1 بسم الله الرحمن الرحيم. 2 what is pain ??? "an unpleasant sensory or...
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الرحيم الرحمن الله بسم الرحيم الرحمن الله بسم
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What is Pain???
" An unpleasant sensory or emotional
experience associated with actual or
potential tissue damage, . Pain is
always subjective .
It is a Protective Mechanism for body
IASP (International Association for Study of Pain )
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Classification of fibers in peripheral nervesFiber Group Innervations Diameter µm Velocity (m/sec)
A-alpha M-spindle motor to skeletal 15 100
A-beta C-touch & pressure afferent 8 50
A-gama M-to muscle spind 6 20
A-delta Mech-ther Nocice < 3 15
B Sympathetic pre g 3 7
C *
Mech-ther Nocice Sympathetic post g
1 1
*
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Peripheral Receptors
.1First (Fast) pain: Well-localized & brief Sharp & Pricking , Receptors are High-threshold
Mechanoreceptors (specific noci-ceptors)
2. Second (Slow) pain : More diffuse & protracted Dull & Aching , (Polymodal
noci-ceptors) Visceral Pain
Sources, Pathways, Perception &
Treatments, are very different .
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Analgesic: (opioids & NSAIDs)
روي • هستندكه داروهائي رسپتورهاياپوئيدهاميكنند عمل مركزي عصبي سيستم اختصاصي
از • يكسري عمل محل رسپتورها پپتيدهاي پلياين
مثل هستند اندورفينو انكفاليناندوژن اپوئيدهاي • شبيه ضددردي خواص پپتيدها پلي اين
دارند تزريقي راو • استم برين خاكستري زياددرماده باغلظت انكفالين
وجوددارد نخاعومدت بتاآندرفين• درشت ملكولهاي
غده از زياد ترشح پيتوئيتراثرطوالنيتروباغلظت ميشود
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Opiates and their receptors
Opioid receptor: delta, kappa & mu .
In brain, & Spinal cord for pain & other functions. mu receptors, are in, parabrachial nuclei ,
Locus coeruleus & Ventral tegmentum.
(stimulation cause, Respiratory depression.)
Some believe that μ1 and μ2 receptors are with pain and respiratory depression .
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Endogenous opioids Enkephalins, Endorphins and Dynorphins.
Enkephalins act on delta receptors, Dynorphins act on kappa receptors,
Endorphin act on mu & delta receptors, Morphine is mu agonist. . mu & delta receptors act on same cells,
stimulation of one receptor increase affinity of other! Beta endorphin is also
"neurohormone,“ effects on neurones with mu receptors, after released
from hypothalamus.
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الرحيم الرحمن اللهبسم
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PhenanthrenPolycyclic Arumatic Hydrocarbon
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ريشه اصلي تمام
نارکوتيکها
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Agonist = dose-dependent agonist effect
Antagonist = antagonising effect
Agonist / Antagonist = agonist effects at one Receptor & antagonist effects at another .
( biphasic clinical effects .). . e g antagonism of opioid-induced analgesia at low doses
& .analgesia at high doses .
Partial-agonists = agonist-like effects in low concentration but increased doses have no further effect .
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Classification of Opioids•A-Opioid Agonists:• 1-Natural opium Alkaloids• a-Morphine• b-Codeine• 2-Semisynthetic opium Alkaloids• Diamorphine• 3-Synthetic opioids a-
Pethidine b-Fentanyl c-Alfentanil •b-Sufentanil e-Remifentanil
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Classification of Opioids
•B-Partial opioid Agonists• 1-Bupernorphine• 2-Meptazinol
•C-Opioid Agonist/Antagonist• 1-Pentazocine• 2-Nalbuphine
•D-Opioid Antagonist• 1-Naloxone(naline-nalorphine)• 2-Naltrexone
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فارماكولوژي تحريكاثرات رسپتورها •Effect mu kappa sigma
•Analgesia Yes Yes No
•Ventilation Dep Dep Stimu
•Behaviour Euph Sed Dys
•Pupil Mio Myd Myd
•Phy depend Yes No No
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روي اپوئيدي داروهاي اثراتDrug mu kappa sigmaرسپتورها
Morphine Ago Ago No activBupernorphine P-Ago No activ No activMeptazinol P-Ago No activ No activ
Pentazocine Anta P-Ago AgoNalbuphine Anta P-Ago AgoNalorphine Anta P-Ago AgoNaloxone Anta Anta Anta
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Morphine
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Actions & Side effects of Morphine• Central Depressant•1 -Analgesia•2 -Sedation•3 -Depression of cough reflex
•4 = = -Respiratory centre
•5 = = -Metabolic rate
•6 = = -Vasomotor centre17
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Actions & Side effects of Morphine • Central Excitatory•1-Euphoria . Hallucination•2-Convulsion (in very high dosage)•3-Miosis (stimul of 3th N) •4-Vomiting (stimul of CTZ)•5-Nausea) = = ( •6-Bradycardia (Vagal stimul)•7-Release of ADH•8-Supres of ACTH . FSH . LH
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Actions & Side effects of Morphine• Peripheral (Non-nociceptive)
• A-Increase in smooth muscle tone
• B-Histamine release• 1-Broncho-spasme• 2-Hypotension• 3-Erythema• 4-Sensation of Warmth & Flushing
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Pharmacokinetic & dynamic of Morphine
Less lipid soluble, Tertiary amine, week base , More water soluble, Effective in
Dull & Continuous Pain, Diminished Psychological & Emotional of Pain ,
R.S. Depress Ventilation &Tidal volume ,C.V.S. Hypotension, Arteriolar & Venous dilation,G.I.S. Nausea & Vomit,6-8h, Reduce Peristalsis,
Increase Non-peristalsis, Delay G. Empty , Constipation, Sphincter, Oddi, Bladder ,&
Ureter .
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Distribution & Elimination35% bound protein. Enterohepatic recirculation ,
Liver Metabolism: dealkylation, oxidation, & conjugation with glucuronide .
Metabolite: Morphine-6-glucuronide .
Half-life: 2-4h ,Excrete: Kidney, Cross Placenta barrier .
Dose & Administration: 10 – 15 mg IV – IM – Or.
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Diamorphine:
•Diacetyl morphine
•semisynthetic• 2x morphine
•rapid onset•least res. Arrest
•no vomiting or nausea
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papavertum•Analgesia and
relaxation of
smooth muscles
•more sedation less respira.
depression
•Its alkaloids are:
•codeine•tebaine•narcotine•papaverin
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Pethidine
•Synthetic•Analgesic•Relax Smooth M.
•causes Arrhythmia•Norpethidine is its
metabolite which causes
seizure and
irritability
•Renal excretion•not be used in renal failure
•with MAO inh. Causes
seizure, coma,
hypertension•100mg of Peth =
10 mg of Morph
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Pethidine cholinergic eff
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Dose 25 – 50 mg IV , 100 – 150 mg IM ,
Duration 2 – 3 h Cross Placenta
Convulsion, Coma ,&Hypertension with
MAOI
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الرحيم اللهبسم الرحمن
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Buprenorphine •Tebaine derivative•synthetic•10 mg of M = 0.4 mg OF buprnorphine •Duration: 6 – 8 h ,•Dose: 0.3 -0.6 mg use IV IM & Oral
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Fentanyl
•Synthetic•actions like pethidine•100x more potent than
morphine•Duration: 20-30 min
•Dose in adults: 50-100 micg IV
•Very Lipid-soluble 29
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Fentanyl
Onset: 1-2 min ,
Duration: 20 – 30 min
Dose: 50 -100 micg IV
R.S. depression
C.V.S. hypotension & bradycardia
Need IPPV & ITU for 24 h (in large dose) .
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Alfentanil & Remifentanil
•Synthetic•fentanil derivative
•Dose: 500 micg
•Duration:5-10 min
•Very Lipid-soluble
•R.S. Less depression
•C.V.S. depress more than fentanil .
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MethadoneLong-acting mu-receptor like Morphine .
Onset, oraly 20 – 30 min Duration, peak= 4h, half-life= 15-40h .
Therapeutic: Chronic pain, & opioid abstinence
Syndromes, & treatment Heroin users, & Antitussive .
Dose: oral,2.5 – 15mg. IV & IM, 2.5 – 10mg.
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Other OpioidsPhenoperidine
Levorphanol
Rapifen
Sufentanil
Meptazinol
Nalbuphine
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Opioid antagonists:
•Naloxone•Nalorphine•Naltrexone•Levallorphan
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Naloxone
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Non opioid analgesics: NSAIDs•Inhibit the action of COX•examples are:
•ASA (acetic-salicilic-acid)
•Indomethacin•Diclofenac•keterolac•Paracetamol
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اداره درد حاد - بیدردی کنترل بعدازعمل
شده توسط بیمار
- بیدردی نوروآگزیال
رویکردهای - جایگزین دراداره
دردحاد بعداز عمل
- بلوک های عصبی محیطی
- بیدردی ناحیه ای داخل پلور
- تحریک الکتریکی عصب
از راه جلد
-نوروفیزیولژی درد
- درک درد - تعدیل درک
درد - سیستمهای
ارائه بیدردی - تجویز خوراکی
- تجویز داخل عضالنی
- تجویز داخل وریدی
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Descending Systems•Three major functionally interrelated
components:
Opioid
Noradrenergic,
Serotonergic systems.
: عملکرد مهم مرتبط جزء سه
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Modulation of NociceptionHistamine & Inflammatory mediators, such as:
Peptides (e.g., bradykinin), Lipids (e.g., prostaglandins),
Neurotransmitters (e.g. serotonin), & Neurotrophins (e.g. nerve growth factor)
: ریلیز موجب جراحی برش
شدن. فعال موجب سرانجام که میشوندانتقال وشروع محیطی های نوسیسپتورمرکزی عصبی سیستم به درد اطالعات
میشوند.
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Preemptive and Preventive Analgesia
پیشگیری ازدرد. بعداز برش جراحی یا یک تروما .
حساسیتزائی محیطی یا مرکزی ایجاد میشود.
تعریف دقیق ازپیشگیری درد یکی از مباحث عمده
کنترل درد است . بیدردی پیشگیرانه شبیه یک تداخل
ضد دردی است که باید قبل از شروع برش جراحی اقدام نموده وازانتقال تحریکات دردناک به
سیستم عصبی مرکزی جلوگیری نمود .) قبل از
عمل. حین عمل . وبعدازعمل.(
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درد درک تعدیلمسیرحسی مختلف پیش آوراندرسطوح
: . مثال میدهد رخ درکورتکس درد ازدرکدر دردناک ایمپالس تعدیل منشاءمیتواند
) ودر ) درد های گیرنده هرنقطهتحریکحسی . آورانازمسیرهای جائیکه صعودی
. سیناپتیک انتقال بگیرد صورت میدهد رخازطریق تعدیل میتواند درد بیشتردرک
که نزولی وابران مهاریمسیرهای . ساقهدرسطح دهد رخ میگیرد منشاء مغز
Modulation of Nociception
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تعدیل درک دردمحیطی
یا با آزادسازی ویا با حذف مدیاتورهای
آندوژن التهابی در مجاورت گیرنده درد
صورت میگیرد.
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پروستاگالندینهاهیستامین
برادیکینینسروتونین
کولین استیلاسیدالکتیک
هیدروژن ینپتاسیم ین
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تحریکیگلوتاماتآسپارتات
ای روده پپتیدهای پلیسیستوکینین عروق کله
کننده آزاد پپتیدهایآنژیوتنسینگاسترین
پی مادهدهنده وقفه
انکفالیناندورفین
تاتین تس سوما
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Epidural Administrationازروش تزریق. مخدر اپیدورالاستفاده با
بصورت یا برای. مداوم انفوزیون متناوب. بعدازعمل بیدردی
تزریق اپیدورال فضای مخدرداخل وقتیاز. باید . دوراشد رسپتورهای وبه بگذرد
. ژالتینی مادهمخدر دوزمخدر برسد نخاعنیازتقریبا اینتراتکال دهمورد برابرروش
دوست. چربی اثرداروهای میباشد. فنتانیل) بعلت( عروقزودترظاهرمیشود
. داخل تزریق مشابه اپیدورال فضای. وریدی سیستمیک اثرات وهمان است
. تنفسی تهویه سرکوب) رادارد(
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یک کردن مثل مخدرکوتاهاضافه فنتانیلاثرحاوی محلول ازعمل. مرفینبه قبل
. موئثر بیدردیموجب است بیداری بهنگامدر 1 )بوپیواکائین ( 1میلیگرم راهم میلیلیتر
. درآن که کرد اضافه محلول به میتواندر آوران ایمپالسهای دومحلصورت
با کامل دومکانیسممختلف بیدردی موجبدوآگونیست میشود . کلونیدینها )آلفا
آن( دکسمتودومدین به میتوان راهم . بهره کامل وازبیدردی نمود اضافه محلول
( . شد دوزهمراه مند کاهشعوارض (. کاهش
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