GASTROINTESTINAL DRUGS

1. Reduction of gastric acid secretion(a) H2 antihistamines :

Cimetidine RanitidineFamotidineRoxatidine

(b) Proton pump inhibitors: OmeprazoieLansoprazolePantoprazoleRabeprazoleEsomeprazole

(c) Anticholinergics : PirenzepinePropanthelineOxyphenonium

(d) Prostaglandin analogueMisoprostol

2. Neutralization of gastric acid (Antactids)(a)Systemic:

Sodium bicarbonate Sod.citrate

(b) Non Systemic:Magnesium hydroxide gelMag. TrisilicateAluminium hydroxideMagaldrateCalcium carbonate

3. Ulcer protectives: SucralfateColloidal bismuth subcitrate (CBS)

4. Anti-H. pylori drugs: AmoxicillinClarithromycinMetronidazoleTinidazoleTetracycline

Mechanisms of Action•Suppress secretory responses to food stimulation and nocturnal secretion of gastric acid via their ability to decrease (indirectly) the activity of the proton pump. H2 blockers also partially antagonize HCl secretion caused by vagal stimulation or by gastrin.

Clinical Uses•Acid peptic disease (overall less effective than proton pump inhibitors)•gastroesophageal reflux disease(GERD)• Zollinger-Ellison syndrome

Adverse Effects•GI distress, dizziness, somnolence; slurred speech and delirium possible in elderly. •Cimetidine is a major inhibitor of Cyt.P450 isoforms Increase drug interaction via increasing effects of quinidine, phenytoin, tricyclic antidepressants and warfarin. Cimetidine decreases androgens gynecomastia

Mechanisms of Action•Omeprazole and related "-prazoles" are irreversible, direct inhibitors of the proton pump(K+/H+ antiporter) in the gastric parietal cell

Clinical Uses•They are more effective than H2 blockers in peptic ulcer disease (PUD) and are also effective in GERD and Zollinger-Ellison syndrome.

•Adverse Effects•May cause mild CNS and GI effects and decrease bioavailability of drugs that require acidity for oral absorption (e.g., fluoroquinolones, ketoconazole). •Inhibit P450 decrease elimination of diazepam, phenytoin and warfarin

Mechanism of ActionAnticholinergic drugs reduce the volume of gastric juicewithout raising its pH unless there is food in stomachto dilute the secreted acid

Mechanisms of Action•PGE2 analog, which is cytoprotective increases mucus and bicarbonate secretion.

Clinical Uses•Selective use in NSAID-induced GI ulcers.

Major problems in the use of misoprostol are- diarrhoea, abdominal cramps, uterine bleeding, abortion, and need for multiple daily doses.

Mechanisms of Action•Ca, Mg, and Al hydroxides that neutralize protons in the gut lumen

Adverse Effects•May increase oral absorption of azoles, fluoroquinolones, and tetracyclinesAntacid alkalo

sisAcid rebound

diarrhoea

constipation

Other toxicity

Al. hydroxide - - - ++ Hypophosphatemia, dementia

Ca. carbonate + ++ - ++ hypercalcemia

Mg. hydroxide _ ++ ++ - Hypermagnesemia, resp. paralysis

Na. bicarbonate

++ ++ _ _ “Gas”

Mechanisms of Action•Polymerizes on GI luminal surface to form a protective gel-like coating of ulcer beds

Clinical Uses•Increase healing and decrease ulcer recurrence.• Sucralfate requires acid pH, antacids may interfere. •Bismuth subsalicylate is also protective.

•Adverse effects•Sucralfate: constipation

hypophosphatemia Dry mouth and nausea are infrequent

• CBS: diarrhoea, headache and dizziness. Prolonged use has the potential to cause osteodystrophy and encephalopathy

Two weeks regimes (mg)

1. Amoxicillin 750 + Tinidazole 500 + Omeprazole 20 all BD2. Amoxicillin 750 + Tinidazole 500 +Lansoprazole 30 all BD3. Clarithromycin 250 + Tinidazole 500 +Lansoprazole 30 all BD4. Clarithromycin 500 + Amoxicillin 1000 +Lansoprazole 30 all BD5. Clarithromycin 500 BD/Amoxicillin 750 BD + Omeprazole 20 BD6 Amoxicillin 500 TDS/Tetracycline 500 QID + Metronidazole 400 QID/Tinidazole 500 BD + Bismuth 120 QID7. Amoxicillin 750 TDS + Metronidazole 500 TDS + Ranitidine 300 OD8. Amoxicillin 750 BD + Clarithromycin 250 BD + Lansoprazole 30 BD

1. Anticholinergics Hyoscine, Dicyclomine

2. H1 antihistaminics Promethazine, Diphenhydramine,

Dimenhydrinate, Doxylamine, Cyclizine, Meclozine, Cinnarizine

3. Neuroleptics Chlorpromazine, Prochlorperazine, Haloperidol, etc

4. Prokinetic drugs Metoclopramide Domperidone,

Cisapride, Mosapride Tegaserod

5. 5-HT3 antagonists Ondansetron,Granisetron

6. Adjuvant Dexamethasone, antiemetics Benzodiazepines,

Cannabinoids

• Opioid analgesics (eg, morphine) have duality ofaction: decrease emesis by activating receptors

that decrease pain transmission and increase emesis by activating receptors In the CTZ

• Mechanisms of Action:• It acts probably by blocking conduction of nerve

impulses across cholinergic link in the pathway leading from the vestibular apparatus to the vomiting centre.

• Use: effective drug for motion sickness.

. Adverse effect:brief duration of actionSedationOther anticholinergic actions

• Mechanisms of ActionIt acts by inhibiting influx of Ca++ from endolymph

into the vestibular sensory cells which mediates labyrinthine reflex.

Uses:-mainly in motion sickness and-to a lesser extent in morning sickness-postoperative vomiting.

Adverse effects:• drowsiness, dry• mouth, vertigo and abdominal upset

• MOAAct by• Blocking D2 receptors in the CTZ• Antagonize apomorphine induced vomiting and • Have additional antimuscarinic as well as H1

antihistaminic property.

Uses• Drug induced and postanaesthetic nausea and vomiting.(b) Disease induced vomiting: gastroenteritis, uraemia, liver

disease, migraine, etc.(c) Malignancy associated and cancer chemotherapy (mildly

emetogenic) induced vomiting.(d) Radiation sickness vomiting (less effective).(e) Morning sickness: should not be used except in

hyperemesis gravidarum

• Adverse effect• sedation. • Acute muscle dystonia may occur after a single

dose, especially in children and girls. • The antiemetic dose is generally much lower than

antipsychotic doses. • These agents should not be administered until

the causeof vomiting has been diagnosed; otherwise specific

treatment of conditions like intestinal obstruction, appendicitis maybe delayed due to symptom relief.

• These are drugs which promote gastrointestinal transit and speed gastric emptying by enhancing coordinated propulsive motility.

• METOCHLOPROMIDEMOA:(a)D2 antagonism(b)5-HT4 agonism(c)5-HT3 antagonism

• Uses1.Antiemetic• postoperative, Drug induced, disease associated

(especially migraine), radiation sickness • is less effective in motion sickness

• 2. Gastrokinetic : To accelerate gastric emptying(a) When emergency general anaesthesia is to be

given and the patient has taken food less than 4 hours before.

(b) To relieve postvagotomy or diabetes associated gastric stasis.

(c) To facilitate duodenal intubation

• 3. Dyspepsia and other functional g.i disorders. Metoclopramide may succede in stopping persistent hiccups

• 4. Gastroesophageal reflux disease(GERD)Metoclopramide may afford symptomatic relief in

milder cases of GERD

• Adverse effects Metoclopramide is generally well tolerated.• Sedation, dizziness, loose stools, muscle

dystonias (especially in children) are the main side effects.

• Long-term use can cause parkinsonism, galactorrhoea

and gynaecomastia.• It should not be used to augment lactation.

Though the amount secreted in milk is small, but suckling infant may develop loose motions, dystonia, myoclonus.

• MOAIt blocks the depolarizing action of 5-HT through 5-HT3

receptors on vagal afferents in the g.i.t as well as NTS and CTZ.

Uses:• cancer chemotherapy/radiotherapy induced

vomiting.

• Adverse effectthe only common side effect is headache• Mild constipation or diarrhoea and abdominal

discomfort occur in few patients