6: Drug administration

Section 6 Drug administration




6.1. Pharmacokinetics and pharmacodynamics


6.2. Medicines management


6.3. Classification of drugs used in children



6.1 Pharmacokinetics and pharmacodynamics


This is about the basic principles of drugs following its administration (see Neal 2002, Galbraith et al 1999). Why are certain drugs given specific routes of administration? Patients are reliant on all nurses to ensure medicines are administered appropriately. It is vital for nurses to have a sound understanding of the two classes of pharmacology: pharmacokinetics, the way the body affects the drug with time (absorption, distribution, metabolism and excretion of drugs) and pharmacodynamics, which is the effects of the drug on the body.



Pharmacokinetic processes


Pharmocokinetics considers the passage of a drug through the body, and is concerned with absorption, distribution, metabolism and excretion.



Absorption


Drugs must be absorbed across a cell membrane (with the exception of IV drugs). Before entering the systemic circulation a drug must traverse the GIT layers before the drug reaches the bloodstream and cell membranes. Oral drugs are absorbed in the upper small bowel because of its large surface area (Neal 2002), which is determined by the chemical nature of the drug. Absorption occurs by simple diffusion, determined by molecular size:



image Drugs absorbed from the GIT enter the portal circulation and some are extensively metabolized as they pass through the liver.


image Drugs that are lipid soluble are readily absorbed orally and rapidly distributed throughout the body.


image Many drugs are bound to albumin and equilibrium forms between the bound and free drug in the plasma. The drug that is bound to albumin does not exert a pharmacological action.


image Bioavailability is the fraction of the administered dose that reaches the systemic circulation – 100% in drugs administered IV.


Drugs administered orally have to overcome the physical barrier of the gut wall. The absorption process is affected by many factors:



image formulation


image stability to acid and enzymes


image motility of gut


image food in the stomach


image degree of first pass metabolism (discussed later)


image lipid solubility.



Distribution


Distribution around the body occurs when the drug reaches the circulation. It must then penetrate tissues to act. Factors that affect drug distribution are:



image plasma protein binding sites albumin – competition


image specific drug receptor sites in tissues


image regional blood flow


image lipid solubility


image blood–brain barrier


image GIT membrane


image highly water-soluble drugs, e.g. gentamicin


image disease


image liver disease – low plasma protein levels


image renal disease – high blood levels.



Metabolism


Metabolism of drugs occurs in the liver and involves a group of enzymes that transform drugs into products that are more water soluble and easier to excrete. The majority of drug metabolism occurs in the liver and involves two general types of reactions:



1. Phase 1 reaction – the biotransformation of the drug – oxidations are the most common reactions and these are catalysed by mixed function oxidases.


2. Phase II reactions – drugs from phase I cannot be excreted efficiently by the kidneys and are made more hydrophilic by conjugation with compounds in the liver.


Metabolism also occurs in the gut lining, kidney and lungs. The majority of drugs that are metabolized are:



image inactivated (propranolol)


image activated (enalapril)


image remain unchanged (atenolol)


image the products of metabolism (metabolites) are longer acting than the original drug (diazepam).


Concomitant drug administration may influence metabolism, for example:



image phenytoin can induce liver enzymes by increasing the metabolism of other drugs


image cimetidine can inhibit liver enzymes by reducing metabolism.


These can have serious consequences if the patient is already on other drug therapies.


Other factors can affect drug metabolism:



image age (including infants/children)


image alcohol consumption


image immaturity of drug-metabolizing enzymes in neonates and infants


image disease (impaired liver function, dose reduction may be necessary for drugs metabolized in the liver), e.g. chlormethiazole


image smoking.



The first pass metabolism


Drugs absorbed from GIT pass into the bloodstream and are immediately transported to the liver. Some drugs are inactivated the first time they pass through the liver; this affects drug dose and route of administration (e.g. propranolol):



image if given IV the dose is 1 mg


image if give orally the dose is 40 mg


image affects possible routes of administration, e.g. GTN cannot be given orally except by by-passing the liver such as sublingually.



Excretion


The main route of excretion is the kidney in the urine. Excretion of drugs can occur in the faeces. The drug is circulated in blood to the liver then passes into the bile into the GIT. If renal or liver impairment is present a reduced dose may be required, for example with digoxin or gentamicin. Drug can be reabsorbed and re-enter the liver. Metabolism can be reversed (by enzymes present in the gut or by gut microflora), converting the drug so that it can be reabsorbed. This can lead to a cycle known as the enterohepatic recirculation and accounts for the prolonged effect of some drugs. Excretion varies with age and can lead to discoloration of the urine or faeces.


Frequent blood samples may be required for some drugs; in order for them to be effective a certain blood level has to be obtained. Drugs are generally poisonous and at higher blood level concentrations can lead to serious consequences, even death. To avoid drug toxicity in infants (<1 year) lower doses are prescribed or their administration intervals widened. For all drugs there is also a minimum effective concentration, below which there will be not any therapeutic effect.


Factors affecting excretion:



image renal failure


image blood flow to the kidneys


image GFR


image Urine flow rate and pH, which indirectly alters:


– passive reabsorption

– active tubular secretion.


Pharmacodynamics


This is the study of effects of drugs on the body or the biological processes. It is concerned with the pharmacological effect of drugs at its site(s) of action and considers mechanisms of action for both therapeutic and adverse effects of the drug.



image Pharmacological responses are initiated by the molecular interactions of drugs with cells, tissues or other body constituents.


image Drug molecules must exert some chemical influence on one or more cellular constituents to produce a pharmacological response.


image To affect functioning of cellular molecules, the drug must approach the molecules closely.


image Another requirement is that the drug must have some sort of non-uniform distribution within the body or the chance of interaction if the drug molecules are distributed at random would be negligible. This means that a drug must bind in some way to constituents of the cell to produce an effect.


image For most drugs the site of action is at a specific biological molecule – the receptor. A receptor is the primary site of action of a drug.


image Various types of receptor exist, and each responds to a different chemical or hormone, e.g. histamine, acetylcholine, epinephrine (adrenaline) and dopamine.


image Many endogenous hormones, neurotransmitters and other mediators exert their effects as a result of high affinity binding or specific macromolecular protein or glycoprotein receptors in plasma membranes or cell cytoplasm.


image When these receptors are bound to a certain chemical, this directs a change to occur in the cell, which then alters an activity of the cell.



The commonest ways in which drugs produce their effects


Not all drugs work via receptors for endogenous mediators and many drugs exert their effect by combining with other regulatory proteins and interfering with their function:



image Ion channels – physical blocking of channel by the drug molecule – sodium channel blocking by local anaesthetics or by binding to accessory sites to facilitate opening of channels.


image Enzymes – many drugs are targeted in this way:


– substrate analogues and act as competitive inhibitors, either reversible inhibitors (neostigmine on acetylcholinesterase) or irreversible inhibitors (aspirin on cyclo-oxygenase).

– many act as a false substrate – fluorouracil replaces uracil and blocks DNA synthesis.

– some drugs are pro-drugs and need enzymic degradation to convert them to the active form, e.g. diamorphine to morphine.

image Transport proteins – drugs may interfere with the uptake of ions or small molecules across the cell membrane:


– cocaine interferes with the re-uptake of noradrenaline (norepinephrine)

– digoxin interferes with the sodium/potassium pump.

image Other cellular macromolecules – these do not involve regulatory proteins:


– chemical action, e.g. antacids (magnesium hydroxide)

– drugs that act by physical action – osmotic diuretics (mannitol)

– drugs that act by a physicochemical action – inhaled anaesthetics, which act by altering the protein of cell membranes.

Most drugs produce their effects by acting on specific protein molecules usually located in the cell membrane. These proteins are called receptors and normally respond to endogenous chemicals in the body. A chemical that binds to a receptor is known as a ligand, many drugs cause their effects by combining with these receptors and are of the following types:



image Agonists – these interact with a receptor mimicking the effect of a natural mediator. Epinephrine (adrenaline) is a beta-receptor agonist, which stimulates the cardiac beta-receptors and increases heart rate.


image Partial agonists – the maximal response falls short of the full response block access of the natural agonist, e.g. pindolol, oxprenolol beta blockers, which are partial agonists.


image Antagonists block a receptor to prevent such an effect. Atenolol is a beta-receptor antagonist that slows heart rate by blocking the cardiac beta-receptors and reducing physiological stimulation. They are selective but not specific (they act on more than one receptor and produce side effects). Amitriptyline (tricyclic antidepressant) blocks cholinergic and histamine receptors, which leads to dry mouth, blurred vision, constipation and drowsiness.



Potency of drugs


The interaction between a drug and the binding site of the receptor depends on the ‘fit’ of the two molecules. The closer the fit and the greater number of bonds the stronger will be the attractive forces between them:



image If a drug is potent it produces effects at low concentration.


image If a drug has a high potency it is a consequence of high affinity for a specific receptor.


image Affinity is the tendency to bind to receptors.


image Efficacy is the ability once bound, to initiate changes, which lead to effects.


image If a drug is specific small changes in drug structure lead to profound changes in potency or causes a change from agonist to antagonist:


– selectivity is the phenomenon that allows drugs to be useful; a drug must act selectively on particular cells and tissues

– specificity is reciprocal – individual classes of drug bind only to certain targets, and individual targets only recognize certain classes of drug

– no drug acts with complete specificity – will only produce one effect.

image Potency is independent of efficacy and efficacy is usually more important than potency when selecting a drug for clinical use.


image The lower the potency of a drug and the higher the dose needed, the more likely that sites of action other than the primary one will assume significance:


– this is often associated with the appearance of unwanted side effects, of which no drug is free – varies from trivial to fatal

– pharmaceutical companies try hard to manufacture drugs that are more selective and thus less dangerous to other tissues.


Mode of action


If the basic mode of action of a drug is via a receptor then it is likely that:



image it will be potent


image it will have biological specificity and may produce opposite effects on apparently similar tissue type


image it will have chemical specificity and changes in the chemical structure of a drug molecule may have a large or small effect on its pharmacological activity


image specific antagonists will abolish the effects of the drug on the tissue


image if plasma concentration of the drug is too high (outside the therapeutic range) toxicity will occur


image if plasma concentration is too low treatment will fail


image the aim of treatment is to keep the plasma concentration within the therapeutic range via blood levels.



Drug interactions


Drugs are chemicals and may interact with one another. When this happens, a drug’s action may be:



image suppressed


image rendered completely inactive


image increased.


The therapeutic action of one drug can interfere with the therapeutic action of another.


Combinations of drugs must be carefully considered to avoid drug interactions.


As the number of medications prescribed for a patient increases (polypharmacy) so does the potential for drug interactions. With so many drugs given at the same time and so many drugs available, it is impossible to predict the interactions that can occur. Any adverse reaction needs to be reported to the appropriate authorities. The British National Formulary (BNF) and the BNF for children website (www.bnf.org/bnf/) contain lists of known interactions, and these should always be consulted before drug mixtures are administered. Some produce minor problems, others can be fatal. The types of drug interactions that occur are:



image outside the body – generally due to storage conditions, too much light, oxygen or moisture, interactions with containers whereby the chemicals contained within the drug are prone to degradation


image in the GIT – some food chemicals may react with drugs


image after absorption – where the most known interactions take place, usually when more than one drug is administered concurrently.



Pharmacogenetics


After taking all of the issues related to pharmacokinetics and pharmacodynamics, and the age, level of nutrition, occupation, state of health into consideration, there are still individual differences in drug metabolism. This is described in terms of a person’s genetic make-up. How some patients metabolize or inactivate drugs and facilitate their excretion is to a large extent determined by inheritable traits. In addition, different ethnic groups show different pharmacokinetic profiles for a number of drugs.


There are many issues to consider administering individual patient therapy. A good understanding of the fundamental principles of drug therapy should help nurses to optimize patient care. An increase in nurses’ contribution to multidisciplinary care in relation to drug administration/therapy is currently being explored.



Drug calculations


In children there are cardiac support and other drugs, which require careful and meticulous calculations to ensure the correct dose is given to patients. Included here are some of the common drug formulas and other useful information.


IV and oral therapy are common administration routes for drugs. It is in your interest to use some of your time to observe and learn about some of the drugs that patients are prescribed. In addition to this, in your role as a nurse you will be expected to check a drug and later to ensure correct calculation, draw up and calculate drug dosages.


The following are some of the drug calculation formulae that may help you in this role:



1000 μg in 1 mg


1000 mg in 1 g


Ampicillin 500 mg in diluted in 10 ml, you require 200 mg



image



Epinephrine comes in strengths of 1:1000 (1 mg/ml) and 1:10 000 (10 mg/ml)




(i) If you require 1.6 mg of 1:1000 strength epinephrine, use the formula



image



(ii) If you require 2.5 mg of 1:10 000 strength epinephrine, use the formula



image



Lidocaine comes in either a 1% solution or a 2% solution; this means that:



image

There are other drugs used for infusion such as dopamine, epinephrine (adrenaline), dobutamine, noradrenaline (norepinephrine), which require to be calculated in μg/kg/min.


First calculate μg/ml


For these drugs use the formula. This is a different calculation to the % concentrations / dosages that adrenaline comes in:



image




Nurse prescribing


Nursing is moving into the reality of nurse prescribing (Jones 2004, Beckwith and Franklin 2007). Any children’s nurse who is interested in the extension of nurse prescribing rights will appreciate the significance of the Crown Report, which proposed a new framework for prescribing, supply and administration of medicines inside and outside the NHS and made three main recommendations:



1. The majority of patients continue to receive medicine on an individual patient basis.


2. The current prescribing authority of doctors, dentists, and certain nurses (in respect of a limited list of medicines) continues.


3. New groups of professionals would be able to apply for authority to prescribe in specific clinical areas, where this would improve patient care and patient safety could be assured.


It is the third recommendation, that a ‘new group of professionals’ who currently do not have prescribing rights might apply for this authority to be extended to them and this can happen in two ways:



1. Independent prescribing


This is identified as someone who is responsible for assessment of patients with undiagnosed conditions and for decisions about the clinical management required, including prescribing (DH 1999 p 39).


Children’s nurses who are currently prescribing from the Children’s Nurse Formulary can continue to do so. However, nurses not currently able to prescribe, who are in a position to undertake the assessment of patients with undiagnosed conditions (e.g. hypokalaemia) and make a prescribing decision (e.g. potassium added to fluids can become newly legally authorized independent prescribers). This will entail a childrens’ nurse to undertake a relevant nurse prescribing course. There is a larger space definition in the page above.


2. Dependent prescribing


Crown defines the dependent prescriber as someone who does not have the diagnostic and assessment ability to make a decision about an initial prescription, but will have sufficient knowledge to determine whether that prescription should be continued, or whether to alter the dosage. Furthermore, a dependent prescriber may still be able to prescribe a drug for the first time, but this would be within the parameters of clinical guidelines for a given condition, and the care plan of a patient. This is about protocol arrangement.


There is no reason in the area of children’s nursing whereby practitioners would consider themselves working at specialist level could, by undertaking a recognized accredited nurse prescriber course, become an independent or dependent prescriber.



6.2 Medicines management



Safe use of medicines


This includes the clinical, cost effective and safe use of medicines to ensure patients get the maximum benefit from the medicines they need, while at the same time minimizing potential harm or side effects of the drug (www.mhra.gov.uk).


Healthcare professionals must adhere to the five ‘rights’ medication administration (NMC 2008). These are:



Right medication – check the name of medication against the prescription.


Right patient – check the name against the prescription and verify with parent/carer.


Right dose – check that the dose is correct for the age of the child.


Right route – check that the route is correct for the child and that the correct medication has been prescribed.


Right time and frequency – check that time and frequency of the drug is correct for the child.


The key contributors to the management of medicines are:



image The primary care trust


image social services, care workers, home help


image primary care pharmacist


image care home staff


image GPs and practice staff


image families and carers


image voluntary organizations


image hospital and all staff


image community pharmacy


image community nurses.


This list shows the complexity of the number of people and organizations involved in the delivery of safe and effective medicines management.


The nurses’ role in medicines management:



image interpretation of prescription


image assessing the child


image administering the drug prescribed


image communicating with the child and family, other health care professionals, e.g. doctors and pharmacists


image providing information about the drug to the family, e.g. action and side effects, when to take it


image teaching and support for the patient, e.g. being a patient advocate


image anticipate any potential side effects


image monitor the drug for effectiveness, the patient’s response to the medication


image evaluate and review the response to the drug treatment e.g. blood pressure, nausea


image record the administration of the drug


image report any changes in the child after administration of the drug


image this may involve:


– diagnosis

– solving any problems

– prioritization

– analysis of the child’s condition.

Most nurses see medicine management as just their involvement in the task of its administration. Yet nurses do more than this; they facilitate the engagement of patients and their families, so enabling them to make what they see as best use of their prescribed medicines.


The key priorities influencing and directing medicines management are:



image National standards framework (NSF) – these are national standards for key conditions and diseases, which are central to improving quality of services to patients.


image Management of medicines – a resource to support implementation of the wider aspects of medicines management for the NSFs for diabetes, renal services and long-term conditions.


image National Institute for Clinical Excellence (NICE) – provides patients, health professionals and public with guidance on best practice for some medicines and treatments


image The expert patient programme – NHS-based training initiative that provides people with new skills to manage their condition.


image The medicines partnership programme, which supports patients and professionals to enable patients to be more involved in decisions about their medicines.


These priorities are proposed to give patients informed choice and control over care, allowing medicines management to be more personalized and encourages patients, health professionals to work together.



Polypharmacy


There is no widely accepted definition, but in the UK when four or more medicines are prescribed for an individual this is considered as polypharmacy (DH 2001). A child with multiple diseases and complicated medicine regimes may affect a child and their family’s ability to manage their own medication regime.


The reasons for polypharmacy are:



image multiple pathologies – a child may have more than one condition


image multiple prescribers – patients may see several doctors and nurses each of whom may prescribe


image self medication – some children may take over-the-counter, herbal and homeopathic medicines given by their parents or carers


image misuse – there may be confusion following discharge and patients may continue to take their previous regime as well as the new regime


image expectations – many patients (parents) expect to leave a consultation with a prescription in their hand.


There needs to be improvement in this area of medicines management:



image non-compliance with prescribed medications


image large quantities of unused medicines returned to pharmacies


image increase in admissions attributed to adverse drug reactions


image poor control of chronic conditions despite effective medicines being available


image unmet patient and carer needs for information concerning treatment


image poor review of treatment


image patients not tolerating side effects that affect their quality of life.


The nurses’ role in improving medicines management:



image Ensuring treatment is evidence based – using the NICE guidelines to ensure consistence of care, involvement of a nurse specialist or nurse prescriber.


image When treatments are stopped – the nurse needs to co-ordinate care to ensure unwanted medicines are not continued to be prescribed.


image Identify where under treatment is occurring – children may benefit from additional medicines and identify where under treatment is occurring


image Managing the introduction of new drugs – nurses need to be involved in decisions regarding new treatments, this will involve examining the evidence of effectiveness, the clinical significance of benefit, advantages over existing treatment and cost-effectiveness.


image Monitoring medicine taking – conducting a medication review, encouraging discussion between the health care professional and the child and parent and offer the an opportunity to ask questions such as:


– are medicines being taken?

– are they being taken correctly?

– does the child or parent understand how to take their medication?

– will a change in dose affect the child’s lifestyle in any way?

image Treatment review – some people have reported not being asked about their medicines by their doctor or other health care professional.



Concordance


Concordance advocates a partnership approach to medicine prescribing and taking, and suggests:



image Negotiation between equals.


image It must be recognized that children and parents can make their own decisions about whether or not to take a prescribed treatment.


image That it must be acknowledged that well-informed children and parents may decline treatment after learning about the relative benefits and risks.


image That a child/parents’ beliefs about their medicines are likely to be the most important consideration in whether to take their medications or not.


image More involvement of the child and parents.


Concordance means:



image Children and parents should have enough knowledge to participate as partners:


– children and parents are helped to access information about their condition

– the relevant medication which is based on their needs, clear, accurate and in sufficient detail

– children and parents need information about:

• what the medication is for and what it does

• how to use it

• the dos and don’ts

• side effects and what to do about them

• how to tell if the medicine is working

• information about the disease or condition

• this information will need to be tailored to individuals

image Prescribing consultations involve the child and their parents as partners:


– children and parents are involved in treatment decisions

• children and parents are invited to talk about their diagnosis and to express any concerns

• professionals explain the agreed treatment fully

• children and parents are invited to talk about their understanding of and ability to follow treatments.

– children and parents are supported in taking medication:

• all opportunities are used to discuss medicines and medicine taking

• children and parents are asked for their views on how their treatment is progressing

• information is effectively shared between professionals

• medicines are reviewed regularly with child and parents

• practical issues in taking medicines are addressed.


Compliance


Compliance describes the patients’ medicine taking in relation to the prescribers’ instructions. The reasons for non-compliance (BNF 2008) can be complex but involves the following:



image difficulty in taking the medication


image child or parents forgets


image child and parents make a conscious decision not to take the medicine


image treatment regime is complicated, instructions and purpose of medication unclear


image unpleasant taste, side effects are perceived to be risky


image child and parents are having difficulty coming to terms with the diagnosis


image complicated lifestyle


image certain health beliefs of the family


image a child and families support network


image the cost of the medicines


image breakdown in communication between services e.g. hospital and home


image poor knowledge levels.



6.3 Classification of drugs used in children


The classification of drugs (Table 6.1) is massive and is thus too huge to do it all justice. The classes of drugs outlined in this section are brief. However, there are many texts (Neal 2004, Galbraith et al 2007, BNF for children updated twice per year) that go into much more detail regarding the drugs used in children. For further information it is recommended that you use these and/or others for more in-depth information.


Table 6.1 Classes of drugs







































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Related posts:

  1. 1: General principles of children’s nursing
  2. 2: Assessment and investigations of a child
  3. 4: Common conditions in children and reasons for admission
  4. 3: Children’s nursing interventions

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Jun 15, 2016 | Posted by in NURSING | Comments Off on 6: Drug administration

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Class of drug Action of drug class
Anti-emetic Nausea, vomiting
Anti-coagulant Prevent or reduce clotting of the blood in blood vessels, e.g. heparin or warfarin
Antiplatelet Decrease platelet aggregation – aspirin and dipyridamole
Antihypertensive Used to reduce blood pressure – examples are beta-adrenergic antagonists (beta blockers) such as atenolol, ACE inhibitors such as captopril, calcium channel blockers, e.g. nifedipine and diuretics such as bendrofluazide
Analgesic Relieves pain
Hypnotic Induces sleep – dependency producing, e.g. triazolam.
Anxiolytic Relieves anxiety – used to alleviate acute and severe anxiety states, e.g. diazepam
Anaesthetic Insensible stimuli – loss of sensation
Local anaesthesia – sensory nerve impulses are blocked and the patient remains alert
General anaesthesia – loss of consciousness and patient is unaware of and unresponsive to painful stimulation, can be maintained by inhalation of anaesthetic gases
Antibiotic Anti-bacterial: length of treatment depends on the nature of the infection and the response to treatment, e.g. penicillin, ampicillin, erythromycin, metronidazole and vancomycin
Antacids Neutralize the acidity of the gastric juice, given in dyspepsia, gastritis, peptic ulcer and oesophageal reflux
Anti-arrhythmic Given to prevent or reduce cardiac irregularities of rhythm, e.g. digoxin, amiodarone