The document provides a comprehensive classification of opioid compounds, including naturally occurring, semisynthetic, and synthetic opioids, as well as their actions at opioid receptor subtypes (μ, δ, κ). It details the mechanisms of action of various opioid compounds, categorizing them as agonists, partial agonists, and antagonists along with their uses and side effects. Additionally, it highlights specific examples of opioids within each category and the health implications associated with their use.

1. OPIOIDS

2. CLASSIFICATION OF OPIOID COMPOUNDS
Naturally occurring • Phenanthrenes (morphine and codeine)
• Benzylisoquinolines (papaverine)
Semisynthetic • Heroin
• Dihydromorphone
• Morphinone
• Thebaine derivatives (e.g., etorphine, buprenorphine)
Synthetic • Morphinan derivatives (levorphanol, butorphanol)
• Diphenyl or methadone derivatives (methadone, d-propoxyphene)
• Benzomorphans (phenazocine, pentazocine)
• Phenylpiperidine derivatives (meperidine, fentanyl, sufentanil, alfentanil,
and remifentanil).

3. ACTIONS PRODUCED AT EACH OPIOID RECEPTOR SUBTYPE
µ (Mu) • Supraspinal and spinal analgesia
• Sedation
• Respiratory depression
• Slowed gastrointestinal transit
• Euphoria
• physical dependence
δ (Delta) • Supraspinal and spinal analgesia
• Depression of ventilation
• Physical dependence
• Modulation of hormone and neurotransmitter release
κ (Kappa) • Supraspinal and spinal analgesia
• Psychotomimetic effects
• Slowed gastrointestinal transit

4. OPIOID ACTION AT RECEPTORS
Full agonist • Compounds that are able to elicit a maximal response following receptor
occupation and activation
Partial agonist • Compounds that can activate receptors but are unable to elicit the
maximal response of the receptor system
Antagonist • Compounds that exert no biological effect when binding to a receptor.
• Antagonists cause a downward shift of the overall action of the receptor
system

5. OPIOIDS BY MECHANISM OF ACTION
AGONIST AGONIST-ANTAGONIST ANTAGONIST
• Morphine
• Methadone
• Hydromorphone
• Meperidine
• Fentanyl
• Alfentanil
• Sufentanil
• Remifentanil
• Levorphanol
• Oxymorphone
• Codeine
• Oxycodone
• Dextromethorphan
• Diphenoxylate
• Difenoxin
• Loperamide
• Pentazocine
• Nalbuphine
• Butorphanol
• Buprenorphine
• Naloxone
• Naltrexone

6. PARTIAL AGONIST WEAK AGONIST AGONIST-ANTAGONIST
HYDROCODONE,
OXYCODONE ,
DIHYDROCODEINE
DEXTROMETORPHAN,
CODEINE
PROPOXYPHENE ,
LEVOPROPOXYPHENE,
DEXTROPROPOXYPHENE
BUPRENORPHINE,
NALBUPHINE ,
BUTORPHANOL ,
PENTAZOCINE,
LEVALLORPHAN
MOA Strong agonist at μ and k
receptors. Inhibits pain
neurotransmission at spinal
and supraspinal sites, binds
NMDA receptors and
antagonizes the effects of
glutamate
Decreases sensitivity of
cough
receptors. Depressing the
medullary cough center
through sigma receptor
stimulation
Weak agonist at μ
receptors.
Inhibits pain
neurotransmission
Partial μ receptors agonist,
antagonist at k & d receptors.
Inhibits pain neurotransmission.
USES Moderate to severe pain,
Cancer pain, Neuropathic pain
(postherpetic neuralgia, DM
neuropathy), Chronic pain,
opioid dependence, opioid
withdrawal
Cough suppression Mild to moderate pain,
Restless legs syndrome,
Opioid withdrawal
Moderate to severe pain, Opioid
dependence, Alcohol
dependence, Balanced
anesthesia, opioid withdrawal
states (buprenorphine),
Postoperative shivering
(Butorphanol)
SE Miosis, Respiratory depression,
Increased ICP,
Postural hypotension,
Constipation, Urinary
retention, Pruritus,
Addiction liability,
Hypogonadism, Hearing loss
Hallucinations, Confusion,
Excitation, Increased or
decreased pupil size,
Nystagmus,
Seizures, Coma, Respiratory
depression, Addiction
liability
Miosis, Respiratory
depression, Increased ICP,
Postural hypotension,
Constipation, Urinary
retention, Pruritus,
Addiction liability, Seizures,
Pulmonary edema,
Fatal arrhythmias
Sedation, Dizziness, Sweating,
Nausea, Anxiety, Hallucinations,
Nightmares,
Respiratory depression (less),
Tolerance,
Dependence liability

7. FULL AGONIST
PHENANTHRENES
MORPHINE (opioid prototype),
Hydromorphone, Oxymorphone,
HEROIN (Synthetic derivatives of
Morphine)
PHENYLPIPERIDINE
FENTANYL, SUFENTANIL,
ALFENTANIL, REMIFENTANIL,
OHMEFENTANYL
MEPERIDINE (Pethidine) PHENYLHEPTYLAMINES
METHADONE,
LEVOMETHADYL
ACETATE, LEVORPHANOL
MOA Strong agonist at μ receptors. Inhibits pain neurotransmission at
spinal and supraspinal sites. Variable activity at d and k receptors
Strong agonist at μ and k
receptors. Inhibits pain
neurotransmission.
Muscarinic blocking actions.
Strong agonist at μ
receptors. NMDA
antagonist. Blocks
monoamine
reuptake transporters.
USES Severe pain, Pain associated
with acute myocardial
infarction, Pulmonary edema,
Adjunct in anesthesia
Severe pain, Adjunct in
anesthesia, Chronic pain,
Breakthrough cancer pain
Moderate to severe pain, Labor
analgesia, Postoperative
Shivering,
Preoperative sedation
Moderate to severe pain
(resistant to morphine),
Opioid dependence
(especially for a relapsing
chronic heroin addict),
Opioid withdrawal
SE Miosis, Restlessness,
Respiratory depression,
Increased ICP, Postural
hypotension, Constipation,
Urinary retention, Pruritus,
Addiction liability, Pain
associated with myocardial
ischemia, Bradycardia
Restlessness, Respiratory
depression, Increased ICP,
Postural hypotension,
Constipation, Urinary
retention, Pruritus,
Addiction liability
Tachycardia, Hypotension
(pronounced in patients with
decreased circulating volume),
Seizures, Delirium, Restlessness,
Respiratory depression,
Increased
ICP, Postural hypotension,
Constipation, Urinary retention,
Pruritus, Addiction liability (less)
Miosis, Restlessness,
Respiratory depression,
Increased ICP, Postural
hypotension, Constipation,
Urinary retention, Pruritus,
Addiction liability (less)
Hepatic dysfunction, QT
prolongation (specific to
methadone)

8. ANTAGONIST
NALOXONE , NALTREXONE, NALMEFENE,
ALVIMOPAN, METHYLNALTREXONE
MOA Competitively blocks μ, d and k receptors.
Rapidly reverses effects of opioid agonists
USES DOC for Opioid overdose (NALOXONE),
Opioid and alcohol dependence (NALTREXONE only)
SE Pruritus, Nausea, Vomiting