Basic Training Program

RPGLS
Digestive System
The Digestive System

Allows the body

to break down

food and
nutrients!
Introduction to the Digestive System

• Digestion:
mechanical and chemical
breakdown of foods and
absorption of the
resulting nutrients by
cells
• Digestive System:
consists of the alimentary
canal and several
accessory organs.
Processes of the Digestive System

• Ingestion
• Motility
• Secretion
• Digestion:
enzymatic
• Absorption
• Elimination
• (Self protection)
 Layers of the GI Tract
 Mucosa: The mucosa is the absorptive and
secretory layer.

 Sub mucosa: The sub mucosa is relatively

thick. The absorbed elements that pass through
the mucosa are picked up from the blood vessels
of the sub mucosa.

 Muscularis: The muscularis is responsible for

segmental contractions and peristaltic movement
in the GI tract.

 Serosa: The last layer is a protective layer.

 Digestive System
Alimentary canal-
mouth to anus
Processes of the Mouth

• Mastication (chewing) of food

• Mixing masticated food with saliva
• Initiation of swallowing by the tongue
• Allowing for the sense of taste
 Pharynx Anatomy
• The pharynx is a tube that
connects the mouth to
both the larynx & the
esophagus.
• It does not engage in
digestion process.
• There is a valve called
epiglottis which separates
the food pipe & wind pipe
in pharynx.

C
 Oesophagus
• Approximately 25cm
long
• Moves food from the
throat to the stomach
– Muscle movement
called peristalsis
• If acid from the
stomach gets in here
that’s heartburn.
 Esophagus
• Peristalsis: Wave-like muscular contractions.
Peristalsis and Segmentation
 Stomach
• J-shaped, pouch-like
organ
• Receives food from
esophagus
• Mixes food with
gastric juice
• Initiates protein
digestion
• Carries on limited
absorption
• Moves food into
small intestine
 Parts of the Stomach

• Cardiac Region
• Fundic Region
• Body Region
• Pyloric Region
 Gastric Glands
Gland Secretion Action
Goblet cells mucus Cytoprotection

Parietal cells HCl Converts pepsinogen

to pepsin, helps in
protein digestion

Chief cells Pepsinogen Protein synthesis

Enterochromaffin-like histamine and Stimulates HCl

cells (ECL) serotonin production.
G cells gastrin Stimulates HCl
production
 Regulation of Gastric Secretions

• Gastric juice is produced continuously

• Rate varies and is controlled neurally and
hormonally
• Parasympathetic impulses travel along the
vagus nerve in response to smell, taste or
visual of appetizing food or if food enters the
stomach.
• Acetlycholine (Ach) is released from nerve
endings and stimulates gastric glands to
secrete large amounts of gastric juice and the
peptide hormone, gastrin.
• Gastrin increases secretory activity of gastric
glands.

• When food moves into upper part of small

intestine, acid triggers sympathetic nerve impulses
that inhibit gastric juice secretion.

• Proteins and fats in intestine cause intestinal wall

to release hormone cholecystokinin, which
decreases gastric motility as small intestine fills
with food.
 Phases of Gastric secretion

• Gastric motility and secretion are automatic.

• Waves of contraction are initiated spontaneously
by pacesetter cells.
• Extrinsic control of gastric function is divided into
3 phases:
– Cephalic phase.
– Gastric phase.
– Intestinal phase.
 Cephalic Phase
• Stimulated by sight, smell, and taste of food.
• Activation of vagus:
– Stimulates chief cells to secrete pepsinogen.
– Directly stimulates G cells to secrete gastrin.
– Directly stimulates ECL cells to secrete histamine.
– Indirectly stimulates parietal cells to secrete HCl.
• Continues into the 1st 30 min. of a meal.
 Gastric Phase
• Arrival of food in stomach stimulates the gastric
phase.
• Gastric secretion stimulated by:
– Distension.
– Chemical nature of chyme (amino acids and
short polypeptides).
• Stimulates G cells to secrete gastrin.
• Stimulates chief cells to secrete pepsinogen.
• Stimulates ECL cells to secrete histamine.
– Histamine stimulates secretin of HCl.
 Intestinal Phase

• Inhibits gastric activity when chyme enters the small

intestine.
Activates sensory neurons of vagus and produces an
inhibitory neural reflex:
• Inhibits gastric motility and secretion.
• In the presence of fat, enterogasterone inhibits
gastric motility and secretion.
• Hormone secretion:
– Inhibit gastric activity:
• Somatostatin, CCK, and GLP-1.
 The Small Intestine
• Duodenum
– ~10 inches in length
– Primary site of digestion
• Jejunum
– ~4 feet in length
– Some digestion
• Ileum
– ~5 feet in length
– Little digestion
Anatomy of the Large Intestine
Food Breakdown and Absorption
in the Large Intestine

• No digestive enzymes are produced

• Resident bacteria digest remaining nutrients
• Produce some vitamin K and B
• Release gases
• Water and vitamins K and B are absorbed
• Remaining materials are eliminated via feces
 Rectum

Store house for waste product.

Feces Formation and Defecation

• Chyme dehydrated• Control

to form feces
– Parasympathetic
• Feces composition
– Water – Voluntary
– Inorganic salts
– Epithelial cells
– Bacteria
– Byproducts of
digestion
• Defecation
– Peristalsis pushes
feces into rectum
– Rectal walls stretch
 GI Tract
Food Mouth
Bolus Esophagus
Stomach
Chyme Duodenum
Jejunum
Ileum

“Waste” Cecum
Ascending colon
Transverse colon
Descending colon
Sigmoid colon
 Functions of the GI Tract

Ingestion Taking food into the mouth.

Mastication Chewing the food and mixing it
with saliva.
Deglutition Swallowing the food.
Peristalsis Rhythmic wave-like contractions
that move food through GI tract.
Digestion Breakdown of food particles into
subunits (chemical structure
change).
Absorption Process of the passage of
digestion (chemical subunits) into
the blood or lymph.
 Accessory Organs
• Secrete substances used in the process of
digestion
• Includes:
Salivary glands Liver
Gallbladder Pancreas
 Saliva

• Mixture of mucus and serous fluids

• Helps to form a food bolus
• Contains salivary amylase to begin starch
digestion
• Dissolves chemicals so they can be tasted

Copyright © 2003 Pearson Education, Inc. publishing as Benjamin Cummings

 Liver
• Functions
– Makes bile
• Detergent – emulsifies
fats
• Release promoted by:
– Vagus n.
– CCK
– Secretin
• Contains
– Water
– Bile salts
– Bile pigments
– Electrolytes
– Cholesterol
– Lecithin
 Liver
– Detoxifies/removes
• Drugs
• Alcohol
– Stores
• Gycolgen
• Vitamins (A, D, E, K)
• Fe and other minerals
• Cholesterol
– Activates vitamin D
– Fetal RBC production
– Phagocytosis
– Metabolizes absorbed food
molecules
• Carbohydrates
• Proteins
• Lipids
 Gall Bladder
• Stores bile from the
liver
• Delivers bile when
food is digested
• Fatty diets can
cause gallstones
 Functions of Bile Salts
• Aid digestive enzymes
• Emulsification: break up fat globules (like dish
detergent) to increase total surface area of fatty
substance for more efficient fat digestion by
lipases.
• Enhance absorption of fatty acids, cholesterol,
and fat-soluble vitamins A, D, E, and K.
• Lack of bile salts results in poor lipid absorption
and vitamin deficiencies.
 Pancreas
• Produces compounds
to digest fats and
proteins
• Neutralizes acids that
enter small intestine
• Regulates blood
sugar by producing
insulin
 Pancreatic juice

Enzyme Action

Pancreatic amylase carbohydrate-digesting enzyme.

Splits starch or glycogen into
disaccharides.

Pancreatic lipase fat-digesting enzyme. Breaks

triglyceride molecules into fatty
acids and glycerol.

Nucleases enzymes that break down nucleic

acid molecules into nucleotides.

Trypsin, Chymotrypsin, Protein digestion

Carboxypeptidase
 A Summary
ORGAN FUNCTIONS

Mouth Chewing
Digestion of starch

Esophagus Passage way

Stomach Food Storage

Acid kills bacteria
Some protein digestion

Small Intestine Final digestion

Absorption

Large Intestine Absorption of water, minerals

Anus Elimination

Liver Production of bile

Gallbladder Store and release bile

Pancreas Enzymes and bicarbonate

 Write the name of each colored organ:

• Green:
• Red:
• Pink:
• Brown:
• Purple:
• Green:
• Yellow:
 Answers
• Green: Oesophagus
• Red: Stomach
• Pink: Small Intestine
• Brown: Large Intestine
• Purple: Liver
• Green: Gall Bladder
• Yellow: Pancreas
 H+ Excretion
Blood Cell Lumen

CO2 + H2O
k+
C.A. H+
H2CO3
ATPase
HCO3 -

HCO3- + H+
Cl- Cl-

Mechanism of acid secretion

 HCl Production

• HCl production is • HCl Functions:

stimulated:
– Indirectly by gastrin.
– Indirectly by ACh.
• ACh and gastrin stimulate
release of histamine.
– Histamine: • Activates pepsinogen to
• Stimulates parietal
cells to secrete HCl.
Makes gastric juice very
acidic.
– Denatures ingested
proteins (alter tertiary
structure) so become
more digestible.
pepsin.
– Pepsin is more active at
pH of 2.0.
Nausea and Vomiting
• Nausea-conscious desire to vomit
• Vomiting-ejection of emesis from upper
GI tract
 Physiology of nausea & vomiting

• Coordination of nausea and vomiting is performed by

the vomiting centre, located in the brainstem.The
vomiting centre receives information from 4 main areas
within the body.
– Chemoreceptor Trigger Zone (CTZ) eg. Drugs and toxins
stimulate it.
– Vestibular Centre (brainstem) eg. sea sickness, motion
sickness
– Cerebral Cortex (memory of unpleasant stimulus/ anticipatory
nausea) eg. drug previously causing nausea-chemotherapy
– Gut (GIT) via the vagus nerve eg. gastric irritation by drugs,
dyspepsia
Nausea and Vomiting—Etiology

• GI disorders
– Non GI disorders
• Pregnancy
• Infections
• CNS disorders
• Cardiovascular disorders
• Metabolic disorders
• Stress
• Medications
• Motion
Nausea and Vomiting
Clinical Manifestations

• Nausea-subjective
• If vomiting prolonged
– Dehydration
– Water, electrolytes lost
– Loss of extracellular fluid leading to
circulatory collapse
– Metabolic alkalosis can occur-gastric loss
or
– Metabolic acidosis if small intestine
contents lost (less common)
Characteristics of Vomiting

• Color
– “Coffee grounds”-bleeding in
stomach
– Blood changes to dark brown
as result of interaction with
HCL
– Bright red blood-active
bleeding
– Green-bile
Medications to Alleviate Nausea/Vomiting

• Metroloperamide and Domperidone

– Antiemetics
– Act on Dopamine receptors
– Enhance release of acetylcholine
– Increased gastric emptying
(prokinetics)
– Side effects of Reglan:
hallucinations, tremors, dyskinesias
 What is the epidemiology of APD?

• Lifetime prevalence of APD is approximately

10% i.e. atleast 1 in 10 suffer from APD
sometime during life.
• Upper GIT-related symptoms account for
nearly 3-4% of all GP consultations.
• Nearly 5,00,000 new cases of APD are
presented to the clinician every year and there
are about a million ulcer recurrences.
• 50% of healthy individuals experience
heartburn on a daily basis.
 Since all of us have acid pepsin in our
stomach, why do we not develop APD?

• APD are produced when the aggressive effects

of acid-pepsin dominate the protective effects
of gastric or duodenal mucosal resistance.
• Under normal conditions there is a balance
between both the aggressive and defensive
factors.
 Acid Peptic Diseases

Defensive factors:
Aggressive factors:
• Mucosal barrier
• Hydrochloric acid
• Mucus
• Pepsinogen
• Blood flow
• Bile acids
• Prostaglandins
• Microorganisms
• Bicarbonates
Objectives of APD Management

– Provide relief from pain

– Correct the APD
– Accelerate the healing of
inflammation or ulcer
– Prevent recurrence and
complications
 Gastritis
• Gastritis?
– Gastritis means inflammation of the stomach. It means
that white blood cells move into the wall of the stomach
as a response to some type of injury. Gastritis does not
mean that there is an ulcer or cancer. It is simply
inflammation–either acute (present for a short period) or
chronic (for a longer duration).
• Breakdown in normal gastric mucosa from:
– Medications i.e. steroids, NSAID’s
– Diet i.e. spicy, ETOH
– Microorganisms i.e.. H. Pylori, Salmonella, Staph
– Smoking
– Pathophysiology i.e. burns, stress, renal failure, sepsis, shock
– Trauma i.e. NGT, endoscopy
 Manifestations of Gastritis

• Acute gastritis
– Anorexia
– Nausea
– Vomiting
– Epigastric tenderness
– Feeling of fullness
– Chronic gastritis
– May be asymptomatic
Nursing Care of the Client with Acute
Gastritis

• Antiemetics
• Antacids
• H2 blockers
• Proton pump inhibitor
 Duodenitis

Duodenitis is basically inflammation and irritation

of the wall of the first part of the small intestine.

• Symptoms are similar to Peptic Ulcer Disease or

duodenal ulcers. There can be stomach pain,
bleeding from the intestine, nausea, vomiting, loss
of appetite, and, rarely, intestinal obstruction.

• It is similar to ulcers but less severe. Treatment is

similar to ulcers.
 Dyspepsia

“Dyspepsia means bad digestion & is commonly

known as indigestion”.
Symptom:
Epigastric discomfort, Bloating, Nausea,
Heartburn, Feeling of fullness just after eating.
Types:
Ulcer like dyspepsia- Pain
Motility like dyspepsia- Bloating, fullness
Reflux like dyspepsia- Heartburn
NUD - when clear cause of symptom is not
identified.
Treatment of Dyspepsia

• The drugs used for the

treatment of Dyspepsia
include antisecretory drugs,
prokinetic drugs,
cytoprotective agents &
antacids
 H. Pylori

 Introduction:
 It is a spiral shaped gram (-)ve bacilli. It resides in mucus
gel coated endothelial cells. H. Pylori secretes urease that
protects it from being destroyed in acid environment.

 How H.Pylori causes damage of gastric lining?

 This bacteria resides below the mucus protective layer &
hence protected from Hcl. From there it start attacking the
mucosal cells. Finally it may also disrupt the mucus layer so
that acid can get in contact with damaged mucosal area &
damage it further.
 Believed to be acquired in childhood and survives.
 Can play a major role in gastritis, peptic ulcer, duodenal ulcer.
 Diagnosis & Treatment

• Diagnosis: • Treatment:
– Tissue test – Antibiotc
– Biopsy • Metronidazole
• Tetracycline
– Urease test
• Clarithromycin
– Culture test • Amoxycilin
– Blood test – Antacid:
• H2 Receptor antagonist
• PPI
 GERD

• Gastro-esophageal Reflux Disease is

defined as chronic symptoms or mucosal damage
produced by the abnormal reflux of gastric
contents into the esophagus”.

• Classic GERD symptoms

– Heartburn (pyrosis): substernal burning
discomfort
– Regurgitation: bitter, acidic fluid in the mouth
when lying down or bending over
 GERD (Contributing factor)

The exact cause of GERD is not known. But there are

certain factor which has been observed to cause
GERD.
1.Excess of alcohol
2. Overweight
3. Pregnancy
4. Smoking
\

Certain foods are also suppose to cause GERD

1. Citrus food
2. Chocolate
3. Drinks with caffeine
4. Fatty & fried foods
5. Spicy foods
6. Garlic & onion
 Symptoms of GERD

• Heartburn
• Regurgitation
• Cough
• Nausea
• Atypical chest pain
• Dysphagia
– Difficulty swallowing: food sticks or hangs up
• Odynophagia
– Retrosternal pain with swallowing
• Bleeding
Complications
• Deep ulcers,
• Bleeding,
• Esophageal stricture, and replacement
of normal esophageal epithelium with
abnormal (Barrett’s) epithelium,
• Cancer of oesophagus, and reflux
laryngitis
 Treatment Goals for GERD

• Eliminate symptoms
• Heal esophagitis
• Manage or prevent complications
• Maintain remission
 Lifestyle Modifications are Cornerstone of
GERD Therapy

• Elevate head of bed 4-6 inches

• Avoid eating within 2-3 hours of bedtime
• Lose weight if overweight
• Stop smoking
• Modify diet
– Eat more frequent but smaller meals
– Avoid fatty/fried food, peppermint,
chocolate, alcohol, carbonated beverages,
coffee and tea
• OTC medications prn
 Acid Suppression Therapy for
GERD

Proton Pump Inhibitors

H2-Receptor Antagonists

Omeprazole
Cimetidine
Lansoprazol
Ranitidine
Rabeprazole
Famotidine
Pantoprazole
Nizatidine Esomeprazole
 Effectiveness of Medical Therapies for
GERD

Treatment Response

Lifestyle modifications/antacids 20 %

H2-receptor antagonists 50 %

Single-dose PPI 80 %

Increased-dose PPI up to 100 %

 Peptic Ulcers
• Pathophysiology
– Erosions in the gastric mucosa
caused by gastric acid
– Terminology based on the
portion of tract affected
– Causes: Hyperacidity caused
by:
• NSAID use
• Alcohol/tobacco use
• H. pylori
 Causes of peptic ulcer

• Recent research has shown that there are

2 main causes of ulcer :
– Infection with H. pylori bacteria (H. pylori-
associated ulcers)
– NSAID drugs like ibuprofen, aspirin and others
(NSAID-associated ulcers).
• Others are:
– Hyperacidity
– Bile reflux
Risk factors associated for Duodenal or
Gastric Ulcers?
Endogenous Factors
• Genetic Predisposition
• Abnormalities in Secretion
of Acid & Pepsin
• Reflux of Bile & Pancreatic
Juice
• Abnormalities of Mucosal
Defense (blood flow,
bicarbonate secretion,
Prostaglandins)
• Emotional Stress
• Delayed Gastric Emptying
Exogenous Factors:
• Cigarette Smoking
• Non-steroidal Anti-
inflammatory Drugs
(NSAIDs)
• Systemic Corticosteroid
Therapy
• Alcohol or Caffeine -
Containing Beverages
Symptoms of peptic ulcers

• A gastric ulcer typically causes a sharp

pain in the stomach soon after eating,
whereas the pain of a duodenal ulcer is
typically relieved by eating, or by drinking
milk. Other symptoms may include:
– Belching
– General discomfort in the stomach
– Loss of appetite or, rarely, increased appetite
– Nausea
– Vomiting
– `Loss of weight
What are the complications of ulcers?

• Haematemesis (vomiting of blood)

• Melena (black faeces containing blood)
• Iron deficiency anaemia
• Perforation
• Peritonitis (inflammation of peritonium)
 Complications
Upper GI Bleeding
• Hemorrhage
– 15 %

• Perforation
– 6-7 %
 Peptic Ulcers

• Signs and Symptoms

– Belching, loss of appetite, discomfort
in the stomach, nausea, vomiting, loss
of weight.
• Complication
– Abdominal pain, hematemesis, melena
• Treatment
– Follow general treatment guidelines.
– Consider administration of histamine
blockers and antacids.
Gastroenteritis

• Gastroenteritis is the irritation and

inflammation of the digestive
tract.
• causes of Gastroenteritis:
– Food poisoning, stress, excessive
alcohol or tobacco use, viral
infections, food allergies, improper
diet, certain drugs, food consumed
in foreign countries and intestinal
parasites are all possible causes for
this condition
 Symptoms of Gastroenteritis

• The symptoms of
gastroenteritis can include:
– Abdominal cramps
– Nausea and vomiting
– Diarrhea
– Loss of appetite
– Weakness
– Fever or chills
– Dehydration
 Treatment for Gastroenteritis

• In cases of dehydration, fluid replacement is the primary

factor in treatment. If signs of dehydration (wrinkled skin, dry
mouth, excess thirst or absence of urination for over six
hours) appear, a doctor should be consulted as soon as
possible. A doctor should also be consulted if the any of the
following occur:
– Symptoms persisting for more than 48 hours
– Mucus or blood in stools
– Fever over 1010 F
– Severe abdominal or rectal pain
– Vomiting and diarrhea after being treated
• In severe cases where vomiting is prolonged, a doctor may
prescribe an anti-emetic suppository or give medication by
injection. Prolonged diarrhea is often treated with
medications that harden stools and reduce bowel activity. As
soon as bowels resume normal function, this medication is
stopped.
 Antacids
&
Acid-Controlling Agents

Antacids

H2 Antagonists

Proton Pump Inhibitors

 Antacids
OTC formulations available as:

– Capsules & tablets.

– Powders.

– Chewable tablets.

– Suspensions.

– Effervescent granules and tablets.

 Antacids
Magnesium salts:

• Forms: carbonate hydroxide, oxide, trisilicate.

• Commonly cause a laxative effect.
• Usually used with the other agents to counteract this
effect.
• Dangerous when used with renal failure-the Failing kidney
cannot excrete magnesium, resulting in accumulation.
• Example :magnesium hydroxide(MOM);combination
products such as Maalox,aluminium & magnesium.

Calcium salts:
• Forms: many but carbonate is the most common.
• May cause constipation.
• Their use may result in kidney stones.
• Long duration of acid action may cause increase of gastric
acid secretion (hyperacidity bound)
• Often advertised as an extra source of dietary calcium.
• Example: Calcium carbonate
 Antacids
Sodium Bicarbonate:

• Highly soluble.
• Quick onset, but short duration.
• May cause metabolic alkalosis.
• Sodium content may cause problems in patients
with hypertension or renal insufficiency.

Aluminum salts:

• Forms: carbonate, hydroxide, phosphate.

• Have constipating effects.
• Often used with magnesium to counteract
constipation.
Example: aluminum carbonate
 Antacids & Antiflatulents
• Antiflatulents:

-Used to relieve the painful symptoms

associated with gas.
-Several agents are used to bind or alter
intestinal gas and are often added to antacid
combination products.

• OTC Antiflatulents:
-Activated charcoal.
-Simethicone:
ｏ Alters elasticity of mucus-coated bubbles,
causing them to break.
ｏ Used often, but there are limited data to
support effectiveness.
 Antacids Side effects
Minimal and depend on the compound used:
• Aluminum and Calcium:
-Constipation

• Magnesium:
-Diarrhea

• Calcium carbonate:
-Produce gas and belching; often combined
with simethicone.
 Histamine
(H2) antagonists

• What are H2 receptors

antagonists?
• Blocks H2 receptors on parietal cells,
and antagonize normal stimulatory
effect of histamine on acid secretion
e.g. Ranitidine, Cimetidine, Famotidine.

• Inhibit acid secretion for 6 to 24 hrs

and are very useful for people who
need persistent acid suppression
 H2 Antagonists
Drug Effect:
• Suppressed acid secretion in the stomach.

Therapeutic uses:
• Shown to be effective for:
-Gastric ulcer.
-Upper GIT bleeding.
-Gastro esophageal reflux disease (GERD)
-Duodenal ulcer with or without H.Pylori.

• Can be also effective for:

-Stress ulcers
-Peptic esophagitis.
 H2 Antagonists
• Side Effects:
-Overall, less than 3% incidence of side effects.
-Cimetedine may induce impotence and gynecomastia.

• Drug Interactions:
- Cimetedine:
ｏ Binds with P-450 microsomal oxidase system in the
liver, resulting in inhibited oxidation of many drugs and
increased drug levels.

ｏ All H2 antagonists may inhibit the absorption of drugs

that require an acidic GI environment for absorption.
 H2 Antagonists

• Shortcoming of H2 receptor antagonists

– Not effective in meal-stimulated acid secretion
which is required for management of Erosive
oesophagitis & for relief of reflux symptoms.
– Rapid development of tolerance.
– Rebound acid hypersecretion after withdrawal
Proton Pump Inhibitors

• What are the Proton pump

inhibitors?
– Acts by blocking enzyme system i.e. H+,
K+ - ATPase, which is found at acid
secretory surface of parietal cells that
mediates final transport of H+ ions in
exchange of K+ into gastric lumen.
– These drugs inhibit H+, K+ - ATPase which
activate proton pump.
– More potent & long acting than H2 receptor
antagonists
– E.g are Omeprazole, lansoprazole and
pentoprazole
 Proton Pump Inhibitors

• Advantages of PPIs
– Remains the mainstay of treatment in suppression of
gastric acid secretion.
– Very effective for suppressing gastric acidity to all
known stimuli.
– Drug of choice in serious or refractory acid related
diseases (GERD)
– Once-daily dosing in the morning is more effective.
 Proton Pump Inhibitors
Therapeutic uses:
• GERD maintenance therapy.
• Erosive esophagitis
• Short-term treatment of active duodenal and
begin gastric ulcers.
• Zollinger-Ellison syndrome.
• Treatment of H.Pylori-induced ulcers.

Side Effects:
• Safe for short-term therapy.
• Incidence low and uncommon.
 Other Drugs
Sucralfate:
 Cytoprotective agent.
 Used for stress ulcers, erosions, PUD.
 Attracted to and binds to the base of ulcers
and erosions, forming a protective barrier
over these areas.
 Protects these areas from pepsin, which
normally breaks down proteins ( making
ulcers worse).
 Little absorption from the gut.
 May cause constipation, nausea and dry
especially tetracycline.
 Binds with phosphate.
 CAN NOT be administered with other
medications.
 Other Drugs

Misoprostol:
– Synthetic prostaglandin analogue.

– Prostaglandins have Cytoprotective activity:

-Protect gastric mucosa from injury by enhancing local
production of mucus or bicarbonate.
-Promote local cell regeneration.
-Help to maintain mucosal blood flow.

– Used for preventation of NSAID-induced gastric ulcers.

– Doses that are therapeutic enough to treat duodenal

ulcers often produce abdominal cramps and diarrhea.
 Prokinetic agents

• What are the Prokinetic agents?

– Prokinetic Agents: Rather than neutralizing acid,
prokinetic agents increase both gastric emptying and
lower esophageal sphincter pressure. These agents
are used when esophagus is not injured.
– E.g Cisapride and mosapride
– Cisapride acts by increasing acetylcholine
concentrations in the myenteric plexus. Because of
the cholinergic side effects associated with these
older prokinetic agents are no longer frequently
prescribed.
– The side effects of cisapride are generally limited to
abdominal cramping and diarrhea. Cisapride should
not be used in conjunction with antibiotics,
antifungals, protease inhibitors, antiallergics, angina,
arrhythmias, depression and psychosis
 Acid Peptic Disease
•Peptic ulcer
– Gastric ulcer
– Duodenal ulcer
– Stress ulcer (Stress erosions)
– Z E syndrome
– NSAID induced

•GERD

•Non ulcer dyspepsia

 Goals of therapy

•To relieve pain

•T enhance ulcer healing
•Prevent ulcer recurrence
•To prevent complications
– Bleeding, perforation
 Comparison of first and
second generation PPIs

First generation: Second generation:

OME, PANTO or LANSO RAB or ESO

• Slow onset of action • Fast onset of action

• Variable acid inhibition • Consistent acid inhibition
• Interactions • Few if any interactions
 Mechanism of action
 Proton Pump Inhibitors (Benzimidazole)
 Accumulates in the secretory canaliculus of the
parietal cell
 Protonated to the active form – Sulfenamide
 Binds irreversibly to a sulfhydryl group on the H+, K+ -
ATPase
 Prevents the secretion of acid into the gastric lumen.
Rabeprazole – Additional effects

• Fastest inhibitor of PP followed by

lansoprazole, omeprazole & then
pantoprazole

• Highest Pka of 5 of rabeprazole ( 4.01 for

OMP, 4.13 for LNP, 3.96 for PNP) allows for
greater accumulation of the drug in the
parietal canaliculi, causing rapid onset of
action & greater acid suppression.
Rabeprazole over Pantoprazole

Rabeprazole is the fastest acting &

pantoprazole is the slowest acting of all PPIs

• Highest Pka of 5.0 for rabeprazole vs Pka of

3.96 for pantoprazole
• Binds to all 4 cysteine residues of alpha sub
unit of proton pump while pantoprazole
binds to only 1 cysteine residue.
• Sulfenamide binds covalently to alpha sub
unit of proton pump leading to inhibition of
pump beyond the half life of 1-2 hrs
Activation Time (min)
PH Pantoprazol Rabeprazol
e e

1.2 4.6 min 1.3 min

5.1 282 min 7.2 min

Pharmacology 1998; 56:57-70

Rabeprazole over Pantoprazole

• Increases intracellular mucin content and

new mucin synthesis in gastric mucosa.

• Omeprazole decreased mucin content and

new mucin synthesis whereas lansoprazole
has no effect.
• Rabeprazole does not suppress collagen
regeneration or delay healing of gastric
lesions.
• Rabee offers faster onset of action.
 Rabeprazole over Pantoprazole

US FDA approved indications:

PANTOPRAZOLE RABEPRAZOLE

• GERD • Duodenal ulcer

• ZE syndrome • GERD
• Erosive esophagitis
(Treatment &
maintenance)
• H.pylori triple drug
therapy
• Hypersecretory
conditions
 Pharmacokinetics

•Bioavailability - 52% (oral)

•T ½ - 1.02 hrs
•PPB – 94.8 to 97.5 %
•Excretion - Kidney
 Adverse Effects

•Well-tolerated in both short-term and long-term

trials.
•Adverse events – mild to moderate
•Malaise, Headache, Dizziness
•Diarrhea
Dosage & A

Indication
 Drug interaction

An interaction with compounds (reduction in

absorption) which are dependent on gastric pH for
absorption may occur due to the magnitude of acid
suppression observed with rabeprazole

•Ketoconazole
•Digoxin
•Diazepam
 Summary

• Second generation PPI

• Fastest action
• Greater antisecretory activity than Omeprazole
•Lesser drug interactions
• More effective than H2 blocker
 GASTRO-ESOPHAGEAL REFLUX
DISEASE
Etiology
 PRECIPITATING FACTORS

• Smoking

• Drugs like NSAIDs

• Hot and spicy food

• Overweight
 CLINICAL FEATURES OF GERD

• Heartburn Delayed gastric emptying

• Nausea

• Vomiting

• Abdominal pain

• Anorexia

• Dysphagia

Acidic reflux Dysmotility

 DYSPEPSIA

• Dyspepsia refers to episodic or recurrent

abdominal pain or discomfort thought to arise
in the proximal gastrointestinal tract
• Two types : Non Ulcer Dyspepsia
Ulcer like Dyspepsia
 MANAGEMENT OF UPPER GI DISORDERS

Non Pharmacological Therapy :

Change in life style
Avoid
– Alcohol
– Smoking
– Offending drugs like NSAIDs
– Hot & spicy food
– Stress
– Irregular eating habits
 MANAGEMENT OF UPPER GI DISORDERS

Drug Therapy :
– Acid neutralizing agents like Antacids

– H2 receptor blockers like Ranitidine,Famotidine

– Proton pump inhibitors like Esomeprazole,

Omeprazole,Lansoprazole,Rabeprazole,
Pantoprazole

– Prokinetic agents like Domperidone,

Metoclopramide
LIMITATIONS OF CURRENT THERAPY

• Monotherapy
- Inadequate response
- Less patient compliance
- Diminished quality of life
 THERAPEUTIC NEEDS

• Upper GIT disorders-Multifactorial aetiology

A Need To Target The Vicious Triad

 Acidic reflux
 Dysmotility
 Delayed gastric emptying
Combination of PPI with Prokinetic agent

Fulfils……

all the……

therapeutic needs
 RATIONALE FOR RABEE-D

1. Rational synergistic combination

Rabeprazole + Domperidone

1.Inhibits acid secretion

2.Faster activation than Prokinetic with antiemetic
other PPI's in highly effect
acidic environment (acidic pH)

TOTAL SYMPTOMATIC RELIEF

 RATIONALE OF RABEE-D

1.Hyperacidity and Hypomotility are common GIT

problems and frequently co-exist.
2.Excess hydrochloric acid and defective
clearance of the acid and other gastric content
from the stomach together or individually give
rise to nausea ,vomiting and upper abdomen
discomfort due to irritation of gastric mucosa.
 RATIONALE OF RABEE-D

3. Only acid suppression or only Prokinetic

therapy by itself would not serve the purpose.
4.Rabeprazole is a drug of choice for acid
suppression and Domperidone is a drug of
choice for stimulation of gastric motility.
 RATIONALE OF RABEE-D

5. Both the drugs are devoid of any major side

effects. Domperidone does not cross Blood
Brain Barrier (BBB), so no extra pyramidal
syndrome.
6. Both the drugs are in pellet form. Different
colour pellets are packed in same capsule, so
the compliance of the patient will be excellent.
 RATIONALE OF RABEE-D

7. Domperidone has short half-life, which makes it

necessary to take it three times a day. Therefore
it has been formulated as sustained release
pellets. The advantages of domperidone
sustained release pellets include round the clock
symptom control and better patient compliance
with fewer side effects.
 RATIONALE OF RABEE-D

8. Rabeprazole 20mg is formulated as enteric-

coated pellets. It reduces fluctuations in drug
plasma concentrations, improves effectiveness
and releases the drug only in the alkaline pH.
9. Combination of Rabeprazole and Domperidone
gives a complete symptomatic relief from
Dyspepsia, heartburn, and Acid-Pepsin disorder
associated with nausea, vomiting and epigastric
pain.
TRICAINE MPS

INTRODUCTION

 Composition
 Indications
 TRICAINE MPS
COMPOSITION

Each 5ml of the gel contains :

Aluminium hydroxide I.P. 300mg

Magnesium hydroxide 150mg
Simethicone I.P. 125mg
Oxethazaine B.P. 10mg
 TRICAINE MPS

INDICATIONS

GI symptoms associated with acid

peptic disorders :
• gastritis
• peptic ulcer
• heartburn
 TRICAINE MPS

PATHOPHYSIOLOGY (contd.)

• Integrity of walls maintained since balance exists

between :
Defensive factors - Mucosal Barrier
(Protective) Mucus
Blood Flow
Bicarbonates
Prostaglandins
Cell Restitution

Chopra S, Pathophysiology of Gi diseases, 1989, 1st Ed., 97-123.

 TRICAINE MPS
PATHOPHYSIOLOGY (contd.)

Imbalance between Defensive & Aggressive factors

Inflammation (Gastritis, duodenitis)

Erosion (superficial lesion extending to mucosa)

Peptic ulcer (Hole penetrating into submucosa or deeper)

Chopra S, Pathophysiology of Gi diseases, 1989, 1st Ed., 71-96

 TRICAINE MPS
CLINICAL FEATURES

Epigastric Pain
Heartburn
Discomfort
Flatulence

COMPLICATIONS
Obstruction, Hemorrhage, Perforation
 TRICAINE MPS
MANAGEMENT
• Objectives of treatment
° Relief from pain
° Ulcer healing accelerated
° Prevention of complications
• Strategies
– Reduce gastric acid secretion (H2 antagonists,
Anticholinergics, Proton pump inhibitors)
– Neutralise the acid (Antacids)
– Cytoprotection (Sucralfate, Prostaglandins,
Bismuth, Carbenoxolone)

Chopra S, Pathophysiology of Gi diseases, 1989,

1st Ed., 71-96
 TRICAINE MPS
MECHANISM OF ACTION
Magnesium hydroxide
Most potent non-systemic antacid
Reacts rapidly with HCl to form poorly absorbed salt

Aluminium hydroxide
Reacts with HCl slowly but action is sustained

Combination Advantage
Laxative and constipating effects balanced
Rapid & sustained action

Munson PL, Principles of Pharmacology, 1995; 1072-73.

Greenberger NJ, Drug Treatment of Gastrointestinal Disroders, 1978;11
 TRICAINE MPS

MECHANISM OF ACTION (contd.)

Simethicone

• Changes surface tension of gas bubbles

• Coalesces them
• Easy passage of flatus

Munson PL, Principles of Pharmacology, 1995; 1072-73.

Greenberger NJ, Drug Treatment of Gastrointestinal Disroders, 1978;11
 TRICAINE MPS

MECHANISM OF ACTION (contd.)

Oxethazine
• Produces surface anaesthesia of mucous
membrane - relieves pain
• Inhibits stimulation of sensory nerve endings by
food - decreases acid secretion.
• No effect on GI motility.

Farrar GE, Pennsylvania Med J, Nov 1962; 1369-72.

Glassman JM, Toxicology & Applied Pharmacology, 1963; 5: 184-200.
 TRICAINE MPS

Dosage:
5 - 10 ml 3-4 times daily after meals
and at bed time
 TRICAINE MPS

SUMMARY

5-GOOD REASONS FOR

PRESCRIBING
TRICAINE MPS
 USPS OF TRICAINE – MPS

• Doctor combination of Al (OH)3 & Mg (OH)2 offers

Sustained Acid neutralization & because of 2:1 ration patient
will not have G.I. complication.

• Doctor Tricaine offers complete therapeutic dose of

simethicone hence oofers prompt relief from flatulence.

• Oxethazaine in Tricaine MPS offers quick symptom relief &

prevents rebound acidity.

• American mint flavor: Better patient compliance

• Tricaine MPS is complete homogeneous mixture hence will

have therapeutic concentration of each ingredient in every
dose.
MANAGEMENT OF
DIARHOEA

WITH

Peditral
 Diarrhea

Definition
Diarrhea--loose,watery stools occurring more than
three times in one day.

Diarrhea causes dehydration causing an electrolyte

imbalance.
 DEFINITION

• Watery Diarrhea: 3 or more

liquid or watery stools in 24 h
• Dysentery: Presence of
blood and/or mucus in stools
• Persistent Diarrhea: Diarrhea
lasting for 14 days or more
TYPES OF DIARRHEA

D i a r r h e a

W a t e r y Dd i y a s r e r hn P et e ea r r y s i s t e

R o
t a v i r S u hs i d g i e Ca l r l a ro uh s se i es a s a
E . c o l i d A i am r re h b e i a s i s
C h o l e r a
 Causes of diarrhea

• Bacterial infection (shigella)

• Viral infection (rotavirus)
• Parasites (entamoeba hystolica)
• Food intolerance (lactulose)
• Reaction to medicines
(antibiotics like amoxycillin)
• Intestinal disease (IBD)
 INCIDENCE / PREVALANCE

• Viral diarrhea is most common in young children.

– Rotavirus and adenovirus - prevalent in
children younger than 2 years.

• Very young children - susceptible to secondary

dehydration and secondary nutrient
malabsorption.
 PERSON AT RISK

Cholera: 2 years and above, uncommon in very young

infants

Shigellosis: more common in young children aged

below 5 years

Rotavirus diarrhea: more common in young infants

and children aged 1-2 years

E. coli diarrhea: can occur at any age

Amebiasis: more common among adults

 TRANSMISSION

Most of the diarrheal agents are transmitted by the

fecal-oral route.

Some viruses (such as rotavirus) can be

transmitted through air.

Nosocomial transmission is possible.

Shigella (the bacteria causing dysentery) is mainly

transmitted person-to-person
 Symptoms

• Cramping

• Abdominal pain

• Bloating

• Nausea
 Dehydration

General signs of dehydration include

• Thirst
• Less frequent urination
• Dry skin
• Fatigue
• Light-headedness
• Dark colored urine
 REHYDRATION

DEHYDRATION
 Dehydration

Signs of dehydration in children:

• Dry mouth and tongue

• No tears when crying
• No wet diapers for 3 hours or more
• Sunken abdomen, eyes, or cheeks
• High fever
• Restlessness or irritability
• Skin that does not flatten when pinched
 ASSESSMENT OF DEHYDRATION

Dehydration
Mild Moderate Severe
Appearanceirritable, irritable, lethargy,
thirsty very coma, or
thirsty unconscious
Anterior normal depressed markedly
Fontanelle depressed
Eyes normal sunken sunken
 ASSESSMENT OF DEHYDRATION

Dehydration
Mild Moderate Severe
Tongue normal dry very dry,
furred
Skin normal slow very slow
retraction retraction
Breathing normal rapid very rapid
 ASSESSMENT OF DEHYDRATION

Dehydration
Mild Moderate Severe
Pulse normal rapid and feeble or
low imperceptible
volume
Urine normal dark scanty
Weight < 5% 6 - 9% 10% or more
loss
 TREATMENT

• Rehydration– replace the

loss of fluid and electrolytes
• Treat the Cause – according
to the type of pathogens
COMPLICATIONS:
DIARRHEA
• Dehydration
• Electrolyte imbalances
• Tetany
• Convulsions
• Hypoglycemia
• Renal failure
LOW OSMOLARITY ORS

The Advantages

Peditral
Electrolyte Imbalance
Fluid and Electrolyte imbalance in diarrhea

Increased Sodium & bicarbonate excretion

to a decrease in the pH of blood.

Acidosis

Potassium loss
 Electrolyte Imbalance

Goal
Oral replacement of fluid and electrolyte losses and
subsequent maintenance of electrolyte equilibrium in
mild or moderate dehydration associated with
diarrhoea and acute gastrointestinal disorders in
infants, children and adults
 Oral Rehydrating Solution

Ideal Requirements
Na+ :Compensate Na+ depletion
Bicarbonate, Citrate :Correct acidosis
K+ :Compensate K+ depletion
Glucose :Carrier that transports
Water and salts to circulation
 BACKGROUND

• Under 5 Diarrhea- 1.5 Billion Episodes & 1.5 to 2.5

Million deaths(5M. 20 yrs. back). JAMA. 2004;291:2628-2631.

• Widespread use of standard ORS in past 3 decades is

with promising results. JAMA. 2004;291:2628-2631.

• Most diarrhea deaths are caused by dehydration, which

can be treated by replacing fluid loss with ORS in over
90% of cases. BMJ 2001;323:59-60
Randomized controlled trial…

A no. of RCTs have been conducted comparing the

standard (1975 WHO) and reduced-osmolarity (2002

WHO) solutions. In a trial of 300 adult patients with

cholera, those who received low osm. ORS had no

differences in stool output, duration of diarrhea, or

need for unscheduled intravenous therapy compared

with those treated with the standard WHO ORS.

…….. WHO and UNICEF joint meet 2001

WHO/UNICEF recommended oral rehydration salts
solution for the treatment of all causes of diarrhoea in
all age groups.
OLD –ORS New ORS

Ingredients mmol/L mmol/L

Sodium 90 75
Potassium 20 20
Chloride 80 65
Citrate 10 10
Glucose 111 75
Osmolarity 311 mosmol/L 245 mmol/L

Recommended in 1976 Recommended in July, 2001

 Composition of
Standard ORS Vs Peditral

ORS Standard Peditral

ORS Reduced
Osmolarity

Contents mEq/L mEq/L

Glucose 111 75
Sodium 90 75
Chloride 80 65
Potassium 20 20

Citrate 10 10
311 245
 Role Of
Sodium chloride & Sodium citrate

Sodium chloride
Compensates for sodium depletion
Maintains electrolytes in Isotonic medium

Sodium citrate
Citrate increases the shelf life of the product
Citrate enhances sodium absorption
Citrate also helps to correct acidosis.
 Role of
Potassium Chloride & Glucose

Potassium chloride
Compensates for potassium depletion

Glucose
The most critical component as
Enhances sodium absorption
(glucose linked sodium - co transport)
Adds osmolarity
Drawbacks of Std. ORS

Standard ORS

 Does not reduce stool output and duration of

diarrhea

 Sodium level is high in comparison with stool

loss in children, especially with rotavirus
diarrhea .

 Potential risk of hypernatremia

Advantages Of Peditral

 The beneficial effect of hypo-osmolar ORS

may be a result of low osmolarity of the
solution and complete absorption of glucose,
thus reducing the risk of osmotic diarrhea.
 Decreases the mean duration of diarrhea,
stool output, and need for ORS
 Decreases need for IV infusions
 Enhances effect of Antidiarrheal like
Racecadrotil.
 Uses:
Hypo-osmolar ORS (sodium content 75
mmol/L) should be used for rapid rehydration,
and maintenance of hydration in children with
Acute diarrhea.
 Indications

For electrolyte imbalance and

fluid loss following….

Diarrhoea
Vomiting
Excessive Sweating
In burns
 Dose and Mode of use

Childrens & infants: A dose of 75ml per Kg body

weight to be given over a period of 6 hours.
Alternatively, 50ml to 200ml after each loose stool,
based on the severity of dehydration.

Adults: 2 to 3 litres ( 10 to 15 sachets of Peditral)

daily.
If the conditions warrants, upto 800ml (4 sachets of
Peditral) per hour may be given till rehydration.
 Dose and Mode of use

Correction (Rehydration)
•Mild 50-75ml/kg in 4-6h (child)
•Moderate Upto 1L per hour (adult)

Maintenance

•Mild to moderate 100-200ml/kg per day

•Continuing diarrhoea 15ml/kg/hour till diarrhoea stops

Use best available drinking water.

Inflammation
 Introduction:

• “Inflame” – to set fire.

• Inflammation is “dynamic response of
vascularised tissue to injury.”
• Is a protective response.
• Serves to bring defense & healing mechanisms
to the site of injury.
 INFLAMMATION

Local response that

reflects the body’s attempt to get rid
of injured cells or infectious material.
 PAIN

An unpleasant sensory & emotional

experience associated with actual or
potential damage
CAUSES OF INFLAMMATION

Physical
Trauma e.g. knife wound or impact
Electromagnetic (heat, UV light)

Chemical
Simple – e.g. acids
Enzymatic – e.g. Microbial or endotoxin
Ischaemic necrosis

Immunological
Activated phagocytes
Mast cell / basophil triggering
 TYPES OF INFLAMMATION

Acute inflammation
It is usually of sudden onset and
accompanied by one or more cardinal
signs
e.g. burns, trauma or infections

Chronic Inflammation
Results from an injurious agent which
persists in the tissue and cause damag
e.g. Rheumatoid arthritis
 Cardinal Signs of Inflammation

Calor Rubor Tumor Dolor Loss of Function

Surgical wound inflammation

Red, Warm & Swollen (Flare, Flush & Weal )

Calor, Rubor, Dolor, Tumor, Loss of function.
 The nomenclature used to describe
inflammation in different tissues employs the
tissue name and the suffix “-itis”
e.g
pancreatitis
meningitis
pericarditis
arthritis
Flowchart of Events in Inflammation

Figure 21.2
 Lox pathway

Arachidonic acid

5-LOX
12-Lox 15Lox

5S-HETE
12s-HETE
15s-HETE

LTA4 (Stimulates
neutrophils)

Hepoxylins Lipoxin-A
(Neutrophil Promotes inflamm.
LTC4,LTD4,LTE4
Resolution, Inhibits neutrophil
Causes Chemoattractents & Release &
vasoconstriction Increases vascular promotes wound healing
permeability
 COX Pathway

Arachidonic acid

Cox-1 Cox-2

Thromboxane
(causes vasoconstriction Prostacyclin(PGI2)
& have thrombotic Which causes vasodilatation
property & inhibits platelets aggregation

Prostaglandin which
Offers GI cytoprotection
& help platelet aggregation
& PGE2 causes release of
DC & T-cell polarization
Prostaglandin which
Causes inflammation ,pain
& fever( PGD2,PGF2)
Functions of prostaglandins
1. Activation of the inflammatory response, production of
pain,and fever.

2. Blood clots form when a blood vessel is damaged.

Thromboxanes stimulate constriction and clotting of platelets.
Conversely, PGI2 is produced to have the opposite effect
on the walls of blood vessels where clots should not be
forming.

4. Prostaglandins are involved in several other organs

-increase blood flow in kidneys
-increase secretion of protective mucus in GI tract
-inhibit acid synthesis in GI tract
-leukotrienes, related molecules, promote
constriction of
bronchi associated with asthma
Action Metabolite

Vasoconstriction Thromboxane A2,

Leukotrien C4, D4, E4

Vasodilation PGI2, PGE1, PGE2,

PGD2

Bronchospasm Leukotrien C4, D4, E4

Platelet aggregation Thromboxane A2

Pain mediation, Fever induction PGE2

 Cyclooxygenase (COX) Enzymes

COX-1 COX-2
• Always active
• Activated by injury
• Maintains normal function of
stomach, intestines, kidneys, • Expressed at site of injury
and platelets (blood clotting) • Mediates pain, inflammation, and
• Thromboxane (causes fever
vasoconstriction & have • Prostacyclin(PGI2) Which causes
thrombotic property. vasodilatation & inhibits platelets
aggregation.
• Prostaglandin which Offers GI
• Prostaglandin which Causes
cytoprotection & help platelet
aggregation & PGE2 causes release ofinflammation ,pain &
DC & T-cell polarization fever( PGD2,PGF2).
 The Onset of Inflammation (Auto immune)

• there are always some phagocytic cells in the

tissue at all times

• upon tissue injury or infection, these cells

become active

• continue digesting foreign Ag and necrotic cells;

secrete CYTOKINES
 TISSUE INJURY

IL-6
Increased antibody productio
IL-1
Activates
lymphocytes

IL-8
Recruits neutrophil & Basophil
To the site of infection
TNF-α
Increases vascular
Permeability & increases
Fluid drainage to lymph nodes

IL-12
Activates NK cell & also
Establish differentiation
In between antigen & antibody
 Systemic Effects of Cytokines

IL-1/IL-6/ TNF-α

Liver-
Activation of
opsonization
Dendritic cell-
Hypothalamus-
TNF-α
Increased
Promotes migration
Body temp.
to lymph node

Bone marrow-
Activation of
Fat & muscle-
Neutrophil-
Protein & energy
phagocytosis
mobilization
To allow increase in temp.
 Classes of NSAIDS

– Salicylic acid derivatives

• Aspirin, sodium salicylate, choline magnesium trisalicylate,
salsalate, diflunisal
– Para-aminophenol derivatives
• Acetaminophen
– Indole and indene acetic acids
• Indomethacin, sulindac
– Heteroaryl acetic acids
• Tolmetin, diclofenac, ketorolac
– Propionic acids
• Naproxen, ibuprofen, flurbiprofen, ketoprofen, fenoprofen,
oxaprozin

Source: Goodman and Gilman’s The Pharmacological Basis of Therapeutics, 10th edition
Classes of NSAIDS

– Anthranilic acids (fenamates)

• Mefenamic acid, meclofenamic acid
– Enolic acids
• Oxicams (piroxicam, meloxicam)
– Alkanones
• Nabumetone
– Coxibs
• Celecoxib, valdecoxib, rofecoxib (withdrawn)
 Relatively COX-1 selective
Highly COX-1 selective
Fenoprofen
Flurbiprofen
Piroxicam
Ketoprofen
Sulindac

Highly COX-2
selective: Relatively COX-2
Celecoxib : selective
Rofecoxib Diclofenac
L-743, 337 Etodolac
NS-398 Meloxicam
SC 58125 Nimesulide
6-MNA
Equally Selective
Aspirin
Ibuprofen
indomethacin
Ketorolac
Naprosen
Oxaprosin
Tenoxicam
Tolmetin
 Drug Trade COX-2 : COX-1 Selectivity
Name Name ratio

valdecoxib Bextra 28000 : 1 COX-2

etoricoxib Arcoxia 106 : 1

rofecoxib Vioxx 35 : 1

etodolac Lodine 23 : 1

meloxicam Mobic 11 : 1

celecoxib Celebrex 9:1

diclofenac Voltarol 4:1 Mixed

ibuprofen Nurofen 0.38 : 1 COX-1

naproxen Naprosyn 0.33 : 1

indomethaci Indocid 0.23 : 1

n
What could it be?
It’s like Diabetes

What would happen if you

developed diabetes?

It doesn’t go away
A Chronic Illness
Arthritis is like an Iceberg
It’s what you don’t see!
 Work

Cooking

Dressing
Bathing Pleasure
Cleaning
Grooming

Shopping
 What Joints are Involved Now?

• Number of Joints
– Monoarthritis (1)
– Oligoarthritis (2-4)
– Polyarthritis (>4)
• Distribution of Involvement
– Degenerative Pattern
– Inflammatory Pattern
 What are the Symptoms?

Inflammatory Degenerative Chronic Pain

Joint Pain Yes Yes No

Joint Swelling Yes Yes No

Joint Redness Yes No No

Morning > 1 hour 15-20 minutes > 1 hour

Stiffness
Fatigue New and Mild Severe
Severe
Loss of Rapid Slow Rapid
Function
Fever Possibly Never Never

Weight Loss Possibly Unusual Unusual

 Skeletal System

• Function:
– Protection
– Hematopoiesis
– Mineral homeostasis
• Calcium
• Phosphorus
• Carbonate
• Magnesium

207
 Skeletal System

• What is a joint?
– A joint can be defined simply as the union of two or
more bones. In other words, it is the site at which two
or more bones come together.
• What are the main components of a
synovial joint?
– The main components of a synovial joint include:
• Bones
• Joint capsule: Covers the joint from outside
• Synovial membrane: Lining of the capsule
• Synovial fluid: Fluid present in the synovial cavity
• Articular cartilage: Covering the ends of the two bones
inside the bones.
209
 Skeletal System
• What is Synovium and Synovial
fluid?
– The synovial membrane or synovium is a
thin, delicate membrane that lines the inner
surface of the fibrous capsule and also
covers the areas of the joint.
– The synovial fluid provides lubrication for
smooth and painless movements and also
serves to absorb strong shocks to the joint
structures during physical activities such as
walking and running.
– Lastly, it provides nutrition and oxygen to
the articular cartilage, as the cartilage does
not have a blood supply of its own.
 Skeletal System

• What is an articular cartilage?

– The articular cartilage is a smooth and
slippery connective tissue that covers the
ends of the bones.
– It is formed by cells called chondrocytes.
Chondrocytes also replicate (divide) poorly,
therefore once damaged, they are very
rarely replaced.
 Skeletal System
• What are muscles?
– Muscle is another type of tissue. Muscles are bundles of fibers that can
contract.
– Skeletal muscles, which are responsible for posture and movement, are
attached to bones, so are called skeletal muscles.
• What are the different types of muscles?
– There are 3 kinds of muscle tissues:
– Skeletal muscles: Skeletal muscles are of the voluntary type.
– Smooth muscles: Smooth muscles are muscles found in the internal
organs like the lungs, digestive system and urinary system. They are
involuntary and are controlled by the autonomic nervous system.
– Cardiac muscles: Cardiac or myocardial muscles are found only in
heart.

• What is a tendon?
– Tendon is a part of the skeletal muscle that joins the bone. It is
composed mainly of very strong fibrous tissue.
• What is a ligament?
– A joint capable of a wide range of movements needs more supporting
tissues in order to remain stable. Assisting the capsule are several
strong, fibrous tissues that bind the two bones of the joint, called joint
ligaments.
Arthritis

 More than 100 different types of inflammatory or degenerative

diseases that damage the joints.

 Symptoms – pain, stiffness, and swelling of a joint.

 Acute forms are caused by bacteria and are treated with

antibiotics.

 Chronic forms include osteoarthritis, rheumatoid arthritis,

and gouty arthritis.
 Rheumatoid Arthritis (RA)

• Autoimmune disease, causing chronic systemic

inflammatory disease
• Affects children and adults
• Remissions and exacerbations lead to progressive
damage to the joints
• 1st affects smaller jts, then larger jts
• Varies form mild to severe, depending on the # of
jts affected, degree of inflammation, and rapidity of
progression
 RA—Pathophysiology

• 1st step is abnormal immune response

– Causes inflammation of synovial membrane
• Vasodilation, increased permeability,
formation of exudate
– Causes red, swollen, painful jt
– Synovitis
» Results from immune abnormality
• After 1st period of acute inflammation, it may
appear to recover fully
• During subsequent exacerbations process
continues
RA—Pathophysiology

• Synovitis: inflammation recurs, synovial cells proliferate

• Pannus formation: granulation tissue from synovium
spreads over articular capsule
– Pannus releases enzymes and inflammatory
mediators which destroy the cartilage
• Fibrosis
– Pannus between bone ends becomes fibrotic, limits
movement
• Cartilage erosion
– By enzymes from pannus; pannus also cuts off
nutrients
• Ankylosis
– Jt fixation and deformity
Disability in Early RA

• Inflammation
– Swollen
– Stiff
– Warm
• Fatigue
 Disability in Late RA

• Damage
– Bones
– Cartilage
– Ligaments and other
structures
• Fatigue
• Not Reversible
 osteoarthritis

• Breakdown of
Cartilage
• e.g. osteoarthritis
 Osteoarthritis

Normal Joint
Joint with
Osteoarthritis
 Osteoarthritis
• "Osteoarthritis" is derived from the Greek word "osteo",
meaning "of the bone", "arthro", meaning "joint", and "itis",
meaning inflammation,.

• Signs and symptoms :

Acute pain, loss of ability and often stiffness.
"Pain" is generally described as a sharp ache, burning
sensation in the associated muscles and tendons.
OA can cause a crackling noise (called "crepitus") when
the affected joint is moved or touched, and patients may
experience muscle spasm and contractions in the tendons.
What Causes Osteoarthritis?

The cause of osteoarthritis is unknown. Factors

that might cause it include:

Being overweight
Getting older
Joint injury
Joints that are not properly formed
A genetic defect in joint Cartilage
Stresses on the joints from certain jobs and playing
sports.
How is OA diagnosed?

The best way to diagnose osteoarthritis is through x-rays of the affected

joint which reveal evidence of cartilage damage.

Warning signs of osteoarthritis are:

Stiffness in a joint after getting out of bed or sitting for a long

time

Swelling or tenderness in one or more joints

A crunching feeling or the sound of bone rubbing on bone.

How Is Osteoarthritis Treated?
Doctors often combine treatments to fit a patient's needs,
lifestyle, and health. Osteoarthritis treatment has four main
goals:
Improve joint function
Keep a healthy body weight
Control pain
Achieve a healthy lifestyle.
Osteoarthritis treatment plans can involve:
Exercise
Weight control
Rest and joint care
Nondrug pain relief techniques to control pain
Medicines
Complementary and alternative therapies
Surgery
 Gouty Arthritis

• A metabolic disease
resulting from an
accumulation of uric
acid in the blood. Far
more prevalent in men.
• It takes approx.15 to 20
years for sufficient
urates to accumulate
causing S/S.
Characterized by “Tophi”
• Stones containing
sodium urate
deposits in large
quantities.
Typically, the big
toes are involved.

• Excruciating pain
and swelling no
matter which joint
is affected.
ANKYLOSING SPONDYLITIS

• What is Ankylosing Spondylitis?

– Ankylosing spondylitis is a form of chronic
inflammation of the spine and the sacroiliac joints.
The sacroiliac joints are located in the low back
where the sacrum (the bone directly above the
tailbone) meets the iliac bones (bones on either side
of the upper buttocks). Chronic inflammation in these
areas causes pain and stiffness in and around the
spine.

– Ankylosing spondylitis is 2-3 times more common in

males than in females. Ankylosing spondylitis affects
all age groups, including children. The most common
age of onset of symptoms is in the second and third
decades of life.
ANKYLOSING SPONDYLITIS

• What causes Ankylosing

Spondylitis?
– The initial inflammation may be a result of
an activation of body’s immune system by a
bacterial infection. Once activated, the
body’s immune system becomes unable to
turn itself off, even though the initial
bacterial infection may have long subsided.
ANKYLOSING SPONDYLITIS

• What are the symptoms of Ankylosing

Spondylitis?
– The symptoms of ankylosing spondylitis are related
to inflammation of the spine, joints, and other organs.

– Inflammation of the spine causes pain and stiffness

in the low back, upper buttock area, neck, and the
remainder of the spine.
Naprosyn

RPG Medical
 Naproxen

• Naproxen, a nonsteroidal anti-inflammatory

drug (NSAID), belongs to the chemical class
propionic acid derivatives
• Naproxen has anti-inflammatory, analgesic and
antipyretic properties
• Naproxen known to inhibit platelet aggregation
• The major differences between members of the
NSAID class are potency and pharmacokinetics
Naprosyn has the active S isomer

Advantage of giving only active form

• Only pure active drug is administered
• Pt is not exposed to X mg of chemical which
does not have any effect but might have
potential undesirable side effects’
• Pts kidney is not burdened with cleaning of
additional potentially inactive drug from the
plasma since only active form is used.
Indication - Chronic
Conditions
1. Rheumatoid Arthritis(RA)
2. Osteoarthritis
3. Ankylosing Spondylitis
4. Juvenile Rheumatoid arthritis
5. Chronic pain states with inflammatory component.
Who prescribes Naprosyn
Which Indication

Naprosyn is prescribed by
Neurologist Migraine and Headache
Orthopaedicians Rheumatoid Arthritis, Osteoarthritis
Ankylosing Spondilytis, Acute
Gout
Gynecologist Pain associated with Low backache,
Menstrual Migraine,
Dysmenorrhoea
What is the Dose of Naprosyn
in these indication

Migraine
In Acute Attacks: 750mg at onset and add 250-
500mg half an hour later
As Prophylaxis: 500mg twice Daily

Rheumatoid Arthritis, Osteoarthritis

Ankylosing Spondilytis: 250 -500mg given twice
daily then dosage adjusted according to the
clinical response
What is the Dose of
Naprosyn
in these indication

Acute Gout : Initial Dose of 750mg then 250mg

every 8 hours until the subsidence of attack

Pain associated with Primary Dysmenorrhoea

Menstrual Migraine: 250-500mg given twice daily
for 1 to 3 days as per the clinical response

Low backache: 250-500 mg daily

Contraindication

In patients who have had allergic reactions to

Naproxen.

In patients in whom aspirin or other nonsteroidal anti-

inflammatory/analgesic drugs induce the syndrome of
asthma, Rhinitis, and nasal polyps.

If such symptoms occur during therapy, treatment

should be discontinued.
Warnings

Risk of GI Ulceration, Bleeding and Perforation

With NSAID Therapy

Serious gastrointestinal toxicity such as bleeding,

ulceration, and perforation, can occur at any time,
with or without warning symptoms, in patients treated
chronically with NSAID therapy
Recently Cardiac S/E & Stroke to be kept in mind
Warnings

In patients observed in clinical trials of several

months to 2 years duration, symptomatic upper GI
ulcers, gross bleeding or perforation appear to occur
in approximately 1% of patients treated for 3-6
months, and in about 2-4% of patients treated for 1
year. Physicians should inform patients about the
signs and/or symptoms of serious GI toxicity and
what steps to take if they occur.
 Anti platelet effect
• Within seconds of injury, platelets adhere to
collagen fibrils through glycoprotein (GP)
Ia/IIa receptors .

• An adhesive glycoprotein, von Willebrand

factor (vWF) allows platelets to stay attached
to the sub endothelial vessel wall (via GP Ib)
despite high shear forces.

• Following adhesion, platelets are activated to

Secrete a variety of agonists including
thrombin, serotonin, adenosine diphosphate
(ADP), and thromboxane A2 (TXA2).
• These agonists, which further augment the platelet
activation process, bind to specific receptor sites
on the platelets to activate the GP IIb/IIIa receptor
complex, the final common pathway to platelet
aggregation. Once activated, the GP IIb/IIIa
receptor undergoes a conformational change that
enables it to bind with fibrinogen.
 Bioavailability Half- Peak Protein Renal
(%) life (hours) binding elimination
(hour (%) (%)
s)
Diclofenac 50 to 60 2 2 > 99 65

Indomethacin 98 4.5 2 90 60

Celecoxib NS 11 3 97 27

Mefenamic NSa 2 2 to 4 > 90 52

acid

Piroxicam NSa 50 3 to 5 98.5 NSa

Ibuprofen > 80 1.8 to 21 to 2 99 45 to 79

Naproxen 95 12 to 2 to 4 > 99 95
17
Naproxen vs Diclofenac & Ibuprofen

• Selective COX 2 inhibitors are associated with

a moderate increase in the risk of vascular
events, as are high dose regimens of ibuprofen
and diclofenac, but high dose naproxen is not
associated with such an excess.
27 December 2006 bmj.com
 Naprosyn has lowest risk of AMI

• The risk of myocardial infarction varies with

individual NSAIDs. An increased risk was
observed for diclofenac and rofecoxib, the
latter one with a clear dose-response trend.
There was a suggestion of a small increased
risk with ibuprofen. Also, data suggest a small
reduced risk for naproxen present only in non-
users of aspirin, mainly people free of clinically
apparent vascular disease.
Basic Clin Pharmacol Toxicol. 2006 Mar;98(3):266-74.
 Naproxen vs Diclofenac
• Extensive use of diclofenac substantially
increases the risk of AMI. There is little
suggestion of such an effect in users of
ibuprofen and naproxen.
• Diclofenac demonstrates a significant risk
while naproxen appears to pose the lowest,
albeit nonsignificant, risk for cardiovascular
morbidity

Br J Clin Pharmacol. 2007 May 17

Ann Pharmacother. 2007 Jul;41(7):1163-73. Epub 2007 Jul 3.
 Naproxen vs Etoricoxib

• A greater proportion of patients had a

thrombotic CV event in the etoricoxib group
than in the naproxen group
• A trend toward more events with etoricoxib
versus naproxen was observed.
Ann Rheum Dis. 2007;66:945-951
Curr Med Res Opin. 2006 Dec;22(12):2365-74. .
A Prospective Study Comparing Celecoxib with Naproxen
in Children with Juvenile Rheumatoid Arthritis

Objective- To compare the efficacy and safety of

celecoxib and naproxen in children with juvenile
rheumatoid arthritis (JRA).
Conclusion- Celecoxib 3 mg/kg bid and 6 mg/kg bid
were at least as effective as naproxen 7.5 mg/kg bid in
treating the signs and symptoms of JRA over 12 weeks.
All treatments were generally well tolerated.
(J Rheumatol First Release Nov 15 2008; doi:10-3899/jrheum.080073)
Cardiovascular outcomes in high-risk patients with
osteoarthritis treated with Ibuprofen, Naproxen, or
Lumiracoxib

Methods:
The Therapeutic Arthritis Research and Gastrointestinal Event Trial
(TARGET) of 18,325 osteoarthritis patients comprised 2 parallel sub-
studies, comparing lumiracoxib (COX-2 inhibitor) to either ibuprofen or
naproxen. We performed a post hoc analysis stratified by baseline
cardiovascular risk, treatment assignment, and low-dose aspirin use.
The primary composite endpoint was cardiovascular mortality,
nonfatal myocardial infarction, and stroke at 1 year; a secondary
endpoint was the Development of congestive heart failure (CHF).

Conclusions: These data suggest that ibuprofen may confer an

increased risk of thrombotic and CHF events relative to lumiracoxib
among aspirin users at high cardiovascular risk. Our study indicates
that naproxen may be associated with lower risk relative to lumiracoxib
among non-aspirin users.

Ann Rheum Dis. Published Online First: 5 April 2007

Naproxen in rheumatoid arthritis.
Extended trial
Naproxen is a useful drug for long-term use in
patients with rheumatoid arthritis, including
those who have proved intolerant of or
experienced inadequate symptomatic relief
from other nonsteriodal anti-inflammatory
agents.

(Annals of the Rheumatic Diseases)

 Post-Marketing Clinical Trials

• VIGOR
– Randomized RA patients ≥ 50 yo (or ≥ 40 yo and
receiving long-term glucocorticoid therapy) into either
rofecoxib 50mg qd (N=4,047) or naproxen 500mg bid
(N=4,029)
– Overall rate of cardiovascular events reported in
association with naproxen is consistent with that
expected in this population
– MI: Rofecoxib (0.4%) vs. naproxen (0.1%)
– Ischemic cerebrovascular events: 0.2% in both arms

Source: Bombardier C et al. NEJM 2000; 343:1520-8

Talking point for Naprosyn
• Pure— Only active S isomer is used which
offers better analgesia
• Safe ---- Naproxen is safer to selective Cox II
inhibitors as well as non selective NSAIDs like
Diclofenac and Ibuprofen as the relative risk of
Myocardial infarction is much lesser with
Naproxen.Naprosyn provides possible
protection against vascular events by 10%
reduction in risk of MI.
• Sure --- Naprosyn offers better efficacy with
regards to analgesia as recommended by
Goodman & Gilman.T
 USP for Naprosyn
• Time Tested internationally acclaimed NSAID’s
• Faster Pain Relief
• Safe on long term Usage
• Protects from cardiovascular events due to
antiplatelet effects.
• No ill effects on the chodrocytes.
• Low incidence of renal side effects.
NAPROXEN & NAPROXEN Sodium

They are two different salts of Naproxen.

Regarding the efficacy both are same & only
difference is in the pharmacokinetics where
Naproxen sodium because of its sodium salt is
absorbed half hour earlier than Naproxen palin.
But adding sodium also becomes a risk factor
for patients of Hypertension & other cardiac
diseases. Since majority of rheumatic disorders
like osteoarthritis are seen in old age, the
sodium salt can increase the risk in these
patients.
 What is Naprosyn Sr?

• Naprosyn Sr is a sustained release form of

Naproxen .The release pattern is 10%
immediate and 90% sustained released. We
have another sustained released formulation
Napexar which as a released pattern as 50%
immediate and 50% sustained release.
What is the sustained release
technology & what are their
benefits?

• In Sustained release technology, the release of

drug is modified in such a way that it maintains
the levels of drug for a longer duration than the
regular drug.
• The obvious benefit of sustained release drug
is improved compliance of the patient.
What is the matrix technology?

• Matrix is a mould in which a drug is embedded. The

classification of matrix systems is based on matrix structure,
release kinetics, controlled release properties (diffusion,
erosion, swelling), and the chemical nature and properties of
employed materials Matrix systems are usually classified in
3 main groups: hydrophilic, inert, and lipidic (significance of 3
phases)?
• The matrix system has several advantages as follows,
• 1. It is very simple and easy to establish a formulation.
• 2. The tablet is completely dissolved and thus achieves good
bioavailability. (Why, How?)
• 3. Offers sustained release of drug with OD advantage

• What is the polymer used in Naprosyn Sr?

• Naprosyn Sr involves hydrophilic Hydroxypropyl Methylcellulose
[HPMC] as a polymer.
 Summary

• A review of the observational studies shows no

increased risk of MI with naproxen
• A review of the postmarketing surveillance data
shows no signal for MI or cerebrovascular
events
• The published clinical trials do not provide
evidence of an increased risk of MI or
cerebrovascular events
• Unadjudicated preliminary findings of ADAPT
are inconsistent with the known data and
pharmacologic properties of naproxen
MICROBIOLOGY
 MICROBIOLOGY

It is a science or study of small living creatures

called microorganisms or microbes.

Microorganisms are small living creatures which

cannot be seen by naked eye and require
microscope to be observed.
 Microbiology

Definition
Branch of biology that deals with the smallest living
organisms, which cannot be seen by naked human
eye.

Branches of Microbiology

Bacteriolog Mycolo
y gy
Virolo Parasitol
gy ogy
 Microbiology

• Bacteriology Study of Bacteria

• Virology Study of Viruses
• Mycology Study of Fungi
• Parasitology Study of protozoa
 Microbiology

• In 1632 a device was invented to see the

microorganism by Antony Van Leeuwenhoek
called microscope.

• In 1665, Robert Hook (Englishman) reported

that living things were composed of little boxes
or cells.
History of Microbiology

The Germ Theory of Disease

1876: provided proof that a bacterium causes
anthrax and provided the experimental
steps, Koch’s postulates, used to prove that
a specific microbe causes a specific
disease.
Koch was a physician and Pasteur’s young
rival
History of Microbiology

1928: discovered the first antibiotic.

He observed that Penicillium fungus made
an antibiotic, penicillin, that killed S. aureus.
1940s: Penicillin was tested clinically and mass
produced.
 Flora

• Normal flora is the natural population of

microorganisms living on and within us. There are
two types: Resident and Transient.
 Resident flora
Resident flora :
• These residents live in specific sites,& do not cause
harm .
However, residents may become pathogenic if they are
introduced into abnormal sites. If E. coli, for example,
gains access to the urinary bladder, it causes an
infection called cystitis.

Transient flora :
Transient flora is the population of microorganism which
is not pathogenic in normal immune condition but may
become pathogenic when the host’s resistance is
lowered .
 BACTERIA

Bacteria are very simple unicellular organisms.

All are microscopic in size, and a magnification
of 1000 times is usually necessary to see them
clearly
Bacterial Cell
 Bacterial Structures
• Flagella
• Pili
• Capsule
• Plasma Membrane
• Cytoplasm
• Cell Wall
• Lipopolysaccharides
• Teichoic Acids
• Inclusions
• Spores
BACTERIAL STRUCTURE

• NUCLEUS- Mostly consists of the DNA & is not

bound by a nuclear membrane.

• CYTOPLASM- The cytoplasm of a bacterial cell

lacks mitochondria. The functions of the mitochondria
is carried out in the cell membrane.

• RIBOSOMES- Ribosomes are present in the

cytoplasm. Ribosomes consists of RNA & protein
which are responsible for protein synthesis.
BACTERIAL STRUCTURE
• CYTOPLASMIC MEMBRANE- It is the
membrane which surrounds the cytoplasm

• CELL WALL- Rigid structure lying outside the

cytoplasmic membrane & gives a shape to
bacteria.

• FLAGELLA- Thread like structure which

gives the organism motility.
 Classification of
Bacteria

According to :

♦ Shape
♦ Requirement of oxygen
♦ Staining with Gram stain
Identifying organisms by shapes
 Classification by shape

• The bacteria may be of the following shape :

• Cocci ( from KAKKOS; meaning berry):
– Cocci in pair- diplococci
– Cocci in chain- streptococci
– Cocci in cluster- staphylococci
 Classification by shape
• Bacilli (from bacillus; meaning rods)

Coccobacilli Length may be equal to width

( Brucella)

Corynebacteria Chinese letter arrangement

(C.Diptheriae)

Vibrio They are coma shaped , curved

rods& derive the name from
their vibratory motility.
(V.Cholorae)

Spirochete( SPIRIA- Coil, Having several coils(Treponema

CHETE-Hair)- pallidum, Aquaspirillium)
 Classification by shape

Actinomycetes (Actis- ray, mykes- fungus)-They

are branching filamentous
bacteria & resembles like
radiating sun ray

Mycoplasma They don’t have cell wall &

hence do not possess stabe
morphology.

Plemorphic They can exhibit a variety of

shape. (Arthrobacter).
 Staining Characteristics

i. Grams staining
ii. Acid fast staining

Grams staining – In 1884 Christian Gram

devised this staining method.
what are the different reagents
used in the Gram stain?

Primary Stain
Mordant ( iodine)
Decolorizer (alcohol)

Counterstain
 Gram +ve and Gram -ve bacteria

Microorganism + Methylviolet dye + iodine

Washed with acetone / alcohol and water

Counterstain with safranin stain

Gram positive Gram negative

Organisms retain
Lose original violet
original violet stain
stain pink with
safranin
What are the results of the Gram
stain?
ATYPICAL BACRTERIA

On staining some of the bacteria does not

changes colour because they don’t have cell
wall.

Legonella Pneumophila, Chlamydia

Pneumoniae, Mycoplasma Trachomatis,
Ureaplasma urea Lacticum, Chlamydia
Hominis.
 BASED ON GASEOUS REQUREMENT

• Aerobic : Requires oxygen for growth. They are

of two types :
– Obligate- oxygen requirement is must. Eg.
Vibrio
– Facultative- may survive in absence of
oxygen. Eg. sreptococcus
• Anaerobic : Do not use oxygen for growth.
• (a) Stringent anaerobes- Cl. Tetani
• (b) Macroaerophillic – requires low oxygen
only. Cl.welchi.
 Gram (+)ve
Staphylococcus Aureus on the skin, Abscess, Food
Nasopharynx, GI tract poisoning,

Osteomylitis, sepsis in
wounds & burns.
Staphylococcus On skin Carbuncle
Epidermis Fruncle,Boils,Abscess

Streptococcus On skin, In oral cavity, pus formation,

Pyogenes In female urinary tract Tonsilillitis, Pharyngitis,
Impetigo.

Sreptococcus in Nasopharynx, URTI- Pneumonia, Meningitis,

Pneumoniae
Empyema,Otitis media,
Sinusitis,Pericarditis
 Gram (+)ve
Corenybacterium Mainly in man & diphtheria.
Diptheriae predominantly in
Nasopharynx

Clostridium welchi Large intestine of man gas gangrene, food

poisoning

Clostridium botulinum widely distributed in non pathogenic

nature

Clostridium tetani In intestine & soil tetanus (synaptic

inhibition causes
muscle rigidity &
spasm.

Clostridium difficile intestine acute colitis.

 Gram (-)ve
Neisseria meningitidis Nasopharynx Crebrospinal
Meningitidis,
meningococcal
septicemia

Neisseria gonorrhoeae- urinary tract- sexualy transmitted

disease

Klebsiella intestine rare but serious

pneumonia, UTI

Proteus-). intestine & skin- UTI & Pyogenic

infction(mirabilis,morga
nii,rettgeri,vulgaris,provi
dentia
 Gram (-)ve
E.coli Large intestine- UTI,
Gastroenteritis,septicem
ia

Salmonella Intestine enteric fever, food

poisioning

Shigella intestine Dysentery

Vibrio cholerae intestine cholera

Haemophilus Nasopharynx Influenza, Chronic

influenzae- -. Bronchitis,Pneumonia,
Meningitis
 Gram (-)ve

Haemophilus ducreyi Vagina chancroid, soft sore.

Brodetella Respiratoy tract whooping

cough( pertusis,parap
ertusis,bronchiseptica

Pseudomonas Man, water, soil- infantile

Aeruginosa diarrhoea,septicemia,
UTI,otitis media,
pulmonary infection
 AEROBES
Staphylococcus Aureus
• Staphylococcus Epidermis
• Streptococcus Pyogenes
• Sreptococcus Pneumoniae
• Corenybacterium Diptheriae
• Neisseria meningitidis
• Klebsiella
• E.coli
• Proteus
• Shigella
• Salmonella
• Vibrio cholerae
• Brodetella
• Pseudomonas Aeruginosa
• Mycobacterium tuberculosis
• Mycobacterium laprae
 ANAEROBES

• Clostridium welchi
• Clostridium botulinum
• Clostridium tetani
• Clostridium difficile
• Haemophilus influenzae
• Haemophilus ducreyi
• Mycoplasma pneumoniae
• Mycoplasma hominis
 Anaerobes

“Below Diaphragm”
“Above Diaphragm”
Clostridium perfringens,
Peptococcus sp.
tetani, and difficile
Peptostreptococcus sp.
Bacteroides fragilis,
Prevotella disastonis, ovatus,
Veillonella thetaiotamicron
Actinomyces Fusobacterium
Pathogens most likely to cause infections
in specific organs and tissue
Newborn Infants : Children :
• E .coli • Strep.pneumoniae
• Listeria • Neisseria meningitidis
monocytogenes • H . influenzae
• Staph.aureus • Staph. aureus
• Strep. Pyogenes • Strep. Pyogènes
• Enterococci • E. Coli
• Strept.pneumoniae
Pathogens most likely to cause infections in
specific organs and tissue

Adults : Bone :
• E .coli • Staph.aureus
• Staph.aureus • Salmonella
• Strep.pneumoniae • Strep. Pyogenes
• Bacteroides • M .tuberculosis
• Strep.pyogenes • Bacteroids
• Staph.epidermidis
• Neisseria gonorrhoeae
• Candida albicans
• Neisseria meningitidis
Pathogens most likely to cause infections in
specific organs and tissue

Skin infection : Mouth :

• Staph.aureus • Herpes viruses
• Sterp.pyogenes • Candida albicans
• Candida albicans • Bacteroids
• Herpes simplex • Actinomyces
• Treponema pallidium • Treponema pallidium
 Pathogens most likely to cause infections in
specific organs and tissue

Lungs :
• Mycoplasma
pneumoniae
• Sterp.pneumoniae
• H .influenzae
• Bacteroids
• Staph.aureus
• Klebsiella
• Legionella pneumophilla
• Chlamydia pneumoniae
• Rickettsia
• Myco.tuberculosis
• Pneumocystis carini
Gastro-intestinal
tract :
• Salmonella
• E .coli
• Shigella
• Entamoeba histolytica
• Giardia lamblia
• Staph.aureus
• Treponema pallidium
• Neisseria gonorrhoeae
• Vibrio parahaemolyticus
• Candida albicans
Pathogens most likely to cause infections in
specific organs and tissue

Urinary tract :
• E .coli
• Staph.aureus
• Neisseria gonorrhoeae
• Enterococci
• Candida albicans
• Chlamydia
• Treponema pallidium
• Trichomonas vaginalis
• Ureaplasma urealacticum
Bacteria by Site of Infection

Mouth
Peptococcus
Peptostreptoc
 Infection

It is defined as the invasion of any living tissue by

living micro organisms in order to grow & multiply
at the expense of the host
 INFECTION

Infection is a process in which an organism

enters, establishes & multiplies in host.
TYPES-
1.Primary infection
2. Secondary infection
3.Reinfection
4.Nosocomial infection
5. Mixed infection
6. Community acquired pneumonia
 CLINICAL TYPES OF
INFECTION

• ACUTE INFECTION
• CHRONIC INFECTION
SOURCE OF INFECTION

• Man
• Animal
• Insects
• Soil
• Water
• Food
 Phase of Infection
• Inoculation
• Incubation
• Acute phase
• Convalescence
 CLINICAL MANIFESTATION

• FEVER
• INFLAMMATION
• ACHES
• PAINS
• WEAKNESS
• INCREASED HEART RATE
• CHILLS
ANTIMICROBIAL DRUGS
 What is an Antibiotic?
• An antibiotic is a selective poison.
• It has been chosen so that it will kill the
desired bacteria, but not the cells in your
body. Each different type of antibiotic affects
different bacteria in different ways.
– For example, an antibiotic might inhibit a bacteria's
ability to turn glucose into energy, or the bacteria's
ability to construct its cell wall. Therefore the bacteria
dies instead of reproducing.
 Antibiotic/Antimicrobial

• Antibiotic: Chemical produced by a

microorganism that kills or inhibits the growth
of another microorganism
• Antimicrobial agent: Chemical that
kills or inhibits the growth of microorganisms
 Bacteriostatic
Bacterial growth is inhibited, but no killing
occurs

 Frequently inhibitor of protein synthesis

and act by binding to ribosomes  do not
bind thightly, removed by lower
concentration
 Bactericidal

Bactericidal agents kill cell but lysis or

cell rupture doesn’t occur

 Class of chemical agents that

generally bind thightly to their cellular
targets & not removed by dilution
MECHANISMS OF ACTION OF
ANTIBACTERIAL DRUGS

• Mechanism of action include:

– Inhibition of cell wall synthesis
– Inhibition of protein synthesis
– Inhibition of nucleic acid synthesis
– Inhibition of metabolic pathways
– Interference with cell membrane integrity
 Inhibition of Cell wall synthesis

• Inhibition of Cell wall synthesis

– Bacteria cell wall unique in construction
• Contains peptidoglycan

– These drugs have very high therapeutic index

• Low toxicity with high effectiveness

– Antimicrobials of this class include

• β lactam drugs( Penicillin's, Cephalosporin's)
• Vancomycin
• Bacitracin
Cell Wall Biosynthesis - the Target
of β -Lactams
Transpeptidases, also known
The bacterial cell wall is built
as penicillin-binding proteins (or
from strands of sugar molecules PBPs) react with one end of the
that have peptide side chains. peptide side chain (the
"acceptor") to form a covalent
intermediate.
Cell Wall Cross-linking Gives Stability
The covalently attached PBP then Thus, a strong covalent link is
binds another peptide side chain built between neighbouring sugar
(the "donor") and promotes its attack strands. These peptide cross-
on the previously attached acceptor bridges are essential for the
chain. mechanical strength of the cell
wall.
 β -Lactams Inhibit Cell Wall
Biosynthesis
b-Lactams mimic the
peptide side chains. They
are bound by PBPs and
undergo a reaction similar
to that observed with the
peptide.

The covalent intermediate

formed with a b-lactam cannot
cross-link the cell wall.

Without the cross-bridges, the

cell wall remains in a fragile
state and it cannot protect the
cell against lysis.
 Penicillin's
Penicillin class Drug Antimicrobial spectrum

Natural Penicillins Penicillin G gram+ cocci and bacilli,

Penicillin V some
gram– cocci (Neisseria
Penicillinase resistant Cloxacillin Staphylococcus aureus
Dicloxacillin
Oxacillin

Broad-spectrum Ampicillin Same as Pen G plus

(Amino penicillins) Amoxicillin some
Bacampicillin gram– organisms

Extended spectrum Ticarcillin (Ticar) Same as broad

Piperacillin (Pipracil) spectrum
Carbenicillin (Geocillin) plus additional gram–
Mezlocillin (Mezlin) coverage, including
Pseudomonas
Adverse Effects of Penicillins
• Allergy
• Diarrhea
– ampicillin
• Rash
– ampicillin
• Sodium overload, inhibition of platelet
function
– ticarcillin
• Antibiotic-associated colitis
(Pseudomembranous colitis)
 Cephalosporins

First gen. Second gen. Third gen. Fourth gen.

Cefazolin Cefuroxine Ceftriaxone Cefepime

Cephalexin Cefamandole Cefotaxime

Cefadroxil Cefoxitin Ceftozoxime

Cephalothin Cefotetan Cefoperozone

Cephradine Cefonicid Ceftibutin

Cephapirin Cefprozil Cefpodoxime

Cefaclor Cefixime

Lorcaebef Cefditoren
Cephalosporin's
Drug Gram– Resistance to Penetration
Generation activity β-lactamases into CNS

First Cefazolin Low Low Poor

Cephalexin

Second Cefaclor Higher Higher Poor

Cefoxitin

Third Cefixime Highest Highest Good

Ceftazidime
Adverse Effects of
Cephalosporins

• Allergic reactions

• Antibiotic-associated colitis
Inhibition of protein synthesis

• Inhibition of protein synthesis :

– Drugs of this class include

• Aminoglycosides
• Tetracyclins
• Macrolids
• Chloramphenicol
 MECHANISMS OF ACTION OF ANTIBACTERIAL
DRUGS

• Aminoglycosides :
– Irreversibly binds to 30S ribosomal subunit

– Not effective against anaerobes, enterococci and

streptococci

– Often used in synergistic combination with β-lactam

drugs

– Allows aminoglycosides to enter cells that are often

resistant
Aminoglycosides

– Gentamicin
– Tobramycin
– Amikacin

Antimicrobial spectrum

– Aerobic gram-negative organisms

Pseudomonas, Klebsiella, E. coli,
others
Adverse Effects of
Aminoglycosides

• Ototoxicity

• Nephrotoxicity
 MECHANISMS OF ACTION OF
ANTIBACTERIAL DRUGS
• Macrolids :
– Reversibly binds to 50S ribosome

– Effective against variety of Gram + organisms and those

responsible for atypical pneumonia

– Often drug of choice for patients allergic to penicillin

– Macrolids include
• Erythromycin, clarithromycin and azithromycin
Macrolides
– Erythromycin
– Clarithromycin
– Azithromycin

Antimicrobial spectrum
– Gram-positive and some gram-
negative
– Also Mycoplasma pneumoniae,
Chlamydia

Adverse effects
– GI disturbances
--Liver toxicity
Tetracyclines
• Mechanism of action- Inhibit bacterial
protein synthesis
• Bacteriostatic
Antimicrobial spectrum
– Broad spectrum
– Also Mycoplasma pneumoniae, Chlamydia,
Rickettsia, Lyme disease

Specific agents
– Tetracycline, Doxycycline,Minocycline

Adverse Effects of Tetracyclines

• GI irritation, Antibiotic-associated colitis, Hepatic
toxicity, Kidney toxicity
• Photosensitivity, Discoloration of teeth
 Inhibition of nucleic acid
synthesis
• Inhibition of nucleic acid synthesis
– These include
• Fluoroquinolones
• Rifamycins
Inhibition of nucleic acid synthesis

• Fluoroquinolones
– Inhibit action of topoisomerase DNA gyrase
• Topoisomerase maintains supercoiling of
DNA
– Effective against Gram + and Gram -
– Examples include
• Ciprofloxacin and ofloxacin
– Resistance due to alteration of DNA gyrase
Generation Drug Names Spectrum
1st nalidixic acid Gram- but not
cinoxacin Pseudomonas species

2nd norfloxacin Gram- (including

ciprofloxacin Pseudomonas species),
some Gram+ (S.
enoxacin
aureus) and some
ofloxacin atypicals

3rd levofloxacin Same as 2nd generation

sparfloxacin with extended Gram+
and atypical coverage
moxifloxacin
gemifloxacin

4th *trovafloxacin Same as 3rd generation

with broad anaerobic
coverage
Adverse Effects of Quinolones
and fluoroquinolones
• Headache
• Candida infections
• Tendonitis or tendon rupture
• Cartilage deterioration in young
animals
• Phototoxicity
 Inhibition of nucleic acid
synthesis
• Rifamycins
• Block initiation of transcription
– Rifampin most widely used rifamycins

– Effective against many Gram + and some

Gram - as well as members of genus
Mycobacterium

– Primarily used to treat tuberculosis and

Hansen’s disease as well as preventing
meningitis after exposure to N. meningitidis
Inhibition of metabolic pathways
• Inhibition of metabolic pathways
– Most useful are folate inhibitors
• Mode of actions to inhibit the production of folic acid

– Antimicrobials in this class include

• Sulfonamides
• Trimethoprim
Antimicrobial Selection Based on
Four-Quadrant Method
Gram-Positive Aerobes
Beta-Lactams,
Chloramphenicol,
Fluoroquinolones,
Lincosamides, Macrolides,
Sulfonamides, Tetracyclines
Gram-Positive Anaerobes
Beta-Lactams,
Chloramphenicol, Macrolides,
Metronidazole, Sulfonamides,
Tetracyclines

Gram-Negative Aerobes Gram-Negative Anaerobes

Aminoglycosides,
Beta-Lactams,
Beta-Lactams,
Chloramphenicol, Chloramphenicol,
Fluoroquinolones, Sulfonamides, Lincosamides, Macrolides,
Tetracyclines
Metronidazole, Sulfonamides,
Tetracyclines
Characteristic of an ideal
antimicrobial

Selectively toxic to the microbes but non

toxic to host cell.
Microbicidal rather than microbistatic.
Readily delivered to the site of infection.
Should have broad spectrum.
Assist the activities of host defense.
Doesn’t lead to development of
antimicrobial resistance.
Safe & well tolerated.
Does not disrupt the host health.
Reasonably priced
 Phamacokinetic Definitions

• Clearance is the removal of the drug from plasma and relates the rate at
which a drug is given and eliminated to the resultant plasma levels
(volume/time)

• Cmax is the maximum concentration reached at the site of infection, usually

taken as the peak serum level.

• tmax is the time taken, after dosage, to reach the Cmax .

• Half-life (t½) is the time taken for the concentration of the drug in the plasma
to decrease by half. This is often used as an indicator as to how often the
drug should be administered.
 Phamacokinetic Definitions

• Area Under the Curve (AUC) is the parameter that links

clearance to dosing. It is easily calculated: Initial
concentration / Elimination rate constant.

• Area Under the Inhibitory Curve (AUIC) is an

antimicrobial adaptation of AUC, it refers to the
concentration of the drug which is able to exert
antibacterial activity over a given organism for a
specific time. The AUIC is the drug concentration (AUC)
divided by the MIC90 for a specific bacterial species.
 NUFEX BETA

CEFIXIME + CLAVULANIC ACID

Structure of β -lactam drugs
 WHAT IS NUFEX BETA?

• NUFEX BETA is an oral antibacterial

combination consisting of :

CEFIXIME and the Beta -lactamase

inhibitor CLAVULANIC ACID
MECHANISM OF ACTION

• Cefixime in Nufex Beta inhibit the cell wall

synthesis and stops the growth of susceptible gram-
positive, gram-negative, anaerobic microorganisms.

• Cefixime is, however, susceptible to degradation by

Beta-lactamases

• Clavulanic acid in NUFEX BETA protects Cefixime

from degradation by beta-lactamase enzymes

• Effectively extends the antibiotic spectrum of

cefixime
ORGANISMS COVERED

GRAM-POSITIVE AEROBES : Streptococcus

pneumoniae, Streptococcus pyogenes,viridans
group Streptococcus .

GRAM-NEGATIVE AEROBES :Enterobacter species

Escherichia coli, Haemophilus influenzae,
Klebsiella species , Moraxella catarrhalis, Neisseria
gonorrhoeae, Proteus mirabilis .

ANAEROBES : Bacteroides species, including

Bacteroides fragilis, Fusobacterium species ,
Peptostreptococcus species .
 Pharmacokinetic profile

GROUP Cmax(μg/ Tmax(h) AUC T1/2(h) fe(% dose

mL) (μg.h/mL)

5.68 4.3 49.5 4.2 24.6

 Antimicrobial resistance
• A hypothesis of the mechanism by which S
pyogenes is protected from penicillin by a β-
lactamase–producing copathogen is depicted in
the diagram.1-3
• The nasopharynx is cocolonized by the
pathogens S pyogenes and
S aureus. Parenterally or orally administered
penicillin leaves the bloodstream, enters the
tonsillopharyngeal tissue, and is inactivated by
β-lactamase produced by S aureus before the
penicillin can have bactericidal effect on S
pyogenes.1-3
 Beta-Lactamase Inhibitors

• Clavulanic Acid, Sulbactam and Tazobactam

• Mechanism of action: These drugs have poor

antimicrobial activity. They are “suicide inhibitors” of bacterial
beta-lactamase.

• They are potent inhibitors of many bacterial beta-lactamases

and can protect penicillins from inactivation by these
enzymes.
Beta-lactamase inhibitors

They are available only in fixed

combinations with specific penicillins:

• Ampicillin + Sulbactam
• Amoxicillin + Clavulanic acid
• Cefixime + Clavulanic acid
• Piperacillin + Tazobactam
 Advantage of this combination

• A solution for treatment of bacterial infections caused by

beta lactam resistant pathogens.

• Prevents resistance to cefixime

• Has a broad spectrum antibiotic activity.

• Highly effective combination in switch therapy.

• The combination of clavulanic acid with an antibiotic has

proven to be clinically effective on betalactam – resistant
microbial infections, especially those in which the
Cefixime alone was ineffective.
 RATIONALE OF COMBINING
CLAVULANIC ACID WITH CEFIXIME

• Cefixime is ineffective in the presence of beta

lactamase producing micro organisms.
Clavulanic acid which is a beta lactamase
inhibitor protects Cefixime from hydrolysis by
beta lactamases thus enhances the spectrum
of Cefixime
 UNIQUE FEATURES

• Broad spectrum antibiotic

• Effective against ß-lactamase producing
pathogens
• Well tolerated
• Administered only once or twice daily therefore
good patient compliance
 INDICATIONS AND USAGE

• Typhoid

• Respiratory Tract Infections

• Otitis Media, Sinusitis,

• Urinary Tract Infection

• Pelvic inflammatory disease, Gonorrhoea

• Diabetic wounds
 Target DR’s

• Physicans
• General Practitioners
• ENT Dr’s
• Paediatricians
• Surgeons
• Gynaecologists
 Adverse Reactions

• Well tolerated.

• Side effects seen are diarrhea (9%),

nausea (3%), skin rashes and urticaria
(3%)., vomiting (1%) and vaginitis (1%).
 DOSAGE AND ADMINISTRATION

The usual adult dose is :

• Nufex Beta 100 mg DT- 12 hrly

( Cefixime 100 mg + Clavulanic Acid 62.5 mg)

• Nufex Beta 200 mg - 12 hrly

( Cefixime 200 mg + Clavulanic Acid 125 mg)
 Summary

Advantage:
 The combination of cefixime and clavulanic
acid provides.
 A solution for treatment of bacterial infections
caused by beta lactam resistant pathogens.
 Prevents resistance to cefixime.
 Has a broad spectrum antibiotic activity.
 Highly effective combination in switch
therapy.
 Nufex-Beta as
an Ideal switch therapy

In practice of critical care or hospital care, it is now

well accepted that the patients on intravenous
therapy should be switched over to oral therapy
as soon as stability of vital signs are achieved
and the patient is alert enough to take drugs by
oral route.

This process of switching the patients form i.v./i.m

to oral therapy is called “switch therapy,
sequential therapy, transitional therapy,
antibiotic streamlining or step down therapy.
Guideline for switch therapy
• 1) Clinical condition from which patient is
suffering
• 2) Empirical Intravenous therapy which is to be
administered
• 3) Oral medication which is best suited for
switch therapy
 Criteria for selection of antibiotics to be used
for oral conversion

• 1) Antibiotic that can be used orally for switch therapy

should have pharmacokinetic profile and microbial
spectrum more or less similar to that of the parenteral
antibiotic used.
• 2) Choosing the right antibiotic depends mainly on the
likely pathogen.
• 3) A thorough understanding of the likely microbial cause
of the infection
• 4) Local susceptibility patterns
• 5) Properties of the antimicrobials, namely spectrum of
activity and potency (including activity versus known
resistance mechanisms)
• 6) Pharmacokinetic profile tolerability and safety of oral
antibiotic
 Switch Therapy Approach to Treatment

Hospital Admission

Switch Therapy
of Infection
Severity

Hospital Discharge
IV
Therapy
PO Cure
Therapy

Inpatient Outpatient Time

Treatment Treatment
The Annals of Pharmacotherapy 1998; 32:
S22-26.
 Intravenous Product & Oral Conversion
Product
Ampicillin Ampicillin 250-500 mg po qid
orAmoxicillin 250-500 mg tid
Ampicillin-sublactam Amoxicillin+clavulanic acid 250-
500 po q8h
Cefazolin Cefadroxil 500 mg po
q12h,Cephalexin 500 mg po q6h,
or Cefaclor 500 mg po q8h
Cefotaxime CEFPODOXIME 100-200 mg po
q12h,Cefixime 400 mg po qd, or
Ceftibuten 400 mg po qd
Cefoxitin Cefuroxime 250-500 mg bid,
Cefixime 400 mg po qd
Ceftizoxime Cefixime 400 mg po qd

Ceftriaxone CEFPODOXIME 100-200 mg po

q12h, Cefixime 400 mg po qd

Cefuroxime Cefuroxime 250-500 mg q12h

Infection Intravenous agent Oral agent

Acute bacterial meningitis Ceftriaxone sodium Chloramphenicol

Community-acquired pneumonia
Typical Ceftriaxone Azithromycin,or cefuroxime
or ceftizoxime sodium axetil
or levofloxacin or cefixime

Atypical levofloxacin Doxycycline,or azithromycin

or levofloxacin

Intra-abdominal sepsis (excluding

biliary tract)
Mild/moderate Ampicillin/sulbactam Metronidazole
or ceftizoxime PLUS,levofloxacin
or cefixime
Severe metronidazole PLUS Metronidazole PLUS
gentamicin levofloxacin
or ceftriaxone,or or cefixime
levofloxacin

Biliary tract sepsis Ampicillin/sulbactam Levofloxacin,or

or cefoperazone amoxicillin,or
sodium cefixime
Urosepsis

Gram-negative Aminoglycoside,or levofloxacin***,or

levofloxacin, cefixime

Gram-positive (groups B Ceftizoxime Doxycycline

and G streptococci) or amoxicillin/potassium
clavulanate

Skin and soft-tissue Ceftizoxime Cephalexin,or cefuroxime

infections or cefixime
MICs of Cefixime vs Parental formulation
Bacterial Species Cefotax Ceftizox Ceftaz Ceftriax Cefixime

S. aureus 2 16 16 4 17

S. epidermidis 8 32 >32 >32 61.8

S. pneumoniae < 0.1 0.1 0.5 0.08 .29

S. pyogenes 0.1 0.25 0.12 0.1 .16

E. Coli 0.1 0.25 0.5 0.1 .71

Klebsiella spp. < 0.5 0.25 0.5 0.1 .34

Citrobacter spp 16 8 0.5 0.1 1.54

Morganella 1 1 4 0.25 17

Proteus spp <1 .25 1 4 .25

Serratia spp 8 .25 1 4 12.9

Pseudomonas >64 >64 4 >64 53

S. multophilia >32 >32 32 >32

MICs90 of Cefixime vs other Cephalosporins

H. M.catarrh E.coli S.pneumo S.aureusb

influenza alisa niae
ea
Cephale 16 16 16 4 4
xin

Cefadrox 16 4 16 8 8
il
Cefuroxi
me
2 2 4 0.12 2
Cefixime 0.13 .40 0.71 0.29 16
Cefpodo
xime
0.12 0.50 1 .03 2
 MICs90 of Cefixime vs other Quinolones
Bacterial Species Gemi Moxi Gati Cipro Cefixime

S. aureus 128 128 128 128 17

S. pneumoniae 0.06 0.25 .5 4 .29

S. pyogenes 0.25 .5 .5 1 .16

E. coli 64 64 8 128 .71

Klebsiella spp. 4 4 2 2 .34

Enterobacter 16 16 16 16 20

Morganella 16 32 8 8 17

Proteus spp 8 8 2 1 .25

Serratia spp 16 16 16 8 12.9

Pseudomonas 128 128 64 64 53

m.cattarhalis 0.03 .06 .5 4 0.4

H.Influ .03 .06 .03 .03 0.13

 Pneumonia

• Is an infection of the
pulmonary parenchyma
that can be caused by
various bacterial species,
viruses, fungi etc.
 Pneumonia leads causes of childhood
deaths

Source: WHO estimates of the causes of death in children, 2000-03 Bryce,

Lancet, 26 March 2005
Risk factors for pneumonia
• Low birth weight • Indoor air pollution
• Malnutrition • Household crowding
• Bottle feeding • Cold exposure
• Vitamin A deficiency
• HIV infection
 What causes Pneumonia: Viruses

• Respiratory Syncytial • Rhinovirus

Virus

• Parainfluenza
• Adenovirus /Influenza
 What causes Pneumonia: Bacteria

• Streptococcus pneumoniae • Haemophilus

influenzae

Source: CF. Laine, T Sugishita, J Rabke-Verani , M Cavicchia

 Other URTI
Sinusitis-Inflammation of sinus cavities is called as sinusitis

Pharyngitis - is an inflammation of pharynx leading to sore

throat.

Tonsillitis - is an inflammation of tonsils. Tonsils are lymph

nodes in the back of the mouth/top of the throat.

Otitis media - is an inflammation of middle ear

Causative organisms :
Streptococcus pneumoniae
H.influenza, Moraxella catarrhalis
 Lower Respiratory Tract Infection

Tuberculosis - it is an infection of lungs caused by

Mycobacterium tuberculosis
Bronchitis - it is an inflammation of the bronchi .
Chronic bronchitis - clinically defined as presence of a
cough productive of sputum not attributable to other
causes on most days for at least 3 months over 2
consecutive years.
AECB Symptoms - Increased sputum purulence.
Increased sputum thickness, increased sputum volume,
worsening of cough, fever and breathlessness.
Causative organisms :
Streptococcus pneumoniae,Mycoplasma pneumoniae ,
Moraxella catarrhalis, Chlamydia pneumoniae,
H. influenza
 Community-acquired respiratory
tract pathogens

Prevalence in infection (%)

S. pneumoniae H. influenzae M. catarrhalis

Acute otitis media (AOM) 42 38 17

Acute sinusitis 42 29 22

Community-acquired
pneumonia (CAP) 20–75 3–10 –

Acute exacerbations
of chronic bronchitis 15 32 13

Hoberman et al. Pediatr Infect Dis J 1996; 15:955–962

Bartlett & Mundy. NEJM 1995; 333:1618–1624
Zeckel et al. Clin Ther 1992; 14:214–228
 Comparative Activity of Antibiotics
Against S. pneumoniae based on PK/PD

Highest Ceftriaxone
Amoxicillin * NOTE: Drugs
Amoxicillin-clavulanate * listed alphabetically
Cefdinir in each cluster
Cefpodoxime proxetil
Cefixime
Cefuroxime axetil
Clindamycin
Azithromycin
Clarithromycin
Cefaclor
Loracarbef
Trimethoprim-sulfamethoxazole
Lowest
Ceftibuten
* Double dose: 80 – 100 mg/kg/d amoxicillin
Pichichero. Am Family Physician 2000;61:2410-2416
 Comparative Activity of Antibiotics Against
H. influenzae ß-lactamase+ based on PK/PD

Cefixime
Highest
Ceftibuten
Ceftriaxone
Amoxicillin-clavulanate NOTE: Drugs
Cefdinir listed alphabetically
Cefpodoxime in each cluster
Cefuroxime
Cefprozil
Cefaclor
Clarithromycin
Loracarbef
Trimethoprim-sulfamethoxazole
Azithromycin

Lowest Amoxicillin

Pichichero. Am Family Physician 2000;61:2410-2416

 MICs90 of Cefixime vs other Cephalosporins

H. M.catarrh S.pneumonia
influenzaalisa e
ea
Cefuroxime 2 2 0.12

Cefixime 0.13 .40 0.29

Cefpodoxim 0.12 0.50 .03
e
Co- 0.5 0.5 0.02
Amoxyclav

Community-acquired pneumonia
(Recommendation from Journal
of chemotherapy)

Typical Ceftriaxone Azithromycin,or cefuroxime

or ceftizoxime sodium axetil
or levofloxacin or cefixime
Atypical levofloxacin Doxycycline,or azithromycin
or levofloxacin
 Typhoid Fever
• Typhoid fever is an acute infectious disease of digestive tract
caused by typhoid bacillus.
 Clinical feature
 sustained fever
 relative slow pulse
 toxic symptoms
 a rose-color rash
 splenomegaly and hepatomegaly
 leukopenia
 Complication
 hemorrhage & perforation
 Route of transmission Fecal-oral route:
 contaminated food or water
 contagious spread
 spread by insect
Clinical manifestation
Incubation period: 7-23 day(average 10 to
14 days)
Typical typhoid fever:
 Initial period
 onset: insidious, gradual
 fever: T stepwise fashion rising
 non-special symptoms
 Fastigium
 Defervescence
 Convalescence
 Clinical manifestation
 Fastigium
 sustained fever
 toxic symptoms(tinnitus, delirium,lethargy, coma
 DS anorexia, abdominal Pain, diarrhea Constipation
 CS relative slow pulse, bradycardia, myocarditis)
 rose-colored rash:
 occur on 6~13 days
 upper abdomen
 hepatomegaly and splenomegaly

 Devervescence
 Convalescence
Salmonella-The culprit
 Salmonella

• Gram-negative, motile bacilli

• Found in the intestines and feces of most birds,
reptiles, and mammals (more than 2,000
species)
• Currently, most salmonella infections in
humans are the result of consumption of food
contaminated with animal feces
• Poultry and eggs are particularly common
sources of Salmonella
 Salmonella typhi

• Infection occurs via ingestion of food or

water contaminated with sewage
containing bacteria from carriers
• Bacteria can pass through the intestines
into the bloodstream and into the liver,
spleen, bone marrow, and gall bladder
• Bacteria from the gall bladder can
reinfect the intestines, producing
gastroenteritis and a recurrence of
bacteremia
 Nufex-Beta

Cefixime 0.21mcg • The mic required for

/ml cefixime is very low as
compared to co-amoxyclav
& other cephalosporin.
• The conc. Of cefixime in gall
Amoxy-clav 1mcg/ml bladder & spleen is higher
as compared to other
antibacterial.
• Temp. defervescence will
take by 3-4 day as
Cefuroxime 4mcg/ml compared to 5-6 day with
co-amoxyclav.
axetil
• What is a urinary tract infection (UTI)?

• A urinary tract infection (UTI) is a bacterial

infection of the urinary tract system. It usually
develops in the lower part of the urinary tract
(bladder and urethra) and if not treated, can move
to the upper urinary tract (ureters and kidneys).

• What are sign & symptoms of UTI?

 You urinate a lot but only a little bit each time.

 It burns when you urinate.
 You have to urinate suddenly.
 There is blood in your urine.
 Your urine is not clear.
 Your urine smells bad.
E.Coli- The culprit
 Cystitis

• Signs/Symptoms
– Irritative voiding symptoms
• Frequency
• Urgency
• Dysuria
– Suprapubic discomfort
– Gross hematuria
– SYMPTOMS OFTEN APPEAR
following sexual intercourse
 Cystitis
• Organisms • Treatment
– Escherichia coli (90%) – Trimethoprim-
sulfamethoxazole (Bactrim)
– Klebsiella pneumoniae 160/800 mg – BID x 3 days
– Staphylococcus – Nitrofurantoin 100 mg QID x
saprophyticus 7 days
– Proteus mirabilis – Fluoroquinolone
– Mycoplasma hominis • Ciprofloxacin 250-500
mg Q12H x 3 days
• Ofloxacin 200 mg Q12H
x 3 days
• Norfloxacin 400 Q12H x
3 days
– Cefixime 400mg QD x 3 day
 Nufex-Beta in Cystitis

Cefixime Ofloxacin Amoxy-clav

Escherichia coli 0.71 0.12 8

(90%)

Klebsiella 0.10 0.2 4

pneumoniae

Staphylococcus 16 1 1
saprophyticus

Proteus mirabilis 0.06 0.2 4

Mycoplasma 0.80 1 4
hominis
 Urethritis
• Signs/Symptoms/Co • Organisms
nsiderations – Gonococcal urethritis
(80% of cases)
– Urethral discharge • Neisseria gonorrhoeae
– Dysuria – Nongonococcal urethritis
– Itching • Chlamydia trachomatis
(30-40% of cases)
– Orchalgia • Ureaplasma urealyticum
(40-60% of cases)
• Mycoplasma hominis (5-
10% of cases)
• Trichomonas vaginalis
(<5% of cases)
– Rare cases
• lymphogranuloma
venereum
• herpes simplex
• syphilis
Urethritis-N. gonorrheae
 Urethritis

• Treatment

• Ceftriaxone, 125 mg IM/IV single dose

• Cefixime, 400 mg PO single dose
• Ciprofloxacin, 500 mg PO single dose
• Ofloxacin, 400 mg PO single dose
Nufex-Beta in Urethritis
Cefixime Ofloxacin Amoxy-clav

Escherichia 0.71 0.12 8

coli (90%)

Ureaplasma 0.71 2 2
urealyticum

Neisseria 0.06 0.06 0.71

gonorrhoeae

Chlamydia 0.50 0.5 1

trachomatis

Mycoplasma 0.80 1 4
hominis
 Pyelonephritis

• Signs/Symptoms/Cons
iderations • Diarrhea
– Fever (103o F) • Tachycardia
– Flank Pain • Irritative voiding
• PRONOUNCED symptoms
• Costovertebral angle – Urgency
(CVA) tenderness – Frequency
• Commonly unilateral – Dysuria
– Shaking chills • PT LOOKS ILL
– Nausea/vomiting
 Pyelonephritis
• Organisms • Treatment
– Escherichia coli (70- – Ampicillin 1g IV Q6H with
gentamicin 1 mg/kg IV
95%) q8h x 21 days
– Staphylococcus – Vancomycin 500 mg to 2
saprophyticus g/d IV divided tid/qid x 7-
10 days
– Klebsiella – Ciprofloxacin 750 mg PO
pneumoniae Q12H x 21 days
– Proteus mirabilis – Cefixime, 400 mg PO x 21
days
– Staphylococcus
– Trimethoprim-
aureus sulfamethoxazole 160/800
– Pseudomonas mg PO Q12H x 21 days
aeruginosa
Pyelonephritis
Nufex-Beta in Pyelonephritis
Cefixim Ofloxacin Amoxy-clav
e
Escherichia coli (90%) 0.71 0.12 8

Klebsiella 0.10 0.2 4

pneumoniae

Staphylococcus 16 1 1
saprophyticus

Proteus mirabilis 0.06 0.2 4

Pseudomonas 53.10 1 100

aeruginosa
 Probability of Achieving Requisite
pharmacodynamic Exposure for Oral β-Lactam
Regimens against Haemophilus influenzae in
Children

Objective: To define contemporary levels of

resistance of Haemophilus influenzae to
antibacterials commonly used to treat children
for bacterial respiratory infections, and to assess
the probability of achieving the requisite
pharmacodynamic exposures for regimens
against recent respiratory H. influenzae isolates
using Monte Carlo simulation.
Results: β-Lactamase production was demonstrated in 67 (28.8%) of
the H. influenzae isolates and varied by isolation site (38% acute otitis
media, 36% sinusitis, and 21% lower respiratory tract infections).
Regarding susceptibility, the rank order of the tested antimicrobials was
ceftriaxone = cefixime (100%) > cefpodoxime (99.6%) > ceftibuten =
amoxicillin/clavulanic acid (99.1%) > cefdinir (98.7%) > cefuroxime
(97.4%) > cefprozil (93.1%) > cefaclor (92.3%) > amoxicillin (63.1%).
The most active agents based on pharmacodynamic assessment (50%
fT>MIC) were cefpodoxime (98.9%), ceftibuten (95.3%), and high-dose
amoxicillin/clavulanic acid (90.4%). Several amoxicillin regimens also
achieved a high likelihood of pharmacodynamic target attainment
(91.8- 98.6%) when β-lactamase-positive strains were excluded from
the analysis.

Conclusion: Against H. influenzae, the antibacterials most likely to

achieve optimal in vivo exposures in children are cefixime,
cefpodoxime, ceftibuten, and amoxicillin/clavulanic acid.

Source: Pediatric Drugs, Volume 10, Number 6, 2008 , pp. 391-397(7)

Cefixime: an oral option for the treatment of multidrug-
resistant enteric fever in children

• Affiliation: Department of Pediatrics, Dow Medical

College, Civil Hospital, Karachi, Pakistan.
• BACKGROUND: Enteric fever is a serious public
health problem in Pakistan, where multidrug-resistant
salmonellosis causes enteric fever with increased
morbidity and mortality. Costly parenteral therapy and
lack of an established safety profile for the use of
quinolones in children necessitate evaluation of an oral
treatment option. This study is meant to assess the
efficacy, safety, and cost effectiveness of an oral third-
generation cephalosporin (cefixime) in the treatment of
multidrug-resistant enteric fever.
• CONCLUSIONS: Cefixime is a safe, effective, and
cheaper oral option for the treatment of multidrug-
resistant enteric fever. Further studies are needed,
however, to validate this observation.}
Cefixime for Switch Therapy
Jeremy Hamilton-Miller

Department of Medical Microbiology, Royal Free Hospital

School of Medicine, London, UK

Switch therapy, or step-down therapy, is the concept of

switching from an intravenous antibiotic to an oral
preparation after a few days, once the condition of the patient
has improved and the pathogen and its susceptibility have
been determined. The orally active third-generation
cephalosporin cefixime is a primary candidate for switch
therapy owing to its very good efficacy and safety profile.
Preliminary studies have shown excellent clinical outcomes
with switch therapy to cefixime after 2-3 days for a variety of
serious infections. Importantly, dramatic cost benefits have
also been found, particularly with respect to reduced length
of hospital stays.