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).
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.