This document discusses physiology and pharmacology of pain. It defines pain and describes nociceptors, types of pain pathways, and opioid analgesics. It focuses on the mechanism of action, efficacy, and adverse effects of morphine, the prototypical opioid analgesic. It summarizes morphine's pharmacological actions including analgesia, tolerance, dependence, and interactions with other drugs.
Pain is the common symptom in many chronic conditions such as cancers, neuropathies, and chronic disease. It is also experienced in trauma varying from mild to severe based on the location and degree of trauma. This presentation is a brief outline on types of pain, classification of pain, pain pathways and management of pain
Pain is the common symptom in many chronic conditions such as cancers, neuropathies, and chronic disease. It is also experienced in trauma varying from mild to severe based on the location and degree of trauma. This presentation is a brief outline on types of pain, classification of pain, pain pathways and management of pain
local anaesthesia is defined as a loss of sensation in a circumscribed area of the body caused by a depression of excitation in nerve endings
Or an inhibition of the conduction process in peripheral nerves; no loss of consciousness occurs
Local anesthetics interfere with the excitation process in the nerve membrane in one or more of the following ways:
1) Altering the basic resting potential of the nerve membrane
2) Altering the threshold potential (firing level)
3) Decreasing the rate of depolarization*
4) Prolonging the rate of repolarization
This interesting ppt is the continuation of the Pharmacology of Opioid analgesics I... This impressive ppt highlight the pharmacology, advantages and disadvantages of opioid analgesics other than morphine with illustrations....!!
local anaesthesia is defined as a loss of sensation in a circumscribed area of the body caused by a depression of excitation in nerve endings
Or an inhibition of the conduction process in peripheral nerves; no loss of consciousness occurs
Local anesthetics interfere with the excitation process in the nerve membrane in one or more of the following ways:
1) Altering the basic resting potential of the nerve membrane
2) Altering the threshold potential (firing level)
3) Decreasing the rate of depolarization*
4) Prolonging the rate of repolarization
This interesting ppt is the continuation of the Pharmacology of Opioid analgesics I... This impressive ppt highlight the pharmacology, advantages and disadvantages of opioid analgesics other than morphine with illustrations....!!
this is an important topic in palliative care. a form of care each of us may need when we suffer terminal illness and severe trauma at one point in our life time.
opioid analgesics with detailed description of introduction, mechanism of action, adverse effect, uses and contraindication along with examples for under graduates.
The Indian Dental Academy is the Leader in continuing dental education , training dentists in all aspects of dentistry and
offering a wide range of dental certified courses in different formats.
Immunosupressants and Immunostimulants their pharmacology, uses etc. Basics of immunology, innate immune response, acquired immune response, role of complement in innate immune response. Major histocompatibility complex, antibody structure. classification of immunosupressants, their mechanism of action, uses and adverse effects.
Pharmacology of antimalarial drugs with treatment of malaria. mechanism of action, uses, adverse effects of antimalarial drugs like chloroquine, quinine, artemisinin compounds.
Antileprosy drugs have been described with their pharmacology also this topic covers Multidrug treatment for leprosy including paucibacillary and multibacillary leprosy and lepra reactions
Pharmacology of cephalosporins, monobactums and carbapenums including their mechanism of action, indications, adverse effects.
The various generations of cephalosporins and their spectrum of action
Pharmacology of Penicllins (Beta lactam antibiotics), description of their mechanism of action, mechanism of resistance, classification, indications and adverse effects
Drugs for treatment of Diabetes MellitusNaser Tadvi
These slides contain the brief description of Insulin and the other oral drugs indicated in the treatment of Diabetes Mellitus. Their mechanism of action, effects, uses, Adverse effects etc.
Introduction to Autonomic Nervous systemNaser Tadvi
Lecture intends to give a brief overview of autonomic nervous system.
it includes the anatomical distribution of ANS, Neurohumoral transmission, co-transmission, receptors for ANS and synthesis of the neurotransmitters, Acetylcholine and Catecholamines
Lecture covers the pharmacology of anticholinergic drugs. Includes classification, therapeutic uses, adverse effects of anticholinergics. Atropine has been described as prototype drug.
Lecture includes definition of bioassay, Types of Assay and Bioassay , Indications, principles, advantages of bioassay. Example of a Bioassay with calculations. This lecture will be of help for postgraduate pharmacology students as well as undergraduates
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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
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
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.
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.
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
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.
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
2. “But pain is a perfect misery
The worst of evils
Excessive overturns
All patience”
John Milton
In Paradise Lost
3. Objectives
• Definition of pain
• Nociceptors : Location, types
• Types of pain
• Pathway of Pain
• Opioid analgesics
– Mechanism of action
– Morphine
– Other opioid analgesics
4. Pain
• Unpleasant sensory and emotional experience
associated with actual or potential damage
• Pain is redefined as a perception instead of a
sensation because it is always a psychological
state.
– Latin word "peona " meaning punishment
• Pain is always subjective
• It is differently experienced by each individual.
5. Nociception
– Coined by Sherrington
– Latin: noxa means injury
– it means the ´perception of noxious stimuli´
• Mechanism by which noxious peripheral
stimuli are transmitted to the central nervous
system to elicit a mechanical response .
6. Pain - Receptors
• Specialized naked nerve endings found in almost every
tissue of the body.
• Activated by stimuli (mechanical, thermal, chemical)
• Distinguished from other receptors by
– their higher threshold, and
– they are normally activated only by stimuli of noxious
intensity-sufficient to cause some degree of tissue damage.
• Aδ: Myelinated
• C: Unmyelinated
7. Characteristic features of Aδ & C fibres
Feature Aδ fibre C fibre
Number Less More
Myelination Myelinated Unmyelinated
Diameter 2-5 µm 0.4-1.2 µm
Conduction 12-30 m/s 0.5 -2 m/s
velocity
Specific Most sensitive to Most sensitive for
stimulus pressure chemical agents
Impulse Fast component of Slow component
conduction pain of pain
8. Location of nociceptors
• Superficial skin layers
• Deeper tissues
– Periosteum, joints,
arterial wall, liver
capsule, pleura
• Other deeper tissues
– Sparse pain nerve
endings
– But wide spread
tissue damage results
in pain
9. Types of Nociceptors
• Somatic
– Free nerve endings of Aδ & C fibres
– Unimodal, polymodal, silent
• Visceral
– Wide spread inflammation, ischemia, mesentric
streching , spasm or dilation of hollow viscera
produces pain
– Probably strech receptors
10. Pain stimuli
• Mechanical / thermal stimuli
– Fast pain: Sharp well localized , pricking type
• Chemical stimuli
– Slow pain: poorly localized, dull, throbbing
– K+, ADP, ATP
– Bradykinin, histamine
– Serotonin, Prostaglandins
– Substance P, CGRP
11. Clinical types of pain
• Somatic
• Visceral
• Referred pain
– Convergence & facilitation theory
• Projected pain
• Radiating Pain
• Hyperalgesia
17. Analgesics
• Drugs which relieve pain due to multiple
causes with out causing loss of consciousness
• Drugs which relieve pain due to single causes
or specific pain syndromes (ergotamine,
carbamazepine, nitrates) are not classified as
analgesics
• Corticosterroids also not classified as
analgesics
18. Analgesics
• Opioid analgesics
– Morphine and morphine like drugs
• Non steroidal anti-inflammatory drugs
– Paracetamol, diclofenac, ibuprofen etc
20. Opioid Receptors
• Opioid receptors found in the brain, spinal cord and
peripheral nervous system
• Mu (μ1 and μ2 )
• Kappa (k1 & k3)
• Delta (δ)
• Nociceptin/Orphanin (N/OFQ)
22. Mu-Receptor: Two Types
μ1 μ2
– Located outside spinal – Located throughout CNS
cord – Responsible for
– Higher affinity for • spinal analgesia,
morphine • Respiratory
– Supraspinal analgesia depression,
– Selectively blocked by • constipation
naloxone • physical
dependence, and
euphoria
23. Kappa Receptor
• Only modest analgesia(spinal κ1 and
supraspinal κ3)
• Little or no respiratory depression
• Little or no dependence
• Dysphoric effects
• Miosis
• Reduced GI motility
24. Delta Receptor
• High affinity for Leu/Met enkephalins endogenous
ligands.
• The δ mediated analgesia is mainly spinal
• Affective component of supraspinal analgesia
appears to involve δ receptors as these receptors are
present in limbic areas—also responsible for
dependence and reinforcing actions.
• The proconvulsant action is more prominent in δ
agonists.
25. Spinal sites of opioid action.
hyperpolarize
second-order pain transmission neurons by increasing
K+ conductance, evoking an inhibitory
postsynaptic potential
reduce transmitter release
from presynaptic terminals of nociceptive
primary afferents
26. The descending control system, showing the main
sites of action of opioids on pain transmission
28. Efficacy
• Morphine is a strong analgesic.
• Higher doses can mitigate even severe pain
• Degree of analgesia increasing with dose.
• Simultaneous action at spinal and supraspinal
sites greatly amplifies the analgesic action.
29. Selectivity
• Suppression of pain perception is selective
• No affect on other sensations
• proportionate generalized CNS depression
(contrast general anaesthetics).
30. Type of pain
• Dull, poorly localized visceral pain is relieved
better than sharply defined somatic pain
• Nociceptive pain arising from stimulation of
peripheral pain receptors is relieved better
than neuritic pain due to inflammation or
damage of neural structures
31. Mood and subjective effects
• Morphine has a calming effect.
• The associated reactions to intense pain
– apprehension,
– fear,
– autonomic effects are also depressed.
• Perception of pain and reaction to it are both
altered so that pain is no longer as unpleasant
or distressing, i.e. patient tolerates pain
better.
32. Mood and subjective effects
• Other effects include
– feeling of detachment,
– Lack of initiative,
– limbs feel heavy and body warm,
– mental clouding and inability to concentrate.
• In normal people, in the absence of pain or
apprehension, these are generally appreciated
as unpleasant
33. Mood and subjective effects
• Patients in pain or anxiety and addicts
– specially perceive it as pleasurable
– Refer it as 'high'.
• Rapid IV injection by addicts - gives
them a 'kick' or 'rush' which is intense,
pleasurable—akin to orgasm.
• Thus one has to learn to perceive the euphoric
effect of morphine.
34. Mood and subjective effects
In patients - Pain relief In normal persons
Dependence and
No addiction Addiction
35. Other pharmacological actions
Gastrointestinal system :
– Increase in tone ,
– reduced motility ,
– contraction of sphincters ,
– decrease of G.I. secretions
– leading to constipation .( , k , receptors ).
36. Other effects
Respiratory centre
• Morphine depresses respiratory centre in a
dose dependent manner
• Rate and tidal volume are both decreased
• Death in poisoning is due to respiratory failure
• Neurogenic, hypercapnoeic and later hypoxic
drives are suppressed in succession
37. Other effects
• C.V.S. :
– Vasodilatation due to direct decrease of tone of
blood vessels
– Shift of blood from pulmonary to systemic circuit
– histamine release and
– depression of vasomotor centre
• Urinary bladder
– Detrusor contraction leading to urgency .
– Sphincter contraction leading to retention of urine
38. Other effects
• Bronchoconstriction
– due to histamine release by morphine .
• Uterus may be relaxed .
• Mild hyperglycemia due to central
sympathetic stimulation .
• It has weak anticholinesterase action .
39. Other effects
• Endocrine
– Growth hormone and prolactin and ADH levels
are increased .
– FSH ,LH and ACTH levels are decreased .
40. Pharmacokinetic features
• Oral absorption is unreliable
• Metabolized by glucuronide conjugation.
• Morphine-6-glucuronide is an active
metabolite (more potent than morphine)
• freely crosses placenta
• t1/2of morphine averages 2-3 hours
• Effect of a parenteral dose lasts 4-6 hours
41. ADVERSE EFFECTS
• The toxic effects of morphine are an extension
of their pharmacological effects
• Idiosyncrasy and allergy
– Urticaria, itch,swelling of lips.
– A local reaction at injection site
may occur due to histamine release.
• Allergy is uncommon and anaphylactoid
reaction is rare.
42. ADVERSE EFFECTS
• Apnoea This may occur in new born when
morphine is given to mother during labour.
• The BBB of foetus is undeveloped, morphine
attains higher concentration in foetal brain
• Naloxone 10 µg/kg injected in chord is the
treatment of choice.
43. Tolerance
Onset
• Tolerance to morphine develops rapidly and
can be detected within 12 – 14 hours of
morphine administration
• within 3 days the equianalgesic dose is
increased 5 fold .
44. Tolerance - effects
• Tolerance extends to most actions of
morphine
– analgesia ,
– euphoria ,
– respiratory depression
• not to the constipation miosis and
convulsions
• Cross tolerance occurs between drugs acting
at the same receptor , but not drugs acting on
different receptor
45. Tolerance - Mechanism
• The tolerance is not pharmacokinetic but due
to the true cellular adaptive response
• Two proposed mechanisms
– upregulation of cAMP system
– Downregulation of μ receptors
• Recent research suggests tolerance results
due to uncoupling between μ receptor and G
proteins
• Leading to reversal of second messenger
(cAMP) and ion channel system
46. Tolerance - Mechanism
• Recently the NMDA antagonists and nitric
oxide synthase inhibitors have been found to
block morphine tolerance and dependence in
animals.
• Thus, analgesic action of morphine can be
dissociated from tolerance and dependence
which contribute to its abuse by
– NMDA receptor antagonists
– Agents that recouple μ receptor and G proteins
47. Dependence
Dependence comprises two components
• Physical dependence - associated with the
withdrawal syndrome, lasting for a few days
• Psychological dependence - associated with
craving, lasting for months or years.
48. Withdrawal symptoms
• Withdrawal of the drug causes significant
distress to cause a drug seeking behavior
manifested by
– sweating ,lacrimation, dehydration,fear
– anxiety , restlessness , mydriasis , tremor , colic
– hypertension , tachycardia and weight loss .
• Weak long acting receptor agonist methadone
used to relieve withdrawal syndrome.
49. Psychological dependence
• Opioids facilitate DA transmission in
mesolimbic /mesocortical pathways and
activate endogenous reward pathways in brain.
• Important in intiating and mantaining drug
seeking behaviour
• Psychological dependence rarely occurs in
patients being given opioids as analgesics
50. Acute morphine poisoning
• 50 mg morphine i.m. produces serious toxicity.
• lethal dose : 250 mg.
• Manifestations are extension of pharm. action.
• Stupor, flaccidity, shallow
breathing, cyanosis, miosis, ↓BP & shock.
Convulsions, pulmonary edema,coma occur at
terminal stages
• Death is due to respiratory failure.
51. Treatment
• Respiratory support
• Maintenance of BP
• Gastric lavage with pot. Permanganate
• Naloxone 0.4-0.8 mg i.v. repeated every 2-3
min till respiration picks up. Repeat every 1- 4
hrs later on, according to response.
• preferred specific antagonist : does not have
any agonistic action and resp. depression
52. Precautions and C/I
• Infants and the elderly
• Patients with respiratory insufficiency
• Bronchial asthma
• Head injury
• Hypotensive states and hypovolemia
• Undiagnosed acute abdominal pain
• Elderly male
• Hypothyroidism, liver and kidney disease
• Unstable personalities
53. Drug interactions
• Drugs which poteniate morphine
– Phenothiazines, TCA, MAO inhibitors,
– Amphetamine and Neostigmine
• Morphine retards absorption of many orally
administered drugs by delaying gastric
emptying..
54. Dose
• 10-50 mg oral,
• 10-15 mg i.m. or s.c. or
• 2-6 mg i.v.
• 2-3 mg epidural/intrathecal;
• children 0.1-0.2 mg/kg
55. Therapeutic uses
• Morphine / parenteral congeners indicated as
analgesic in
– traumatic, visceral, ischaemic (myocardial
infarction),
– postoperative, burns, cancer pain.
• Relieves anxiety and apprehension in serious
and frightening disease accompanied by pain:
myocardial infarction,
56. Therapeutic uses
Acute left ventricular failure (cardiac asthma)
• Morphine rapid i.v. affords dramatic relief by
– ↓ preload and peripheral pooling of blood.
– shift blood from pulmonary to systemic circuit
– relieves pulmonary congestion and edema.
– Allays air hunger by depressing respiratory centre.
– Cuts down sympathetic stimulation by calming
the patient, reduces cardiac work.
57. Epidural and intrathecal injection of
Morphine
• It is being used for
– analgesia in abdominal, lower limb and pelvic surgeries
– labour, postoperative, cancer and other intractable pain.
– Preanaesthetic medication
• produces segmental analgesia for 12 hour without
affecting sensory, motor or autonomic modalities.
• Resp. depression occurs after delay due to ascent
through subarachnoid space to the resp. centre.
58. Codiene (Methyl Morphine)
• low-efficacy opioid a prodrug (t1/2 3 h).
• lacks efficacy for severe pain
• most of its actions 1/10th those of morphine.
• Large doses cause excitement.
• Dependence much less than with morphine.
• principal use: mild to moderate pain & cough
• 60 mg coeine = 600 mg aspirin
59. Pethidine
• Pethidine differs from morphine in that it:
• does not usefully suppress cough
• less likely to constipate
• less likely to cause urinary retention & prolong
childbirth
• little hypnotic effect
• shorter duration of analgesia (2-3 h).
• Dose: 50-100mg SC or IM
60. Methadone
• principal feature of methadone is long
duration, analgesia may last for 24 h.
• If used for chronic pain in palliative care (12-
hourly) an opioid of short t ½ should be
provided for breakthrough pain rather than an
extra dose of methadone.
• Also used in opioid withdrawal
• Dose: 2.5 mg to 10 mg oral or IM
61. Fentanyl
• Pethidine congener 80-100 times potent than
morphine in analgesia and resp. depression
• High lipid solubility peak effect in 5 min
• Duration of action 30-40 min
• Injectable form exclusively used in anaesthesia
• Transdermal patch available used in cancer or
other types of chronic pain
• Dose: 25-75 µg /hr acts for 72 hours
62. Patient controlled analgesia (PCA)
• An attractive technique of postoperative pain
control
• patient himself regulates the rate of i.v.
fentanyl infusion according to intensity of pain
felt.
• Transdermal fentanyl is a suitable option for
chronic cancer and other terminal illness pain
63. Dextropropoxyphene
• Less analgesic, antitussive, and less
dependence
• Its analgesic usefulness equal to codeine.
• Commonly combined with paracetamol
• Dextropropoxyphene interacts with
warfarin, enhancing its anticoagulant effect.
• Dose= 60-120 mg
64. Tramadol
• Relieves pain by opioid as well as other
mechanisms
• 100 mg IV Tramadol = 100 mg IM morphine
• Dose: 50-100 mg TDS
• Less respiratory
depression, sedation, constipation, urinary
retention, ↑intrabiliary pressure & dependence
than morphine
• As effective as pethidine for postoperative pain
and as morphine for moderate chronic pain.
65. Pentazocine
• Weak µ antagonist action and marked κ
agonist action
• Analgesia is primarily spinal (K1)
• can cause a withdrawal syndrome in addicts
• Dose= 30-60 mg IM OR 50 -100 mg oral
• shorter duration of pain relief 4-6 hrs,
• less dependence, sedation & resp. depression
• Use: post operative, moderately severe burns
66. Butorphanol
• K analgesic like pentazocine but more potent
• Psychomimetic effects less marked
• Neither substitute nor antagonize morphine
• Dose: 1-4 mg IM / IV
• Use:
– Post operative
– Short lasting painful conditions (renal colic)
67. Buprenorphine
• High-efficacy partial agonist of µ receptor and
an antagonist of the K-receptor.
• Less liability to induce dependence and
respiratory depression than pure agonists
• Duration of action = 6-8hrs
• Dose: 0.3-0.6 mg IM, SC, 0.2 -0.4 mg SL
• Use: cancer, MI, Post Operative, morphine
dependence Contraindiacted In labour pain
71. Benefits due to PG Synthesis inhibition
• Analgesia: prevention of pain nerve ending
sensitization
• Antipyretic
• Anti-inflammatory
• Antithrombotic
• Closure of ductus arteriosus
72. Toxicities due to PG synthesis inhibition
• Gastric mucosal damage
• Bleeding: inhibition of platelet function
• Limitation of renal blood flow : Na and water
retention
• Delay/prolongation of labour
• Asthma and anaphylactoid reactions in
susceptible individuals
73. Adverse effects of NSAIDs
Gastrointestinal-
• Gastric irritation, erosions, peptic ulceration,
gastric bleeding/perforation, esophagttis
Renal
• Na and water retention, chronic renal
failure, interstitial nephritis, papillary
necrosis (rare)
Hepatic
• Raised transaminases, hepatic failure (rare)
75. USES
• Analgesic- headache, backache, myalgia, joint
pain, dysmenorrhoea;
• Antipyretic-fever of any origin; paracetamol
being safer.
• Acute rheumatic fever- the first drug to be
used
76. • Rheumatoid arthritis - Aspirin in a dose of 3-5
g/day is effective in most cases; produces
relief of pain, swelling and morning stiffness.
• Osteoarthritis - It affords symptomatic relief
only; paracetamol is the first choice analgesic
• Post myocardial infarction and post stroke
patients By inhibiting platelet aggregation it
lowers the incidence of reinfarction.
77. Other uses are:
• Pregnancy induced hypertension and
pre eclampsia.
• To delay labour
• Patent ductus arteriosus
79. • Better tolerated than aspirin.
• The analgesic, antipyretic and
antiinflammatory efficacy is lower than high
dose of aspirin.
• All inhibit PG synthesis- naproxen being most
potent;
• They inhibit platelet aggregation and prolong
bleeding time.
80. Indomethacin
Potent antiinflammatory drug comparable to
phenylbutazone.
Potent and promptly acting anti-pyretic.
Analgesic action is better than phenylbutazone,
but it relieves only inflammatory or tissue
injury related pain.
highly potent inhibitor of PG synthesis and
suppresses neutrophil motility.
81. Uses
• Rheumatoid arthritis not controlled by aspirin;
• Ankylosing spondylitis, acute exacerbations of
destructive arthropathies and psoriatic
arthritis.
• It acts rapidly in acute gout.
• Malignancy associated fever refractory to
other antipyretics.
• Medical closure of patent ductus arteriosus
82. MEPHENAMIC ACID
• Analgesic, Antipyretic and Anti-inflammatory
drug which inhibits COX & antagonizes actions
of PGs.
• Exerts peripheral & central analgesic action.
83. Uses
• analgesic in muscle, joint and soft tissue pain
- strong anti-inflammatory action is not
needed.
• It is quite effective in dysmcnorrhoea.
• useful in some cases of rheumatoid and
osteoarthritis
85. DICLOFENAC SODIUM
• An analgesic-antipyretic-antiinflammatory
drug similar in efficacy to naproxen.
• short lasting antiplatelet action.
• Neutrophil chemotaxis and superoxide
production at the inflammatory site are
reduced.
86. USE
• most extensively used in rheumatoid and
osteoarthritis, bursitis, ankylosing spondylitis,
dysmenorrhoea, post-traumatic and
postoperative inflammatory conditions—
affords quick relief of pain and wound edema.
Editor's Notes
Pain is unpleasant sensation which only sufferer casn appraise as such is not capable of any satisfactory objective definitionThe word unpleasant comprises whole range of disagreeable feelings from being merely inconvinienced to misery, anguish, anxiety, depression Because pain is universally accepted as signal of disease it is most common symtom that brings the patient to doctor Thuis this topic is important
Pain can occur without nociception merely by its expectation andNociception does not invariably cause pain
Conduct impulses only in response to noxious stimuli Conduct impulses in response to to thermal and mechanical stimuli
Accompaniment of fast pain: withdrawl reflex, symp response Accompaniment of slow pain: emotional perception, autonomic symptoms, skeletal muscle tone
Causalgia
This system regulates the passage of impulses from the peripheral afferent fibres to the thalamus via transmission neurons originating in the dorsal horn. Neurons in the substantiagelatinosa (SG) of the dorsal horn act to inhibit the transmission pathway. Inhibitory interneurons are activated by descending inhibitory neurons or by non-nociceptive afferent input. They are inhibited by nociceptive C-fibre input, so the persistent C-fibre activity facilitates excitation of the transmission cells by either nociceptive or non-nociceptive inputs. This autofacilitation causes successive bursts of activity in the nociceptive afferents to become increasingly effective in activating transmission neurons
An emotional state characterized by anxiety, depression, or unease.
Opioids excite neurons in the periaqueductal grey matter (PAG) and in the nucleus reticularisparagigantocellularis (NRPG), which in turn project to the rostroventral medulla, which includes the nucleus raphemagnus (NRM). From the NRM, 5-HT- and enkephalin-containing neurons run to the substantiagelatinosa of the dorsal horn, and exert an inhibitory influence on transmission. Opioids also act directly on the dorsal horn, as well as on the peripheral terminals of nociceptive afferent neurons. The locus ceruleus (LC) sends noradrenergic neurons to the dorsal horn, which also inhibit transmission. The pathways shown in this diagram represent a considerable oversimplification but depict the general organisation of the supraspinal control mechanisms. Blue shaded boxes represent areas rich in opioid peptides. DLF, dorsolateralfuniculus; 5-HT, 5-hydroxytryptamine. (For more detailed information, see Fields & Basbaum 1994.)
Elimination is almost complete in 24 hours and morphine is noncumulative. Small amounts may persist due to enterohepatic circulation.
It is accidental,suicidal or seen in drug abusers.
Respiratory support (positive pressure respiration also ↓ pulmonary edema formation) and Maintenance of BP (i.v. fluids, vasoconstrictors). Gastric lavage should be done with pot. permanganate to remove unabsorbed drug.
Infants and the elderlyMore susceptible to respiratory depressionObstetric analgesia, pethidine is preferred Patients with respiratory insufficiency emphysema, pulmonary fibrosis,corpulmonale, sudden deaths have occurred.Bronchial asthma: retains CO2 ↑ intracranial tensionEven therapeutic doses can cause markedrespiratory depression in these patients.Vomiting, miosis and altered mentationproduced by morphine interfere withassessment of progress in head injurycases.morphine can aggravate certain conditionsEg. diverticulitis, biliary colic, pancreatitis. Inflamed appendix may rupture. Morphine can be given after the diagnosis is established.
either by retarding its metabolism or by a pharmacodynamic interaction at the level of central neurotransmitters.
should not be restricted in case of pain of terminal illness(cancer)In other chronic conditions, due consideration must be given to their addicting liabilitiesPrevents neurogenic shock and other autonomic effects of excruciating pain.
It is also indicated to relieve pulmonary edema due to infarction of lung and other causes but not due to irritant gases.
Natural , 1/6 to 1/10 potency Can be used to control diarrhoeaCough linctusAdverse effect is constipation
but its effect in theupper small intestine is similar to morphineincluding contraction of the sphincter of OddiPethidine attracted attention as a possible analgesic because it caused the tails of laboratory mice to stand erect (Straub phenomenon), a characteristic of morphine-like drugs caused by spasm of the anal sphincter.Pethidine binds to the mu and kappa -receptors; it is effective for moderate or severe pain but its duration of action is shorter than that of morphine. It is effective against pain beyond the reach of codeine.Despite its substantial structural dissimilarity to morphine, pethidine has many similar properties including that of being antagonised by naloxone.Norpethidine retains pharmacological activity and may accumulate dangerously when renal function is impaired. Pethidine causes vomiting about as often as does morphine; it has atropine-like effects, including dry mouth and blurred vision (cycloplegia and sometimes mydriasis, though usually miosis). Overdose or use in renal failure can cause central nervous system stimulation (myoclonus, convulsions) due to norpethidine.There is disagreement on the extent to which pethidine depresses respiration. It is probable that in equianalgesic doses it is as depressant as morphine. Pethidine dependence occurs, with some tolerance, especially to the side-effects, but its psychic effects are less constant and less marked than those of morphine. Pethidine has evident advantages over morphine for pain that is not very intense, and it is widely used. It is usually given orally (50-100 mg) s.c. or i.m. (25-100 mg), when its effects last 2-3 h. Itis widely used in obstetrics because it does not delay labour like morphine; but it enters the fetus and can depress respiration at birth.
Synthetic drug structurally and pharmacologically related to morphine acts on mu receptors Largely metabolized to products that are excreted in urine half life= 8 hrs Causes less dependence than merphine and heoinMetadone in oioidwithdrawl :Occupancy of opioid receptors by methadone reduces the desire for other opioids, and their effects, should any be taken; the slow offset diminishes the severity of the withdrawal. Addicts who are cooperative enough to take oral methadone feel reduced craving and less 'kick/buzz/rush' from i.v. heroin or morphine because their opioid receptors are already occupied by methadone and the i.v. drug must compete.Reports of deaths in addicts entering prescribed methadone substitution programmes have been attributed to the cardiovascular effects of a membrane stabilising action,unlike morphine.
Small doses of opioids given with induction can usefully reduce the dose requirements of drugsused during anaesthesia. Those used are: fentanyl, alfentanil, sufentanylInanalgesic doses it produces fewer few cardiovascular effects, less histamine release Fentanyl is so potent that discarded patches may yet contain sufficient drug to be dangerous.Alfenatil (tl/21.5 h), given i.v., provides maximum analgesia in 90 seconds, which lasts about 5-10 min from a single dose; it is used for brief (painful) operations.Remifentanil is rapidly metabolised, not in the liver but by blood and tissue esterases. Its short duration of action renders it well suited for continuous i.v. infusion without accumulation.
structurally similar to methadone Demethylated metabolite of dextropoxyphene is cardiotoxic and also seizures dangerous in overdose only partly antagonized by nasloxoneAbuse potential similar to coieneBecsause of reported fatalities, no clear advantage of combinations over paracetamol alone such combinations have been withdrawn in uk
Affinity fror mu redceptoris low and kappa and delta is very low, umlike other opioids its inhibnits the reuptake of NA and 5 HT AND ACTIVATES MONOAMINEWRGIC INHIBITION OF PAINANALGESIC ACTION ONLY PARTIALLY REVERSED BY NALOXONEConfusion, convulsions, hallucinations and anaplhylaxis have been reported with its use.
it can also induce psychological and physical dependence (agonist effect), and this can be severe. It has not proved to be the solution to separating the property of analgesiafrom that of producing dependence, as was hoped for initially. Its analgesic efficacy approximates to that of morphine, but its potency (weight for weight) is about one-third of morphine.
a respiratory stimulant(doxapram) may be needed in overdose,ormechanical ventilation.little effect on the cardiovascular system and may spare the sphincter of Oddi from induced spasm. Its tl/2 is 5 h.respiratory depression is only partially reversed by naloxone25 times more potent than morphine With repe3ated use duration of action may increase to 24 hrs