Diabetes mellitus is a clinical syndrome characterized by an increase in plasma blood glucose (hyperglycemia).
Diabetes has many causes but is most commonly due to type 1 or type 2 diabetes
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.
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.
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
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.
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
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.
Manish yadav .M Pharm First year
Pharmacology . Under -guidence of
Professor Dr. Govind Singh .
M.D.University Rohtak
Department Pharmaceutical science
introduction to oral hypoglycemic agents with description about sulphonylurea and glinides along with their MOA, indication, side effects and brand name
Pancreas makes a hormone called insulin. It helps your cells turn glucose, a type of sugar, from the food you eat into energy. Diabetes happens when one or more of the following occurs:
Your pancreas does not make any insulin.
Your pancreas makes very little insulin.
Your body does not respond the way it should to insulin
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
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
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
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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
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
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.
- 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
3. Introduction
• Diabetes mellitus is a clinical syndrome
characterized by an increase in plasma blood
glucose (hyperglycemia).
• Diabetes has many causes but is most
commonly due to type 1 or type 2 diabetes.
4. • Type 1 diabetes is caused by autoimmune
destruction of insulin-producing cells (β cells)
in the pancreas, resulting in absolute insulin
deficiency.
6. • Type 2 diabetes is characterized
by resistance to the action of
insulin and an inability to produce sufficient insulin to
overcome this ‘insulin resistance’.
8. • Hyperglycemia results in both acute and long-term
problems.
• Acutely, high glucose and lack of insulin can result
in marked symptoms, metabolic decompensation
and hospital-isation.
• Chronic hyperglycemia is responsible for diabetes-
specific ‘microvascular’ complications affecting
the eyes (retinopathy), kidneys (nephropathy) and
feet (neuropathy).
9. • Fasting plasma glucose ≥ 7.0 mmol/L
(126 mg/dL)
• Glucose 2 hours after an oral glucose
challenge ≥ 11.1 mmol/L (200 mg/dL)
Diagnostic criteria for diabetes:-
10. Drugs to reduce hyperglycemia
• For many years, there were only a few choices of
drugs available for type 2 diabetes – the
biguanide metformin, the sulphonylureas and
insulin. Insulin is the only treatment for type 1
diabetes.
• Since the late 1990s, however, several new classes
of agents have been approved for use in type 2
diabetes, with more in development.
• Newer drugs include thiazolidinediones,
dipeptidyl peptidase 4 (DPP-4) inhibitors,
glucagon-like peptide 1 (GLP-1) receptor agonists,
and sodium and glucose transporter 2 (SGLT2)
inhibitors.
11. • The older drugs are cheaper and have
established benefits for reducing
microvascular disease.
• Use of the newer drugs is not
supported by evidence for reduction
in microvascular-lar disease (because
the trials have not yet
beencompleted) and they are much
more expensive, so are often
reserved for later therapy after failure
of metformin and sulphonylureas.
12. Sites of action of the most widely used oral antihyperglycemic
agents.
15. Sulphonylureas
• It is the first antidiabetic drug
that been discoveered at 1942
• Sulphonylureas used in
Patients with T2DM ,obese,not
respond to dietary measures
and exercise alone
16. Mechanism of action
• Sulphonylureas are insulin
secretagogeus that act through
specific recepter which is
linked to a k+ channel on the
surface of pancreatic Beta cells
k+ transport trigers insulin
secretion .
17. Slide Title
• Make Effective Presentations
• Using Awesome Backgrounds
• Engage your Audience
• Capture Audience Attention
18. Sulphonylureas generations
• First generation
• Tolbutamide: mildest one has short
duration of action usually adminstered
8 -12 hourly it useful in elderly
• Chlorpropamide: half life about 36hr
taken once daily rarely used
19. Second generation
Gliclazide few side effects
Glibenclamide avoid in elderly
Glimepiride and modified release
form of gliclazide taken once daily
with no risk of hypoglycemia
20. pharmacokinetics
• Sulphonylureas absorbed by intestine
after oral use.
• Hyperglycemia reduse sulphonylureas
absorption as it impaire intestinal motility
• For this reason sulphonylureas taken 30
min. before meals and dose increase every
2 wk if there is uncontrolled BS
• But the first dose is low
21. Side Effects of Sulphonylureas
• Signs of low blood sugar, such as sweating,
dizziness, confusion, or nervousness
• Hunger
• Weight gain
• Skin reactions
• Upset stomach
• Dark-colored urine
23. Drug interaction
• Salicylates, phenylbutazone and antifungal
potentiate hypoglycemic effect of
sulphonylureas by displacing them from
plasma protein binding sites.
25. • Metformin is the only biguanide available, and it
is now widely used as first-line therapy for type 2
diabetes, irrespective of body weight.
Metformin is also used increasingly as an adjunct
to insulin therapy in obese patients with type 1
diabetes.
• However, it is less well tolerated than
sulphonylureas because of a higher incidence of
side-effects, particularly gastrointestinal
symptoms.
26. Mechanism of action :
• The mechanism of action of metformin has not been precisely
defined. It has no hypoglycaemic effect in non-diabetic
individuals, but in diabetes, insulin sensitivity and peripheral
glucose uptake are increased, possibly through inhibition of
mitochondrial respiration and activation of AMP-regulated
kinase (AMPK) in muscle. There is some evidence that it also
impairs glucose absorption by the gut and inhibits hepatic
gluconeogenesis.
• Although secretion of some endogenous insulin is mandatory for
its glucose-lowering action, it does not increase insulin secretion
and seldom causes hypoglycaemia.
27.
28. Indications:
• Administration of metformin is not associated with a rise in body
weight and it may be beneficial for the overweight or obese
patient.
• In addition, as the glucose lowering effect of metformin is
synergistic with that of sulphonylure as the two can be combined
when either alone has proved inadequate. It can also be given in
• combination with most other anti-diabetic medications.
• can also be used in polcystic ovarian syndrome.
29. • Metformin is given with food, usually starting
with 500 mg 12-hourly, gradually increased as
required to a maximum of 1 g 8-hourly.
• Excretion of the drug is through the kidneys
30. Contraindications :
• Its use is contraindicated in patients with
impaired renal or hepatic function and in
those who drink alcohol in excess in whom the
risk of lactic acidosis is significantly increased.
31. • It should be discontinued, at least
temporarily, if any other serious medical
condition develops, especially one
causing severe shock or hypoxaemia. In
such circumstances,treatment with
insulin should be substituted.
32. • history of congestive heart failure
• acute myocardial infarction
• use of IV contrast media: This can affect
kidneys function and put patient at risk for
lactic acidosis
• major surgical procedures
• people with diabetic ketoacidosis
33. Metformin during pregnancy :
• Metformin is safe and effective treatment option for
women with type 2 diabetes in pregnancy with or without
add-on insulin who require pharmacological treatment for
glycemic control .
• Metformin has advantages over insulin such as less
maternal weight gain, no maternal hypoglycemia, being
cheap, being oral therapy, and requiring no vigorous
monitoring and frequent hospital admissions with good
compliance and acceptability.
• Metformin treatment when compared with insulin
treatment showed less maternal hypertensive
complications and less risk of neonatal hypoglycemia with
few neonatal intensive care admissions.
34. • Metformin treatment is suitable for non
obese type 2 diabetes patients in
pregnancy without complications.
• Metformin treatment in type 2 diabetes in
pregnancy required lower dose of add-on
insulin, at a later gestational age for
maintaining glycemic control when
compared with insulin treatment.
36. Serious side effects
• lactic acidosis. Symptoms include:
• tiredness
• weakness
• unusual muscle pain
• trouble breathing
• unusual sleepiness
• Abdominal pain , nausea, or vomiting
• dizziness or lightheadedness
• slow or irregular heart rate
37. • Metformin does not usually cause low blood sugar (hypoglycemia). Low blood
sugar may occur if this drug is prescribed with other diabetes medications.
low blood sugar. Symptoms include:
• headache
• weakness
• confusion
• shaking or feeling jittery
• drowsiness
• dizziness
• irritability
• sweating
• hunger
• fast heart rate
38.
39. Meglitinides
• These act, like the sulfonylureas, but they
don’t have sulfonylurea moiety.
• These include repaglinide and nateglinide
• MOA : Same as sulfonylureas .
• Short duration of action and a low risk of
hypoglycaemia.
• Given orally, rapidly metabolized by liver
enzymes and excreated in the bile .
40.
41.
42.
43.
44. Thiazolidinediones
Thiazolidinediones (TZDs) reduce insulin resistance, act as insulin
sensitizers; thus, they require the presence of insulin to work. They must be
taken for 12-16 weeks to achieve maximal effect.
These agents are used as monotherapy or in combination with
sulfonylurea, metformin, meglitinide, DPP-4 inhibitors, GLP-1 receptor
agonists, or insulin. They are the only antidiabetic agents that have been
shown to slow the progression of diabetes (particularly in early disease).
most likely through activation of PPAR-γ, a nuclear receptor that regulates
the transcription of several insulin-responsive genes that regulate
carbohydrate and lipid metabolism.
45. The biologic effect of TZDs is principally mediated by stimulation
of peripheral glucose metabolism.
PPAR-γ activation also attenuates lipolysis and stimulates
peripheral adipocyte differentiation, thereby redistributing fat
stores from the liver and muscle to subcutaneous depots.
This effect may be largely responsible for the “insulin-sensitizing”
effects of the TZDs.
There is a concomitant modulation in the circulating levels of
adipocytokines, particularly in adiponectin, which is increased
two- to three-fold after TZDherapy.
46. In 1997, troglitazone was the first TZD approved for
use in the United States; although effective, the
drug was withdrawn from the market 2 years later
because of concerns about idiosyncratic
hepatotoxicity.
Rosiglitazone and pioglitazone were later approved;
these agents have no significant hepatotoxicity.
47.
48.
49. pharmacokinetic:
Both pioglitazone and rosiglitazone are absorbed very
well after oral adminstration and are extensively bound
to serum albumin
both undergo extensive metabolism bt different
cytochrome p450 isozymes
50. the therapeutic range for pioglitazone is
15–45 mg/d in a single daily dose, the
majority of the active drug and metabolite
are excreated in the bile and eliminated in
the feces.
and for rosiglitazone the total daily dose is
2–8 mg/d administered either once daily or
twice daily in divided doses.the metabolite
are excreated in the urine.
51.
52.
53. Adverse effects: A few cases of liver toxicity have been reported
with these drugs, and periodic monitoring of liver function is
recommended.
Weight gain can occur because TZDs may increase
subcutaneous fat and cause fluid retention. [Note: Fluid retention
can worsen heart failure. These drugs should be avoided in
patients with severe heart failure.] TZDs have been associated
with osteopenia and increased fracture risk. Pioglitazone may also
increase the risk of bladder cancer. Several meta-analyses identified
a potential increased risk of myocardial infarction and death
from cardiovascular causes with rosiglitazone. As a result, use of
rosiglitazone was limited to patients enrolled in a special restricted
access program. After a further review of safety data, the restrictions
on rosiglitazone use were subsequently lifted.
55. Mechanism of action :
• Alpha-glucosidase inhibitors work on two different enzymes in
the small intestine:
– Intestinal enzymes (acarbose and miglitol)
• Intestinal cells contain an enzyme called alpha-glucosidase that
metabolizes carbohydrates so that they can be absorbed into the
bloodstream
• Alpha-glucosidase inhibitors block alpha-glucosidase thereby
inhibiting the metabolism of carbohydrates and slowing their
absorption into the bloodstream
– Pancreatic enzymes (acarbose only)
• When a person consumes food, the pancreas secretes enzymes that
help digest the food so that it can be absorbed into the bloodstream
• Alpha-amylase is a pancreatic enzyme that metabolizes
carbohydrates
• Acarbose blocks alpha-amylase thereby inhibiting the metabolism of
carbohydrates and slowing their absorption into the bloodstream
56.
57.
58. • Acarbose and miglitol are available and are taken with
each meal.
• Both lower post-prandial blood glucose and modestly
improve overall glycaemic control. They can be combined
with a sulphonylurea. they must be taken at the start of
main meals to have maximal effect. Their effects on blood
sugar levels following meals will depend on the amount of
complex carbohydrates in the meal.
59. • The main side-effects are flatulence,
abdominal bloating and diarrhoea.
• Patients with inflammatory bowel disease,
colonic ulceration, or intestinal obstruction
should not use these drugs.
• The drug is not recommended in pregnancy
and lactation.
60. Incretin-based therapies: Dipeptidyl peptidase-4 inhibitors
and GLP-1 analogues
DPP4 # inhibit the enzyme DPP-4, which is responsible for the
degredation of incretin hormones such as GLP-1.
The incretin effect is the augmentation of insulin secretion
seen when a glucose stimulus is given orally rather
than intravenously, and reflects the release of incretin
peptides from the gut .
61. The incretin hormones are primarily glucagon-like
peptide 1 (GLP-1) and gastric inhibitory
polypeptide (GIP),which act to potentiate insulin
secretion .
These are rapidly broken down by the peptidase
DPP-4 (dipeptidyl peptidase 4).
The incretin effect is diminished in type 2 diabetes,
and this has stimulated the development of two
incretin-based therapeutic approaches.
62.
63. The ‘gliptins’, or DPP-4 inhibitors, prevent
breakdown and therefore enhance
concentrations of endogenous GLP-1 and
GIP. The first DPP-4 inhibitor to market was
sitagliptin; others now available include
vildagliptin, saxagliptin and linagliptin.
These drugs are very well tolerated and are
weight-neutral .
The GLP-1 receptor agonists have a similar
structure to GLP-1 but have been modified
to resist breakdown by DPP-4. These agents
are not orally active and have to be given by
subcutaneous injection.
64. . Recently, GLP-1 receptor agonists and long-acting insulin
analogue have been combined, enabling co-
administration of insulin and GLP-1 receptor agonists
with one injection.
However, they have a key advantage over the DPP-4
inhibitors: because the GLP-1 activity achieved is
supra-physiological, it delays gastric emptying and, at
the level of the hypothalamus, decreases appetite.
Thus, injectable GLP-1 analogues lower blood glucose
and result in weight loss – an appealing therapy, as the
majority of patients with type 2 diabetes are obese.
65. •Currently available GLP-1 receptor agonists include exenatide
(twice daily), exenatide MR (once weekly) and liraglutide (once
daily).
66. • All the incretin-acting drugs have been reported to
be associated with an increased risk of
pancreatitis, although this risk is small: between 1
and 10 cases per 1000 patients treated.
• Unlike sulphonylureas, both incretin-based
therapies only promote insulin secretion when
there is a glucose ‘trigger’ for insulin secretion.
Thus, when the blood glucose is normal, the
insulin secretion is not augmented and so these
agents do not cause hypoglycaemia.
67. sodium and glucose transporter 2 (SGLT2)
inhibitors
The sodium and glucose transporter 2 (SGLT2) inhibitor,
dapagliflozin, was licensed for use in 2012. Glucose is filtered
freely in the renal glomeruli and reabsorbed in the proximal
tubules. SGLT2 is involved in reabsorption of glucose.
68.
69. • Inhibition results in approximately 25% of the
filtered glucose not being reabsorbed, with
consequent glycosuria. Although this helps to
lower blood glucose and results in calorie loss and
subsequent weight loss, the glycosuria does result
in increased urinary tract and genital fungal
infections.
• Euglycaemic diabetic ketoacidosis (i.e. DKA not
associated with marked hyperglycaemia) has been
recognised as a rare complication of this class of
drugs.