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PHARM 345 - Other > Inflammatory Bowel Disease Drug Effects > Flashcards

Inflammatory Bowel Disease Drug Effects Flashcards

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1
Q

Where do the different IBD Drugs act

A

Sulfasalicyclates:
- Directly on Large/Small Bowel Lining

Corticosteroids
- On adrenal gland

Immunosuppressants
- On Large/Small bowel

Biologics:
- On Large/Small bowel

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2
Q

Aminosalicylates
- Efficacy

A

Onset 2-4 weeks

Response 4-8 weeks

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3
Q

Aminosalicylates
- Role

A

New diagnosis or mild symptoms
- Induction Therapy: Mild to Moderate UC>CD (Sulfasalazine only for CD)
- Maintenance Therapy: Remission UC (Sulfasalazine only for CD)

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4
Q

Aminosalicylates
- Dose for Induction vs Maintenance Therapy

A

Higher dose for Induction Therapy
Lower dose for Maintenance Therapy

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5
Q

Aminosalicylates
- MOA

A

Acts directly on lining of small and large bowel

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6
Q

Aminosalicylates
- Route

A
  • Oral
  • Rectal
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7
Q

Sulfasalazine
- Adverse Effects

A

Dose Related
- Nausea
- Dizziness

Non-Dose Related
- Hypersensitivity

  • Slow acetylators have greater adverse effects
  • Reduces Folate absorption (Supplementation needed in pregnancy)
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8
Q

5-ASA
- Adverse Effects

A
  • Flatulence
  • Abdominal pain
  • Thrombocytopenia
  • Olsalazine (Diarrhea)

Used when pt can not tolerate SSZ

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9
Q

Aminosalicylates
- Considerations

A
  • For Chron’s disease only Sulfasalazine is usable
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10
Q

Aminosalicylates
- Choosing a Route

A

Use suppositories for distal disease
- Mezera
- Salofalk
- Pentasa

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11
Q

Corticosteroids
- MOA

A

Anti-inflammatory

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12
Q

Corticosteroids
- Routes

A
  • Oral
  • Rectal
  • Injection
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13
Q

Corticosteroids
- Choosing a Route

A

In acute severe disease where oral prednisone has failed or if pt is hospitalized use injection formulation
- Once pt returns back to normal can switch back to oral

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14
Q

Corticosteroids
- Role

A

Anti-inflammatory used in moderate to severe relapses
- Induction Therapy: Moderate to Severe UC/CD
- Maintenance Therapy: No role

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15
Q

Corticosteroids
- Onset

A

Oral: Fast (Within 1-2 weeks)

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16
Q

Prednisone
- Considerations

A
  • Take in the morning to avoid difficulty sleeping
  • Taper 5 mg weekly or 5 mg every 2-3 days
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17
Q

Budesonide
- Considerations

A

Entocort
- Induction therapy for mild to moderate CD (For up to 3 months)

Cortiment
- Induction therapy for mild to moderate UC (Reassess 1-2 months

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18
Q

Prednisone vs Budesonide

A

Budesonide has less systemic AE
- Extensive first pass metabolism d
- Decreased systemic levels

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19
Q

Corticosteroids
- Adverse Effects

A

Short Term
- Increases infections
- Hyperglycemia
- Dyspepsia
- Acne
- Mood

Long Term
- HPA Axis Suppression
- Cushing’s
- Osteoporosis

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20
Q

HPA Axis Suppression
- Symptoms

A
  • Difficulty sleeping
  • Feeling cold
  • Anxiety
  • Depression
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21
Q

Immunosuppressants
- MOA

A

Decreases immune system response

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22
Q

Immunosuppressants
- Routes

A
  • Oral
  • Injection
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23
Q

Thiopurines
- Onset

A

2-6 months (Slow)

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24
Q

Thiopurines
- Role

A

Severe Symptoms or if Steroid Dependent
- Induction: Moderate to Severe (UC)
–> Have to be combined with steroids

  • Maintenance: UC/CD
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25
Thiopurines - Adverse Effects
Dose-Related - Nausea, diarrhea - Bone marrow suppression - Elevated liver enzymes Non-Dose Related - Hypersensitivity - Sun Sensitivity - Pancreatitis - Hepatitis
26
Thiopurines - Considerations
TPMT inactivates AZA/6-MP - Poor TPMT metabolizers = Increased bone marrow suppression and adverse effects Drugs that inhibit xanthine oxidase increases active metabolites - Allopurinol, Febuxostat = Increases severe adverse effects
27
Thiopurines - Contraindications
- Cancer - Immunodeficiency - Blood Disorders - Liver Failure - Pregnancy/Breastfeeding (However AZA is often used)
28
Methotrexate - Dose
Given weekly - Reduce dose by 50% if CrCl is 10-50 mL/min - May avoid if CrCl is less than 30 mL/min
29
Methotrexate - Onset
Onset 2-4 weeks Symptomatic Response in 12-16 weeks
30
Methotrexate - Role
Severe Symptoms or if Steroid Dependent - Induction: Moderate to Severe (CD) - Maintenance: CD Only use in UC is to combine with biologics to reduce antidrug antibodies
31
Methotrexate - Adverse Effects
Common: - Nausea - Fatigue, Malaise, Difficulty concentrating Less Common - Photosensitivity - Hair Loss Rare: - Pneumonitis (Hypersensitivity) - Cancer (Reversible Lymphoma)
32
Methotrexate - Managing Adverse Effects
Nausea / Vomiting, ALT/AST Elevation, Low WBC/Platelets - Folic Acid Fatigue, Malaise, Difficulty Concentrating 24-48h after dose - Dextromethorphan Photosensitivity, - Sunscreen Hair Loss - Folic Acid, Vit B12, Biotin, Collagen
33
Folic Acid - MOA
Acts as a rescue agent for rapidly dividing cells - Works against MTX inhibition of dihydrofolate reductase
34
Dextromethorphan - MOA
Blocks neurostimulation of homocysteine at NMDA receptors in brain - Preventing headaches, malaise, lethargy
35
Methotrexate - Considerations
- Avoid binge drinking and drinking alcohol 24h after dose - Avoid 3 months prior to conception
36
Methotrexate - Drug Interactions
NSAIDs, Penicillins, PPIs (Considered safe to combine) - Though may reduce renal excretion of MTX --> Hematological adverse effects Trimethoprim (Avoid combined use) - Both increases hematological adverse effects - Decreases renal excretion of MTX --> Hematological adverse effects
37
Biologics - MOA
Binds or blocks specific targets
38
TNFa Inhibitors - Onset
Onset 2-4 weeks Symptomatic Response 8-12 weeks
39
TNFa Inhibitors - Role
Can combine with MTX or AZA - Moderate to Severe (UC/CD) and not respondign to other therapy Effective at healing fistulas
40
TNFa Inhibitors - Continuing Therapy
If responding can continue TNFi for long term - Increase dose Can also switch to immunomodulatory therapy after achieving remission with TNFi - Step-down therapy
41
Adalimumab - Indication
UC and CD
42
Certolizumab - Indication
UC - Not covered
43
Golimumab - Indication
UC
44
Infliximab - Indication
UC and CD
45
TNFa Inhibitors - Specific Adverse Effects
Acute Infusion Reactions - Infliximab Injection Side Reaction -Adalimumab and Golimumab: Delayed Hypersensitivity Reaction - Infliximab
46
Acute Infusion Reaction
Within 10 mins, up to 4 hours - Mild: Pain, itching, fever, chills, flush - Severe: Hypotension, chest pain, dyspnea Treatment: - Premedicate with Cetirizine/Loratadine and Acetaminophen +/- Steroid - Discontinue infusion
47
Injection Site Reaction
Occurs within 24-48h - Common with 2nd and 3rd injection, then disappears - Mild: Red, itchy, painful Treatment: - Treat with Cetirizine/Loratadine - If long lasting use Montelukast
48
Delayed Hypersensitivity Reaction
Occurs 24h to 14d after repeated infliximab infusion - Fever, hives, malaise, joint pain Treatment: - Antihistamine, acetaminophen x3 days - Use steroid if needed - Avoid further infliximab use
49
TNFa Inhibitors - Adverse Effects
Common: - Upper Respiratory Tract Infections, GI, aches Uncommon: - Lupus, skin conditions Rare: - Reactivation of infections (Test for TB and Hep B/C) - Serious infections (Can be masked)
50
TNFa Inhibitors - Contraindications
- Current infection - Moderate to severe heart failure - Demyelinating disorder (MS) - Live attenuate vaccines (Mumps, measles, rubella) - Other biologics / targeted therapy Caution in: - Family history of demyelinating disorders - Lymphoma, skin cancer
51
Anti-Integrin Therapy - MOA
Binds alpha4beta47 integrin on memory T lymphocytes of the gut - Selectively inhibits adhesion to mucosal addressin cell adhesion molecule 1
52
Anti-Integrin Therapy - Onset
UC: Symptomatic improvement 8-14 weeks CD: Symptomatic improvement 10-15 weeks
53
Anti-Integrin Therapy - Role
Can be combined with MTX or AZA - Used in moderate to severe UC or CD where TNFi are not working
54
Anti-Integrin Therapy - Adverse Effects
Similar to TNFi - Upper Respiratory Tract Infections, GI, Aches - Increase in bilirubin and liver enzymes
55
IL-12/23i - MOA
Antagonist to p40 subunit shared by IL-12 and IL-23
56
IL-12/23i - Onset
Symptomatic improvement 6-10 weeks
57
IL-12/23i - Role
Can combine with MTX or AZA - Moderate to Severe CD/UC when TNFi therapy has failed
58
IL-12/23i - Adverse Effects
Similar to TNFi - Upper Respiratory Infections, GI, Aches
59
IL-12/23i - Contraindications
- Current infection - Live vaccines - Other biologic/targeted therapy
60
IL-23i (Mirikizumab) - MOA
Binds p19 subunit of IL-23
61
IL-23i (Mirikizumab) - Onset
Symptomatic response at 12 weeks
62
IL-23i (Mirikizumab) - Role
Can be combined with MTX or AZA - Used in moderate to severe UC when biologic or JAKi do not work
63
IL-23i (Mirikizumab) - Adverse Effects
Similar to TNFi - Upper respiratory infection, GI, Aches
64
IL-23i (Mirikizumab) - Contraindications
- Current infection - Live attenuated vaccine - Other biologic/targeted therapy
65
IL-23i (Risankizumab) - MOA
Selectively binds p10 subunit of IL-23
66
IL-23i (Risankizumab) - Role
Can be combine with MTX or AZA - Used in moderate to severe CD when biologics have failed and/or if steroid dependent
67
IL-23i (Risankizumab) - Adverse Effects
Similar to TNFi - Upper respiratory infection, GI, Aches May cause liver enzyme elevation
68
JAK Inhibitors - MOA
Inhibits JAK-induced pro-inflammatory cytokine production
69
JAK Inhibitors - Role
Can be combined with MTX or AZA - Used in moderate to severe UC/CD when biologics have failed
70
JAK Inhibitors - Considerations
- Risk of GI perforation with history of diverticulitis - Baricitinib can cause VTE, closely monitor for all JAKs - CV risks and Cancer risks - Contraindicated in pregnancy (D/C 6 weeks prior)
71
Tofacitinib vs Upadacitinib
Tofacitinib - Moderate to Severe UC - D/C if not responding by week 16 - AE: Diarrhea, Bradycardia Upadacitinib - Moderate to Severe UC/CD - D/C if not responding
72
JAK Inhibitors - Adverse Effects
Common: - URTI, Headache Less Common: - Serious infections - Decreased WBC and Hb - Masks elevated cholesterol (Does not affect cholesterol itself though) - ALT/AST elevations
73
SP-1 Receptor Agonist - MOA
Activates Sphingosine 1-phosphate receptor modulator on lymphocyte - Reduces lymphocyte release into intestine
74
SP-1 Receptor Agonist - Onset
D/C if no benefit by week 10
75
SP-1 Receptor Agonist - Role
Used in moderate to severe UC when biologic therapy has failed
76
SP-1 Receptor Agonist - Adverse Effects
Similar to TNFi - Upper respiratory infection, GI, Aches - Decrease in Absolute Lymphocyte Count - Serious infections - Decrease Heart Rate - Macular Edema - Increase Liver Enzymes
77
SP-1 Receptor Agonist - Contraindications
- Recent CV Event - AV block - Active infection - Use of MAOi
78
Cyclosporine - Onset
Rapid response within 1-2 weeks
79
Cyclosporine - Role
Induction for acute severe UC refractory to corticosteroids - Not used much in CD
80
Antibiotics - Onset
Short 2-4 week courses (can be repeated)
81
Antibiotics - Role
Used in CD with perianal or colonic involvement OR Used in CD with fistulas
82
Surgery - Role
Used in: - Strictures, abscesses - Fistulae in CD - Colectomy Curative in UC (Removal of diseased parts of colon)

PHARM 345 - Other (36 decks)

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