Transcript Chapter 18 Opioid Analgesics

Chapter 21 Opioid-analgesics
Classification of
analgesics basied on their
mechanism of action:
• opium receptor agonists;
• opium receptor partial agonists;
• others.
Opioid Analgesics
[Mechanism of action]
• Opioid agonists produce analgesia by binding to
specific receptors, located primarily in brain and
spinal cord regions involved in the transmission and
modulation of pain.
• Receptor types: The major classes of receptors are µ
(mu for morphine) delta(δ), and kappa(κ). All are
members of the G-protein-coupled family of receptors.
• Analgesia, as well as the euphoriant, respiratory
depressant, and physiologic dependence properties of
morphine result principally from actions at mu
receptors.Most of the currently available opioid
analgesics act primarily at the mu receptor.
含阿片生物碱类植物： 罂粟
Opioid Analgesics
• [Source]
• Opium is obtained from the opium
poppy by incision of the seed pod
after the petals of the flower have
dropped.The white latex that oozes
out turns brown and hardens on
standing.
• This sticky brown gum is opium. It
contains about 20 alkaloids, including
morphine, codeine etc.The principal
alkaloid in opium is morphine,present
in a concentration of about 10%.
Opioid Analgesics---Narcotic analgesics
[Pharmacological Effects]
• Central effects
• Peripheral effects
Morphine 吗啡
Opioid Analgesics---Morphine
[Central effects]
• 1.Analgesia:
• Pain consists of both sensory and affective(emotional)
components.
• 2.Sedation and change in mood
• After a dose of morphine, a patient in pain or an
addict experiences a pleasant floating sensation and
freedom from anxiety and distress.However,other
patients and some normal subjects(not in pain)
experience dysphoria rather than pleasant effects after
a dose of opioid analgesics.
Opioid Analgesics---Morphine
• 3.Respiratory depression:
• All of the opioid analgesics can produce significant
respiratory depression by inhibiting the sensitivity of
brain stem respiratory center to CO2 .
• 4.Cough suppression:
• Opioids directly suppress the cough center in medulla.
• 5.Emesis
• Nausea and vomiting are an unpleasant side effect by
direct stimulation of CTZ.
• 6.Miosis:
• It is valuable in the diagnosis of opioid overdose.
Opioid Analgesics---Morphine
[Peripheral effects ]
• 1. Histamine release
• Causing peripheral arteriolar,venous dilation,and bronchoconstriction.
• 2. Effects on smooth muscles
• (1) Gastrointestinal tract: Constipation has long been recognized as an
effect of opioids.motility(rhythmic contraction and relaxation) may
decrease but tone (persistent contraction) may increase, particularly in the
central portion.
• (2) Biliary （胆道的）tract: The opioids constrict biliary smooth muscle
and sphincter of Oddi, which may result in biliary colic(绞痛）.
• (3) Other smooth muscle:
Uterus (子宫) tone is decreased and duration of childbirth is prolonged.
Genitourinary tract: Ureteral(输尿管) and bladder tone are increased by
therapeutic doses of the opioid analgesics. Increased sphincter tone may
precipitate（加重） urinary retention,especially in postoperative patients.
Bronchial smooth muscle can constrict in higher dose of morphine,
which may precipitate bronchial asthmia.
Opioid Analgesics---Morphine
[Clinical use of opioid analgesics]
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1.pain
Opioids relieve moderate to severe acute pain from various causes.
2.Dyspnea
The relief produced by intravenous morphine in dyspnea(呼吸困难) from
pulmonary edema associated with left ventricular failure is remarkable.
The mechanism probably include:
(1) reduction of the patient anxious and fear due to the sedative effects of
opioids;
(2) decrease in cardiac preload and afterload by lowering peripheral
resistance due to opioid-induced histamine releasing;
(3)decrease of the sensitivity of respiratory center to CO2 and relief of
shallow breathing.
3.Diarrhea
4.Anesthesia
Opioid Analgesics---Morphine
[untoward effects]
• 1. Direct toxic effects of the opioid analgesics that are
extensions of their acute pharmacologic actions
include respiratory depression, nausea, vomiting and
constipation...
• 2. Tolerance
• 3.Physical dependence:
Failture to continue administering the drug results in a
abstinence syndrome(戒断症状), including mydriasis,
muscular aches, vomiting, diarrhea, anxiety.
吗啡耐受和依赖性的产生机制
受体向下调节（脱敏）
SYMPTOMS OF WITHDRAWAL
Opioid Analgesics---Morphine
[Toxicity ]
3. Acute morphine poisoning :coma, severe
respiratory depression and miosis with blood
pressure decreased, and urinary retention.
Respiratory paralysis often is the mainly lethal
reason.
Treatment: respiratory support and intrvenous
injection of naloxone.
[contraindication and Cautions in therapy]
• 1. Use in patients with head in injuries: Carbon dioxide
retention caused by respiratory depression results in cerebral
vasodilation; in patients with elevated intracranial pressure,
this may lead to lethal alterations in brain function.
• 2. Use in patients with impaired pulmonary function : The
respiratory depression properties of the opioid analgesics may
lead to acute respiratory failure.
• 3. Use during pregnancy and delivery :Since the opioid
analgesia readily traverse the placenta,their use for obstetric
analgesia can result in delivery of an infant with depressed
respiration.
• 4. Use in patients with impaired hepatic or renal function.
Characterization of individual narcortic
agonists
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A.strong agonists
1.Morphine
2.meperidine and fentanyl
B.Moderate agonists
1.codeine
2.propoxyphene
C.Mixed agonist-antagonist(MAA)
Buprenorphine
Opioid Analgesics--- Pethidine (哌替啶)
• Pethidine/meperidine and fentanyl(芬太尼) are the
most widely used agents in this family of synthetic
opioids.
• The principal effects of pethidine with affinity for
mu receptors are on the central nervous system.
[Pharmacological Effects]
The pharmacological effects of Pethidine is similar to
morphine, primarily at the mu receptor.It has less potent
analgesics than morphine,and has a shorter duration of
action. Pethidine dosn`t delay delivery.
Clincal Use
• 1. Analgesia : Pethedine which be considered as a
replacement for morphine is used for wound,
postoperative and terminal cancer pain, etc.
• 2. Acute pulmonary edema (cardiac asthma )
• 3. (1)Applications in anesthesia
It is used as premedicant drugs before anesthesia
and surgery .
(2) artificial hibernation:with chlorpromazine and
promethazine(异丙嗪)
The Opioid Antagonists
• The opioid antagonist drugs naloxone and naltrexone
are morphine derivatives.
• When given in the absence of an agonist drug these
antagonists are almost inert at doses that produce
marked antagonism of agonist effects.
• When given intravenously to a morphine-treated
subject,the antagonist will completely and
dramatically reverse the opioid effects within 1-3 min.
The Opioid Antagonists
Clincal Use
• The major application of naloxone is in the
treatment of acute opioid overdose.
• In individuals who are acutely depressed by an
overdose of an opioid,the antagonist will
effectively normalize respiration,level of
consciousness,pupil size.
• More recently,considerable interest has been
aroused by reports that naltrexone decreases
craving for alcohol in chronic alcoholics,and it has
been approved by the FDA for this purpose.