How drugs work – an introduction to pharmacokinetics and pharmacodynamics
At the end of this chapter, the practitioner will be able to:
Demonstrate the principles of safe medication administration
Understand what pharmacodynamics means
Understand the general principles of pharmacokinetics
Understand what is meant by adverse drug reactions and medication interactions.
Prior to the administration of medication by any route (not just intravenous), the healthcare practitioner must demonstrate an adequate level of knowledge of:
Pharmacokinetics, i.e. the way medication is absorbed, distributed, metabolised and eliminated
Key issues such as patient consent, professional accountability, negligence, and vicarious liability (NMC 2008)
The local healthcare provider’s policy on medicines management
How to calculate drug dosages effectively
The healthcare practitioner must equally demonstrate safe, evidence-based practice, and have due regard for their level of competence and patient safety (Endacott, Jevon & Cooper 2009). To ensure safe administration of medication, it is very helpful to memorise the ‘5 Rs’ checklist (Clayton 1987):
The healthcare practitioner must also be able to demonstrate adequate knowledge of the specific medication that is being administered. This includes:
Action and indications for the medicine being used
Potential medication interactions
Need for patient monitoring (pre-dose, during administration and post-dose)
Normal therapeutic dose and range of doses
Storage, stability, usability (or potential for contamination) and expiry date
Sources of advice and support (e.g. local clinical guidelines, pharmacist, etc.)
Any legislation relating to the type of medicine being administered.
Find and read the following pieces of legislation on www.legislation.gov.uk/. Then consider how each one addresses the administration of medication:
The Medicines Act (1968)
The Misuse of Drugs Act (1971)
Health Act (2006)
Controlled Drugs (Supervision of Management and Use) Regulations (2013)
As a healthcare practitioner, it is important to have a good working knowledge of how medicines work, and how an individual’s body can affect a medication that is administered. Pharmacodynamics focuses on ‘what the medication does to the body’. In most cases, pharmacodynamics is the study of a medication’s interaction with an intended receptor (or target within the body) that binds the medication given to an individual’s physiological system.
For most medicines to work, they must target a receptor in the body, or a particular micro-organism (such as a bacterial infection). A receptor is a specific type of protein that sticks out from a cell’s body. The medication includes a different protein, called a ligand, which can connect with that particular receptor. The two proteins snap together, like pieces in a jigsaw puzzle, and the binding acts like a trigger, setting a course of chemical reactions in motion, and thus beginning the process of combating a disease.
Knowing which sort of ligand to attach to a medicine is an important part of pharmacodynamics. One of the most significant areas of pharmacodynamics is ensuring that medicines are efficient across a wide range of ages and stages of disease. Medicines need receptors to bind to. Medications may therefore need to be created with multiple ligands, which can bind to multiple receptors to cover a broad age range.
Another facet of pharmacodynamics concerns the effects that a medication might have in the body, once it has bound to its intended receptor. Medicines are supposed to change what is happening in the body. For instance, they can alter how a virus is replicating; they can inhibit tumour growth or strengthen the immune system. In the early stages of medication development, pharmacodynamics is used to study the unintended consequences of medicine binding. These side effects might include causing damage to the body’s cells, inducing cell mutation leading to cancerous growths, or (in a worst-case scenario) increasing a disease’s potency.
All our body systems are mediated by control systems, which depend upon genetic makeup, DNA and enzyme production. When an individual receives a medicine, it interferes with these systems, and the interaction of the medication within our body’s cells produces a biochemical or physiological change. To work effectively, the medication given must reach the target cell in the body in either a specific or non-specific way.
Medications work in one of the following ways:
Replacing a deficiency to provide a normal physiological response (e.g. insulin is administered for diabetes mellitus)
Affecting cell growth and division (e.g. chemotherapy is used to target cancer cells)
Changing the way cells work in the body. Most common chronic diseases (such as hypertension, arthritis, heart disease, and some types of mental illness) are caused by cells functioning abnormally. These abnormalities may be caused by cell ageing, genetics and lifestyle issues (such as smoking, lack of exercise, poor eating habits, and environmental stress and pollution). Medications work to target these cell abnormalities.
Pharmacokinetics is essentially the reverse of pharmacodynamics. Pharmacokinetics is the study of what the body does to a drug (medicine). In simple terms this is the study of drug transport through the body (pharma = drug, kinetics = movement) (Endacott, Jevon & Cooper 2009). In order to be effective, the medication needs to be available at the right site, in the right concentration and at the right time.
Medication also needs to be administered using a suitable route, absorbed through the skin, bronchi or gastro-intestinal tract, and distributed to the site of action (generally through the circulation). For intravenous (IV) therapy, the absorption phase of pharmacokinetics is bypassed, as the medicine is being administered directly into the circulatory system, and it is ready to be distributed appropriately. Following distribution, the medication is broken down (metabolised), and finally excreted (or removed) from the body.
Absorption is the movement of the medicine from the administration site into the circulatory system. Essentially, absorption brings the medicine into the bloodstream. The amount of the medicine absorbed and the rate of absorption can vary, depending on certain factors:
The nature of the dosage form (e.g. tablet or capsule)
Whether or not food is present in the stomach
The composition of the gastric/intestinal PH
Whether or not other drugs are being administered at the same time
The mesenteric blood flow.
Bioavailability is the term used to identify the proportion of the administered medication that reaches the circulatory system. Bioavailability refers to the amount of the medication that is available to be distributed to the intended site of action. Drugs administered using an IV route are considered to have 100 per cent bioavailability (Boyd 2013).
When a medication enters the circulatory system, it is diluted and transported around the body. This is known as the distribution phase. Movement from blood to the tissues can be influenced by numerous factors. Plasma protein can bind to medication, meaning that only the unbound portion is free to move from the bloodstream into the tissues, where it has a pharmacological effect. The blood-brain barrier within the nervous system is highly selective for lipid-soluble (fat-soluble) medicines. For example, penicillin diffuses well within body tissues, but does not penetrate well into the cerebrospinal fluid (Boyd 2013). The placenta provides a barrier between the mother and foetus during pregnancy. Some medicines cross the placenta easily (e.g. morphine), whereas others do not.
Metabolism modifies or alters the chemical composition of the medicine, ready for the final phase, excretion. The main site of metabolism is the liver, but other organs or tissues may metabolise medicines, such as the lungs, kidneys, blood and intestine. Not all medications are metabolised – digoxin, for example, is excreted unchanged.
Most medication interactions occur during the metabolism phase; and this can cause unwanted side effects, or increase the action of a medicine. Some medication interactions can be particularly harmful to patients.
What factors do you think predispose some patient groups to medication interaction?