What is opioids? Classification of opioids.

1. AN
OPIOIDS
NIDHI SHARMA

2. INTRODUCTION-
• Though morphine is the most widely known extract of P. somniferum, four
naturally occurring alkaloids (plant-derived amines) can be isolated from it:
morphine, codeine, papaverine and thebaine.
• Following Sertürner’s isolation of morphine as the active component of the
opium poppy, simple chemical manipulations of these basic opiate alkaloids
began to yield a range of semi-synthetic opioids useful in clinical medicine
(agents such as diamorphine, dihydrocodeine, buprenorphine, nalbuphine,
naloxone and oxycodone).
• During the 20th century a number of synthetic opioids were also produced
either by design or serendipitously. These synthetic compounds can be
divided into four chemical groupings: the morphinan derivatives
(levorphanol, butorphanol), the diphenylheptane derivatives (methadone,
propoxyphene), the benzomorphan derivatives (pentazocine, phenazocine)
and the phenylpiperidine derivatives (pethidine, alfentanil, fentanyl,
sufentanil and remifentanil)

3. • Opioids are substances that act on opioid receptors to produce morphine-like effects.
• Medically they are primarily used for pain relief, including anesthesia.
• Other medical uses include-
Suppression of diarrhea
Replacement therapy for opioid use related disorder
Reversing opioid overdose
Suppressing cough
Suppressing opioid induced constipation
• Opioids are also frequently used non-medically for their euphoric effects or to
prevent withdrawal.

4. Classification Examples
Strong Agonists Phenanthrenes
· Morphine
· Hydromorphone
· Oxymorphone
Phenylheptylamines
· Methadone
Phenylpiperidines
· Fentanyl
· Meperidine
Mild to Moderate Agonists Phenanthrenes
· Codeine
· Oxycodone
· Hydrocodone
Phenylheptylamines
· Propoxyphene
Phenylpiperidines
· Diphenoxylate
· Loperamide

5. Opioids with Mixed Receptor Actions Phenanthrenes
· Nalbuphine
· Buprenophrine
Morphinans
· Butorphanol
Benzomorphans
· Pentazocine

7. OPIOID RECEPTOR-
Changes in the classification of the classical opioid receptors over time-
Pre cloning Post cloning IUPHAR 1996 IUPHAR 2000
δ DOR OP1 DOP
κ KOR OP2 KOP
µ MOR OP3 MOP

8. Opioid receptors and their endogenous ligands and precursors-
Receptor Precursor Peptide
DOP Pro-enkephalin [Met]-enkephalin
[Leu]-enkephalin
KOP Pro-dynorphin Dynorphin-A
Dynorphin-B
MOP POMC β-Endorphin
Unknown Endomorphin-1
Endomorphin-2
NOP Pre-pro-nociceptin N/OFQ
Receptor Precursor Peptide

9. MECHANISM OF ACTION-
Opioids produce their actions at a cellular level by activating opioid receptors.
These receptors are distributed throughout the central nervous system (CNS) with
high concentrations in the nuclei of tractus solitarius, peri-aqueductal grey area
(PAG), cerebral cortex, thalamus and the substantia gelatinosa (SG) of the spinal
cord. They have also been found on peripheral afferent nerve terminals and many
other organs. The efficacy of centrally applied opioids is well recognized, but when
applied peripherally, for example in post-traumatic and inflammatory states, their
actions are less reliable. Opioid receptors are coupled with inhibitory G-proteins
and their activation has a number of actions including: closing of voltage sensitive
calcium channels; stimulation of potassium efflux leading to hyperpolarization and
reduced cyclic adenosine monophosphate production.

10. Overall, the effect is a reduction in neuronal cell excitability that in turn results in reduced
transmission of nociceptive impulses. Pure opioid agonists (morphine, diamorphine,
pethidine and fentanyl) bind to opioid receptors avidly and demonstrate high intrinsic
activity at the cellular level as described above.
Partial opioid agonists (buprenorphine, pentazocine) bind to opioid receptors, but produce
a sub-maximal effect compared to pure agonists and so have less intrinsic activity
associated with receptor binding. Opioid antagonists (naloxone, naltrexone), have receptor
affinity but no intrinsic activity.

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