5
Non-Pain Symptoms
The stories that ill people tell come out of their bodies. The body sets in motion the need for new stories when its disease disrupts the old stories.
Arthur Frank, The Wounded Storyteller: Body, Illness and Ethics
I sighed quietly, having had similar discussions many times before. “Yes,” I replied, “We can. The question is—would those therapies be helpful relative to what we are trying to do?”
The resident explained that Mr. A. had bowel obstruction and was receiving the usual care. He had a nasogastric tube (NG) in place and an IV running. His nausea was being treated with lorazepam. The problem was that Mr. A. wanted to see his son, who was in the Philippines, before he died. There were visa issues, and it might take a few weeks to get things straightened out. Thus, the family was interested in keeping him alive until then. Again, the resident apologized. Life prolongation seemed to be against hospice philosophy, but the resident asked if we could make an exception in this case given the importance of the son’s visit. Unfortunately, Mr. A. was not alert, but it would be so important to the family.
I explained that hospice is not opposed to people living longer. Life is an important aspect of quality of life, so if there were simple things we could do to increase the chance that Mr. A. would get see his son, this was completely in keeping with hospice philosophy and fine with me. In the meantime, I wondered out loud, would the team be interested in some suggestions for his care?
“Please!” replied the resident. I suggested that octreotide be added to his drug regimen and that a different antiemetic be used, as lorazepam was likely doing little other than sedating the patient. It was fine to keep the NG and IV in place for now. We would reevaluate their use when he came to hospice.
When we arrived we found Mr. A. sitting up in bed, smiling. “He woke up!” said his wife. His chart revealed that the amount of fluid draining from the NG had decreased dramatically following administration of octreotide. Over the next few days with various interventions we managed to discontinue the NG and the IV. He began to eat despite his continuing obstruction and became ambulatory. He was discharged to home hospice, where he lived for two months until shortly before his death, when he returned to our unit. Unfortunately, his son did not make it in time. However, his family remarked on how precious the extra time at home had been.
I share this story because it illustrates several points. First, palliative care should not be so much about what we do (IVs or antibiotics) as about why we do it. What is our intent, and how does this intent relate to the goals of care established by the patient, family, and clinicians? Second, many view the choice between palliative or hospice care and traditional medical care as a choice between being comfortable (but inevitably dying sooner) in hospice and living longer, albeit with less comfort, in traditional care. In most cases this is a false choice. There is no good evidence that people, appropriately selected, who elect a palliative approach to care die sooner than do those in traditional care. It is also a false choice in that it implies to some that living longer in hospice is necessarily a bad thing, or is antithetical to hospice philosophy, which it is not.
As I will discuss further in the section on bowel obstruction, I believe Mr. A. lived better and longer because he received palliative care. “Standard therapy” for bowel obstruction, including long-term NG suction and IV fluids, may result in patients dying sooner than they would with state-of-the art palliative care. The treatment of Mr. A.’s nausea with lorazepam was inept and even harmful, but not unusual. Although people are just beginning to understand how little clinicians learn and know about pain management, few are aware that, if possible, ignorance of effective therapies for many non-pain symptoms is even greater than it is for pain.
One day many years ago an intern with whom I was working asked a very simple question: “What is the difference between Phenergan [promethazine] and Compazine [prochlorperazine]?” Although I had been doing palliative care for more than a year, I was embarrassed to admit to her and to myself that I did not know. Hence, I tried to find out. I was shocked to find that these medicines, which I had been using for years almost interchangeably, were almost exact opposites in their pharmacology. I just did not know.
Since then, I am still amazed at how little attention non-pain symptoms receive in medical education. I recall a conference I attended several years ago. Half the conference was devoted to pain management and the other half to various aspects of end-of-life care. I was asked to speak about non-pain symptoms. I thought, “This a peculiar balance—half the conference on one symptom, pain, and a one-hour session on non-pain symptoms.” Of course, it was impossible to cover every non-pain symptom in one hour, and it is equally impossible to do justice here to the wide array of non-pain symptoms that may arise. Still, I will highlight some distressing symptoms often encountered in practice.
In Chapter 3 I discussed a general approach to thinking about the pathophysiology of symptoms. In brief review, symptoms typically have central and peripheral physical components and mental (psychological, social, and spiritual) components. However, an almost too basic questions is still unaddressed—why do we have symptoms? Leaving aside deeper spiritual ponderings about the nature and meaning of suffering, I tend to approach this question from a Darwinian perspective. That is, I believe symptoms evolved because there was some survival advantage to them. This is perhaps easiest to see with pain. Unpleasant as pain is, one can well imagine that not being aware of damage signaled by pain would be a problem, as highlighted by rare cases in which people cannot sense pain.1 More simply, symptoms evolved because they served a purpose. Understanding that original purpose can help us understand the pathophysiology of the symptom and devise strategies for treatment in situations in which symptoms no longer serve a helpful function, as is generally true in chronic illness.
Nausea and Vomiting
Why Do We Experience Nausea and Vomiting?
Nausea and vomiting, unpleasant as they are, serve an important purpose. They protect us from ingesting and absorbing toxic substances, a clear evolutionary advantage. The ability to vomit evolved in mammals above the level of rodents, establishing a series of fail-safes. The first set of fail-safes kick in before we ingest anything. Our senses of sight and smell serve to protect us from eating substances that might be bad for us. A useful rule of thumb is that if something looks gross or smells terrible, it probably is. Memory also serves as a protective mechanism. If eating something made you sick before, it probably will do so again. The memory of nausea and vomiting associated with that substance is itself a potent stimulus for nausea. The next fail-safe in series is taste. If something tastes awful, bitter, or caustic, it likely is bad for you. Unfortunately, looks, smell, and taste can sometimes be deceiving, so we may still end up eating something poisonous. If ingested, a toxic substance may irritate the stomach or intestine, stimulating special chemoreceptors and giving rise to nausea and vomiting, thus limiting absorption of the poison. However, even this is not adequate protection. Some toxins may get through all these safeguards. The brain has a variety of receptors that test for potential toxins. Stimulation of these receptors triggers nausea and vomiting, causing the person to vomit whatever has been eaten, hopefully before more toxins are absorbed.
Unfortunately, nausea and vomiting arise with certain illnesses and secondarily to certain therapies in ways that offer no such survival advantage. Indeed, nausea and vomiting in such cases may increase the morbidity and mortality of illness through dehydration, electrolyte imbalance, and limitation of food intake.
Pathophysiology of Nausea and Vomiting
Good evidence exists that various stimuli that affect nausea and vomiting come together in an area in the brain known as the vomit (or emetic) center in the medulla. This “center” is not a discrete nucleus, but a complex array of neurons coordinated by a “central pattern generator.”2 Still, for our purpose, it is useful to think of a final pathway that gives rise to vomiting. The vomit center receives input from four major areas: the GI tract, the chemoreceptor trigger zone (CTZ), the vestibular apparatus, and the cerebral cortex. (The center also has intrinsic chemoreceptors that can modulate, stimulate, and repress nausea.3,4) Each of these four areas responds to certain types of stimuli, modulated by specific neurotransmitters that bind specific receptors. Understanding how these areas modulate nausea and vomiting helps us tailor specific therapies for specific problems.
The GI Tract
As the primary source of toxin absorption is the gut, the effect of the GI tract on the vomit center is complex. Stimulation of the gut chemoreceptors and stretch receptors triggers nausea and vomiting via vagal nerve afferents and fibers associated with the sympathetic nervous system. Serotonin, acetylcholine, histamine, and substance P are major neurotransmitters involved in stimulating these receptors. Chemoreceptors in the gut appear to be major mediators of the toxic effects of certain chemotherapeutic agents, such as cisplatin, even when such drugs are given intravenously via binding to gut 5HT3 receptors. In addition to being a neurotransmitter that stimulates nausea, acetylcholine also increases gut motility and gut secretion. Histamine mediates transmission of nausea via the vagus nerve. Substance P binds neurokinin-1 receptors in the gut (and directly in the vomit center in the brain).5,6
The Chemoreceptor Trigger Zone
The CTZ senses chemicals in the blood. The CTZ is particularly sensitive to increasing blood levels of potentially toxic substances. If a toxic substance is detected, nausea is experienced and the vomit reflex initiated—hopefully before more toxin is absorbed.
The CTZ is an amazing organ. The brain is separated from the blood that flows through it by a blood–brain barrier, which protects the brain from bad things like bacteria in the blood. However, there is a downside to such a separation. Ideally, one would like to identify toxins that might damage the brain before they cross the barrier. This is where the CTZ comes in. The CTZ is part of the CNS, but in part it crosses the blood–brain barrier, enabling it to evaluate certain types of molecules for possible toxicity. But what is safe and what is toxic? The CTZ applies a “test” of sorts to the myriad molecules floating by. It asks (a) is this molecule something “foreign,” and (b) if it is seen as “foreign,” is it increasing in concentration? If the answer to both these questions is “yes,” then it might be dangerous. The CTZ then sends a signal to stop eating, by way of promoting nausea, and finally to empty whatever might remain in the stomach.
Two major neurotransmitters are involved in signaling within the CTZ—dopamine, acting on D2 receptors, and serotonin, acting on 5HT3 receptors. Different toxin responses are mediated through different neurotransmitters. Opioid-related nausea appears to be most related to stimulation of D2 receptors. Understanding this has helped with selective blockage of specific receptors in specific disorders.
The Vestibular Apparatus and CNS Receptors
Unfortunately, not all toxins can be detected by gut receptors or the CTZ. Some neurotoxins, such as ethyl alcohol, a small molecule, may still get through to the brain. The vestibular apparatus and more central receptors may respond to such toxins. Motion sickness, such as car sickness and seasickness, is mediated through the vestibular apparatus, as are inner-ear diseases, such as Ménière’s disease. The vestibular apparatus may serve as a sensor for certain neurotoxins (such as alcohol) that can produce disequilibrium. Stimulation of the vestibular apparatus by alcohol may provide a survival advantage in keeping our species from, literally, drinking ourselves to death. Stimulus of the vestibular apparatus is mediated largely through histamine and acetylcholine receptors. The vomit center in the medulla also has intrinsic histamine and acetylcholine receptors. Most over-the-counter antiemetics work on these receptors.
The Cerebral Cortex
Higher cortical structures modulate complex experiences such as taste, sight, and smell as well as memory (involved in anticipatory nausea) and emotion. Discrete neuropathways are less well understood. However, higher cortical effects are still important and can be extremely powerful in stimulating nausea and vomiting. I recall a Christmas many years ago, when our son was young. I gave a gift of “Gack,” a slimy gel, appealing to boys of a certain age. Upon opening the container of Gack Cody put his fingers into it and immediately vomited on me and the Christmas tree. “Cool!” he said. “It made me hurl!” I marveled at the speed of this response. I know of no agent I could administer parenterally that could act so quickly. Higher cortical pathways can function very rapidly.
Principles of Therapy
A useful mnemonic for remembering causes of nausea and vomiting is VOMIT. Recalling these causes will help to figure out which approaches are best in treating particular patients:
Vestibular
Patients who have vestibular involvement may complain of poor balance, nausea stimulated by rapid head movement or motion, and other inner-ear symptoms, such as changes in hearing or ear ringing. Minimizing movement can help to minimize nausea mediated through this system. Medications with strong antihistaminic and anticholinergic properties are most useful. Many medications are available that block both histamine and acetylcholine receptors. All available medications are sedating. Newer nonsedating antihistamines cannot be used because their lack of sedation relates to poor penetration across the blood–brain barrier. Thus, while they are good for blocking histamine receptors peripherally, they are not useful for blocking central receptors.
Obstruction (and Opioids)
Obstruction and poor gut motility result in the backup of the contents of the gut. Mechanoreceptors and chemoreceptors are stimulated, and nausea is triggered. The more distal the obstruction in the gut, the more the abdomen will be distended and the longer it will take for gut contents to back up. (See the section on bowel obstruction.) Obstruction can be mechanical or “functional.”* The most common cause of obstruction is constipation. In at-risk patients, this should be ruled out by history, rectal examination, and X-ray examination, if necessary.
Palliative Care Note
Especially in geriatric patients, “look out below” when they present with nausea and vomiting. Ask when their last bowel movement was.
Various diseases may cause bowel dysmotility. Diabetics may have gastric neuropathies. Patients on opioids and anticholinergic drugs commonly experience dysmotility of both the upper and lower gut. Patients who have dysmotility often complain less of frank nausea than of early satiety. Classically, they will have a modest appetite, then are able to eat very little, followed shortly by abrupt regurgitation of undigested food. Unless contraindicated (as in Parkinson’s disease or advanced renal failure), metoclopramide is the drug of choice for such dysmotility of the upper GI tract. Removing offending agents that slow the gut may improve dysmotility. Anticholinergic drugs antagonize the activity of metoclopramide and should therefore be decreased or eliminated, if possible, when starting this drug. Metoclopramide works by binding 5HT4 receptors, which in turn release acetylcholine, stimulating motility. Anticholinergic drugs antagonize this effect.
Palliative Care Note
Avoid using anticholinergic drugs with metoclopramide, as these antiemetics antagonize the action of this drug.
A common problem in palliative care is the “squashed stomach syndrome.” Patients who have enlarged livers due to cancer or hepatitis may present with early satiety and abrupt vomiting in a syndrome clinically indistinguishable from dysmotility as described above.7 Although technically a form of mechanical bowel obstruction due to extrinsic compression, therapy is identical to that for dysmotility, stressing promotility agents such as metoclopramide.
Mind
The mind can have a powerful effect on the experience of nausea and vomiting, as highlighted by my son’s experience with Gack. A peaceful environment with appealing sights, smells, and tastes can promote appetite. A lack thereof can cause or exacerbate nausea, as can anxiety and depression. Anxiolytics such as benzodiazepines can be helpful for anxiety and are specifically indicated for anticipatory nausea associated with chemotherapy.8 (Please note that there is no evidence to support the use of lorazepam as an agent for the treatment of nausea outside of these indications. Lorazepam can induce sedation and theoretically increase the risk of aspiration in a sedated vomiting patient. The case of Mr. A. highlights this point.) Depression, when present, should be addressed. Adjusting food presentation for ill patients can be a challenge. Fatty and spicy foods are best avoided. With serious illness tastes may change. In advanced cancer meat is often said to taste bad. Very sweet substances may be poorly tolerated. Slightly sour, cooler, easy-to-digest foods are often best.
Infection/Irritation/Inflammation
Nausea and vomiting may be a nonspecific sign of an acute GI infection and require little more than sympathy and perhaps treatment with an anticholinergic/antihistaminic agent, such as promethazine. Irritation of the stomach and intestinal tract may be ameliorated with coating agents, such as sucralfate or bismuth-containing preparations, such as Pepto-Bismol. Nausea may be an early sign of more serious infection, such as pyelonephritis, pneumonia, or a CNS infection. These causes should be considered, as appropriate.
Various therapeutic agents and medications can induce inflammation. Inflammation anywhere in the body may result in the release of substances that stimulate nausea through a direct effect on the brain. Gut inflammation through the use of chemotherapeutic agents and radiation therapy is a potent stimulant of nausea. The exact mechanisms through which nausea is stimulated in this way are still being worked out. Preliminary work suggests that serotonin binding of 5HT3 receptors and substance P binding of neurokinin-1 receptors in the gut may be particularly important. Randomized controlled trials have demonstrated superiority for the use of 5HT3 antagonists for radiation enteritis.9,10,11
These studies suggest the possibility that when gut inflammation is thought to be a major contributor to nausea, anticholinergic and antihistaminic agents may be fine for minor or self-limited nausea. However, for more severe forms of nausea, 5HT3 antagonists may be preferable. Neurokinin-1 antagonists may also be helpful for this form of nausea.12
Toxins
The major toxins of today are not found in strange plants, as was the case for our distant ancestors, but in the medications we give our patients. Many drugs can cause nausea and vomiting as side effects. Most clinicians are quick to suspect opioids, such as morphine. They may forget such common drugs as digoxin, nonsteroidal anti-inflammatory agents (NSAIDs), and antidepressants such as fluoxetine (Prozac) or sertraline (Zoloft). New-onset nausea should always prompt a medication review and consideration of withholding possibly offending agents.
Because opioid-related nausea is so common, it will be discussed separately. Opioids result in nausea through two major mechanisms: inhibition of gut motility and stimulation of the CTZ. Stimulation of the CTZ relates more to increases in blood opioid levels than it does to absolute opioid levels. Thus, initiating opioid therapy or raising the opioid dose is likely to result in nausea. However, if a new steady-state blood level is maintained, nausea usually subsides within two to three days. During this time aggressive treatment of nausea usually allows patients to tolerate opioid therapy. This is particularly important if the oral route is used for administration. Patients may enter a vicious cycle of nausea interrupting oral opioid administration, resulting in fluctuating blood opioid levels and perpetual nausea (in addition to unnecessary pain). In severe cases a non-oral route of administration should be used, at least until nausea is under control, in order to escape this cycle. As stimulation of the CTZ is primarily mediated through D2 receptors, dopamine blockade is central to drug therapy. Anticholinergic and antihistaminic agents are less effective for this form of nausea, although they may help with relatively minor stimulation of the vestibular apparatus by opioids. Anticholinergic and antihistaminic agents may increase undesired sedation, especially in geriatric patients, associated with initiation or upward titration of opioids, and may also exacerbate poor gut motility, adding to these serious side effects of opioids. Anticholinergic and antihistaminic agents dry the mouth, a common and troubling side effect in elderly patients or seriously or terminally ill patients. Thus, a strong argument can be made for maximizing dopamine-blocking effects, except where contraindicated, as in Parkinson’s disease, and minimizing anticholinergic and antihistaminic effects in choosing an antiemetic for opioids.
Specific Medications for Nausea
Few randomized controlled studies have compared specific medications for specific causes of nausea. However, as discussed above, research has progressed in understanding the relationship between receptors and nausea (summarized in Fig. 5.1). Based on in vitro receptor binding, Peroutka and Snyder developed Table 5.1, in which lower numbers indicate tighter binding and therefore greater blockade of the receptor. For example, scopolamine is strongly anticholinergic, as a small concentration of the drug (0.8 in nanomoles) is needed to block the cholinergic receptor.
Scopolamine
As is readily seen in Table 5.1, scopolamine is a pure anticholinergic agent. It can be useful in treating motion-related nausea and when sedation or other anticholinergic effects are desired, such as decreasing gut secretions and alleviating cramping due to bowel obstruction. Marketed for motion sickness, scopolamine is available as a patch. It can be given SC. Effects last approximately six hours.
Table 5.1. Receptor Binding of Common Antiemetics
| Drug Group | Dopamine 2 | Musc. Cholinergic | H1 Histamine |
| Scopolamine | >10,000 | .08 | >10,000 |
| Promethazine | 240 | 21 | 2.9 |
| Prochlorperazine | 15 | 2100 | 100 |
| Chlorpromazine | 25 | 130 | 28 |
| Metoclopramide | 270 | >10,000 | 1,100 |
| Haloperidol | 4.2 | >10,000 | 1600 |
Source: Adapted from Peroutka and Snyder.13
Promethazine (Phenergan)
Promethazine has strong anticholinergic and antihistaminic effects. Its weak binding of dopamine receptors suggests it would be a poor choice as an antiemetic for opioid-related nausea. Despite this, it is commonly used for opioid-related nausea (perhaps based on misguided extrapolations from its use in combination with meperidine and chlorpromazine as a pediatric sedative in emergency rooms).14 Therefore, promethazine is not recommended for pure opioid-related nausea. It is available in oral, IM, IV, and rectal suppository forms. Promethazine may be a drug of choice when a drug, especially a suppository, is needed for motion-related nausea and when other anticholinergic and antihistaminic effects are desired, as in viral gastroenteritis.
Prochlorperazine (Compazine)
Prochlorperazine has strong dopamine and histamine receptor binding, with weak cholinergic receptor binding. It is mildly sedating. It is available in oral (tablet, liquid), IV, IM, and suppository forms. Prochlorperazine may be considered a good choice when a suppository is needed for opioid-related vomiting and anticholinergic effects are to be avoided.
One of the few randomized controlled studies done for non–chemotherapy-related nausea compared promethazine to prochlorperazine for the treatment of “nonspecific” nausea and vomiting in 84 patients in an emergency room. Although the precise causes of such nausea were not given in the study, presumably the majority were self-limited inflammatory states such as viral gastroenteritis. The study found that prochlorperazine was superior to promethazine in a number of regards: (1) superior nausea relief on a visual analog scale, (2) shorter time to onset, (3) fewer treatment failures, and (4) a superior side-effect profile—less sedation and no greater extrapyramidal side effects.15 These results are striking in that they are contrary to what we might expect based on receptor binding. It is not clear why prochlorperazine, which is principally an anti-dopaminergic agent, would be superior to anticholinergic, antihistaminic promethazine. This highlights the need for clinical studies in this area.
Figure 5.1. A final pathway for nausea.
Chlorpromazine (Thorazine)
Like haloperidol, chlorpromazine is an antipsychotic agent. Given the development of newer antipsychotic agents with less sedating and extrapyramidal side-effect profiles, chlorpromazine is rarely used today for this purpose. However, it may be helpful in palliative care. From Table 5.1 it can be seen that this agent has a strong affinity for all three receptors—dopamine, cholinergic, and histamine. It can therefore be useful in opioid-related nausea as well as in other forms when anticholinergic and antihistaminic effects are desired. However, it should be avoided if sedation is undesirable. It can be given PO, IM, or rectally but should not be given SC. Chlorpromazine also blocks alpha receptors and therefore can cause or exacerbate postural hypotension. Chlorpromazine can, in addition, lower the seizure threshold and thus should be used with caution, if at all, in patients prone to seizures.
Metoclopramide (Reglan)
Metoclopramide has relatively weak binding across the board. Binding is strongest at dopamine receptors, and (not shown here) in high doses it can be effective in blocking 5HT3 serotonin receptors. As discussed above, metoclopramide is useful primarily when an upper GI tract prokinetic agent is desired, especially in the presence of opioids. It can be given PO, IV, or via SC infusion.16 It works by binding 5HT4 receptors in the gut, which in turn release acetylcholine, which stimulates gut motility. Metoclopramide should be avoided in renal failure.
Haloperidol (Haldol)
Haloperidol has the strongest dopamine receptor binding, with little anticholinergic or antihistaminic effects. It is therefore ideal for opioid-related nausea. It is also useful in the treatment of delirium, dementia, and psychosis when sedation is undesirable. Haloperidol (as with other anti-dopaminergic agents, such as prochlorperazine, chlorpromazine, and metoclopramide) is contraindicated in Parkinson’s disease. Haloperidol strongly blocks D2 receptors and has minimal anticholinergic and antihistaminic effects.17 It is minimally sedating. It can be given PO (tablet or liquid), IM, or by slow SC infusion. Unfortunately, no rectal form is available. Because haloperidol is marketed as an antipsychotic, most physicians are not familiar with the use of haloperidol for nausea despite wide experience in palliative care and the hospice community with this selective agent.
5HT3 Antagonists
Chemotherapy with certain agents can cause intense nausea largely mediated through 5HT3 serotonin receptors, found both in the gut and in the CTZ. This class of drugs may be useful for nausea related to bowel obstruction and may have broader use for inflammatory states involving the bowel, as suggested by data that support their use in radiation enteritis. They have also been found to be helpful in postoperative nausea.18 They may also be used in CTZ-related nausea when anti-dopaminergic drugs are strongly contraindicated, as in Parkinson’s disease.
Other Agents
Antihistamines such as meclizine and diphenhydramine are useful in the treatment of motion sickness. Steroids may be considered for nausea related to chemotherapy and radiation therapy.19 Steroids also actively stimulate the appetite, may give rise to mild euphoria (or delirium), and can be helpful in certain pain syndromes. They are helpful, therefore, in a variety of cancer-related conditions but can have serious side effects, especially with prolonged use. The antidepressant mirtazapine may be helpful in treating nausea associated with chemotherapy when 5HT3 receptors are being stimulated. It has some blocking activity at such receptors and may also act as an anxiolytic through blockade of 5HT2 receptors.20 It may also help with gastroparesis, possibly through agonism of central and peripheral 5-HT1A serotonin receptors.21 Dronabinol and other marijuana-related compounds have shown significant efficacy in chemotherapy-related nausea and can increase appetite.22 Psychological effects associated with this class of drugs may be viewed as beneficial or deleterious (Table 5.2).
Constipation
Constipation is a common problem for many patients.23,24 Therapy should be individually tailored; what is very good therapy for one type of constipation may be poison for another. It is difficult for young people, who may never have experienced constipation, to relate to the distress caused by this disorder. For those afflicted, the whole tone of the day may be set by the presence or absence of a good bowel movement (BM).
Understanding how a normal BM is created helps us understand how the process can go awry. Our goal in treating constipation is not to “cure” something; rather, it is to help the patient return to the best possible balance that will allow a normal BM to be passed.
Table 5.2. Summary Table Relating Type of Nausea, Receptor, Drug Class, and Example of Drug of Choice
| Type of Nausea | Receptors Causing Nausea | Drug Class Useful | Examples |
| Vestibular | Cholinergic, histaminic | Anticholinergic, antihistaminic | Scopolamine patch, promethazine |
| Obstruction of bowel caused by constipation | Cholinergic, histaminic,? 5HT3 | Stimulate myenteric plexus | Senna products |
| dysMotility of upper gut | Cholinergic, histaminic,? 5HT3 | Prokinetics stimulate 5HT4 receptors | Metoclopramide |
| Infection, Inflammation | Cholinergic, histaminic,? 5HT3 | Anticholinergic, antihistaminic | Promethazine, prochlorperazine |
| Toxins stimulating the CTZ in the brain such as opioids | Dopamine 2, 5HT3 | Antidopaminergic, 5HT3 antagonist | Prochlorperazine, haloperidol, ondansetron |
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