ANALGESICS

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ANALGESICS
Lector prof. Posokhova K.A.
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ANALGESICS

• I. Opioid (narcotic) analgesics
• 1. Agonists of opioid receptors morphine
  hydrochloride, promedol, omnopon, fentanyl,
  codein
• 2. Agonists antagonists and partial agonists of
  opioid receptors pentasocin, buprenorphine.
• II. Nonopioid analgesics and nonsteroidal
  antiinflammatory drugs - NSAIDs
• acetysalycylic acid, paracetamol, analgin,
  indometacin, butadion, ibuprofen, pyroxicam,
  diclofenac-sodium, ketorolac, ketoprofen.
• III. Substances with mixed mechanism of action
  (opioid and nonoioid components)
• tramadole

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OPIOIDANALGESICS
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• The following structures take part in perception
  of pain thalamus, hypothalamus, reticular
  formation, limbic system, occipital and frontal
  areas of cortex
• System which conducts and perceives pain -
  nociceptive
• System which protects organism from pain
• antinociceptive
• Visceral pain
• from inner organs
• Somatic pain
• from bones, muscles, joints, teeth, ligaments,
  nerves

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Opioid system

• contains
• opioid receptors
• endogenic opioid substances endorphins,
  encephalines, dinorphines
• Subtypes of opioid receptors
• mu, delta, kappa, epsilon, sigma

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Subtypes of opioid receptors

• mu
• Analgesia, depression of breathing, euphoria,
  addiction development, sedative effect,
  depression of contents mocing through digestive
  tract, miosis
• kappa
• Analgesia, sedative eefect, psychotomimetic
  action
• delta
• Analgesia, euphoria, behaviour changes
• sigma
• Mania, increasing of breathing frequency,
  hallucinations, midriasis

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Poppy

• Papaver
• rhoeas L.
• 2. Papaver
• somniferum L.

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• "Among the remedies which it has pleased
  Almighty Godto give to man to relieve his
  sufferings, none isso universal and so
  efficacious as opium."
• Thomas Sydenham(1624 - 1689)

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• Morphine was first isolated by Friedrich
  Wilhelm Serturner in 1805.
• Sertürner named his discovery after Morpheus, the
  Greek god of dreams. Morpheus is the son of
  Hypnos, the god of sleep.

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Morphine hydrochloride

• mosaic action on central nervous system
• Effects of depression
• analgesia
• decreasing of frequency and depth of breathing
• depressing of central links of coughing reflexes
• from the side of psychical activity somnolence,
  retardness
• Effects of stimulation
• vomiting (excitation of trigger zone of vomiting
  center)
• bradycardia (increasing of tone of vagal nerve
  nuclei)
• miosis (increasing of tone of n. oculomotorius
  nuclei)
• euphoria (condition of full psychological
  wellness with pleasant emotional feelings and
  feelings of physical comfort)
• increasing of activity of spinal cord
  intermediate neurons

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ADMINISTRATION OF OPIOID ANALGESICS

• prophylaxis and treatment of pain shock
• traumas
• burns
• acute myocardium infarction
• premedication for potentiation of action of
  narcosis drugs, analgesia in postoperative period
• colics
• to relieve sufferings of oncologic patients of
  4th clinical group (cant be treated radically)
• acute abdomen (strong pain in abdominal cavity,
  caused by perforation of ulcer, acute
  appendicitis, acute intestinal impassability
  etc.) only from the moment then diagnosis
  becomes clear

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• Morphine
• preparations

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MORPHINE HYDROCHLORIDE

• routes of administration
• subcutaneously and intramuscularly
• (analgesic action after 10-15 min)
• after oral administration presystemic
  elimination
• ( 20-60 enters general blood
  circulation)
• sublingually quick absorption
• into epidural, subarachnoidal
• into brain ventricles
• Duration of analgesic action 4-6 hours
• Maximum single dose of morphine is 0,02 g,
• maximum daily dose 0,05 g

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Other cases of morphine administration

• acute left-ventricular cardiac insufficiency
• (morphine promotes depression of tone of
  vaso-motor centers with dilation of arterioles
  and venules and decreasing of heart load)
• traumas of thorax accompanied by cough
  (morphine depresses central links of coughing
  reflexes)

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Side effects of morphine

• addiction
• vomiting (excitation of starting zone of vomiting
  center)
• bradycardia (increasing of tone of n. vagus
  nuclei)
• spasm of sphincters of gastro-intestinal tract
  accompanied by constipations
• increasing of tone of smooth musculature of
  urinary and bile-excreting tracts (retentions of
  urination, bile stasis)
• Bronchial spasm
• tolerance

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CONTRAINDICATIONS FOR ADMINISTRATION OF MORPHINE

• pain that accompanies chronic diseases. In
  exceptional occasions it is introduced (not more
  than 1-2 injections) in case of pain which
  threatens development of pain shock, for,
  example, acute attach of ulcer disease
• children before the age of 2 years
• for aged from 2 to 6 years and elderly the drug
  should be administered very carefully (breathing
  depression is possible)
• pregnancy and lactation
• anesthesia during child delivery (fetus breathing
  depression)
• skull traumas, brain hemorrhages (increasing of
  intracranial pressure)
• depression of function of breathing center,
  damage of respiratory organs, bronchial asthma

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OMNOPON

• contains mixture if opium alkaloids
• (48-50 morphine)
• does not cause spasms of smooth musculature, as
  it contains alkaloids of isoquinoline raw
• is used for analgesia according to all the
  indications of morphine hydrochloride, for
  example, colics

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Promedol

• duration of analgesic action - 3-4 hours
• moderate spasmolytic influence on smooth
  musculature of internal organs
• stimulation of rhythmic contractions of uterus
• does not depress breathing
• can be used for analgesia and stimulation of
  child delivery
• in case of pain syndrome connected with spasms of
  smooth musculature

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Phentanyl

• synthetic opioid analgesic of short action
• analgesic activity is 300 times higher than of
  morphine
• analgesic effect after intravenous introduction
  after 1-3 min, lasts for 15-30
  min
• used with a neuroleptic droperidol (complex drug
  talamonal) for neuroleptanalgesia a variant
  of general anesthesia

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Phentanyl
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Codeine

• opium alkaloid
• analgesic action is not strong, but anticough
  effect is considerable
• administered as an anticough drug of central
  action
• analgesic with weak activity combined with
  non-opioid analgesics (paracetamol) for
  potentiation of the effect

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• PARACETAMOLCODEINE

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Pentazocin

• agonist-antagonist of opioid receptors
• comparatively with morphine, it is a bit less
  dangerous in the aspect of addiction development
• indicated in case of pain of medium intensity in
  such conditions like other opioid analgesics. In
  case of strong pain its administration is limited
  as in case of increasing of dose of the drug
  excitation appears
• it can cause increasing of blood pressure and
  tachycardia thats why its not advised to use in
  case of acute myocardium infarction
• if it is administered for people with narcotic
  addiction manifestations of abstinence develop

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Buprenorphine

• Partly agonist of mu-opioid receptors
• Acts longer than morphine (approximately 6 hours)
  
• Analgesic activity is higher than of morphine,
  thats why its used in doses of 0,3-0,6 mg
• In case of breathing depression, which it causes,
  naloxon is less effective since buprenorphine is
  slowly released from the connection with
  mu-receptors
• Indicated for pain decreasing in the same
  situations as other narcotic analgesics
• May be used for detoxication and supporting
  treatment of individuals who is addicted to
  heroine

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Buprenorphine
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Acute poisoning with opioid analgesics

• It is often observed in drug addicts
• death from breathing depression
• SYMPTOMS
• dizziness
• nausea, vomiting (rarely), heavy sweating
• general weakness, somnolence, which after
  transfers into deep dream and coma
• pale and cyanotic skin, decreased body
  temperature
• weak pulse, decreased blood pressure
• rare and superficial breathing
• Triad in case poisoning with morphine
• Acute miosis
• pathological breathing of Chain-Stocks type
• saved tendon reflexes

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Treatment of acute poisoning

• Naloxon (antagonist of opioid receptors)
• intravenously - 0,4-1,2 mg
• general dose of naloxon should not overcome 10
  mg
• stomach lavage (for morphine enterohepatic
  circulation is typical) with 0,05-0,1 solution
  of potassium permanganate and 0,5 tannin
  solution
• suspension of 20-30 g of activated charcoal
• salt laxative agents (sodium sulfate)
• forced diuresis
• atropine sulfate
• inhalation of carbogen (5-7 ??2 and 93-95 O2)

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Naloxon
antagonist of opioid receptors
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• All narcotic analgesics cause
• drug addiction narcotic dependence
• Manifestations
• psychological dependence
• physical dependence
• tolerance
• abstinence syndrome

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NON-OPIOID ANALGESICS
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Types of action of non-opioid
analgesics

• Analgesic
• Antipyretic
• Anti-inflammatory (except
  paracetamol)

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Mechanism of action of non-opioid analgesics

• depression of cyclooxygenases activity
• decreasing of prostaglandins synthesis in
  peripheral tissues and in central nervous system
• decreasing of sensitivity of nervous endings and
  depression of transmission of nociceptive
  impulses on the level of CNS structures
• pain-relieving action of non-opioid analgesics is
  partly connected with their anti-inflammatory
  activity

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Indications for administration of non-narcotic
analgesics

• headache
• toothache
• radiculitis
• neuritis, neuralgias
• myositits, myalgia
• arthritis, arthralgia
• pain, connected with pelvic organs (dysmenorrhea)
  
• for potentiation of their action combinations
• paracetamol with codein,
• analgin with dimedrol, analgin with codein

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Acetylsalicylic acid

• Blocks cyclooxygenase irreversably
• As antipiretic and analgesic drug 0,25 and 0,5
  g per time
• As an antiinflammatory 3-4 g per day (for
  arthritis, myocarditis, pleuritis, bronchitis
  etc.
• As platelets inhibitor - for prophylaxis of
  thrombus-formation (in case of ischemic heart
  disease, thrombophlebitis etc.) daily dose
  80-100 mg

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Analgin (metamizol-sodium)
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Baralgin (maxigan, spazgan, spazmalgon,
trigan)analginpitophenon hydrochloridepheniveri
nium bromide

• Ampoules
• tablets
• suppositories
• Analgesic and spasmolytic activity

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Paracetamol

• analgesic and antipyretic drug
• maximal effect if the drug is introduced orally
  after 2 hours, lasts approximately for 4 hours
• in case of durable administration of big doses
  damaging of liver and kidneys, production of
  met-hemoglobin

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Paracetamol

• Tablets
• Suppositories
• Syrups
• Soluble tablets
• Capsules

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PARACETAMOL
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Panadol (paracetamol)
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Ketorolak (ketanov)

• according to analgesic activity it prevails over
  effect of acetylsalicylic acid, indometacin and
  equals to opioid analgesics
• moderate anti-inflammatory, antipyretic and
  anti-aggregate effects
• high effectiveness in case of pain in
  postoperative period, in oncology, during child
  delivery, traumas, colics
• i. m., i. v. introduction, orally
• NOT indicated
• for chronic pain syndrome

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Ketorolak (ketanov)
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Ketoprophen (ketonal)

• strong analgesic, anti-inflammatory and
  antipyretic agent
• administered in case of arthroses and arthritis,
  ancilizing spondilitis, pain of different genesis
  (after surgeries, in case of traumas, painful
  menstruations etc.)
• administered orally, intramuscularly, in forms of
  suppositories and ointments

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TRAMADOL

• Analgesic activity is similar to the activity of
  morphine
• In case of intravenous administration effect
  develops after 5-10 min, if administered orally
  after 30-40 min, action lasts for 3-5 hours.

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ADMINISTRATION OF TRAMADOL

• surgery, traumatology, gynecology, neurology,
  urology, oncology
• For all kinds of acute and chronic pain of
  moderate and considerable intensity, including
  postoperative, traumatic pain
• neuralgias
• diagnostic and therapeutic interventions
• oncologic pathology
• Provokes dependence