This document provides an overview of hematopoietic growth factors and hematinics. It discusses iron, folic acid, vitamin B12, and various growth factors that stimulate red blood cell, white blood cell, and platelet production. These include erythropoietin, G-CSF, GM-CSF, IL-11, and romiplostim. The document covers the chemistry, mechanisms of action, indications, and side effects of these substances used to treat anemia and thrombocytopenia.
Detailed information of all terms like Thyroid gland, Thyroxine, Triidothyronine, Calcitonine, growth and development , propylthiouracil, Calorigenesis, tadpole to frog, Oligomenorrhoea, snehal chakorkar, pharmacology, Cretinism, Myxoedema coma, Graves disease, Thiocynates, Perchlorate, Nitrates.
Radioactive iodine, I131
Lecture slides for undergraduate MBBS class in Pharmacology on " Drugs for Diarrhoea" . It includes various treatment modalities which are used in the management of Diarrhoea. Basic source of information for preparing this slides is" Essentials of Pharmacology by KD tripathi, 7th Edition". Images are searched with the help of google images.
Detailed information of all terms like Thyroid gland, Thyroxine, Triidothyronine, Calcitonine, growth and development , propylthiouracil, Calorigenesis, tadpole to frog, Oligomenorrhoea, snehal chakorkar, pharmacology, Cretinism, Myxoedema coma, Graves disease, Thiocynates, Perchlorate, Nitrates.
Radioactive iodine, I131
Lecture slides for undergraduate MBBS class in Pharmacology on " Drugs for Diarrhoea" . It includes various treatment modalities which are used in the management of Diarrhoea. Basic source of information for preparing this slides is" Essentials of Pharmacology by KD tripathi, 7th Edition". Images are searched with the help of google images.
Presentation for Medical undergraduates for teaching pharmacology. It deals with Physiology of steroid hormones and their action along with agents which are used therapeutically with their action, adverse effects and therapeutic uses.
Presentation for Medical undergraduates for teaching pharmacology. It deals with Physiology of steroid hormones and their action along with agents which are used therapeutically with their action, adverse effects and therapeutic uses.
Renal disease may produce disturbances in red blood cells, white blood cells, platelets, and coagulation factors
the abnormalities do not parallel the status of renal function but rather reflect the activity of the disease process that results in renal dysfunction.
Hemochromatosis is an iron storage disorder in which there is excessive accumulation of iron in parenchymal cells with eventual tissue damage and functional insufficiency of organs
It is the most common autosomal recessive genetic disorder and the most common cause of severe iron overload.
In hereditary hemochromatosis regulation of intestinal absorption of dietary iron is abnormal leading to net iron accumulation of 0.5 to 1gm/yr.
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
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
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
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.
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!
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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.
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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
3. haemtopoeisis
• Production of all types of blood cells including
formation , development & differentiation of
blood cells.
Definition
• Haematinics – substances required in
formation of blood and are used for
treatment of anemia.
• Haematopoietic growth factors - proteins
that regulate proliferation and
differentiation of hematopoietic cells.
4. • Iron deficiency - most common cause of
chronic anemia.
Daily iron requirement
▫ Adult male – 0.5 - 1 mg
▫ Mensturating female – 1- 2mg
▫ Pregnant female – 3- 5mg
▫ Children – 25 micro gram /kg
IRON
5. • Good source of iron - Liver , egg yolk , beans
,dry fruits.
• Poor sources of iron - Milk & its products.
• Reducing substances like ascorbic acid &
gastric acid - ↑ Absorption
• Alkalies , phosphates , phytates ,
tetracyclines - ↓ Absorption
6.
7. • Iron – prophylaxis or treatment of iron
deficiency anemia ( microcytic hypochromic
anemia)
• Parenteral route indicated -
▫ Oral iron not tolerated
▫ Oral iron not absorbed
▫ Non compliance to oral iron
▫ Severe iron deficieny with chronic bleeding
▫ Along with erythropoietin
8. Oral preparations
• Ferrous sulphate – 20% elemental iron
• Ferrous gluconate – 12% elemental iron
• Ferrous succinate -35% elemental iron
• Reticulocyte count - ↑ in 2 weeks & peak in 4
weeks
• Rise of haemoglobin - 0.5- 1 gm /dl per week
considered adequate
9. • Major adverse effects of oral iron
preparations - Poor compliance
1. Epigastric pain
2. Nausea
3. Vomiting
4. Metallic taste
Elemental iron content in preparation
10. Parenteral iron preparations
Iron dextran Iron sorbitol citrate
Can be given IV or IM Only IM
Not excreted in urine Excreted 30% in urine
Absorbed through
lymphatics
Absorbed directly in
circulation
Not bound to transferrin Bound to transferrin
Adverse effects – Pain at
injection site ,fever,
palpitation
Adverse effects – Incidence
of immediate reaction ,
ventricular tachycardia, A- V
block , hypotension - Higher
11. Ferrous sucrose
▫ High molecular weight complex of iron hydroxide
with sucrose
▫ IV injection
▫ Safer than older formulations
▫ Incidence of hypersensitivity reaction very low
Indicated for anaemia in kidney disease but
reports of kidney damage are on record
12. Ferric carboxymaltose
▫ Ferric hydroxide core is stabilised by a
carbohydrate shell
▫ Injected IV
▫ In clinical trials it has caused rapid increase in
haemoglobin level in anaemia patients &
replenished stores.
▫ Acute reaction - Low
13. • To avoid the serious toxicity associated with
iron overload – chronic parenteral iron
therapy
• Iron stores estimated - basis of
▫ Serum concentrations of ferritin and
▫ Transferrin saturation(ratio of the total serum
iron concentration to the total iron-binding
capacity (TIBC)
Important to monitor iron storage levels
15. Clinical Toxicity
• Acute iron toxicity – exclusively seen in
young children – accidentally ingest iron
tablets.
• Adult patients taking oral iron preparations
should be instructed
Store tablets in child-proof containers out of the
reach of children
16. • Children poisoned with oral iron experience
necrotizing gastroenteritis, severe metabolic
acidosis, coma, and death.
• Urgent treatment - Necessary.
• Whole bowel irrigation - To flush out unabsorbed
pills.
• Gastric lavage with sodium bicarbonate – To render
iron insoluble
• Desferrioxamine - Potent iron-chelating compound,
can be given intravenously to bind iron that has
already been absorbed & to Promote its excretion in
urine and feces
17. • Iron overload - Hemochromatosis
• Most commonly occurs in patients
▫ Inherited hemochromatosis, a disorder
characterized by excessive iron absorption
▫ Patients - receive many red cell transfusions
over a long period of time (eg individuals with ß-
thalassemia).
18. • Chronic iron overload in absence of anemia -most
efficiently treated by intermittent phlebotomy.
• One unit of blood - removed every week or so until all
of the excess iron is removed.
• Iron chelation therapy using
▫ Parenteral desferrioxamine or
▫ Oral iron chelator deferasirox is
Less efficient more complicated, expensive, and hazardous.
Used for iron overload cannot be managed by phlebotomy
(Inherited and acquired causes of refractory anemia such as
thalassemia major, sickle cell anemia, aplastic anemia etc.)
19. Folic acid
• Consist pteridine, para amino benzoic acid,
glutamic acid
• Dietary folic acid – polyglutamates- cleaved of in
intestine - Maximum absorption – jejunum
• Folic acid is transported in blood -Methyl tetra
hydrofolate.
• THFA participates in many one carbon transfer
reaction
20. Metabolic functions
Conversion of homocysteine to methionine
Methyl THFA B12 methionine
THFA methyl B12 homocysteine
Generation of thymidylate – essential constituent of DNA
Conversion of serine to glycine requires THFA → results in
formation of methylene THFA - utilised in thymidylate
synthesis.
Purine synthesis & Generation & utilisation of formate pool.
Histidine metabolism – mediating formimino group transfer.
21. Main uses –
• Treatment of megaloblastic anemia.
• Indicated in pregnancy – To prevent neural
tube defects.
• Leucovorin – Used to prevent toxicity of
methotrexate.
22. Vitamin B12
• Contains cobalt
• Forms present in diet – Cyanocobalamin &
hydroxycobalamin
• Present – Animal foods
• Vegetable source – Legumes
• Vitamin B12 + intrinsic factor – Absorbed in terminal ileum
Deficiency of Vitamin B12 –
1) Megaloblastic anemia
2) Sub acute combined degeneration of cord
23. Metabolic functions
1. Conversion of homocysteine to methionine –methionine is
needed as methyl group donor in many metabolic
reactions and protein synthesis.
2. Purine & pyrimidine affected – defective one carbon
transfer.
3. Conversion of malonic acid to succinic acid- important
step in propionic acid metabolism & links carbohydrate
metabolism with lipid metabolism.
4. Conversion methionine to S adenosyl methionine – SAM
is needed in synthesis of phoshpholipids & myelin.
5. Essential for cell growth & multiplication
25. Erythropoiesis Stimulating Agents
Pharmacological substance stimulates red blood cell
production.
• Recombinant human erythropoietin (rHuEPO,
epoetin alfa) –
▫ Produced in a mammalian cell expression system.
▫ Half -life - 4 -13 hours in patients with chronic
renal failure.
▫ Epoetin alfa is generally administered three times
a week.
26. Erythropoetin
Darbepoetin alfa
▫ Modified form of erythropoietin more heavily
glycosylated as a result of changes in amino acids.
▫ 2 to 3 fold longer half-life than epoetin alfa.
▫ Darbepoetin is administered weekly.
27. Methoxy polyethylene
glycol epoetin beta
▫ Isoform of erythropoietin covalently attached
to a long polyethylene glycol polymer.
▫ Single IV or SC dose at 2-week or monthly
intervals.
▫ Methoxy polyethylene glycol-epoetin beta should
not be used for treatment of anemia caused by
cancer chemotherapy
Clinical trial found significantly more deaths among
patients receiving this form of erythropoietin.
28. Pharmacodynamics
• Stimulates erythroid proliferation and
differentiation by interacting with
erythropoietin receptors on red cell
progenitors.
• Erythropoietin receptor is member of the
JAK/STAT superfamily of cytokine
receptors.
• Inverse relationship exists between the
hematocrit or hemoglobin level & serum
erythropoietin level.
29. • Endogenous Erythropoietin levels are low - Renal
disease
• Endogenous erythropoietin levels are high
Primary bone marrow disorders (aplastic anemia,
leukemias, myeloproliferative and myelodysplastic
disorders etc) and
Most nutritional and
Secondary anemias
Less likelihood of a response to exogenous
erythropoietin
Most likely to respond to treatment with exogenous
erythropoietin
30. Clinical Pharmacology
• Availability of erythropoiesis-stimulating
agents (ESAs) significant positive impact for
patients with several types of anemia.
• Dosages of ESAs - Maintain a target
hemoglobin up to, but not exceeding, 10-12
g/dL.
• Oral or parenteral iron supplementation - To
support increased erythropoiesis
31. Indications
A. Patients with chronic renal failure.
B. HIV-infected patients treated with zidovudine.
C. Cancer patients treated with myelosuppressive
cancer chemotherapy.
D. Patients scheduled for elective, non cardiac ,non
vascular surgery.
32. • ESAs improve -
• Reticulocyte count - 10 days
• Hematocrit & hemoglobin level - 2 weeks
• Often eliminate the need for transfusions
• Improve quality of life
33. Toxicity
• Most common adverse effects of erythropoietin are
▫ Hypertension and
▫ Thrombotic complications.
• In March 2007, FDA issued a warning that patients
with chronic renal failure or cancer whose serum
hemoglobin is raised to more than 12 g/dL with an
ESA
Face a greater risk of a thrombotic event
or with advanced head and neck cancers - faster tumor
growth.
34. MYELOID GROWTH FACTORS
Chemistry & Pharmacokinetics
Recombinant human G-CSF ( rHuG-CSF- filgrastim)
▫ Produced in a bacterial expression system
▫ Nonglycosylated peptide of 175 amino acids, with a
molecular weight of 18 kDa
Recombinant human GM-CSF( rHuGM-CSF- sargramostim)
▫ Produced in a yeast expression system
▫ Partially glycosylated peptide of 127 amino acids with three
molecular species with molecular weights of 15,500; 15,800;
and 19,500.
▫ Serum half-lives of 2 hours after IV or SC administration.
35. Pharmacodynamics
• Myeloid growth factors stimulate
▫ Proliferation &
▫ Differentiation by interacting with specific
receptors (members of JAK/STAT superfamily)
found on myeloid progenitor cells.
• G-CSF - Remarkable ability to mobilize
hematopoietic stem cells, i.e, to increase their
concentration in peripheral blood.
• Peripheral blood stem cells (pbscs) are used for
autologous & allogeneic hematopoietic stem cell
transplantation.
36. GM-CSF
• Broader biologic actions than G-CSF.
• Multipotential hematopoietic growth factor that
stimulates
▫ Proliferation and
▫ Differentiation of early and late granulocytic
progenitor cells as well as erythroid and
megakaryocyte progenitors.
• GM-CSF acts together with interleukin-2 to stimulate
T-cell proliferation.
37. Clinical Pharmacology
A. Cancer Chemotherapy-Induced Neutropenia
• Growth factor accelerates the rate of neutrophil
recovery after dose-intensive myelosuppressive
chemotherapy.
• Reduces the duration of neutropenia and raises the
nadir count (lowest neutrophil count seen following a
cycle of chemotherapy.)
38. Clinical guidelines recommend G-CSF for
patients at high risk for
Febrile neutropenia based on age, medical history & disease
characteristics
Patients receiving dose-intensive chemotherapy regimens that
carry a greater than 40% risk of causing febrile neutropenia
Prior episode of febrile neutropenia after cytotoxic
chemotherapy
At high risk for febrile neutropenia
Patients who are unlikely to survive an episode of febrile
neutropenia
39. • GM-CSF reduces the duration of neutropenia
after cytotoxic chemotherapy.
• Growth factors accelerate neutrophil
recovery and reduce infection rates and days
of hospitalization.
• G-CSF and GM-CSF have FDA approval for
treatment of patients with AML.
40. Pegfilgrastim
▫ Covalent conjugation product of filgrastim and a form of
polyethylene glycol
▫ Longer serum half-life than recombinant G-CSF -
▫ Alternative to G-CSF for prevention of chemotherapy-
induced febrile neutropenia.
▫ Shorten the period of severe neutropenia slightly more
than G-CSF.
Injected once per myelosuppressive chemotherapy
cycle instead of daily for several days
42. B. Other Applications
• G-CSF and GM-CSF - proved to be effective
neutropenia associated with
Congenital neutropenia
Cyclic neutropenia
Myelodysplasia and
Aplastic anemia.
• Myeloid growth factors play an important role
in autologous stem cell transplantation for
patients undergoing high-dose chemotherapy.
43. • Allogeneic bone marrow transplantation for
treatment of hematologic malignancies or bone
marrow failure states.
• G-CSF is most commonly used for PBSC mobilization
because of its increased efficacy and reduced
toxicity compared with GM-CSF.
• Dose - 5- 10mcg/kg/d subcutaneously for 4 days.
• On the fifth day they undergo leukapheresis.
• Goal is to infuse at least 5 × 10 6 CD34 cells/kg
44. Plerixafor
Plerixafor can be added to G-CSF for patients with
multiple myeloma or non-hodgkin’s lymphoma who
respond suboptimally to G-CSF alone, the novel
hematopoietic stem cell mobilizer.
45. Toxicity
• G- CSF & pegfilgrastim can cause bone pain –
Reversible
• GM-CSF - more severe side effects- at higher doses.
▫ Fever
▫ Malaise
▫ Arthralgias
▫ Myalgias and
▫ Capillary leak syndrome (peripheral edema and pleural or
pericardial effusions)
• Splenic rupture - rare but serious complication of
the use of G-CSF for PBSC
46. MEGAKARYOCYTE GROWTH
FACTORS
• Patients with thrombocytopenia have a high risk of
hemorrhage.
• Recombinant form of IL-11 was the first agent to
gain FDA approval for treatment of
thrombocytopenia.
• Romiplostim was approved by the FDA for idiopathic
thrombocytopenic purpura in 2008.
47. Chemistry & Pharmacokinetics
• Oprelvekin - Recombinant form of IL-11 is
produced by expression in Escherichia coli.
• Half-life - 7- 8hours when the drug is
injected subcutaneously.
48. • Romiplostim (AMG 531) is a member of new
class of therapeutics called peptibodies.
• Half -life is inversely related to the serum
platelet count
Romiplastim has longer half-life in patients with
thrombocytopenia and a shorter half-life in patients
whose platelet counts have recovered to normal levels
49. Eltrombopag
• Orally active small molecule agonist at
thrombopoietin receptor.
• Licensed in 2008 for use in patients with severe
idiopathic thrombocytopenia {have failed to
respond adequately to first-line treatments.}
• Because of concerns about hepatotoxicity and
hemorrhage, eltrombopag is restricted to use by
registered physicians and patients and its use
requires close monitoring of liver enzymes.
50. Pharmacodynamics
• Interleukin-11 acts - Specific cell surface cytokine
receptor to stimulate the growth of multiple lymphoid
and myeloid cells.
• Acts synergistically with other growth factors to
stimulate the growth of
▫ Primitive megakaryocytic progenitors
▫ Increases the number of peripheral platelets and
neutrophils
• Romiplostim - high affinity for the human Mpl
receptor. It causes a dose-dependent increase in
platelet count that begins on day 5 after subcutaneous
administration and peaks at 12-15 days.
51. Clinical Pharmacology
• Oprelevkin - Secondary prevention of
thrombocytopenia in patients receiving
Cytotoxic chemotherapy for Treatment of
nonmyeloid cancers.
• Clinical trials show that it reduces the
number of platelet transfusions required by
patients who experience severe
thrombocytopenia after a previous cycle of
chemotherapy.
52. • Oprelevkin is given by subcutaneous injection
at a dose of 50 mcg/kg/d.
• It is started 6-4 hours after completion of
chemotherapy and continued for 14 -21 days
or until the platelet count passes the nadir
and rises to more than 50,000 cells/L.
53. Toxicity
• Most common adverse effects of oprelevkin are
fatigue, headache, dizziness, and cardiovascular
effects. (reversible)
• Cardiovascular effects include
▫ Anemia (due to hemodilution),
▫ Dyspnea (due to fluid accumulation in the lungs), and
▫ Transient atrial arrhythmias.
▫ Hypokalemia.
• Romiplostim - Well tolerated
- Potential long-term concern treated
with romiplostim - ↑ in bone marrow reticulin, (marker
of myelodysplastic or myeloproliferative processes)
54. summary
Mechanism of action Clinical application
Iron Required for biosynthesis of heme
& heme-containing proteins,
hemoglobin
& myoglobin
Microcytic hypochromic
anemia
Vitamin B12 Cofactor required for essential
enzymatic reactions
Megaloblastic
anemia ,
pernicious anemia
Folic acid Precursor of an essential
donor of methyl groups
used for synthesis of
amino acids, purines, and
deoxynucleotide
Megaloblastic anemia &
Prevention of
congenital neural tube
defects
55. Growth factor Drug Mechanism of
action
Clinical applications
Erythropoietin Epoietin α
Darbopoietin α
Methoxy
polyethylene
glycol epoetin
beta
Agonist of
erythropoietin
receptors
expressed by
red cell
progenitors
Anemia in CRF,
Myelosuppressive drug use
G-CSF
GM- CSF
Filgrastim
Pegfilgrastim
Lenograstim
Sargromostim
Proliferation &
differentiation
of myeloid
growth factors
Neutropenia due to
anticancer drugs ,severe
chronic neutropenia stem
cell transplantation ,
mobilisation of PBSC
IL 11
Thrombopoietin
Oprelevkin
Romiplastin
Eltrombopag
Activates IL-11
receptors
Activate
thrombopoietin
receptor
Thrombocytopenia due to
anticancer drugs,
ITP
56. References
• The pharmacological basis of therapeutics -
Goodman and gillman (12th edition)
• Basic and clinical pharmacology – Bertram
Katzung (12th edition)
• Principles of pharmacology- H.L. Sharma(2nd
edition)
57.
58.
59.
60. • Erythropoietin has been used successfully to
offset the
▫ Anemia produced by zidovudine treatment in
patients with HIV infection and
▫ Treatment of the anemia of prematurity.
• It can also be used to reduce the need for
transfusion in high-risk patients undergoing
elective, non-cardiac, nonvascular surgery.
61.
62. • Plerixafor is eliminated primarily by the renal
route and dose must be adjusted for patients
with renal impairment.
• Drug is well tolerated.
• Most common adverse effects associated with its
use are
1. Injection site reactions
2. GI disturbances
3. Dizziness
4. Fatigue &
5. Headache.
Editor's Notes
Oral iron therapy - subject to the regulatory mechanism provided by the intestinal uptake system.
Parenteral administration - bypasses this regulatory system can deliver more iron than cant be safely stored
As few as 10 tablets of any of the commonly available oral iron preparations can be lethal in young children.
(vomiting, abdominal pain, and bloody diarrhea followed by shock, lethargy, and dyspnea)
results when excess iron is deposited in the heart, liver,pancreas, and other organs.
as is the case for many individuals with
Nonanemic individuals have serum erythropoietin levels of less than 20 IU/L.As the hematocrit and hemoglobin levels fall and anemia becomes
more severe, the serum erythropoietin level rises exponentially. Patients with moderately severe anemia usually have erythropoietin levels in the 100・00 IU/L range, and patients with severe anemia may have levels of thousands of IU/L. The most important exception to this inverse relationship is in the anemia of chronic renal failure. that use protein phosphorylation and transcription factor activation to regulate cellular function.
Kidneys cannot produce growth factor.
Folate supplementation may also be necessary in some patients
ESAs are used routinely in patients with anemia secondary to chronic kidney disease.
Allergic reactions to ESAs have been infrequent
Based on the accumulated evidence, it is recommended that the hemoglobin level not exceed 12 g/dL in patients with chronic kidney disease receiving an ESA, and that ESAs be used conservatively in cancer patients (eg, when hemoglobin levels are <10 g/dL) and with the lowest dose needed to avoid transfusion.
G-CSF and GM-CSF, the two myeloid growth factors currently available for clinical use
G-CSF stimulates proliferation and differentiation of progenitors already committed to the neutrophil lineage.
Activates the phagocytic activity of mature neutrophils and prolongs their survival in the circulation.
Neutropenia is a common adverse effect of the cytotoxic drugs used to treat cancer and increases the risk of serious infection in patients receiving chemotherapy.
It has been more difficult to show that GM-CSF reduces the incidence of febrile neutropenia, probably because GM-CSF itself can induce fever.
High-dose regimens produce extreme myelosuppression; the myelosuppression is then counteracted by reinfusion of the patient his own hematopoietic stem cells (which are collected prior to chemotherapy).
Growth factors speed the recovery from neutropenia without increasing the incidence of acute graft-versus-host disease.
It may take several separate leukaphereses to collect enough CD34 cells, especially from older patients and patients who have been exposed to radiation therapy or chemotherapy. this number of CD34 cells usually results in prompt and durable engraftment of all cell lineages.
Platelet transfusion - commonly used to treat thrombocytopenia, procedure can cause adverse reactions in the recipient;furthermore, a significant number of patients fail to exhibit the expected increase in platelet count.Thrombopoietin and IL-11 both appear to be key endogenous regulators of platelet production.
Interleukin-11 - protein produced by fibroblasts and stromal cells in the bone marrow
Peptibodies which are peptides with key biologic activities covalently linked to antibody fragments that serve to extend the peptides half-life
Mpl-binding peptide has no sequence homology with human thrombopoietin and there is no evidence in animal or human studies that the Mpl-binding peptide or romiplostim induces antibodies to thrombopoietin.After subcutaneous administration, romiplostim is eliminated by the reticuloendothelial system with an averagehalf-life of 3- 4 days.
Although IL-11 has broad stimulatory effects on hematopoietic cell lineages in vitro, it does not appear to have significant effects on the leukopenia caused by myelosuppressive chemotherapy.
Romiplostim well tolerated except for a mild headache on the day of administration
that form tetrahydrofolate, convert
homocysteine to methionine,
& metabolize L-methylmalonyl-CoA( vit b 12)
Erythropoietin is one of the drugs banned by the International
Olympic Committee. The use of erythropoietin by athletes is
based on their hope that increased red blood cell concentration will
increase oxygen delivery to muscles and improve performance.
Early clinical trials of plerixafor revealed a remarkable ability to increase CD34 cells in peripheral blood. Plerixafor mobilizes CD34 cells by preventing chemokine stromal cell-derived factor-1a (SDF-1a) from binding to CXCR4 and directing the CD34 cells to home・to the bone marrow.