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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.
1
2
"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
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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
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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
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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
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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 thrombusformation (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
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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