Administration of Medicines

1. Administration of Medicines

Introduction

This Tutorial covers concepts that you may not have come across if you have not worked in a hospital before. It describes common enquiry types and gives you practical troubleshooting tips for resolving administration problems, but it does not give an in-depth description of each method of giving medicines. Note that many enquiries about administration of medicines involve unlicensed drug use.

Parenteral Administration

1. Intravenous (iv)  The intravenous route provides a rapid way of administering drugs, fluids, blood products and parenteral nutrition. There are two basic methods: – Injection. Direct intravenous injection is the administration of a small volume of drug solution into an entry port sited in a vein such as a cannula or venflon. Direct injections can also be made via existing iv infusion administration lines (or ‘giving sets’). The technique of direct injection is sometimes called an ‘iv push’. The term ‘bolus’ should be avoided as it implies that the injection can be given instantly over a few seconds, whereas most direct injections should normally be given over 2 to 5 minutes. Direct injection gives therapeutic levels of a drug quickly (eg glucose 50% injection for hypoglycaemia), but there can be problems with this technique. For example, direct injection may damage a vein, particularly if the drug is irritant (eg phenytoin). In addition it is impractical if a drug needs to be given slowly or in a large volume. – Infusion. This involves iv administration over a longer time period often using bigger volumes. Plastic tubing (‘iv line’ or ‘giving set’) connects the bag of drug solution to an entry point in a patient’s vein. The infusion may be intermittent (eg metronidazole 500mg in 100ml saline over 20 minutes every eight hours) or continuous over 24hours. Continuous infusion is indicated for drugs with a short half-life (eg glyceryl trinitrate) or when a constant therapeutic drug level is required (eg insulin). Infusions require a drug to be stable in the specified diluent for the duration of administration. They also require the drug to be compatible with the plastic used to make the iv line and infusion bag.  The choice of intravenous administration method depends on the drug (eg indication, volume of infusion fluid, rate of administration, degree of irritancy, pharmacokinetics) and patient factors (eg age, availability of iv access, concurrent disease such as presence of heart failure).  Some drugs may cause pain on injection because of their tonicity, pH or irritancy (eg erythromycin). The vein may become red and inflamed; this is called phlebitis.  A ‘Y-site’ is the point where two iv lines containing drug solutions join to run down the same line forming a ‘Y’ shape. One infusion may be described as being ‘piggybacked’ onto the other.

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 Intravenous injections and infusions may be given via peripheral or central veins. Peripheral lines are usually inserted in the hand or arm. They can become blocked or dislodged easily and, because the veins are quite narrow, they are not usually used for irritant drugs (eg amiodarone), concentrated solutions in fluid-restricted patients (eg potassium) and vasoconstricting drugs (eg epinephrine). Central lines are preferred for these situations and are inserted into larger veins such as the superior vena cava. Central lines can be used for any licensed iv drug.  The iv lines which carry centrally administered drugs may be single, double, triple or quadruple ‘lumen’. Potentially incompatible drugs may be administered through separate lumens of the same line: the drugs will not mix until they reach fast-flowing blood at the end of the line (see Tutorial 6: Compatibility of Parenteral Drugs). Peripheral lines are usually single lumen.

Common enquiries – The rate of administration of a drug (eg phenytoin). – The volume and infusion fluid that a drug needs to be diluted in (eg vancomycin). – How to administer an iv drug in fluid restricted patients (eg potassium). – Choosing between a peripheral or central intravenous line (eg dopamine, amiodarone). – Mixing drugs in the same syringe, bag or line (eg cefuroxime and metronidazole).

2. Subcutaneous (sc)  Administration of drugs and fluids by the subcutaneous route may be by direct injection (eg insulin, enoxaparin), by intermittent or continuous infusion (eg diamorphine, terbutaline) or by implantation (eg testosterone). This route can be used when intravenous access becomes difficult (eg elderly or restless patients) and is particularly used in palliative care (see Tutorial 16).  The subcutaneous compartment can accommodate large volumes of fluid. Subcutaneous administration of fluid (‘hypodermoclysis’) can be a useful method of hydration in patients with terminal illness or following a stroke. The rate of administration should not normally exceed 2 litres in 24 hours.  The subcutaneous route is normally well tolerated, but pain, oedema and bruising can occur. Irritant drugs should not be given subcutaneously (eg prochlorperazine).

Common enquiries – Mixing drugs in the same syringe, particularly in patients with terminal illness. – How to administer infusion fluids subcutaneously.

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3. Intramuscular (im)  Intramuscular injections are used: – To ensure compliance (eg depot antipsychotics). – When other routes are less effective (eg hydroxocobalamin). – When other routes may be dangerous (eg epinephrine for anaphylaxis). – When a prolonged duration of action is desired (eg depot medroxyprogesterone). – As a short-term alternative to intravenous administration (eg morphine).  The intramuscular route is not suitable if a rapid onset of action is required. It is also more uncomfortable for the patient and only small volumes can be given (typically no more than 3mL). IM injection of certain drugs may cause pain, abscesses or bleeding (eg NSAIDs, iron).  The route is avoided in patients with increased bleeding risk (eg raised INR, low platelet count) to prevent injection site haemorrhage, and in those with decreased muscle mass.

Common enquiries – In practice you probably won’t be asked many questions about intramuscular drug administration.

Enteral Administration

1. Oral administration  As a pharmacist working in MI you will often be asked for help in managing oral administration problems. Think laterally and be inventive. For example, if a patient is going to be nil-by-mouth (NBM) prior to surgery but normally takes levothyroxine, it may not matter if they miss one or two doses, as the half-life is about 7 days. Similarly if the patient takes simvastatin for hypercholesterolaemia missing several doses won’t matter, since atherosclerosis is a chronic process. However, if the same patient takes carbamazepine for epilepsy, they cannot miss any doses and you need to think about alternative routes, in this case rectal.  For patients with dysphagia where no licensed liquid formulation exists think about specials manufacturers, alternative routes or drugs, using injections orally, crushing tablets or opening capsules. Some conventional tablets are actually soluble in water (eg ciprofloxacin). Note that certain tablets must not be crushed – see overleaf.  Patients with part of their gut removed may still be able to take medicines orally. Establish exactly which section of gut has been removed and check the site of drug absorption.

Common enquiries – How to manage NBM patients (eg patients undergoing surgery). – How to manage patients with dysphagia (eg patients with stomatitis or after a stroke).

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2. Administration through enteral feeding tubes  Enteral feeding is indicated in patients who cannot ingest food normally but whose gastrointestinal tract is able to digest and absorb sufficient nutrients (eg patients with head and neck cancer or following a stroke). A variety of methods are used to deliver enteral feeds: – Nasogastric (NG) tubes are inserted through the nose into the stomach. They are used for short-term feeding only. – Percutaneous endoscopic gastrostomy (PEG) tubes are inserted through the abdominal wall into the stomach to form a stoma. They are used for long-term feeding. – Jejunostomy tubes are placed directly into the jejunum through the abdominal wall. They are used when PEG tubes are unsuitable.  Enteral feeding tubes can be used to administer drugs but care must be taken to check that the tube does not bypass the site of absorption (eg iron is mainly absorbed in the duodenum and cannot be administered through a jejunostomy tube). In addition, drugs can interact with the feed (eg phenytoin) or cause the tube to block (eg insufficiently crushed tablets). NG tubes are long, fine bore tubes, which block easily. PEG and jejunostomy tubes are shorter with a wider bore.  Enteral feed may be administered as a bolus, intermittent or continuous infusion. Try to administer drugs in the gaps when the tube is not being used for feed, remembering to flush with sterile water before and after each drug.  If a liquid formulation is unavailable then consider using injections orally, changing the drug or route of administration, opening capsules or crushing tablets. However enteric-coated tablets, modified-release tablets or cytotoxic drugs must not be crushed.

Common enquiries – How to administer drugs through enteral feeding lines (eg can tablets be crushed, availability of liquids, can injection be given orally). – Interactions between drugs and enteral feeds (eg sucralfate). – How to unblock enteral feeding tubes.

Other Methods of Administration

 Transdermal: In practice you probably won’t be asked many enquiries about the transdermal route. However it can be a very useful alternative if you are running out of options (eg fentanyl patches for pain in a patient with dysphagia).  Buccal/Sublingual: Similarly the buccal and sublingual routes will not generate many enquiries but can be used occasionally if you’ve exhausted other routes (eg sublingual buprenorphine for heroin withdrawal).  Inhalation: The inhaled route can be used to administer a variety of drugs other than bronchodilators and corticosteroids (eg morphine for dyspnoea, antibiotics for cystic fibrosis, pentamidine for Pneumocystis carinii pneumonia).

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Paediatric Considerations

Special consideration should be given when dealing with enquiries that relate to the administration of medicines to children. The evidence base for the use of many medicines in children is currently scarce. Many company sponsored drug trials do not recruit children because of the ethical concerns and lack of financial return. It follows that the range of medicines that are licensed for use in children is limited. However, the Department of Health has recently published a Childrens’ Medicines Strategy that, along with improving information provision, aims to increase the number of medicines that are appropriately tested and fomulated for children. Therefore the evidence base for paediatric medicines may improve in the future. If asked about the choice of drug in a paediatric patient, always consider if there is an appropriate, licensed drug first. Unlicensed drug use is not illegal, but you will need to take extra steps to check the indication, dose and frequency, suitability of formulation, precautions, interactions and monitoring parameters (also see below ‘Unlicensed Medicines and the Law’). Several classification systems have been developed to define the age ranges in childhood. The most commonly used are as follows:  Neonate – first 30 days of life.  Infant – from 1 month to 1 year.  Child – from 1 year to 12 years. Therefore, for the purpose of medicine administration, children over the age of 12 years are often considered as adults. This is not always appropriate as many 12 year olds are not adult height and weight and have not reached puberty. Unfortunately manufacturers of medicines and regulatory authorities have yet to standardise the age groups referred to in Summary of Product Characteristics (SPCs).

Unlicensed Medicines and the Law

Although medicines cannot be promoted outside the limits of the licence, the Medicines Act does not prohibit the use of unlicensed medicines. It is recognised that informed use of unlicensed medicines or of licensed medicines for unlicensed purposes (‘off-label’ use) is often necessary – particularly in paediatric patients. Crushing tablets and opening capsules for administration through enteral feeding tubes is unlicensed but common practice; investigate all the appropriate licensed options first (eg liquids).

Questions to Ask an Enquirer

It is impossible to give you guidance for every eventuality, however:  If asked about administration of a drug intravenously think about: dose, type of infusion fluid, fluid volume, rate, availability of iv access and whether any other drugs are being given iv.  If asked whether drugs may be put down enteral feeding tubes, ask about the type of tube, where the end of the tube is and the feeding regimen. Think about alternative administration routes or drugs.  If the enquiry is about a patient NBM prior to surgery establish the drugs and doses, and the duration of expected NBM. Again think about alternative administration routes or drugs.  Similarly if a patient becomes dysphagic, ask about the drugs and doses, and when/whether their swallow is expected to improve.

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Example Sources to Use in Answering Enquiries Refer to Tutorial 6, Compatibility of Parenteral Drugs, for details of specialist parenteral sources.  The BNF and SPCs are a good place to start for most straightforward administration questions. For enquiries specific to paediatrics, start with the BNF for Children.  Try your in-house archiving database or find out if you have any relevant local policies.  For help with administering drugs through enteral feeding lines try Administering Drugs through Enteral Feeding Lines 2nd Edition (The Royal Hospitals, Belfast).  Drug and Therapeutics Bulletin ran a helpful series of articles between August and December 1999 called ‘Drugs in the Peri-operative Period’ which may help you manage NBM patients.  Trying to establish exactly where drugs are absorbed in the gastrointestinal tract is notoriously difficult. However, your pharmacology textbooks are a good starting point.  Medical Information departments can help with a variety of drug administration problems.  Don’t forget Micromedex, Medline or Embase as appropriate.  Thomas FC et al. Managing drug therapy in patients receiving enteral and parenteral nutrition. Hospital Pharmacist 2000; 7(6): 155-64.

Exercises

 If you have the MiCAL training programme CD, you could try one or both of the following questions: 18 and 25.  Have a go at the questions on page 1.7 (‘Test Yourself!’). Answers at the back of this book.  There is an example enquiry on page 1.9.  Page 1.11 has some real enquiries that you might like to tackle with your MI tutor.  You may like to arrange a visit to a ward to help you visualise parenteral lines and enteral feeding tubes. Spending time with a dietician may also help you.

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Test Yourself!

1. What is a cannula?

2. What volume of infusion fluid should 750mg vancomycin be diluted in?

3. What is the maximum rate of administration of intravenous furosemide?

4. Can modified-release isosorbide mononitrate tablets be administered through a PEG tube?

5. What is a stoma?

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6. Can diamorphine be given intramuscularly in the acute management of a myocardial infarction?

7. Can norepinephrine be given through a central intravenous line?

8. What is extravasation?

9. Name five drugs that may be given by continuous intravenous infusion.

10. Where would you look to find out how to administer intravenous co-amoxiclav?

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Example Enquiry

MI: Good morning Medicines Information. Dr: Hello Medicines Information, it’s Dr Sadler from Solent ward, I need some advice please. I’ve a difficult patient with multiple myeloma who has just finished her last cycle of chemotherapy but has developed severe stomatitis. She is finding it very difficult to swallow any of her tablets and is even refusing her food. I can’t site a cannula or get a nasogastric tube in so I need to know if any of her medicines can be administered via other routes. MI: Well that sounds fairly straightforward. What medicines is she on? Dr: Right, lets start at the beginning: morphine, domperidone, diclofenac... MI: I’m just writing all these down, maybe we can go through them one at a time. Shall we start with the morphine? Dr: Fine, she normally takes slow-release morphine 60mg twice daily with some morphine liquid for breakthrough pain. MI: Okay, is the rectal route an option? Dr: I’d rather not as she’s suffering from diarrhoea. MI: Right, what about intramuscular? Dr: She’s very emaciated.... MI: Fine, let me think...is the stomatitis likely to be short-term? Dr: Well she’s just finished her chemotherapy so I’d expect it to resolve. MI: Okay, well you could use subcutaneous diamorphine via a syringe driver temporarily. Alternatively if her pain is quite well controlled you could use a fentanyl patch. Dr: Can we put domperidone in the syringe driver as well? MI: Unfortunately it’s not made as an injection, but lots of anti-emetics are, and are suitable for subcutaneous use like cyclizine or haloperidol. In addition they can be mixed with diamorphine in the pump. Alternatively prochlorperazine is available as a buccal preparation if she can tolerate it. Dr: Excellent. Diclofenac for her bone pain? MI: Right, now that’s a little more difficult. Diclofenac is available as suppositories, soluble tablets and i.m. injections, but we’ve ruled all those out. Let me check my BNF.... okay, could she tolerate something that melted on her tongue? Dr: We can only try, what did you have in mind? MI: One of the NSAIDs, piroxicam is available as a melt-on-the-tongue preparation. Alternatively ketorolac can be given subcutaneously but I’ve less experience with this because it’s not used very often. Also it’s an unlicensed route for ketorolac, so I’d recommend that you tried the piroxicam first. Dr: Great...what about dexamethasone? MI: Right, erm, well its not licensed but again you can use the subcutaneous route. It’s normally given as a direct injection. Any other drugs? Dr: Just two more, fluoxetine and warfarin. MI: What dose of fluoxetine is she on? Dr: Twenty milligrams once daily.

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MI: Well you have a few options; fluoxetine can normally be stopped abruptly without causing any withdrawal symptoms if the dose doesn’t exceed 20mg daily. If her stomatitis improves you can restart it. If it doesn’t improve then fluoxetine liquid is absorbed sublingually, again it’s unlicensed but it’s an option if she can tolerate it. Dr: Great. MI: As for the warfarin, why is she on it? Dr: She had a DVT two months ago. MI: Okay, you probably need to change her onto subcutaneous enoxaparin, but check that she doesn’t have thrombocytopenia first. Dr: So, let me write this down, give the diamorphine and cyclizine subcutaneously in a syringe driver. Dexamethasone and enoxaparin can be given as subcutaneous injections. Use melt-on-the-tongue piroxicam and fluoxetine is absorbed sublingually if it’s still needed. MI: Yes, that’s correct. Dr: Excellent, you’ve been very helpful. MI: No problem, don’t hesitate to call if you have any other questions. Dr: I will, goodbye.

So how would you have answered this enquiry? Can you think of any alternative routes?

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Real Enquiries

This section helps you to think about the enquiry answering process. Below are given the details of three real enquiries, as received by a regional MI centre. Decide with your tutor which of these enquiries to do. Then for each one describe: (a) Any further questions you would like to ask the enquirer. (b) The top sources that you would use to answer the enquiry. Your tutor will go through these with you when you have finished. If you like, research a full answer using your local enquiry answering form to document it, but discuss this with your tutor first.

1. Administering medicines prior to surgery A new surgical house officer ‘phones you about a diabetic patient on his ward. The patient normally takes metformin, aspirin, ramipril, co-codamol and sodium valproate but will be nil-by-mouth from midnight in preparation for surgery tomorrow. What should he do?

Further questions for enquirer Sources to use

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2. Intravenous administration of dopamine A nurse from your surgical high dependency unit calls you for advice about administering dopamine. The doctors have prescribed 3 microgram/kg/min. What dose, volume of infusion fluid and rate should your nurse use?

Further questions for enquirer Sources to use

3. Intravenous administration of potassium An anaesthetist ‘phones you for advice. She would like to administer potassium chloride intravenously to a patient with heart failure. What rate should she use? Can she administer intravenous potassium neat?

Further questions for enquirer Sources to use

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