How Do Opioid Combo Analgesics Work?

Opioid combo analgesics are systemic medications prescribed for management of acute and moderate to severe pain. Opioid medications are combined with pain relievers (analgesics) such as acetaminophen, aspirin, caffeine and/or barbiturates. Opioid combos are typically used to manage severe pain when alternative treatments are inadequate.

Opioids block transmission of pain perception in the brain by binding to opiate receptors. Opiate receptors are protein molecules on nerve cell (neuron) membranes in the brain. Modulating sensory perception is one of the functions of opiate receptors.

Analgesics such as aspirin and acetaminophen work on the hypothalamus region of the brain to reduce fever and relieve pain. Caffeine constricts cerebral blood vessels, which can relieve pain. Caffeine also stimulates the brain’s respiratory drive, improving oxygen inflow. Muscle relaxers may be added to drug formulations to treat musculoskeletal pain.

Barbiturates are sedatives that relieve pain by suppressing the central nervous system and slowing down activity in many regions of the brain. Opioids and barbiturates must be used with great caution because they have a high risk for addiction.

Opioid combo analgesics are oral tablets, capsules or solutions usually prescribed for short periods to manage acute, moderate to severe pain. Opioid suppositories may be used to treat pain from ureteral spasms that does not respond to nonopioid analgesics.

Opioid combos should be used with caution in patients with kidney or liver impairment. Opioid combos are typically tapered before weaning off and not abruptly discontinued. Opioid overdose can have severe consequences, and naloxone, a medication used to reverse opioid effects, is used in case of opioid overdose.

Opioid combo analgesics are used in the management of:

• Acute severe pain
• Acute short-term pain
• Moderate to severe pain
• Chronic pain
• Intermittent or breakthrough pain
• Ureteral spasm pain
• Tension headaches
• Musculoskeletal pain
• Cough (off-label)

Side effects of opioid combo analgesics may include the following:

• Lightheadedness
• Dizziness
• Drowsiness
• Nausea
• Vomiting
• Constipation
• Peptic ulcer
• Fatal hepatic necrosis (liver tissue death, rare and associated with high/chronic acetaminophen use)
• Renal tubular necrosis (kidney tissue death)
• Mood effects such as:
  • Agitation
  • Dysphoria (unease)
  • Depression
  • Depersonalization
  • Euphoria (feeling of high)
  • Mood swings (emotional lability)
  • Restlessness
• Skin reactions such as:
  • Pruritus (itching)
  • Urticaria (hives)
  • Maculopapular rash (flat lesions with raised bumps)
  • Stevens-Johnson syndrome (a rare medical emergency with flu-like symptoms and a painful rash)
  • Toxic epidermal necrolysis (a severe skin condition with widespread redness, skin cell death and exfoliation which can lead to sepsis)
  • Photosensitivity
• Hypersensitivity reactions such as:
  • Angioedema (swelling in the tissue under the skin or mucous membranes)
  • Laryngeal edema (swelling of larynx)
  • Tongue edema
  • Anaphylaxis (serious allergic reaction)
• Insomnia
• Nightmares (paroniria)
• Nervousness
• Irritability
• Tremor
• Tinnitus (ringing in the ear)
• Headache or migraine
• Fatigue
• Lethargy
• Weakness (asthenia)
• Malaise
• Chills (rigors)
• Cognitive effects such as:
  • Mental clouding
  • Sedation
  • Confusion
  • Difficulty concentrating
• Biliary tract spasm
• Hallucinations
• False feeling of well being
• Circulatory collapse
• Histamine release
• Urinary tract spasm
• Low heart rate (bradycardia)
• Cardiac arrest
• Decreased urination (oliguria)
• Shortness of breath (dyspnea)
• Hypotension (low blood pressure)
• Stupor
• Coma
• Respiratory depression
• Physical and psychological dependence with prolonged use
• Drug abuse
• Withdrawal syndrome
• Abdominal distention and pain
• Flatulence
• Syncope (fainting)
• Hot flush
• Chest discomfort
• Inflammation of nasal passage (rhinitis)
• Eye itching
• Loss of sensation (hypoesthesia)
• Diarrhea
• Gastroesophageal reflux disease (GERD)
• Vomiting blood (hematemesis)
• Adrenal insufficiency
• Androgen insufficiency
• Serotonin syndrome, when opioids are administered with serotonergic drugs
• Dry mouth (xerostomia)
• Blurred vision
• Urinary retention
• Flushing
• Rapid heart rate (tachycardia)
• Palpitations
• Paradoxical CNS stimulation
• Anorexia (loss of appetite)
• Ureteral spasm
• Abnormal liver function
• Hepatotoxicity (toxicity to the liver)
• Intoxicated feeling
• Heartburn
• Dyspepsia (indigestion)
• Reduced blood cell counts causing conditions such as:
  • Leukopenia (low level of leukocytes, a type of immune cell)
  • Agranulocytosis (low granulocytes, immune cells with granules)
  • Hemolytic anemia (anemia from rapid destruction of red cells)
  • Pancytopenia (decrease in all types of blood cells)
  • Neutropenia (low levels of neutrophil, a type of immune cell)
  • Thrombocytopenia (decrease in platelet count)
  • Thrombocytopenic purpura (easy bruising and bleeding due to thrombocytopenia)
• Increased urination (with caffeine)
• Orthostatic hypotension (low blood pressure when standing up from sitting or lying down)
• Diaphoresis (sweating)
• Abnormal thinking
• Abnormal vision
• Aggravated hypertension
• Aggravated migraine
• Albuminuria (excessive albumin level in the urine)
• Loss of memory (amnesia)
• Irregular heartbeat (arrhythmia)
• Loss of coordination (ataxia)
• Chest pain
• Convulsions
• Dysphagia (swallowing difficulties)
• Increased muscle tone (hypertonia)
• Involuntary muscle contractions
• Impotence
• Black, tarry stools (melena)
• Urinary retention or incontinence (micturition disorders)
• Prickling sensation (paresthesia)
• Vertigo
• Weight decrease
• Gastrointestinal bleeding

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 combo analgesic drugs include:

• acetaminophen/caffeine/dihydrocodeine
• Anexsia
• Apadaz
• B and O Suppositories
• belladonna and opium
• benzhydrocodone/acetaminophen
• butalbital/aspirin/caffeine/codeine
• codeine/acetaminophen
• codeine/acetaminophen/butalbital/caffeine
• codeine/aspirin/carisoprodol
• Fioricet with Codeine
• Fiorinal with Codeine
• hydrocodone/acetaminophen
• Norco
• oxycodone/acetaminophen
• pentazocine/naloxone
• Percocet
• tramadol/acetaminophen
• Trezix
• Tylenol #3
• Tylenol #4
• Tylenol with Codeine
• Ultracet