Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC) (http://emc.medicines.org.uk), or the British National Formulary (BNF) (www.bnf.org).

• On 1 February 2006 the supply of home oxygen was transferred from community pharmacies to regional oxygen supply companies in England and Wales. These companies are responsible for supplying cylinders, concentrators, and liquid oxygen as part of an integrated service.
• Oxygen is ordered from one of four regional supply companies using the Home Oxygen Order Form (HOOF), which has replaced prescribing of oxygen on FP10 prescriptions. Contact telephone numbers for the companies are:
• Air Products: 0800 373 580
• Allied Respiratory: 0500 823 773
• BOC Vitalair: 0800 136 603
• Linde Gas: 0808 202 0999
• Key documentation for Home Oxygen Services (including HOOFs) is available from your local Primary Care Trust or online at www.pcc.nhs.uk.

• Oxygen therapy has potential psychosocial and drug-induced adverse effects which can influence patient acceptability and tolerability, and hence compliance.
• Psychosocial adverse effects include:
• Psychological dependence. Being deprived of oxygen for even a short period may provoke acute anxiety and hence dyspnoea.
• Social restriction. Oxygen equipment severely limits mobility inside and outside the house, and some people feel a social stigma and embarrassment.
• Drug-induced adverse effects include:
• Oxygen toxicity. High concentrations over long periods can cause lung damage.
• Lung atelectasis. Oxygen is very soluble and may cause a reduced amount of air in part of the lungs, resulting in a loss of lung volume.
• Drying of airways. Oxygen therapy contains less water vapour than air, which can lead to discomfort owing to its drying effect, particularly on the nasal mucosa when using nasal cannulae.
• Combustibility. People receiving oxygen therapy must not smoke or use oxygen while close to gas stoves or lighted fireplaces because of the fire hazard.

[Booth and Dudgeon, 2006]

• Once a decision has been made to prescribe oxygen, consider the need for oxygen concentrators, oxygen cylinders, and liquid oxygen. The choice is determined primarily by the person's lifestyle and mobility and the need for either short-burst oxygen therapy or long-term therapy.
• A mask or nasal cannulae (consisting of two prongs) are options for oxygen delivery. Nasal cannulae are generally preferred to a mask because they do not impair speech or eating and drinking [Regnard and Hockley, 2004b], However, nasal cannulae can cause dryness and soreness of the nasal mucosa [Twycross et al, 2002].
• Oxygen should be prescribed at the lowest flow rate possible to produce benefit because of potential adverse effects:
• Clinical assessment may involve measuring breathlessness scores at different flow rates of oxygen. Most people require a flow rate of 2–4 L/min.
• People starting oxygen therapy should be provided with education and written instructions which include advice about the dangers of smoking near oxygen therapy.
• People should be reassessed regularly after commencing therapy, to determine the continuing efficacy of supplemental oxygen over the longer term.

[Booth and Dudgeon, 2006]

• Normal-release oral morphine is the usual opioid of choice.
• If the person cannot take oral medication, use a subcutaneous bolus of diamorphine when required or a subcutaneous continuous infusion of diamorphine delivered through a syringe driver [Lothian Palliative Care Guidelines Group, 2004b; Pan-Glasgow Palliative Care Algorithm Group, 2005].

• This recommendation is based on palliative care guidelines [Lothian Palliative Care Guidelines Group, 2004b; NHMRC, 2004; ICSI, 2007] and expert opinion from the palliative care literature [Kvale et al, 2003; Doyle et al, 2004; Booth, 2006].

• There is a wide variation in regimens used in clinical practice. CKS cannot be prescriptive here but can only offer a general guide based on assessment of the literature and on the professional opinion of expert reviewers. A morphine dose regimen should always be tailored to an individual's needs and requirements. If a clinician is still unsure how best to manage a person in this scenario, then seek specialist advice.
• The initial starting dose depends on the person's previous exposure to opioids (as well as other factors such as age of the person, degree of frailty, associated morbidity such as chronic obstructive pulmonary disease or interstitial lung disease, and renal and liver function). In people with dyspnoea, morphine should be increased more cautiously than when used for palliative care pain relief.
• In an opioid-naive person:
• Start with oral morphine 2 mg or 2.5 mg.
• Most people can take this dose every 4 hours and as required, although people with breathlessness may not need as frequent dosing (e.g. people with dyspnoea on exertion can just take the morphine dose when required as long as they plan their activity, and take the morphine dose about 30 minutes in advance).
• In a person taking a weak opioid (e.g. codeine):
• Start an oral morphine dosage of 2.5 to 10 mg every 4 hours and as required (only continue the weak opioid if appropriate).
• As previously, if people with dyspnoea on exertion plan their activity, they may take the morphine dose just 'as required'.
• If the person is already receiving regular (analgesic) morphine, increase the regular dose of morphine by in the region of 30% every 2 to 3 days until symptoms are controlled or adverse effects prevent further dose increases.
• Reassess after 2 days. If, after a clinical assessment, the person has no adverse effects and the morphine is demonstrating some benefit, then reassess the morphine dose and increase if necessary, taking into account factors such as the age of the person, degree of frailty, associated morbidity, and renal and liver function.
• Repeat this process every 2 days until breathlessness is controlled (also checking for any adverse effects). Once a stable dose has been reached, the new 4-hourly and 'as required' dose is one sixth of the new total daily dose (unless a person with dyspnoea on exertion is controlled on an 'as required' dose as explained previously). If the person needs regular morphine dosing throughout the day for dyspnoea then convert to once- or twice-daily administration of modified-release morphine. However, if only one or two doses are needed each day to control symptoms, then it may be fine to stick with 'as required' doses of standard release morphine.

• Adverse effects are less serious when morphine is used to relieve the symptoms of dyspnoea than when it is used for analgesia, because the doses used for symptom relief of dyspnoea are generally lower.
• Drowsiness occurs commonly at the start of treatment or after dose increases. People should be warned to avoid activities in which drowsiness may be detrimental. Most people develop tolerance to drowsiness within a few days. Persistent sedation may be resolved by dose reduction or an opioid switch.
• Constipation is a common ongoing problem, because tolerance to this adverse effect does not develop with morphine use:
• When using an opioid cough suppressant, co-prescribe a regular stimulant laxative (e.g. senna or bisacodyl) with a faecal softener (e.g. docusate or lactulose), or a laxative likely to have both properties (e.g. co-danthramer or co-danthrusate) to prevent opioid-induced constipation. Note: people taking dantron-containing laxatives may experience reddening of the perianal area.
• Other common adverse effects of morphine (especially in elderly people) include nausea, vomiting, and unsteadiness:
• An anti-emetic (e.g. haloperidol or metoclopramide) should be prescribed [Twycross et al, 2002]:
• Regularly for the first week to prevent opioid-induced nausea and vomiting if the person has experienced nausea with a weak opioid, or
• On standby, for use on an 'as required' basis for a week, in case the person experiences nausea with morphine but has not previously had nausea with a weak opioid.
• Other adverse effects of strong opioids include dry mouth, sweating, pruritus, hallucinations, myoclonus, and bronchoconstriction.
• Note: respiratory depression from opioids is rare, and these agents do not hasten death if appropriately titrated [Fraser Health, 2006].

[Twycross et al, 2002; BNF 53, 2007]

• Diazepam, lorazepam, and midazolam are the benzodiazepines recommended for anxiety associated with dyspnoea.
• The initial dose of a benzodiazepine depends on the person's age, general condition, previous benzodiazepine use, the intensity of distress, and the urgency of relief. In general, therapy in elderly and debilitated people should be started at low doses.
• Lorazepam is useful in the acute scenario because it is a short-acting benzodiazepine (half-life of 12–15 hours) and has a fast onset of action. Lorazepam works within 10 minutes when administered sublingually (although this route is outside the product licence).
• Diazepam may be more appropriate for more chronic anxiety-related dyspnoea symptoms because it is a medium- to long-acting benzodiazepine with a half-life of 20–100 hours.
• Midazolam can be used for intractable breathlessness when required or by continuous subcutaneous infusion to relieve symptoms. It has a half-life of 2–5 hours, although the half-life is prolonged up to 3 times in people older than 60 years of age. Its main advantage is that it is water soluble with most of the drugs commonly given by continuous subcutaneous infusion.

[Twycross et al, 2002]

• This recommendation is based on palliative care guidelines [International Association for Hospice and Palliative Care, 2004; Lothian Palliative Care Guidelines Group, 2004b; NHMRC, 2004; Pan-Glasgow Palliative Care Algorithm Group, 2005; NCCN, 2006] and expert opinion from the palliative care literature [Doyle et al, 2004; Regnard and Hockley, 2004b].

• The most frequent adverse effects are drowsiness, sedation, muscle weakness, and ataxia. These effects are caused by depression of the central nervous system, and they generally decrease with continued use of the drug [Micromedex, 2007].
• Less frequent adverse effects include vertigo, headache, confusion, depression, amnesia, and paradoxical excitation [Sweetman, 2005].