Opioid Partial Agonists Data - Uses, Dosage, Drug class, Brand name, Warnings, etc

Pharmacology

Opioid partial agonists produce analgesia but have an analgesic ceiling, where higher doses do not increase analgesia but may cause adverse effects. Tramadol is metabolized by CYP2D6 to an active metabolite (M1) that binds to mu opioid receptors. Poor metabolizers of debrisoquine/sparteine (~7% of Caucasians) produce negligible M1, reducing analgesia, though some pain relief persists via tramadol enantiomers activating monoaminergic antinociceptive pathways.

Administration, Dosage, and Dosage Forms

Refer to the Opioid Analgesics Comparison Chart for specific agents (e.g., buprenorphine, butorphanol, dezocine, nalbuphine, pentazocine, tramadol).

Patient Instructions

- Take as directed; do not exceed recommended dosage
- May cause drowsiness; avoid driving or operating machinery until effects are known
- Avoid alcohol and other CNS depressants
- Report severe constipation, difficulty breathing, or unusual symptoms (e.g., seizures, hallucinations) to your physician

Adverse Reactions & Side Effects

Frequent:
- Sedation, sweating, dizziness, nausea, vomiting, euphoria, dysphoria (delta receptor activity), hallucinations
Occasional:
- Insomnia, anxiety, anorexia, constipation, dry mouth, syncope, visual blurring, flushing, decreased blood pressure, tachycardia
Rare (parenteral use):
- Diaphoresis, sting on injection, respiratory depression, transient neonatal apnea (from maternal use during labor), shock, urinary retention, altered uterine contractions
Rare (general):
- Muscle tremor, toxic epidermal necrolysis
Long-term parenteral (pentazocine):
- Local skin reactions, ulceration, fibrous myopathy at injection site
Tramadol-specific:
- Seizures (even at recommended doses, increased with overdose or drugs lowering seizure threshold: heterocyclic antidepressants, SSRIs, MAO inhibitors, neuroleptics; or conditions like epilepsy, head trauma, metabolic disorders, withdrawal, CNS infection)
- Anaphylactoid reactions
Butorphanol nasal spray:
- Dependence/addiction, major psychological disturbances

Contraindications

- Tramadol: Prior allergy to any opiate; acute intoxication with alcohol, hypnotics, centrally acting analgesics, opioids, or psychotropic drugs
- Hypersensitivity to specific partial agonists

Precautions & Warnings

- Use cautiously in MI patients (pentazocine, butorphanol increase cardiac workload)
- Can produce dependence and withdrawal symptoms with extended use
- Use with caution in patients with respiratory disease, head injury, increased intracranial pressure, hepatic/renal impairment, or history of seizures
- Tramadol: Naloxone use in overdose may increase seizure risk

Drug Interactions

- CNS depressants (e.g., alcohol, antipsychotics, anesthetics, antidepressants, sedative-hypnotics) increase respiratory depression risk
- Except tramadol, may precipitate acute withdrawal in narcotic-dependent individuals
- Tramadol: Drugs lowering seizure threshold (e.g., SSRIs, MAO inhibitors, neuroleptics) increase seizure risk

Parameters to Monitor

- Monitor pain control, respiratory rate, sedation, and signs of adverse effects (e.g., seizures, withdrawal)
- Assess for psychological disturbances or dependence, especially with butorphanol nasal spray

Class and Drug Brand Names

- Class: Opioid Partial Agonists
- Brand Names: Buprenorphine (Buprenex, Subutex), Butorphanol (Stadol), Dezocine (Dalgan), Nalbuphine (Nubain), Pentazocine (Talwin), Tramadol (Ultram)

Notes

- Not recommended for cancer pain due to analgesic ceiling, risk of precipitating opioid withdrawal, and significant adverse effects
- Pentazocine effects antagonized by naloxone; Talwin NX contains oral naloxone to deter parenteral abuse, though IV abuse with tripelennamine reported
- Tramadol’s dual mechanism (opioid and monoaminergic) provides some analgesia in poor metabolizers

Opioid Receptor Specificity Comparison Chart

Drug	Mu	Kappa	Delta
Buprenorphine	Partial agonist-antagonist	Unknown	Minimal activity
Butorphanol	Partial agonist-antagonist	Agonist	Unknown
Dezocine	Partial agonist-antagonist	Agonist	Minimal agonist activity
Morphine	Agonist	Minimal agonist activity	Unknown
Nalbuphine	Antagonist	Agonist	Agonist
Pentazocine	Partial agonist-antagonist	Agonist	Unknown
Tramadol	Partial or pure agonist*	Minimal activity	Unknown

*Not a classic agonist-antagonist; little/no antagonist properties, partial mu receptor agonist activity; also blocks norepinephrine/serotonin reuptake.

Patient-Controlled Analgesia (PCA) Guidelines Chart

Drug	IV Bolus Dose (mg)	Lockout Interval (min)
Buprenorphine	0.03–0.2	10–20
Fentanyl	0.02–0.1	3–10
Hydromorphone	0.1–0.5	3–15
Meperidine*	5–30	5–15
Methadone	0.5–3	10–20
Morphine	0.5–3	5–20
Nalbuphine	1–5	5–15
Oxymorphone	0.2–0.8	5–15
Pentazocine	5–30	5–15
Sufentanil	0.003–0.015	3–10

*Use with caution (preferably avoid) for PCA; seizure risk with >100 mg every 2 hr for >24 hr, renal failure, or seizure history.
Note: Some clinicians combine PCA with basal continuous infusion, adjusted every 8–24 hr based on bolus use, infusion rate, and pain response. Typical starting basal rate for morphine in a 70 kg adult: 0.5–3 mg/hr.

Intraspinal Narcotic Administration Guidelines Chart

Route and Drug	Bolus Dose (mg)	Onset (min)	Duration (hr)
Epidural: Alfentanil	0.7–2	Rapid	1.5–1.7
Epidural: Fentanyl	0.025–0.15	5	2–4
Epidural: Hydromorphone	1–2	15	10–16
Epidural: Methadone	1–10	10	6–10
Epidural: Morphine	1–10	30	6–24
Epidural: Sufentanil	0.015–0.05	15	4–6
Intrathecal: Morphine	0.1–0.5	15	8–24

References

Hand of Clinical Drug Data