Opioid Agonist and Antagonist

Synthetic opioid
 Fentanyl, sulfentanyl, remifentanyl

Classification

Mekanisme kerja
 Bekerja sebagai agonis reseptor opioid presinaps dan polisinaps
 Opioid reseptor ada 4: miu 1, miu 2, kappa, delta
Common opioid side effects:

Cardiovascular system (intinya histamine release vasodilatasi; dan

bradikardia)
 Morphine decreases sympathetic nervous system tone to peripheral
veinsvenous pooling, menurunnya venous return, cardiac output, and
blood pressure
 Drug induced bradikardia or histamine release lead to hypotension (due
to stimulation of vagal nucle in medulla, or due to effect on SA node and
slow conduction to the AV node)
 Cara untuk mengurangi/meminimalkan efek morphine induced histamine
release dan hipotensi adalah:
Limiting the rate of morphine infusion to 5 mg per minute iv
Maintaining the patient I supine to slightly head down position
Optimizing iv volume
 Opioid have been increasingly recognized as playing a role in protecting
the yocardium from ischemia
 Opioid prevent painful surgical stimulation, but once this response has
occurred, administration of additional opioid is unlikely to be effective.
 Dibandingkan morfin, fentayl lebih sedikit histamine release
  Kombinasi opioid dan benzodiazepine menyebabkan penurunan SVR dan
Tekanan darah, sementara efek ini tidak terjadi dengan penggunaan obat
sendiri2.

Ventilation
 Opioid induce depreesion of ventilation. Mekanismenya bagaimana?
Primarily through an effect at mu2 receptors leading to a direct
depressant effect on brainstem ventilatory center.
 Opioid induced depression of ventilation is characterized by decreased
responsiveness of these ventilation centers to carbon dioxide as
reflected by an increase in the resting PaCo2 and displacement f the
carbon dioxide response curve to the right.
 Secara klinis manifestasi depresi nafas opioid: Menurunnya RR namun
kompensasinya tingginya TV (napas sedikit RR namun dalam2).
 Opioid increase airway ressistance due to a direct effect on bronchial
smooth muscle and an indirect action due to release of histamine.

Cough Suppression
 Opioid depress cough by effects on the medullary cough center that are
distinct from the effects of opioids on ventilation.

CNS
 Tanpa hipoventilasi, opioid menurunkan aliran darah otak dan
menurunkan TIK.
 Hati2 penggunaan opioid pad pasien cedera kepala karena:
Associated effects on wakefulness
Production of miosis
Depresi ventilasi yang menyebabkan peningkatan PaCO2 yang
menyebabkan peningkatan TIK.
 Pada cedera kepala merusak integritas BBB sehingga lebih sensitive
terhadap opioid.
 Opioid tidak mempengaruhi respons terhadap NMBA.
 Opioid menyebabkan skeletal muscle rigidity (terutama otot dada dan
abdomen ) bila diberikan dosis besar opioid secara iv bolus cepat.
 Miosis oleh opioid disebabkan karena eksitasi opioid pada saraf otonom
komponen dari Edinger-Westphal nucleus of the oculomotor nerve.

Rigidty
 Generally term chest wall rigidity (rapid iv, large dose, especially fentanyl
and its derivate)
 Meskipun dinamakan rigiditas dada, bukti menunjukkan bahwa tahanan
pada ventilasi ditemukan banyak akibat kontraksi otot2 laringeal,
 Mekanisme: akibat dari inhibisi striatal release of GABA and increased
dopamine production.
 Insidensi difficult ventilasi setelah moderate dose of sufentanil beriksar
antara 84% - 100%.
 Treatment rigidity dengan muscle relaxan NMBA atau antagonis opioid
dengan nalokson

Sedation
 Postoperative titration of morphine frequently induces sedation that
precedes theonset of analgesia.
 The usual recommendation for morphine titration includes a short
interval between boluses (5-7 menit) to allow evaluation of its clinical
effect
 Sedation occur 60% of patients during morphine titration

Billiary Tract
 Opioid can cause spasm of biliary smooth muscle, resulting in increase in
biliary pressure that may be associated with epigastric distress or biliary
colic
 Naloxone will relieve pain caused by biliary spasm but not myocardial
ischemia
 Nitroglycerine will relieve pain due to either biliary spasm or myocardial
ischemia
 Equal analgesic doses of fentanyl, morphine, meperidine, and
pentazocine increase common bile duct pressure 99%, 53%, 61%, and
15% above predrug levels.
 During surgeryopioid induced spasm of the spinchter oddi.
 Treatment of opioid induced spasm:
Naloxone
Glucagon 2 mg IV , does not antagonize the analgesic effect of the opioid.
 Incidence of sphincter oddi spasm is 3%, in patients receiving fentanyl as
a supplement to inhaled anesthetics
 Contraction of smooth muscle of pancreatic duct increase plasma
amylase and lipase
GI Tract
 Efek opioid adalah spasme GI smoot muscle  konstipasi, kolik biliar, dan
pengosongan lambung melambat.

Butorphanol
 Merupakan agonis antagonis analgesic bekerja parsial agonis pada
reseptor mu dan antagonis reseptor kappa
 Peggunaan bersamaan dengan agonis opioid (seperti fentanyl) tidak
efektif karena terjadi down regulasi reseptor mu