Mellar P. Davis

Methadone for relief of cancer pain: A review of pharmacokinetics, pharmacodynamics, drug interactions and protocols of administration

Abstract Methadone, a synthetic opioid, has unique pharmacodynamics and pharmacokinetics, which contribute to its unique ability to relieve pain unresponsive to other potent opiates and its unique dosing and drug interactions. Several guidelines of administration have been established. Physicians who are involved in pain management should have a fundamental understanding of methadones unique properties.

Demographics, Assessment and Management of Pain in the Elderly

The prevalence of pain increases with each decade of life. Pain in the elderly is distinctly different from pain experienced by younger individuals. Cancer is a leading cause of pain; however, other conditions that cause pain such as facet joint arthritis (causing low back pain), polymyalgia rheumatica, Paget’s disease, neuropathies, peripheral vascular disease and coronary disease most commonly occur in patients over the age of 50 years. Poorly controlled pain in the elderly leads to cognitive failure, depression and mood disturbance and reduces activities of daily living. Barriers to pain management include a sense of fatalism, denial, the desire to be ‘the good patient’, geographical barriers and financial limitations.Aging causes physiological changes that alter the pharmacokinetics and pharmacodynamics of analgesics, narrowing their therapeutic index and increasing the risk of toxicity and drug-drug interactions. CNS changes lead to an increased risk of delirium.Assessment among the verbal but cognitively impaired elderly is satisfactorily accomplished with the help of unidimensional and multidimensional pain scales. A comprehensive physical examination and pain history is essential, as well as a review of cognitive function and activities of daily living. The goal of pain management among the elderly is improvement in pain and optimisation of activities of daily living, not complete eradication of pain nor the lowest possible drug dosages. Most successful management strategies combine pharmacological and nonpharmacological (home remedies, massage, topical agents, heat and cold packs and informal cognitive strategies) therapies.A basic principle of the pharmacological approach in the elderly is to start analgesics at low dosages and titrate slowly. The WHO’s three-step guideline to pain management should guide prescribing. Opioid choices necessitate an understanding of pharmacology to ensure safe administration in end-organ failure and avoidance of drug interactions. Adjuvant analgesics are used to reduce opioid adverse effects or improve poorly controlled pain. Adjuvant analgesics (NSAIDs, tricyclic antidepressants and antiepileptic drugs) are initiated prior to opioids for nociceptive and neuropathic pain. Preferred adjuvants for nociceptive pain are short-acting paracetamol (acetaminophen), NSAIDs, cyclo-oxygenase-2 inhibitors and corticosteroids (short-term). Preferred drugs for neuropathic pain include desipramine, nortriptyline, gabapentin and valproic acid. Drugs to avoid are pentazocine, pethidine (meperidine), dextropropoxyphene and opioids that are both an agonist and antagonist, ketorolac, indomethacin, piroxicam, mefenamic acid, amitriptyline and doxepin. The type of pain, and renal and hepatic function, alter the preferred adjuvant and opioid choices. Selection of the appropriate analgesics is also influenced by versatility, polypharmacy, severity and type of pain, drug availability, associated symptoms and cost.

Mirtazapine for Pruritus

Pruritus is a relatively rare but distressing symptom associated with cholestasis, renal failure, and malignancies. Medical management recently has included the use of ondansetron and paroxetine. We report four patients whose pruritus responded to mirtazapine.

Systematic Review of the Treatment of Cancer-Associated Anorexia and Weight Loss

PURPOSE We systematically assessed the efficacy and safety of appetite stimulants in the management of cancer-related anorexia. Literature databases were searched for randomized controlled trials of appetite stimulants in the treatment of cancer anorexia. MATERIALS AND METHODS Studies were graded according to quality. Fifty-five studies met inclusion criteria. RESULTS Only two drugs have evidence to support their use for anorexia (progestins and corticosteroids). There is strong evidence against the use of hydrazine sulfate. The outcomes of these trials have been mixed and patient population heterogeneous. CONCLUSION The optimal dose, time to start, and duration of treatment for many appetite stimulants for cancer anorexia is still unknown. A more systematic approach to research methodology with universal outcome measure and prospective randomized studies are need. Combination regimens are needed but this cannot at the present time be supported by the data presented.

Methylphenidate for fatigue in advanced cancer: a prospective open-label pilot study.

Psychostimulants such as methylphenidate are used for fatigue in cancer patients. We report a prospective, open-label, pilot study of the successful use of methylphenidate to treat fatigue in nine of 11 consecutive patients with advanced cancer. Seven had received radiation or chemotherapy, a median of three weeks (range from one to 30 weeks) prior to methylphenidate. A rapid onset of benefit was noted, even in the presence of mild anemia. Sedation and pain also improved in some. Only one patient had side effects severe enough to stop the medication.

Appetite and Cancer-Associated Anorexia: A Review

Appetite is governed by peripheral hormones and central neurotransmitters that act on the arcuate nucleus of the hypothalamus and nucleus tactus solitarius of the brainstem. Cancer anorexia appears to be the result of an imbalance between neuropeptide-Y and pro-opiomelanocortin signals favoring pro-opiomelanocortin. Many of the appetite stimulants redress this imbalance. Most of our understanding of appetite neurophysiology and tumor-associated anorexia is derived from animals and has not been verified in humans. There have been few clinical trials and very little translational research on anorexia despite its prevalence in cancer.

Normal-release and controlled-release oxycodone: pharmacokinetics, pharmacodynamics, and controversy.

Abstract. Oxycodone has become one of the most popular opioids in the United States. It is superior to morphine in oral absorption and bioavailability, and similar in terms of protein binding and lipophilicity. Gender more than age influences oxycodone elimination. Unlike morphine, oxycodone is metabolized by the cytochrome isoenzyme CYP2D6, which is severely impaired by liver dysfunction. Controlled-release (CR) oxycodone has become one of the most frequently utilized sustained-release opioids in the United States. Both its analgesic benefits and its side effects are similar to those of CR morphine. CR oxycodone is similar to morphine and other opioids in its abuse potential. Deaths attributable to oxycodone are usually associated with polysubstance abuse in which oxycodone is combined with psychostimulants, other opioids, benzodiazepines or alcohol. Oxycodones kappa receptor binding has little role in abuse or addiction. The cost of CR oxycodone is prohibitive for most American hospices.

Epidemiology of cancer pain and factors influencing poor pain control

Pain is one of the most commonly experienced and feared symptoms of advanced cancer. Most cancer patients experience pain, usually of moderate to severe intensity, and most also have a number of distinct pains. The most common type of pain is related to bone metastases. Neuropathic pain occurs in one-third of patients, alone, or as a mix of nociceptive and neuropathic pain. The failure to manage pain properly is due to several factors. In developing countries, it is likely to be related to geography and limited resources. Legal restrictions also present barriers. In developed countries, failure to manage pain properly is usually related to a “disease” rather than a “symptom” model of care, which minimizes symptom management. Other factors include lack of physician education and failure to follow existing guidelines. Patients fear addiction, drug tolerance, and side effects. Despite adequate resources, pain is still undertreated.

A phase II study of methylphenidate for depression in advanced cancer

This study evaluated the use of methylphenidate for depression in advanced cancer. Design: Phase II open-label prospective study. Eligibility criteria: No previous use of methylphenidate or current use of other antidepressants. Evaluation: Depression and response to treatment were determined by asking the patient: “are you depressed?” Patients were assessed at baseline and at days 3, 5, and 7. Treatment: Starting dose was 5 mg at 8:00 a.m. and 12:00 noon. The dose was titrated for lack of response on any of the assessment days. Response criteria: A negative response to the question: “are you depressed?” Results: Some 41 patients were enrolled and 30 (15 men, 15 women) completed the study. Median age was 68 years (range: 30-90). Methylphenidate was stopped for six patients because of side effects and five were not evaluable; 21 responded to 10 mg/day on day 3; the other nine responded to 20 mg/day on day 5; 29 maintained their positive response through day 7. Anorexia, fatigue, concentration, and sedation also improved in some. All who completed the study had tolerable side effects, none of which caused treatment to stop. Conclusions: Methylphenidate is effective for depression in advanced cancer. A starting dose of 10 mg in divided doses is effective in most patients. Dose escalation may be needed. Improvement occurs within three days. Close monitoring of side effects is recommended.

Treatment of nausea and vomiting in advanced cancer

Abstract Nausea and vomiting unrelated to chemotherapy is common in advanced cancer patients. The etiology of nausea and vomiting may from evident by the pattern of vomiting, associated symptoms, review of medications and physical examination. Radiographic studies are particularly helpful if bowel obstruction is suspected or central nervous system metastases are a possibility. Laboratory studies are helpful in a minority of cases. Multiple classes of medications are available to palliate nausea and vomiting. Classes of agents are discussed, pharmacology and cost being among the aspects covered. A four-step approach to the medical management of nausea and vomiting is presented.