Antiemetics adverse effects

Antineoplastic drugs are potentially toxic and their administration is often associated with many serious adverse reactions. At times, some of these adverse effects are allowed because the only alternative is to stop treatment of the malignancy. A treatment plan is developed that will prevent, lessen, or treat most or all of the symptoms of a specific adverse reaction. An example of prevention is giving an antiemetic before administering an antineoplastic drug known to cause severe nausea and vomiting. An example of treatment of the symptoms of an adverse reaction is the administration of an antiemetic and intravenous (IV) fluids and electrolytes when severe vomiting occurs. 

TABLE 17-2. Antiemetic Agents Adult Doses and Adverse Effects... 

Ask patients about adverse effects to the antiemetics used. Use this information to assess efficacy and tailor the patient s antiemetic regimen. 

Develop a plan to prevent treatment-related adverse effects. Are the antiemetics appropriate Does the patient understand the possible adverse effects and when to call the physician versus when patient-directed care is appropriate ... 

In anesthesia drugs from several groups are used as premedication. Pre-anesthetic medication can decrease the anesthetic doses which otherwise would be required to induce anesthesia and so decrease the risk for adverse effects. Pre-anesthetic medication will increase the rate of induction of anesthesia and can reduce pre-operative pain and anxiety. Drugs include benzodiazepines for sedation and their muscle relaxant properties, opiates for pain relieve and anticholinergics or histamine Hi receptor antagonists against nausea and vomiting. Neuroleptics are also used as premedication for their antiemetic effects. 

Tramer MR, Walder B. Efficacy and adverse effects of prophylactic antiemetics during patient-controUed analgesia therapy a quantitative systematic review. Anesth Analg 1999 88(6) 1354-61. 

Trimethobenzamide (Tigan) One of the least effective antiemetic drugs, yet it can cause extrapyramidal adverse effects. High... 

In the course of clinical treatment with methadone, certain situations relating to adverse effects are characteristic. Nausea is a general opiate effect, but complaints most frequently relate to the methadone mixture. This preparation does have a syrupy consistency, but the problem for clinicians is that the alternatives - sugar-free mixture or methadone tablets - are both more injectable, and therefore requests or implied requirements for these are often manipulative. So are requests for the antiemetic cyclizine tablets, which are crushed and injected by drug misusers along with injected methadone. As indicated in Chapter 4, thankfully these particular claims have become less common now that guidelines are much more discouraging of any use of methadone tablets. 

When levodopa is given without a peripheral decarboxylase inhibitor, anorexia and nausea and vomiting occur in about 80% of patients. These adverse effects can be minimized by taking the drug in divided doses, with or immediately after meals, and by increasing the total daily dose very slowly antacids taken 30-60 minutes before levodopa may also be beneficial. The vomiting has been attributed to stimulation of the chemoreceptor trigger zone located in the brain stem but outside the blood-brain barrier. Fortunately, tolerance to this emetic effect develops in many patients. Antiemetics such as phenothiazines should be avoided because they reduce the antiparkinsonism effects of levodopa and may exacerbate the disease. 

Nausea is often troublesome, especially at the initiation of apomorphine treatment accordingly, pretreatment with the antiemetic trimethobenzamide (300 mg three times daily) for 3 days is recommended before apomorphine is introduced and is then continued for at least 1 month, if not indefinitely. Other adverse effects include dyskinesias, drowsiness, chest pain, sweating, hypotension, and bruising at the injection site. Apomorphine should be prescribed only by physicians familiar with its potential complications and interactions. 

Pregnancy can be prevented following coitus by the administration of estrogens alone, progestin alone, or in combination ("morning after contraception). When treatment is begun within 72 hours, it is effective 99% of the time. Some effective schedules are shown in Table 40-4. The hormones are often administered with antiemetics, since 40% of the patients have nausea or vomiting. Other adverse effects include headache, dizziness, breast tenderness, and abdominal and leg cramps. 

Substituted benzamides include metodopramide (discussed previously) and trimethobenzamide. Their primary mechanism of antiemetic action is believed to be dopamine-receptor blockade. Trimethobenzamide also has weak antihistaminic activity. For prevention and treatment of nausea and vomiting, metodopramide may be given in the relatively high dosage of 10-20 mg orally or intravenously every 6 hours. The usual dose of trimethobenzamide is 250 mg orally, 200 mg rectally, or 200 mg by intramuscular injection. The principal adverse effects of these central dopamine antagonists are extrapyramidal restlessness, dystonias, and parkinsonian symptoms. 

Chlorpromazine is a tranquilizing and antiemetic agent that may cause a number of side effects in the circulatory and nervous system and adverse effects on blood cells, skin, and the eye. Recent studies suggest a possible genotoxic activity for chlorpromazine, whereas it has been established that certain reactive metabolic intermediates are capable of binding with macromolecules including DNA. 

Prostaglandins have been used intravenously, both for induction of mid-trimester abortion and for induction of labor in cases of intrauterine death. The same adverse effects as described above occur, and are usually very pronounced. Routine premedication with an antiemetic and an antidiarrheal agent significantly reduces gastrointestinal adverse effects. 

Aspirin, paracetamol, and hydrocortisone are used to control febrile reactions of amphotericin. Patients with a history of adverse effects with amphotericin should be prophylactically treated with antipyretics and hydrocortisone. Antiemetics and pethidine also are used for the treatment of adverse effects of amphotericin. With sodium supplements and hydration therapy, damage to the kidney can be reduced. If conventional amphotericin is not well tolerated by the patient, colloidal carriers can be used as alternative options. Administration of amphotericin with a nephrotoxic drug, such as cyclosporin, may further increase toxicity. Diuretics and anticancer drugs should be avoided with amphotericin. 

Supportive care, administration of antiemetics, corticosteroids, and nutritional supplements may be used to treat the adverse effects of anticancer drugs. Scalp... 

Cannabis is one of the oldest and most widely used drugs in the world. In different Western countries the possible therapeutic use of cannabinoids as antiemetics in patients with cancer or in patients with multiple sclerosis has become an issue, because of the prohibition of cannabis, and has polarized opinion about the seriousness of its adverse effects (1,2). 

Hepatic adverse effects secondary to antiemetic therapy are usually asymptomatic. Metoclopramide has been reported as causing cholestasis and the formation of arteriovenous shunts in the liver [12]. The 5HTj-receptor antagonists have all been documented as occasionally causing mild increases in liver fimction tests. Cholestatic jaundice has been reported with cyclizine, prochlorperazine and promethazine, and hepatitis has been reported with cyclizine. 

Domperidone may be the antiemetic of choice in this patient. Despite being extensively metabolised by the liver it has few adverse effects and does not cross the blood-brain barrier. 

Domperidone may be the antiemetic of choice in this patient. Despite being extensively metabolised by the Hver it has few adverse effects and does not cross the blood-brain barrier. The bioavailability is hkely to be increased as first-pass metabolism will be reduced because of portal hypertension. There may also be accumulation of domperidone owing to reduced metabolic capacity. Consequently the dose should be reduced to 50% and titrated up to 10 mg three times a day if necessary. 

Nabilone is a synthetic cannabinoid and has properties similar to tetrahydrocannabinol (the active constituent of marijuana) which has an antiemetic action. It is used to relieve nausea or vomiting caused by cytotoxic drugs. Adverse effects include somnolence, dry mouth, decreased appetite, dizziness, euphoria, dysphoria, postural hypotension, confusion and psychosis. These may be reduced if prochlorperazine is given concomitantly. 

The adverse effects of aldesleukin include fever, chills, malaise, skin rash, nausea, vomiting (often resistant to antiemetics), diarrhea, fluid retention, myalgia, insomnia, disorientation, life-threatening hypotension, and the capillary leak syndrome (which can be preceded by weight gain) (SEDA-15, 491) (2). 

Domperidone is a neuroleptic antiemetic, a dopamine receptor antagonist. It produces the expected range of dystonic and extrapyramidal adverse effects (1), which seem, as with metoclopramide, to be more likely to occur in children (2). It is difficult to accept that claims for lower frequencies than with metoclopramide are justified, particularly when one reads a report of neuroleptic malignant sjmdrome (3). Like its congeners, domperidone has repeatedly been shown to cause sjmptoms attributable to hyperprolactinemia (galactorrhea, amenorrhea, and breast tenderness), despite claims that there is a lower incidence of effects on prolactin concentrations. However, a study in patients with Parkinson s disease using domperidone did not suggest that the adverse effects are especially problematical in these patients (4). 

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