Analgetics Opiods and its Antagonist
• https://www.youtube.com/watch?v=VY7xPVZ c5Xs
The IC50 is the concentration of an inhibitor where the response (or binding) is reduced by half.
• https://www.youtube.com/watch?v=98JaiKH2 q3E
Drug interactions with NSAIDs Drugs Diuretics Beta-blockers ACE inhibitors Anticoagulants Sulfonylurea Cyclosporine GCS Alcohol
Result Decrease diuresis Decrease antihypertensive effect Decrease antihypertensive effect Increase of GI bleeding Increase hypoglycemic risk Increase nephrotoxicity Increase of GI bleeding Increase of GI bleeding
Three Opioid Receptors • Mu (μ): efek analgesik mirip morfin, euforia, depresi napas, miosis, motilitas sal cerna • Kappa (κ) : analgesia, sedasi, miosis, depresi napas, namun tidak sekuat reseptor μ • Delta (δ) : depresi pernapasan
Method of Action
In general, opioids act upon mu-, delta-, and kappa-receptors on CNS neurons producing: Analgesia via decreased neuronal transmitter release and decreased nociceptive impulse propagation Appears to work by elevating the pain threshold, thus decreasing the brain’s awareness of pain
Receptor Location type
Effects
μ
Brain, spinal cord
Analgesia, respiratory depression, euphoria, addiction, ALL pain messages blocked
κ
Brain, spinal cord
Analgesia, sedation, all non-thermal pain messages blocked
δ
Brain
Analgesia, antidepression, dependence
PRECISE MECHANISM OF OPIOIDS As with many drug therapeutics that cross the BBB and take effect in the CNS, the mechanism of opioid derivatives is not completely understood For this reason, there is still biochemical/pharmacological studies being conducted to try to understand how these drugs work A new study from last year was able to biotinylate various opioid derivatives to aid in these types of studies which are still very common Biotinylation-process of covalently attaching a biotin (vitamin H or B7) tag to a molecule or surface
Mekanisme kerja opiod • https://www.youtube.com/watch?v=BKMlHN qlQsM
Delta Receptor • It is unclear what delta’s responsible for. • Delta agonists show poor analgesia and little addictive potential • May regulate mu receptor activity
Mu-Receptor: Two Types • Mu-1 – Located outside spinal cord – Responsible for central interpretation of pain
• Mu-2 – Located throughout CNS – Responsible for respiratory depression, spinal analgesia, physical dependence, and euphoria
Kappa Receptor • Only modest analgesia • Little or no respiratory depression • Little or no dependence • Dysphoric effects
Mu and Kappa Receptor Activation Response Analgesia Respiratory Depression Euphoria Dysphoria Decrease GI motility Physical Dependence
Mu-1
Mu-2
Kappa
Terminology • Pure Agonist: has affinity for binding plus efficacy • Pure Antagonist: has affinity for binding but no efficacy; blocks action of endogenous and exogenous ligands • Mixed Agonist-Antagonist: produces an agonist effect at one receptor and an antagonist effect at another • Partial Agonist: has affinity for binding but low efficacy
M.o.r.f.i.n • Daya utk menimbulkan adiksi berbeda: – Heroin terbesar: euforiayg kuat dan tdk disertai mual / konstipasi – Kodein jarang: sedikit menimbulkan euforia, jika dosis ditingkatkan efek yg tidak menyenangkan sudah terjadi sebelum euforia muncul – Penyalahgunaan opioid terutama yg bersifat agonis pd reseptor μ terkait euforia 53
M.o.r.f.i.n
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• Interaksi obat efek depresi SSP dpt diperhebat & diperpanjang oleh fenotiazin, MAO inhibitor & antidepresi trisiklik • Sediaan – Alkaloid murni: pulvus opii 10% morpin, pulvus doperi 10% pulvus opii – Morfin sediaan injeksi, 1%, 2% – Kodein tablet 10,15, 30 mg 54
Fentanyl Pharmacokinetics Routes of Administration * Oral, and transdermal (possibly intravenous) *Highly lipophilic *latency to onset (7-15 minutes oral; 12-17 hours transdermal *duration of action ( 1-2 hours oral; 72 transdermal) *80 – 85% plasma protein bound *90 % metabolized in the liver to inactive metabolites Other properties * 80 times the analgesic potency of morphine and 10 times the analgesic potency of hydromorphone. *high efficacy for mu 1 receptors. *most effective opiate analgesic
• •
Antagonis Opioid (1) • Umumnya tidak memberikan banyak efek, kecuali sebelumnya telah ada efek agonis opioid, atau kondisi opioid endogen tinggi • Nalokson, naltrekdon antagonis kompetitif pd ketiga reseptor opioid, namun afinitas thdp reseptor μ tinggi • Efek tanpa pengaruh opioid – – – –
Menurunkan ambang nyeri Antagonis efek anelgetik plasebo Antagonis analgesia krn efek akupungtur Depresi napas nalorfin, levlorfan efek pd reseptor κ
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Antagonis Opioid (2) • Efek dengan pengaruh opioid – Semua efek agonis pd reseptor μ diantagonis oleh nalokson dosis kecil (0,4-0,8mg) IV – RR meningkat 1-2 menit pd pasien depresi napas krn opioid – Efek sedatif & efek thdp tekanan darah jg segera dihilangkan – Fenomena “overshoot” peningkatan RR melebihi frekuensi sebelum dihambat opioid – Dosis kecil pd ketergantungan fisik thdp morfin dpt menimbulkan gejala putus obat yg berat mirip penghentian morfin yg mendadak timbul bbrp menit setelah suntikan s/d 2 jam
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Antagonis Opioid (1) • Farmakokinetika
– Nalokson hanya diberikan parenteral hampir seluruhnya mengalami metabolisme lintas I – T ½ 1 jam, masa kerja 1-4 jam – Naltrekson efektif scr oral, T ½ 3jam, masa kerja 24 jam – Naltrekson lebih poten dari naloksson
• Ketergantungan fisiK penyalahgunaan <<<: – Tdk sebabkan ketergantungan fisik – Tdk menyokong ketergantungan fisik morfin – Obat yg kurang menyenangkan bagi pecandu
• Indikasi : depresi napas neonatus yg ibunya medpt opioid, over dosis morfin 61
TERIMA KASIH dan SELAMAT BELAJAR!!!
