Analgetics Opiods and its Antagonist...Analgetics Opiods and its Antagonist . ... K-safest analgesic due to less of the dangerous side effects. PRECISE MECHANISM OF OPIOIDS As with

Analgetics Opiods and its Antagonist

• https://www.youtube.com/watch?v=VY7xPVZc5Xs

The IC50 is the concentration of an inhibitor where the response (or binding) is reduced by half.

• https://www.youtube.com/watch?v=98JaiKH2q3E

Drugs Result Diuretics Decrease diuresis Beta-blockers Decrease antihypertensive effect ACE inhibitors Decrease antihypertensive effect Anticoagulants Increase of GI bleeding Sulfonylurea Increase hypoglycemic risk Cyclosporine Increase nephrotoxicity GCS Increase of GI bleeding Alcohol Increase of GI bleeding

Drug interactions with NSAIDs

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 type

Location 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=BKMlHNqlQsM

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 Mu-1 Mu-2 Kappa

Analgesia

Respiratory Depression

Euphoria

Dysphoria

Decrease GI motility Physical

Dependence

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

53

• 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

M.o.r.f.i.n (7)

54

• 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

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)

59

• 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

Antagonis Opioid (2)

60

• 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

Antagonis Opioid (1)

61

• 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

TERIMA KASIH dan

SELAMAT BELAJAR!!!