DRUGS ACTING ON GASTROINTESTINAL SYSTEM

TREATMENT OF PEPTIC ULCER

Medical treatment

A) Neutralization of gastric acid (Antacids)

• Systemic: Sodium bicarbonate, sodium citrate
• Non systemic: Magnesium hydroxide, magnesium trisilicate

B) Reduction of gastric acid

• H_{2} receptor antagonist: Cimetidine, Ranitidine, famotidine, Nizatidine
• Proton pump inhibitors: Omeprazole, Pantoprazole, Esmoprazole, Lansoprazole
• Mucosal protectant: Sucralfate, colloid bismuth subcitrate (CBS)
• Anti-helicobacter pyloric drug:  Amoxicillin, Clarithomycin, Tinidazole, Mertonidazole

Surgical treatment

Gastrectomy: Billroth I, Billroth II

Gastrojejunostomy

Vagotomy: Truncal, Selective

ANTACIDS

These are basic substances which neutralize gastric acid and raise pH of gastric content.

Examples: Sodium bicarbonate, Magnesium hydroxide, magnesium trisilicate

Mechanism of Action

Promote the gastric mucosal defense mechanisms:

• Mucus: Protective barrier against HCI
• Bicarbonate: Helps buffer acidic properties of HCI
• Prostaglandins: Prevent activation of proton pump
• Antacids do not prevent prevent the overproduction of acid.
• Acids do neutralize the acid once it's in the stomach.

Promote the gastric mucosal defense mechanisms:

• Secretion of:

-Mucus: Protective barrier against HCI.

-Bicarbonate: Helps buffer acidic properties of HCI.

-Prostaglandins: Prevent activation of proton pump.

• Antacids DO NOT prevent the over- production of acid.
• Acids NEUTRALIZE the acid once it's in the stomach.

Types of Antacids

• Systemic antacids: these are absorbable & if given in excessive dosage for prolonged period they can produce systemic alkalosis. E.g.: Sodium Bicarbonate, Sodium citrate etc.
• Non systemic antacids: these are not -absorbed from GIT and do not produce systemic alkalosis. E.g:

-Physically acting: milk, mucin etc

-Physico-chemically acting: Magnesium trisilicate, Aluminum Hydroxide etc

-Chemically acting: These drugs neutralize acid by chemical reaction. Eg: Mg-oxide, Mg-hydroxide, Mg-carbonate, Ca-carbonate, bismuth sub carbonate.

SODIUM BICARBONATE

It is a quick-acting systemic antacid. Mechanism of action

NaH*C_{3} + HCl -> NaCl + H_{2}*O + C*O_{2}

Indication

• Hyperacidity, gastritis, acidosis, Peptic ulcer

Dose

• Dissolved in 50ml water and take 3-4 times daily by mouth

Contraindication

• Oedema, cardiac failure, hypertension, renal failure, 1 pH level

Side effect

• Alkalosis, hypercalcemia

Nursing consideration

• Nurses are suggested to monitor intake and output, daily weight, edema and breath sounds of the patients.
• Consult the physician, if signs and symptoms of acidosis (disorientation, headache, weakness, dyspnea hyperventilation) are seen in concerned patient
• Consult the physician, if signs and symptoms of alkalosis (Confusion, irritability, paresthesia, tetany and altered breathing pattern) are seen in the patients.
• Similarly consult the physician, if signs and symptoms of hypernatremia (edema, weight gain, hypertension, tachycardia, fever, flushed skin and mental irritability) are seen in patients.
• Nurses are also suggested to monitor the potassium,
• Serum calcium, sodium, bicarbonate concentrations, serum osmolarity, acid- base balance and renal function before and throughout the therapy.

MAGNESIUM HYDROXIDE

It is a non systemic, fast acting & efficacious

Mechanism of action

Mg(OH) 2 + 2HCl -> MgC*l_{2} + 2H_{2}*O

Indication:

• Hyperacidity, Constipation, Peptic ulcer

Dose:

• Adult: 250-500mg tid or qid

Contraindication

• Severe diarrhoea

Side effects:

• Nausea, diarrhoea, mental dipression, hypotension

Nursing consideration

• Tablet must be chewed before swallowing.
• Suspension should be shaken well before use.
• Monitor periodic serum calcium and phosphorus levels with prolonged high- dose therapy or impaired renal function.

MAGNESIUM TRISILICATE

Mechanism of actions

• MgSiO * 8nH * 2O + HCl -> MgCl * 2 + SiO * 2 + H * 2O
• This neutralization effect reduces acid concentration in the stomach which helps to protect the mucus layer of gastrium from burning.

Indication:

• Symptomatic relief of gastric hyperacidity associated with gastritis.
• Treatment of esophageal reflux,
• To promote healing in gastric& duodenal ulcer.
• Dyspepsia
• Short-term constipation treatment of occasional constipation.

Dose:

• Adult: 5 to 10ml tid or qid or 250-500mg tid or qid.

Contraindications:

• Severe diarrhoea, intestinal obstruction, fecal impaction, appendicitis

Side effect

• Diarrhoea, dementia, mental depression, hypotension, hypophosphatemia. hypomagnesemia,

Nursing consideration

Same as Magnesium hydroxide

H2 RECEPTOR ANTAGONIST

The H2 receptor antagonists are competitive antagonists of histamine at the parietal cell's H₂ receptor. H₂ receptor antagonists are most popular drugs for treatment of acid-related disorders

Cimetidine, Famotidine, 'Ranitidine, Nizatidine are examples of H2 receptor antagonists

Mechanism of action:

• Block histamine (H2) at the receptors of acid-producing parietal cells: Combination of histamine to H2 receptors located on the basolateral membrane of the gastric parietal cell, blocking histamine effects.
• Inhibition gastric acid secretion: Production of hydrogen ions is reduced, resulting in decreased production of HCI.

Indication

• Peptic ulcer
• Zollinger-ellison syndrome
• Acute stress ulcers
• Gastro esophageal reflux disease (GERD)

CIMETIDINE

Cimetidine belongs to H_{2} receptor antagonist.

Dose

• Adult: 800mg bd or 400mg tid (ac)

Contraindication

• Gastric cancer, porphyria, hepatic problems, renal disease with reduction in kidney function

Side effects

• Antiandrogenic action (gynaecomastia, loss of libido), Bolus iv injection can cause bradycardia and arrythmia, CNS effects like confusion and hallucination, Dizziness, Bowel upset.

Nursing consideration

• Antacid & Cimetidine should not be given at the same time (at least 4 hours apart)
• Concomitant use of cimetidine and Vitamin B12 is prohibited, otherwise there will be deficiency of vitamin B2 in our body.
• Monitor pulse & blood pressure of patient during therapy. Notify physician if bradycardia present. or hypertension is
• Do not breast feed while taking this drug.
• Monitor I & O ratio and pattern: Particularly in the older peoples, severely ill, and in patients with impaired renal function.
• Rapid IV administration has been associated with rare cases of arrhythmia & hypotension, so that monitor pulse & blood pressure regullary.
• For IV injections, dilute in 0.9% sodium chloride injection, 5% or 10% dextrose injection, lactated Ringer's solution, 5% sodium bicarbonate injection to a volume of 20 mL. Solution is stable for 48 hr at room temperature. For IV infusions, dilute 300 mg in at least 50 mL of 5% dextrose injection or one of above listed solutions.
• Inject by direct injection over not less than 2 minutes; by infusion, slowly over 15-20 minutes.
• Administer IM dose undiluted deep into large muscle group.
• If using one dose a day, administer drug at bedtime.

RANITIDINE

It is also H2 receptor antagonist. Ti is five times more potent then Cimetidine.

Indication

• Acid-reflux disorders (GERD)
• Peptic ulcer
• Zollinger-ellison syndrome
• Acute stress ulcers

Dose

• Adult: For ulcer healing 150 mg twice a day for 4-8 weeks

For maintenance dose 150 mg at night

Contraindication

• Hypersensitivity to H2 receptor antagonist.

Side effects

• Headache, Diarrhoea/Constipation, Dizziness

Nursing consideration:

• Intermittent infusion preferred over direct injection to decreases risk of bradycardia.
• Antacid & Ranitidine should not be given at the same time (at least 4 hours apart).
• Ranitidine crosses into breast milk and multiple dosing results in higher concentrations in breast milk than in serum, especially towards the end of a 12 hour dosing interval.
• Regular supervision is recommended for patients taking NSAIDs concomitantly with Ranitidine.
• Ranitidine is excreted via kidneys and caution is required in patients with impaired kidney function due to the potential for increased plasma levels.

Oral route

• It should be given before food.
• If using one dose a day, administer drug at bedtime.

IV route:

• Direct IV: Dilute each 50 mg in 20 ml of normal saline or 5% dextrose saline for injection.
• Rate: Administer over at least 5 minutes at a maximum of 10mg/minutes. Rapid administration may cause bradycardia, hypotension and arrhythmias.
• Intermittent Infusion: Dilute each 50 mg in 100 ml of normal saline or dextrose 5% saline. Diluted solution is stable for 48 hrs at room temperature. Do not use solution that is discolored or that contains precipitate. Rate: Administer over 15-20 minutes.

IM Injection: usual dose: 50 mg IM or IV every 6 to 8 hours,(Maximum dose: 400 mg / d * ay ) Injectable formulations do not require dilution when given as an IM injection.

-Ranitidine enters breast milk, do not breast feed while taking this drug without consulting physician.

-Renal clear ranitidine from the body, so that ranitidine must be reduced in people with poor kidney function, including renal impairment.

-Patients should be instructed to contact their physician if symptoms do not improve or worsen during treatment.

-Advise patients to speak to their physician if they become pregnant, intend to become pregnant, or are breastfeeding.

-Notify physician if black, tarry stools, fever, sore throat, diarrhea, dizziness, rash, confusion or hallucinations present. Instruct patient to take medication as directed for the full course of therapy, even if feeling better.

FAMOTIDINE

It is also H₂ receptor antagonist. It is eight time more potent than Ranitidine.

Indication

• Same as ranitidine

Dose

• Adult: 20mg bid or 40mg hs for 4-8 weeks Contraindication Hypersensitivity ti H_{2} receptor antagonist.

Side effects

• Headache, Dizziness, Bowel upset,Disorientation

Nursing consideration:

Oral route

• May be given with or without meals.
• If using one dose a day, administer drug at bedtime.

- If antacids or sucralfate are used concurrently for relief of pain, avoid administration of antacids within 1 hrs of nizatidine and take sucralfate 2 hrs after nizatidine; may decrease the absorption of Famotidine.

-Direct IV: Dilute 20 mg (2 ml) famotidine IV solution (containing 10 mg / m * l ) with D5, NS, or other compatible IV diluent to a total volume of 5 or 10 mL. IV Infusion: Dilute 2 mL famotidine IV with 100 mL compatible IV solution.

• Direct IV: Rate: Administer over 2 minutes.
• IV Infusion: Infuse over 15-30 minutes.

-Do not breast feed while taking this drug without consulting physician.

-May cause drowsiness or dizziness. Caution patient to avoid driving or other activities requiring alertness until response to the drug is known.

Notify physician if black, tarry stools, fever, sore throat, diarrhea, dizziness, rash, confusion hallucinations or present.

-Dose adjustment may need in patients with impaired renal function.

-Instruct patient to take medication as directed for the full course of therapy, even if feeling better.

NIZATIDINE

It is currently the H2 receptor antagonist with the shortest half life.

Dose:

• Adult: 150mg bid or 300mg od (hs) for4. 8 weeks

Contraindication:

• Hypersensitivity

Side effect:

• Dizziness, somnolence, arrhythmia, uritcaria, sweating, hepatitis, hyperuricemia.

Nursing consideration:

• If antacids or sucralfate are used concurrently for relief of pain, avoid administration of antacids within 1 hr of nizatidine & take sucralfate 2 hr after nizatidine; may decrease the absorption of nizatidine.
• Inform patient that smoking interferes with the action of histamine antagonists. Encourage patient to quit smoking or at least not to smoke after last dose of the day.
• May cause drowsiness or dizziness. Caution patient to avoid driving or other activities requiring alertness until response to the drug is known.
• Advise patient to avoid alcohol, products containing NSAIDs, and foods that may cause an increase in Gl irritation.
• Inform patient that increased fluid and fiber intake and exercise may minimize constipation.
• Advise patient to report onset of black, tarry stools, fever, sore throat, diarrhea, dizziness, rash, confusion, hallucinations to physician promptly. 
• Instruct patient to take medication as directed for the full course of therapy. even if feeling better.

PROTON PUMP INHIBITORS

There are a number of PPIs available. The medications are structurally and chemically similar. Rabeprazole and pantoprazole have better suppression of stomach acid compared to omeprazole. Esomeprazole is a new and very potent PPI. All PPI oral absorption, 50% in small intestine. Drug is metabolized rapidly, metabolites are excreted in urine and faeces.

• The parietal cells release positive hydrogen ions (protons) during HCl production.
• This process is called the "proton pump."
• H2 blockers and antihistamines do not stop the action of this pump.

Omeprazole, Lansoprazole, Pantoprazole, Rabeprazole, Esomeprazole are examples of PPI.

Mechanism of action

PPIs block the gastric hydrogen potassium ATPase (H+/K+ ATPase) and inhibit gastric acid secretion.

•  Irreversibly bind to H+/K+ ATPase enzyme.
• This bond prevents the movement of hydrogen ions from the parietal cell into the stomach.
• In order to return to normal acid secretion the parietal cell must synthesize new H+/K+ ATPase.

Indication:

• Oesophageal, duodenal and stomach ulcers
•  Eradication of Helicobacter pylori
•  Symptomatic disease gastroesophageal reflux (GERD)
• Erosive esophagitis (EE) due to acid- mediated GERD in patients
• Pathologic hypersecretory conditions

OMEPRAZOLE

Dose

• Adult: 20mg bid or 40mg od for 4 - 6 weeks (ac).

Contraindication

• Hypersensitivity, renal & hepatic dysfunction

Side effect

• Dry mouth, rash, back pain, upper respiratory infection, epistaxis, pneumonia

Nursing consideration:

• Report to physician if severe headache, unresolved severe diarrhea, or changes in respiratory status present.
• Report to physician if any changes in urinary elimination such as pain or discomfort associated with urination, or blood in urine.
• Inform physician if patient is or intends to become pregnant.
• Oral absorption & bioavailability is decreased 50% by food, so that it should be given before meal.
• Advice patient to avoid alcohol and not smoking (smoking make delay wound/scar healing) & NSAIDS that may cause an increase in GI irritation.
• Capsule should be swallowed whole with water, not chewed or crushed. Advice to clients to stop breast feed while taking this drug.
• Take special precaution in malignancy, hepatic impairment & pregnancy.
• Instruct patient to take medication as directed for the full course of therapy. even if feeling better.

PANTOPRAZOLE

Indication & Dose:

-IV therapy:

-GERD:20-40mg od or bd

-Erosive oesophagitis associated with GERD: 40mg/day for 7-10 days.

-Hypersecretory disorders: 80mg bd, adjust dosage based on acid output measurements; 160 - 240mg / d * ay in divided doses has been used for up to 7 days.

Note: IV therapy should be discontinued as soon as the patient tolerates oral therapy.

Oral therapy:

-Duodenal ulcer, gastric ulcer: 40mg po x ac for 4-8 weeks.

Side effect:

Headache, depression, nausea, vomiting, flatulance, diarrhoea, dizziness, chest pain, tachycardia, angina, palpitation, hyper or hypotension, insomnia, anxiety, confusion, urticaria, acne, dry skin, hyperglycemia, hyperlipemia, thrombocytopenia, leukopenia, hepatitis, muscle cramps, myalgia, arthralgia, rhinitis.

Nursing consideration:

• Monitor bowel function. Diarrhea, abdominal cramping, fever, andbloody stools should be reported to physicia promptly as a sign of pseudomembranous colitis. May begin up to several weeks following cessation of therapy.
• Oral dose may be administered with or without food. Do not break, crush, or chew tablets.
• Take special precaution in patients who are risk for Zinc deficiency.
• It disturbs the normal flora in GI tract which leads to vitamin B-complex deficiency.
• 2 minutes IV infusion: the volume of reconstituted solution (4mg / m * l) to be injected may be administered IV over at least 2 minutes.
• 15 minutes IV infusion: infuse over 15 minutes at a rate not to exceed 3 mg/ minute.
• Instruct patient to take medication as directed for the full course of therapy. even if feeling better.

LANSOPRAZOLE

It is more potent than omeprazole.

Indication & Dose

Duodenal Ulcer

Adult: 15mg od for 4 weeks.

Erosive Esophagitis

Adult: 30mg od for 8 weeks, then decrease to15mg od

GERD

Adult: 15mg od for up to 8 wk

Hypersecretory Disorder

Adult: 60mg od (max: 120mg / d * ay in divided doses),

Contraindication

Hypersensitivity, severe hepatic impairment, lactation, infants.

Side effect

• Fatigue, nausea, dizziness, headache, diarrhea, constipation, anorexia/increased appetite, rash.

Nursing consideration:

• Oral dose should be swallowed whole with a glass of water, not crush or chew capsules.
• For IV: Add 5 ml of sterile water for injection to each 30 mg vial 6 mg/ml.
• Further dilute in 50 ml of NS, RL, or D5. If reconstituted with NS or LR, administer within 24 hours. If reconstituted with D5, administer within 12 hours. Infuse over 30 min through the in-line filter provided. Monitor CBC, kidney & liver function tests periodically.
• Inform physician of significant diarrhea.
• Take special precaution for gastric malignancy.
• Do not breast feed while taking this drug.
• Lansoprazole serum concentrations may be decreased if taken with food, so that it should be given before food.
• Instruct patient to take medication as directed for the full course of therapy, even if feeling better.
• Advise patient to avoid alcohol, NSAIDs, and foods that may cause an increase in Gl irritation.

ESMOPRAZOLE

Indication & Dose

Healing of Erosive Esophagitis

Adult: 20-40mg qid for 4-8 weeks (a.c.)

GERD, Erosive Esophagitis Maintenance

Adult: 20 mg qid. (a.c.)

Duodenal Ulcer

Adult: 40mg qid (a.c.)

Contraindication

• Hypersensitivity, gastric malignancy, lactation.

Side effect

• Headache, nausea, vomiting, diarrhea, constipation, abdominal pain, flatulence, dry mouth.

Nursing consideration:

• Report to physician if severe headache, unresolved severe diarrhea, or changes in respiratory status present.
• Report to physician if any changes in urinary elimination such as pain or discomfort associated with urination, or blood in urine.
• Inform physician if patient is or intends to become pregnant.
• Oral absorption & bioavailability is decreased 50% by food, so that it should be given before meal.
• Advice patient to avoid alcohol and not smoking (smoking make delay wound/scar healing) & NSAIDs that may cause an increase in GI irritation.
• Capsule should be swallowed whole with water, not chewed or crushed.
• Advice to clients to stop breast feed while taking this drug.
• Take special precaution in malignancy, hepatic impairment & pregnancy.
• Instruct patient to take medication as directed for the full course of therapy. even if feeling better.

Nursing consideration:

• Tablets may be dispersed in 10-15ml of water. Do not chew tablet.
• Should not ginen with H2 blockers or antacids, which reduce the acidic environment required for activation of sucralfate.
• If antacids are being administered, do not give antacids within 30 minutes. before or 1 hour after sucralfate.
• This drug avoid if renal impairment, pregnancy, & lactation.
• It should be given with mouth three or four times per day, given one hour before meals and at bedtime

ULCER PROTECTIVE

It is a cytoprotective agent, which is basic aluminium salt of sulfated sucrose and has viscous consistency in acidic medium. Absorbs bile, inhibits the enzyme pepsin, and blocks back diffusion of H+ ions.

SUCRALFATE

Aluminum salt of sulfated sucrose reacts with gastric acid to form a thick paste, whichselectively adheres to the ulcer surface.

Mechanism of action:

• Attracted to and binds to the base of ulcers and erosions, forming a protective barrier over these areas.
• Protects these areas from pepsin, which normally breaks down proteins (making ulcers worse).
•  Also, protective action is enhanced by augmented gastric mucosal PG synthesis. It is considered superior in patients who continue to smoke.

Indication

• Treatment of duodenal ulcer.

Dose

• Adult: 1gm qid. Maintenance 1gm bid

Contraindication

• Hypersensitivity.

Side effect

• Nausea, gastric discomfort, constipation, diarrhea.

Nursing consideration:

• It is against the acid related diseases as GERD,peptic ulcer etc
• The negatively charged sucrose sulfate binds to positively charged proteins in the base of ulcers or erosions, forming a physical barrier that restricts further caustic damage.
• It should not given with H₂ recept antagonist or antacid.
•  If antacids are being administered, do not give antacid within 30 minutes before or 1 hour after sucralfate.
• This drug needs to be avoided if patients with renal impairment, pregnancy and lactation
• It should be given by mouth 3 or 4 times a day (one hour before meals and at bed time)