Omeprazole, sold under the brand names Prilosec and Losec, among others, is a medication used in the treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease, and Zollinger–Ellison syndrome.It is also used to prevent upper gastrointestinal bleeding in people who are at high risk. Omeprazole is a proton-pump inhibitor (PPI) and its effectiveness is similar to other PPIs. It can be taken by mouth or by injection into a vein.
Common side effects include nausea, vomiting, headaches, abdominal pain, and increased intestinal gas.[1][9] Serious side effects may include Clostridium difficile colitis, an increased risk of pneumonia, an increased risk of bone fractures, and the potential of masking stomach cancer.[1] It is unclear if it is safe for use in pregnancy.[1] It works by blocking the release of stomach acid.[1]
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones
Omeprazole, sold under the brand names Prilosec and Losec, among others, is a medication used in the treatment of gastroesophageal reflux disease (GERD), peptic ulcer disease, and Zollinger–Ellison syndrome.It is also used to prevent upper gastrointestinal bleeding in people who are at high risk. Omeprazole is a proton-pump inhibitor (PPI) and its effectiveness is similar to other PPIs. It can be taken by mouth or by injection into a vein.
Common side effects include nausea, vomiting, headaches, abdominal pain, and increased intestinal gas.[1][9] Serious side effects may include Clostridium difficile colitis, an increased risk of pneumonia, an increased risk of bone fractures, and the potential of masking stomach cancer.[1] It is unclear if it is safe for use in pregnancy.[1] It works by blocking the release of stomach acid.[1]
Corticosteroids are a class of steroid hormones that are produced in the adrenal cortex of vertebrates, as well as the synthetic analogues of these hormones
Lecture slides for undergraduate MBBS class in Pharmacology on " Drugs for Diarrhoea" . It includes various treatment modalities which are used in the management of Diarrhoea. Basic source of information for preparing this slides is" Essentials of Pharmacology by KD tripathi, 7th Edition". Images are searched with the help of google images.
Antileprosy drugs have been described with their pharmacology also this topic covers Multidrug treatment for leprosy including paucibacillary and multibacillary leprosy and lepra reactions
Pharmacological Classification, Mechanism of Action, Clinical Uses, Administration Routes, Dosing for Adults and Pediatrics, Pharmacokinetics, Dose Adjustments, Patient Counseling, Adverse Effects, Drug Interactions, Contraindications, Personal Experience with Ondansetron, Future Clinical Uses of Ondansetron
This PPT covers drug therapy for tuberculosis. It includes classification of antitubercular drugs, chemotherapy for tuberculosis, strategies for addressing resistance and pharmacotherapy of antitubercular drugs
Lecture slides for undergraduate MBBS class in Pharmacology on " Drugs for Diarrhoea" . It includes various treatment modalities which are used in the management of Diarrhoea. Basic source of information for preparing this slides is" Essentials of Pharmacology by KD tripathi, 7th Edition". Images are searched with the help of google images.
Antileprosy drugs have been described with their pharmacology also this topic covers Multidrug treatment for leprosy including paucibacillary and multibacillary leprosy and lepra reactions
Pharmacological Classification, Mechanism of Action, Clinical Uses, Administration Routes, Dosing for Adults and Pediatrics, Pharmacokinetics, Dose Adjustments, Patient Counseling, Adverse Effects, Drug Interactions, Contraindications, Personal Experience with Ondansetron, Future Clinical Uses of Ondansetron
This PPT covers drug therapy for tuberculosis. It includes classification of antitubercular drugs, chemotherapy for tuberculosis, strategies for addressing resistance and pharmacotherapy of antitubercular drugs
Diarrhea is a very common daily based issue with lots of contributing factors. The need is to determine the underlying causes, otherwise the consequences may get worsen.
Fluid therapy in pediatrics/ oral dehydration solution/Dehydration.Haneen Hassan
Introduction.
Oral rehydration solution.
How to prepare ORS.
How to administer ORS.
How to give ORS.
Limitation of ORS.
Definition of Dehydration.
Degree of dehydration.
REVIEW OF LITERATURE AND SOURCES OF INFORMATIONAmeena Kadar
Different types of reviews of literature and it's sources are included in this PowerPoint. A review of the literature is an inevitable part of the research process.
GENETIC POLYMORPHISM IN DRUG METABOLISM.pptxAmeena Kadar
Genetic Polymorphism is one of the factors that affects the Drug metabolism. Cytochrome P - 450, one of the prominent group of metabolizing enzymes. In this ppt, genetic polymorphism of cytochrome p 450 is discussed.
Anemia is one of the most commonly seen condition predominantly in women due to various causes such as some chronic infection conditions and all. There are different types of anemias are there here we discuss mainly about Iron deficiency and sickle cell anemia.
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
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Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
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Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
2. It is an ―abnormal frequent passage of loose stools‖ or
―passage of stools with increased frequency, fluidity and
weight or increased stool water excretion.
It can range from an acute self limiting episode to
severe chronic illness.
According to WHO, it is 3 or more loose or watery stools
in a 24 hour period.
In pathological terms, it occurs due to passage of
excess water in faeces.
This may be due to:
•Decreased electrolyte and water absorption.
• Increased secretion by intestinal mucosa.
• Increased luminal osmotic load.
• Inflammation of mucosa and exudation into lumen.
3. PATHOPHYSIOLOGY
There are numerous causes of Diarrhoea, but in almost all cases, this
disorder is a manifestation of one of the 4 basic mechanisms are:
Osmotic Diarrhoea
Secretory Diarrhoea
Inflammatory and infectious Diarrhoea
Diarrhoea associated with Deranged motility.
5. TYPES OF DIARRHOEA
1. On the basis of Duration
Acute diarrhoea; Diarrhoea lasts for less than 14 days
Chronic diarrhoea; Diarrhoea lasts for more than 14 days.
2. On the basis of Clinical
Acute Watery diarrhoea; It lasts for several hours or days and occurs
in condition like cholera.
Acute Bloody diarrhoea; Diarrhoea with blood in stool, with or
without mucus is known as Dysentery.
DIAGNOSTIC EVALUATION
a) History : Number and description o stools per day, body weight,
fluid intake, frequency of urination etc.
b) Physical examination : To asses degree of dehydration.
c) Stool examination : Helps to identify Micro-orgamisms
d) Blood test : Hematocrit, BUN, WBC, serum sodium, serum
bicarbonate, serum chloride.
6. PRINCIPLES OF MANAGEMENT
Therapeutic measures may be grouped into:
(a) Treatment of fluid depletion, shock and acidosis.
(b) Maintenance of nutrition.
(c) Drug therapy
(d) Prevention of diarrhoea.
(a) Treatment of fluid depletion, shock and acidosis.
Rehydration
In majority of cases, this is the only measure needed. Rehydration can
be done orally or I.V.
Intravenous rehydration:
It is needed only when fluid loss is severe, i.e. > 10% body weight, (if
not promptly corrected, it will lead to shock and death) or if patient is
losing > 10 ml/kg/ hr, or is unable to take enough oral fluids due to
weakness, stupor or vomiting.
The recommended composition of i.v. fluid (Dhaka fluid) is:
NaCl 85 mM = 5 g
KCl 13 mM = 1 g
NaHCO3 48 mM = 4 g,
in 1L of Water or 5% of Glucose solution.
7. Volume equivalent to 10% BW should be infused over 2–4 hours; the
subsequent rate of infusion is matched with the rate of fluid loss.
In most cases, oral rehydration can be instituted after the initial volume
replacement.
Oral rehydration :
Advent of oral rehydration therapy (ORT) is considered a major advance of
recent times.
If the fluid loss is mild (5–7% BW) or moderate (7.5–10% BW) ORT can be
instituted from the very beginning.
Rationale of ORS composition
The sodium and water absorption by the small bowel is very much
enhanced by the addition of glucose to the oral fluid.
However, dehydration can be successfully treated with oral fluids
containing glucose, once the initial hypovolemia is corrected by 2-4 litres
of IV fluid replacement.
Mild to moderate dehydration and acidosis due to diarrhoea can be
corrected in 3-6 hours by oral therapy alone.
In many cases it is a lifesaving measure.
The treatment should continue even when diarrhoea is not controlled.
8.
9.
10. The ORT has many advantages:
(1) It is far less expensive than IV fluids.
(2) No expertise is needed to administer the fluid.
(3) The solution need not be sterile and can be prepared on spot with
components purchased from the local bazaar, and plain water available at
home.
(4) It can be given by family members and non-professionals as well as by
health workers.
It capitalizes on the intactness of glucose coupled Na+ absorption, even
when other mechanisms have failed or when intestinal secretion is excessive,
because the secreted fluid lacks glucose and cannot be reabsorbed.
The composition of oral rehydration salt/solution (ORS) has been debated.
The general principles are:
(a) It should be isotonic or somewhat hypotonic, i.e. total osmolarity 200–310
mOsm/L (diarrhoea fluids are approximately isotonic with plasma).
(b) The molar ratio of glucose should be equal to or somewhat higher than
Na+ (excess glucose will be utilized in absorbing Na+ present in the
intestinal secretions in addition to that present in ORS itself), but not exceed
110 mM.
(c) Enough K+ (15–25 mM) and bicarbonate/ citrate (8–12 mM) should be
provided to make up the losses in stool.
11. In 2002, a new formula low Na+ low glucose ORS was released by the WHO.
The new formula ORS has proven as effective and as safe in cholera as well,
but there is some risk of hyponatremia in adults with cholera.
The WHO and UNICEF have recommended replacement of standard (310
mOsm/L) ORS formula by the new (245 mOsm/L).
Reduced osmolarity ORS grams/litre Reduced osmolarity ORS mmol/litre
Sodium chloride 2.6 Sodium 75
Glucose, anhydrous 13.5 Chloride 65
Potassium chloride 1.5 Glucose, anhydrous 75
Trisodium citrate, dihydrate 2.9 Potassium 20
Citrate 10
Total Osmolarity 245
Potassium is an important constituent of ORS, since in most acute
diarrhoeas K+ loss is substantial.
The base (bicarbonate, citrate, lactate) is added to correct acidosis due to
alkali loss in stools.
It may independently promote Na+ and water absorption. However, relying
on the ability of the kidney to restore acid-base balance, acidotic states
have been managed without an exogenous base.
Base free ORS has been found to be equally effective in rehydrating, but
correction of acidosis is slower. Thus, there is a trend to consider base as a
nonessential constituent of ORS, but if present it may be beneficial,
especially in severe cases with over acidosis.
12. Administration of ORT :
Patients are encouraged to drink ORS at ½–1 hourly intervals.
Initially 5–7.5% BW volume equivalent is given in 2–4 hours (5 ml/kg/hr in
children). Thirst due to volume depletion provides an adequate driving
force.
In a weak child who refuses to drink ORS at the desired rate, it can be given
by intragastric drip; restoring hydration within 6 hours should be aimed.
ORT is not designed to stop diarrhoea, but to restore and maintain
hydration, electrolyte and pH balance until diarrhoea ceases, mostly
spontaneously.
Non-diarrhoeal uses of ORT :
(a) Post surgical, post burn and post-trauma maintenance of hydration and
nutrition (in place of I.V. infusion).
(b) Heat stroke.
(c) During changeover from intravenous to enteral alimentation.
Cereal-based oral rehydration solution (CORS):
Nature of ORS has provided foods containing starches such as cereals and
roots which have low osmolality in solution.
Studies have indicated that ORS in which rice and other food sources of
starch are substituted for glucose effectively replace lost fluids, decrease
vomiting, and reduce the severity of diarrhoea.
13. Glucose based ORS does not decrease and may slightly increase the stool
volume.
The cereal (rice) based solutions, on the other hand, are equally effective in
reducing volume losses, and may also shorten the duration of illness.
Rice contains a low molecular weight fraction which has a direct effect on
the chloride channel.
Physiologically, cereal-based ORS are identical to their glucose based
counterparts.
The dominant component in the cereals is starch from rice, corn, wheat,
potato, sorghum, millet or even plantain.
Starch is a large polymer of glucose that, on exposure to amylase in the
intestine, is digested into smaller polymers that are then split by maltase
into glucose at the intestinal brush border.
This digestive process supplies a larger number of glucose molecules for
transfer of sodium ions from lumen into the blood, while generating less
luminal osmotic ―back drag‖ than would the direct ingestion of an
equivalent amount of glucose.
The cereal proteins also provide small peptides and amino acids which also
facilitate the absorption of additional sodium ions.
Of course, the presence of sufficient digestive enzyme is essential for the
success of such solutions.
14. Zinc supplemented ORS:
Zinc supplementation is also considered as an adjunct therapy in diarrhea
because zinc maintains the GI mucosal integrity.
It is also imparts local immunity.
Deficiency of zinc has been shown to worsen diarrhea.
Moreover diarrhea itself leads to zinc deficiency.
Hence, UNICEF&WHO have proposed zinc supplemented ORS.
This ORS also has shown to reduce duration of diarrhea and the stool
frequency.
In children less than 6 month, 10 mg/day of zinc and for the older children
20 mg/day of zinc is advocated.
All children with acute diarrhoea should be given Zinc supplementation
along with ORS and continued for the next 10–14 days.
The mechanism of benefit of Zinc in diarrhoea is not known.
In vitro studies have suggested that Zinc could reduce fluid secretion in the
intestine by indirectly inhibiting cAMP dependent Cl¯ transport across the
mucosa through an action on the basolateral membrane K+ channels.
It could also strengthen the immune response and help regeneration of
intestinal epithelium.
Zinc can be administered to children by dissolving Zinc sulfate dispersible
tablets.
15. (b) Maintenance of Nutrition.
Contrary to traditional view, patients of diarrhoea should not be starved.
Fasting decreases brush border disaccharidase enzymes and reduces
absorption of salt, water and nutrients; may lead to malnutrition if diarrhoea
is prolonged or recurrent.
Feeding during diarrhoea has been shown to increase intestinal digestive
enzymes and cell proliferation in mucosa.
Simple foods like breast milk or ½ strength buffalo milk, boiled potato, rice,
chicken soup, banana, sago, etc. should be given as soon as the patient can
eat.
Avoiding fats, high fibre foods and alcohol generally improves patient
comfort.
(c) Drug Therapy.
Drugs used in diarrhoeas may be categorised into:
1. Specific antimicrobial drugs
2. Probiotics
3. Nonspecific antidiarrhoeal drugs.
4. Drugs for inflammaory bowel disease (IBD)
16.
17. 1. Antimicrobials in diarrhoea
One or more antimicrobial agent is almost routinely prescribed to most
patients of diarrhoea.
However, such drugs have a limited role in the overall treatment of
diarrhoeal diseases; the reasons are:
• Bacterial pathogen is responsible for only a fraction of cases.
• Even in bacterial diarrhoea, antimicrobials alter the course of illness only in
selected cases.
• Antimicrobials may prolong the carrier state.
Diarrhoea patients can be broadly placed in one of the two categories:
(a) Noninvasive diarrhoea:
Abundant watery diarrhoea lacking mucus or blood, usually dehydrating with
frequent vomiting, but little or no fever.
o These are generally caused by adhesive but noninvasive enterotoxigenic
bacteria such as cholera, ETEC, Salmonella enteritidis or by rota virus and
other viruses which stimulate massive secretion by activating cAMP in
intestinal mucosal cell.
o ORS and not antimicrobials are the main therapy.
(b) Invasive diarrhoea:
Slightly loose, smaller volume stools, frequently with mucus and/or blood,
mild dehydration, usually attended with fever and abdominal pain, but not
vomiting.
18. o These symptoms are indications of mucosal invasion, generally caused by
enteroinvasive organisms like Shigella, enteropathogenic E. coli (EPEC),
Campy. jejuni, Salmonella typhimurium, Yersinia enterocolitica, E.
histolytica, Clostri. difficile.
o Antimicrobials are needed in many of these.
A. Antimicrobials are of no value:
In diarrhoea due to non-infective causes, such as:
(i) Irritable bowel syndrome (IBS)
(ii) Coeliac disease
(iii) Pancreatic enzyme deficiency
(iv) Tropical sprue (except when there is secondary infection)
(v) Thyrotoxicosis.
Rotavirus is an important pathogen of acute diarrhoea, especially in children
in developed countries.
Along with other diarrhoea causing viruses, it is not amenable to
chemotherapy.
Salmonella food poisoning is generally a selflimiting disease.
Antibiotics have been widely used, but may be harmful rather than
beneficial.
19. B. Antimicrobials are useful only in severe disease (but not in mild cases):
Salmonella food poisoning is generally a selflimiting disease.
Antibiotics have been widely used, but may be harmful rather than
beneficialTreated patients have been found to pass organisms in stool for
longer periods than untreated patients.
However, very severe illness or that in infants/elderly or
immunocompromized patients may be treated with ciprofloxacin or
azithromycin or I.V. ceftriaxone.
Travellers’ diarrhoea: mostly due to ETEC, Campylobacter or virus:
cotrimoxazole, norfloxacin, doxycycline reduce the duration of diarrhoea
and total fluid needed only in severe cases.
Rifaximin It is a minimally absorbed oral rifamycin (related to rifampin)
active against E. coli and many other gut pathogens.
It is recently approved by US-FDA for the empiric treatment of travellers’
diarrhoea caused by non-invasive strains of E.coli.
A review of data from controlled trials using rifaximin 200 mg TDS for 3
days has rated it to be superior to placebo, and as effective as ciprofloxacin
in reducing duration of travellers’ diarrhoea, irrespective of whether the
causative pathogen was identified or not.
It has also been used in diarrhoeal phase of IBS as well as for prophylaxis
before and after gut surgery.
20. A higher strength (550 mg) tablet is marketed for reducing risk of hepatic
encephalopathy recurrence by suppressing NH3 forming gut bacteria.
The tolerability profile of rifaximin is similar to placebo.
Side effects are :
Flatulence
Abdominal pain
Defecation urgency
Headache.
Because of poor absorption, systemic toxicity is not expected.
Clinical experience with rifaximin is limited, and efficacy for empirical
treatment of diarrhoea is still to be convincingly established against local
strains of the bacteria.
EPEC: is less common, but causes Shigella like invasive illness.
Cotrimoxazole, or a fluoroquinolone or colistin may be used in acute cases
and in infants.
Shigella enteritis: only when associated with blood and mucus in stools may
be treated with ciprofloxacin or norfloxacin.
Cotrimoxazole and ampicillin are alternatives, but many strains are
resistant to these.
21. (iv)Non-typhoid Salmonella enteritis is often invasive; severe cases may be
treated with a fluoroquinolone, cotrimoxazole or ampicillin.
(v) Yersinia enterocolitica: common in colder places, not in tropics.
Cotrimoxazole is the most suitable drug in severe cases; ciprofloxacin is an
alternative.
23. Brief Description of Antimicrobial agents in Diarrhoea
Norfloxacin; A synthetic fluoroquinolone with broad-spectrum antibacterial
activity against most gram-negative and gram-positive bacteria.
MOA: The bactericidal action of Norfloxacin results from inhibition of the
enzymes topoisomerase II (DNA gyrase) and topoisomerase IV, which are
required for bacterial DNA replication, transcription, repair, and
recombination.
Ciprofloxacin; It is a second generation fluoroquinolone that has spawned
many derivative antibiotics.
It is formulated for oral, intravenous, intratympanic, ophthalmic, and otic
administration for a number of bacterial infections.
The first ciprofloxacin containing product was FDA approved on 22 October
1987.
MOA: Ciprofloxacin acts on bacterial topoisomerase II (DNA gyrase) and
topoisomerase IV.Ciprofloxacin's targeting of the alpha subunits of DNA
gyrase prevents it from supercoiling the bacterial DNA which prevents DNA
replication.
24. Ofloxacin;
.
A synthetic fluoroquinolone (fluoroquinolones) antibacterial
agent that inhibits the supercoiling activity of bacterial DNA gyrase, halting
DNA replication.
Rifaximin; It is a semisynthetic, rifamycin-based non-systemic antibiotic,
meaning that the drug will not pass the gastrointestinal wall into the
circulation as is common for other types of orally administered antibiotics.
It has multiple indications and is used in treatment of traveller's diarrhea
caused by E. coli; reduction in risk of overt hepatic encephalopathy
recurrence; as well as diarrhea-predominant irritable bowel syndrome (IBS-
D) in adult women and men.
It is marketed under the brand name Xifaxan by Salix Pharmaceuticals.
MOA: Acts by inhibiting RNA synthesis in susceptible bacteria by binding to
the beta-subunit of bacterial deoxyribonucleic acid (DNA)-dependent
ribonucleic acid (RNA) polymerase enzyme. This binding blocks translocation,
which stops transcription.
Cotrimoxazole ; It is used to treat certain bacterial infections, It also is
used to treat 'travelers' diarrhea.
Cotrimoxazole is a combination of trimethoprim and sulfamethoxazole and
is in a class of medications called sulfonamides.
25. MOA: Sulfamethoxazole inhibits bacterial synthesis of dihydrofolic acid by
competing with P-aminobenzoic acid(PABA). Trimethoprim blocks the
production of tetrahydrofolic acid from dihydrofolic acid by binding to and
reversibly inhibiting the required enzyme, dihydrofolate reductases.
Thus, it blocks the two consecutive steps in the biosynthesis of nucleic
acids and proteins essential to many bacteria.
Tetracycline ; It is a broad spectrum polyketide antibiotic produced by the
Streptomyces genus of Actinobacteria.
MOA: It exerts a bacteriostatic effect on bacteria by binding reversible to the
bacterial 30S ribosomal subunit and blocking incoming aminoacyl tRNA
from binding to the ribosome acceptor site. It also binds to some extent to
the bacterial 50S ribosomal subunit and may alter the cytoplasmic
membrane causing intracellular components to leak from bacterial cells.
Erythromycin ; It is a bacteriostatic antibiotic drug produced by a strain of
Saccharopolyspora erythraea (formerly Streptomyces erythraeus) and
belongs to the macrolide group of antibiotics which consists
of Azithromycin, Clarithromycin, Spiramycin and others.
It was originally discovered in 1952. Erythromycin is widely used for
treating a variety of infections, including those caused by gram-positive and
gram-negative bacteria.It is available for administration in various
forms, including intravenous, topical, and eye drop preparations.
26. MOA: Erythromycin acts by inhibition of protein synthesis by binding to the
23S ribosomal RNA molecule in the 50S subunit of ribosomes in susceptible
bacterial organisms. It stops bacterial protein synthesis by inhibiting the
transpeptidation/translocation step of protein synthesis and by inhibiting
the assembly of the 50S ribosomal subunit.
Metronidazole ; It is a commonly used antibiotic, belonging to the
nitroimidazole class of antibiotics. It is frequently used to treat
gastrointestinal infections as well as trichomoniasis and giardiasis, and
amebiasis which are parasitic infections. Metronidazole has been used as an
antibiotic for several decades, with added antiparasitic properties that set it
apart from many other antibacterial drugs, allowing it to treat a wide variety
of infections. It is available in capsule form, tablet form, and topical form,
and suppository preparations for the treatment of various infections.
MOA: The exact mechanism of action of metronidazole has not been fully
established, however, it is possible that an intermediate in the reduction of
metronidazole which is only made by anaerobic bacteria and protozoa,
binds deoxyribonucleic acid and electron-transport proteins of organisms,
blocking nucleic acid synthesis.
27. 2. Probiotics in diarrhoea
These are microbial cell preparations, either live cultures or lyophillised
powders, that are intended to restore and maintain healthy gut flora or have
other health benefits.
Diarrhoeal illnesses and antibiotic use are associated with alteration in the
population, composition and balance of gut microflora.
Recolonization of the gut by nonpathogenic, mostly lactic acid forming
bacteria and yeast is believed to help restore this balance.
Organisms most commonly used are— Lactobacillus sp., Bifidobacterium,
Streptococcus faecalis, Enterococcus sp. and the yeast Saccharomyces
boulardii, etc.
Several reviews and metaanalysis of clinical trials have suggested that
probiotics significantly reduce antibiotic-associated diarrhoea, acute
infective diarrhoea and risk of traveller’s diarrhoea.
While probiotics appear to be useful adjuncts to conventional therapy of
acute infectious diarrhoea, convincing evidence of their efficacy is lacking.
This prevents them from being accepted as a standard component of
diarrhoea therapy.
Stronger evidence of efficacy has emerged against antibiotic-associated
diarrhoea, but there is no justification yet for routine use of probiotics along
with antibiotics.
28. Natural curd/yogurt is an abundant source of lactic acid producing
organisms, which can serve as probiotic.
For all practical purposes, probiotics are safe, Infections and acidosis
caused by probiotics are very rare, though caution may be prudent in
immunocompromized patients.
29. Mechanism of Probiotics in the Treatment of Diarrhoea:
a. Protect the intestine by competing with pathogens for attachment.
b. Strenghthening tight junctions between enterocytes.
c. Enhancing the mucosal immune response to pathogens.
a
b
c
30. 3.Nonspecific antidiarrhoeal drugs
These drugs can be grouped into:
A. Absorbants and adsorbants
B. Antisecretory drugs
C. Antimotility drugs
A. Absorbants :
These are colloidal bulk forming substances like ispaghula, methyl
cellulose, carboxy methyl cellulose which absorb water and swell.
Modify the consistency and frequency of stools
But do not reduce the water and electrolyte loss.
They are of value in selected conditions like diarrhoea phase of IBS, and to
increase the consistency of faeces in colostomy patients.
Ispaghula and other bulk forming colloids are useful in both constipation
and diarrhoea phases of IBS and reduce abdominal pain as well.
Substances that do not ferment in colon are preferred for diarrhoea.
Adsorbants :
Like kaolin (Hydrated magnesium aluminiun silicate), pectin (Indigestable
carbohydrate), attapulgite (Magnesium aluminium phyllosilicate ), are
believed to adsorb bacterial toxins in the gut and coat/protect the mucosa.
They were ones very popular ingredients of diarrhoea remedies, but are
now banned in India, because there is no objective proof of their
efficacy.
31. B. Antisecretory drugs:
Racecadotril: This recently introduced prodrug is rapidly converted to
thiorphan, an enkephalinase inhibitor.
It prevents degradation of endogenous enkephalins (ENKs) which are mainly
δ opioid receptor agonists.
It decreases intestinal hypersecretion, without affecting motility (motility
appears to be regulated through μ receptors) by lowering mucosal cAMP
due to enhanced ENK action.
32. It is indicated in the short term treatment of acute secretory diarrhoeas.
In contrast to loperamide/diphenoxylate, it is not contraindicated in
children.
The elimination t½ as thiorphan is 3 hr.
Side effects are:
Nausea
Vomiting
Drowsiness
Flatulence
Dose: 100 mg (children 1.5 mg/kg) TDS for not more than 7 days.
Bismuth subsalicylate : Taken as suspension (60 ml 6 hourly) it is thought to
act by decreasing PG synthesis in the intestinal mucosa, thereby reducing
Cl¯ secretion.
They have an astringent, adsorbent and antimicrobial actions.
They are devoid of serious toxicity.
They also act against Helicobater pylori
It has some prophylactic value in travellers’ diarrhoea (probably due to weak
antibacterial action as well), but it is rather inconvenient to carry and take.
Anticholinergics : Atropinic drugs can reduce bowel motility and secretion,
but have poor efficacy in secretory diarrhoeas.
33. They may benefit nervous/drug (neostigmine, metoclopramide) induced
diarrhoeas and provide some symptomatic relief in dysenteries,
diverticulitis.
Octreotide : This somatostatin analogue has a long plasma t½ (90 min) as
well as potent antisecretory/ antimotility action on the gut.
It has been used to control diarrhoea in carcinoid and vasoactive intestinal
peptide (VIP) secreting tumours, and for refractory diarrhoea in AIDS
patients, but needs to be given by S.C. injection.
C. Antimotility drugs:
These are opioid drugs which increase small bowel tone and segmenting
activity, reduce propulsive movements and diminish intestinal secretions
while enhancing absorption.
They afford only symptomatic relief in diarrhoea.
The major action appears to be mediated through µ opioid receptors
located on enteric neuronal network, but direct action on intestinal smooth
muscle and secretory/ absorptive epithelium has also been demonstrated.
The δ receptors are believed to promote absorption and inhibit secretion,
while the μ receptors enhance absorption and decrease propulsive
movements.
They increase resistance to luminal transit and allow more time for
the absorptive processes.
34. Codeine; This opium alkaloid has prominent constipating action at a dose
of 60 mg TDS.
The antidiarrhoeal effect is attributed primarily to its peripheral action on
small intestine and colon.
It does have central effects, but dependence producing liability is low.
Side effects are:
Nausea
Vomiting
Dizziness.
Diphenoxylate :(2.5 mg) + atropine (0.025 mg):
Dose: 5–10 mg, followed by 2.5–5 mg 6 hourly.
It is a synthetic opioid, chemically related to pethidine; used exclusively as
constipating agent; action is similar to codeine.
The antidiarrhoeal action is most prominent, but because it is absorbed
systemically and crosses blood-brain barrier—CNS effects do occur.
Atropine is added in subpharmacological dose to discourage abuse by
taking several tablets.
Abuse liability is rated low, and overdose will produce disturbing atropinic
side effects.
It has caused respiratory depression, paralytic ileus and toxic megacolon in
children.
Contraindicated below 6 years of age.
35. Loperamide : It is an opiate analogue with major peripheral µ opioid and
additional weak anticholinergic property.
As a constipating agent it is much more potent than codeine.
Because of poor water solubility—little is absorbed from the intestines.
Entry into brain is negligible—CNS effects are rare and occur only with high
doses; no abuse liability.
Duration of action is longer (12 hr).
It also inhibits secretion.
Loperamide inhibits peristaltic activity by a direct effect on the circular and
longitudinal muscles of the intestinal wall. It is a non-selective calcium
channel blocker and binds to opioid mu-receptors.
Direct interaction with calmodulin may be responsible for the antidiarrhoeal
action.
Adverse effects: Abdominal cramps and rashes
Paralytic ileus, toxic megacolon with abdominal distension is a serious
complication in young children—fatalities have occurred, probably due to
absorption of toxins from the intestines.
It is contraindicated in children < 4 yr.
Most effective and most suitable of the antimotility antidiarrhoeal drugs.
Use in non infective diarrhoea & mild traveller’s diarrhoea.
36. Contraindicated in infective diarrhoea-delay the clearance of pathogen.
Careful use in mild IBD.
Can be used to induce short term constipation eg; after anal surgery, reduce
the volume, fluidity and bag cleaning frequency in ileostomy/colostomy
patients.
4. Drugs for inflammatory bowel disease (IBD)
IBD is a chronic relapsing inflammatory disease of the ileum, colon, or both,
that may be associated with systemic manifestations.
It is idiopathic.
The two major types of IBD are:
Ulcerative colitis (UC) - colon
Crohn’s disease (CrD) – any part of the GIT.
The drugs used in UC and CrD are the same, but their roles and efficacy do
differ.
Drugs used in IBD can be grouped into:
5-Amino salicylic acid (5-ASA) compounds
Corticosteroids
Immunosuppressants
TNFα inhibitors.
37. 5-Amino salicylic acid (5-ASA) compounds :
Sulfasalazine (Salicylazosulfapyridine) : It is a compound of (5-ASA) with
sulfapyridine linked through an azo bond, and has a specific therapeutic
effect in IBD.
Low solubility, it is poorly absorbed from the ileum.
The azo bond is split by colonic bacteria to release 5-ASA and sulfapyridine.
The former exerts a local antiinflammatory effect, the mechanism of which is
not clear.
Though it inhibits both COX and LOX, decreased PG and LT production
appears to play a minor role in the therapeutic effect.
Inhibition of cytokine, PAF, TNFα and nuclear transcription factor (NFκB)
generation seems to be more important.
38.
39. A dose of 3–4 g/day induces remission over a few weeks in many patients,
but relapses are common after stoppage.
Maintenance therapy with 1.5–2 g/day has been found to postpone relapse
in majority, but not all cases.
The primary value of sulfasalazine is in maintaining remission in UC, but
not in CrD, while corticosteroids are reserved to treat acute exacerbations.
The sulfapyridine moiety only serves to carry 5-ASA to the colon without
being absorbed proximally.
However, most of the released sulfapyridine is absorbed in the colon and is
responsible for adverse effects like rashes, fever, joint pain, haemolysis and
blood dyscrasias.
Nausea, vomiting, headache, malaise and anaemia are other frequent dose
related side effects.
Oligozoospermia and male infertility is reported.
It interferes with folate absorbtion.
Folic acid supplementation should always be given during its use.
Sufasalazine has also been used as a disease modifying drug in rheumatoid
arthritis.
The absorbed sulfapyridine moiety appears to be responsible for the
therapeutic effect.
40. Mesalazine (Mesalamine) :
5-ASA compound.
Primary use in preventing relapse of UC.
Not effective orally.
Better tolerated.
Side effects:
Nausea
Abdominal pain
Nephrotoxic
Enhance the gastric toxicity of corticosteroids and hypoglycemic action of
sulfonylureas.
MOA :
The MOA of mesalazine is not fully understood, it is believed to possess a
topical anti-inflammatory effect on colonic epithelial cells.
Mucosal production of arachidonic acid metabolites, both through the
cyclooxygenase pathways, i.e., prostanoids, and through the lipoxygenase
pathways, i.e., leukotrienes and hydroxyeicosatetraenoic acids, is increased
in patients with chronic inflammatory bowel disease, and it is possible that
mesalazine diminishes inflammation by blocking cyclooxygenase and
inhibiting prostaglandin production in the colon.
41. It also has the potential to inhibit the activation of Nuclear Factor kappa B
(NKkB) and consequently the production of key of pro-inflammatory
cytokines.
It has been proposed that reduced expression of PPAR gamma nuclear
receptors (gamma form of peroxisome proliferator-activated receptors)
may be implicated in ulcerative colitis.
There is evidence that mesalazine produces pharmacodynamic effects
through direct activation of PPAR gamma receptors in the colonic/rectal
epithelium as well.
Increased leukocyte migration, abnormal cytokine production, increased
production of arachidonic acid metabolites, particularly leukotriene B4, and
increased free radical formation in the inflamed intestinal tissue are all
present in patients with inflammatory bowel disease it is also believed that
mesalazine has in-vitro and in-vivo pharmacological effects that inhibit
leukocyte chemotaxis, decrease cytokine and leukotriene production and
scavenge for free radicals.
42.
43. Olsalazine : It consists of two molecules of 5-ASA coupled together by azo
bond.
Poorly absorbed in the ileum.
Balsalazide : This is 5-ASA linked to 4-aminobenzoyl-β-alanine as the
carrier which, unlike sulfapyridine, is inert.
The 5-ASA is released in the colon, and the carrier is poorly absorbed.
It can be used as a safer alternative to sulfasalazine.
Corticosteroids :
Prednisolone:
40-60mg/day effective in controlling remission in both UC and CD.
Symptomatic relief starts within 3-7 days and remission is induced in 2-3
weeks.
In severe cases with systemic manifestations I.V. Methylprednisolone 40-
60mg 12 to 24 hourly for few days.
Hydrocortisone enema or foam can be used for topical treatment of
proctitis.
44. Generally used for short term
Neither effective nor suitable for maintaining remission.
Immunosuppressants :
Long-term management of IBD, especially CrD.
Azathioprine:
Purine antimetabolite
Indicated in steroid resistant, steroid dependent and severe cases of IBD.
Side effects bone marrow hyper sensitivity.
Dose 1.5-2mg/kg/day.
Methotrexate :
Dihydrofolate reductase inhibitor.
Acts faster than azathioprine
Doses effective in IBD are higher than those for RA.
Weekly parenteral therapy is needed
Toxicity is more.
45. Cycloserine:
Potent immunosuppresant used in UC.
I.V. cycloserine usually controls symptoms in 7-10 days, bridge therapy for
2-3 months till azathioprine takes effects.
Renal toxicity
Poor efficacy in IBD.
TNF alpha inhibitors:
Infliximab, Adalimumab, Certolizumab :
Indicated in severe active CrD, fistulating CrD and severe UC.
Infused every 2-8 weeks, it decreases acute flareups and helps in fistula
closure.
46.
47. REFERENCES:
Essentials of Medical Pharmacology by K D Tripathi , 8th edition, Page
No.727-737.
Pharmacology & Pharmacotherapeutics by R.S Satoskar ,Nirmala N. Rege,
S.D. Bhandarkar , 24th edition , Page No. 925-935.
Lippincott Illustrated Reviews Pharmacology by Karen Whalen , 7th
edition , Page No.1560-1564 .