This document summarizes the pharmacotherapy of migraine. It outlines the pathophysiology including vascular, neurogenic, and neurovascular theories. It discusses acute treatment with non-specific medications like NSAIDs and specific treatments like triptans. Preventive treatment options are also covered including antidepressants, beta-blockers, anti-epileptics, calcium channel blockers, and newer targets such as CGRP antagonists and nitric oxide synthase inhibitors.
learning objective includes : pathogenesis,clinical features, classification of migraine, pharmacology about specific antimigraine drugs, coverage to newer triptan- Lasmiditan and newer prophylactic drug Erenumab a CGRP receptor antagonist.
learning objective includes : pathogenesis,clinical features, classification of migraine, pharmacology about specific antimigraine drugs, coverage to newer triptan- Lasmiditan and newer prophylactic drug Erenumab a CGRP receptor antagonist.
Lecture covers the pharmacology of anticholinergic drugs. Includes classification, therapeutic uses, adverse effects of anticholinergics. Atropine has been described as prototype drug.
Hello friends. In this PPT I am talking about antiepileptic drugs. If you like it, please do let me know in the comments section. A single word of appreciation from you will encourage me to make more of such videos. Thanks. Enjoy and welcome to the beautiful world of pharmacology where pharmacology comes to life. This video is intended for MBBS, BDS, paramedical and any person who wishes to have a basic understanding of the subject in the simplest way.
Lecture covers the pharmacology of anticholinergic drugs. Includes classification, therapeutic uses, adverse effects of anticholinergics. Atropine has been described as prototype drug.
Hello friends. In this PPT I am talking about antiepileptic drugs. If you like it, please do let me know in the comments section. A single word of appreciation from you will encourage me to make more of such videos. Thanks. Enjoy and welcome to the beautiful world of pharmacology where pharmacology comes to life. This video is intended for MBBS, BDS, paramedical and any person who wishes to have a basic understanding of the subject in the simplest way.
Management of Refractory, Super refractory SE and.pptxsumeetsingh837653
diagnosis and treatment of refractory and super refractory status epilepticus and NORSE
treatment guidelines of status epilepticus
dosages of various antiepileptic used in management of status epilepticus
Impact of drug therapy on various neurological conditions and its effects on rehabilitation; conditions like stroke, parkinson's disease,vertigo and also its effects on various impairments like spasticity, sensory impairments, cognition
Anti-epileptic Drugs : Applications Outside Epilepsy
(Reverse Engineering)
Anti-epileptic Drugs are Approved and Used Outside Epilepsy. Phenytoin, Carbamazepine, and Oxcarbazepine have proven efficacies in Trigeminal Neuralgia.
Gabapentin and Pregabalin are established in the treatment of postherpetic neuralgia (PHN) and painful diabetic neuropathy (PDN).Divalproex sodium is approved for use in the treatment of bipolar disorder and prevention of migraine.
Overlapping pathophysiology of some disorders and mechanisms of action of many Anti-epileptic Drugs : Applications Outside Epilepsy
(Reverse Engineering)antiepileptic drugs are evidently responsible for the applications of anti-epileptic drugs (AEDs) in clinical conditions outside epilepsy.
New drug candidates will, therefore, be developed for both the sets of therapeutic applications (epilepsy and outside epilepsy).
Clinicians and healthcare professionals need to familiarize themselves with AI, including its applications and appropriate implementation. Here I am explaining about AI in the context of the disease life cycle.
Pharmacokinetic concepts and principles in humans in order to design individualized dosage regimens which optimize the therapeutic response of a medication while minimizing the chance of an adverse drug reaction.
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
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
Recomendações da OMS sobre cuidados maternos e neonatais para uma experiência pós-natal positiva.
Em consonância com os ODS – Objetivos do Desenvolvimento Sustentável e a Estratégia Global para a Saúde das Mulheres, Crianças e Adolescentes, e aplicando uma abordagem baseada nos direitos humanos, os esforços de cuidados pós-natais devem expandir-se para além da cobertura e da simples sobrevivência, de modo a incluir cuidados de qualidade.
Estas diretrizes visam melhorar a qualidade dos cuidados pós-natais essenciais e de rotina prestados às mulheres e aos recém-nascidos, com o objetivo final de melhorar a saúde e o bem-estar materno e neonatal.
Uma “experiência pós-natal positiva” é um resultado importante para todas as mulheres que dão à luz e para os seus recém-nascidos, estabelecendo as bases para a melhoria da saúde e do bem-estar a curto e longo prazo. Uma experiência pós-natal positiva é definida como aquela em que as mulheres, pessoas que gestam, os recém-nascidos, os casais, os pais, os cuidadores e as famílias recebem informação consistente, garantia e apoio de profissionais de saúde motivados; e onde um sistema de saúde flexível e com recursos reconheça as necessidades das mulheres e dos bebês e respeite o seu contexto cultural.
Estas diretrizes consolidadas apresentam algumas recomendações novas e já bem fundamentadas sobre cuidados pós-natais de rotina para mulheres e neonatos que recebem cuidados no pós-parto em unidades de saúde ou na comunidade, independentemente dos recursos disponíveis.
É fornecido um conjunto abrangente de recomendações para cuidados durante o período puerperal, com ênfase nos cuidados essenciais que todas as mulheres e recém-nascidos devem receber, e com a devida atenção à qualidade dos cuidados; isto é, a entrega e a experiência do cuidado recebido. Estas diretrizes atualizam e ampliam as recomendações da OMS de 2014 sobre cuidados pós-natais da mãe e do recém-nascido e complementam as atuais diretrizes da OMS sobre a gestão de complicações pós-natais.
O estabelecimento da amamentação e o manejo das principais intercorrências é contemplada.
Recomendamos muito.
Vamos discutir essas recomendações no nosso curso de pós-graduação em Aleitamento no Instituto Ciclos.
Esta publicação só está disponível em inglês até o momento.
Prof. Marcus Renato de Carvalho
www.agostodourado.com
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!
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Title: Sense of Smell
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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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.
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
- 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
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
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.
2. • Outline
• Migraine
• Pathophysiology
Theories
Vascular theory
Neurogenic theory
Neurovascular theory
• Acute treatment of migraine
Non-specific treatment
Specific treatment
• Preventive treatment of migraine
• Newer targets and drugs
3. Migraine headache
First description of migraine with visual aura.
• Second most common type of primary headache
• Migraine is chronic neurological disorder
characterized by episodic attacks of headache
and associated symptoms.
• Migraine prevalence is approximately 18% in
females and 6% in males.
• The brain of the migraineur is particularly
sensitive to environmental and sensory stimuli.
4. • A recent economic model estimated that losses due
to decreased productivity are roughly $1.9 million for
a company with 10,000 employees
5. Pathophysiology of migraine
• Vascular theory-attributes the phenomenon of
vasodilatation.
• Neurogenic theory- neuronal events, cortical
spreading depression.
• Third theory - accommodate vascular
modifications with neuronal dysfunction.
6. Vascular theory
• Harold G Wolff first one to explain
• Vasoconstriction and ischemia accounts for
symptoms of migraine aura,
• Reactive vasodilatation activate primary
sensory neurons.
• Therapies provides evidence for this theory.
7. Cortical spreading depression
• NMDA receptors involved in the genesis and propagation of
CSD. CSD was blocked by NMDA receptors antagonists in
various experimental models
Long lasting depression of
neuronal activity.
8. Cortical spreading depression
perivascular trigeminal and
parasympathetic nerve activation, release
of vasodilator mediators, CGRP,
neurokinen A, substance P
(pain signal)trigeminal ganglion
trigeminal nucleus caudalis
trigeminocervical complex
14. Goals for acute treatment
1. Treat attacks rapidly and consistently without
recurrence.
2. Restore the patient’s ability to function.
3. Minimize the use of back-up and rescue
medications.
4. Be cost-effective for overall management.
5. Have minimal or no adverse events.
15. Non-specific Rx of migraine
“NSAIDs”
• PGE2 and PGI2 reduce the threshold to
stimulation of nociceptors, causing peripheral
sensitization
• CGRP release from the terminals of the
trigeminal sensory neurons is modulated by
PGE2
• Blockade cyclooxygenase (COX) and hence
reduced synthesis of PG
16. Forest plot of comparison: Ibuprofen
400 mg versus placebo
26% 12%
• Cochrane Database of Systematic Reviews 2010, Issue 10. Art. No.:
CD008039
19. Anti-emetics/caffeine – combination
with NSAIDs
• Metoclopramide effective for nausea and
vomiting associated with certain types of
headaches.
• D2 antagonistic action might be responsible
for relieve of migraine
• Caffeine, Block the adenosine receptor,
Vasoconstricting action.
20. Efficacy and Safety of Acetaminophen, Aspirin, and Caffeine in
Alleviating Migraine Headache Pain: Double-blind,
Randomized, Placebo-Controlled Trials
• Arch Neurol. 1998;55(2):210-217
21. Specific acute treatment
• Triptan-Sumatriptan, naratriptan,
rizatriptan, eletriptan, zolmitriptan,
almotriptan & frovatriptan
• Selective activity on 5-HT1B/1D agonist.
• Mechanisms of action
Cranial vasoconstriction
Modulating neurotransmitter release from
neuronal terminals.
22.
23. • The triptans -preventing the peripheral release of
vasoactive peptides (CGRP), reduce PPE.
• Also inhibit the abnormal activation of peripheral
nociceptors.
• The 5-HT1D receptor-selective agonist PNU-
142633 showed greater potency than
sumatriptan in blocking electrically induced PPE,
and had little to no detectable vascular activity in
carotid, meningeal arteries
24. Adverse Effects and Contraindications
• coronary artery vasospasm, transient myocardial
ischemia, atrial and ventricular arrhythmias, MI
• Irritation at the site of injection. The most
common side effect of sumatriptan nasal spray is
a bitter taste.
• Contraindicated- coronary artery disease ,
history of stroke or transient ischemic attacks,
cerebrovascular or peripheral vascular disease,
27. Ergot alkaloids
• The pharmacological effects of the ergot
alkaloids are varied and complex; partial
agonists or antagonists at serotonergic,
dopaminergic, and adrenergic receptors
• Ergot alkaloids at 5-HT1B/1D receptors likely
mediate their acute anti-migraine effects
28. Selection of patients – ergot
• Which patients?
Patients requiring migraine-specific therapy
Patients established on ergotamine
• Special cases
Patients with very long attacks
Patients with frequent headache recurrence
29. Adverse Effects and Contraindications
of Ergot Alkaloids
• Nausea and vomiting, due to a direct effect on
CNS emetic center.
• contraindicated in pregnant, peripheral vascular
disease, coronary artery disease, hypertension,
impaired hepatic or renal function
• In contrast to triptans, the contractile effect of
ergotamine in the human isolated coronary
artery is long- lasting and persists even after
repeated washings
30. • Comparison of vasoconstriction action of
ergotamine and triptan
• MaassenVanDenBrink et al., 1998
32. Indications
1. Two or more attacks per month that
significantly interfere with the patient’s daily
routine activity
2. An unsatisfactory response to acute therapy
3. contraindication to acute treatments and
adverse effects (AEs) related to them.
4. Uncommon migraine conditions, including
hemiplegic migraine, migraine with
prolonged aura or migrainous infarction.
33. The potential mechanisms of migraine
preventive medications
• Raising the threshold to migraine activation by
stabilizing a more reactive nervous system
• Enhancing antinociception
• Inhibiting CSD
• Inhibiting peripheral and/or central
sensitization
• Blocking neurogenic inflammation
35. Antidepressants
• Amitriptyline alters the 5-HT synthetic rate at
the dorsal raphe nucleus.
• Enhancement of the pain threshold produced
by AMT seems to be mediated by sodium
channels, L-type calcium channels inhibition.
• Chronic daily administration of AMT
suppresses CSD, whereas acute treatment is
ineffective.
36. 50% reduction in migraine headaches
TCA Vs placebo
Jackson, JE., et al. (2010). Tricyclic antidepressants and headaches: systematic review and
meta-analysis. Bmj, 341(oct20 1)
37. • SSRI- In a recent review, SSRIs resulted as
efficacious as placebo for preventing migraine
and less effective than TCA.
• In a randomized controlled study fluoxetine,
venlafaxine, duloxetine versus placebo,
reduced frequency of migraine attacks, but
not significant.
38. Beta blocker
• Clinical findings support the efficacy of
propranolol, timolol, atenolol, nadolol and
metoprolol in migraine preventive treatment.
• Exhibit high affinity for 5-HT receptor( 1a,
1b/d,2a)
• propranolol blocked CSD in rats, without
altering regional cerebral blood flow and
systemic arterial blood pressure
39. Cont…
• 53 studies including meta-analysis involving
2403 patients who are treated with either
propranolol and/or placebo , propranolol
yielded 44% reduction in migraine attack.
• Two clinical trials valproic acid compared with
propranolol, in both trials efficacy is identical.
40. Anti-epileptics
• An unbalanced activity b/w excitatory
glutamatergic transmission and GABAnergic
inhibition, abnormal activation of voltage-
operated ionic channels; Na , Ca channels ,
has been postulated in these two pathological
condition.
• “Valproate, topiramate”, gabapentin,
lamotrigine are best for prophylaxis.
41. Cont..
• VPA, TPM, Effect on voltage gated Na channels
modify the neuronal excitability(CSD), role of
Na channels are proved in FHM.
• VPA reduces the neurogenic inflammation,
plasma extravasation (Cutrer et al., 1997),
possibly through a GABA-mediated
mechanism
42. Calcium channel blockers
• In an experimental model of neurogenic
inflammation, blockade of L-type channels
attenuates dural vasodilatation.
• flunarizine could exert its antimigraine effect
by reducing neural NO synthase (NOS) activity
• In a double- blind study, flunarizine 5 mg/day
was as effective as propranolol 160 mg/day in
reducing the attack frequency.
43. Newer targets and drugs
• Non-triptan 5-HT1 agonist,
5-HT1D agonists (PNU-109291 and PNU- 142633)
are potent inhibitors of dural plasma protein
extravasation (PPE)
LY334370, which is a selective 5-HT1F agonist,
inhibits single cell firing in the trigeminal nucleus
caudalis (TNC)
44. CGRP antagonist-
BIBN4096BS(olcegapant)
• CGRP mediates dilation of cerebral
vasculature and increases in cerebral blood
flow.
• CGRP-induced vasodilation can activate
nociceptors on cerebral vessels.
• In humans, intravenous human CGRP
administration induces migraine-like headache
in susceptible migraineurs
45.
46. CGRP Antagonist BIBN 4096
BS(olcegapant) Vs placebo
• N Engl J Med. 2004 Mar 11;350(11):1104-10
47. Nitric oxide synthase inhibitor
• An intravenous infusion of nitroglycerin (NTG)
releases NO, causes migraine in more than 60%
of migraineurs , and activates trigeminal neurons
in experimental animals.
• In a small RCT, 546C88, a non-selective NOS
inhibitor, was administered intravenoulsy to
migraineurs during an acute attack (Lassen et al.,
1998). The 2-hr headache response rate was 67%
(10/15) on 546C88 versus 14% (2/14) on placebo
Primary headaches are those in which headache and its associated features are the disorder in itself, whereas secondary headaches are those caused by exogenous disorders(subarchoidhemmarage, brain tumor, head injury)@@Nausea,Photophobi,Lightheadedness,Scalp tenderness,Vomiting@@Some people who get migraines have warning symptoms, called an aura, before the actual headache begins. An aura is a group of symptoms, including vision disturbances, that are a warning sign that a bad headache is coming---@@10-45yr, female, families, This sensitivity is amplified in females during the menstrual cycle. Headache can be initiated or amplified by various triggers, including glare, bright lights, sounds, or other afferent stimulation; hunger; excess stress; physical exertion; stormy weather or barometric pressure changes; hormonal fluctuations during menses; lack of or excess sleep; and alcohol or other chemical stimulation.
significant burden for both the individual and society, including loss of productivity, limitations in activity, and decreased quality of life , Migraine attacks can severely impair the ability to work and require bed rest, A recent economic model estimated that losses due to decreased productivity are roughly $1.9 million for a company with 10,000 employees
since experimental observations showedthat the diameters of the extracranial arteries in migraine patientswere dilated. Consequently, the firstclass of drugs proposed for the treatment of migraine was thosethat produce vasoconstriction.The second hypothesis, the neurological theory, considersmigraine attacks as a result of neuronal events, occurring in different brain areas and mediated by alterations in neurotransmision system.3This theory regards as amajor pathogenic step of migraine the release of inflammatoryneuropeptides from the trigeminal system, with a consequentdilatation of meningeal vessels.
Support of the vascular theory comes from studies demonstrating oligemia during migraine aura, and increase in blood flow during the headache phase. Also, when a patient with migraine is given a vasodilator such as nitrate, the headache----- fuctional imaging testing shows, hypreemia starts and oligemia is not appreciated, no clear evidence of significant increase in diameter of middle cerebral atrey during migraine attack. Recent study shows migraine can be induced without dilation of vessles.( N methyl D aspertic acid &kainic acid induced hyperalgesia)
cortical spreading depression (CSD), a short-lasting, intense wave of neuronal and glial cell depolarization. CSD spreads slowly over the cortex at a rate of approximately 2–5 mm/ min and is followed by long lasting depression of neuronal activity. migraine is caused by abnormal brain activity, which can be triggered by a number of factors. However, the exact chain of events remains unclear.Karl lashley neurologist migraine patient observed his own barin activity during aura and headache and explained scotoma is due to neuronal inactivation in the region occipotal cortex and scintillation is due to hyperctivation…….. Lean given the name CSD expained detail in animal model.
In some cases, dilated superficial temporal arteries visibly pulsate. Those symptoms led migraine theorists in the 1940s to believe vascular dilation and pulsation caused the associated headache pain. Neurokinen A, substance P, Activation of these Atrigeminal fibers cause the release of CGRP(Goadsby et al., 1988) that in turn causes vasodilation of cranial blood vessels (Williamson et al., 1997c). Recent clinical trial evidence suggests that blockade of CGRP has a potent acute antimigraine effect (Olesen et al., 2003).
The key pathway for pain in migraine is the trigeminovascular input from the meningeal vessels, which passes through the trigeminal ganglion and synapses on second-order neurons in the trigeminocervical complex (TCC). These neurons in turn project in the quintothalamic tract and, after decussating in the brainstem, synapse on neurons in the thalamus. Important modulation of the trigeminovascular nociceptive input comes from the dorsal raphe nucleus, locus coeruleus, and nucleus raphe magnus
According to “US headache consortium” While headache and migraine are often considered synonymous, they are not. Migraine is always more than headache. Learning the non-headache symptoms associated with your migraine is essential to early recognition of an attack.
Acute rx stop the progression of attack, reduce the pain and functional impression, preventive- to prevent the frequency and severity of anticipated attack
Treatmnet depends on subtype, frequency, severity ,, non specific drugs used to releive the pain and associated symptome , specific treatmet controls migraine attack but the are not usefull in non headache pain disorder.
In scientific studies the percentage of people achieving pain-free status within 2 hours of treatment has been almost double for those treating early (whenheadache is mild in intensity) vs those treating when headache is moderate or severe.
NSAIDs also have important central actions in the spinal cord and brain. Both COX-1 and COX-2 are expressed in the spinal chord under basal conditions and release PGs in response to peripheral pain stimuli
Forest plot of comparison: 2 Ibuprofen 400 mg versus placeboThe proportion of participants pain-free at 2 hours with ibuprofen 400 mg was 26% (401/1553; range 14% to 33%)• The proportion of participants pain-free at 2 hours with placebo was 12% (128/1042; range 2% to 24%)The final meta analysis results, the diamond doesn’t cross the ‘line of no effect’,
Figure 3. Forest plot of comparison: 1 Paracetamol 1000 mg versus placebo, outcome: 1.3 Headache relief at 2 hours.
is a dopamine and serotonin antagonist that is used off-label to treat migraine headaches, A meta-analysis published in 2004 analyzed 13 randomized controlled trials evaluating parenteral metoclopramide for the treatment of migraine.The A2A receptor is responsible for regulating myocardial blood flow by vasodilating the coronary arteries,
Initial choice in moderate to severe migraine if it is not releved by NSAIDs and any combination, The vasoconstrictive properties of triptans are mediated by an action on 5-HT1B in arterial smooth muscle, it is still unclear whether triptan activation of vascular 5-HT1B receptors is necessary for the treatment of migraine, capacity of these receptors to cause constriction of intracranial blood vessels including arteriovenous anastomoses, both 5-HT1B and 5-HT1D receptors serve as presynaptic autoreceptors
abnormal activation of nociceptors in the dura mater triggers vascular changes, including plasma protein extravasation (PPE), In animal models and in humans, CGRP is elevated in the external jugular vein after stimulation of the trigeminal ganglion as well as during migraine attacks. Consistent with a peripheral action for triptans, treatment with sumatriptan reduces CGRP levels as the migraine subsides
predominantly in patients with risk factors for coronary artery disease
In order to select one drug among 8 aviabletritan in market, for treatment in patient, NNT, DNT is gives very valuable information about efficay and cost effictivenees,,,,,,,,,,, number of patients who must be treated in order for one patient to derive a desired level of efficacy from the treatment…… When currently aviaable triptan were comparered using a NNT/ DNT showed– most of studies has done using primary endpoint as headache response within 2hr of post treatment. To measure the Therapeutical effectiveness NNT is better primary endpoint then traditional headche response of 2hr after treatment,,, this placebo effect is also included, BUT, Funding for this research was provided by Pfizer, Inc., manufacturer of eletriptan,
No. of doses needed to treat in a population to achive a desired level of efficacy in one patient, DNT 1 signify single dose is effective in all patinets.
The multiple pharmacological effects of ergot alkaloids have complicated the determination of their precise mechanism of action in the acute treatment of migraine
Nausea about 10% is most probably caused by a direct effect onCNSemetic centres. Ergotamine has a low degree of receptor selectivity which increases the risk of experiencing a drug-induced side-effect,,,,,,,,,,,,, contraindicated in pregnant because the drugs may cause fetal distress and miscarriage
Contraindication – pregnancy, peripheral vascular disease, coronary hearth disease, uncontrolled hypertension, stroke, impaired hepatic or renal function, and sepsis. ergotamine should not be taken within 6 h of the use of triptans, and similarly triptans should not be administered within24hof ergotamine.
Aim- reduce the frequency, duration and/or severity of migraine attack. Improving the responsiveness to acute
a , FDA approved, b inconclusive
Amitriptyline is a first-line agent for migraine prophylaxis4 and is the only antidepressant with consistent evidence supporting its effectiveness for this use Use of antidepressants in migraine prophylaxis is based on the hypothesis of dysfunction of central 5-HT availability in migraine. Depression and migraine can be considered disorders of low brain serotonergic activity.
Discovered by chance, no beta 1 since selective(metaprolol), non selective(propronolol) both are effective drugs, atenololtimolol are not lipophilic, so penetration into CNS not, ,,, B blockers with intrensicsympathomimetic action , pindolol, acebutolol fail to demonstrate effcicacy in migraine.
Efficacy – reduction in frequency of attack.
AED might increase threshold of induction of CSD, reduce the progression.
VPA, by enhancing GABAergic inhibition, reduces the neurogenic inflammation implicated in migraine , A heterozygous missense mutation in the neuronal voltage-gated Na+ channel gene SCN1A has been found in families with FHM and also in some forms of epilepsy, Sensitization of sensory neurons following the release of inflammatory mediators is associated with an increase in Na+ conductance [33], and increases in the expression of Na+ channels occur in models of persistent inflammation……….. VPA and TPM inhibit the persistent Na+ current at concentrations lower than those blocking the fast Na+ current. rapidly activating and inactivating “transient” Na currents that are grossly similar across cells. Nevertheless, neurons differ in the amplitude of “persistent” Na current remaining after transient currents inactivate …. VPA decreases dural plasma extravasation induced either by trigeminal stimulation or by intravenous substance P administration [57]. The same effect is caused by muscimol, a GABAA receptor agonist
1d failed in human,,,,,,,,,, L– reached Phase 2 trial,
First, CGRP is located on sensory terminals of the trigeminal nerve, and is released following stimulation of the nerve,
The rate of response to pain two hours after treatment — the main end point of the study — was significantly higher after the infusion of BIBN 4096 BS than after the infusion of placebo………. Significantly more patients (66%) reported relief of headache (primary endpoint, improvement from moderate or severe pain to mild or none at 2hr)
α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (also known as AMPA receptor, AMPAR, orquisqualate receptor) is a non-NMDA-type ionotropic transmembrane receptor for glutamate that mediates fastsynaptic transmission in the central nervous system (CNSMerck discontinued the development of telcagepant, a promising new drug which represents a new class of migraine drugs, so-called CGRP antagonists. These drugs appear to be as effective as sumatriptan (Imitrex) and other triptans in aborting a migraine attack, but do not carry an increased risk of strokes and heart attacks which can occur, albeit very rarely, with triptans. Telcagepant was also tested as a daily preventive dr ug for migraines and in those trials some patients developed minor liver abnormalities