Antidiarrheal Drugs for IBD- 5ASA compounds

Name of the IBD- 5ASA compounds Drugs

• Sulfasalazine
• Mesalazine 
• Balsalazide 
• Olsalazine 

1.Sulfasalazine

Mechanism of Action

As a prodrug of sulfapyridine and 5-aminosalicylic acid (mesalamine), delivers more sulfapyridine and mesalamine to the colon than either metabolite could provide alone. Sulfapyridine provides antibacterial action along the intestinal wall; mesalamine inhibits cyclooxygenase, thereby decreasing the production of arachidonic acid metabolites and reducing colonic inflammation.

Pharmacokinetics

• Bioavailability: <15% of parent drug; 60% (sulfapyridine); 10-30% (5-ASA)
• Peak plasma time: 6 hr; 10 hr (sulfapyridine and 5-ASA)
• Protein bound: >99% to albumin; 70% (sulfapyridine)
• Metabolism: Approximately 90% of sulfasalazine is converted by colon bacteria into its active components, sulfapyridine and mesalamine
• Half-life: 10.4-14.8 hr (sulfapyridine)
• Renal clearance: 37%
• Excretion: Urine (systematically absorbed sulfapyridine and 5-ASA); feces (majority of 5-ASA)

Administration

• Give after meals and space doses evenly to reduce GI effects.
• Give with a full glass of water.
• Administer delayed-release tablets whole. Don’t let patient crush or chew them.

Contraindications

• Hypersensitivity to drug, its metabolites, other sulfonamides, or salicylates
• Porphyria
• Urinary tract or intestinal obstruction

Precautions :

• Renal or hepatic disease, bronchial asthma, G6PD deficiency, group A beta-hemolytic streptococcal infections, blood dyscrasias
• History of multiple allergies
• Pregnant or breastfeeding patients
• Children younger than age 2.

Adverse reactions

• CNS: headache, depression, hallucinations, insomnia, drowsiness, vertigo, fatigue, apathy, anxiety, ataxia, polyneuritis, peripheral neuropathy, seizures
• CV: allergic myocarditis or pericarditis
• EENT: periorbital edema, optic neuritis, transient myopia, tinnitus
• GI: nausea, vomiting, abdominal pain, stomatitis, glossitis, pancreatitis, dry mouth, anorexia, pseudomembranous colitis
• GU: hematuria, proteinuria, orangeyellow urine, reversible oligospermia, crystalluria, toxic nephrosis with oliguria and anuria, renal failure Hematologic: megaloblastic anemia, agranulocytosis, aplastic anemia, thrombocytopenia, leukopenia, hemolytic anemia
• Hepatic: jaundice, hepatitis, hepatocellular necrosis Respiratory: shortness of breath, pleuritis, cyanosis, allergic pneumonitis, pulmonary infiltrates, fibrosing alveolitis
• Skin: generalized skin eruption, urticaria, pruritus, alopecia, local irritation, orange-yellow skin discoloration, exfoliative dermatitis, photosensitivity reaction, erythema multiforme, epidermal necrolysis, Stevens-Johnson syndrome
• Other: reversible immunoglobulin suppression, chills, drug fever, hypersensitivity reactions including anaphylaxis, serum sickness, lupus like syndrome

Patient monitoring

• Monitor CBC with white cell differential. Watch for evidence of blood dyscrasias.
• Stay alert for signs of erythema multiforme. Report early signs before condition can progress to StevensJohnson syndrome.
• Monitor patient for signs and symptoms of superinfection, including fever, tachycardia, and chills.
• Monitor liver function tests; watch for signs and symptoms of hepatitis.
• Check kidney function tests weekly. Evaluate patient’s fluid intake, urine output, and urine pH. Report hematuria, oliguria, or anuria right away.
• Monitor neurologic status. Report seizures, hallucinations, or depression.
• If patient takes drug for rheumatoid arthritis, monitor therapeutic response 4 to 12 weeks after therapy begins.

Patient teaching

• Tell patient to take on regular schedule as prescribed, along with a full glass of water. Instruct him to drink plenty of fluids to minimize crystal formation in urine.
• Urge patient to complete full course of treatment, even if he feels better after a few days.
• Instruct patient to watch for and immediately report signs and symptoms of hypersensitivity reaction, especially rash.
• Tell patient drug can cause blood disorders, GI and liver problems, serious skin reactions, and other infections. Describe key warning signs and symptoms (easy bruising or bleeding, severe diarrhea, unusual tiredness, yellowing of skin or eyes, sore throat, rash, cough, mouth sores, fever). Instruct him to report these right away.
• Advise patient to promptly report scant or bloody urine or inability to urinate.
• Instruct patient to contact prescriber if he develops depression.
• Teach patient effective ways to counteract photosensitivity effect. Tell him that dong quai and St. John’s wort  increase phototoxicity risk and should be avoided during therapy.
• Inform patient that drug may discolor skin and body fluids orangeyellow and may permanently stain contact lenses.
• Advise female patient to inform prescriber if she is pregnant. Caution her not to take drug near term or when breastfeeding
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, foods, herbs, and behaviors mentioned above

Nursing Considerations

• Monitor CBC, liver function test results, and BUN and serum creatinine levels before and periodically during prolonged sulfasalazine therapy.
• Be aware that sulfasalazine doses over 4 g or a blood level over 50 mcg/ml increases the risk of adverse and toxic reactions.
• Monitor fluid intake and output and urine color, pH, and consistency. Acidic urine may require alkalization to prevent crystalluria.

2.Mesalazine 

Mechanism of Action

May reduce inflammation by inhibiting the enzyme cyclooxygenase and decreasing production of arachidonic acid metabolites, which may be increased in patients with inflammatory bowel disease. Cyclooxygenase is needed to form prostaglandins from arachidonic acid. Prostaglandins mediate inflammatory activity and produce signs and symptoms of inflammation. Mesalamine also may reduce inflammation by interfering with leukotriene synthesis and inhibiting the enzyme lipoxygenase, both of which take part in inflammatory response.

Pharmacokinetics

• Bioavailability: Immediate-release is extensively and rapidly absorbed; extended-release 20-30% absorbed
• Protein bound: 43% (5-ASA); 78% (N-acetyl-5-ASA)
• Metabolism: Rapidly acetylated in colon wall and liver, independent of pt acetylator status, into N-acetyl-5-aminosalicylic acid
• Metabolites: N-acetyl-5-aminosalicylic acid (inactive)
• Half-life: 0.5-10 hr (5-ASA); 2-15 hr (N-acetyl-5-ASA )
• Excretion: Feces 72%; urine: 19-30%

Administration

• Give Apriso capsules with or without food. Don’t give concurrently with antacids.
• Give Lialda tablets with meal.
• Make sure patient swallows tablets whole without crushing or chewing
• For best effect, have patient retain suppository for 1 to 3 hours

Contraindications

• Hypersensitivity to drug, its components, or salicylates

Precautions :

• Severe hepatic or renal impairment
• Allergy to sulfasalazine
• Pyloric stenosis (delayed-release tablets)
• Conditions predisposing to development of myocarditis or pericarditis
• Pregnant or breastfeeding patients
• Children younger than age 18 (safety and efficacy not established).

Adverse reactions

• CNS: headache, dizziness, malaise, weakness
• CV: chest pain, mesalamine-induced cardiac hypersensitivity reactions (myocarditis and pericarditis) EENT: rhinitis, pharyngitis
• GI: nausea, vomiting, diarrhea, eructation, flatulence, anal irritation (with rectal use), pancreatitis GU: interstitial nephritis, renal failure
• Musculoskeletal: back pain
• Skin: alopecia, rash
• Other: fever, acute intolerance syndrome, anaphylaxis, acute intolerance syndrome

Patient monitoring

• Monitor carefully for mesalamineinduced cardiac hypersensitivity reactions (myocarditis and pericarditis).
• Closely monitor patients with history of allergic reactions to sulfasalazine or sulfite sensitivity (if using enema).
• Assess kidney and liver function before and periodically during therapy.
• Monitor for suppository efficacy, which should appear in 3 to 21 days. However, know that treatment usually continues for 3 to 6 weeks.
• Watch for signs and symptoms of intolerance syndrome, such as cramping, acute abdominal pain, bloody diarrhea, fever, headache, and rash. If these occur, discontinue drug and notify prescriber.
• Watch for signs and symptoms of intolerance syndrome, such as cramping, acute abdominal pain, bloody diarrhea, fever, headache, and rash. If these occur, discontinue drug. Drug may be restarted later only if clearly needed, under close medical supervision and at reduced dosage.

Patient teaching

• Instruct patient to swallow tablets or capsules whole.
• Tell patient to contact prescriber if partially intact tablets repeatedly appear in stools.
• Advise patient using suppository to avoid excessive handling and to retain suppository for 1 to 3 hours or longer for maximum benefit.
• Teach patient about proper enema administration. Tell him to stay in position for at least 30 minutes and, if possible, retain medication overnight.
• Advise patient to immediately report breathing difficulties, allergic symptoms, cramping, acute abdominal pain, bloody diarrhea, fever, headache, or rash.
• As appropriate, review all other significant and life-threatening adverse reactions, especially those related to the drugs mentioned above.

Nursing Considerations

• Use mesalamine cautiously in patients with sulfite sensitivity. Some drug formulations contain sulfites, which may cause hypersensitivity reactions in these patients.
• Use mesalamine cautiously in patients with liver disease because hepatic dysfunction may occur.
• Ensure that suppository is firm before inserting it. If it’s too soft, chill in refrigerator for 30 minutes or run under cold water before removing wrapper. Moisten with water-soluble lubricant or tap water before insertion. Have patient retain suppository for 1 to 3 hours, as directed.
• Give rectal suspension at bedtime, and have patient retain for prescribed time— about 8 hours, if possible. Retention time ranges from 3.5 to 12 hours.
• Be aware that rectal suspension may darken slightly over time but that this change doesn’t affect potency. Discard rectal suspension that turns dark brown.
• Assess patient for evidence of acute intolerance similar to flare-up of inflammatory bowel disease: acute abdominal cramps and pain, bloody diarrhea, and, possibly, fever, headache, and rash.
• For patients with impaired renal function, expect to monitor renal function test results periodically during long-term therapy because drug may cause nephrotoxicity.
• Monitor patient’s CBC with differential for eosinophilia, which may indicate an allergic reaction.

3.Balsalazide 

Mechanism of Action

After it has been metabolized to 5-ASA, balsalazide may reduce inflammation by inhibiting the enzyme cyclooxygenase and decreasing production of arachidonic acid metabolites, which may be increased in patients with inflammatory bowel disease. Cyclooxygenase is needed to form prostaglandin from arachidonic acid. Prostaglandin mediates inflammatory activity and produces signs and symptoms of inflammation. By inhibiting prostaglandin synthesis, balsalazide may reduce signs and symptoms of inflammation in inflammatory bowel disease. Balsalazide also interferes with leukotrine synthesis and inhibits the enzyme lipoxygenase. These substances are involved in the inflammatory response.

Pharmacokinetics

• Bioavailability: Low absorption
• Protein bound: 99%
• Metabolism: Following oral administration, balsalazide passes intact into colon where it is cleaved by intestinal flora to form mesalamine and 4-aminobenzoyl-b-alanine
• Half-life: Undetermined due to large intersubjective variability
• Excretion: Feces (as metabolites) >65%; urine (as metabolites) >25%

Administration

• Advise patient to swallow capsules whole, either always with or always without food.
• For those patients who can’t swallow capsules whole, carefully open capsules and sprinkle contents on applesauce and have patient swallow contents immediately without chewing

Contraindications

 ● Hypersensitivity to balsalazide, salicylates, or mesalamine

Precautions :

• Renal impairment
• Pyloric stenosis
• Breastfeeding patients
• Children younger than age 5 (safety and efficacy not established)

Adverse reactions

• CNS: headache, insomnia, dizziness, anxiety, confusion, agitation, coma
• EENT: blurred vision, eye irritation, tinnitus, earache, epistaxis, sinusitis, sore throat, nasopharyngitis
• GI: nausea, vomiting, diarrhea, constipation, abdominal pain, dyspepsia, anorexia, oral blisters, oral candidiasis, GI hemorrhage
• GU: urinary tract infection
• Musculoskeletal: arthralgia; myalgia; bone, back, neck, or limb pain
• Respiratory: cough, upper respiratory tract infection Skin: erythema
• Other: generalized pain

Patient monitoring

• Assess character and frequency of stools.
• Monitor CBC and liver and kidney function test results.

Patient teaching

• Instruct patient to take drug only as directed.
• Instruct patient to carefully open capsules and sprinkle contents on applesauce and swallow contents immediately without chewing if patient can’t swallow capsules whole.
• Tell patient that teeth and tongue staining may occur when drug is taken by sprinkling on applesauce.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs mentioned above.

Nursing Considerations

WARNING Monitor patients who are sensitive to sulfasalazine or olsalazine for possible cross-sensitivity to balsalazide.

• Monitor patients with pyloric stenosis for decreased or delayed drug effects due to prolonged gastric retention of balsalazide capsules.
• Monitor patient for possible exacerbation of colitis symptoms.

4.Olsalazine 

Mechanism of Action

Exerts anti-inflammatory action in GI tract after being converted by colonic bacteria to mesalamine (5-aminosalicylic acid), which inhibits cyclooxygenase. Inhibition of cyclooxygenase reduces prostaglandin production in intestinal mucosa. This in turn reduces production of arachidonic acid metabolites, which may be increased in patients with inflammatory bowel disease. Olsalazine also exerts an anti-inflammatory effect by indirectly inhibiting leukotriene synthesis, which normally catalyzes production of arachidonic acid.

Pharmacokinetics

• Peak plasma (single 1 g dose):  1.6-6.2 umol/L
• Protein bound: 99%
• Metabolism: liver
• Half-Life: 0.9 hr

Administration

● Give with meals to reduce GI irritation.

Contraindications

 ● Hypersensitivity to drug or other salicylates

Precautions:

• Hepatic or renal impairment, severe allergy, bronchial asthma
• Pregnant or breastfeeding patients
• Children younger than age 14.

Adverse reactions

• CNS: headache, fatigue, depression, vertigo
• GI: nausea, vomiting, diarrhea, abdominal pain, cramps, dyspepsia, bloating, stomatitis
• Musculoskeletal: joint pain
• Respiratory: upper respiratory infection
• Skin: rash, itching

Patient monitoring

• Monitor neurologic status. Stay alert for depression.
• Assess GI symptoms. Encourage adequate fluid intake to avoid dehydration.
• Monitor urinalysis, blood urea nitrogen, and creatinine in patients with renal impairment

Patient teaching

• Instruct patient to take with food and to continue taking drug even after symptoms improve.
• Tell patient to eat appropriate foods in small, frequent servings to minimize GI upset.
• Advise patient to contact prescriber if symptoms worsen or don’t improve after 1 to 2 months of therapy.
• Tell patient he may require periodic proctoscopy and sigmoidoscopy to determine response to drug.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects mood and wakefulness.
• As appropriate, review all significant adverse reactions and interactions, especially those related to the drugs and foods mentioned above.

Nursing Considerations

• Assess patient for aspirin allergy before giving olsalazine.
• If patient has severe allergies or asthma, watch closely for worsening symptoms during olsalazine therapy, and notify prescriber immediately if they occur.
• Assess quantity and consistency of stools and frequency of bowel movements before, during, and after therapy.
• Give drug with food to decrease adverse GI reactions.
• Monitor skin for adequate hydration.
• Assess patient for abdominal pain and hyperactive bowel sounds.
• Monitor renal and hepatic status in patient with underlying renal or hepatic dysfunction because drug may further impair these functions

REFERENCES

1. Robert Kizior, Keith Hodgson, Saunders Nursing Drug handbook,1st edition 2024, Elsevier Publications. ISBN-9780443116070
2. McGraw Hill- Drug Handbook, Seventh Edition, 2013, McGraw Hill Education Publications,9780071799430.
3. April Hazard, Cynthia Sanoski, Davi’s Drug Guide for Nurses -Sixteenth Edition 2019, FA Davis Company Publications,9780803669451.
4. Jones and Bartlet, Pharmacology for Nurses, Second Edition, 2020, Jones and Bartlet Learning Publications, ISBN 9781284141986.
5. Nursebro.com, Search – Nursebro

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