Prommer, Eric

Methylphenidate is a psychostimulant originally used for the treatment of attention-deficit disorder. Methylphenidate inhibits neuronal neurotransmitter transporters involved in the uptake of dopamine and norepinephrine at the level of the synapse. Inhibition of these transmitter transporters leads to increased concentrations of dopamine and norepinephrine in the synapse, which results in increasing alertness. The stimulant effect of methylphenidate has been used for the treatment of major depression, poststroke depression, cognitive enhancement in patients with brain tumors, neurodegenerative disorders, HIV disease, fatigue, and as a treatment for delirium and sedation associated with opioid use. Other areas where methylphenidate has been evaluated include gait disorders in the elderly individuals and the treatment of apathy in dementia. Analgesic effects have been demonstrated in preclinical models but true analgesic effects remain to be proven in humans. This article reviews the current use of methylphenidate for symptom management with a critical look at the evidence base for its efficacy in the conditions described.

Haloperidol is a butyrophenone neuroleptic agent characterized as a high-affinity dopamine antagonist, originally used for the treatment of schizophrenia. Awareness of the role dopamine plays in many symptoms in palliative care, such as nausea, vomiting, and delirium, has led to the use of dopamine antagonists such as haloperidol for the treatment of these symptoms in the palliative care setting. Listed as 1 of the 25 important drugs in palliative care, haloperidol can be administered by multiple routes and can be given without dose alteration in the setting of both renal and hepatic insufficiency. Haloperidol is extensively metabolized in the liver, with CYP3A4 the chief cytochrome oxidase responsible for metabolism. This article will review the pharmacology, pharmacokinetics, and current uses of haloperidol in palliative medicine. There will be an examination of the evidence base for the use of haloperidol in palliative medicine.

Pain is one of the most common and incapacitating symptoms experienced by patients with advanced cancer. Methadone is a potent opioid with strong affinity for the µ opioid receptor. In addition to being a potent µ opioid receptor ligand, methadone blocks the N-methyl-D-aspartic acid receptor and modulates neurotransmitters involved in descending pain modulation. These 3 properties enhance analgesic activity. Methadone's lack of active metabolites makes it an attractive option when opioid responsiveness declines and renal insufficiency complicates opioid therapy. A lipophilic opioid, methadone can be given by multiple routes. Clinical trial data show equivalence with morphine as an analgesic in moderate to severe cancer pain. Further investigations are needed to define the role of methadone in the management of breakthrough pain and neuropathic pain and to determine whether it is truly superior to morphine, the gold standard of cancer analgesia.

Dexmedetomidine, is a α 2 adrenergic agonist approved by the Food and Drug administration for sedation and analgesia. A highly potent α 2 adrenergic agonist, it has quick onset of action, with peak effects within 1 hour of administration. It is metabolized in the liver and eliminated in the urine as a glucuronide. Dexmedetomidine is a substrate and inhibitor of cytochrome oxidase 2D6, but clinical evidence of significant drug interactions is lacking. Clinical trials suggest efficacy for the treatment of delirium in the intensive care unit setting with efficacy comparable to haloperidol and benzodiazepines. Dexmedetomidine also has an opioid-sparing action and can act to enhance analgesia. The purpose of this article is to review the pharmacodynamics and pharmacology of dexmedetomidine, and examine its potential use in the palliative care population, especially with regard to the management of delirium.

After decades of disuse because of its teratogenic effects, thalidomide has had a resurgence of use as a promising therapeutic agent for multiple myeloma. Its mechanism of action involves activation of the immune system, antiangiogenic effects, and inhibition of cytokines. Thalidomide does not interact with the cytochrome oxidase system. It is not significantly metabolized, but it does undergo nonenzymatic hydrolysis in plasma. The resulting products are inactive. Despite the potential adverse effects of peripheral neuropathy, constipation, deep vein thrombosis, somnolence, rash, and orthostatic hypotension, thalidomide is an effective first-line agent for multiple myeloma in combination with dexamethasone or melphalan and prednisone. It has also been studied in the palliative care of patients with cytokine-based syndromes such as anorexia-cachexia syndrome. This review describes its use in oncology, hematology, and palliative care.