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ANALGESICS
Lector prof. Posokhova K.A.
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
OPIOID
ANALGESICS
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
Opioid system
contains:
• opioid receptors
• endogenic opioid substances –
endorphins, encephalines, dinorphines
Subtypes of opioid receptors:
mu, delta, kappa, epsilon, sigma
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
Poppy
1. Papaver
rhoeas L.
2. Papaver
somniferum L.
2
1
"Among the remedies
which it has pleased
Almighty God
to give to man to
relieve his sufferings,
none is
so universal and so
efficacious as opium."
Thomas Sydenham
(1624 - 1689)
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.
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
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
(can’t 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
Morphine
preparations
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
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)
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
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
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
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
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
Phentanyl
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
PARACETAMOL+CODEINE
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
that’s why it’s not advised to use in case of acute
myocardium infarction
• if it is administered for people with narcotic addiction
manifestations of abstinence develop
Buprenorphine
• Partly agonist of mu-opioid receptors
• Acts longer than morphine (approximately 6 hours)
• Analgesic activity is higher than of morphine, that’s why
it’s 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
Buprenorphine
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
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 % СО2 and 93-95 % O2)
Naloxon
antagonist of opioid receptors
All narcotic analgesics cause
drug addiction – narcotic dependence
Manifestations
psychological dependence
physical dependence
tolerance
abstinence syndrome
NON-OPIOID
ANALGESICS
Types of action of
non-opioid analgesics
• Analgesic
• Antipyretic
• Anti-inflammatory
(except paracetamol)
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
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
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
Analgin
(metamizol-sodium)
Baralgin (maxigan, spazgan,
spazmalgon, trigan)
analgin+pitophenon hydrochloride+pheniverinium bromide
• Ampoules
tablets
suppositories
• Analgesic and
spasmolytic
activity
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
Paracetamol
• Tablets
• Suppositories
• Syrups
• Soluble tablets
• Capsules
PARACETAMOL
Panadol (paracetamol)
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
Ketorolak (ketanov)
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
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.
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

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7243085.ppt

  • 2. 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
  • 4. 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
  • 5. Opioid system contains: • opioid receptors • endogenic opioid substances – endorphins, encephalines, dinorphines Subtypes of opioid receptors: mu, delta, kappa, epsilon, sigma
  • 6. 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
  • 7. Poppy 1. Papaver rhoeas L. 2. Papaver somniferum L. 2 1
  • 8. "Among the remedies which it has pleased Almighty God to give to man to relieve his sufferings, none is so universal and so efficacious as opium." Thomas Sydenham (1624 - 1689)
  • 9. 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.
  • 10. 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
  • 11. 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 (can’t 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
  • 13. 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
  • 14. 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)
  • 15. 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
  • 16. 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
  • 17. 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
  • 18. 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
  • 19. 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
  • 21. 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
  • 23. 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 that’s why it’s not advised to use in case of acute myocardium infarction • if it is administered for people with narcotic addiction manifestations of abstinence develop
  • 24. Buprenorphine • Partly agonist of mu-opioid receptors • Acts longer than morphine (approximately 6 hours) • Analgesic activity is higher than of morphine, that’s why it’s 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
  • 26. 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
  • 27. 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 % СО2 and 93-95 % O2)
  • 29. All narcotic analgesics cause drug addiction – narcotic dependence Manifestations psychological dependence physical dependence tolerance abstinence syndrome
  • 31. Types of action of non-opioid analgesics • Analgesic • Antipyretic • Anti-inflammatory (except paracetamol)
  • 32. 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
  • 33. 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
  • 34. 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
  • 36. Baralgin (maxigan, spazgan, spazmalgon, trigan) analgin+pitophenon hydrochloride+pheniverinium bromide • Ampoules tablets suppositories • Analgesic and spasmolytic activity
  • 37. 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
  • 38. Paracetamol • Tablets • Suppositories • Syrups • Soluble tablets • Capsules
  • 41. 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
  • 43. 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
  • 44. 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.
  • 45. 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