiprine (imuran)?

A

A prodrug metabolized to 6-MP

57
Q

Immunosuppressives- 6-Mercaptopurine (6-MP), Azathioprine (Imuran)- MOA

A

Antagonizes purine metabolism; inhibits DNA, RNA and protein synthesis
Steroid-sparing achieve or maintain control and allow reduction or discontinuation of steroids

58
Q

Is immunosuppressive maintenance therapy less toxic than chronic steroid therapy?

A

yes

59
Q

Immunosuppressives- 6-Mercaptopurine (6-MP), Azathioprine (Imuran)- Toxicity bone marrow and pancreas5

A 
Bone marrow suppression 2-5%
Dose related
Managed by dose reduction/withdrawal
Leukopenia, thrombocytopenia, pancytopenia
RISK OF LYMPHOMA 4 FOLD INCREASE

Pancreatitis 1.3-3.3%
Dose independent
Occurs within 3-4 weeks of start
Resolves with stopping drug

60
Q

Immunosuppressives- 6-Mercaptopurine (6-MP), Azathioprine (Imuran)- Toxicity GI effects, others, and Infections

A

GI effects
N/V, abdominal pain
Occurs early, improves with time or with dose reduction

Other
Fever, rash, arthralgias
Dose independent

Infections
Disseminated CMV, herpes zoster, pneumonia, Q fever, viral hepatitis
Occur without leukopenia
Increased risk if combined with steroids

61
Q

Immunosuppressives- 6-Mercaptopurine (6-MP), Azathioprine (Imuran)- drug interactions

A 
Inhibition of metabolism leading to increased myelosuppression
Sulfasalazine, mesalamine
Allopurinol
Aspirin
Furosemide
62
Q

What is the immunodulator drug?

A

Methotrexate

63
Q

Immunodulator- Methotrexate- MOA

A

Folic acid antagonist with anti-inflammatory effects
Reduces steroid needs
Improves disease control

64
Q

Immunodulator- Methotrexate- ADRs

A

Nausea

Elevated transaminases- huge problem have to monitor for LFT

65
Q

Immunodulator- Methotrexate- Toxicities

A

Leukopenia
N/V
Absolute contraindication in pregnancy (Category X)
–Stop therapy 3 months prior to conception
–Folate supplementation prior to conception
–Contraindicated in breastfeeding
Hypersensitivity pneumonitis (rare)
Hepatic fibrosis
–Most significant in long term therapy
–Risk with >1500 mg total cumulative dose and daily dosing
–DC if moderate/severe fibrosis or cirrhosis found on biopsy

66
Q

Cyclosporin (Neoral or Sandimmune)-MOA

A

MOA: inhibits production and release of IL-2  inhibits activation of T-lymphocytes

Concomitant IV steroids recommended

Cyclosporin alone unable to maintain remission
Requires “bridging” with AZA or 6-MP
Convert IV to PO
PO dose is 2x IV dose
Wean off cyclosporin and steroids over next few months

67
Q

Cyclosporin (Neoral or Sandimmune)- toxicities

A 
HTN
Hypertrichosis- abnormal hair growth on the body
ELECTROLYE ABNORMALITIES
NEPHROTOXICITY
Opportunistic Infections
Requires PCP prophylaxis
68
Q

Tacrolimus (Prograf)-MOA

A

inhibits T-lymphocyte activation

Fungus (streptomyces)

69
Q

Tacrolimus (Prograf)- adverse reactions

A 
Tend to resolve with dose reductions
HA
Increased serum creatinine
Nausea
Insomnia
Leg cramps
Paresthesias
Tremors
70
Q

What are the monoclonal antibodies?

A

Infliximab (Remicade)
Adalimumab (Humira)
Natalizumab (tysabri)

71
Q

Infliximab (remicade)- MOA

A

Monoclonal Antibodies
Monoclonal antibody that binds to TNF-alpha
Inhibits inflammatory cytokines, inhibits leukocyte migration and activation of neutrophils

72
Q

Infliximab (remicade)- Contraindications

A 
NYHA class III/IV heart failure
Dose should not exceed 5mg/kg in other pts with congestive heart failure

Hepatitis
Reactivation of hepatitis B
Autoimmune hepatitis
Discontinue use with LFTs 5x ULN

73
Q

Infliximab (remicade)- antibodies to infliximab

A

Increased risk of infusion rxn, shorter duration of response

regularly scheduled less immunogenic than episodic

74
Q

Infliximab (remicade)- Toxicities infections and infusion reactions

A

INFECTIONS
Bacterial, mycosal, mycobacterium
Higher TB rates with more extrapulmonary involvement

INFUSION REACTIONS
During or after (1-2 hrs)
HA, dizziness, nausea, erythema at site, flushing, fever, chills, chest pain, cough, dyspnea, pruritis
Mechanism unclear- not IgE type 1
Doesn’t occur till after 1st infusion; not at every infusion

75
Q

Infliximab (remicade)- Toxicities delayed hypersensitivity, autoantibodies, and malignancy and lymphoproliferative disorder

A

Delayed hypersensitivities
3-14 days after infusion
Myalgia, arthralgia, fever, rash, pruritis, dysphagia, urticaria, HA
Resolve spontaneously or require steroids
Prednisone 40mg PO or methylprednisolone 100mg IV 30 min before
Risk factor: long interval between treatments

Autoantibodies
15-40% develop anti-dsDNA ANA
Development of drug-induced lupus rare
Reversible with DC

Malignancy and lymphoproliferative disorder
Longstanding CD and tx with immunosuppression more likely to develop lymphomas

76
Q

Adalimumab (Humira)- MOA

A

recombinant fully-human immunoglobulin-1 anti-tumor necrosis factor (TNF)-alpha monoclonal antibody
Evaluate for TB before starting therapy

77
Q

Adalimumab (Humira)- Side effects

A

BLACK Box Warning of serious infections
TB, invasive fungal, other opportunistic infections

Rash, injection site rxn, HA, URI, development of autoantibodies to drug, development of anti-nuclear antibodies (ANA)

Risk of reactivating hepatitis B

78
Q

What are adalimumab (humira) recommended for?

A

Only crohns disease

79
Q

How do you get Natalizumab (tysabri)?

A

Pts must be enrolled in special restricted distribution program
Crohn’s Disease-Tysabri Outreach Unified Commitment to Health (CD-Touch) Prescribing Program

80
Q

Natalizumab (tysabri)- MOA

A

recombinant immunoglobulin-4 monoclonal antibody

81
Q

Natalizumab (tysabri)- adverse effects

A

Major adverse effect: progressive multifocal encephalopathy

82
Q

What are the antibiotics used to treat IBD?

A 
Metronidazole (Flagyl)
Ciprofloxacin
Metronidazole + ciprofloxacin
Rifamixin
Clarithromycin
83
Q

Metronidazole (Flagyl)- indications

A

For treatment of ileocolitis or colitis
Failure to respond to sulfasalazine
For treatment of abscesses, rectovaginal fistulas, proctocolectomy wounds
Low dose maintenance therapy to minimize recurrence of perineal disease

84
Q

Metronidazole (Flagyl)- ADRs

A

GI upset, metallic taste, paresthesias, antabuse-like rxn

85
Q

Ciprofloxacin

A

Effective in resistant disease when used in combination with standard tx

86
Q

Metronidazole + ciprofloxacin

A

Improve and can promote closure of fistulas

Tend to recur once drugs stopped

87
Q

Rifamixin

A

Data from open-label trial found statistically significant response in mild-moderate disease

88
Q

Clarithromycin

A

Response in pts otherwise unresponsive

89
Q

Opiates

A

Provide symptomatic relief of diarrhea
Diphenoxylate/atropine, codeine, tincture of opium, paregoric, loperamide
MOA: inhibits excessive GI motility and GI propulsion

Pharmacology II (23 decks)

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