week 7- IBS and IBD

Question 1

MOA

Lubiprostone (Amitiza)

Class/use

Answer 1

Lubiprostone activates chloride channels → secretion of chloride-rich intestinal fluid → increase in intestinal motility → eases passage of stool

IBS-C

Question 2

Adverse Effects

Lubiprostone (Amitiza)

Answer 2

nausea, abdomnal pain, diarrhea, headache, chest tightness

Question 3

MOA

Linaclotide (Linzess)

ClaSS

Answer 3

Linaclotide is a guanylate cyclase-c agonist → cGMP → stimulation of chloride secretion→ increase in luminal fluid → accelerated intestinal transit

Question 4

Adverse Effects

Linaclotide (Linzess)

Answer 4

diarrhea, abdominal pain, headache

Question 5

MOA

Eluxadoline (Viberzi)

class/USE

Answer 5

mixed opiod agonist and antagonist

14. “Deluxe Massage Chairs”: Eluxadoline is a prescription-only treatment for diarrhea-predominant IBS 15. Mu Kappa Delta shirt: Eluxadoline is a mu and kappa opioid receptor agonist and selective delta opioid receptor antagonist 16. Pancreatitis sponge: Eluxadoline is associated with pancreatitis and is contraindicated in patients with history of pancreatic or gallbladder disorders

IBS-D- anti diarrhea

Question 6

MOA

Rifaximin (Xifaxan)

use/class

Answer 6

antibiotic, anti inflammatory effects

23. Fisherman kid: Rifaximin (a poorly absorbed antibiotic) eradicates ammonia-producing intestinal bacteria (treats hepatic encephalopathy)

Question 7

Adverse Effecs

Eluxadoline

Answer 7

constipation, nausea, abdominal pain

Question 8

Adverse Effects

Rifaximin

Answer 8

dizziness, fatigue, nausea

Question 9

MOA

mesalamine
sulfasalazine

use/class

Answer 9

works locally in the intestinal mucosa by inhibiting cyclooxygenase (COX) and lipoxygenase pathways, reducing the production of pro-inflammatory prostaglandins and leukotrienes. This leads to decreased inflammation in the colon and rectum​.

38. 5-pointed star of USA: inflammatory bowel disease is treated with 5-ASA (sulfasalazine, mesalamine)

Ulcerative Colitis: First-line treatment, particularly for mild to moderate disease.
Crohn’s Disease: Less effective than in UC, but sometimes used for mild colonic involvement.

Question 10

Adeverse effects

mesalanine
sulfasalazine

Answer 10

some abdominal pain/nausuea/headache- rare cases of nephrotoxicity

Question 11

MOA

azathioprine
mercaptopurine

use/class

Answer 11

Azathioprine is a prodrug that is metabolized into 6-mercaptopurine (6-MP) in the body.
6-MP is further converted into active metabolites that **inhibit purine nucleotide synthesis** by blocking the enzyme PRPP amidotransferase. This leads to** impaired DNA and RNA synthesis**, suppressing the proliferation of rapidly dividing cells, including immune cells (B and T lymphocytes).
By reducing immune cell proliferation, these drugs exert an **immunosuppressive and anti-inflammatory effect**​.

## Footnote

Inflammatory Bowel Disease (IBD): Used as maintenance therapy for both ulcerative colitis (UC) and Crohn’s disease (CD).
Also used in autoimmune diseases like rheumatoid arthritis and for preventing organ transplant rejection​.

Question 12

adverse effects

mercaptopurinee
azathioprine

Answer 12

Bone Marrow Suppression: Dose-dependent myelosuppression leading to leukopenia, anemia, and thrombocytopenia. Patients should have regular CBC monitoring.
Gastrointestinal (GI) Toxicity: Nausea, vomiting, pancreatitis, and hepatotoxicity.
Hepatotoxicity: Elevated liver enzymes; monitor liver function tests (LFTs).
Increased Risk of Infection: Due to immunosuppression.
Increased Risk of Malignancy: Long-term use is associated with a higher risk of lymphoma and skin cancers.

16. Depleted birdseed marrow: AZA/6-MP and mycophenolate can cause myelosuppression 17. Immunosuppressed cane: AZA/6-MP can cause immunosuppression and increased risk of infection 18. Squeezed pancreas sponge: AZA/6-MP can cause pancreatitis 19. Liver stain: AZA/6-MP can cause hepatitis

Question 13

MOA

Methotrexate

Answer 13

Methotrexate is a folic acid analog that inhibits dihydrofolate reductase (DHFR), an enzyme responsible for converting dihydrofolate (DHF) into tetrahydrofolate (THF).**
THF is essential for the synthesis of thymidine and purines (nucleotides needed for DNA replication). By depleting THF, methotrexate disrupts DNA, RNA, and protein synthesis, leading to cell death, especially in rapidly dividing cells​.

10. Meat stix: methotrexate (MTX - cytotoxic folate analog) 11. Blocked leaf chef: MTX irreversibly blocks dihydrofolate reductase (inhibits synthesis of THF) 12. Buildup of 2 leaf boats: inhibition dihydrofolate reductase (by MTX) causes increased levels of DHF

Question 14

adverse effects

Methotrexate

Answer 14

Bone Marrow Suppression: Dose-dependent myelosuppression (leukopenia, anemia, thrombocytopenia). Can be reversed with leucovorin (folinic acid) rescue.
**Hepatotoxicity: **Elevated liver enzymes and hepatic fibrosis with long-term use. Requires monitoring of LFTs.
GI Toxicity: Nausea, vomiting, diarrhea, and stomatitis (oral ulcers).
Pulmonary Fibrosis: Rare but serious complication presenting with progressive dyspnea and cough.
**Nephrotoxicity: **At high doses, methotrexate can precipitate in renal tubules, leading to acute kidney injury (AKI).
Teratogenicity: Contraindicated in pregnancy due to its effects on rapidly dividing fetal cells​.

22. Falling foliage: MTX can cause folate deficiency 23. Blasting fireworks: MTX can cause megaloblastic anemia (due to folate deficiency) 24. Depleted bone pan: MTX, 5-FU and hydroxyurea can cause myelosuppression and pancytopenia 25. Immunosuppressed cane: MTX, 5-FU and hydroxyurea can cause immunosuppression and increased risk of infection 26. Fibrotic lung bonsai: MTX can cause pulmonary fibrosis (restrictive lung disease) 27. Liver spot: MTX can cause hepatotoxicity 28. Bald: MTX can cause alopecia 29. Poking mouth: MTX can cause mucositis

Question 15

clinical uses

Methotrexate

Answer 15

Autoimmune Diseases:

Inflammatory Bowel Disease (IBD): Used as maintenance therapy for Crohn’s disease (CD), but less commonly for ulcerative colitis (UC).
Rheumatoid Arthritis (RA): First-line treatment due to its anti-inflammatory effects.
Psoriasis and psoriatic arthritis.
Cancers (at higher doses):

Leukemias (e.g., acute lymphoblastic leukemia, ALL), lymphomas, choriocarcinoma, and **ectopic pregnancy **(by inducing abortion via inhibition of trophoblastic growth).

15. Cracked cancer crab: MTX treats a range of malignancies (e.g. leukemias, lymphomas, breast cancer, head and neck cancer, and lung cancer) 16. Emptying uterus bag: MTX (with misoprostol) can be used as an abortifacient 17. Ectopic key chain: MTX treats ectopic pregnancy 18. Dumping mole: MTX treats invasive molar pregnancy, trophoblastic tumors, and choriocarcinoma 19. Silvery scale kneepads: MTX treats psoriasis 20. Rheumatoid lantern: MTX is a first line treatment for rheumatoid arthritis (disease modifying antirheumatic drug - DMARD) 21. Torn antibody: MTX is useful for immunosuppressive therapy (e.g. treatment of IBD, SLE, vasculitis, dermatomyositis)

Question 16

MOA

Infliximab
Adalimumab

Answer 16

Both infliximab and adalimumab are monoclonal antibodies that target tumor necrosis factor-alpha (TNF-α), a pro-inflammatory cytokine involved in systemic inflammation. preventing it from binding to its receptors.

2. Alpha-shaped TiN Fish: TNF inhibitors suppress TNF-alpha 3. Antibody-shaped fishing rod: Monoclonal antibody TNF inhibitors = infliximab, adalimumab, certolizumab, golimumab 4. Inflictor lure: Monoclonal antibody TNF inhibitors = infliximab [chimeric (mouse/human) anti-TNF-alpha monoclonal antibody] 5. A doll lure: Monoclonal antibody TNF inhibitors = adalimumab (human anti-TNF-alpha monoclonal antibody) 6. Certified lure: Monoclonal antibody TNF inhibitors = certolizumab (antigen-binding fragment of humanized monoclonal antibody)

Question 17

clinical uses

Infliximab
Adalimumab

Answer 17

Inflammatory Bowel Disease (IBD):

**Crohn’s Disease (CD):** Used for moderate to severe cases and for maintaining remission.
**Ulcerative Colitis (UC):** Effective in moderate to severe cases resistant to conventional therapies.
Other Autoimmune Diseases:

**Rheumatoid Arthritis (RA):** Often used in combination with methotrexate.
**Ankylosing Spondylitis and Psoriatic Arthritis.**
**Plaque Psoriasis​.**

Question 18

adverse effects

Infliximab
Adalimumab

Answer 18

Increased Risk of Infection:
Most notably reactivation of latent tuberculosis** (TB)**. Patients must undergo PPD testing or IGRA testing before starting therapy.
**Opportunistic Infections: **Increased susceptibility to fungal infections and other opportunistic pathogens.
Infusion Reactions:
Infliximab, given intravenously, can cause fever, chills, pruritus, and hypotension during infusion.
Adalimumab, administered subcutaneously, typically has fewer infusion-related side effects.
Autoimmune Reactions: Rare cases of drug-induced lupus-like syndrome.
Malignancy Risk: Slight increase in risk of lymphomas, particularly in children and young adults.

18. Sunburnt skin: TNF inhibitors = ↑ risk of skin reactions 19. Bug lights: TNF inhibitors = ↑ risk of opportunistic infections 20. Cavitary lung cactus: TNF inhibitors = ↑ reactivation of latent TB 21. Screen around cactus: Order tuberculin skin test or interferon gamma release assay to screen for latent TB before starting a TNF inhibitor 22. Wolf dog: TNF inhibitors = ↑ risk of drug-induced lupus (most commonly seen with infliximab and etanercept) 23. Crab: TNF inhibitors = ↑ risk of malignancy 24. White stones: TNF inhibitors = ↑ risk of malignancy (e.g. lymphomas, nonmelanoma skin cancers)

Question 19

MOA

vedolizumab (entyvio)

Answer 19

Vedolizumab is a monoclonal antibody that selectively binds to α4β7 integrin, a protein expressed on the surface of T lymphocytes.
By blocking α4β7 integrin, vedolizumab **prevents T lymphocytes from adhering **to MAdCAM-1 (mucosal addressin cell adhesion molecule-1) on endothelial cells in the gastrointestinal tract.
This inhibits the migration of lymphocytes into the gut-associated lymphoid tissue (GALT), reducing gut inflammation without widespread immunosuppression​.

Question 20

Clinical Uses

vedolizumab (entyvio)

Answer 20

Inflammatory Bowel Disease (IBD):
Ulcerative Colitis (UC): For moderate to severe cases, especially when first-line therapies (like 5-ASA, corticosteroids, or TNF-α inhibitors) fail.
Crohn’s Disease (CD): Used for moderate to severe disease that is refractory to conventional treatments.
Unlike TNF-α inhibitors (e.g., infliximab, adalimumab), vedolizumab has **gut-specific effects, **making it less likely to cause systemic immunosuppression​.

Question 20

adverse effects

vedolizumab (entyvio)

Answer 20

**Common: **Headache, nasopharyngitis, arthralgia, and nausea.
Serious: Risk of infections (though lower compared to systemic immunosuppressants), hypersensitivity reactions, and liver injury.
Progressive Multifocal Leukoencephalopathy (PML): Unlike natalizumab (which targets α4 integrin), vedolizumab’s gut-selectivity significantly reduces the risk of PML​.

Question 21

What is the mechanism of action of Ustekinumab?

Answer 21

• Monoclonal antibody targeting the p40 subunit of IL-12 and IL-23 cytokines.\n- Inhibits the differentiation and activation of Th1 and Th17 cells, reducing inflammation.

Question 22

What are the clinical uses of Ustekinumab?

Answer 22

• Treats moderate to severe Crohn’s disease (CD) and ulcerative colitis (UC), especially in patients who fail conventional therapies.\n- Also used for psoriasis and psoriatic arthritis.

Question 23

What are the common and serious adverse effects of Ustekinumab?

Answer 23

”- Common: Headache, fatigue, and injection site reactions.-
Serious: Increased risk of infections, including upper respiratory infections and tuberculosis (TB).\n- Key Note: Unlike TNF