Rational Pharmacotherapy for Pain
G. Lipman
Pharmacology is the science that deals with the origin, nature, chemistry, effects, and uses of drugs. Commonly, pharmacology is subdivided into pharmacodynamics (how drugs work; mechanisms of action) and pharmacokinetics (how drugs are absorbed, distributed, biotransformed [metabolized], and eliminated) in the body. Pharmacology is nonclinical science done largely in animal and in vitro models in the laboratory setting. Clinical pharmacology, often termed therapeutics in the United Kingdom and some other countries, is the discipline intended to translate findings from the laboratory bench to the patient bedside. Despite attempts in the United States to develop clinical pharmacology as a subspecialty of internal medicine, and subsequently pediatrics and psychiatry, very few clinical pharmacologists are in practice and fewer still are in training programs today. By definition, the terms pharmacology and even clinical pharmacology are somewhat restrictive.
Pharmacotherapy is, simply put, the treatment of disease by medicines. This is now a recognized health science discipline and describes the practice of clinicians including many physicians, pharmacists, advanced practice nurses, pharmacologically oriented psychologists, and others. Pharmacotherapy encompasses what those who attempted to develop clinical pharmacology envisioned without restricting practice to subspecialty-certified physicians. It is an academic discipline and numerous respected journals, and an increasing number of health science textbooks now have pharmacotherapy in their titles. This more inclusive term includes those aspects of pharmacology and findings from clinical pharmacology that apply directly to the use of pharmacologically active substances in patient care.
Clinicians must have access to contemporary information on how drugs work to use them optimally in managing pain. Pharmacology is the science of how the drugs work, not their application in treating patients. Thus, this section of Bonica’s Management of Pain has been renamed Pharmacotherapy.
Pharmacotherapy is a potent tool in pain management. However, we must use drugs wisely to provide optimal patient benefit. Several core concepts in rational pharmacotherapy are introduced in this chapter as a prelude to the four subsequent chapters on specific pharmacotherapy for pain management.
Drugs Are Both Underused and Overused in Pain Management
There is a broad consensus among pain clinicians that pain, especially chronic nonmalignant pain, is often undertreated.1 One of the reasons for this is concern about medication misuse. Increasing reports of adverse events and even fatalities associated with analgesic use indicate that some practitioners may use analgesic pharmacotherapy unwisely or excessively. It is important to view drugs as tools that can be used well or poorly. Adverse events are not due to the drugs per se; they are due to the way the drugs are used. Clinicians are encouraged not to label any class of drugs as “good” or “bad” but to recognize that they only become so designated because of the way they are used. However, there are some drugs within various classes that one should consider suboptimal, for example, meperidine,2 as discussed in more detail in the opioids chapter (Chapter 79). This section attempts to identify medication use that is more apt to have positive outcomes than adverse outcomes.
Pharmacotherapy Alone Is Rarely Optimal Therapy for Chronic Pain
Analgesic pharmacotherapy often is appropriate alone for acute pain. However, chronic malignant and nonmalignant pain usually responds better to multimodal treatment.3 Many adverse events due to medications might not occur if lower drug doses are used, and concurrent nonpharmacologic therapy often reduces drug dose requirements (Table 77.1). Using multiple drugs to address symptoms of other drugs, that is, polypharmacy, sometimes leads to complex regimens with adverse events.4 Although it is usually wise to simplify drug regimens, use of more than one drug in combination may reduce the risk of adverse events when the drugs are additive or synergistic and the adverse events are commonly dose-related. A common
example is concurrent use of an opioid and a nonsteroidal antiinflammatory drug (NSAID) because these two drug classes are mutually dose sparing. One might consider such use of multiple drugs for pharmacotherapy as “rational polypharmacy.”
example is concurrent use of an opioid and a nonsteroidal antiinflammatory drug (NSAID) because these two drug classes are mutually dose sparing. One might consider such use of multiple drugs for pharmacotherapy as “rational polypharmacy.”
TABLE 77.1 Examples of Pain Intervention Alternatives to Increasing Opioid Dose | ||||||||||||||||
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It is often useful to consider medications for chronic nonmalignant pain as temporary interventions to facilitate the patient’s adapting to self-management techniques such as physical activation, cognitive restructuring, or responding to medical procedures such as serial nerve blocks.
EVERY USE OF MEDICATION FOR PAIN IS AN EXPERIMENT
It is axiomatic that every drug has the potential to do harm. We should only use pharmacotherapy when the potential benefit outweighs the potential harm; that is, there is a favorable risk-to-benefit ratio. Clinicians should consider initial pain pharmacotherapy as a trial to determine outcome before committing to ongoing pharmacotherapy. All medication orders should expire at a predetermined time and only be continued after it is clear that the benefits outweigh the risks. It is helpful in most cases to tell patients that new medications are being ordered for a limited time to determine if they should be continued. This practice would eliminate many adverse outcomes from ongoing drug therapy. This practice might also lessen inappropriate patient expectations about their drug therapy for pain. It is usually unwise to continue any medication without a clear determination that it is more helpful than harmful.
In addition to risk-to-benefit considerations, clinicians should always consider cost-benefit issues. Frequently, new drugs and dosage forms offer incremental advantages over previously available agents, but the new agents do so at a markedly greater cost. The pharmaceutical industry often aggressively markets new and patent-protected drugs and dosage forms, although there is rarely a financial incentive for a pharmaceutical manufacturer or distributor to promote generic drugs because pharmacists can legally substitute generic equivalent drugs unless the prescriber specifies otherwise. At the extreme, entire older classes of drugs, which may still be agents of choice, have been largely replaced by newer, far more expensive agents. For example, tricyclic antidepressants are still drugs of choice for neuropathic pain, but no company promotes them. Aggressive marketing of various antiepileptic and serotonin norepinephrine reuptake-inhibiting drugs that are as effective or nearly as effective as the tricyclic antidepressants for this indication has resulted in the newer, more expensive drugs being considered by many clinicians as the only drugs for neuropathic pain.
PATIENT PREFERENCE: SYMPTOM CONTROL VERSUS SIDE EFFECTS
Patients vary both in their desire to take medications to manage their pain and in their response to the medications. Many patients are highly averse to taking medications, especially opioids, even when those medications can greatly reduce the pain. This aversion may be due to fears or misconceptions about the medications, and clinicians should inquire about their patients’ beliefs and preferences when considering pharmacotherapy. When a patient with allergies indicates a preference for a particular antihistamine, we normally provide that medication. However, when a chronic pain patient expresses a preference for a particular opioid, many clinicians become suspect that there is an ulterior motive for specifying a drug of choice. The perceived preference may be due to prior experience, observation of other patients’ good or bad response to opioids, or misconceptions. We should ascertain the basis for our patients’ expressed preferences when feasible rather than draw our own—often inaccurate—conclusions. Obviously, we should correct wrong information on which patients express preferences.
Some chronic pain patients prefer to be more alert even though the trade-off may be more intense pain. Others prefer as much pain relief as possible with the accompanying dulling of their senses. Neither preference is right or wrong. It is very reasonable to counsel patients about the side effects of the analgesics and adjuvants we are considering and ask them their preferences regarding comfort versus alertness. One of the most problematic misconceptions among chronic pain patients is that medication will “cure” their pain. It is important to determine if the patient harbors such beliefs and to correct them when possible.
There is great interpatient variability in response to analgesics. We see this commonly with NSAIDs but cannot explain the mechanism. With opioids, it also is common, and we know several sources of genetic polymorphism that cause interpatient variability5 as described in more detail in Chapter 79. Clinicians should actively counsel patients about the need to adjust medications and doses to optimize response: One size does not fit all.
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