Biomedical subjects
G W Hanks
Publications and source records attributed to G W Hanks.
Pain management in cancer patients.
Cancer pain in general responds in a predictable way to analgesic drugs and drug therapy is the mainstay of treatment, successfully controlling pain in 70 to 90% of patients. Some pains do not respond so well but can usually be ameliorated by the judicious use of adjuvant analgesics, non-drug measures and the active involvement of the multi-disciplinary team.
Tranexamic acid and rectal bleeding.
Explore the source record for details and available documents.
Analgesics in cancer pain: current practice and beliefs.
Prescribing practices for patients with cancer pain among populations of doctors in the United Kingdom have been assessed by means of a postal questionnaire. The results indicate that amongst the sample of doctors completing the questionnaire the basic principles of pain control in cancer appear to be understood. Regular oral morphine or diamorphine are most often chosen with the dose being determined mainly by the severity of pain with no arbitrary upper limit. Fears of addiction and respiratory depression, and a relatively long prognosis no longer appear to be major deterrents to the use of strong opioid analgesics. These data indicate considerable shifts in opinion in the doctors responding to the questionnaire and these results and their implications for current and future teaching about the management of cancer pain are discussed.
Opioid-responsive and opioid-non-responsive pain in cancer.
Cancer pain in general responds in a predictable way to analgesic drugs and drug therapy is the mainstay of treatment, successfully controlling pain in 70-90% of patients. The two major problem areas are pain associated with nerve damage, and 'incident' (movement-related) bone pain. Nerve damage pain tends not to respond well to morphine or other opioids. The difficulty with severe incident pain is that if the dose of opioid is titrated sufficiently to relieve the pain on weight-bearing or on movement and is then given regularly at this level, it is too much for the patient at rest. The patient may then experience excessive side-effects at rest, but still have pain on movement. Other examples of pain which may be resistant to treatment with opioid analgesics are bladder and rectal tenesmus, pancreatic pain, and pain associated with decubitus ulcers or other superficial ulcers subjected to pressure or shearing forces. Management of non-opioid-responsive pain may include a variety of treatments involving adjuvant analgesic drugs and non-drug measures.
Opioid agonist-antagonist drugs in acute and chronic pain states.
The agonist-antagonist opioid analgesics are a heterogeneous group of drugs with moderate to strong analgesic activity comparable to that of the pure agonist opioids such as codeine and morphine but with a limited effective dose range. The group includes drugs which act as an agonist or partial agonist at one receptor and an antagonist at another (pentazocine, butorphanol, nalbuphine, dezocine) and drugs acting as a partial agonist at a single receptor (buprenorphine). These drugs can be classified as nalorphine-like or morphine-like. Meptazinol does not fit into either classification and occupies a separate category. Pentazocine, butorphanol and nalbuphine are weak mu-antagonists and kappa-partial-agonists. All three drugs are strong analgesics when given by injection: pentazocine is one-sixth to one-third as potent as morphine, nalbuphine is slightly less potent than morphine, and butorphanol is 3.5 to 7 times as potent. The duration of analgesia is similar to that of morphine (3 to 4 hours). Oral pentazocine is closer in analgesic efficacy to aspirin and paracetamol (acetaminophen) than the weak opioid analgesics such as codeine. Neither nalbuphine nor butorphanol is available as an oral formulation. At usual therapeutic doses nalbuphine and butorphanol have respiratory depressant effects equivalent to that of morphine (though the duration of such effects with butorphanol may be longer). Unlike morphine there appears to be a ceiling to both the respiratory depression and the analgesic action. All of these 3 drugs have a lower abuse potential than the pure agonist opioid analgesics such as morphine. However, all have been subject to abuse and misuse, and pentazocine (but not the others) is subject to Controlled Drug restrictions. Buprenorphine is a potent partial agonist at the mu-receptor, and by intramuscular injection is 30 times as potent as morphine. A ceiling to the analgesic effect of buprenorphine has been demonstrated in animals and it is also claimed in humans. However, there are no reliable data available to define the maximal dose of buprenorphine in humans. A practical ceiling exists for sublingual use in that the only available formulation is a 2 micrograms tablet and few patients will accept more than 3 or 4 of these in a single dose. The duration of analgesia is longer than that of morphine, at 6 to 9 hours. There have been suggestions that buprenorphine causes less respiratory depression than morphine, but viewed overall it appears that in equianalgesic doses the 2 drugs have similar respiratory depressant effects.(ABSTRACT TRUNCATED AT 400 WORDS)
Morphine pharmacokinetics and analgesia after oral administration.
The well established use of oral morphine in the treatment of chronic cancer pain has developed empirically and a knowledge of its pharmacokinetics is not necessary in order to use the drug effectively. However recent information about the pharmacokinetics of morphine may help resolve the controversy about oral to parenteral relative potency ratios, and may also in the future shed some light on the problem of patients whose pain does not respond to morphine.
CSF concentrations of morphine-6-glucuronide after oral administration of morphine.
Explore the source record for details and available documents.
Subcutaneous midazolam infusion in palliative care.
This article describes the use of a subcutaneous infusion of midazolam to control restlessness and agitation in 23 patients during the final stages of advanced cancer. Midazolam effectively controlled symptoms in 22 of the patients at an initial dose of 0.4-0.8 mg/hr rising to a mean maximum dose of 2.9 mg/hr. Midazolam mixed in the same syringe as diamorphine was well tolerated at injection sites. The wide dose range emphasizes the need for careful titration of dose for individual patients. At high doses, the volume of injection required presented some practical difficulties, but otherwise there were no major problems with this technique. Midazolam by subcutaneous infusion is a well-tolerated, safe and effective treatment for terminal restlessness and agitation, and deserves more extensive evaluation.
Long-term management of respiratory symptoms in advanced cancer.
Respiratory symptoms are a common cause of distress in patients with advanced cancer. Optimal palliative therapy requires careful assessment and the appropriate use of symptomatic measures in conjunction with specific antitumor treatments. The etiology and management of the three major respiratory symptoms, dyspnea, cough and hemoptysis, are described. The indications for antitumor treatments and surgical procedures are briefly outlined, and symptomatic treatments, including drug and nondrug measures, are discussed in detail.
Morphine: pharmacokinetics and clinical practice.
Explore the source record for details and available documents.
Drainage of malignant effusions.
Explore the source record for details and available documents.
Controlled-release morphine (MST Contin) in advanced cancer. The European experience.
The published data relating to the clinical evaluation and use in Europe of oral controlled-release morphine tablets (MST Continus, [MST] Napp Laboratories, United Kingdom) in the treatment of chronic cancer pain are reviewed. There are three evaluable published reports of double-blind randomized controlled studies and a number of prospective open studies and retrospective reviews. There are also several published pharmacokinetic studies and substantial accumulated clinical experience with MST since its introduction in the United Kingdom in 1981. A critical review of the evidence indicates that MST is effective in patients with opioid-responsive pain; that for almost all patients twice-daily administration is sufficient; that the potency ratio compared with standard (immediate-release) oral morphine formulations is one to one; and that the side effect profile is similar. An immediate-release morphine preparation is preferable during the dose titration period when frequent dose adjustment may be required. However, once patients have been stabilized MST is much more convenient and simpler to use than conventional morphine elixirs or tablets and is the preferred formulation for maintenance treatment.
Morphine and dryness of the mouth.
Explore the source record for details and available documents.
Controlled-release morphine in cancer pain. Is a loading dose required when the formulation is changed?
Nineteen patients with pain from advanced cancer stabilised on oral 4-hourly aqueous morphine who were to be converted to twice daily controlled-release morphine tablets (MST Continus) completed this study. Patients were randomised to receive either their usual 4-hourly morphine dose or placebo with the first dose of MST tablets. There were no significant differences between the treatment groups in ratings of pain intensity, pain relief or side effects, or in any of the measured pharmacokinetic parameters. No patients in the placebo group experienced any breakthrough pain, and nursing staff were unable to identify which patients had received the active dose of morphine elixir. We conclude that there is no need for a loading dose when aqueous morphine is changed to MST tablets.
The bioavailability and pharmacokinetics of morphine after intravenous, oral and buccal administration in healthy volunteers.
1. The absolute bioavailability of morphine from oral aqueous solution, a controlled release oral tablet (MST-Continus) and a controlled release buccal tablet has been investigated in six healthy volunteers. 2. Analysis of plasma samples for morphine and its active metabolite morphine-6-glucuronide (M6G) was by means of a differential radioimmunoassay technique. Absolute bioavailability for morphine was estimated to be 23.9% after oral solution, 22.4% after MST-Continus and 18.7% after the buccal tablet. Maximum plasma morphine concentrations were seen at 45 min (oral solution), 2.5 h (MST) and 6 h (buccal). 3. There was no difference in the amount of M6G appearing in plasma after intravenous, oral or buccal administration but the mean ratio of AUCs for M6G: morphine in plasma after intravenous morphine was 2 : 1 compared with 11 : 1 after oral and buccal morphine.
Diamorphine stability in aqueous solution for subcutaneous infusion.
The influence of temperature and concentration on diamorphine stability during storage over 8 weeks has been investigated. Ampoules containing diamorphine hydrochloride in concentrations from 0.98-250 mg mL-1 have been stored at -20, 4, 21 and 37 degrees C for 8 weeks. Their content of diamorphine, 6-monoacetylmorphine and morphine, on measurement by high performance liquid chromatography after 1, 2, 4, 6 and 8 weeks storage changed to slow degradation of diamorphine at all concentrations at temperatures of 4 degrees C and above. This was accompanied by a corresponding increase in 6-monoacetylmorphine and morphine. There was an associated fall in pH and development of a strong odour characteristic of acetic acid. Precipitation and a white turbidity seen in solutions of 15.6 mg mL-1 and above, appeared after 2 weeks incubation.
The influence of blood sample preparation on measured levels of morphine and its major metabolites.
The effect of six different methods of blood sample preparation on concentrations of morphine (M), morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) have been investigated using a specific high performance liquid chromatography assay. No difference between glass or plastic tubes was seen in concentrations of M, M3G, or M6G; and no difference between plasma and serum in M and M6G concentrations. M3G concentrations, however, were significantly lower in plasma compared with serum. Heparin had no effect on M, M6G or M3G, whereas citrate in a glass tube produced consistently lower concentrations of M, M3G and M6G. Standardization of sample collection using plasma samples in plastic heparin tubes is recommended for future studies.