How Do Opioid Antagonists Work?

Opioid antagonists are medications used to reverse opioid effects from opioid dependence, overdose, or therapeutic administrations such as anesthesia. Opioid antagonists bind to opioid receptors and block them from being stimulated by opioid agonists, which are drugs that enhance the activity of opioid receptors.

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 neurotransmitters, chemicals that neurons release to communicate with each other.

Some of the functions of opioid receptors include modulating pain, stress response, mood, and emotions. Most opioid antagonists work by blocking mu-opioid receptors, a type of opioid receptors responsible for the feeling of euphoria, pain relief, and dependence, in addition to other functions.

Some opioid antagonists block the opioid receptors on certain neurons known as pro-opiomelanocortin (POMC), which prevents the feedback of hunger sensation from the body and is used to treat obesity. Some of the opioid antagonists are combined with other classes of medications for eliciting dual effects, which include:

• Partial opioid agonists: Partial opioid agonists have partial effects because they work as agonists in some receptors and antagonists in others. Opioid antagonists combined with partial agonists are used for pain relief while blocking euphoric effects, useful when treating opioid dependence.
• Dopamine reuptake inhibitors: Dopamine reuptake inhibitors increase the levels of dopamine, a neurotransmitter that regulates pleasure sensation and appetite. Dopamine stimulates POMC neurons, which reduces appetite and increases energy expenditure. The combination with opioid antagonists regulates the dopamine reward system and reduces food cravings.

Opioid antagonists may be administered through many routes including:

• Oral: Tablets
• Buccal film: Applied inside the cheek (buccal tissue) and left to dissolve and be absorbed
• Sublingual film or tablet: Placed under the tongue
• Injections:
  • Intramuscular (IM)
  • Subcutaneous (SC)
  • Intravenous (IV

Opioid antagonists and opioid antagonist combinations are used to treating conditions that include:

FDA-approved

• Opioid dependence
• Obesity
• Opioid overdose
• Opioid reversal post-anesthesia
• Reversal of respiratory depression with therapeutic opioid doses
• Postoperative opioid depression
• Alcohol dependence

Orphan designation

• Autoimmune hepatitis
• Postherpetic neuralgia
• Crohn’s disease in pediatric patients

Pending FDA approval

• Major depressive disorder

Side effects of opioid antagonists may include the following:

• Headache
• Nausea
• Vomiting
• Withdrawal symptoms such as:
  • Drug craving
  • Confusion
  • Visual hallucinations
  • Pain
• Injection site reactions such as:
  • Bruising
  • Induration (hardening of the skin)
  • Nodules
  • Pain and tenderness
  • Pruritus (itching)
  • Swelling
• Insomnia
• Constipation
• Abdominal pain
• Decreased appetite
• Diarrhea
• Asthenia (weakness)
• Dizziness
• Anxiety
• Depression
• Somnolence (drowsiness)
• Fatigue
• Lethargy
• Malaise
• Tremor
• Arthralgia (joint pain)
• Myalgia (muscle pain)
• Muscle cramps
• Back pain
• Jaw pain
• Upper respiratory tract infection
• Pneumonia
• Pharyngitis (throat inflammation)
• Viral gastroenteritis
• Influenza
• Urinary tract infection
• Staphylococcal infection
• Hyperhidrosis (excessive sweating)
• Hot flash
• Vasodilation
• Peripheral edema
• Chills
• Dry mouth
• Rash
• Increased creatinine phosphokinase (CPK)
• Increased liver enzymes
• Tinnitus (ringing in the ears)
• Vertigo
• Motion sickness
• Dysgeusia (taste disorder)
• Hypertension (high blood pressure)
• Palpitations
• ECG changes
• Tachycardia (rapid heartbeat)
• Hypotension (low blood pressure)
• Ventricular tachycardia
• Ventricular fibrillation (irregular heartbeat in the ventricles)
• Myocardial infarction
• Cardiac arrest
• Pulmonary edema
• Phlebitis (inflammation of a vein)
• Dyspnea (shortness of breath)
• Labored breathing
• Paresthesia (prickling sensation)
• Tonic-clonic seizures
• Restlessness
• Feeling jittery
• Disturbance in attention
• Memory impairment
• Amnesia (memory loss)
• Mental impairment
• Abnormal dreams
• Nervousness
• Dissociation
• Tension
• Agitation
• Mood swings
• Presyncope (feeling faint)
• Loss of consciousness
• Balance disorder
• Shivering
• Yawning
• Sneezing
• Eructation (belching)
• Thirst
• Dehydration
• Piloerection (goosebumps)
• Lip swelling
• Rhinorrhea (nasal discharge)
• Hematochezia (blood in stool)
• Hernia
• Cholecystitis (inflammation of the gallbladder)
• Hepatotoxicity (toxicity to the liver)
• Liver injury
• Kidney infection
• Increased creatinine clearance in urine
• Decreased hematocrit
• Intervertebral disc protrusion
• Vaginal hemorrhage
• Vulvovaginal dryness
• Irregular menstruation
• Erectile dysfunction
• Alopecia (hair loss)
• Adrenal insufficiency
• Anaphylaxis (serious allergic reaction)
• Serotonin syndrome (a potentially life-threatening drug reaction)
• Glossodynia (tongue pain and burning)
• Glossitis (tongue inflammation)
• Oral mucosal erythema (redness in the mouth)
• Oral hypoesthesia (numbness in the mouth)
• Stomatitis (burning mouth syndrome)

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 antagonist drugs include:

• buprenorphine/naloxone
• buprenorphine/samidorphan (pending FDA approval)
• bupropion/naltrexone
• Contrave
• naloxone
• naltrexone
• Narcan
• Suboxone
• Vivitrol
• Zubsolv