How Do Opioid Partial Agonist Analgesics Work?

Opioid partial agonist analgesics are medications prescribed for pain management and to treat opioid use disorder. Opioid medications work by binding to opioid receptors. Opioid agonists enhance the activity of opioid receptors, opioid partial agonists have partial efficacy, and opioid antagonists block opioid receptor activity.

Opioid receptors are protein molecules on nerve cell (neuron) membranes in the central and peripheral nervous systems. Opioid receptors mediate the body’s response to most hormones and some of their functions include modulating pain, stress response, mood and emotion. The five different opioid receptors discovered in the human body are:

• Mu receptor (MOR)
• Kappa receptor (KOR)
• Delta receptor (DOR)
• Nociceptin receptor (NOR)
• Zeta receptor (ZOR)

Opioid agonists bind to one or more of the opioid receptors and inhibit the release of neurotransmitters and pain transmission by the neurons. Partial opioid agonists elicit a partial functional response because they work as agonists in some receptors and antagonists in others, and consequently, produce fewer adverse effects, while being effective for pain relief (analgesia).

Opioid antagonists bind to opioid receptors but do not produce any functional response. Opioid antagonists prevent agonists from binding to the particular opioid receptor and are useful in treating opioid dependence.

Opioid medications have a high risk for addiction and must be used with great caution. Opioid overdose can have severe consequences, and naloxone, an opioid antagonist, is administered in case of opioid overdose. Naloxone is often combined with opioid partial agonists to treat opioid use disorder.

Opioid partial agonist analgesics are available in several forms such as:

• Buccal film: Applied inside the cheek (buccal tissue) and left to dissolve and be absorbed
• Sublingual film or tablet: Placed under the tongue
• Injectable solution: Administered as an intramuscular or intravenous injection
• Subdermal implant: Implanted under the skin on the inner side of the upper arm, for slow release of medication that lasts up to six months
• Transdermal patch: Applied as a skin patch that slowly releases medication over 7 days, and is absorbed through the skin
• Long-acting subcutaneous injection: Monthly injection into the tissue under the skin
• Nasal spray: Sprayed into the nostril
• Oral tablets: Swallowed orally

Opioid medications are typically used to manage severe pain when alternative treatments are inadequate. Opioid partial agonists should be used with caution in patients with kidney or liver impairment. Opioid partial agonist analgesics are used in the following situations:

• Chronic severe pain
• Weaning off from full opioid agonists
• Opioid addiction and dependence (opioid use disorder)
• Moderate to severe pain
• Major depressive disorder (pending FDA approval)
• Balanced anesthesia
• Labor pain
• Preoperative and pre-anesthesia

Side effects of opioid partial agonist analgesics may include:

• Nausea
• Constipation
• Headache
• Migraine
• Vomiting
• Dizziness
• Vertigo
• Drowsiness
• Drug withdrawal syndrome
• Insomnia
• Pain
• Excessive sweating (hyperhidrosis)
• Weakness (asthenia)
• Lethargy
• Fatigue
• Malaise
• Abdominal pain
• Diarrhea
• Vasodilation
• Peripheral edema
• Chills/cold
• Flushing/warmth
• Infection
• Back pain
• Joint pain (arthralgia)
• Joint swelling
• Chest pain
• Low blood pressure (hypotension)
• Slow heart rate (bradycardia)
• Respiratory depression (hypoventilation)
• Shortness of breath (dyspnea)
• Cessation of breathing (apnea)
• Bluish skin due to low oxygen (cyanosis)
• High blood pressure (hypertension)
• Rapid heart rate (tachycardia)
• Palpitations
• Constriction of pupils (miosis)
• Inflammation of the nasal passage (rhinitis)
• Inflammation of the pharynx (pharyngitis)
• Nasal congestion
• Nasal irritation
• Bleeding from the nose (epistaxis)
• Sinus congestion
• Inflammation of the sinuses (sinusitis)
• Flu syndrome
• Depression
• Depersonalization
• Euphoria
• Nervousness and anxiety
• Floating feeling
• Hallucinations
• Abnormal dreams
• Psychosis
• Tremor
• Pallor
• Sedation
• Confusion
• Slurred speech
• Dry mouth (xerostomia)
• Fever
• Indigestion (dyspepsia)
• Stomach discomfort
• Loss of appetite (anorexia)
• Flatulence
• Accidental injury
• Falls
• Pain in extremities
• Abscess
• Runny eyes
• Blurred vision
• Double vision (diplopia)
• Visual abnormalities
• Lazy eye (amblyopia)
• Ringing in the ear (tinnitus)
• Ear pain
• Toothache
• Taste abnormalities
• Cough
• Oropharyngeal pain
• Inflammation of the bronchial tubes (bronchitis)
• Upper respiratory tract infection
• Inflammation in the eye (conjunctivitis)
• Prickling sensation (paresthesia)
• Loss of sensation (hypoesthesia)
• Urinary retention
• Urinary tract infection
• Atrioventricular nodal block (Wenckebach block)
• Coma
• Injection site reactions
• Implant site reactions such as:
  • Pain
  • Itching (pruritus)
  • Redness (erythema)
  • Hematoma
  • Hemorrhage
  • Edema
  • Laceration
  • Lesion
  • Transdermal patch site reactions such as:
  • Erythema
  • Rash
  • Pruritus
  • Skin picking (excoriation)
  • Scratching
  • Skin reactions such as:
  • Pruritus
  • Rash
  • Erythema
  • Abnormal enzyme levels with an increase in:
  • Creatine phosphokinase (CPK)
  • Alanine aminotransferase (ALT)
  • Aspartate aminotransferase (AST)
  • Gamma-glutamyl transferase (GGT)
  • Adrenal insufficiency
  • Androgen insufficiency
  • Serotonin syndrome, when opioids are administered with serotonergic drugs
  • Toxicity to the liver (hepatotoxicity)
  • Anaphylaxis (serious allergic reaction)
  • Burning pain in the tongue (glossodynia)
  • Inflammation of the tongue (glossitis)
  • Burning mouth syndrome
  • Reduced sensation in the mouth (oral hypoesthesia)

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of opioid partial agonist analgesic drugs include:

• Belbuca
• Buprenex
• buprenorphine
• buprenorphine buccal
• buprenorphine subdermal implant
• buprenorphine transdermal
• buprenorphine, long-acting injection
• buprenorphine/naloxone
• buprenorphine/samidorphan (pending FDA approval)
• butorphanol
• Butrans
• pentazocine/naloxone
• Probuphine
• Sublocade
• Suboxone
• Zubsolv