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Department of Pharmacology, DSMA
Analgesics
1. Opioid Analgesics.
2. Nonopioid Analgesics.
Department of Pharmacology, DSMA
Opioid Analgesics
Department of Pharmacology, DSMA
General mechanisms of pain
reception
nociceptive systems:
Nociceptive system is the system of pain reception and it's psychical appre
Antinociceptive system is the system of excessive pain reception supression. If
Department of Pharmacology, DSMA
The phases of pain
Department of Pharmacology, DSMA
Schematic presentation of pain pathway and
potential therapeutic options for achieving pain
relief.
Department of Pharmacology, DSMA
Mechanism of pain transmission and interference
Department of Pharmacology, DSMA
Classification of opioid receptors and effects of their
exitation
μ-(mju)-receptors: analgesia, euphoria,
physical dependence, inhibition of breathing,
decrease of digestive tract's motility,
bradycardia, myosys.
K-(kappa)-receptors: analgesia, sedative effect,
disphoria, psychosomymetic effect.
δ-(delta)-receptors: analgesia.
ε-(epsylon)-receptors: are insufficiently
discovered.
σ-(sigma)-receptors: are insufficiently
discovered.
Department of Pharmacology, DSMA
Opiates are drugs derived from opium and include
morphine, codeine, and a wide variety of
semisynthetic congeners derived from them and
from thebaine, another component of opium. The
term opioid is more inclusive, applying to all
agonists and antagonists with morphine-like activity
as well as to naturally occurring and synthetic opioid
peptides. Endorphin is a generic term referring to the
three families of endogenous opioid peptides: the
enkephalins, the dynorphins, and b- endorphins
Endorphin
Opiate receptor
Morphine
Department of Pharmacology, DSMA
– Opium is withered milky
juice educed from the
unripe seed pots of
opium poppy.
– Opium contains about 20
alcaloids.
Source and Composition of Opium. Because the laboratory synthesis
of morphine is difficult, the drug is still obtained from opium or extracted
from poppy straw. Opium is obtained from the unripe seed capsules of the
poppy plant, Papaver somniferum. The milky juice is dried and powdered
to make powdered opium, which contains a number of alkaloids. Only a
fewѕ morphine, codeine, and papaverineѕ have clinical usefulness. These
alkaloids can be divided into two distinct chemical classes, phenanthrenes
and benzylisoquinolines. The principal phenanthrenes are morphine (10%
of opium), codeine (0.5%), and thebaine (0.2%). The principal
benzylisoquinolines are papaverine (1.0%), which is a smooth muscle
relaxant, and noscapine (6.0%).
Department of Pharmacology, DSMA
Morphine
is the ancestor of the group of opioid analgesics derived
from the opium
History. Although the psychological effects of opium
may have been known to the ancient Sumerians, the
first undisputed reference to poppy juice is found in
the writings of Theophrastus in the third century
B.C. The word opium itself is derived from the Greek
name for juice, the drug being obtained from the
juice of the poppy, Papaver somniferum. Arabian
physicians were well versed in the uses of opium.
Paracelsus
(1493-1541)
is
credited
with
repopularizing the use of opium in Europe after it
had fallen into disfavor because of its toxicity. By the
middle of the sixteenth century, many of the uses of
opium were appreciated. In 1680, Sydenham wrote,
"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."
Department of Pharmacology, DSMA
Opium contains more than 20 distinct
alkaloids. In 1806, Serturner
reported the isolation of a pure
substance in opium that he named
morphine, after Morpheus, the
Greek god of dreams. The
discovery of other alkaloids in
opium quickly followed that of
morphine (codeine by Robiquet in
1832, papaverine by Merck in
1848). By the middle of the
nineteenth century, the use of pure
alkaloids rather than crude opium
preparations began to spread
throughout the medical world.
Department of Pharmacology, DSMA
ation of opioid analgesics
1. Agonists of opioid receptors:
- Opium alcaloids:
■ phenanthrenes - MORPHINE, CODEINE, OMNOPON;
■ isochinalines - PAPAVERIN, NARCOTIN.
- Syntetic drugs:
■ phenylpiperidines - PROMEDOLUM [Trimeperidine], FENTAN
■ phenylheptylamines - PHENADONE.
2. Agonists-antagonists:
■ phenanthrenes - NALBUFINE (agonist-K; antagonist-μ), BUP
■ phenylpiperidines - PENTAZOCIN (agonist-K, δ; antagonist-
3. Antagonists of opioid analgesics (blockers of o
Department of Pharmacology, DSMA
Pharmacological effects of morphine
1. Central effects:
- Analgesic - opression of pain of any origin.
- Psychotropic:
-
influence upon the psychical appreciation of pain - opression fear of
pain;
euphoria - unreasonable improvement of mood, feeling of mental
comfort.
- Sedative - decrease of emotional exitability.
- Effects upon hypothalamus:
- hypothermic - decrease of body temperature below normal level;
- increase of antidiuretic hormone production.
- Exitation of centre of Nervus oculomotorius - myosis.
- Inhibition of breathing centre.
- Opression of coughing centre.
- Inhibition of vomiting centre (but exitation of chemoceptors of the
trigger-zone).
- Exitation of centres of Nervus vagus.
Department of Pharmacology, DSMA
Pharmacological effects of morphine
2. Peripheral effects:
- Increase of smooth muscle tonus and sphincters' tonicity of
GIT organs - constipation, abdominal pain.
- Increase of smooth muscle tonus and sphincters' tonicity of biliferous
and urinary tracts
- Increase of tonicity of bronchial smooth muscles
- Increase of hystamine release.
- Dilation of peripheral veins.
Department of Pharmacology, DSMA
Repeated use of Morphine
- Psychological dependence
- Physical dependence
- Tolerance
- Withdrawal syndrome
Department of Pharmacology, DSMA
Tolerance and Physical Dependence.
The development of tolerance and physical dependence
with repeated use is a characteristic feature of all the
opioid drugs. Tolerance and dependence are
physiological responses seen in all patients and are
not predictors of abuse. For example, cancer pain
often requires prolonged treatment with high doses of
opioids, leading to tolerance and dependence. Yet,
abuse in this setting is very unusual. Neither the
presence of tolerance and dependence nor the fear
that it may develop should interfere with the
appropriate use of opioids. Opioids can be
discontinued in dependent patients without subjecting
them to withdrawal. Suppression of withdrawal
requires only minimal doses. Clinically, the dose can
be decreased by 50% every several days and eventally
stopped without signs and symptoms of withdrawal.
However, decreases in dosage may lead to a reduction
in the degree of pain control.
Department of Pharmacology, DSMA
Methadone
• Methadone is primarily a μ agonist with pharmacological
properties qualitatively similar to those of morphine.
• The outstanding properties of methadone are its effective
analgesic activity, its efficacy by the oral route, its
extended duration of action in suppressing withdrawal
symptoms in physically dependent individuals, and its
tendency to show persistent effects with repeated
administration. Miotic and respiratory-depressant effects
can be detected for more than 24 hours after a single dose
and, upon repeated administration, marked sedation is
seen in some patients. Effects on cough, bowel motility,
biliary tone, and the secretion of pituitary hormones are
qualitatively similar to those of morphine.
• The primary uses of methadone hydrochloride
(DOLOPHINE) are relief of pain, treatment of opioid
abstinence syndromes, and treatment of heroin users.
Department of Pharmacology, DSMA
Acute Opioid Poisoning
The patient who has taken an overdose of an opioid is usually
stuporous or, if a large overdose has been taken, may be in a
profound coma. The respiratory rate will be very low (sometimes
only 2 to 4 breaths per minute), and cyanosis may be present. As
respiratory exchange decreases, blood pressure, at first likely to be
near normal, will fall progressively. If adequate oxygenation is
restored early, the blood pressure will improve; if hypoxia persists
untreated, there may be capillary damage, and measures to combat
shock may be required. The pupils will be symmetrical and pinpoint
in size; however, if hypoxia is severe, they may be dilated. Urine
formation is depressed. Body temperature falls, and the skin
becomes cold and clammy. The skeletal muscles are flaccid. Frank
convulsions occasionally may be noted in infants and children.
When death occurs, it is nearly always due to respiratory failure.
Even if respiration is restored, death still may occur as a result of
complications that develop during the period of coma, such as
pneumonia or shock.
Department of Pharmacology, DSMA
Treatment of acute poisoning
The first step is to establish a patent airway and ventilate
the patient. Opioid antagonists can produce dramatic
reversal of the severe respiratory depression, and the
antagonist naloxone is the treatment of choice. However,
care should be taken to avoid precipitating withdrawal in
dependent patients, who may be extremely sensitive to
antagonists. The safest approach is to dilute the
standard naloxone dose (0.4 mg) and slowly administer
it intravenously, monitoring arousal and respiratory
function.
The End