The document discusses thyroid hormones, their synthesis and regulation, and effects of drugs on thyroid function. Some key points:
- The thyroid gland secretes T4 and T3 hormones which increase metabolism. T3 is more potent than T4.
- T4 and T3 are synthesized through iodination and coupling steps in the thyroid follicle and released into circulation.
- Thyroid secretion is regulated by TSH from the pituitary and inhibited by thyroid drugs.
- Hyperthyroidism is characterized by increased thyroid hormone levels and symptoms like weight loss, tremors, and increased metabolism. Graves' disease and toxic nodular goiter are causes of hyperthyroidism.
Thyroid function tests help to determine if your thyroid is not working correctly. If blood levels of thyroid hormone are high, the brain senses this and sends a message to stop producing TSH.
Introduction:
@ Thyroid releases T3 & T4
@ The ratio of T4 to T3 is 5:1, so most of the hormone released is
thyroxine
@ Most of the T3 in the blood is derived from thyroxine
@ T3 is three to four times more potent than T4
@ The affinity of the receptor site for T3 is about ten times higher than that for T4
Thyroid function tests help to determine if your thyroid is not working correctly. If blood levels of thyroid hormone are high, the brain senses this and sends a message to stop producing TSH.
Introduction:
@ Thyroid releases T3 & T4
@ The ratio of T4 to T3 is 5:1, so most of the hormone released is
thyroxine
@ Most of the T3 in the blood is derived from thyroxine
@ T3 is three to four times more potent than T4
@ The affinity of the receptor site for T3 is about ten times higher than that for T4
Thyroid hormone,
structure of hormone,
synthesis of thyroid hormone,
mechanism of Thyroid hormone action,
Physiological effect of Hormone,
Disorders related with thyroid hormone,
drugs used in treatment for the thyroid disorders.
This is a content made by the students of Pharmacy dept of Comilla University about the Endocrine system, In this you can easily find the glands in out body and their functions. and specific organs which secrete specific hormones for our body. figures are added to make it more convenient. thank you all.
Thyroid function tests (TFTs) are the most frequently ordered endocrine investigations in children and adolescents.
Abnormalities in TFTs can help in diagnosis of primary thyroid disorders (i.e. disorders in which the defect is at the thyroid level) as well as secondary or central thyroid disorders (in which defect is at the pituitary level).
Thyroid hormone,
structure of hormone,
synthesis of thyroid hormone,
mechanism of Thyroid hormone action,
Physiological effect of Hormone,
Disorders related with thyroid hormone,
drugs used in treatment for the thyroid disorders.
This is a content made by the students of Pharmacy dept of Comilla University about the Endocrine system, In this you can easily find the glands in out body and their functions. and specific organs which secrete specific hormones for our body. figures are added to make it more convenient. thank you all.
Thyroid function tests (TFTs) are the most frequently ordered endocrine investigations in children and adolescents.
Abnormalities in TFTs can help in diagnosis of primary thyroid disorders (i.e. disorders in which the defect is at the thyroid level) as well as secondary or central thyroid disorders (in which defect is at the pituitary level).
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.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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
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
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
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
New Drug Discovery and Development .....NEHA GUPTA
The "New Drug Discovery and Development" process involves the identification, design, testing, and manufacturing of novel pharmaceutical compounds with the aim of introducing new and improved treatments for various medical conditions. This comprehensive endeavor encompasses various stages, including target identification, preclinical studies, clinical trials, regulatory approval, and post-market surveillance. It involves multidisciplinary collaboration among scientists, researchers, clinicians, regulatory experts, and pharmaceutical companies to bring innovative therapies to market and address unmet medical needs.
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.
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
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.
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
1. THYROID HORMONES AND ANTI- THYROID
DRUGS.
Hormones secreted from the thyroid gland
include:L-thyroxine (l- tetra iodo –l thyronine or T4
and triiodo-l thyronine or T3.
Term thyroxine or thyroid hormone is commonly
used to include both T3 and T4
T3 is 3- 5 times more potent than T4 and is the
major physiologically active thyroid hormone
Thyro- calcitonin is also secreted by the thyroid
gland and is involved in calcium metabolism .
2. SYNTHESIS ,RELEASE AND
METABOLISM OF THYROID HORMONES
• The functional unit of the thyroid gland is
the thyroid follicle-consists of a cavity
lined with a single epithelial cell layer.
• The lumen of the follicle is filled with
thyroglobulin-large glycoprotein of MW
600,000
• Throglobulin is synthesized in the thyoid
and has 115 tyrosine residues.
4. SYNTHESIS ,RELEASE AND
METABOLISM OF THYROID HORMONES
Cont…
• Synthesis of thyroid hormone occurs in steps:
• Step 1- Iodide trapping or uptake of
circulating iodides by follicle cells.
• Energy dependent active process ,stimulated by
TSH and is also dependent on thyoid iodine
concentration
• Uptake is stimulated in case of iodine deficiency
and decreased when the thyroid iodine content
is high.
5. SYNTHESIS ,RELEASE AND METABOLISM OF
THYROID HORMONES Cont…
• Step 2-Oxidation of iodide to iodine atom or
free radical .
• Reaction occurs inside the follicle lumen and is
catalyzed by the enzyme thyroperoxidase.
• Thyroperoxidase requires hydrogen peroxide as
the oxidizing agent.
• Step3-Iodination of tyrosine residues of
thyroglobulin.
• Process also under the influence of
thyroperoxidase.
• Mono iodo tyrosine (MIT) and di iodo tyrosine
(DIT) are formed.
6. SYNTHESIS ,RELEASE AND METABOLISM OF
THYROID HORMONES Cont…
• Step 4- Coupling of iodotyrosine molecules to
form T3 andT4.
• MIT +DIT =T3 and DIT + DIT=T4—these
reactions are all under peroxidase.
• The iodinated thyroglobin is secreted and
stored in the follicular lumen.
• Step 5-Uptake of iodinated thyroglobulin TG.
• Under the influence of thyrotropin (TSH), the
iodinated thyroglobulin is taken back by the follicle
cells by aprocess of endocytosis where the cells
engulf some amount of the thyroglobulin colloid.
7. SYNTHESIS ,RELEASE AND METABOLISM OF
THYROID HORMONES Cont…
• Step6 Release of thyroid hormone into
circulation.
• Thyroglobulin is acted upon by proteolytic
enzymes to release thyroid hormones into
the circulation.
• Most of the hormone released is T4 , and
80% of T4 is de iodinated in peripheral
tissues into active T3.
8. • Step 1 Trapping of iodide—inhibited by
Thiocyanates ,perchlorates and nitrates.
These anions in high concentration
competitively inhibit the iodide transport
into the cell.
• Iodide trapping is stimulated by TSH.
DRUG ACTION ON THE THYROID GLAND
9. DRUG ACTION ON THE
THYROID GLAND
• Ionic inhibitors are no longer used in
hyperthyroidism:
1.Perchlorates-produce hypersensitivity
reactions-rashes, fever, aplastic anaemia
and agranulocytosis.
2.Thiocyanates- can cause liver, kidney,
bone marrow and brain toxicity.
3.Nitrates-induce methaemoglobinemia and
vascular effects
10. • Step 2 –oxidation of iodide—stimulated
by TSH but inhibited by antithyroid agents
and iodides.
11. DRUG ACTION ON THE
THYROID GLAND
• Step3 iodination of tyrosine into
MITand DIT –stimulated by TSH and
inhibited by antithyroid agents.
• Step 4 Coupling of MIT and DIT into
T3andT4 –stimulated by TSH and
inhibited by antithyroid agents.
• Step 5 endocytosis of thyroglobulin,TG
into follicular cells –stimulated by TSH
12. DRUG ACTION ON THE
THYROID GLAND
• Step6 proteolytic release of T4 and T3
–stimulated by TSH and inhibited by
iodides.
• Step 7 –de iodination of T4 into T3 –
inhibited by propyl thio uracil, propranolol
and ipodate.
13. TRANSPORT OF T3 AND T4
• They are transported in plasma bound to
plasma proteins.
• The main binding plasma protein is the
thyroxine binding globulin(TBG ) and
thyroxin binding albumin (TBA)
• Binding of thyroid hormones is important
because:
1.Only the free or unbound hormone is
pharmacologically active
14. TRANSPORT OF T3 AND T4.
2. Only the free or unbound hormone is
metabolized or excreted. Binding therefore
prolongs the duration of action of the
hormones by increasing their half lifes.
3.Certain factors affect the levels of TBA
and TBA and hence the pharmacological
actions of T3 and T4.
15. • TBG and TBA levels in plasma are raised
by: estrogens ,oral contraceptives
,clofibrate ,neuroleptics and pregnancy
TRANSPORT OF T3 AND T4
16. TRANSPORT OF T3 AND T4 Cont…
• In the presence of the above factors, more
thyroxine is bound and plasma
concentration is low. WHAT IS THE
THERAPEUTIC IMPLICATION?
• Concentrations of TBG andTBA are
lowered by corticosteroids, androgens
,anabolic steroids, furosemide.
• In the presence of the above factors less
thyroxine is bound and concentration of
thyroxine in plasma is high. WHAT IS THE
THERAPEUTIC IMPLICATION?
17. TRANSPORT OF T3 AND T4 Cont…
• Phenytoin and salicylates displace thyroid
hormones from plasma protein binding sites
and increases levels of the free hormone.
• Systemic factors e.g. liver disease. porphyria
and HIV infection decrease the binding
proteins.
• Plasma protein binding of thyroid hormones
increases their half lifes by protecting them
from metabolism and excretion,(free unbound
T4 in plasma is 0.03% and T3 0.3% )
18. METABOLISM OF THYROID HORMONES.
• Part of T4 is de iodinated to active T3
• The thyroid hormones are enventually de-
iodinated in the liver ,deaminated and
partly conjugated.
• Free and conjugated metabolites are
excreted in bile and urine.
19. REGULATION OF THYROID FUNCTION
• Secretion is mainly under thyrotropin
(TSH) secreted by the anterior pituitary.
• Secretion of thyrotropin is increased by the
hypothalamic TRH and decreased by
somatostatin.
• TSH stimulates all aspects of thyroid
hormone synthesis I.e steps 1-6.
20. REGULATION OF THYROID FUNCTION
Cont…
• TSH exerts a trophic effect on thyroid follicular cells
and influences thyroid circulation .Increase TSH
activity will thus lead to hypertrophy of follicular cells
,increase in blood flow and stimulation of thyroxin
synthesis and release.
• Plasma iodide levels also influence the thyroid
function i.e iodine defiency results in reduced
plasma iodide levels, reduced thyroxine synthesis
and increased levels of TSH and vice-versa.
• Iodide administration will lead to decrease in size
and vascularity of the thyroid gland due to reduced
TSH activity.
21. EFFECTS OF DRUGS ON THYROID FUNCTION/
drug interactions involving thyroid hormones
• Dopamine, l-dopa corticosteroids—
Inhibition of TRH and TSH secretion.
• Iodides, lithium--- Inhibition of thyroxine
synthesis and hypothyroidism.
• Cholestyramine
,colestipol,sucralfate,aluminium salts---
Inhibit thyroxine absorption from the gut.
• Phenytoin ,carbamazepine ,rifampicin,
phenobarbitone--- Enzyme inducers and
may increase T3 and T4 metabolism.
22. EFFECTS OF DRUGS ON THYROID
FUNCTION Cont…
• Propyl thiouracil, amiadarone,
corticosteroids ,beta blockers--- Inhibition of
conversion of T4 to T3.
• Androgens, glucocorticoids---- Decrease
thyroxin- binding globulin.
• Estrogens, tamoxifen ,mitotane--- Increase
thyroxin –binding globulin.
• Salicylates ,mefenamic acid furosemide----
DisplacesT3 andT4 from thyroxin binding
globulin.
23. PHARMACOLOGICAL EFFECTS OF
THYROID HORMONE.
• The physiological effects are mainly due to T3
because it is 3-5 times more potent than T4.
• REGULATION OF GROWTH AND
DEVELOPMENT.
– Regulation of growth and development of the skeletal
system and CNS.
– Above effect is partly direct and partly by
• GH ,parathormone and calcitonin potentiation.---
may involve protein synthesis by inducing
synthesis of specific MRNA and proteins in
target cell
• Thyroid hormone deficiency during fetal and
post natal growth and development –cretinism(
physical and mental retardation.)
24. METABOLIC EFFECTS.
• Stimulate metabolism of carbohydrates, proteins
and lipids.
• Above effects may be exerted directly or by
modulating effects of other hormones e.g.
insulin,glucagon catecholamine ,corticosteroids
and parathormone. WHAT WOULD BE THE
EFFECT OF THYROXINE ON INSULIN LEVELS?
• Basal metabolic rate is increased by calorigenic
effect i.e increased oxygen consumption by the
tissues.
• Uptake and utilization of glucose is increased and
lipolysis in tissues results in increased levels of
triglycerides, cholesterol and free fatty acids.
25. CARDIAC EFFECTS.
• Increased HR and cardiac output due to
sensitization of cardiac beta receptors to
catecholamines
AUTO REGULATION OF THYROID FUNCTION
• By negative feedback inhibition of
thyrotopin (TSH) from the pituitary by T3
and T4.
26. C N S. AND G.I.T
C N S.
• Increased thyroid hormone leads to
nervousness and many psycho neurotic
tendencies e,g anxiety , paranoia and
extreme worries.
• G .I.T
– Increase appetite and food intake.
– Increased rate of secretion of digestive juices.
– Increased gut motility I.e hyperthyroidism can
cause diarrhea and hypothyroidism can lead
to constipation.
27. EFFECT ON MUSCLE FUNCTION
• Increased thyroid hormone---increase in
skeletal muscle contractility.
• Hyperthyroidism manifests with fine
muscle tremors. This is caused by
increased reactivity of the neuronal
synapses in the areas of the spinal cord
that controls muscle tone
• Very high levels_----muscle weakness
due to excessive protein catabolism.
28. EFFECT ON SLEEP
• Hyperthyroidism leads to exicitability and
lack of sleep due to CNS excitation.
• Hypothyroidism causes extreme
somnolence ,with sleep lasting 12-14 hrs
a day.
29. EFFECT ON SEXUAL FUNCTION
• Hypothyroidism causes loss of libido in males
while very high levels may lead to impotence.
• In women ,hypothyroidism may cause:
• a) Menorrhagia ( excessive menstrual bleeding )
• b) Poly menorrhea (frequent menstrual bleeding)
• c) Irregular periods and amenorrhea.
• d) Decreased libido.
• Above effects may be due to excitatory and
inhibitory effects of thyroid hormones on anterior
pituitary hormones that control sexual function
(FSH and LH).
• Normal thyroid hormone levels is required for
maintenance of pregnancy and lactation.
30. VITAMIN REQUIREMENT
• Increases vitamin requirement because of
increase metabolic rate.
• Metabolic reactions require enzymes
which need vitamins as co- factors.
• Hyperthyroidism may cause vitamin
deficiency unless dietary intake is
increased.
31. Mechanism of action of thyroid
hormones
• Thyroid hormones, T3 and T4 penetrate
cells by active transport and produce most
of their actions by combining with a
nuclear thyroid hormone receptor (TR)
which belong to the steroid and retinoid
super family of intracellular receptors.
• There is increased synthesis of RNA
which leads to accelerated protein
synthesis and enhanced enzymatic and
cellular activities.
32. Mechanism of action of thyroid
hormones.
• Thyroid hormones also stimulate sodium –
potassium ATP- ase directly thus
facilitating membrane transport of sodium
and potassium and increasing cellular
utilization of oxygen.
33. Summary of Pharmacological
actions of thyroid hormones
• Increase rate of metabolism, total heat
production and oxygen consumption in
most body tissues.
• Promote normal physical and mental
development and growth.
• Potentiate the cardiovascular and
metabolic actions of catecholamines.
34. Summary of Pharmacological
actions of thyroid hormones
• At cellular level, they accelerate protein
synthesis, mainly by T3 .
• Approximately 1/3 of T4 is converted to T3
in the periphery, liver, kidneys and the
primary effect of the thyroid hormones is
apparently due to T3 activity.
35. DISORDERS IN THYROID GLAND FUCTION
HYPERTHYROIDISM. (THYROTOXICOSIS).
In most patients manifests with:
• Increase in size of thyroid gland 2-3
times its normal size.( hyperplasia)
• Each follicular cell increases the rate
of secretion of thyroid hormone 5-15
times the normal.
• Two types: Graves disease and toxic
nodular goiter.
36. Graves Disease./Exophthalmic goiter
/Diffuse toxic goiter.
• Auto immune disease in which antibodies
called thyroid stimulating immunoglobulin
(TSIs) form against the TSH receptor in
the thyroid (TD ).
• The antibodies bind with the same
membrane receptors that bind TSH and
induce continual activation of the cAMP
system of the the cells with resultant
development of hyperthyroidism.
37. Graves Disease./Exophthalmic goiter
/Diffuse toxic goiter. Cont…
• The TSI have a stimulating effect on the
thyroid gland (12 hr effect in contrast to
1hr for TSH).
• The high level of thyroid hormone
secretion caused by TSI in turn
suppresses the anterior pituitary formation
of TSH.
• TSH concentration is therefore less than
normal.
38. Toxic Nodular Goitre.
• Localised benign adenoma or tumour in
the TD tissue may cause hyperthyroidism
by secreting large quantities of TD
hormone.
• There is no evidence of an auto immune
disease.
• Increased secretion of TD hormones by the
adenoma depresses the TSH levels by the
pituitary gland .This in turn suppresses all
the secretory functions in the remainder of
the TD gland.
39. Other causes
• Anti arrhythmic drug amiadarone is rich in
iodine and can cause either hyper or hypo
thyodism .
40. GENERAL SYMPTOMS OF HYPERTHYROIDISM.
• A state of excitability.
• Intolerance to heat.
• Increased sweating
• Mild to extreme weight loss (50 kg or less).
• Varrying degrees of diarrhea.
• Muscle weakness.
• Nervousness or other psychic disorders.
• Extreme fatigue but inability to sleep.
• Tremors of the hands.
• Exopthalmos or protrusion of the eye ball.
41. Exopthalmos
• Affects about a third of hyperthyroidism patients
especially of diffuse toxic goiter. Toxic nodular
goiter does not present with exophalmos.
• Protrusion of the eyeball stretches the optic
nerve which in turn leads to poor vision.
• The eyes are eventually damaged because the
eyelids do not close completely when the person
blinks or falls asleep.
• There is increased irritation, ulceration and
infection of the cornea,
• Patients have high levels of circulating TSIs ,
suggesting an auto immune component.
42. DIAGNOSIS OF HYPERTHYROIDISM.
• Direct measurement of free T4 OR T3 in the
plasma by radio immuno assay.
• Measurement of basal metabolic rate .-usually
increased to +30 to +60 in severe
hyperthyroidism
• Concentration of TSH in the plasma is measured
by radioimmuno assay. In thyrotoxicosis TSH
levels are low.
• The concentration of TSI is measured by radio
immuno assay. it is usually high in Graves
disease but low in toxic nodular goiter.
43. TREATMENT OF HYPER THYROIDISM.
– 1) Surgical removal of most of the thyroid.
Propyl thio uracil is administered before
surgery to reduce the basal metabolic rate.
– 2) Iodides : given for 1-2 weeks before
surgery .Iodides cause the gland to recede in
size and its blood supply to diminish.
– Procedures 1 and 2 before surgery reduces
operative mortalities .( 1 in 1000 ,before it was
1:25)
44. TREATMENT OF HYPER THYROIDISM.
Cont…
• Radio active iodine - -Destroys most of
the secretory cells of the TD because
when hyperplastic the TD can absorb
about 90% of iodine. 5millicuries of
radioactive iodine is given for several
weeks.Additional doses may be
administered until normal thyroid states
is achieved.
• Others: Perchlorates ,lithium, and
propranolol.
45. HYPOTHYROIDISM.
Effects are opposite to hyperthyroidism.
• Autoimmune component that destroys the
gland and not stimulate it ( Hashimoto
disease).
• There is decreased secretion of TD
hormones due to fibrosis of the gland.
• Due to low production of TD hormones
there is an associated enlargement of the
TD gland.
46. TYPES OF HYPOTHYROIDISM.
• Endemic Colloidal Goitre
–Due to dietary iodide deficiency.
–Lack of iodine leads to no production of
T3 andT4 by the TD gland.
–T4 and T3 always exert a negative
feedback on TSH levels.TSH production
rises and this causes the TD to to
increase the conc. Of thyroglobulin
colloid into the follicles causing the TD
gland to enlarge.
47. Idiopathic non toxic colloid goiter
• These people do not suffer from iodine
deficiency but goitrous glands may secrete
low quantities of thyroid hormones.
• Colloid goiter may be caused by the
abnormality in the enzyme system required
for the formation of the thyroid hormones e.g.
• Deficient iodide trapping mechanism – iodine
is not pumped adequately into the thyroid
cells.
• Deficient peroxidase system – in which
iodides are not oxidized to iodine state.
• Deficient coupling of iodinated tyrosines in
the thyroglobulin molecule, so the final thyroid
hormone cannot be formed.
48. Myxedema (Adult hypothyroidism)
• This develops in patents with almost total lack of
thyroid hormone function. Manifests with:
• Baggines under the eyes .
• Swelling of the face.
• Pitting oedema due to increase in intestinal fluid.
• Development of atherosclerosis (lack of thyroid
hormones causes increase blood cholesterol
because of altered fat and cholesterol metabolism
and dimished liver excretion of cholesterol in bile.
• Atherosclerosis can occur in other types of
hypothyroidism but is more enhanced in myxedema
• Atherosclerosis will lead to peripheral vascular
diseases, coronary artery disease and early death.
49. Cretinism
• This is called congenital or neonatal
hypothyroidism: It is due to:
• Dysgenesis or poorly formed thyroid.
• Iodine deficiency .
• In born errors of iodine metabolism.
50. Other causes of Hypothyroidism
• Goitrogenic substances – excessive intake
of these substances e.g cabbages and
turnips. These foods contains compounds
with anti thyroid activity (similar to propyl
thiouracil) and cause TSH stimulated
enlargement of the thyroid gland.
51. Clinical manifestation of hypothyroidism
• Hypothroidism may be due to:
• Thyroiditis or thyroid inflammation.
• Endemic colloid goiter.
• Destruction of the thyroid gland by
irradiation .
• Surgical removal of the thyroid .
• Myxedema and cretinism .
52. Effects Of hypothyroidism
• Fatigue and extreme somnolence with prolonged
sleep of upto 14hrs a day .
• Extreme muscular sluggishness.
• Slowed heart rate.
• Decrease CO, decrease BV.
• Increase BW .
• Constipation, mental sluggishness .
• Depressed growth of hair and scaliness of the
skin .
• Development of frog like husky voice.
• In severe cases development of odematous
appearance throughout the body called
myxedema.
53. EFFECTS OF HYPOTHYROIDISM.
• Mental retardation and dwarfism due to
delayed skeletal maturation
• Thick dry skin, protruding tongue,
hypothermia and lethargy.
54. Diagnosis of hypothyroidism
• Free thyroxin in the blood- decreases
• Basal metabolic rate in myxedema
range from -30 and -50.
• Secretion of TSH by anterior pituitary
when a test dose of TRH is
administered is usually increased.
55. Treatment of Hypothyroidism
• Use thyroid hormone replacements
• Preparations
• Thyroxine – Sodium salt of L-thyroxine
• Liothyronine Sodium (T3) – NOT for long
term use because of high potency and
incidence of cardiac side effects. 25 ug of T3
has similar clinical response as 100ug of
thyroxine.
• Liotrix (25 ug T4 with 6.5 ugT3. It does not
offer any special advantage over l-thyroxine.
56. Therapeutic uses Of Thyroid Hormones
• Replacement or substitution therapy of
primary hypothyroidism e.g cretinism,
myxedema, non toxic goiter, hypothyroid
states of childhood.
• Also hypothyroidism resulting from other
causes e.g. surgery, radiation, drugs,
pregnancy or ageing.
• Adjuncts to thyroid – inhibiting agents.
• Adjunctive therapy of follicular and
papillary carcinoma of the thyroid in
conjuction with radioactive iodine.
57. Side effects /adverse of thyroid
hormones
• Palpitations, sweating, nervousness
• Heat intolerance
• Insomnia
• Allergic skin reaction
• CCF and shock
58. Contra indications and precautions
thyroid hormones
• CI – patients with thyrotoxicosis, nephrosis and
myocardial infarction, obesity.
• Caution – CVS diseases (angina)
• concomitant diabètes mellitus or adrenal isufficiency.
Interactions involving thyroid hormones
• Potentiates cardiovascular effects of catecholamines.
• Potentiate effects of oral anticoagulants
• Thyroid hormones increase effectiveness and toxicity of
cardiac glycosides
• May increase blood glucose levels thus increasing
requirement for insulin and oral hypoglycemics.
59. ANTITHYROID DRUGS
These drugs are used in hyper
thyroidism.
a) Thioamides
• These reduce the synthesis of thyroid
hormones and include carbimazole,
methimazole and propylthiouracil. They
are called antithyroid drugs.
• b) Iodide – In high doses
• c) Radioactive iodine – 131
60. ANTITHYROID DRUGS
Cont…
d) Ionic inhibitors – These inhibit iodide
uptake e.g. thiocyanates, perchlorates,
nitrates. Their use is obsolete due to toxicity.
e) Propranolol – use as an adjunct therapy
in thyrotoxicosis.
61. Thioamides
Mechanism of action
These drugs inhibit all the steps catalyzed
by thyroperoxidase- steps 2 3 and 4 in the
biosynthetic pathway viz:
• Preventing conversion of iodide to iodine
atom or free radical, inhibiting iodination of
tyrosine and coupling of iodotyrosine to
form T3 and T4
• In addition propylthiouracil inhibits the
peripheral conversion of T4 toT3.
62. Mechanism of action of
thioamides
• There is also evidence to suggest that the
drugs may suppress the synthesis of auto
antibodies implicated in the aetiology of
Graves disease.
63. PHARMACOKINETICS OF
THIOAMIDES
• Drugs are absorbed orally
• Carbimazole is a pro-drug and is converted to methimazole
.
• T ½ (methiomazole 4 hrs, propylthioracil 2 hrs)
.
• These short t ½ are not clinically important because there is
cumulation of these drugs in the thyroid where they act for
25-35hrs.
64. PHARMACOKINETICS OF
THIOAMIDES
• A single dose of carbimazole or
propylthiouracil can reduce iodination of
tyrosine by 70-90% within 7-12 hrs.
• These drugs are excreted in urine and
mothers milk and cross the placental
barrier.
• Methimazole crosses the placental barrier
to a greater extent than propyl thiouracil.
65. THERAPEUTIC USES
THIOAMIDES
1. Graves disease
• Carbimazole orally 30-60mg/day until
remission of symptoms with maintenance
dose of 5 -15 mg/d.
• Propyl thiouracil – orally 300 – 450mg/d
maintenance dose 50-150 mg/day
66. THERAPEUTIC USES
THIOAMIDES
ii) Toxic nodular goiter
iii) Prior to surgery for hyperthyroidism
iv) Combined with radioactive iodine to
decrease symptoms of hyperthyroidism
before radiation effects are manifested.
67. ADVERSE EFFECTS OF
THIOAMIDES
• Pruritic rash and hypothyroidism- most
common
• Rare effects include: Vasculitis, arthralgia,
Cholestatic jaundice, lymphadenopathy,
Hair pigmentation and SLE like syndrome.
68. ADVERSE EFFECTS OF
THIOAMIDES
• Adverse effects are reversible on
discontinuation of the drug.
• Adverse cross sensitivity between propyl
thiouracil and methimazole is 50% i.e. one
cannot be substituted for the other.
69. Iodides
• Iodides after food intake are selectively
trapped by the thyroid gland, uptake being
increased in hyperthyroidism and reduced
in hypothyroidism.
• Large doses of iodides:e.g. lugols iodine
(5%iodine in 10% potassium iodide
solution):
70. MECHANISMS OF ACTION OF
IODIDES
1. Inhibit secretion of thyroid hormones
2. Inhibit hormone release by inhibiting
thyroglobulin proteolysis
3. Decrease vascularity of the gland.
71. THERAPEUTIC USES OF
IODIDES
1. Pre-operative use in thyroid surgery.
Potassium iodide 60mg orally tds. Antithyroid drugs
are first used to control symptoms of
hyperthyroidism and iodides are began 10 days
before surgery to reduce gland size and vascularity
.
2. Thyroid crisis – defined as sudden aggravation of
hyperthyroidism (thyrotoxicity)
72. THERAPEUTIC USES OF
IODIDES
3. Accidental over-dosage of radioactive
iodine. It appears to protect the thyroid
follicles.
4. Prophylactic use in endemic goitre. It is
added to salt (1:100,000 parts ) as iodized
salts.
5. As an expectorant
6. As antiseptic for topical use
73. ADVERSE DRUG REACTIONS
OF IODIDES
• Acute hypersensitivity Rx e.g.
angioedema, skin haemorrhage and drug
fever
• Iodism on chronic administration
(salivation, lacrimation, soreness of throat)
conductivities, coryza like symptom, skin
rashes.
74. ADVERSE DRUG REACTIONS
OF IODIDES
• Foetal or neonatal goiter can occur after
administration to pregnant or lactating
mothers.
75. RADIOACTIVE IODINE
Mechanism
• Emits both beta and gamma rays. It is
absorbed after oral administration and is
trapped by the thyroid follicles and
incorporated into thyroblogulin.
• The emitted beta rays have a short range
and act on thyroid tissues without injuring
surrounding areas including the
parathyroid gland.
76. THERAPEUTIC USES OF RADIOACTIVE
IODINE
• It is used as radio active sodium iodide
• Radioactive sodium iodide is administered
orally in the dose of 5-8 millicurie in the
following conditions:
77. THERAPEUTIC USES OF
RADIOACTIVE IODINE
1. Graves disease – including relapse after
sub total thyroidectomy.
2. Toxic nodular goiter
3. Thyroid carcinoma
Clinical response with radioactive iodine is
slow and may take 6-12 weeks for
suppression of hyperthyroid symptoms.
Repeated doses may be necessary in
some cases.
78. ADVERSE DRUG REACTIONS
OF RADIOACTIVE IODINE.
• Hypothyroidism is fairly common.
• Should be avoided in children (mutagenic
effect) and pregnancy (teratogenicity and
cretinism.
• Lactating mothers (hypothyroidism,
cretinism).
79. PROPRANOLOL
• It is not strictly an anti-thyroid drug but is a
beta adrenergic antagonist which inhibits
many symptoms of hyperthyroidism e.g.
palpitation or tachycardia, tremors, anxiety
and thyrotoxic periodic paralysis due to
increased muscle activity.
80. THERAPEUTIC USES OF
PROPRANOLOL
1. In thyroid crisis
2. As an adjunct in thyrotoxicosis or
hyperthyroidism
3. Prior to thyroid surgery to reduce
symptoms like tachycardia
4. Thyroiditis (or inflammation of the thyroid)
– prevents palpitations.
81. THYROID CRISIS OR
THYROID STORM
• Hyperthyroidism / thyrotoxicosis
with sudden elevation of thyroid
hormones.
• It is a medical emergency.
83. THYROID CRISIS/STORM
PROPRANOLOL
• Given I.V 5-10mg followed by oral
administration 20-40 mg 6hourly.
• Propranolol decreases palpitations,
agitations, and anxiety and muscle
tremors.
• It also prevents peripheral conversion of
T4 TO T3.
84. THYROID CRISIS OR
THYROID STORM
DILTIAZEM
• 5-10mg IV is used if adequate control is
not attained by propranolol or in cases
where propranolol is contraindicated
(CHF, bronchial asthma.)
85. THYROID CRISIS OR
THYROID STORM
SODIUM IODIDE.
• I.V 1-2 g/day followed by saturated
solution of potassium iodide 10 drops
orally daily.
• Increased concentration of iodides
prevents hormone synthesis and
peripheral conversion of T4 to T3.
86. THYROID CRISIS OR
THYROID STORM
PROPYL THIOURACIL
• The antithyroid drug is given orally or
through orogastric tube 150-200mg 4-6
hourly.
• It prevents incorporation of iodine into
tyrosine residues and peripheral
conversion of T4 to T3.
87. THYROID CRISIS OR
THYROID STORM
GLUCOCORTICOIDS E.G.
HYDROCORTISONE.
• Is given I.V 100-200 mg 8 hourly.
• It prevents peripheral conversion of T4 to
T3.
• Increased thyroid hormones may lead to
increased glucocorticoid secretion and
possible adrenal suppression. This is one
reason for glucocorticoid administration (IV
hydrocortisone is used).