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