DRUGS ACTING ON THE GIT

 

DRUGS ACTING ON THE GIT

PREPARED BY MR. ABHIJIT DAS

ANTI ULCER DRUGS

PEPTIC ULCER

A peptic ulcer is a sore (wound) that develops in the lining of the lower part of esophagus (esophageal ulcer) or various part of stomach (gastric ulcer) or small intestine (duodenal ulcer).

When we eat, the stomach produces highly acidic digestive juices also known as stomach acid to help break down food.

Then the food passes into the duodenum for further digestion and absorption into the bloodstream.

To protect organs from the corrosive effects of stomach acid, a layer of mucus coats the lining of the stomach and duodenum.

When the protective mucus layer breaks down, stomach acid can destroy the lining of stomach or duodenum and cause ulcer.

CAUSES

Most peptic ulcers are caused by the bacteria Helicobacter pylori (H.pylori) through contaminated food or through close contact with an infected person. As the bacteria grow inside your stomach they damage the mucus layer allowing stomach acid to reach the stomach or duodenum lining. Together the bacteria and the stomach acid cause ulcer.

Some peptic ulcers are linked to heavy uses of ‘non-steroidal anti-inflammatory drugs’ (NSAIDs), including aspirin and ibuprofen. These drugs reduce the ability of stomach and duodenum to protect themselves from the effects of stomach acid.

 

DRUGS USED FOR THE TREATMENT OF PEPTIC ULCER

1.    REDUCTION OF GASTRIC ACID SECRETION

a.     H₂ BLOCKERS: Cimetidine, Ranitidine, Famotidine, Roxatidine

b.    PROTON PUMP INHIBITORS: Omeprazole, Lansoprazole, Pantoprazole, Rabeprazole, Esomeprazole

c.     ANTICHOLINERGICS: Pirenzepine, Propantheline, Oxyphenonium

d.    PROSTAGLANDIN ANALOGUE: Misoprostol

2.     NEUTRALIZATION OF GASTRIC ACIDS (ANTACIDS)

a.     SYSTEMIC: Sodium bicarbonate, Sodium citrate

b.    NONSYSTEMIC: Magnesium hydroxide, Magnesium trisilicate, Aluminium hydroxide gel, Magaldrate, Calcium carbonate

3.    ULCER PROTECTIVES: Sucralfate, Colloidal bismuth subcitrate (CBS)

4.    ANTI H.PYLORY DRUGS: Amoxicillin, Clarithromycin, Metronidazole, Tinidazole, Tetracyclin

H₂ BLOCKERS

MECHANISM OF ACTION

All four drugs have similar mechanism of action.

Binding of histamine with H₂ receptors present on the surface of gastric parietal cell increases HCl secretion.

But when H₂ receptor blockers bind with the H₂ receptor and block the binding of histamine with H₂ receptors, resulting in inhibition of HCl secretion.

PHARMACOLOGICAL ACTIONS

H₂ BLOCKADE: H₂ blockers block histamine induced gastric secretion.

BLOOD VESSELS: They cause fall in blood pressure

LUNGS: They cause bronchial relaxation. So H₂ blockers are used in histamine induced bronchospasm.

ADVERSE EFFECTS

1.    Diarrhoea

2.    Muscle pain

3.    Dry mouth

4.    Rashes

5.    Dizziness

6.    Headache

THERAPEUTIC USES

1.    They are used to treat duodenal ulcer and gastric ulcer

2.    They are used to treat Zolinger-Ellison Syndrome (a rare digestive disorder that results in too much gastric secretion).

3.    They are also used to treat GERD (gastro esophageal reflux disease).

PPIs (Proton Pump Inhibitors)

Examples of PPI Drugs:

Ø Omeprazole

Ø Pantoprazole

Ø Lansoprazole

Ø Rabeprazole

MOA:

PPIs block the proton pump that secretes H⁺ into the stomach, and without H⁺, HCl can't be formed, so acid secretion decreases.

Uses:

Ø Peptic ulcer disease (PUD)

Ø Gastroesophageal reflux disease (GERD)

Ø Zollinger-Ellison syndrome

Side Effects:

Ø Headache, nausea, diarrhoea

Ø Long-term use may cause:

o   Vitamin B₁₂ deficiency

o   Hypomagnesemia

ANTI-EMETICS

DEFINITION

Antiemetic drugs are medications that prevent or alleviate the symptoms of nausea and vomiting. They are used to treat various conditions, including motion sickness, chemotherapy-induced nausea, and postoperative vomiting.

CLASSIFICATION

1.    Dopamine D₂ Blockers:

·        Example: Domperidone, Metoclopramide

2.    5-HT₃ Blockers:

·        Examples:

·        Ondansetron

·        Granisetron

·        Palonosetron

DOPAMINE D2 BLOCKERS

MOA

Dopamine D₂ blockers work by blocking a specific type of receptor called D₂ receptors in the brain, particularly in a region called the "chemoreceptor trigger zone" (CTZ). By blocking these receptors, they help reduce the signals that can trigger feelings of nausea and vomiting.

ADVERSE EFFECTS

• Movement Disorders (extrapyramidal symptoms)
• Sedation and Drowsiness
• Endocrine Effects (hyperprolactinemia)
• Gastrointestinal Disturbances
• Hypotension (low blood pressure)
• Allergic Reactions

THERAPEUTICAL USES

1.    Treatment of Nausea and Vomiting

2.    Gastrointestinal Motility Disorders

3.    Psychiatric Conditions (e.g., schizophrenia and psychotic disorders)

5HT₃ BLOCKERS

MOA

The mechanism of action (MOA) of 5-HT₃ blockers involves blocking the serotonin (5-HT₃) receptors in both the gastrointestinal tract and the chemoreceptor trigger zone (CTZ). By blocking these receptors, 5-HT₃ blockers prevent serotonin from binding to its receptors in the CTZ, which is an area in the brain that triggers the sensation of nausea and vomiting.

ADVERSE EFFECTS

1.    Headache: Some individuals may experience headaches as a side effect of these medications.

2.    Constipation: 5-HT3 blockers can cause gastrointestinal disturbances, including constipation.

3.    Fatigue and Drowsiness: These drugs may lead to feelings of fatigue and drowsiness in some individuals.

THERAPEUTICAL USES

1.    Prevention of Chemotherapy-Induced Nausea and Vomiting (CINV)

2.    Prevention of Postoperative Nausea and Vomiting (PONV)

3.    Management of Nausea and Vomiting in Radiation Therapy

LAXATIVES AND PURGATIVES

CONSTIPATION

Constipation means difficult passage of stools. A person is considered to be constipated when bowel movements result in passage of small amounts of hard, dry stool, usually fewer than three times a week.

PURGATIVES

Purgatives are drugs that promotes defecation. They are also called laxatives or cathartics. Laxatives are milder evacuants while cathartics are more powerful evacuants.

CLASSIFICATION OF PURGATIVES

1.    BULK FORMING AGENTS

Dietary fiber: Bran, Psyllium (Plantago), Ispaghula, Methylcellulose

2.    STOOL SOFTNER

Docusates (DOSS), Liquid Paraffin

3.    OSMOTIC PURGATIVES

Magnesium Sulfate, Magnesium Hydroxide, Sodium Sulfate, Sodium Phosphate, Lactulose

4.    STIMULANT PURGATIVES/IRRITANT PURGATIVES

A.   DIPHENYLMETHANES: Phenolphthalein, Bisacodyl, Sodium Picosulfate

B.   ANTHRAQUINONES (EMODINS): Senna, Cascara Sagrada

C.   5-HT4 AGONIST: Tegaserod

D.   FIXED OIL: Castor Oil

BULK FORMING AGENTS

These agents include indigestible vegetable fiber and hydrophilic colloids that increase the volume of intestinal contents forming a large, soft, solid stool.

STOOL SOFTNER

·       Normally, the surface tension of the stool prevents the entry of water and fatty materials into the stool. Docusate salts lower this surface tension and as a result the stool incorporates water and fatty substances, resulting in softening of the stool.

·       Liquid paraffin is a mineral oil that is not digested. It lubricates and softens feces.

OSMOTIC PURGATIVES

Osmotic purgatives are solutes that are not absorbed in the intestine.

They retain water and increase the volume of intestinal contents which increase peristalsis to evacuate stool.

STIMULANT PURGATIVES/IRRITANT PURGATIVES

These are powerful purgatives. They produce peristalsis in the small or large intestine which helps in purgation.

They may cause abdominal cramps.

Larger doses of stimulant purgatives can cause excess purgation resulting in fluid and electrolyte imbalance.

1.   BISACODYL

MOA:

Bisacodyl is converted to active metabolite in the intestine. It irritates colonic mucosa to increase fluid secretion as well as stimulates enteric neurons to promote peristalsis.

2.   SODIUM PICOSULFATE

MOA:

It is hydrolyzed by colonic bacteria to the active form, which then acts locally to irritate the mucosa and activate the enteric neurons, resulting in peristalsis.

3.    SENNA

MOA:

They are activated into their active form in the intestines and stimulate the enteric neurons in the colon, resulting in peristalsis.

4.   CASTOR OIL

MOA:

Castor oil is hydrolyzed in the upper small intestine to ricinoleic acid, a local irritant that increases intestinal motility.

DIARRHOEA AND ANTI-DIARRHOEAL DRUGS

Definition

• Diarrhoea is the frequent passage of liquid stool.
• According to WHO: 3 or more watery stools in 24 hours.

Causes

• ↓ Water and electrolyte absorption → ↑ water in stool
• ↑ Secretion from intestinal mucosa → watery stool
• Fast intestinal motility
• Inflammation of mucosa → fluid enter the lumen
• Infection
• Drug-induced

Examples of Infectious Agents

• Viruses: Rotavirus, Astrovirus, Coronavirus
• Bacteria: E. coli, Salmonella, V. cholerae

Drug-Induced Diarrhoea

• Ampicillin
• Colchicine
• Magnesium sulphate

Treatment Approaches

• Replacement of fluid and electrolytes
• Treatment of the underlying cause
• Use of anti-diarrhoeal agents

CLASSIFICATION OF ANTI-DIARRHOEAL DRUGS

·       Antimicrobial Agents: Norfloxacin, Ciprofloxacin, Ofloxacin, Tetracycline, Cotrimoxazole, Erythromycin, Metronidazole

·       Probiotics: Lactobacillus, Enterococcus, Bacillus clausii

·       Anti-motility agents: Codeine, Loperamide, Diphenoxylate

·       Antisecretory drugs: sulfasalazine

·       Absorbents: ispaghula

ANTIMICROBIAL AGENTS

Norfloxacin

MOA

• Inhibits bacterial DNA gyrase → prevents DNA replication.

Uses

• Bacterial diarrhoea
• UTIs
• Prostatitis

Adverse Effects

• Nausea, headache
• Tendonitis
• Photosensitivity

 

Ciprofloxacin

MOA

• Inhibits DNA gyrase & topoisomerase IV.

Uses

• Traveller’s diarrhoea
• Typhoid, shigellosis
• Respiratory & urinary infections

Adverse Effects

• GI upset
• Dizziness
• Tendon rupture (rare)

 

Ofloxacin

MOA

• Inhibits DNA gyrase → blocks DNA synthesis.

Uses

• Diarrhoea
• UTIs
• STDs like chlamydia

Adverse Effects

• GI upset
• CNS effects (headache, dizziness)
• Tendon damage (rare)

 

Tetracycline

MOA

• Inhibits protein synthesis by binding 30S ribosome.

Uses

• Cholera
• Traveller’s diarrhoea
• Acne, Rickettsial infections

Adverse Effects

• Teeth discoloration
• Photosensitivity
• GI upset

 

Cotrimoxazole (Trimethoprim + Sulfamethoxazole)

MOA

• Sequential blockade of folate synthesis → bactericidal.

Uses

• Traveller’s diarrhoea
• UTIs
• Pneumocystis pneumonia

Adverse Effects

• Rash, nausea
• Bone marrow suppression
• Stevens-Johnson syndrome (rare)

 

Erythromycin

MOA

• Inhibits protein synthesis by binding 50S ribosome.

Uses

• Campylobacter diarrhoea
• Respiratory tract infections
• Pertussis

Adverse Effects

• GI irritation
• Cholestatic jaundice

 

Metronidazole

MOA

• Forms free radicals → damages DNA in protozoa.

Uses

• Amoebic dysentery
• Giardiasis
• C. difficile colitis

Adverse Effects

• Metallic taste
• Nausea

 

PROBIOTICS

Definition

• Live microorganisms that, when given in adequate amounts, help restore and maintain the natural balance of gut flora.

Mechanism of Action

• Compete with harmful bacteria
• Boost local immunity in the intestine

Examples

• Lactobacillus
• Enterococcus
• Bacillus clausii

Uses

• Diarrhoea (especially antibiotic-associated)
• Irritable bowel syndrome
• Inflammatory bowel disease

ANTI-MOTILITY AGENTS

• These drugs slow down intestinal motility, allowing more time for water and electrolyte absorption.
• Used in mild to moderate non-infectious diarrhoea to reduce stool frequency.

Examples: Loperamide, Diphenoxylate, Codeine

ANTISECRETORY DRUGS

Sulfasalazine

MOA

• In the colon, it breaks into 5-ASA (anti-inflammatory) and sulfapyridine (antibacterial).
• Reduces inflammation by inhibiting prostaglandins and cytokines.
• [Note: ASA full form-aminosalicylic acid]

Uses

• Ulcerative colitis
• Crohn’s disease
• Rheumatoid arthritis

Adverse Effects

• Nausea, vomiting
• Headache
• Skin rash

ABSORBANTS

Ispaghula

In diarrhoea, it absorbs excess water from the stool → makes stool less watery.

Thank you

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