Analgesics
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2-Jun-22 2
Analgesics
Drugs that selectively relieve pain
by acting in central nervous
system or on peripheral
mechanisms without affecting
consciousness.
These relieve pain as a symptom
without altering its cause.
 These are NOT analgesics……
 Local anaesthetics relieve pain by
nonselective desensitisation of tissues
 Demulcents, protective or soothing effects
 Antacids, chemical neutralisation
 General anaesthetics, alter consciousness
2-Jun-22 3
Types of analgesics:
 Opioid analgesics or narcotic or morphine
like analgesics (addictive)
 Non-opioid analgesics or non-narcotic or
aspirin like analgesics (Non addictive)
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Pain
An ill-defined, unpleasant sensation usually
evoked by an external or internal noxious
stimulus, signal for the injury or insult of
an area
A protective and diagnostic method
if not treated, becomes unbearable and starts
affecting normal body functioning.
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Types of pain
 Pricking, burning, itching pain
 Dull or sharp
 Superficial
 Visceral pain
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Mechanism of pain
 Painful stimuli
 Pain neurotransmitters
 Prostaglandins
 Pain receptors
 Pain perceiving neurons
 Inhibitory neurotransmitters
OPIOID ANALGESICS
 Very potent
 Induce analgesia by stimulation of central
opioid receptors.
 Induce sedation
 Primary use is to reduce the intensity of
pain and anxiety.
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OPIOID
 Any natural, semisynthetic or synthetic
substance that produces morphine like
effects by binding to opioid receptors.
OPIATE
 More restrictive to morphine like drugs
obtained from juice of opium poppy and
resembling structurally to morphine
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NARCOTICS
 Used to refer to opioid analgesic.
 In therapeutics, this term refers to drugs
that induce deep sleep
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OPIOID ANALGESICS
Divided into
 Opioid agonists
 Opioid mixed agonists, antagonist and
partial agonists
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 Most opioids are mu agonists with varying
activity on kappa receptors.
 Opioid receptors are 7 transmembrane
spanning proteins that are coupled to
inhibitory G-proteins.
 When activated, they decrease adenyl
cyclase production of the secondary
messenger cyclic adenosine
monophosphate.
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 This causes a decrease in calcium influx
from inhibition of voltage-gated calcium
channels and results in the activation of
potassium channels, which leads to
hyperpolarization. The hyperpolarized state
causes inhibition of neuronal signaling,
which in this case inhibits pain
transmission.
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 Opioids are classified into categories,
depending on receptor binding and affinity.
These classifications are agonist, partial
agonist, and antagonist. There are opioids
that have dual agonist and antagonist
functions.
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A. OPIOID AGONISTS:
 I. Natural opium alkaloids e.g. morphine
and codeine
 II. Semi-synthetic opioids e.g. heroin,
etorphine etc.
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III. Synthetic Opioids
 1. Phenylpiperidines: Pethidine, prodine
etc.
 2. Anilidopiperidines: Fentanyl,
sufentanil etc.
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 3. Diphenylpropylamine derivatives:
Methadone, Loperamide etc.
 4. Morphinans e.g. Levorphanol and
levomethorphan
 5. Benzomorphans e.g. Phenazocine
 6. Miscellaneous drugs: Tramadol, Tilidine
etc.
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B. Opioid mixed agonist-
antagonists and partial agonists
 I. Semi-synthetic opioids: e.g.
Buprenorphine and nalbuphine
 II. Synthetic opioids
 i. Benzomorphans e.g. Pentazocine and
cyclazocine
 ii. Morphinans e.g. Butorphanol.
 iii. Miscellaneous agents: Meptazinol
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Mechanism of Action:
 Morphine or other opioids interact with 4
families of opioid receptors
 These receptors are present on neurons in
CNS and peripheral tissues and are
designated by the Greek letters Mu (μ),
Kappa (κ), Delta and Sigma.
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Opioid agonist (Natural Opium
Alkaloids) e.g. Morphine
 Principal alkaloid of opium
 Morphine sulphate is the principal salt
 In 1804 by F. W. A. Serturner
 A standard against which the analgesic
potency and actions of other opioid
analgesics are compared.
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Pharmacological Effects: CNS
 Opioid receptor agonist and its main effect
is binding to and activating the μ-opioid
receptors in CNS (analgesia, sedation,
euphoria, physical dependence and
respiratory depression).
 Irregular and species specific
 Site specific depressant and stimulation
actions on CNS
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Analgesic action:
 Strong analgesic
 Fear, anxiety and autonomic effects
associated with pain are also depressed
 High doses can mitigate all types of pain
 Degree of analgesia increases with dose
 Does not affect touch, vision, hearing,
smell and consciousness.
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CNS depression/Sedation
 In all species, there is at least an initial
period of stimulation followed by
depression
 Morphine usually exhibits sedating and
calming effect in all species when they are
suffering from pain.
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Emetic Centre
 The emetic effect is a result of direct
stimulation of the CTZ
 Horses, ruminants and swine do not
respond to the emetic effect of morphine
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Cough Centre
 Morphine is an effective antitussive agent.
 Depresses cough centre that appears to be
more susceptible to morphine than other
medullary centres.
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Respiratory Centre
 Morphine is a potent resp. depressant.
 It depresses respiratory centre in a dose
dependent manner
 As the CNS depression increases,
respiration is also depressed
 It can also cause bronchoconstriction
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Spinal Cord
 Morphine exerts both stimulant and
depressant actions on the spinal cord
Other Central Effects:
Stimulation of vagal nucleus by morphine
produces parasympathetic responses like
slowing of heart, increased tone and
motility of GI tract, increased salivary and
bronchial secretions.
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Side/ Adverse effects:
 Pupil constriction
 Peripheral vasodilation
 Hypotension
 Vomiting
 Defecation followed by constipation
 Urinary retention
 Sweating
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Treatment
 In morphine toxicity, naloxone is the agent
of choice.
 Mechanical respiratory support is also
considered in cases of severe respiratory
depression.
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Drug Interactions
 CNS depressant effects can be enhanced
by barbiturates, inhalant anaesthetics,
antihistamines and phenothiazines
 Analgesic efficacy of morphine can be
potentiated by tricyclic antidepressants and
amphetamine.
2-Jun-22 33

Analgesics.pdf

  • 1.
  • 2.
    2-Jun-22 2 Analgesics Drugs thatselectively relieve pain by acting in central nervous system or on peripheral mechanisms without affecting consciousness. These relieve pain as a symptom without altering its cause.
  • 3.
     These areNOT analgesics……  Local anaesthetics relieve pain by nonselective desensitisation of tissues  Demulcents, protective or soothing effects  Antacids, chemical neutralisation  General anaesthetics, alter consciousness 2-Jun-22 3
  • 4.
    Types of analgesics: Opioid analgesics or narcotic or morphine like analgesics (addictive)  Non-opioid analgesics or non-narcotic or aspirin like analgesics (Non addictive) 2-Jun-22 4
  • 5.
    2-Jun-22 5 Pain An ill-defined,unpleasant sensation usually evoked by an external or internal noxious stimulus, signal for the injury or insult of an area A protective and diagnostic method if not treated, becomes unbearable and starts affecting normal body functioning.
  • 6.
  • 7.
    2-Jun-22 7 Types ofpain  Pricking, burning, itching pain  Dull or sharp  Superficial  Visceral pain
  • 8.
    2-Jun-22 8 Mechanism ofpain  Painful stimuli  Pain neurotransmitters  Prostaglandins  Pain receptors  Pain perceiving neurons  Inhibitory neurotransmitters
  • 9.
    OPIOID ANALGESICS  Verypotent  Induce analgesia by stimulation of central opioid receptors.  Induce sedation  Primary use is to reduce the intensity of pain and anxiety. 2-Jun-22 9
  • 10.
    OPIOID  Any natural,semisynthetic or synthetic substance that produces morphine like effects by binding to opioid receptors. OPIATE  More restrictive to morphine like drugs obtained from juice of opium poppy and resembling structurally to morphine 2-Jun-22 10
  • 11.
  • 12.
  • 13.
    NARCOTICS  Used torefer to opioid analgesic.  In therapeutics, this term refers to drugs that induce deep sleep 2-Jun-22 13
  • 14.
    OPIOID ANALGESICS Divided into Opioid agonists  Opioid mixed agonists, antagonist and partial agonists 2-Jun-22 14
  • 15.
     Most opioidsare mu agonists with varying activity on kappa receptors.  Opioid receptors are 7 transmembrane spanning proteins that are coupled to inhibitory G-proteins.  When activated, they decrease adenyl cyclase production of the secondary messenger cyclic adenosine monophosphate. 2-Jun-22 15
  • 16.
     This causesa decrease in calcium influx from inhibition of voltage-gated calcium channels and results in the activation of potassium channels, which leads to hyperpolarization. The hyperpolarized state causes inhibition of neuronal signaling, which in this case inhibits pain transmission. 2-Jun-22 16
  • 17.
     Opioids areclassified into categories, depending on receptor binding and affinity. These classifications are agonist, partial agonist, and antagonist. There are opioids that have dual agonist and antagonist functions. 2-Jun-22 17
  • 18.
    A. OPIOID AGONISTS: I. Natural opium alkaloids e.g. morphine and codeine  II. Semi-synthetic opioids e.g. heroin, etorphine etc. 2-Jun-22 18
  • 19.
    III. Synthetic Opioids 1. Phenylpiperidines: Pethidine, prodine etc.  2. Anilidopiperidines: Fentanyl, sufentanil etc. 2-Jun-22 19
  • 20.
     3. Diphenylpropylaminederivatives: Methadone, Loperamide etc.  4. Morphinans e.g. Levorphanol and levomethorphan  5. Benzomorphans e.g. Phenazocine  6. Miscellaneous drugs: Tramadol, Tilidine etc. 2-Jun-22 20
  • 21.
    B. Opioid mixedagonist- antagonists and partial agonists  I. Semi-synthetic opioids: e.g. Buprenorphine and nalbuphine  II. Synthetic opioids  i. Benzomorphans e.g. Pentazocine and cyclazocine  ii. Morphinans e.g. Butorphanol.  iii. Miscellaneous agents: Meptazinol 2-Jun-22 21
  • 22.
    Mechanism of Action: Morphine or other opioids interact with 4 families of opioid receptors  These receptors are present on neurons in CNS and peripheral tissues and are designated by the Greek letters Mu (μ), Kappa (κ), Delta and Sigma. 2-Jun-22 22
  • 23.
    Opioid agonist (NaturalOpium Alkaloids) e.g. Morphine  Principal alkaloid of opium  Morphine sulphate is the principal salt  In 1804 by F. W. A. Serturner  A standard against which the analgesic potency and actions of other opioid analgesics are compared. 2-Jun-22 23
  • 24.
    Pharmacological Effects: CNS Opioid receptor agonist and its main effect is binding to and activating the μ-opioid receptors in CNS (analgesia, sedation, euphoria, physical dependence and respiratory depression).  Irregular and species specific  Site specific depressant and stimulation actions on CNS 2-Jun-22 24
  • 25.
    Analgesic action:  Stronganalgesic  Fear, anxiety and autonomic effects associated with pain are also depressed  High doses can mitigate all types of pain  Degree of analgesia increases with dose  Does not affect touch, vision, hearing, smell and consciousness. 2-Jun-22 25
  • 26.
    CNS depression/Sedation  Inall species, there is at least an initial period of stimulation followed by depression  Morphine usually exhibits sedating and calming effect in all species when they are suffering from pain. 2-Jun-22 26
  • 27.
    Emetic Centre  Theemetic effect is a result of direct stimulation of the CTZ  Horses, ruminants and swine do not respond to the emetic effect of morphine 2-Jun-22 27
  • 28.
    Cough Centre  Morphineis an effective antitussive agent.  Depresses cough centre that appears to be more susceptible to morphine than other medullary centres. 2-Jun-22 28
  • 29.
    Respiratory Centre  Morphineis a potent resp. depressant.  It depresses respiratory centre in a dose dependent manner  As the CNS depression increases, respiration is also depressed  It can also cause bronchoconstriction 2-Jun-22 29
  • 30.
    Spinal Cord  Morphineexerts both stimulant and depressant actions on the spinal cord Other Central Effects: Stimulation of vagal nucleus by morphine produces parasympathetic responses like slowing of heart, increased tone and motility of GI tract, increased salivary and bronchial secretions. 2-Jun-22 30
  • 31.
    Side/ Adverse effects: Pupil constriction  Peripheral vasodilation  Hypotension  Vomiting  Defecation followed by constipation  Urinary retention  Sweating 2-Jun-22 31
  • 32.
    Treatment  In morphinetoxicity, naloxone is the agent of choice.  Mechanical respiratory support is also considered in cases of severe respiratory depression. 2-Jun-22 32
  • 33.
    Drug Interactions  CNSdepressant effects can be enhanced by barbiturates, inhalant anaesthetics, antihistamines and phenothiazines  Analgesic efficacy of morphine can be potentiated by tricyclic antidepressants and amphetamine. 2-Jun-22 33