Side effects of opioids

Opioids have many side effects. Side effects are more likely to occur in people with certain disorders:
kidney failure, a liver disorder, chronic obstructive pulmonary disease (COPD), untreated sleep apnea,
dementia, or another brain disorder.

The following commonly occur when opioids are used:

Drowsiness

Mental fuzziness or confusion

Nausea and vomiting

Constipation

Less common side effects of opioids include

Retention of urine

Involuntary contraction of muscles (called myoclonus)

Itching

A dangerous slowing of breathing

Death

Drowsiness is a common side effect of opioids. For some people who take opioids, drowsiness
disappears or decreases within a few days. If people continue to feel drowsy, a different opioid can be
tried because the degree of drowsiness caused by different opioids varies. Before an important event
that requires alertness, people may be given a stimulant drug (such as methylphenidate or modafinil) to
offset the drowsiness. For some people, drinking a caffeinated beverage helps offset the drowsiness.
When feeling drowsy after taking an opioid, people should avoid driving and take extra care to prevent
falls and accidents.

Confusion can also result from taking opioids, especially if people are older. Opioids increase the risk of
falls in older people.

Nausea sometimes occurs in people with pain, and opioids can increase the nausea. Antiemetic drugs
taken by mouth, suppository, or injection help prevent or relieve nausea. Some commonly used
antiemetic drugs are metoclopramide, hydroxyzine, and prochlorperazine.

The itching caused by taking opioids may be relieved by an antihistamine such as diphenhydramine,
taken by mouth or given intravenously.
Constipation often develops, especially in older people. Stimulant laxatives, such as senna, help prevent
or relieve the constipation. Increasing the intake of fluids and the amount of fiber in the diet can also
help. Osmotic agents such as polyethylene glycol can also be useful. These agents pull large amounts of
water into the large intestine to stimulate bowel movements. Some people need enemas. When these
measures are not effective, doctors may prescribe a drug (such as methylnaltrexone) that blocks only
the effects of opioids in the stomach and intestine and does not lessen the pain relief.

Retention of urine can result from taking opioids, especially in men with an enlarged prostate. Trying to
urinate a second time after a brief pause (double voiding) or applying gentle pressure on the lowest part
of the abdomen (the area over the bladder) during urination may help. Sometimes a drug that relaxes
muscles of the bladder (such as tamsulosin) is used.

For most people, nausea and itching disappear or decrease within a few days. But constipation and
retention of urine usually decrease much more slowly, if at all.

Serious side effects can occur when people take too much of an opioid. These side effects include a
dangerous slowing of breathing (respiratory depression), coma, and even death. The following adds to
the risk of developing respiratory depression and of dying from respiratory arrest:

Having certain conditions (such as liver, kidney, respiratory, or mental health disorders)

Having a substance use disorder

Taking other drugs that cause drowsiness (such as benzodiazepines)

Drinking alcohol

Some of these side effects can be reversed with naloxone, an antidote usually given intravenously or
sprayed into the nose.

For people who are at increased risk of opioid side effects (including respiratory depression), doctors
may prescribe naloxone when they prescribe the opioid. Nurses and family members or caregivers
should watch for serious side effects of opioids and, if such side effects occur, be ready to inject
naloxone or spray it into the person's nose. Doctors or pharmacists usually teach the person taking the
opioid and family members or caregivers how to administer naloxone.

Tolerance occurs in some people who take opioids repeatedly over time. They need higher doses
because their body adapts to and thus responds less well to the drug. However, for most people, the
same opioid dose remains effective for a long time. Often, the need for a higher dose means that the
disorder is worsening, not that tolerance is developing.

Physical dependence usually develops in people who take opioids for a long time. That is, they
experience withdrawal symptoms if the drug is stopped. Withdrawal symptoms include chills, abdominal
cramping, diarrhea, trouble sleeping, and a jittery feeling. When opioids are stopped after long-term
use, doctors reduce the dose gradually over a period of time to minimize the development of such
symptoms.

Physical dependence is not the same as opioid use disorder (addiction). Dependence is characterized by
a craving for the drug and compulsive, uncontrolled use of the drug despite the harm done to the user
or other people. Most people who take opioids to control pain and have not previously had problems
with drug abuse do not become addicted to opioids. Nonetheless, doctors regularly monitor people who
are taking opioid analgesics for signs of addiction.

Administration of opioids

When possible, opioids are taken by mouth (orally). When opioids are taken by mouth, the dose and
time they are taken can be adjusted more easily. When they need to be taken for a long time, they may
be given by mouth or through a patch placed on the skin (transdermally). Opioids are given by injection
(into a muscle or vein) when pain occurs suddenly or when people cannot take them by mouth or
through a skin patch.

Some people who need to take opioids for a long time and are helped by an opioid taken by mouth
cannot tolerate its side effects. For these people, an opioid can be injected directly into the space
around the spinal cord through a pump (intrathecally).

Problems with use of opioids

Opioids are now the leading cause of accidental death and fatal drug overdose in the United States.
Problems with using opioids include opioid misuse, diversion, and abuse.

Opioid misuse may be intentional or unintentional. It includes any use that differs from what is
prescribed.

Diversion involves selling or giving a prescribed drug to others.

Abuse refers to recreational use of the drug. That is, the drugs are taken for the feelings of pleasure or
sensations they produce, rather than to treat pain or another medical condition.

Up to one third of people taking opioids for a long time to treat chronic pain misuse them.

Opioid use disorder is the preferred term for what previously was called opioid addiction. It refers to
compulsive use of opioids despite having problems caused by taking them. Also, people who have this
disorder may require higher and higher doses to achieve the same effects and may experience
withdrawal symptoms when they stop taking the opioid. They may try to stop taking opioids or reduce
the amount they are taking but cannot. Taking high doses of opioids for a long time increases the risk of
developing opioid use disorder.

Adjuvant Analgesics
Adjuvant analgesics are drugs that are usually used to treat other disorders, but can also relieve pain.

Adjuvant analgesics are thought to work by changing the way nerves process pain.

An adjuvant analgesic is the first and only drug used to treat pain due to nerve damage (neuropathic
pain) and conditions such as fibromyalgia.

The adjuvant analgesics most commonly used for pain are

Antidepressants (such as amitriptyline, bupropion, desipramine, duloxetine, nortriptyline, and

venlafaxine)

Antiseizure drugs (such as gabapentin and pregabalin)

Oral and topical local anesthetics

Antidepressants

Antidepressants can often relieve pain in people even when they do not have depression. Tricyclic
antidepressants (such as amitriptyline, nortriptyline, and desipramine) may be more effective for this
purpose than other antidepressants, but newer antidepressants, such as selective serotonin reuptake
inhibitors (SSRIs) and norepinephrine reuptake inhibitors (SNRIs, including duloxetine, venlafaxine, and
milnacipran) may have fewer of the side effects that limit how much of the drug can be taken.

Tricyclic antidepressants are effective for neuropathic pain, headaches, fibromyalgia, and visceral
(organ) hypersensitivity syndromes (such as chronic abdominal pain or pelvic pain). The doses of tricyclic
antidepressants used to treat pain are usually too low to treat depression or anxiety. Thus, if tricyclic
antidepressants are used to treat pain, additional drugs are usually needed to treat depression or
anxiety if present.

Duloxetine appears to be effective for neuropathic pain due to diabetes (called diabetic neuropathy),
fibromyalgia, chronic low back pain, chronic musculoskeletal pain, and nerve pain due to chemotherapy.
The doses of duloxetine used to treat pain are also adequate to treat depression or anxiety if present.
Venlafaxine has similar effects. Milnacipran is effective for fibromyalgia.

People may respond to one antidepressant and not to others, so sometimes doctors try a few drugs until
an effective one is found.

Antiseizure drugs

Antiseizure drugs may be used to relieve neuropathic pain. Gabapentin and pregabalin are commonly
used, but many others, including carbamazepine, clonazepam, lacosamide, lamotrigine, oxcarbazepine,
phenytoin, topiramate, and zonisamide, help relieve pain in some people.
Gabapentin can be used to treat the pain that can result from shingles (postherpetic neuralgia) and
many other types of neuropathic pain.

Pregabalin can be used to relieve pain caused by fibromyalgia or nerve damage due to diabetes (diabetic
neuropathy), postherpetic neuralgia, or neuropathic pain due to a problem in the brain or spinal cord.

Antiseizure drugs, such as topiramate, can prevent migraine headaches.

Anesthetics

A local anesthetic, such as lidocaine, may be injected into the skin to control pain due to an injury or
even neuropathic pain. Local anesthetics can also be injected around nerves to block pain—a procedure
called a nerve block. It is often used to treat pain caused by damage to a specific large nerve. For
example, a sympathetic nerve block involves injecting a local anesthetic around a group of nerves near
the spine—in the neck for pain in the upper body or in the lower back for pain in the lower body. (A
sympathetic nerve block can relieve pain caused by overactivity of the sympathetic nervous system,
which prepares the body for stressful or emergency situations.)

Topical anesthetics, such as lidocaine applied as a lotion, an ointment, or a skin patch, can be used to
control pain due to some conditions.

Mexiletine, used to treat abnormal heart rhythms, is sometimes used to treat neuropathic pain.

These anesthetics are usually used for a short period of time. For example, rinsing with small amounts of
an anesthetic mouthwash a few times a day can relieve pain due to mouth sores. However, some people
with chronic pain benefit from using topical anesthetics for a long time. For example, a lidocaine patch
or gel can help relieve postherpetic neuralgia.

Other drugs

Corticosteroids, such as prednisone and dexamethasone, can be taken by mouth if severe pain is caused
by inflammation (as occurs in gout).

Some evidence suggests that baclofen (a muscle relaxant) can help relieve neuropathic pain due to
trigeminal neuralgia.

Pamidronate (used to treat certain bone disorders) can help relieve neuropathic pain due to complex
regional pain syndrome.

Low doses of ketamine (an anesthetic) are sometimes given intravenously in a hospital to people who
have complex regional pain syndrome when other treatments are ineffective.

Tizanidine (a muscle relaxant), taken by mouth, and clonidine (used to treat high blood pressure), taken
by mouth or applied to the skin as a patch, can help relieve neuropathic pain or prevent migraines.

High-strength capsaicin (a substance found in hot peppers), given in a patch, helps relieve neuropathic
pain due to postherpetic neuralgia. A low-strength capsaicin cream may also help reduce the pain
caused by postherpetic neuralgia and by other disorders such as osteoarthritis. The cream is most often
used by people with localized pain due to arthritis. This cream must be applied several times a day.

Nondrug Pain Treatments

In addition to drugs, many other treatments can help relieve pain.

Applying cold or warm compresses directly to a painful area often helps (see Treatment of Pain and
Inflammation).

Neuromodulation methods use electric stimulation to change how nerves process pain. Techniques
include the following:

Transcutaneous electrical nerve stimulation (TENS)

Spinal cord stimulation

Peripheral nerve stimulation

Physical or occupational therapy may be used to relieve chronic pain and help people function better.
Sometimes doing exercises or increasing activity level helps. For example, walking regularly can help
relieve lower back pain more effectively than resting in bed.

Complementary and integrative medicine may be used to treat chronic pain. For example, doctors may
suggest one or more of the following:

Acupuncture

Mind-body techniques (such as meditation, yoga, and tai chi)

Manipulation and body-based therapies (such as chiropractic or osteopathic manipulation and

massage therapy)

Energy-based therapies (such as therapeutic touch and Reiki)

Acupuncture involves inserting tiny needles into specific areas of the body. How acupuncture works is
poorly understood, and some experts still doubt the technique’s effectiveness. Some people find
substantial relief with acupuncture, at least for a time.

Biofeedback and other cognitive techniques (such as relaxation training, hypnosis, and distraction
techniques) can help people control, reduce, or cope with pain by changing the way they focus their
attention. In one distraction technique, people may learn to visualize themselves in a calm, comforting
place (such as in a hammock or on a beach) when they feel pain.

Cognitive behavioral therapy may reduce pain and pain-related disability and help people cope. This
type of therapy includes counseling to help people focus on coping with the pain, rather than on its
effects and limitations. It may include counseling to help people and their family work together to
manage pain.

The importance of psychologic support for people in pain should not be underestimated. Friends and
family members should be aware that people in pain suffer, need support, and may develop depression
and anxiety, which may require psychologic counseling.