Opioids are potent central nervous system depressants that have many associated risk factors. They should only be used as a last resort when other less addictive pain management options prove ineffective.

When opioids are used on their own, they have a high risk for potentially life-threatening complications. When taken in conjunction with other substances, the associated health risks increase dramatically.

This article covers the substances that can cause complications when taken with opioids.

Mixing Central Nervous System Depressants with Opioids

Central nervous system depressants include a wide variety of substances ranging from alcohol to Xanax. Depending on the drug, they treat everything from pain to anxiety.

Commonly prescribed central nervous system depressants include opioids, anxiolytic (anxiety-reducing) tranquilizers, benzodiazepines like Xanax, non-benzodiazepine sedative/hypnotics, general anesthetics, antipsychotics, muscle relaxants, anticonvulsants, and alcohol.

Central nervous system depressants slow down bodily functions. They often produce a feeling of relaxation and euphoria in therapeutic doses. At high doses, central nervous system depressants can produce dangerous side effects in the body and brain.

The primary risk factor of central nervous system depressants is severe respiratory depression. Central nervous system depressants act directly on the area of the brain that controls breathing. In the event of an overdose, the respiratory drive becomes suppressed to the point being ineffective. This can result in carbon dioxide poisoning and oxygen deprivation.

The combined use of opioids with other central nervous system depressants can increase the likelihood of clinically significant respiratory depression and drug overdose.

Mixing Alcohol with Opioids

Alcohol is the most widely used central nervous system depressant. The combined use of alcohol and opioids can increase the adverse effects of both substances.

The concomitant use of alcohol and opioids increases the risk of blackouts and memory loss. Individuals may progress rapidly from functioning normally to experiencing slurred speech, poor coordination, and difficulty staying awake. Nausea and vomiting are more likely to occur when opioids are combined with alcohol consumption.

Both alcohol and opioids are primarily processed by the liver. When alcohol and opioids are simultaneously present in the liver, the liver can struggle to metabolize them. This may lead to extended elimination times, meaning that it takes longer to clear the drugs from the body.

Extended clearance rates can lead to elevated plasma concentrations. This means that alcohol and opioid metabolites are present in the blood at higher levels, potentially resulting in opioid/alcohol toxicity.

Mixing Serotonergic Drugs with Opioids

Serotonergic drugs boost serotonin levels in the brain. They’re most commonly used to treat depression and various other psychiatric disorders. Opioids also affect the serotonergic transporter system.

Examples of serotonergic drugs include selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), serotonin and norepinephrine reuptake inhibitors (SNRIs), 5-HT3 receptor antagonists, monoamine oxidase inhibitors (MAOIs), and triptans.

Other drugs that affect the impact of serotonin include trazodone, mirtazapine, tramadol, linezolid, and intravenous methylene blue.

The combined use of opioids with serotonin-enhancing drugs can result in a dangerous condition of serotonin overload known as serotonin syndrome. Serotonin syndrome can result in irreversible psychosis and death in severe cases.

Treatment includes immediate cessation of serotonergic drugs and opioid dose adjustment.

Mixing Diuretics with Opioids

Diuretics are any substances that increase the production of urine. They’re also known as “water pills.”

Diuretics are commonly prescribed to treat high blood pressure, swelling in the lower extremities caused by heart failure (edema), and eye conditions like glaucoma. Diuretics may also be prescribed for osteoporosis, kidney stones, diabetes, and male-pattern baldness in women.

Opioids can reduce the effectiveness of diuretics by increasing the release of antidiuretic hormone.

Mixing Anticholinergic Drugs with Opioids

Mixing opioids with anticholinergic drugs can increase the risk of urinary retention and constipation. In severe cases, this may lead to paralytic ileus.

Anticholinergic drugs block the activity of the neurotransmitter acetylcholine. In doing so, they inhibit the nerve impulses of the smooth muscles that control urination and bowel movements.

Anticholinergic drugs may be prescribed to treat dizziness, vertigo, motion sickness, insomnia, respiratory disorders, gastrointestinal disorders, and insomnia.

When anticholinergic substances and opioids must be used together in a medical setting, patients should be carefully monitored for decreased bowel movements.

Mixing Acetaminophen with Opioids

Acetaminophen (paracetamol), known most widely as Tylenol, is often mixed with opioids like hydrocodone. Norco is a common brand of an opioid/acetaminophen combination drug. Norco combines 5 mg of hydrocodone bitartrate with 325 mg of acetaminophen.

Drugs like Norco should not be used for long-term pain management due to the risk of liver toxicity. Acetaminophen has been associated with cases of acute liver failure.

Effects of Long-term Opioid Use

Long-term opioid use can result in several complications including hormonal imbalances.

Adrenal insufficiency can develop when the adrenal gland is no longer able to produce adequate amounts of the stress hormone cortisol. Other steroid hormones, like aldosterone, may also be affected.

Aldosterone regulates sodium and potassium secretion and water retention. One of the signs of adrenal insufficiency is the intense craving for salt and salty foods due to increased sodium excretion in the urine.

If adrenal insufficiency is left untreated, it can result in extreme fatigue, severe abdominal pains, muscle weakness, vomitings, kidney failure, severely low blood pressure (hypotension), mood swings and changes in personality.

Chronic use of opioids may also result in sexual dysfunctions including impotence, low libido, erectile dysfunction, amenorrhea, or infertility.

When in Doubt, Refer to a Professional

Each patient’s unique metabolism, size, body fat percentage, medical history, the conditions being treated, and genetic tendencies affect the ways that certain medications will react with opioids in the body.

For some, medications that typically mix safely with opioids may cause complications. For others, medical conditions may require doctors to prescribe substances that are usually contraindicated in opioid use. Every medical situation is unique. Always refer to the prescribing physician’s recommendations.

If you or someone you love is struggling with opioid misuse, Stonewall Institute Treatment Center is available to answer any questions you may have. Call us today at 602-535 6468 or email us at info@stonewallinstitute.com.