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keeping the channel open for longer, thereby further inhibiting neuronal activity.

As with enzymes and ion channels, the drugs that bind transport molecules tend to inhibit the transport when they bind. This alters cell function by interfering with the distribution of ions across the cell membrane, thereby altering membrane potential. The cardiac glycoside drug digoxin, used to treat cardiac failure, acts by binding to a transport molecule – the sodium/potassium ATP‐ase or sodium/potassium pumps on the cell membranes of cardiac muscle cells. Digoxin inhibits the function of the sodium/potassium pumps, leading to an accumulation of sodium ions inside cardiac muscle cells, which in turn results in an accumulation of calcium ions in the cells (the additional intracellular sodium ions stimulate another transporter, which pumps sodium ions out of the cell in exchange for calcium ions). The increased level of calcium ions inside the cardiac muscle cells results in stronger contractions, which translates to a stronger, more forceful heartbeat.

Selectivity of binding and its effect

      Some drugs are very selective in their binding sites, and can bind to a very limited number of sites, or only one site, but most drugs will be able to bind to more than one site. For example, a bronchodilator medication that acts as an agonist at adrenergic beta receptors may bind at only beta‐2 receptor subtypes, in which case it would be a selective beta‐2 agonist, but is more likely to bind to both beta‐1 and beta‐2 receptors, because of the degree of chemical similarity between the two receptor subtypes. The more selective a drug is for a single receptor, the fewer effects it is likely to bring about, so a more selective drug is likely to be one with fewer side‐effects. On the other hand, a less selective drug which activates two or three related receptors may have more therapeutic uses, but it will also have more side‐effects. The selectivity of a drug will tend to decrease as the dose increases, because binding to other receptor types will become more likely as the concentration of the drug increases. This helps to explain the dose dependency of many side‐effects of medications.

      Clinical considerations

      Salbutamol, also known as albuterol, is a beta‐2 receptor agonist and is frequently administered in the out‐of‐hospital setting for management of bronchospasm. It can also be used in the management of hyperkalaemia because it stimulates the transport of potassium ions from the blood into skeletal muscle cells. This effect is also mediated by the action of salbutamol on beta‐2 receptors.

      Many patients who have been prescribed salbutamol may have already self‐administered their own ‘puffer’ prior to your arrival and may be tachycardic as a result. This is due to binding to beta‐2 receptors in cardiac muscle after absorption of salbutamol into the bloodstream. Tachycardia may predispose the patient to arrhythmias, so regarding these patients as high risk for a cardiac event is warranted.

      Muscle tremors may also occur in these patients, due to binding of the drug to beta‐2 receptors in skeletal muscle. Although the drug is quite selective for beta‐2 receptors, it will also bind to beta‐1 receptors at high doses, so if the patient has used their puffer very extensively prior to your treatment, there may be additional tachycardia due to an action on beta‐1 receptors in the heart, increasing cardiac risk.

The drug–body interaction is a dynamic process

      The interaction between any administered drug and the person it is administered to is dynamic. From the moment it is administered, the drug will be moving from its administration point to other compartments of the body, being absorbed into the bloodstream, and leaving the blood to enter other tissues or other body compartments, so the concentration of the drug in the blood and in various tissues and body compartments will be changing. As the drug passes through the liver, it will be acted on by metabolic enzymes which will convert it to a different form, which may be more or less pharmacologically active, but certainly more water soluble. The drug travelling in the blood will also be filtered by the kidneys, and the water‐soluble form of the drug will be trapped there and excreted in the urine.

As the drug is being carried around the body, some of it will arrive at and bind to its sites of action, producing its effects. Even the binding of the drug to its receptors is a dynamic process, akin to molecules playing musical chairs with the receptors – molecules of the drug will bind and detach and bind again rather than simply binding and remaining in place. Each time the molecule detaches from its binding site, it may be whipped away and metabolised, and its place on the receptors may be taken by another, competing molecule. This constantly changing relationship between the drug and the living system it has been introduced into explains a great deal about how drugs have their effects. The delay between administration and action of a drug, the duration of action of the drug, and the ability to reverse or overcome the actions of one drug by giving another drug are all the result of this dynamic interaction between drug and living system.

      For the paramedic administering drugs into a system which may be free of other drugs but more likely already contains some pharmacological agents, this constantly changing effect of the drug on the patient will require you to have a good enough grasp on what these agents can do, either alone or in combination, to be able to predict and maintain some control over their actions.

      One challenge we are always faced with is getting enough of a drug from its site of administration to its site of action for it to have a therapeutic effect. The drug is effectively in a race to reach its site of action and have its effect before it is chemically degraded and removed from the body. A drug which has a highly desirable therapeutic action may turn out to be useless from a clinical point of view if it cannot be delivered to its site of action. So, a drug that is going to stand a chance of being useful would usually possess characteristics which allow it to be easily absorbed into the bloodstream, preferably after oral administration, which in turn would mean that the drug would not be destroyed by the acid of the stomach or digestive enzymes. And although it would probably be subject to metabolism by the liver, the metabolism should not be so rapid that it is almost completely gone after a single pass through the liver (a phenomenon known as first‐pass metabolism), as this would mean that very little of the active drug remained in the bloodstream to circulate after absorption. Other routes of administration might avoid the problem of first‐pass metabolism, but each administration route will have its own advantages and disadvantages.

      Clinical considerations

      Administration of medications in the out‐of‐hospital setting can be challenging due to poor lighting, uncontrolled environment or a chaotic scene. Practising all steps of safe medication administration is key to reducing the risk of error (Chapter 4 discusses medicines management and the role of the paramedic). Ensuring the same routine is exercised every single time you administer any medications will embed safe practice so you do not overlook a crucial step during a high‐acuity incident.

      Hand hygiene is important to prevent introduction of harmful pathogens in the out‐of‐hospital environment. Access to running water may not be practical in the out‐of‐hospital setting, so utilisation of alcohol‐based hand rub is the gold standard in this setting. Healthcare‐associated infections generate significant comorbidity and burden for the patient, the community and the healthcare system. Healthcare‐associated infections are avoidable and simple hygienic practice and aseptic technique are crucial in breaking the chain of transmission from community, to patient and into care settings such as hospitals.

      Intravenous cannulation is a key source for bloodstream infections and risk mitigation efforts, such as use of alcohol‐based hand rub and not touching the area between cleaning the skin and immediately prior to cannulation, should be exercised.

      Other routes of administration which are common in the out‐of‐hospital setting include

      intravenous, intramuscular, topical, intranasal, endotracheal and intraosseous. See Chapter 6 for further discussion.

Once

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