prepare a assignments on the topic "recent development in drug therapy of GI ulcers dieseases and Inflammatory bowel diseases " ,provide the separate information for two , use the recent article and research paper to provide the information . also use the references of standard books subject : pharmacotherapeutics i am the student of b pharmacy 4th year

Reading File

Now let me run all the necessary searches in parallel - textbook content for both GI ulcers and IBD, plus recent PubMed literature.

Finding Sources

Searching PubMed

"peptic ulcer" AND "drug therapy" AND "Helicobacter pylori"

Searching PubMed

"inflammatory bowel disease" AND "biologic therapy"

Good results. Now let me get the textbook content and more details from key papers in parallel.

Finding Sources

Reading Article

PMID: 39466269

Reading Article

PMID: 38885678

Reading Article

PMID: 41114682

Finding Sources

Reading Article

PMID: 39626064

Reading Article

PMID: 39384730

Reading Article

PMID: 37378711

Now let me get the actual textbook content from Goodman & Gilman's, Sleisenger & Fordtran's, and Schwartz Surgery for both topics, plus more recent IBD data.

Reading File

Searching PubMed

"potassium competitive acid blocker" OR "vonoprazan" AND "peptic ulcer"

Searching PubMed

"JAK inhibitor" AND "inflammatory bowel disease" AND "upadacitinib" OR "tofacitinib"

Excellent! I now have comprehensive material. Let me get the abstracts from vonoprazan and the AGA IBD guidelines, plus read more of the Goodman & Gilman content.

Reading Article

PMID: 39145848

Reading Article

PMID: 39572132

Reading Article

PMID: 39147217

Reading File

I now have comprehensive information to write the full assignment. Let me compile it now.Here is your full, well-structured assignment:

ASSIGNMENT

Subject: Pharmacotherapeutics

B. Pharmacy – 4th Year

Topic: Recent Developments in Drug Therapy of Gastrointestinal Ulcer Diseases and Inflammatory Bowel Diseases

PART I: RECENT DEVELOPMENTS IN DRUG THERAPY OF GASTROINTESTINAL (PEPTIC) ULCER DISEASES

1. Introduction

Gastrointestinal ulcer disease, commonly termed peptic ulcer disease (PUD), refers to the formation of mucosal defects - most often in the stomach (gastric ulcer) or the proximal duodenum (duodenal ulcer) - that penetrate at least into the submucosa. The annual prevalence of PUD ranges between 0.12% and 1.5% globally. In the United States alone, approximately 54,000 patients are admitted annually for bleeding peptic ulcers, and around 10,000 deaths per year are attributable to this condition (Almadi et al., Lancet, 2024).

The pathophysiology involves an imbalance between aggressive factors (gastric acid, pepsin, H. pylori, NSAIDs) and mucosal defense mechanisms (mucus, bicarbonate, prostaglandins, mucosal blood flow).

2. Etiology and Pathogenesis

The two principal etiological factors are:

Helicobacter pylori infection - accounts for approximately 42% of PUD cases. H. pylori disrupts the mucous layer, impairs bicarbonate secretion, and triggers inflammatory cytokine release, ultimately damaging the gastric epithelium (Vakil N., JAMA, 2024).
NSAID/Aspirin use - responsible for approximately 36% of PUD. NSAIDs inhibit cyclooxygenase (COX-1 and COX-2) enzymes, thereby reducing prostaglandin synthesis, which compromises mucosal protection.
Stress-related mucosal disease (SRMD) - occurs in critically ill patients.
Idiopathic - a smaller subset with no identifiable cause.

3. Classical Drug Therapy of GI Ulcers

3.1 Proton Pump Inhibitors (PPIs)

PPIs remain the cornerstone of PUD therapy. They irreversibly inhibit the H⁺/K⁺-ATPase (the "proton pump") on the parietal cell, producing profound and sustained suppression of gastric acid secretion.

Examples: Omeprazole, Lansoprazole, Pantoprazole, Esomeprazole, Rabeprazole

Mechanism: Prodrugs activated in the acidic secretory canaliculi of parietal cells → form active sulfenamide → covalently bind cysteine residues of H⁺/K⁺-ATPase → irreversible inhibition

Clinical Efficacy:

Acid blockers such as omeprazole can heal peptic ulcers in approximately 80%–100% of patients within 4 weeks; gastric ulcers larger than 2 cm may require 8 weeks (Vakil, JAMA, 2024)
For NSAID-associated ulcers: stopping the NSAID and beginning a PPI (e.g., omeprazole) is the first step; 4-week courses are effective for most patients (Swanson's Family Medicine Review)

Dose: Omeprazole 20–40 mg once daily; Esomeprazole 40 mg IV for bleeding ulcers (intravenous high-dose bolus + infusion)

(Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 14th Ed.)

3.2 H₂-Receptor Antagonists (H₂RAs)

H₂RAs competitively block histamine H₂ receptors on parietal cells, reducing basal and stimulated acid secretion.

Examples: Ranitidine (now withdrawn in many markets due to NDMA contamination), Famotidine, Cimetidine, Nizatidine

Uses: Mild-moderate ulcers, maintenance therapy, nocturnal acid suppression Limitations: Tolerance develops within days (receptor upregulation); less potent acid suppression than PPIs

(Goodman & Gilman's, 14th Ed.)

3.3 Antacids

Provide immediate but short-lived neutralization of gastric acid. Used for symptomatic relief. Examples: Aluminium hydroxide, Magnesium hydroxide, Calcium carbonate

3.4 Cytoprotective Agents

Sucralfate: Polyanionic sucrose-aluminium complex that forms a viscous paste over the ulcer base, protecting it from acid and pepsin. Also stimulates prostaglandin and mucus secretion.
Misoprostol: Synthetic PGE₁ analog; stimulates mucus and bicarbonate secretion and reduces acid secretion. Used mainly for NSAID-induced ulcer prevention. At 800 mcg/day, misoprostol was effective in 73% of patients compared to omeprazole 40 mg in 80% in randomized trials (Sleisenger and Fordtran's Gastrointestinal and Liver Disease, 11th Ed.)
Bismuth salts (Bismuth subcitrate/subsalicylate): Coat the ulcer base, inhibit H. pylori, and have anti-inflammatory properties. Used as part of quadruple therapy regimens.

3.5 H. pylori Eradication Therapy

Eradication of H. pylori decreases peptic ulcer recurrence rates from approximately 50%–60% to 0%–2% (Vakil, JAMA, 2024).

Classic Triple Therapy (10–14 days):

PPI + Clarithromycin 500 mg + Amoxicillin 1 g - each twice daily for 10–14 days
Clarithromycin in combination with omeprazole 20 mg (or lansoprazole 30 mg) and amoxicillin, each administered twice daily for 10–14 days, are effective for treatment of H. pylori-associated PUD (Goodman & Gilman's, 14th Ed.)

Bismuth Quadruple Therapy (BQT):

PPI + Bismuth + Metronidazole + Tetracycline × 14 days
Preferred when clarithromycin resistance is suspected

4. Recent Developments in GI Ulcer Drug Therapy

4.1 Potassium-Competitive Acid Blockers (P-CABs) – A Major Breakthrough

P-CABs represent the most significant pharmacological advance in acid suppression in recent decades. Unlike PPIs, which are prodrugs requiring activation in an acid environment, P-CABs reversibly and competitively block the potassium-binding site of the H⁺/K⁺-ATPase, irrespective of the activation state of the pump.

Key Advantages of P-CABs over PPIs:

Rapid onset: P-CABs achieve maximum acid suppression within the first dose; PPIs typically require 3–5 days for full effect
Food-independent absorption: Unlike PPIs, P-CABs do not need to be taken before meals
No need for acidic activation: Effective even at neutral pH, meaning they inhibit newly synthesized and recycled proton pumps
Prolonged acid suppression: Extended intragastric pH control, especially at night (addresses the unmet clinical need of "nocturnal acid breakthrough" with PPIs)
CYP2C19-independent: Not subject to pharmacogenomic variability that affects PPI efficacy

Currently Available P-CABs:

Drug	Status	Indication
Vonoprazan (Voquezna)	Approved - USA, Japan, Latin America	H. pylori eradication, GERD, PUD
Tegoprazan	Approved - South Korea, Latin America	GERD, H. pylori
Fexuprazan	Approved - South Korea	GERD
Keverprazan	Approved - China	GERD
Linazapran glurate	Under clinical development	-

(Scarpignato & Hunt, Curr Gastroenterol Rep, 2024)

Vonoprazan in H. pylori Eradication: The 2024 ACG Clinical Guideline (Chey et al., Am J Gastroenterol, 2024) recommends:

First-line (treatment-naive): Bismuth quadruple therapy (BQT) for 14 days when antibiotic susceptibility is unknown
Alternative (penicillin-allergy free): Vonoprazan-based dual therapy (Vonoprazan + Amoxicillin) for 14 days - "potassium-competitive acid blocker dual therapy"
Rifabutin triple therapy as another alternative

The guideline emphasizes that clarithromycin or levofloxacin-based salvage regimens should only be used with confirmed susceptibility testing, given rising antibiotic resistance.

Vonoprazan vs. IV PPI in Peptic Ulcer Bleeding: A multicenter randomized noninferiority trial (Geeratragool et al., Gastroenterology, 2024) demonstrated that oral vonoprazan was non-inferior to intravenous PPI for prevention of rebleeding after successful endoscopic hemostasis in high-risk peptic ulcers - a finding with significant implications for simplifying management and reducing healthcare costs.

4.2 Vonoprazan-Amoxicillin Dual Therapy

Traditional H. pylori regimens use 3–4 drugs. Recent trials have shown that Vonoprazan + Amoxicillin as a dual regimen achieves eradication rates of >80%, comparable to triple therapy. This is made possible because the high, stable acid suppression from vonoprazan allows amoxicillin (which is most active against H. pylori in near-neutral pH) to work more effectively. This regimen reduces antibiotic burden and potential resistance.

(Shirley M., Drugs, 2024; Chey et al., Am J Gastroenterol, 2024)

4.3 Antibiotic Resistance and Susceptibility-Guided Therapy

Rising clarithromycin resistance (>20% in many regions) has necessitated a shift away from traditional clarithromycin-based triple therapy. Modern guidelines advocate:

Susceptibility testing before prescribing clarithromycin or levofloxacin-based regimens
Culture-guided therapy in patients with prior treatment failure
Molecular testing (PCR-based) for detection of clarithromycin/fluoroquinolone resistance mutations directly from biopsy specimens

4.4 Rifabutin-Based Triple Therapy

For patients with multiple prior treatment failures, rifabutin (a rifamycin antibiotic) combined with a PPI/vonoprazan and amoxicillin has been shown to achieve eradication rates of ~80%–90%. This is now recommended as a salvage option in the ACG 2024 guideline. The main concern is myelotoxicity (dose-dependent; monitor CBC).

4.5 Management of NSAID-Associated Ulcers: Updated Strategies

If NSAID cannot be stopped: switch to a selective COX-2 inhibitor (celecoxib) + PPI for maximum gastroprotection
Misoprostol (800 mcg/day) remains an option for NSAID ulcer prevention but is used less due to GI tolerability issues
Discontinuing NSAIDs heals 95% of endoscopically identified ulcers and reduces recurrence from 40% to 9% (Vakil, JAMA, 2024)

4.6 Management of Peptic Ulcer Bleeding

Endoscopic hemostasis remains the cornerstone
High-dose IV PPI (e.g., IV esomeprazole 80 mg bolus then 8 mg/hr infusion for 72 hours) is standard post-endoscopy to prevent rebleeding
Vonoprazan oral as non-inferior alternative (Geeratragool et al., 2024)
H. pylori eradication post-bleeding episode is mandatory to prevent recurrence

4.7 Stress Ulcer Prophylaxis Updates

Recent evidence questions the universal use of PPIs for stress ulcer prophylaxis in ICU patients. The emphasis is now on appropriate patient selection - only critically ill patients at highest risk (coagulopathy, mechanical ventilation >48h) benefit from pharmacological prophylaxis; over-use may increase the risk of Clostridioides difficile infection and hospital-acquired pneumonia (Almadi et al., Lancet, 2024).

5. Summary of Drug Classes for GI Ulcers

Drug Class	Example	Mechanism	Recent Role
PPI	Omeprazole, Esomeprazole	H⁺/K⁺-ATPase irreversible inhibition	Still gold standard
P-CAB	Vonoprazan	H⁺/K⁺-ATPase reversible K⁺-competitive block	Emerging first-line for H. pylori
H₂RA	Famotidine	H₂ receptor antagonism	Adjunct; declining primary use
Antacids	Al(OH)₃, Mg(OH)₂	Acid neutralization	Symptomatic relief only
Cytoprotective	Sucralfate, Misoprostol	Mucosal protection / PG analog	NSAID prevention (misoprostol)
Bismuth	Bismuth subcitrate	Anti-H. pylori, mucosal coat	Part of BQT
Antibiotics	Amoxicillin, Clarithromycin, Rifabutin, Metronidazole, Tetracycline	H. pylori eradication	Core of eradication regimens

PART II: RECENT DEVELOPMENTS IN DRUG THERAPY OF INFLAMMATORY BOWEL DISEASES (IBD)

1. Introduction

Inflammatory bowel diseases (IBD) are chronic, relapsing-remitting immune-mediated disorders of the gastrointestinal tract. The two primary entities are:

Crohn's disease (CD): Transmural inflammation that can affect any part of the GI tract from mouth to anus; "skip lesions" are characteristic
Ulcerative colitis (UC): Continuous mucosal inflammation confined to the colon, invariably involving the rectum

IBD has a global prevalence exceeding 0.3% and is rising in newly industrializing regions of Asia, Africa, and South America. The pathogenesis involves dysregulated intestinal immune responses (predominantly T-cell mediated), altered gut microbiota, and genetic susceptibility, particularly in genes encoding innate immunity and epithelial barrier function.

2. Classical Drug Therapy of IBD

2.1 Aminosalicylates (5-ASA Compounds)

Examples: Sulfasalazine, Mesalamine (Pentasa, Asacol), Balsalazide, Olsalazine

Mechanism: These compounds decrease inflammation by inhibition of cyclooxygenase and 5-lipoxygenase in the gut mucosa. They require direct contact with affected mucosa for efficacy (Schwartz's Principles of Surgery, 11th Ed.).

Uses:

First-line agents for mild to moderate UC and Crohn's colitis
Multiple preparations allow delivery to different sites (Pentasa for small bowel; Asacol for terminal ileum and colon; enemas/suppositories for proctitis/proctosigmoiditis)
Maintenance of remission in UC

Key point from AGA 2024 Guideline (Singh et al., Gastroenterology, 2024): In adult patients with moderate-to-severe UC who have escalated to immunomodulators or advanced therapies, the AGA suggests stopping 5-aminosalicylates - they provide no additional benefit in this setting.

2.2 Corticosteroids

Corticosteroids are key components for treating acute exacerbations of both UC and CD. They are nonspecific inhibitors of the immune system; 75%–90% of patients will improve with administration (Schwartz's Principles of Surgery, 11th Ed.).

Examples: Prednisone, Prednisolone (systemic); Budesonide (locally acting)

Limitations:

Significant side effects (osteoporosis, hyperglycemia, adrenal suppression, infection risk, growth retardation in children)
Should be used for the shortest course possible
Failure to wean corticosteroids is a relative indication for surgery

Budesonide: A second-generation corticosteroid with high first-pass hepatic metabolism (>90%), thus minimal systemic toxicity. Available as oral (Entocort EC for ileal/right colon CD) and rectal formulations for proctitis/left-sided colitis.

2.3 Immunomodulators (Thiopurines)

Examples: Azathioprine (AZA), 6-Mercaptopurine (6-MP), Methotrexate (MTX)

AZA / 6-MP: Antimetabolites that interfere with nucleic acid synthesis and reduce proliferation of inflammatory cells. Useful for both UC and CD in patients who have failed 5-ASA or are steroid-dependent/refractory. Important: Onset of action is 6–12 weeks; concomitant corticosteroids are almost always required initially.
Methotrexate: Folate antagonist; used mainly for CD maintenance (15–25 mg/week IM or SC). Evidence in UC is weak (Schwartz's Principles of Surgery, 11th Ed.).
Cyclosporine: Up to 80% of patients with acute severe UC will improve with IV cyclosporine; however, most ultimately require colectomy. Limited by nephrotoxicity, hirsutism, gum hypertrophy.

2.4 Biologic Agents - First Generation (Anti-TNF-α)

Biologic agents revolutionized IBD therapy by targeting specific molecular pathways in the inflammatory cascade.

Anti-TNF-α monoclonal antibodies:

Infliximab (Remicade): Chimeric (25% murine) anti-TNF-α monoclonal antibody; IV infusion. The first biologic agent used to treat Crohn's disease. More than 50% of patients with moderate-to-severe CD improve with infliximab therapy (Schwartz's Principles of Surgery, 11th Ed.). Also approved for UC.
Adalimumab (Humira): Fully human anti-TNF-α; subcutaneous. Approved for CD and UC.
Certolizumab pegol (Cimzia): Pegylated anti-TNF Fab fragment; effective for CD. Notably, certolizumab is also effective for Crohn's disease (Fitzpatrick's Dermatology).
Golimumab (Simponi): Fully human anti-TNF-α; approved for UC (SC dosing).

Key considerations with Anti-TNF therapy:

Combination with an immunomodulator (AZA/6-MP) reduces immunogenicity and increases drug levels - the "combo therapy" strategy
Screening for TB, hepatitis B, and latent infections mandatory before starting
Risk of serious infections, lymphoma (small but real), and demyelinating disease
Smoking is an independent predictor of earlier loss of response to infliximab (HR 3.03 for CD, Yamada's Textbook of Gastroenterology, 7th Ed.)

3. Recent Developments in IBD Drug Therapy

3.1 Anti-Integrin Therapy: Vedolizumab

Vedolizumab (Entyvio) - A humanized anti-α4β7 integrin monoclonal antibody that selectively blocks lymphocyte trafficking to the gut (gut-selective), without systemic immunosuppression.

Advantages:

Favorable safety profile - does not increase risk of systemic infections or PML (unlike natalizumab)
Effective for both UC and CD (induction and maintenance)
Preferred in patients with recurrent infections, elderly patients, or those with concerns about systemic immunosuppression

Position per AGA 2024 UC Guideline (Singh et al., Gastroenterology, 2024):

Vedolizumab is a higher-efficacy recommended agent for moderate-to-severe UC in biologic-naive patients

3.2 IL-12/23 Inhibitors: Ustekinumab

Ustekinumab (Stelara) - A human monoclonal antibody that blocks the p40 subunit shared by IL-12 and IL-23, inhibiting Th1 and Th17 cell activation.

Approved for: Moderate-to-severe CD (2016) and UC (2019) Dosing: Initial IV induction (single weight-based dose), then SC maintenance every 8 or 12 weeks. Advantages: Excellent long-term safety, convenient dosing, effective even in biologic-experienced patients

3.3 Selective IL-23p19 Inhibitors - A Major Recent Advance

This represents one of the most significant recent developments in IBD pharmacotherapy. These agents selectively target the p19 subunit of IL-23 (not IL-12), providing more selective immune modulation with excellent safety profiles.

Risankizumab (Skyrizi): Approved for moderate-to-severe CD (2022) and UC (2023) - IV induction followed by SC maintenance

Mirikizumab (Omvoh): Approved for moderate-to-severe UC (2023) - IV induction followed by SC maintenance

Guselkumab (Tremfya): Recent FDA approval for moderate-to-severe CD (2024-2025) - currently under review for UC

Evidence from Systematic Reviews: A systematic review and meta-analysis by Vuyyuru et al. (Digestive Diseases and Sciences, 2023) analyzing 18 trials (n=5,561 patients) showed:

Targeting IL-23 was significantly superior to placebo for inducing clinical remission (RR = 1.87, 95% CI 1.58–2.21, high certainty evidence)
Superior for endoscopic remission (RR = 3.20, 95% CI 2.17–4.70, high certainty evidence)
Superior for maintaining clinical remission (RR = 1.39, 95% CI 1.10–1.77, high certainty evidence)
Effective in both biologic-naive and biologic-experienced patients
Decreased risk of serious adverse events compared to placebo (RR = 0.55, high certainty evidence)

A 2025 head-to-head network meta-analysis comparing IL-23p19 inhibitors vs. ustekinumab (Dziegielewski et al., Am J Gastroenterol, 2025) demonstrated superiority of selective IL-23 blockers over ustekinumab for both induction and maintenance of remission in CD.

3.4 Janus Kinase (JAK) Inhibitors - Small Molecule Oral Drugs

JAK inhibitors are oral small molecules (not biologics) that inhibit JAK1/2/3 kinases intracellularly, blocking multiple cytokine signaling pathways (IL-6, IL-12, IL-23, IFN-γ, etc.).

Tofacitinib (Xeljanz):

Pan-JAK inhibitor (JAK1/2/3); oral twice daily
Approved for moderate-to-severe UC (not for CD)
Effective for rapid induction of remission (within 8 weeks)
Safety concerns: Increased risk of thromboembolism (DVT, PE), major cardiovascular events, and serious infections - therefore used with caution in patients >50 years or with cardiovascular risk factors

Upadacitinib (Rinvoq):

Selective JAK1 inhibitor; oral once daily (45 mg induction, 15 or 30 mg maintenance)
Approved for moderate-to-severe UC (2022) and moderate-to-severe CD (2023)
In the 2025 AGA evidence synthesis (Singh et al., Gastroenterology, 2025), upadacitinib demonstrated high certainty evidence of efficacy in both biologic-naive and biologic-experienced CD patients
Has a more selective JAK1 profile compared to tofacitinib, potentially offering a better safety profile

Filgotinib (Jyseleca):

Selective JAK1 inhibitor; approved for UC in Europe

Monitoring for JAK inhibitors: CBC, lipid profile, liver function tests, skin cancer screening

(Fudman et al., Clin Gastroenterol Hepatol, 2025; AGA Guideline, 2024)

3.5 Sphingosine-1-Phosphate (S1P) Receptor Modulators

Ozanimod (Zeposia):

Oral S1P₁,₅ receptor modulator that sequesters lymphocytes in lymph nodes, reducing their migration to the gut
Approved for moderate-to-severe UC (2021)
Advantages: Oral dosing; no requirement for IV infusion; favorable safety profile
Monitoring: Cardiac (bradycardia possible at initiation - dose titration required), macular edema, hepatotoxicity

Etrasimod (Velsipity):

Oral S1P₁,₂,₄,₅ receptor modulator
Approved for moderate-to-severe UC (2023)
More selective S1P receptor profile than ozanimod; clinical trials show remission rates comparable to biologics

Per AGA 2024 Guideline: Both ozanimod and etrasimod are classified as higher-efficacy medications for biologic-naive UC patients.

(Fudman et al., Clin Gastroenterol Hepatol, 2025)

3.6 Position of Therapies: AGA 2025 Evidence Synthesis

The 2024 AGA Living Clinical Practice Guideline (Singh et al., Gastroenterology, 2024) for UC and the 2025 AGA Evidence Synthesis for CD (Singh et al., Gastroenterology, 2025) provide an important framework:

For Biologic-Naive Moderate-to-Severe UC:

Higher-efficacy: Infliximab, vedolizumab, ozanimod, etrasimod, upadacitinib, risankizumab, guselkumab
Intermediate-efficacy: Golimumab, ustekinumab, tofacitinib, filgotinib, mirikizumab
Lower-efficacy: Adalimumab

For Biologic-Experienced UC (especially prior TNF failure):

Higher-efficacy: Tofacitinib, upadacitinib, ustekinumab
Intermediate-efficacy: Filgotinib, mirikizumab, risankizumab, guselkumab
Lower-efficacy: Adalimumab, vedolizumab, ozanimod, etrasimod

For Moderate-to-Severe Crohn's Disease (2025 AGA):

In biologic-naive patients: Infliximab, adalimumab, vedolizumab, ustekinumab, risankizumab, mirikizumab, guselkumab all demonstrated moderate-to-high certainty evidence
In biologic-experienced patients: Risankizumab and guselkumab showed superiority over vedolizumab and ustekinumab

3.7 Fecal Microbiota Transplantation (FMT)

FMT, the transfer of processed stool from a healthy donor to a recipient, has shown promising results in UC, particularly for induction of remission in mild-to-moderate UC. Mechanisms include restoration of microbial diversity and reduction of dysbiosis-driven inflammation. FMT is currently not a standard therapy but is under active clinical investigation (Liang et al., Mol Biomed, 2024). Regulatory approval for UC-specific indication is pending in most countries.

3.8 Early Use of Advanced Therapies ("Top-Down" Approach)

A meta-analysis by Law et al. (Inflamm Bowel Dis, 2024) showed that early biologic treatment (initiation within 2 years of diagnosis) decreases the risk of surgery in CD significantly, though the benefit was less clear in UC. This supports a shift from the traditional "step-up" strategy (start with 5-ASA → steroids → immunomodulators → biologics) toward an "accelerated step-up" or "top-down" approach in patients with poor prognostic features (extensive disease, deep ulcers, perianal disease, young age at diagnosis).

4. Summary of Drug Classes for IBD

Category	Drugs	IBD Indication	Recent Role
5-ASA	Mesalamine, Sulfasalazine	Mild-moderate UC, CD colitis	First-line mild UC
Corticosteroids	Prednisone, Budesonide	Acute flares	Induction only; minimize
Thiopurines	AZA, 6-MP	UC and CD maintenance	Combo with anti-TNF
Anti-TNF	Infliximab, Adalimumab, Golimumab	UC and CD	Still widely used
Anti-integrin	Vedolizumab	UC and CD	Preferred: elderly/infection-prone
Anti-IL-12/23	Ustekinumab	UC and CD	Broad utility
Anti-IL-23p19	Risankizumab, Mirikizumab, Guselkumab	UC and CD	Newest, excellent safety
JAK inhibitors	Tofacitinib, Upadacitinib	UC (both); CD (upadacitinib)	Oral; rapid onset
S1P modulators	Ozanimod, Etrasimod	UC	Oral; newer agents
FMT	Donor stool	UC (investigational)	Emerging

REFERENCES

Standard Textbooks

Brunton LL, Hilal-Dandan R, Knollmann BC. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 14th Edition. McGraw-Hill Education, 2023.
Schwartz SI, Brunicardi FC, et al. Schwartz's Principles of Surgery, 11th Edition. McGraw-Hill Education, 2019.
Feldman M, Friedman LS, Brandt LJ. Sleisenger and Fordtran's Gastrointestinal and Liver Disease, 11th Edition. Elsevier Saunders, 2021.
Podolsky DK, Camilleri M, Fitz JG, et al. Yamada's Textbook of Gastroenterology, 7th Edition. Wiley-Blackwell, 2022.
Swanson T, et al. Swanson's Family Medicine Review: A Problem-Oriented Approach, 9th Edition. Elsevier, 2022.
Floch MH, et al. Sabiston Textbook of Surgery: The Biological Basis of Modern Surgical Practice. Elsevier, 2022.
Kang S, et al. Fitzpatrick's Dermatology, 9th Edition. McGraw-Hill, 2019.

Recent Research Articles and Guidelines

Vakil N. "Peptic Ulcer Disease: A Review." JAMA. 2024 Dec 3. doi:10.1001/jama.2024.19094. [PMID: 39466269]
Almadi MA, Lu Y, Alali AA, Barkun AN. "Peptic ulcer disease." Lancet. 2024 Jul 6. doi:10.1016/S0140-6736(24)00155-7. [PMID: 38885678]
Chey WD, Howden CW, Moss SF, et al. "ACG Clinical Guideline: Treatment of Helicobacter pylori Infection." Am J Gastroenterol. 2024 Sep 1. doi:10.14309/ajg.0000000000002968. [PMID: 39626064] (Practice Guideline)
Scarpignato C, Hunt RH. "Potassium-competitive Acid Blockers: Current Clinical Use and Future Developments." Curr Gastroenterol Rep. 2024 Nov. doi:10.1007/s11894-024-00939-3. [PMID: 39145848]
Geeratragool T, et al. "Comparison of Vonoprazan Versus Intravenous Proton Pump Inhibitor for Prevention of High-Risk Peptic Ulcers Rebleeding After Successful Endoscopic Hemostasis: A Multicenter Randomized Noninferiority Trial." Gastroenterology. 2024 Sep. [PMID: 38582271]
Shirley M. "Vonoprazan: A Review in Helicobacter pylori Infection." Drugs. 2024 Mar. doi: . [PMID: 38388872]
Singh S, Loftus EV, Limketkai BN, et al. "AGA Living Clinical Practice Guideline on Pharmacological Management of Moderate-to-Severe Ulcerative Colitis." Gastroenterology. 2024 Dec. doi:10.1053/j.gastro.2024.10.001. [PMID: 39572132] (Practice Guideline)
Singh S, Murad MH, Yuan Y, et al. "Comparative Efficacy of Advanced Therapies for Management of Moderate-to-Severe Crohn's Disease: 2025 AGA Evidence Synthesis." Gastroenterology. 2025. doi:10.1053/j.gastro.2025.08.032. [PMID: 41114682] (Network Meta-Analysis)
Vuyyuru SK, Solitano V, Hogan M, et al. "Efficacy and Safety of IL-12/23 and IL-23 Inhibitors for Crohn's Disease: Systematic Review and Meta-Analysis." Dig Dis Sci. 2023 Sep. doi:10.1007/s10620-023-08014-z. [PMID: 37378711] (Meta-Analysis)
Dziegielewski C, Yuan Y, Ma C. "IL-23p19 Antagonists vs Ustekinumab for Treatment of Crohn's Disease: A Meta-Analysis of Randomized Controlled Trials." Am J Gastroenterol. 2025 Oct. [PMID: 40071763] (Meta-Analysis)
Law CCY, Tkachuk B, Lieto S, et al. "Early Biologic Treatment Decreases Risk of Surgery in Crohn's Disease but not in Ulcerative Colitis: Systematic Review and Meta-Analysis." Inflamm Bowel Dis. 2024 Jul. [PMID: 37506265] (Meta-Analysis)
Fudman DI, McConnell RA, Ha C, Singh S. "Modern Advanced Therapies for Inflammatory Bowel Diseases: Practical Considerations and Positioning." Clin Gastroenterol Hepatol. 2025 Feb. doi:10.1016/j.cgh.2024.06.050. [PMID: 39147217]
Liang Y, Li Y, Lee C, et al. "Ulcerative colitis: molecular insights and intervention therapy." Mol Biomed. 2024 Oct. doi:10.1186/s43556-024-00207-w. [PMID: 39384730]

Prepared by: B. Pharmacy 4th Year Student Subject: Pharmacotherapeutics Date: June 2026

---Your assignment is complete. Here's a quick summary of what's covered:

Assignment Overview

Part I - GI Ulcer Diseases

Classical therapy: PPIs, H₂RAs, antacids, cytoprotectants (sucralfate, misoprostol, bismuth), standard H. pylori triple/quadruple regimens
Recent developments:
- P-CABs (Vonoprazan) - the biggest pharmacological advance in acid suppression in decades: reversible K⁺-competitive H⁺/K⁺-ATPase inhibition, rapid onset, food-independent, no CYP2C19 variability
- Vonoprazan-Amoxicillin dual therapy for H. pylori - reduces antibiotic burden
- ACG 2024 Guideline shift to bismuth quadruple therapy (BQT) as preferred first-line
- Rifabutin-based salvage therapy for multi-drug resistant H. pylori
- Vonoprazan proven non-inferior to IV PPI for peptic ulcer bleeding (RCT, Gastroenterology 2024)

Part II - Inflammatory Bowel Diseases

Classical therapy: 5-ASA, corticosteroids, thiopurines (AZA/6-MP), anti-TNF biologics (infliximab, adalimumab)
Recent developments:
- Selective IL-23p19 inhibitors (Risankizumab, Mirikizumab, Guselkumab) - most significant new class; meta-analysis (5,561 patients) shows high-certainty superior remission and safety
- JAK inhibitors (Upadacitinib, Tofacitinib) - oral small molecules; upadacitinib now approved for both UC and CD
- S1P receptor modulators (Ozanimod, Etrasimod) - fully oral, new mechanism
- AGA 2024 Living Guidelines & 2025 AGA evidence synthesis for therapy positioning
- FMT and gut microbiome-based therapy as emerging approach

References

20 cited sources including 7 standard textbooks (Goodman & Gilman's, Schwartz's Surgery, Sleisenger & Fordtran's, Yamada's GI, etc.) and 13 recent PubMed articles from 2023-2025, including 3 practice guidelines/meta-analyses.

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