Module 8
8.1: Pain
Pain is a basic protective mechanism of the body. The sensation of pain may serve as a warning of imminent danger (fire)
or that there is something wrong in the body (cancer). Alternatively, pain can accompany the normal healing process
(inflammation). When the intensity and duration of a person’s pain begin to affect their ability to function, analgesics can
become very helpful. Analgesics are defined as medications that relieve pain without causing a loss of consciousness.
As there are different types of pain, the appropriate pharmacologic therapy may differ from one type of pain to another.
Acute pain is sudden in onset and usually subsides when treated. Acute pain often lasts 6 weeks or less in duration.
Chronic pain is persistent or recurring and often much more difficult to treat. It is classified as any pain lasting 3-6
months or pain lasting longer than 1 month after healing of an acute injury.
Tolerance refers to a state in which the effectiveness of a drug is significantly reduced following its prolonged use. As the
body adapts, more of the drug becomes required to achieve the same initial physiological effect. Should the drug be
stopped abruptly or smaller dosages given, unpleasant physical and mental symptoms are often observed, a state
referred to as withdrawal. Under such conditions, a physical dependence, which is a need to continue taking a drug to
avoid the unwanted side-effects of its absence, is said to be established. In order to avoid withdrawal, the continual use
of a drug may lead to addiction. Addiction is defined as a chronic neurobiological disease in which genetic, psychosocial,
and environmental factors induce changes in the individual’s behavior to compulsively use drugs despite the harm they
may cause. For these reasons, the treatment of chronic pain can be especially challenging and should be closely
monitored.
Most analgesics can be classified as either opioids or non-opioids.
Opioid analgesics are synthetic drugs that bind to the opiate receptors in the brain and relieve pain. Opioid analgesics
are strong painkillers and are capable of alleviating pain of any origin. They are known to cause tolerance and physical
dependence and therefore should be reserved for moderate to severe pain.
Nonopioid analgesics include painkillers that do not work on opioid receptors, the primary example being Non-Steroidal
Anti-inflammatory Medications (NSAIDs) as introduced in Module 2. NSAIDs are a large, chemically diverse group of
drugs that are analgesics and also possess anti-inflammatory and antipyretic activity.
Neuropathic pain is a unique classification of pain and is defined as pain resulting from a damaged nervous system or
damaged nerve cells. Due to its unique origin, neuropathic pain does not typically respond to traditional pain
medications including opioids and NSAIDs. It can be extremely difficult to manage and is generally treated with a variety
of medications from different classes that have shown to have some effect on neuropathic pain. Examples include
antiseizure medications, antidepressants, and new classes that have been developed to treat neuropathic pain.
Fibromyalgia is one of the most common neuropathic pain conditions and is defined as a disorder characterized by
widespread musculoskeletal pain accompanied by fatigue, and sleep, memory and mood issues. Researchers believe that
fibromyalgia amplifies painful sensations by affecting the way your brain processes pain signals.
Drug Therapy
Opioids
Opioids are often referred to as narcotics. However, when referencing drugs being used medicinally, opioid is the correct
term. Opioids are a class of very strong pain relievers originating from the opium poppy plant. Relatively basic chemical
modifications of these natural opioids have produced three different chemical classes of opioids: (1) morphine-like
,drugs, (2) meperidine-like drugs, and (3) methadone-like drugs. This can be important in selecting a drug for a patient
who has had an adverse reaction to one type of opioid. Table 8.1 summarizes the chemical categories of several opioid
analgesics.
Mechanism of Action:
Opioid analgesics work by binding to the opioid receptors in the brain causing an analgesic response. Most opioids used
for their analgesic properties are classified as opioid agonists (meaning they stimulate opioid receptors). In order to elicit
the effects of pain relief, opioids bind to different types of opioid receptors—the most prevalent being the mu, kappa,
and delta receptors. It is also important to note that opioids differ in their relative potency. Proper knowledge of potency
is critical when these medications are being used clinically, especially when transitioning from one opioid to another. In
order to do this safely, the clinician must know the relative potency of each opioid. A system was devised whereby
morphine would be the opioid that all other opioids are compared to in terms of potency, a practice referred to as
morphine equivalents. Thus, by using morphine there is a standard drug to compare to that is consistently used when
switching between opioids. This helps to standardize the process of converting patients to new regimens. Table 8.2
below summarizes some of the more common opioid analgesics and specifies their relative potency compared to
morphine.
, Adverse Effects:
All opioid drugs have a strong potential for being abused. In addition to the potential for abuse, opioids can cause
histamine release which may cause itching, rash and hemodynamic changes such as flushing and orthostatic hypotension
(a drop in blood pressure upon standing up from a seated position). How much histamine an opioid release is related to
which chemical category they fall into. For example, morphine-like opioids release the most histamine, whereas
meperidine-like opioids release the least amount of histamine. The most serious adverse effect is CNS depression that
can lead to respiratory depression. Patients need to be monitored for signs of respiratory depression. When people die
from an opioid overdose it is almost always from respiratory depression.
Less serious, but very common, are the GI tract adverse effects that occur with opioid medications. There are opioid
receptors in the GI tract that, when stimulated, cause nausea, vomiting, and constipation. The stimulation of GI opioid
receptors stimulates the chemoreceptor trigger zone in the brain which results in nausea and vomiting. Constipation
results from opioids working to slow peristalsis and increasing the absorption of water from the intestines. Nausea and
vomiting often dissipate over time. Constipation, however, does not. In fact, most patients on longer-term opioids need
to be treated with a bowel regimen to prevent constipation.
Toxicity and Overdose:
Naloxone and naltrexone are two opioid antagonists available to treat opioid overdose. Because they are such strong
antagonists, they can actually reverse adverse effects such as respiratory depression caused by an opioid overdose.
Naloxone is available under the trade name Narcan (nasal spray) and Evzio (autoinjector). Due to the growing overdose
8.1: Pain
Pain is a basic protective mechanism of the body. The sensation of pain may serve as a warning of imminent danger (fire)
or that there is something wrong in the body (cancer). Alternatively, pain can accompany the normal healing process
(inflammation). When the intensity and duration of a person’s pain begin to affect their ability to function, analgesics can
become very helpful. Analgesics are defined as medications that relieve pain without causing a loss of consciousness.
As there are different types of pain, the appropriate pharmacologic therapy may differ from one type of pain to another.
Acute pain is sudden in onset and usually subsides when treated. Acute pain often lasts 6 weeks or less in duration.
Chronic pain is persistent or recurring and often much more difficult to treat. It is classified as any pain lasting 3-6
months or pain lasting longer than 1 month after healing of an acute injury.
Tolerance refers to a state in which the effectiveness of a drug is significantly reduced following its prolonged use. As the
body adapts, more of the drug becomes required to achieve the same initial physiological effect. Should the drug be
stopped abruptly or smaller dosages given, unpleasant physical and mental symptoms are often observed, a state
referred to as withdrawal. Under such conditions, a physical dependence, which is a need to continue taking a drug to
avoid the unwanted side-effects of its absence, is said to be established. In order to avoid withdrawal, the continual use
of a drug may lead to addiction. Addiction is defined as a chronic neurobiological disease in which genetic, psychosocial,
and environmental factors induce changes in the individual’s behavior to compulsively use drugs despite the harm they
may cause. For these reasons, the treatment of chronic pain can be especially challenging and should be closely
monitored.
Most analgesics can be classified as either opioids or non-opioids.
Opioid analgesics are synthetic drugs that bind to the opiate receptors in the brain and relieve pain. Opioid analgesics
are strong painkillers and are capable of alleviating pain of any origin. They are known to cause tolerance and physical
dependence and therefore should be reserved for moderate to severe pain.
Nonopioid analgesics include painkillers that do not work on opioid receptors, the primary example being Non-Steroidal
Anti-inflammatory Medications (NSAIDs) as introduced in Module 2. NSAIDs are a large, chemically diverse group of
drugs that are analgesics and also possess anti-inflammatory and antipyretic activity.
Neuropathic pain is a unique classification of pain and is defined as pain resulting from a damaged nervous system or
damaged nerve cells. Due to its unique origin, neuropathic pain does not typically respond to traditional pain
medications including opioids and NSAIDs. It can be extremely difficult to manage and is generally treated with a variety
of medications from different classes that have shown to have some effect on neuropathic pain. Examples include
antiseizure medications, antidepressants, and new classes that have been developed to treat neuropathic pain.
Fibromyalgia is one of the most common neuropathic pain conditions and is defined as a disorder characterized by
widespread musculoskeletal pain accompanied by fatigue, and sleep, memory and mood issues. Researchers believe that
fibromyalgia amplifies painful sensations by affecting the way your brain processes pain signals.
Drug Therapy
Opioids
Opioids are often referred to as narcotics. However, when referencing drugs being used medicinally, opioid is the correct
term. Opioids are a class of very strong pain relievers originating from the opium poppy plant. Relatively basic chemical
modifications of these natural opioids have produced three different chemical classes of opioids: (1) morphine-like
,drugs, (2) meperidine-like drugs, and (3) methadone-like drugs. This can be important in selecting a drug for a patient
who has had an adverse reaction to one type of opioid. Table 8.1 summarizes the chemical categories of several opioid
analgesics.
Mechanism of Action:
Opioid analgesics work by binding to the opioid receptors in the brain causing an analgesic response. Most opioids used
for their analgesic properties are classified as opioid agonists (meaning they stimulate opioid receptors). In order to elicit
the effects of pain relief, opioids bind to different types of opioid receptors—the most prevalent being the mu, kappa,
and delta receptors. It is also important to note that opioids differ in their relative potency. Proper knowledge of potency
is critical when these medications are being used clinically, especially when transitioning from one opioid to another. In
order to do this safely, the clinician must know the relative potency of each opioid. A system was devised whereby
morphine would be the opioid that all other opioids are compared to in terms of potency, a practice referred to as
morphine equivalents. Thus, by using morphine there is a standard drug to compare to that is consistently used when
switching between opioids. This helps to standardize the process of converting patients to new regimens. Table 8.2
below summarizes some of the more common opioid analgesics and specifies their relative potency compared to
morphine.
, Adverse Effects:
All opioid drugs have a strong potential for being abused. In addition to the potential for abuse, opioids can cause
histamine release which may cause itching, rash and hemodynamic changes such as flushing and orthostatic hypotension
(a drop in blood pressure upon standing up from a seated position). How much histamine an opioid release is related to
which chemical category they fall into. For example, morphine-like opioids release the most histamine, whereas
meperidine-like opioids release the least amount of histamine. The most serious adverse effect is CNS depression that
can lead to respiratory depression. Patients need to be monitored for signs of respiratory depression. When people die
from an opioid overdose it is almost always from respiratory depression.
Less serious, but very common, are the GI tract adverse effects that occur with opioid medications. There are opioid
receptors in the GI tract that, when stimulated, cause nausea, vomiting, and constipation. The stimulation of GI opioid
receptors stimulates the chemoreceptor trigger zone in the brain which results in nausea and vomiting. Constipation
results from opioids working to slow peristalsis and increasing the absorption of water from the intestines. Nausea and
vomiting often dissipate over time. Constipation, however, does not. In fact, most patients on longer-term opioids need
to be treated with a bowel regimen to prevent constipation.
Toxicity and Overdose:
Naloxone and naltrexone are two opioid antagonists available to treat opioid overdose. Because they are such strong
antagonists, they can actually reverse adverse effects such as respiratory depression caused by an opioid overdose.
Naloxone is available under the trade name Narcan (nasal spray) and Evzio (autoinjector). Due to the growing overdose
