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Biomedical subjects

Mellar P Davis

Publications and source records attributed to Mellar P Davis.

At least 19 recordsLinked to original sources
PubMed2003

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.

Aged↗
PubMed2003

Olanzapine as an antiemetic in refractory nausea and vomiting in advanced cancer.

Nausea and vomiting are difficult symptoms to manage in patients with advanced cancer. Several classes of antiemetics are available, including phenothiazines, butyrophenones, substituted benzamides and selective serotonin antagonists, as well as corticosteroids. Most patients will respond to either single agents or combinations that frequently include corticosteroids. A minority of patients will have nausea that fails to respond. The atypical antipsychotic, olanzapine, relieves nausea in some patients failing to respond to the usual antiemetics. Two case reports are presented and the rationale for olanzapine's benefit is discussed.

Adult↗
PubMed2003

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.

Acetaminophen↗
PubMed2003

Opioids in cancer pain: common dosing errors.

Many individuals with advanced malignancy continue to suffer from pain and, consequently, impaired quality of life. The clinical scenarios in advanced cancer pain are complex, and successful management may require a more sophisticated and individualized approach than suggested by the World Health Organization guidelines. In patients referred to the Harry R. Horvitz Center for Palliative Medicine in Cleveland, numerous commonly occurring errors in opioid use have been noted. This article describes these errors and offers strategies with which to improve outcomes for patients suffering with cancer pain.

Analgesics, Opioid↗
PubMed2002

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

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. Oxycodone's kappa receptor binding has little role in abuse or addiction. The cost of CR oxycodone is prohibitive for most American hospices.

Adult↗
PubMed2002

Morphine in cancer pain management: a practical guide.

Morphine is the most practical and versatile analgesic for the relief of severe pain associated with advanced cancer. Information is available in the literature about its use in routine clinical practice. Morphine induces analgesia by reducing neurotransmitter release presynaptically and hyperpolarizing dorsal horn neurons at the postsynaptic level, thus preventing rostral transmission of nociception. Morphine has a unique metabolism via glucuronidation (UGT2B7), which results in an active metabolite (morphine-6-glucuronide). The pharmacokinetics of morphine relate to its hydrophilic characteristic, volume of distribution, route of administration and clearance. Renal failure alters its pharmacokinetics more than cirrhosis. The age of the patient and multiple medications will alter morphine pharmacokinetics. Morphine can be given by several different routes: oral, rectal, subcutaneous (s.c.), intravenous (i.v.), epidural and intrathecal. Recent experience confirms benefits of topical morphine for cutaneous pain associated with benign or malignant ulcers. Guidelines for morphine administration are reviewed, and in particular those of the Harry R. Horvitz Center for Palliative Medicine are outlined.

Age Factors↗
PubMed2002

New drugs for the anorexia-cachexia syndrome.

Anorexia and cachexia accompany advancing cancer to a greater extent than any other symptom. Cachexia alone causes 22% of cancer deaths. The pathophysiology of cachexia is distinctly different from that of starvation. Resting energy expenditures are elevated, and abnormal intermediary metabolism, proteolysis, and lipolysis occur independently of caloric intake. A facilatative interaction between catecholamines, prostaglandins, and inflammatory cytokines is responsible for cachexia. Successful treatment requires reduction of energy expenditures, reversal of anorexia, and correction of abnormal intermediary metabolism, lipolysis, and proteolysis. Multiple appetite stimulants can be used in combination. Several new potentially useful biologic agents have been tested in animal tumor models. Several of the anticachectic agents have demonstrated in vivo or in vitro antitumor activity. The biologic and clinical activity of each drug is reviewed herein, and potentially useful combinations are listed.

Animals↗
PubMed2002

A phase II study of topotecan in non-Hodgkin's lymphoma: an Ohio State University phase II research consortium study.

PURPOSE: This multicenter phase II trial evaluated the efficacy and toxicity of the topoisomerase I inhibitor topotecan (TPT, 9-dimethylaminomethyl-10-hydroxycamptothecin) in patients with refractory or relapsing non-Hodgkin's lymphoma. PATIENTS AND METHODS: Thirty-two patients with previously treated non-Hodgkin's lymphoma were accrued in this study from June 1992 to June 1997. Patients were eligible if they had measurable disease and had received two or less chemotherapy treatments for indolent lymphoma or no more than one treatment for aggressive lymphoma. Nineteen patients with aggressive lymphoma including seven with transformed indolent disease and 11 patients with indolent disease were treated. Two additional patients had both indolent and aggressive lymphoma in the bone marrow and lymph nodes at entrance into the study. Topotecan was administered as a 30-min infusion at a dose of 1.25 mg/m2 for five days and repeated at three week intervals. RESULTS: Thirty-two patients were evaluable for toxicity and 29 patients were evaluable for response. There were five objective responses including two complete remissions and three partial remissions (17%; CI 4-30%). Four of the five responders had aggressive disease and had been responsive to prior chemotherapy. The duration of remissions were short, lasting a median of 2 months (range 2-52 months). The major toxicity seen was myelosuppression with 28 of the 32 patients having grade three or greater granulocytopenia. CONCLUSION: Topotecan given as a five day 30 min infusion at a dose of 1.25 mg/m2 has modest activity in previously treated non-Hodgkin's lymphoma as compared to other active agents.

Adult↗
PubMed2002

Management of symptoms associated with advanced cancer: olanzapine and mirtazapine. A World Health Organization project.

Advanced cancer patients are polysymptomatic and often receive multiple medications for symptom relief. Common symptoms include anorexia, weight loss, delirium and depression. Olanzapine and mirtazapine may have several advantages over older agents despite increased acquisition costs. Both medications can treat several symptoms with a low risk for drug-drug interactions and with only once- or twice-daily dosing. Drug side effects are low, compared with more conventionally used agents. The pharmacokinetics and pharmacodynamics of both agents are unique and explain many of the benefits. More research and clinical experience will be necessary to define their role in the palliation of advanced cancer.

Antidepressive Agents↗
PubMed2001

Symptom control in cancer patients: the clinical pharmacology and therapeutic role of suppositories and rectal suspensions.

Rectally administered medications are essential in palliative medicine, particularly in the last days of life. They are underutilized. The pharmacology of rectally administered medications relates not only to the medication but also to the suppository base, additives, drug ionization, p K(a), absorptive surface of the rectum, and rectal health. The pharmacokinetics may differ from those of orally administered medications owing to reduced hepatic first-pass clearance. In this review the pharmacology of rectally administered palliative medications is reviewed and the use of individual drugs is outlined.

Administration, Rectal↗
PubMedDate not supplied

A phase II study of hydrocodone for cough in advanced cancer.

PURPOSE: Cough is a common symptom in advanced cancer. The use of hydrocodone as an antitussive has not been studied previously in this setting. This study evaluates hydrocodone for cough in advanced cancer METHODS: The results presented are from a phase II study with dose titration. SETTING: Palliative medicine program in a tertiary referral center PATIENTS: 25 consecutive patients with cough from irreversible causes, on a stable opioid regimen for the prior 24 hours, and no previous or current use of hydrocodone for cough. INTERVENTION: 5 mg hydrocodone was administered twice daily. The dose was then titrated daily (maximum: 60 mg/24 h), if needed, until a > or = 50 percent improvement of the frequency of cough was achieved and then maintained for three consecutive days. MEASUREMENTS: Cough severity, frequency, complications, and hydrocodone side effects. RESULTS: 20 persons (10 women and 10 men) completed study evaluation. Median age was 63 years (range: 42-82). Nine patients had lung cancer and seven had lung or pleura metastases; 19 patients had at least 50 percent improvement of their cough frequency. The median best response was 70 percent improvement in the cough frequency (range: 50-90 percent). Median hydrocodone dose associated with the best response was 10 mg/day (range: 5-30 mg/day). Cough severity, frequency, associated symptoms and complications, and activities of daily living improved significantly. Side effects of hydrocodone (dry mouth, nausea, and drowsiness) were tolerable and rated as mild. CONCLUSIONS: Hydrocodone is effective and safe to treat cough in advanced cancer A starting dose of 10 mg per day in divided doses seems effective. Dose escalation may be required. Most improved within one day.

Adult↗