DRUGS ACTING ON GIT

Presented by

Dr. Sannithi Nagarjuna

Coordinator for RIPER-GPAT Cell,

Hyderabad Academy &

Online GPAT Academy

7899107907

9885784793

nagarjunaspharma@gmail.com

Diseases - Caused by pathogenic/harmful microorganisms

e.g. Tuberculosis, Leprosy, Typhoid, Malaria

Disorders - due to altered/abnormal functioning of any body

system

e.g. Diabetes mellitus, Peptic ulcer, Hypertension, Hypotension,

Hyperthyroidism, Hypothyroidism

PHYSIOLOGY → Study of normal functioning

of body systems

PATHOPHYSIOLOGY → Study of disorders

PHARMACOLOGY → Study of drugs

MAJOR PARTS OF GIT

1. Stomach → acid/Hcl secretion → digestion(decrease in size),

→ To kill Microorganisms

2. Small Intestine → Absorption

3. Large Intestine → Unabsorbed substances eliminated through

feces and the process called as defaecation

LESS PARTICLE SIZE ( DIGESTED COMPOUNDS WILL REACH)

LARGE SURFACE AREA ( DUE TO VILLI AND MICROVILLI)

LIPOPHILICITY

NONPOLAR

UNIONIZED FORM ( WEAK ACIDIC TO WEAK BASIC PH AND MOST OF

PHARMACEUTICAL DRUGS ARE EITHER WEAK ACIDS OR WEAK

BASES)

SMALL INTESTINE

DISORDERS RELATED TO GIT

1. Peptic Ulcer ( Increased secretion of acid )

2. Achlorhydria ( decreased/ absence of acid secretion)

3. Emesis

4. Diarrhoea ( Increased passage of stools)

5. Constipation (Decreased passage of stools)

DRUGS ACTING ON GIT

1. Antiulcer drugs

2. Drugs for Achlorhydria

3. Emetics & Antiemetics

4. Antidiarrhoeal agents

5. Dugs for constipation/Laxatives

PEPTIC ULCER

❖ Characterized by excessive secretion of acid (acidity)

❖ Ulcers mean injuries/wounds due to long term existence of acidity

❖ Occurs in the areas highly exposed to gastric acid

❖ Stomach and duodenum are highly exposed to acid

❖ Ulcers in the stomach called as gastric ulcers

❖ Ulcers in the duodenum called as duodenal ulcers

Source: Google

Homeostasis

Maintenance of balance /equilibrium inside the body called as

homeostasis.

The major reason for disorders is disturbance in homeostasis.

Ex:

Maintenance of acid secretion, body temperature, blood

pressure, pulse rate etc.

Homeostasis (Acid secretion)

Aggressive factors = Defensive factors

(which ↑ acid secretion) (which ↓ acid secretion)

e.g. e.g.

Acetylcholine Mucus

Histamine HCO3-

Gastrin PGs

ETIOLOGY/CAUSE

Disturbance in homeostasis

↑ Aggressive factors ǂ ↓ Defensive factors

e.g. e.g.

Acetylcholine Mucus

Histamine HCO3-

Gastrin PGs

Helicobacter Pylori

Source: Google

Source: Google

Source: Google

ANTIHISTAMINES(H2 RECEPTOR BLOCKERS

Cimetidine - first drug, antiandrogenic action, withdrawn

from the market

Ranitidine - Popular brand names are RANTAC,

ZANTAC

Famotidine - Most potent drug

Proton Pump Inhibitors (H+ k+ ATPase Inhibitors)

❑ Highly effective

❑ Long term use decrease the release of intrinsic factor

which is essential for the absorption of vitamin B12 that

results in pernicious anemia

ANTICHOLINERGICS

❖Nonselective drugs have side effects like dry

mouth, dry skin, dry eye

❖Selective M1 blockers are preferred

PG ANALOGUES

• Decrease acid secretion

• Increase bicarbonate and mucus secretion

• Also called as cytoprotective agents

• Used to treat NSAIDs induced ulcers

NSAIDs inhibit Cyclooxygenase and inhibit the production

of PGs that result in ulcers ( PGs are defensive factors).

GASTRIN ANTAGONISTS

Proglumide cholecystokinin antagonist, which blocks both

the CCKA and CCKB subtypes .

Not preferred due to toxicity

ANTACIDS

Antacids are basic/alkaline substances due to

their alkalinity they will neutralize the gastric acid.

SYSTEMIC ANTACIDS

They enter into systemic circulation, they produce

systemic alkalosis and they are not preferred due to

this reason.

NONSYSTEMIC ANTACIDS

They will not enter into systemic circulation, produce local action and

they are highly preferred.

Aluminium salts produce constipation and magnesium salts produce

laxation, hence both should be used in combination.

MAGALDRATE is a combination of both in the body broken down into

aluminium hydroxide and magnesium hydroxide.

Source: Google

ULCER PROTECTIVES

They form a layer on the ulcers and they will protect

the ulcers from direct exposure to acid or any other

irritants

ULCER HEALING DRUGS

Carbenoxolone sodium obtained from Glycyrrhiza glabra

( Liquorice).

Due to lignin content and saponins they exhibit wound healing

property.

ANTI H.PYLORI DRUGS

❖ H. Pylori is a gram negative bacteria

❖ Treatment includes some of antibacterials and

antiprotozoals

DRUGS FOR ACHLORHYDRIA

❖ Rarest condition

❖ Majorly seen in children till 3 years of age

❖ Due to this they have frequently indigestion, vomiting and

infections

❖ Drugs used include Cholinergics like Carbachol, Bethanechol

EMETICS & ANTIEMETICS

Emetics are the agents which produce nausea and vomiting.

The only use of emetics is in the treatment of poisoning.

But they have some limitations like/they are not suitable in the

following conditions:

❖ If the patient is unconscious

❖ If the poison is already absorbed

❖ If the poison is strong acid/ strong base/corrosive which cause

further damage to the oesophagus

❖ If the poison is detergents/petroleum products which could be

aspirated into lungs

❖ Substance ingested likely to cause rapid onset of drowsiness or

seizures

Examples:

❑ Apomorphine

❑ Ipecacuanha (Emetine)

❑Mustard

❑ Salt water

ANTIEMETICS:

These are all agents which prevent or stop the

occurance of nausea and vomiting.

CONDITIONS ASSOCIATED WITH VOMITING

Motion sickness (Vomiting during Journey/motion)

Morning sickness ( Vomiting during pregnancy)

Drugs like Levodopa

Conditions like Migraine

Anticancer drugs and radiation therapy

Excessive eating, excessive drinking & Bad smell/odor

Vomiting occurs due to stimulation of Vomiting centre (Emetic centre).

Vomiting centre is controlled by two centres named as CTZ

(Chemoreceptor Trigger Zone, located in CNS) & NTS (Nucleus

Tractus Solitarius, located in GIT).

CTZ is having receptors like D2, 5-HT3 & NK1 receptors and stimulation

of CTZ takes place due to stimulation of any one of the receptors.

Stimulation of NTS takes place due to excessive stimuli from

stomach.

MOTION SICKNESS

Any form of travel on land, in the air or on the water canbring on the uneasy feeling of vomiting.

Children between the ages of 2 and 12 are most likely tosuffer from motion sickness.

Motion sickness is caused by a conflict between signalsarriving in the brain from the inner ear, which forms thebase of the vestibular system, the sensory apparatus thatdeals with movement and balance, and whichdetects motion mechanically.

Motion sickness occurs due to stimulation of muscarinicand H1 receptors in vestibular apparatus which furtherstimulates CTZ.

Receptors Present in CTZ Reason for the Stimulation

D2 Morning sickness

(Vomiting during pregnancy)

Drugs like Levodopa

Conditions like Migraine

5-HT3 Anticancer drugs and radiation

therapy

NK1 Excessive release of substance

P due to chemotherapy

Stimulation of NTS takes place due to excessive stimuli from

stomach observed in case of excessive eating, excessive drinking &

bad smell/odor.

CLASSIFICATION OF ANTIEMETICS

1. Anticholinergics

2. Antihistamines (H1 receptor blockers)

3. D2 receptor blockers (Neuroleptics)

4. 5-HT3 receptor blockers

5. NK1 receptor blockers

6. Gastroprokinetic agents

7. Adjuvant antiemetics

ANTICHOLINERGICS

Ex: Hyoscine (Scopolamine),

Dicyclomine

Hyoscine available as transdermal patches and those

patches applied behind the pinna.

ANTIHISTAMINES (H1 RECEPTOR BLOCKERS)

Ex: Promethazine,

Diphenhydramine,

Dimenhydriate,

Cyclizine

Anticholinergics and antihistamines exclusively used for the

treatment of motion sickness and they should be taken atleast 1

hour before the commencement of journey and they are also

effective in morning sickness.

D2

RECEPTOR BLOCKERS

(NEUROLEPTICS)

Which are mainly used to treat

❖Morning sickness (Vomiting during pregnancy)

❖ Levodopa induced vomiting

❖Migraine induced vomiting

Ex: Chlorpromazine, Haloperidol- Extrapyramidal side

effects (Parkinsonism like symptoms)

5-HT3 RECEPTOR BLOCKERS

Which are mainly used to treat

❖ Anticancer drug induced vomiting

❖ Radiation therapy induced vomiting

Ex: Ondansetron, Granisetron

NK1 RECEPTOR BLOCKERS

Which are used to treat substance P induced

vomiting due to chemotherapy and in case of injuries

Ex: Aprepitant

GASTROPROKINETIC AGENTS

Which increase the motility of GIT allowing the fast passage of

contents from stomach to intestine.

As a result of this mechanism contents present in stomach for less

time hence there is no chance of vomiting.

Due to this mechanism they produce diarrhoea as a side effect.

They stimulate 5-HT4 receptors present in GIT allowing the release

of Acetylcholine which increase the peristaltic movement of GIT.

Ex:

Metoclopramide→ also has D2 receptor blockade mechanism

Domperidone → also has D2 receptor blockade mechanism

Cisapride

Mosapride

Tegaserod

ADJUVANT ANTIEMETICS

Which alone may not have antiemetic property but

they increase the activity of other antiemetics.

Ex: Benzodiazepines

Corticosteroids

Cannabinoids (DRONABINOL, NABILONE)

Condition Drug of Choice

1. Motion Sickness A) Metoclopramide

2. Levodopa induced vomiting B) Hyoscine

3. Chemotherapy induced vomiting C) Aprepitant

4. Substance P induced vomiting D) Cannabinoids

5. Gastroprokinetic with D2 receptor

blockade property

E) Haloperidol

6. Adjuvant antiemetic F) Ondansetron

1. B

2. E

3. F

4. C

5. A

6. D

ANTIDIARRHOEAL

AGENTS

ANTIDIARRHOEAL AGENTS

❖ Used for the treatment of diarrhoea

❖ Diarrhoea is characterized by increase in the frequency of passage of

stools

❖ Mostly diarrhoea is a disease and very few cases it is considered as a

disorder.

❖ Most of the times diarrhoea occurs due to contamination with microorganisms

(Disease) and some times it occurs due to increased peristaltic movement of GIT

(Disorder).

❖ Appearance of more water in the stools called as watery/loose

stools → Indicates bacterial infection

❖ Appearance of blood in the stools called as Dysentery → caused by

Shigella

❖ Appearance of pus in the stools called as Amoebiasis → caused by

Entamoeba histolytica

❖ Severe vomiting with diarrhoea observed in case of Cholera →

caused by Vibrio cholera

❖ Fever with diarrhoea observed in case of Salmonella infection

❖ Travellers diarrhoea Caused by E.Coli

REHYDRATION

Severe diarrhoea results in dehydration, some times lead to death.

Severe stage of dehydration is identified by loss of urine output.

Dehydration will be corrected by Rehydration that can be done by

either oral route or IV depends upon the emergency.

Composition usually includes

Sodium chloride Electrolyte replacement

Potassium chloride Electrolyte replacement

Sodium

bicarbonate/Sodium

citrate

Buffer

Glucose Nutrient replacement

Water Fluid replacement

Antidiarrhoeal agents are classified into two types:

I. Specific Antimicrobial agents

Which are used when the diarrhoea is caused by specific

microorganism

II. Nonspecific Antidiarrhoeal agents

Which are used when the diarrhoea is caused by

increased peristaltic movement of GIT

SPECIFIC ANTIMICROBIAL AGENTS

Antibacterials like

Ex:

Fluoroquinolones like Ciprofloxacin, Norfloxacin, Gatifloxacin,

Levofloxacin

Tetracyclines

Co-trimoxazole

Antiprotozoals like

Metronidazole, Tinidazole

NONSPECIFIC ANTIDIARRHOEAL AGENTS

They are classified into 2 types

I. ANTISECRETORY DRUGS ( Drugs which reduce PGs)

II. ANTIMOTILITY DRUGS

ANTISECRETORY DRUGS

( DRUGS WHICH REDUCE PGS)

1. SULFASALAZINE

Sulfasalazine

Azo Reductase

5-Amino Salicylic acid (5-ASA) + Sulfapyridine (Carrier)

(Active)

Inhibits COX in the colon

Inhibits PGs, Inhibits secretions & Motility

The official name given to 5-Amino Salicylic acid (5-ASA) is

MESALAMINE (MESALAZINE).

2. OLSALAZINE

Which consist of 2 molecules of 5-Amino Salicylic acid (5-ASA).

3. ANTICHOLINERGICS

ANTIMOTILITY DRUGS

Ex:

1. OPIOIDS

Morphine

Loperamide

Diphenoxylate

These drugs act through µ opioid receptors present on colon.

2. ANTICHOLINERGICS

DRUGS FOR CONSTIPATION

Constipation is characterized by decrease in the passage of stools

or difficulty in the passage of stools.

Drugs for constipation include

Aperients → Very milder

Laxatives → Milder

Purgatives → Stronger

Cathartics → very Stronger

CLASSIFICATION OF LAXATIVES

They are classified into 4 types

1. Irritant/Stimulant laxatives

2. Bulk forming laxatives

3. Osmotic/Saline laxatives

4. Surfactant laxatives/ Stool softeners

IRRITANT/STIMULANT LAXATIVES

❖They act by increasing peristaltic movement of GIT

❖They act by increasing PGs

❖They act by increasing secretions

Ex:

1. DIPHENYLMETHANES : Bisacodyl

2. ANTHRAQUINONES : Senna, Cascara

3. FIXED OILS : Castor oil

BULK FORMING LAXATIVES

They are not digested and they are not

absorbed.

Due to indigestion, all bulky material reach to

the large intestine, increases bulkiness and

causes free passage of stools.

Ex:

Ispaghula (Isabgol)

Psyllium (Plantago)

Dietary fibres

OSMOTIC/SALINE LAXATIVES

They are not absorbed and they cause retention of

water.

Unabsorbed compounds will reach large intestine and

due to retention of water swelling takes place that

increases bulkiness.

Ex:

Magnesium Sulphate (Epsom Salt)

Magnesium Hydroxide (Milk of Magnesia)

Sodium Sulphate (Glaubers salt)

Sodium Potassium Tartarate (Rochelle salt)

Polyethylene glycol

Glycerine

Lactulose

Source: Google

SURFACTANT LAXATIVES/ STOOL SOFTENERS

Due to increased reabsorption of water hardening of

stools will result that causes difficulty in the passage of

stools.

Drugs are surfactants which reduce interfacial tension

and increases water incorporation that soften the

stools.

Ex: DOCUSATES (Dioctyl Sodium Sulfosuccinate),

MINERAL OIL

Presented by

Dr. Sannithi Nagarjuna

Coordinator for RIPER-GPAT Cell,

Hyderabad Academy &

Online GPAT Academy

7899107907

9885784793

nagarjunaspharma@gmail.com