This document discusses the pharmacotherapy of inflammatory bowel disease (IBD). IBD includes two major subtypes, ulcerative colitis and Crohn's disease, which are characterized by chronic inflammation of the intestinal tract. Treatment aims to induce and maintain remission of symptoms. First-line therapies include 5-aminosalicylic acid drugs and glucocorticoids. For cases that are steroid-dependent or resistant, immunosuppressants like azathioprine and anti-TNFα antibodies such as infliximab are used. Supportive care involves nutritional supplementation, antidiarrheals, and in severe cases of Crohn's, total parenteral nutrition may be given.
Drugs for treatment of Diabetes MellitusNaser Tadvi
These slides contain the brief description of Insulin and the other oral drugs indicated in the treatment of Diabetes Mellitus. Their mechanism of action, effects, uses, Adverse effects etc.
Drugs for treatment of Diabetes MellitusNaser Tadvi
These slides contain the brief description of Insulin and the other oral drugs indicated in the treatment of Diabetes Mellitus. Their mechanism of action, effects, uses, Adverse effects etc.
Sulfonyl ureas pharmacology Presented by arjumandPARUL UNIVERSITY
Sulfonylureas are most commonly used Oral Hypoglycemic drugs helpful in treating Diabetes Mellitus .
They show their effects on beta cells of the pancreas to release insulin which maintains the blood sugar level.
They are also called as ATP sensitive Potassium[K] channel blockers
Sulfonylureas for Diabetes: A deep insightRxVichuZ
This powerpoint presentation solely deals with Sulfonylureas, that come under Insulin secretagogues. Their complete pharmacological profile, with pharmacovigilance parameters, important catchpoints and mnemonics have been explained.
Prokinetics are the type of drugs which enhances gastrointestinal motility/transit by
increasing the frequency or strength of contractions.
They speed up gastric emptying by enhancing coordinated propulsive motility.
Treat Gastrointestinal symptoms : Abdominal discomfort, Bloating, constipation,
Heart burn, nausea and vomiting. And few gastrointestinal disorders : irritable bowel
Syndrome, gastritis, gastroparesis and functional dyspepsia.
Increases gastric emptying
Relief of gastric stasis
Decreases reflux esophagitis/heart burn
Decreases regurgitation of gastric contents& emesis
Sulfonyl ureas pharmacology Presented by arjumandPARUL UNIVERSITY
Sulfonylureas are most commonly used Oral Hypoglycemic drugs helpful in treating Diabetes Mellitus .
They show their effects on beta cells of the pancreas to release insulin which maintains the blood sugar level.
They are also called as ATP sensitive Potassium[K] channel blockers
Sulfonylureas for Diabetes: A deep insightRxVichuZ
This powerpoint presentation solely deals with Sulfonylureas, that come under Insulin secretagogues. Their complete pharmacological profile, with pharmacovigilance parameters, important catchpoints and mnemonics have been explained.
Prokinetics are the type of drugs which enhances gastrointestinal motility/transit by
increasing the frequency or strength of contractions.
They speed up gastric emptying by enhancing coordinated propulsive motility.
Treat Gastrointestinal symptoms : Abdominal discomfort, Bloating, constipation,
Heart burn, nausea and vomiting. And few gastrointestinal disorders : irritable bowel
Syndrome, gastritis, gastroparesis and functional dyspepsia.
Increases gastric emptying
Relief of gastric stasis
Decreases reflux esophagitis/heart burn
Decreases regurgitation of gastric contents& emesis
Irritable Bowel Syndrome (IBS) and Fecal Microbiota Transplant. A new hope fo...Find Good Health
IBDs including irritable bowel syndrome (ibs) or ulcerative colitis (uc) are a set of diseases developing into an epidemic. The unusual and recent rise in these kind of diseases most notably on developed countries point to a recent and area specific etiology, not a better healthcare and diagnosis.
Recent researchs are pointing to a healthier immune system and intestinal flora in undeveloped countries' population and an imbalance in our gut flora caused by excessive use of antibiotics.
For more information about health and wellbeing visit our site at:
http://findgoodhealth.org/
Detecting Early Liver Fibrosis - A Nutshell for Primary CareJarrod Lee
This presentation summarizes the latest technologies for detecting early liver fibrosis and their role in healthcare today. It is aimed at primary care doctors, to help them better utilize these new developments for their patients.
inflammatory bowel disease is a diagnosis of exclusion and it has two form known as crohn's disease which can affect all GI tract from ''gum to bum'' with skip lesion and the formation of cobblestones. ulcerative colitis affect only the colon and also causes proctitis and toxic megacolon. both of the disease has extraGI symptoms like sclerosing cholangitis, uveitis, ankylosing spondylitis,conjunctivitis, liver cirrhosis, pyoderma gangrenosum, arthropathy and althralgia, etc .
Understant what is obesity and Bariatric Surgery, what are the risk factors and how to overcome on the it. For more information visit at http://gisurgery.info
This presentation comprises of various chemotherapeutic agents used in ENT malignancies and other conditions. Its classifies the agents and briefly discusses the dosage and their common side effects.
All diabetics irrespective of other treatment require some control of their eating and exercise patterns
Dibetics must watch their
- total caloric intake
-types of nutrients and eating schedule
50% of patients may require only diet Another 25% would need to augment their natural insulin with drugs
while the remainder will need insulin
Diet recommendations include
- discouraging fats
encouraging complex carbohydrate and fibre
The recommended diabetic diet except in a few respects is now similar to the normal healthy diet that everyone should eat. i.e regular meals, low in fats, low simple sugars, low in sodium and high in complex carbohydrate (starch) and fibre
Diet recommendations include
- discouraging fats
encouraging complex carbohydrate and fibre
The recommended diabetic diet except in a few respects is now similar to the normal healthy diet that everyone should eat. i.e regular meals, low in fats, low simple sugars, low in sodium and high in complex carbohydrate (starch) and fibre
Diet recommendations include
- discouraging fats
encouraging complex carbohydrate and fibre
The recommended diabetic diet except in a few respects is now similar to the normal healthy diet that everyone should eat. i.e regular meals, low in fats, low simple sugars, low in sodium and high in complex carbohydrate (starch) and fibre Diet recommendations include
- discouraging fats
encouraging complex carbohydrate and fibre
The recommended diabetic diet except in a few respects is now similar to the normal healthy diet that everyone should eat. i.e regular meals, low in fats, low simple sugars, low in sodium and high in complex carbohydrate (starch) and fibre
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
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Title: Sense of Taste
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 structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
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.
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.
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
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.
Acute scrotum is a general term referring to an emergency condition affecting the contents or the wall of the scrotum.
There are a number of conditions that present acutely, predominantly with pain and/or swelling
A careful and detailed history and examination, and in some cases, investigations allow differentiation between these diagnoses. A prompt diagnosis is essential as the patient may require urgent surgical intervention
Testicular torsion refers to twisting of the spermatic cord, causing ischaemia of the testicle.
Testicular torsion results from inadequate fixation of the testis to the tunica vaginalis producing ischemia from reduced arterial inflow and venous outflow obstruction.
The prevalence of testicular torsion in adult patients hospitalized with acute scrotal pain is approximately 25 to 50 percent
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
NVBDCP.pptx Nation vector borne disease control programSapna Thakur
NVBDCP was launched in 2003-2004 . Vector-Borne Disease: Disease that results from an infection transmitted to humans and other animals by blood-feeding arthropods, such as mosquitoes, ticks, and fleas. Examples of vector-borne diseases include Dengue fever, West Nile Virus, Lyme disease, and malaria.
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
3. Montreal classification of IBD
• Ulcerative colitis
1. Ulcerative proctitis
2. Left sided UC (distal UC)
3. Extensive UC (pancolitis)
• Crohn’s Disease (acc. to location)
1. Ileal
2. Colonic
3. Ileocolonic
4. Isolated upper GI disease
4. Etiology
• IBD is currently considered an inappropriate immune
response to the endogenous commensal microbiota within
the intestines
• Factors involved are:
Defective immune regulation
Genetic mutations
Exogenous factors
6. Genetics
•About 100 genetic loci have been
identified
e.g. NOD2 and CCR6
•Many of these muatations are
shared between UC and CD
e.g. JAK2 & IL-23R
•Many loci are also associated with
risk of other diseases like
rheumatiod arthritis and psoriasis
7. Exogenous factors
IBD may be triggered by microbes like
Bacteriodes, Clostridium difficile & E.coli
• This is proved by presence of antibodies
against them e.g. Presence of E.coli
OMP2 antibodies & ASCA
Body may also react against normal
flora
• This is supported by improvement in
symptoms by antibiotics
Psychosocial factors(major life events,
daily stress)
Cause worsening of symptoms
8. Clinical features
Ulcerative colitis
Cardinal symptom is bloody diarrhoea
With colicky abdominal pain, urgency or tenesmus
50% patients experience relapse at least once
Crohn’s disease
Abdominal pain, diarrhoea and weight loss
Systemic symptoms- malaise, fever, anorexia- more common
70-80% of patients require surgery during their lifetime
9. Feature Ulcerative colitis Crohn’s disease
Involvement of GIT Large bowel Any part of GIT
Rectal involvement Frequent Rare
Inflammation Superficial Transmural
Skip areas Absent Present
Ulcers
If present-
Superficial
Deep, serpiginous
Fissures & Fistulae Less comon Very common
Histology
Infiltration is mainly
neutrophilic
Presence of
granulomas
diagnostic; infiltration
mainly lymphocytic
Smoking Protective
Predicts a worse
course
10. Aims of Treatment
Induce remission
Maintain remission
Prevent complications
Maintain nutritional status
Improve quality of life
11. Drugs used in treatment
1. 5-ASA based therapy
2. Glucocorticoids
3. Immunosupressants
4. Anti- TNFα therapy
5. Antibiotics
12. 5-Amino Salicylic Acid
(Meselamine) based therapy
• First-line therapy for mild to moderate UC and
Crohn’s colitis
• Effective in inducing remission in both UC and CD
• Effective in maintenance of remission in UC
13. Mechanism of action
• Not related to COX inhibition
• Its various mechanisms are :
1. Inhibiting IL-1 and TNF-α production
2. Inhibiting Lipo-oxygenase pathway
3. Scavenging of free radicals
4. Inhibiting of NF-κB via PPAR-γ
14. Sulfasalazine
•Azo bond prevents absorption in stomach and small bowel
• Broken down in colon by bacterial azo reductase
•Dose: 3 - 6 g/day for active disease
2 - 4 g/day for maintenance
15. Pharmacokinetics
• 20 to 30% absorbed in the small intestine, which is excreted
unchanged
• 70% reaches the colon
• Splits to release 5-ASA and sulfapyridine
• Generates 400 mg meselamine for every gram of parent
compound
• The sulfapyridine moiety is highly lipid soluble
• It is completely absorbed and undergoes acetylation &
glutathione conjugation
16. Adverse effects
• Primarily due to sulfapyridine
Dose related: Headache, fatigue, nausea
Allergic reactions: Rash, Steven-Johnson syndrome, hepatitis,
bone marrow suppression
Decrease in sperm number and motility: reversible
Nephrotoxicity: Risk of interstitial nephritis, hence renal
function should be monitored
17. 2nd Generation 5-ASA compounds
Higher doses of meselamine can be used with less side
effects
Prodrugs - Contain the same Azo bond but sulfapyridine is
replaced by
Another 5-ASA – Olsalazine
An inert compound (4-
aminobenzoyl- β- alanine)-
Balsalazide
18. Asacol : Enteric-coated form of meselamine
• 5-ASA is liberated at pH > 7
• Site of release: Terminal ileum and colon
• Dose: 2.4–4.8 g/ day (acute)1.6–4.8 g/ day (maintenance)
• Lialda: MMX (Multi-matrix) Technology
• Encloses 5-ASA inside a lipophilic matrix within a hydrophilic
matrix
• It is further encapsulated by a pH-sensitive polymer which
releases drug at pH > 7
• Dose: 2.4–4.8 g/ day
Coated drugs
19. Pentasa: Sustained release formulation of 5 – ASA.
• Disintegration of capsule occurs in the stomach and the
microspheres then disperse throughout the entire GIT
• Ethylcellulose coating to allow water absorption into the small
beads containing the mesalamine
• Water dissolves the 5-ASA, which then diffuses out of the
bead into the lumen
21. Topical 5-ASA formulations
Rowasa:
• Mesalamine suspended in a wax matrix suppository
• Effective in active proctitis
Canasa
• Mesalamine suspended in a suspension enema
• Effective in distal ulcerative colitis
• Advantages: Superior to topical hydrocortisone with 70-
90%response rates
22. Glucocorticoids
• Indication: Moderate to severe IBD
• Not effective in maintenance of remission in either Ulcerative
colitis or Crohn’s disease
• Once remission has been induced they should be tapered very
gradually over many weeks
• According to their response to steroids, patients can be
divided into 3 classes:
1) Steroid-responsive - 40 %
2) Steroid-dependent - 30 – 40 %
3) Steroid-unresponsive - 15 – 20 %
23. Antibiotics
• Metronidazole, Ciprofloxacin and Clarithromycin
• Ulcerative colitis: Antibiotics have no role except in pouchitis
• Crohn’s Disease:
a. For active inflammatory, perianal and fistulizing disease:
Metronidazole - 15-20 mg/kg/day in 3 divided doses OR
Ciprofloxacin – 500 mg BD
b. For preventing post-op recurrence – Metronidazole
• Adverse effects
• Metronidazole- Nausea,metallic taste, peripheral neuropathy
• Ciprofloxacin: Achilles tendinitis and rupture
24. • Oral Prednisolone: 40- 60 mg/day for active UC not
responding to 5-ASA therapy
• Parenteral (i.v.) drugs: in more severe disease
Hydrocortisone: 300 mg/day
Methylprednisone: 40-60 mg/day
• Adverse effects:
Weight gain, fat redistribution, hyperglycemia, cataract,
Emotional changes, osteoporosis, aseptic osteonecrosis
25. • Enemas: useful in patients whose disease is limited to the
rectum (proctitis) and left colon.
• Hydrocortisone is available as a retention enema (100
mg/60 ml),
• Usual dose is one 60-ml enema per night for 2 or 3
weeks.
• Hydrocortisone also can be given once or twice daily as a
10% foam suspension → delivers 80 mg hydrocortisone
per application
• Useful in patients who have difficulty retaining the
enema fluid
Topical steroids
26. • Controlled ileal-release preparation
• Equally efficacious to prednisone for ileocolonic CD
• Topical potency 200 times that of hydrocortisone
• Undergoes extensive first-pass metabolism (10% oral
bioavailability) hence has fewer systemic side effects
• Topical therapy (e.g. enemas and suppositories) also is
effective in treating colitis limited to the left side of the colon.
• Dose: 9 mg/day for 2 to 3 months in mild to moderate Crohn’s
Disease
• Its role in maintenance of remission is not yet determined
Budesonide
28. Azathioprine & 6- Mercaptopurine
• Purine analogs; both are prodrugs
• Mechanism of action: Impair purine biosynthesis & inhibit cell
proliferation
• Treatment of steroid-dependent and steroid- resistant disease
• Uses:
a. Maintain remission in both UC and Crohn’s disease
b. To prevent/delay recurrence of Crohn’s disease after surgical
resection
c. To treat fistulas in Crohn’s disease
30. • Differences in TPMT (ThioPurine Methyl Tranferase)
determine the drug’s fate
• Metabolism shifted towards 6-
thioguanine nucleotides
• Bone marrow suppression
• Weekly monitoring of CBC
Patients with
minimal
TPMT activity
• Metabolism shifted towards 6-MMP
• Hepatotoxicity and reduced
therapeutic response
• LFT monitoring done
Rapid
metabolizers
31. Drug interactions
• Inhibition of Xanthine oxidase by allopurinol diverts
metabolism towards production of 6-thioguanine analogs
• Augments the risk of immunosuppression
• Hence patients on mercaptopurine should be warned about
serious interactions with medications used to treat gout and
hyperuricemia
• If the patient is already taking allopurinol
dose decreased to 25% of standard dose
32. Adverse reactions
Idiosyncratic
• Pancreatitis
• Fever, rash
• Arthralgia
• Nausea,
vomiting
Dose-related
• Suppression
of bone
marrow
• Elevation of
liver enzymes
Serious ADRs
• Cholestatic
hepatitis
• Malignancies
like non-
Hogdkin’s
lymphoma
33. Methotrexate
• Mechanism of action:
Impaired DNA synthesis due to Dihydrofolate reductase
inhibition
Decreased IL-1 production
• Use: Induce & maintain remission in Crohn’s disease
• Response is rapid han that seen with thiopurines
• Dose: given by i.m. or s.c. route
For induction: 25mg/week
To maintenance: 15 mg/week
34. Adverse reactions
• GI toxicity: nausea, vomiting, diarrhoea, stomatitis
Minimized by concurrent administration of folic acid
5mg once weekly
• Hepatotoxicity : Periodic evaluation of liver enzymes
• Leucopenia : Periodic evaluation of CBC
• Pneumonitis
35. Cyclosporine
• Use:
Severe ulcerative colitis that has failed to respond adequately
to steroids
To treat fistulas in Crohn’s disease
• Mechanism of action:
Binds to cyclophilin; the complex then inhibits calcineurin
Ultimately inhibits activation of T-cells and production of IL-2
36. Adverse reactions
Hypertension, gingival hyperplasia, hypertrichosis,
Paresthesias, tremors, headaches
Nephrotoxicity - renal function should be monitored
frequently.
Seizures
Opportunistic infections
37. Tacrolimus
Macrolide antibiotic
MOA - similar to cyclosporine.
Effective in adults with steroid refractory UC and CD
As compared to cyclosporine
• 100 times more potent.
• Have good oral absorption despite proximal small-bowel
Crohn's involvement.
40. Infliximab
Chimeric IgG1 antibody (25% mouse, 75% human)
Mechanism : Binds to membrane-bound TNF-α and causes
cell lysis by antibody-dependent or cell-mediated cytotoxicity
Effective in
1) active CD patients refractory to steroids and thiopurines
2) CD patients with refractory enterocutaneous fistulas
3) Moderate to severe ulcerative colitis
Dose: 5mg/kg i.v. infusion every 8 weeks
41. Adverse reactions
Acute - fever, chills, urticaria, or even anaphylaxis.
Subacute - serum sickness-like reaction.
Increased incidence of respiratory infections - tuberculosis or
other granulomatous infections.
Contraindicated in patients with severe congestive heart
failure (NYHA classes III and IV) .
Possible increased incidence of non-Hodgkin's lymphoma,
leukemia and new-onset psoriasis
42. Antibody formation
Antibodies develop in 10% of patients
Leads to increased risk of infusion reactions and loss of
response
Strategies to minimize the development of these antibodies -
Treatment with glucocorticoids or other immunosuppressives.
Increasing the dose of infliximab (10 mg/kg).
Decreasing the interval between infusions.
43. Adalimumab
• Recombinant human monoclonal IgG1 antibody.
• Binds TNF- α and neutralizes its function by blocking
the interaction between TNF and its cell-surface
receptor.
• Injected subcutaneously.
• Less immunogenic than infliximab.
• Used in active CD patients refractory to steroids and
thiopurines
44. Certolizumab pegol
• Human monoclonal antibody Fab conjugated with PEG
• Does not contain Fc fragment
• Mechanism of action:
a) Inhibits monocyte cytokine production
b) Inhibits mast cell degranulation
• Effective for induction of clinical response in patients with
active inflammatory CD.
• Less immunogenic than infliximab
• Given by s.c. route once monthly
46. • Approved for induction & maintenance of remission in
crohn’s disease
• Especially useful in patients who are refractory or
intolerant to anti- TNFα therapy
• Adverse effects:
Leads to Progressive Multifocal Leucoencephalopathy
(PML)
Hence its use is contraindicated with other immuno-
suppressive drugs- Thiopurines & steroids
47. Supportive therapy
• Iron, calcium and Vitamin D supplementation given in
case of deficiency
• Oral folate routinely given to patients receiving 5-ASA
therapy
• Vitamin B12 serum levels measured annually in case of
ileal Crohn’s
48. Anti- diarrheal agents (Loperamide, Diphenoxylate) & anti-
cholinergic drugs (Dicyclomine)
• To reduce frequency of bowel movements
• To relieve rectal urgency
• Contraindicated in severe disease or suspected obstruction:-
can predispose to toxic megacolon
Bile salt binders (Cholestyramine, Colesevalam)
• Prevent bile-salt induced diarrhea in patients with ileo-colic
resection
49. Nutritional therapy
• Patients with active Crohn’s: Respond to bowel rest and Total
Parenteral Nutrition (TPN)
• As effective as steroids in inducing remission but not for
maintenance
• Enteral nutrition in the form of elemental or peptide-based
preparations are also as effective as glucocorticoids or TPN -
not palatable.
• Dietary intervention has no role in ulcerative colitis
50. Prebiotics
• Non-digestable carbohydrates such as fructo-oligosaccharides
• Broken down by gut flora to short-chain fatty acids
• Their efficacy is unproven till date
Probiotics
• Bacteria or yeast ingested orally as therapy
• Administered as a single organism or as a defined mixture
51. • Mechanism of action:
a) Production of bacteriocins
b) Production of butyrate, necessary for colonocyte
function
c) Ability to downregulate inflammation
• Examples:
• A combination product VSL #3 prevents recurrent
pouchitis
• E. coli Nissle- Equivalent to meselamine in
maintaining remission in UC
52. IBD and Pregnancy
Effect of IBD on fertility:
1. Scarring of fallopian tubes- either
due to involvement of terminal
ileum or as a sequalae of pouch
surgery
2. Dyspareunia- due to perirectal
and perianal abscess and fistulae
3. Decreased sperm count-
secondary to 5-ASA therapy; it is
reversible
53. Effect of IBD on Pregnancy:
1. In mild or quiescent disease, fetal outcome is nearly normal
2. Spontaneous abortions, stillbirths, and developmental
defects are increased with increased disease activity, not
medications. Hence any flare-up is treated aggressively
3. Patients should be in remission for 6 months before
conceiving
4. Most patients of CD can deliver vaginally but C-section is
preferred in case of anorectal and perirectal abcess/ fistulae.
54. Safety of drugs
5-ASA based therapy
• FDA category B drugs
• Oral Sulfasalazine, Meselamine, Balsalazide & Topical 5-
ASA agents- Safe for use in pregnancy and breast-
feeding
• Additional folate supplementation is given- 2mg/day
55. Glucocorticoids
• FDA category C drug
• Generally considered safe in pregnancy
• Indicated for patients with moderate to severe disease
activity
• Are secreted in breast milk in minute amounts and do
not have any significant effect on the nursing infant
56. Antibiotics
• Safest antibiotics to use for short periods of time (for few
weeks)- Ampicillin and Cephalosporins
• Metronidazole can be used after 1st trimester
• Ciprofloxacin (FDA category C drug) should be avoided
• Tetracyclines - Contraindicated
57. Thiopurine drugs
• FDA category D drugs
• Pose minimal risk during pregnancy
• Secreted in negligible amounts in breast milk; pose minimal
risk to the infant
• Scenarios for use:
a) If the patient cannot be weaned from the drug
b) In case of an exacerbation which requires these drugs
58. Cyclosporine A
• FDA Category C drug
• Very limited data on its use in pregnancy
• Avoided unless the patient requires surgery
Methotrexate
• Teratogenic and hence absolutely contraindicated
59. Anti- TNFα drugs
• FDA category B drugs
• Infliximab, adalimumab, certolizumab- can be used in
pregnancy and lactation
• No increased risk of stillbirth or abortion
• Natalizumab- Category C drug; limited data available,
hence avoided
60. Indications of surgery
Ulcerative colitis
Intractable/ fulminant disease
Toxic megacolon
Colonic obstruction/ perforation
Massive colonic hemorrhage
Prophylaxis of colon cancer
Colonic dysplasia/ carcinoma
Crohn’s Disease
Small intestine
Stricture/obstruction unresponsive to
medical therapy
Massive colonic hemorrhage
Refractory fistula
Colon and rectum
Intractable/ fulminant disease
Refractory fistula
Colonic obstruction
Prophylaxis of colon cancer
Colonic dysplasia/ carcinoma
64. Pitfalls
Safety issues: ed risk of TB, opportunistic infections,
malignancies
Cost factor
Majority of patients have mild disease & will be
overtreated
65. Drugs in the pipeline
Adhesion molecule inhibitors:
• Vedolizumab- Anti α4β7 antibody
• Anti MAdCAM-1 antibody
• Alicaforsen: anti ICAM-1 antisense oligonucleotide;
inhibits ICAM-1 production by endothelium by
preventing translation of its m-RNA
66. L.lactis secreting IL-10
Non-invasive non-colonizing bacterium
Genetically modified to secrete IL-10 , a potent anti-
inflammatory molecule
Allows delivery directly at the intestinal site and thus obviates
systemic exposure
Ustekinumab
Anti IL-12/IL-23 antibody
Inhibit cellular activation & cytokine production
Talk about the benefits of PEGylation & not having Fc fragment
Surgery is subtotal colectomy f/b end ileostomy OR IAPP(ileoanal pouch procedure- in which a neorectum is fashioned out of ileum and sutured to the anal canal)