Drug Action
Acts on skeletal muscle cells by interfering with calcium efflux, thereby stopping the contractile process.
PDF page 1439
Loading InternPractice…
Drug reference
Acts on skeletal muscle cells by interfering with calcium efflux, thereby stopping the contractile process.
PDF page 1439
Malignant hyperthermia ▶BY RAPID INTRAVENOUS INJECTION ▶Adult: Initially 2–3 mg/kg, then 1 mg/kg, repeated if necessary; maximum 10 mg/kg per course Chronic severe spasticity of voluntary muscle ▶BY MOUTH ▶Adult: Initially 25 mg daily, then increased to up to 100 mg 4 times a day, dose increased at weekly intervals; usual dose 75 mg 3 times a day Muscle cramps in motor neurone disease (specialist use only) ▶BY MOUTH ▶Adult: Initially 25 mg daily, then increased to up to 100 mg 4 times a day, dose increased at weekly intervals l UNLICENSED USE ▶With oral use g Dantrolene sodium is used for the treatment of muscle cramps in motor neurone disease, l but is not licensed for this indication.
PDF page 1439
▶With oral use Acute muscle spasm. avoid when spasticity is useful, for example, locomotion
PDF page 1439
▶With intravenous use Avoid extravasation (risk of tissue necrosis) ▶With oral use Females (hepatotoxicity). history of liver disorders (hepatotoxicity). if doses greater than 400 mg daily (hepatotoxicity). impaired cardiac function. impaired pulmonary function. patients over 30 years (hepatotoxicity). therapeutic effect may take a few weeks to develop— discontinue if no response within 6–8 weeks
PDF page 1439
Should only be administered by, or under the direct supervision of, personnel experienced in the use of dantrolene when used for malignant hyperthermia.
PDF page 1439
→Appendix 1: dantrolene
PDF page 1439
GENERAL SIDE-EFFECTS ▶Common or very common Abdominal pain. hepatic disorders. nausea. respiratory disorders. skin reactions. speech disorder. vomiting ▶Uncommon Crystalluria. hyperhidrosis ▶Frequency not known Arrhythmias. dizziness. drowsiness SPECIFIC SIDE-EFFECTS ▶Common or very common ▶With oral use Appetite decreased. chills. confusion. depression. eosinophilia. fever. headache. insomnia. nervousness. pericarditis. visual impairment ▶Uncommon ▶With oral use Constipation. dysphagia. haemorrhage. heart failure aggravated. urinary disorders ▶Frequency not known ▶With intravenous use Gastrointestinal haemorrhage. heart failure. localised pain. pulmonary oedema. seizure. thrombophlebitis ▶With oral use Asthenia. diarrhoea. dyspnoea. hypertension . malaise
PDF page 1439
▶With intravenous use Use only if potential benefit outweighs risk. ▶With oral use Although teratological studies in animals have proved satisfactory, dantrolene sodium does cross the placenta, therefore manufacturer advises avoid.
PDF page 1439
▶With intravenous use Present in milk—use only if potential benefit outweighs risk. ▶With oral use Present in milk—manufacturer advises avoid.
PDF page 1439
▶With oral use Manufacturer advises avoid in hepatic impairment.
PDF page 1439
▶With oral use Test liver function before and at intervals during therapy. Anaesthesia
PDF page 1439
There can be variation in the licensing of different medicines containing the same drug. Forms available from special-order manufacturers include: oral suspension, oral solution Powder for solution for injection ▶Dantrium (Forum Health Products Ltd) Dantrolene sodium 20 mg Dantrium Intravenous 20mg powder for solution for injection vials | 12 vial P £612.00 (Hospital only) | 36 vial P £1,836.00 (Hospital only) Capsule CAUTIONARY AND ADVISORY LABELS 2 ▶Dantrium (Forum Health Products Ltd) Dantrolene sodium 25 mg Dantrium 25mg capsules | 100 capsule P £16.87 DT = £16.87 Dantrolene sodium 100 mg Dantrium 100mg capsules | 100 capsule P £43.07 DT = £43.07 Local anaesthesia Anaesthesia (local) Local anaesthetic drugs The use of local anaesthetics by injection or by application to mucous membranes to produce local analgesia is discussed in this section. Local anaesthetic drugs act by causing a reversible block to conduction along nerve fibres. They vary widely in their potency, toxicity, duration of action, stability, solubility in water, and ability to penetrate mucous membranes. These factors determine their application, e.g. topical (surface), infiltration, peripheral nerve block, intravenous regional anaesthesia (Bier’s block), plexus, epidural (extradural), or spinal (intrathecal or subarachnoid) block. Local anaesthetics may also be used for postoperative pain relief, thereby reducing the need for analgesics such as opioids. Bupivacaine hydrochloride p. 1419 has a longer duration of action than other local anaesthetics. It has a slow onset of action, taking up to 30 minutes for full effect. It is often used in lumbar epidural blockade and is particularly suitable for continuous epidural analgesia in labour, or for postoperative pain relief. It is the principal drug used for spinal anaesthesia. Hyperbaric solutions containing glucose may be used for spinal block. Levobupivacaine p. 1421, an isomer of bupivacaine, has anaesthetic and analgesic properties similar to bupivacaine hydrochloride, but is thought to have fewer adverse effects. Lidocaine hydrochloride p. 1422 is effectively absorbed from mucous membranes and is a useful surface anaesthetic in concentrations up to 10%. Except for surface anaesthesia and dental anaesthesia, solutions should not usually exceed 1% in strength. The duration of the block (with adrenaline/epinephrine p. 236) is about 90 minutes. Prilocaine hydrochloride p. 1426 is a local anaesthetic of low toxicity which is similar to lidocaine hydrochloride. A hyperbaric solution of prilocaine hydrochloride (containing glucose) may be used for spinal anaesthesia. Ropivacaine hydrochloride p. 1427 is an amide-type local anaesthetic agent similar to bupivacaine hydrochloride. It is less cardiotoxic than bupivacaine hydrochloride, but also less potent. Tetracaine p. 1429, a para-aminobenzoic acid ester, is an Anaesthesia effective local anaesthetic for topical application; a 4% gel is indicated for anaesthesia before venepuncture or venous cannulation. It is rapidly absorbed from mucous membranes and should never be applied to inflamed, traumatised, or highly vascular surfaces. It should never be used to provide anaesthesia for bronchoscopy or cystoscopy because lidocaine hydrochloride is a safer alternative. Administration by injection The dose of local anaesthetic depends on the injection site and the procedure used. In determining the safe dosage, it is important to take account of the rate of absorption and excretion, and of the potency. The patient’s age, weight, physique, and clinical condition, and the vascularity of the administration site and the duration of administration, must also be considered. Uptake of local anaesthetics into the systemic circulation determines their duration of action and produces toxicity. NHS Improvement has advised (September 2016) that, prior to administration, all injectable medicines must be drawn directly from their original ampoule or container into a syringe and should never be decanted into gallipots or open containers. This is to avoid the risk of medicines being confused with other substances, e.g. skin disinfectants, and to reduce the risk of contamination. Great care must be taken to avoid accidental intravascular injection; local anaesthetic injections should be given slowly in order to detect inadvertent intravascular administration. When prolonged analgesia is required, a long-acting local anaesthetic is preferred to minimise the likelihood of cumulative systemic toxicity. Local anaesthesia around the oral cavity may impair swallowing and therefore increases the risk of aspiration. Epidural anaesthesia is commonly used during surgery, often combined with general anaesthesia, because of its protective effect against the stress response of surgery. It is often used when good postoperative pain relief is essential. Vasoconstrictors in combination with local anaesthetics Local anaesthetics cause dilatation of blood vessels. The addition of a vasoconstrictor such as adrenaline/epinephrine to the local anaesthetic preparation diminishes local blood flow, slowing the rate of absorption and thereby prolonging the anaesthetic effect. Great care should be taken to avoid inadvertent intravenous administration of a preparation containing adrenaline/epinephrine, and it is not advisable to give adrenaline/epinephrine with a local anaesthetic injection in digits or appendages because of the risk of ischaemic necrosis. Adrenaline/epinephrine must be used in a low concentration when administered with a local anaesthetic. Care must also be taken to calculate a safe maximum dose of local anaesthetic when using combination products. In patients with severe hypertension or unstable cardiac rhythm, the use of adrenaline/epinephrine with a local anaesthetic may be hazardous. For these patients an anaesthetic without adrenaline/epinephrine should be used. Dental anaesthesia Lidocaine hydrochloride is widely used in dental procedures; it is most often used in combination with adrenaline/epinephrine. Lidocaine hydrochloride 2% combined with adrenaline/epinephrine 1 in 80 000 (12.5 micrograms/mL) is a safe and effective preparation; there is no justification for using higher concentrations of adrenaline/epinephrine. The amide-type local anaesthetics articaine and mepivacaine hydrochloride p. 1426 are also used in dentistry; they are available in cartridges suitable for dental use. Mepivacaine hydrochloride is available with or without adrenaline/epinephrine and articaine is available with adrenaline. In patients with severe hypertension or unstable cardiac rhythm, mepivacaine hydrochloride without adrenaline/epinephrine may be used. Alternatively, prilocaine hydrochloride with or without felypressin can be used but there is no evidence that it is any safer. Felypressin can cause coronary vasoconstriction when used at high doses; limit dose in patients with coronary artery disease. Toxicity induced by local anaesthesia For management of toxicity see Severe local anaesthetic- induced cardiovascular toxicity below. Severe local anaesthetic-induced cardiovascular toxicity Overview After injection of a bolus of local anaesthetic, toxicity may develop at any time in the following hour. In the event of signs of toxicity during injection, the administration of the local anaesthetic must be stopped immediately. Cardiovascular status must be assessed and cardiopulmonary resuscitation procedures must be followed. In the event of local anaesthetic-induced cardiac arrest, standard cardiopulmonary resuscitation should be initiated immediately. Lidocaine must not be used as anti-arrhythmic therapy. If the patient does not respond rapidly to standard procedures, 20% lipid emulsion such as Intralipid ®[unlicensed indication] should be given intravenously at an initial bolus dose of 1.5 mL/kg over 1 minute, followed by an infusion of 15 mL/kg/hour. After 5 minutes, if cardiovascular stability has not been restored or circulation deteriorates, give a maximum of two further bolus doses of 1.5 mL/kg over 1 minute, 5 minutes apart, and increase the infusion rate to 30 mL/kg/hour. Continue infusion until cardiovascular stability and adequate circulation are restored or maximum cumulative dose of 12 mL/kg is given. Standard cardiopulmonary resuscitation must be maintained throughout lipid emulsion treatment. Propofol is not a suitable alternative to lipid emulsion. Further advice on ongoing treatment should be obtained from the National Poisons Information Service. Detailed treatment algorithms and accompanying notes are available at www.toxbase.org or can be found in the Association of Anaesthetists of Great Britain and Ireland safety guideline, Management of Severe Local Anaesthetic Toxicity and Management of Severe Local Anaesthetic Toxicity – Accompanying notes. ANAESTHETICS, LOCAL
PDF pages 1439, 1440, 1441
Hepatotoxicity ▶With oral use Patients should be told how to recognise signs of liver disorder and advised to seek prompt medical attention if symptoms such as anorexia, nausea, vomiting, fatigue, abdominal pain, dark urine, or pruritus develop. Driving and skilled tasks ▶With oral use Drowsiness may affect performance of skilled tasks (e.g. driving); effects of alcohol enhanced.
PDF page 1439
Initially 2–3 mg/kg, then 1 mg/kg, repeated if
First-line fragment. Read the complete Indications and Dose section above.
PDF page 1439
Initially 25 mg daily, then increased to up to
First-line fragment. Read the complete Indications and Dose section above.
PDF page 1439
Initially 25 mg daily, then increased to up to
First-line fragment. Read the complete Indications and Dose section above.
PDF page 1439