Chapter 4. Drugs and prescribing
General prescribing 106
Common prescribing 107
Common interactions 111
Prescribing errors 113
Drug reactions 114
Dose calculation 115
Drug monitoring 118
Drug use in special circumstances 119
Prescribing fluid and blood 122
GENERAL PRESCRIBING
Choosing treatment
The potential benefit of any medication must be weighed against the risk of side-effects or other problems associated with its use. This requires a knowledge and understanding of the results of clinical trials (see ‘Statistics’, p. 445) and commitment to the practice of evidence-based medicine.
Assuming they are competent, the patient should be included in this decision-making. A well informed patient is likely to be more compliant and tolerant of side-effects. For every new medication, consider the following:
• allergy: check this with every patient before you start a new medication
• potential duplication of similar medicines, e.g. adding diclofenac to ibuprofen
• opposing effects, e.g. prescribing a β-blocker for an asthmatic patient taking salbutamol
• interactions, e.g. clarithromycin in a patient on theophylline
• relative contraindications: these need to be weighed against the necessity for the treatment
• absolute contraindications: these prohibit treatment altogether, e.g. warfarin in pregnancy
• the best route of administration, e.g. a patient with a cerebral infarct could have aspirin per rectum if they cannot swallow safely
• specific dose adjustments: these may be required when certain medications are used in patients with renal or hepatic impairment and also during pregnancy and lactation; see the appropriate appendices in the BNF and ‘Drug use in special circumstances’, p. 119.
Legible and clear prescribing
Using a cardex
Drug cardex (prescription chart) design may vary from hospital to hospital, but the principles for using them remain the same. The patient details section must be completed in full, including the relevant unique patient identifier and documentation of allergy status. All medicine cardexes will have sections for once-only prescribing, regular IV and oral medications and PRN (as required) prescribing. It is important to:
• use the correct section of the document when prescribing
• clearly complete each box and sign and date each new addition or removal
• if the medication is not given every day, document this
• sign and date when stopping medications
• rewrite the line if a dose or frequency changes: do not alter the first prescription
• ensure all medications used are prescribed on the cardex, including those written on other infusion charts, e.g. insulin prescription
• use your local formulary: choose medication that is easily available.
Discharge prescriptions
These can be in paper or electronic form:
• use unambiguous identification, e.g. a unique identifier such as the ‘NHS number’ or ‘Community Health Index (CHI)’, rather than a hospital-specific number
• list all medications, even if they do not need to be dispensed: when medications are not listed, GPs may assume that they have been discontinued
• correctly document the drug name, dose, preparation and frequency
• detail how long each treatment should continue for, e.g. an antibiotic course
• provide enough description of the medication format, e.g. the type of inhaler the patient needs; a minimum dose interval in ‘as required’ prescriptions
• warfarin prescriptions: give a date for the next INR check
• note that controlled drugs need to be prescribed in a specific way by law; see the BNF.
COMMON PRESCRIBING
Acute pain
Analgesia will be required by many patients for simple complaints such as headache, backache or minor wound pain. However, you should always assess the patient before prescribing analgesia, especially at the request of others. Check whether the patient’s symptoms are new, when and how they developed and whether they indicate a significant change in their condition.
Inflammatory and musculoskeletal pain
Consider prescribing a NSAID, e.g. ibuprofen (400 mg PO 8-hourly; max. 1.2 g/24 h). However, such preparations should not be used in patients with a history of GI bleeding, asthma or renal disease. In the elderly or those who will need a prolonged course, consider the use of a proton pump inhibitor, e.g. omeprazole (20 mg daily).
Back pain and other spastic muscle pains can be alleviated by a muscle relaxant, e.g. diazepam (2 mg 8-hourly). Avoid this in patients with respiratory muscle disorders or severe COPD causing respiratory failure.
Colicky pain
Colicky pain may be better managed with an antispasmodic, e.g. oral, IM or IV hyoscine butylbromide (20 mg 6-hourly; a parenteral dose can be repeated after 30 min). This is especially the case if pain is due to constipation, which opiate analgesia will exacerbate. Note that these drugs are contraindicated in glaucoma, myasthenia, paralytic ileus, prostatic enlargement, pyloric stenosis and porphyria; also avoid in Down’s syndrome, the elderly or pregnant/breast-feeding women, in children and those with ulcerative colitis, pyrexia or cardiac disease.
Moderately severe pain
Patients with more intense pain, e.g. postoperative, may need a stronger analgesia, such as a ‘weak opioid’, e.g. dihydrocodeine (30 mg PO 6-hourly; max. 120 mg/24 h) or tramadol (50 mg PO 4-hourly; max. 400 mg/24 h). This should be given in combination with paracetamol, unless otherwise contraindicated. Numerous combination preparations exist, e.g. co-codamol 30/500 (2 tablets 4-hourly; max. 8 tablets/24 h).
Weak opioid preparations may cause nausea, constipation or respiratory depression. Therefore, in addition to the usual cautions in patients with renal or hepatic disease, the elderly or pregnant women, these preparations should be used cautiously in patients with head injury, COPD or disorders of respiratory muscle function. Laxatives may be required (see ‘Constipation’, p. 173).
Severe pain
Patients with an acute organ injury (e.g. MI, renal colic), postoperative pain, labour or trauma will have acute severe pain, and will usually require strong opiate analgesia. They are often unable to eat, vomiting and require prompt relief of symptoms. Therefore, parenteral analgesia should be used and combined, if necessary, with an appropriate antiemetic (see ‘Vomiting’, p. 172) and laxative. See ‘Prescribing in palliative care’, p. 376, for patients with chronic severe pain and for notes on opiate side-effects and cautions.
Patient-controlled analgesia
PCA is commonly used for the control of postoperative pain, in which setting it offers potential advantages over ‘on request’ dosing. A syringe driver is configured to deliver small, usually top-up, doses of analgesia on demand by the patient. The device is controlled by a hand-held trigger and can be set to a maximum dose frequency, above which no further doses will be delivered. PCAs should only be set up and altered by those with specific training and the necessary competencies.
Morphine
Morphine may be given via various routes. Intravenous dosing bypasses first-pass metabolism and the onset of action is more rapid. Therefore, doses are usually two-thirds of those required by IM or SC routes, e.g. 10 mg IV equates to 15 mg IM. Suggested dosing:
• adults: 10 mg adjusted to response and repeated every 4–6 h
• children (12–18 years): 2.5–10 mg
• children (2–12 years): 200 μg/kg
• infants (1–24 months): 100–200 μg/kg.
Pethidine
Pethidine has a shorter duration of action than morphine, is less potent, but is also less likely to cause constipation. It is useful in severe colicky abdominal pain, e.g. biliary colic, renal colic, and is often preferred for the management of obstetric pain. Common regimes include:
• postoperative pain: 25–100 mg, repeated 2-hourly
• obstetrics: 50–100 mg SC, repeated after 1–3 h, up to a maximum of 400 mg/24 h
• other acute pain: 50–150 mg PO, 4-hourly; 25–100 mg SC/IM, 4-hourly; 25–50 mg slow IV bolus 4-hourly.
Reversal of opiate analgesia
This may be necessary if respiratory depression or a disproportionate fall in conscious level results from administration. Naloxone (0.4–2 mg IV) can be given at intervals of 2–3 min up to a maximum of 10 mg. Use this with caution in patients with cardiac instability and opiate dependency, since an acute withdrawal reaction can be precipitated in the latter group.
Anticoagulation
Anticoagulation prescribing is best done by a doctor who knows the patient. If you are called to initiate or modify an existing prescription, you should review recent coagulation results and ensure that there has been no change in the patient’s condition, any injury or evidence of bleeding. Note especially any history of intracranial haemorrhage, haemophilia or other bleeding disorder, severe hypertension, peptic ulcer or significant renal or hepatic disease, each of which would contraindicate or complicate the use of any anticoagulation. Consider potential interactions with concomitant medications that increase the risk of GI bleeding, e.g. NSAIDs. Only prescribe the drug if there is written documentation in the case-sheet that this is required, or you have checked with a senior.
Heparin
Before prescribing heparin consider the following:
• contraindications: recent major trauma or surgery, especially to the eye; severe liver disease; thrombocytopenia
• cautions: renal impairment; pregnancy; hypersensitivity to low molecular weight heparins (LMWH); spinal or epidural anaesthesia
• platelets and potassium, see ‘Side-effects’, below
• which formulation of heparin should be used, i.e. LMWH versus unfractionated (intravenous) heparin (UFH).
Side-effects of all heparins
In addition to bleeding, heparin may cause thrombocytopenia and hyperkalaemia, as well as local and systemic drug reactions such as skin necrosis and urticaria.
Thrombocytopenia is an immune-mediated phenomenon beginning 5–10 days after the onset of treatment. Platelet counts should be measured before treatment and every 4 days thereafter. Treatment should be discontinued if the platelet count drops by 50%, especially if this is associated with evidence of bleeding, bruising or petechiae. LMWH should be avoided and alternative anticoagulants commenced, e.g. lepirudin and danaparoid.
LMWH
Most hospitals will have specific local guidelines or prescription charts that reflect the drugs in use locally. Common examples are given below, but the doses stated assume normal renal and hepatic function and the absence of any contraindication.
• preoperative prophylaxis (moderate risk): enoxaparin SC 20 mg 2 h pre-surgery; 20 mg/24 h for 7 days
• preoperative prophylaxis (high risk): enoxaparin SC 40 mg 12 h pre-surgery; 40 mg/24 h for 7 days
• general DVT prophylaxis: enoxaparin SC 40 mg 24-hourly until ambulant (max. 14 days)
• acute coronary syndrome: enoxaparin SC 1 mg/kg twice daily
• DVT/PTE treatment: tinzaparin 175 units/kg SC daily until established on oral anticoagulants.
Unfractionated heparin
Indications
Unfractionated heparin (UFH) has a short half-life, fast onset of action and can be reversed with protamine. However, it requires regular monitoring of the patient’s APTT and has a limited number of indications in current clinical practice. These include anticoagulation of patients presenting with new onset atrial fibrillation (see ‘Management of AF’, p. 134) and following administration of fibrin-specific thrombolytics. UFH is used instead of warfarin perioperatively where discontinuing anticoagulation completely would lead to an unacceptably high risk of thrombotic complications, e.g. those with mechanical heart valves. The patient’s warfarin can be discontinued a few days before surgery and replaced with IV heparin. This can then be stopped 6 h before surgery and restarted a few hours afterwards.
Prescription and monitoring
Intravenous heparin comes in preparations of 1000 IU/mL (20 000 IU in 20 mL). Many hospitals have specific protocols for its use and you should adhere to these. Where these are not provided, and assuming normal renal and hepatic function and no other contraindications, give a bolus of 80 IU/kg (usually rounded to 5000 units) over 5 min, followed by an infusion of 18 IU per kg per h (usually 1000 IU/h, but note: in adults under 50 kg or children the loading dose should be reduced to 50 IU/kg, followed by an infusion of 15–25 IU per kg per h).
Measure the APTT after 6 h and thereafter every 10 h. Adjust the dose as determined by the APTT, ideally according to a local protocol. Aim for an APTT of 1.5–2.5. If the APTT is >7, stop the infusion and check again 3 h later. If it is between 2.6 and 7, stop the infusion for 30–60 min and, for every increment of 1.0 above 2.5, reduce the infusion rate by 100 IU/h.
Intravenous heparin can be reversed with protamine sulphate (10 mg/mL): 1 mg will tend to reverse 90 IU of heparin. Do not exceed a total dose of 50 mg protamine. Note protamine may not fully reverse LMWH and, if given quickly, can cause hypotension.
Warfarin
Before prescribing warfarin consider the following:
• contraindications: pregnancy; peptic ulcer; bacterial endocarditis
• cautions: recent surgery; hepatic disease; breast-feeding
• interactions: a variety of drugs can affect warfarin metabolism, e.g. amiodarone, simvastatin, carbamazepine, rifampicin.
Initiating warfarin
Local initiation protocols should be consulted, but a commonly used regime is 10 mg given at 1800 h daily, for 2 days (5 mg in the elderly, underweight, those with heart or liver failure or with other reasons for increased warfarin sensitivity). After 2 days, check INR at 0900 daily and adjust dose as per local protocol. The recommended INR range depends on the reason for anticoagulation:
• 2.0–3.0: first DVT/PTE (6 months); AF; dilated cardiomyopathy; rheumatic heart disease; mural thrombus post-MI
• 2.5–3.5 in mechanical aortic valves
• 3.0–4.0 and lifelong in recurrent DVT/PTE while adequately warfarinized (INR >2.0), or mechanical mitral valve.
Reversal
Any decision to reverse warfarin anticoagulation should be taken with caution and not simply undertaken because of a high INR. It makes re-anticoagulation very difficult and can be dangerous in patients with mechanical valves. In patients who are well and not actively bleeding, consider simply stopping the warfarin and admitting for observation.
If reversal is deemed necessary, vitamin K (5–10 mg PO or 0.5–2 mg IV) can be given, although it will take 6–12 h to become effective. If the patient is bleeding and immediate reversal is required, use fresh frozen plasma (see ‘Blood products’, p. 122) after discussion with haematology.
Night sedation
Hospital is a noisy environment and sleep disturbance is common. This impairs recovery and, although night sedation may be helpful, it does not offer the same quality of rest as natural sleep. Be aware that:
• patients may experience ‘hangover’ side-effects the next day
• some patients, especially the elderly, may develop confusion or psychosis
• sedation may worsen respiratory failure and should be avoided in those with respiratory failure or any condition that may cause this, e.g. COPD, myasthenia
• sedation should not be used in pregnant or breast-feeding patients or those with significant hepatic or renal disease
• a new prescription of sedation should only be used for a short period
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