DRUGS ACTING ON GIT · DRUGS ACTING ON GIT Presented by Dr. Sannithi Nagarjuna Coordinator for...
Transcript of DRUGS ACTING ON GIT · DRUGS ACTING ON GIT Presented by Dr. Sannithi Nagarjuna Coordinator for...
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DRUGS ACTING ON GIT
Presented by
Dr. Sannithi Nagarjuna
Coordinator for RIPER-GPAT Cell,
Hyderabad Academy &
Online GPAT Academy
7899107907
9885784793
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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
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PHYSIOLOGY → Study of normal functioning
of body systems
PATHOPHYSIOLOGY → Study of disorders
PHARMACOLOGY → Study of drugs
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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
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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
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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)
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DRUGS ACTING ON GIT
1. Antiulcer drugs
2. Drugs for Achlorhydria
3. Emetics & Antiemetics
4. Antidiarrhoeal agents
5. Dugs for constipation/Laxatives
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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
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Source: Google
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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.
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Homeostasis (Acid secretion)
Aggressive factors = Defensive factors
(which ↑ acid secretion) (which ↓ acid secretion)
e.g. e.g.
Acetylcholine Mucus
Histamine HCO3-
Gastrin PGs
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ETIOLOGY/CAUSE
Disturbance in homeostasis
↑ Aggressive factors ǂ ↓ Defensive factors
e.g. e.g.
Acetylcholine Mucus
Histamine HCO3-
Gastrin PGs
Helicobacter Pylori
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Source: Google
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Source: Google
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Source: Google
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ANTIHISTAMINES(H2 RECEPTOR BLOCKERS
Cimetidine - first drug, antiandrogenic action, withdrawn
from the market
Ranitidine - Popular brand names are RANTAC,
ZANTAC
Famotidine - Most potent drug
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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
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ANTICHOLINERGICS
❖Nonselective drugs have side effects like dry
mouth, dry skin, dry eye
❖Selective M1 blockers are preferred
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PG ANALOGUES
• Decrease acid secretion
• Increase bicarbonate and mucus secretion
• Also called as cytoprotective agents
• Used to treat NSAIDs induced ulcers
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NSAIDs inhibit Cyclooxygenase and inhibit the production
of PGs that result in ulcers ( PGs are defensive factors).
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GASTRIN ANTAGONISTS
Proglumide cholecystokinin antagonist, which blocks both
the CCKA and CCKB subtypes .
Not preferred due to toxicity
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ANTACIDS
Antacids are basic/alkaline substances due to
their alkalinity they will neutralize the gastric acid.
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SYSTEMIC ANTACIDS
They enter into systemic circulation, they produce
systemic alkalosis and they are not preferred due to
this reason.
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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.
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Source: Google
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ULCER PROTECTIVES
They form a layer on the ulcers and they will protect
the ulcers from direct exposure to acid or any other
irritants
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ULCER HEALING DRUGS
Carbenoxolone sodium obtained from Glycyrrhiza glabra
( Liquorice).
Due to lignin content and saponins they exhibit wound healing
property.
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ANTI H.PYLORI DRUGS
❖ H. Pylori is a gram negative bacteria
❖ Treatment includes some of antibacterials and
antiprotozoals
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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
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EMETICS & ANTIEMETICS
Emetics are the agents which produce nausea and vomiting.
The only use of emetics is in the treatment of poisoning.
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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
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Examples:
❑ Apomorphine
❑ Ipecacuanha (Emetine)
❑Mustard
❑ Salt water
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ANTIEMETICS:
These are all agents which prevent or stop the
occurance of nausea and vomiting.
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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
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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.
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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.
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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.
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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
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ANTICHOLINERGICS
Ex: Hyoscine (Scopolamine),
Dicyclomine
Hyoscine available as transdermal patches and those
patches applied behind the pinna.
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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.
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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)
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5-HT3 RECEPTOR BLOCKERS
Which are mainly used to treat
❖ Anticancer drug induced vomiting
❖ Radiation therapy induced vomiting
Ex: Ondansetron, Granisetron
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NK1 RECEPTOR BLOCKERS
Which are used to treat substance P induced
vomiting due to chemotherapy and in case of injuries
Ex: Aprepitant
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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.
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Ex:
Metoclopramide→ also has D2 receptor blockade mechanism
Domperidone → also has D2 receptor blockade mechanism
Cisapride
Mosapride
Tegaserod
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ADJUVANT ANTIEMETICS
Which alone may not have antiemetic property but
they increase the activity of other antiemetics.
Ex: Benzodiazepines
Corticosteroids
Cannabinoids (DRONABINOL, NABILONE)
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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
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1. B
2. E
3. F
4. C
5. A
6. D
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ANTIDIARRHOEAL
AGENTS
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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).
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❖ 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
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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
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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
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SPECIFIC ANTIMICROBIAL AGENTS
Antibacterials like
Ex:
Fluoroquinolones like Ciprofloxacin, Norfloxacin, Gatifloxacin,
Levofloxacin
Tetracyclines
Co-trimoxazole
Antiprotozoals like
Metronidazole, Tinidazole
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NONSPECIFIC ANTIDIARRHOEAL AGENTS
They are classified into 2 types
I. ANTISECRETORY DRUGS ( Drugs which reduce PGs)
II. ANTIMOTILITY DRUGS
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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
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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
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ANTIMOTILITY DRUGS
Ex:
1. OPIOIDS
Morphine
Loperamide
Diphenoxylate
These drugs act through µ opioid receptors present on colon.
2. ANTICHOLINERGICS
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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
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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
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IRRITANT/STIMULANT LAXATIVES
❖They act by increasing peristaltic movement of GIT
❖They act by increasing PGs
❖They act by increasing secretions
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Ex:
1. DIPHENYLMETHANES : Bisacodyl
2. ANTHRAQUINONES : Senna, Cascara
3. FIXED OILS : Castor oil
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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.
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Ex:
Ispaghula (Isabgol)
Psyllium (Plantago)
Dietary fibres
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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.
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Ex:
Magnesium Sulphate (Epsom Salt)
Magnesium Hydroxide (Milk of Magnesia)
Sodium Sulphate (Glaubers salt)
Sodium Potassium Tartarate (Rochelle salt)
Polyethylene glycol
Glycerine
Lactulose
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Source: Google
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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
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Presented by
Dr. Sannithi Nagarjuna
Coordinator for RIPER-GPAT Cell,
Hyderabad Academy &
Online GPAT Academy
7899107907
9885784793