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Opioid Analgesics & Antagonists
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Opioid Analgesics & Antagonists
Analgesik dan antagonis Opoid• Agonis kuat1.Fentanil 2.Heroin3.Meperidin4.Metadon5.Morfin6.sufentanil
• Agonis sedang1.Kodein2.profoksifen
• Antagonis-agonis campuran
1.Buprenorfin2.pentazocin
• Antagonis1.Nalokson2.Naltrekson
Reseptor opoid
• Efek utama opoid diperantarai oleh 4 famili reseptor:
1.μ2.К3.∂4.б
Distribusi reseptor1. Batang otak: mempengaruhi pernafasan,
batuk, mual dan muntah, memelihara tekanan darah, diameter pupil, mengontrol sekresi lambung
2. Talamus medialis: mnyeri dalam yang tdk terlokalisasi, emosi
3. Medula spinalis: reseptor pada substansia gelatinosa terlibat dalam penerimaan dan integrasi hasil pembentukan sensorik→penguragan rasa nyeri
4. Hipotalamus: sekresineoroendokrin5. Sistem limbik: tingkah laku emosi
Opioid AnalgesicsClassification : • Spectrum of Clinical Uses :
• Analgesics• Antitussive• Antidiarrheal drugs
• Strength of Analgesia :• Strong analgesia• Moderate analgesia• Weak Analgesia
• Ratio of Agonists to Antagonist Effects :• Agonists (receptor activator)full or partial• Antagonists (receptor blocker)• Mixed agonist-antagonists (capable of activating one opioid
receptor subtype & blocking another subtype)
Pharmacokinetics
• Most drugs are well absorbed orally & can be given parenterally
• Opioid drugs are widely distributed to body tissues
• They cross the placental barrier & exert effects on the fetus
• The opioid are metabolized by hepatic enzymes
Mechanism of action
• Interaction with specific opioid receptors in the CNS & peripheral tissuesThree major opioid receptors are , , & receptor : contributed to analgesia, respiratory depression, physical dependence receptor : contributed to spinal analgesia & sedative effects of opioid drugs
• Opioid receptors are thought to be activated by endogenous peptides under physiologic conditions.these peptides are enkephalins, dynorphin, beta-endorphin
• Ionic mechanisms
The EffectsAcute Effects • Analgesia :
• Strong agonists (morphine, methadone, meperidone, fentanyl, levorphanol, heroin)
• Mild to moderate agonists (codeine, hydrocodone, oxycodone)
• Weak agonists (propoxyphene)• Sedation & euphoria :
• These effects occur at doses below maximum analgesia doses
• At higher doses, the drugs may cause mental clouding, stuporous, or comatose state
• Respiratory depression :• Decreased response to carbondioxide challenge
• Antitussive actions :• Suppression of the cough
The Effects• Nausea & vomitus
• Caused by activation of the chemoreceptor trigger zone & are increased by ambulation
• Gastrointestinal effects :• Constipation (decreased intestinal peristalsis, which is
probably mediated by effects on opioid receptors in the en teric nervous system
• Smooth muscle :• Contraction of biliary tract muscle• Increased uretral & bladder sphincter tone• Reduction in uterine tone
• Miosis :• Pupillary coonstriction, is a characteristics effects of all
opioid except meperidine
The EffectsChronic Effects• Tolerance
• Involve receptor “uncoupling”
• Physical dependence• Is an anticipated physiologic responese to
chronic therapy with drugs in this group, particularly the strong agonists
• Abstinence syndrome (rinorrhea, lacrimation, chills, gooseflesh, muscle aches, diarrhea, yawning, anxiety, & hostility
Clinical Uses• Analgesia
To treatment of moderate to severe pain• Cough suppression
Include codein & dextromethorphan (orally)• Treatment of diarrhea
Include diphenoxylate & loperamide (selective antidiarrheal opioids)
• Management of acute pulmonary edema Morphine (parenterally) is useful in acute pulmonary edema
because its hemodynamics action & its calming effects to relief of the pulmonary symptoms
• Anesthesia Are used as preoperative medications & intraoperaive adjuntive
agents• Opioid dependence
Methadone is used in the management of opioid withdrawal states & in maintenance programs for addicts
Toxicity
• OverdoseComa with marked respiratory deppression &
hypotensionTreatment : naloxone, ventilatory support
• Drug interactions Interaction with ethanol, sedative hypnotic,
anesthetic, antipsychotics drugs, tricyclic antidepressants, & antihistamine (additive CNS deppression)
Mixed agonist-antagonists & Partial Agonist drugs
Mixed agonist-antagonists drugs :• Prototype : butorphanol, nalbuphine,
pentazocine• Are agonists with weak antagonists
activityPartial Agonists drugs :• Prototype : buprenorphine• Is a partial agonists at receptor
Mixed agonist-antagonists & Partial Agonist drugs
Effects :• Sedation at analgesic doses• Dizzines, sweating, nausea, anxiety,
hallucinations, nightmares• Less intense respiratory deppression
than with pure agonists• Less tolerance• Less physical dependence
Opioid Antagonists
• Prototype : naloxone (duration of action 1-2h), naltrexone (24-48h)
• Clinical uses : management of acute opioid overdose
• Given intravenously