Pharmacology Case Studies for Nurse Prescribers

Donna Scholefield, Alan Sebti

• Publisher: M Publishing
• Year: 2021
• ISBN:
  9781910451755
• Topic: Medicina
• Subtopic: Enfermería

This new edition of the popular Pharmacology case studies for nurse prescribers has been thoroughly revised in the light of the latest research and guidance from NICE, the British National Formulary (BNF), the Royal Pharmaceutical Society, the Nursing and Midwifery Council and the Royal College of Nursing. While the first edition was aimed at students undertaking the non-medical prescribing modules, this updated text has broadened its scope and is relevant to all trainee and qualified nurse prescribers. There are new and additional chapters on pregnancy and breastfeeding, sexual health and contraception, and prescribing for frailty syndrome in the elderly. The latest developments in pharmacology (such as the emergence of biosimilar drugs) are included in the text; and all the chapters from the first edition have been revised and updated by expert healthcare practitioners.Meanwhile, the practical approach and helpful features that made the first edition so popular remain unchanged. The authors offer a basic introduction to pharmacological concepts, embedded in specific conditions, through case studies and self-assessment questions. By utilising a case study approach, they enable the reader to link pharmacological concepts with clinical practice. Reading this book, and carrying out the numerous self-assessment activities, will give the reader an appreciation of the value of having a sound pharmacological knowledge base in order to deliver safe practice, effective prescribing and improved patient care.Praise for the first edition: 'A useful and practical accompaniment for those studying nurse prescribing, this textbook is also a valuable resource for practitioners qualified in this extended role and those who prescribe and administer medications daily.'Valerie McGurk, Practice Development Nurse, Nursing Management'This book is a comprehensive collection of case studies on a number of conditions, from heart failure to eye problems.'Lynda Gibbons, Registered Advanced Nurse Practitioner, Emergency Nurse

1

How the body affects drugs

Dr Kaicun Zhao

PhD, MSc, MB, Clinical Pharmacology

Alan Sebti

BPharm, DipPharmPrac, Principal Pharmacist – Pharmacy Procurement, Royal Free London NHS Foundation Trust, London

This chapter:

Discusses the advantages and disadvantages of different routes of drug administration

Explains the main principles of drug absorption and the importance of these processes to the prescriber

Explores how drugs are metabolised and excreted, as well as factors influencing these processes

Demonstrates the importance of understanding the pharmacokinetics of a drug and how this knowledge assists safe and effective prescribing.

Introduction

Pharmacology includes the pharmacodynamic and pharmacokinetic study of drugs. Pharmaco-dynamics refers to the actions of drugs on different organs, tissues and biological systems, mediated through various mechanisms of action. The drug actions lead to effective correction of pathological conditions. Pharmacokinetics refers to the kinetic behaviour and disposition of drugs in the body – in other words, how the body affects the drug, either chemically or physically. The drug actions and their underlying mechanisms will be addressed in subsequent chapters. This chapter will focus specifically on pharmacokinetics.

For a drug to exert its therapeutic effects, it must reach its target site in an appropriate concentration. From a pharmaceutical formulation to a molecule acting on the target site, a drug must travel through various physical barriers. As drugs are foreign compounds, they have to enter the body and are eventually excreted by it. During this journey through the body, the drug will be affected by various biochemical environments. Generally, the journey involves several processes, namely absorption, distribution, metabolism and excretion (ADME). Figure 1.1 (below) is a schematic representation of a drug’s progress through a biological body.

Figure 1.1: The processes undergone by a drug as it travels through a biological body; po (oral), im (intramuscular), GI (gastrointestinal), iv (intravenous)

Blood drug concentration

In clinical practice, it is difficult or impossible to measure or monitor drug concentration in tissues. However, the tissue concentration of the drug is proportional to the blood level of the drug. Since the blood level is generally easier to measure, it is commonly used as a proxy marker for the tissue concentration. Blood drug concentration is therefore an important indicator for studying and monitoring drug pharmacokinetic properties.

Pharmacokinetic parameters

To obtain effective drug concentration whilst minimising toxicity, it is essential to give the right dose. Designing an appropriate dosage regimen for a drug requires a basic understanding of the drug’s fate in the body, including the way it is absorbed, distributed, metabolised and excreted. The fate of a drug in a biological body is described by its pharmacokinetic parameters. Generally, these parameters are derived from studies involving serial measurements of plasma concentration at various periods after administration of the drug. It is not within the scope of this book to discuss the calculation of the pharmacokinetic parameters. Instead, we will focus on the clinical applications of these parameters. Some key pharmacokinetic parameters and definitions are listed in Table 1.1 below.

Table 1.1: Commonly used pharmacokinetic parameters

Pharmacokinetic parameter	Definition
Cmax	Maximum drug concentration after absorption
Tmax	Time needed to achieve maximum drug concentration
Ke	Drug elimination rate constant
Cl	Systemic clearance of drug from the body
t1/2	Half-life of drug – time taken for 50% of drug to be eliminated from the body
F	Bioavailability of a drug – a measure of both the rate and extent of drug absorption into blood circulation. In day-to-day use, bioavailability is generally used to describe the extent, i.e. the proportion (or percentage) of drug absorbed into blood circulation.
Vd	Volume of distribution – an indicator of the extent of drug distribution into tissues. This is the theoretical volume that would contain the total amount of drug in the body at the same concentration as it is in the blood.

Drug formulations and administration routes

Drugs can be delivered in different ways and in different forms. The administration route and formulation of a drug will influence its fate in the body. In clinical practice, administration route and drug formulation choices are primarily determined by both the physical and chemical properties of the drug, and by the therapeutic demands. Table 1.2 (page 4) lists the most frequently used administration routes and the relevant formulations, with their advantages and disadvantages.

Drug absorption

When a drug is delivered into the body, it will immediately go through absorption. Absorption is the process whereby a drug passes through biological membranes and is transported through tissues to reach the systemic circulation. All administration routes (except the intravenous route) require the drug to go through absorption in order to be transported from the delivery site to the systemic circulation. Intravenous injection will bring a drug directly into the systemic circulation, without the need to go through absorption.

Table 1.2: Drug administration routes and characteristics

Transportation of drugs

Passive diffusion

For a drug to be transported in the biological system, it has to cross the lipid bilayer of cell membranes. Passive diffusion is the most common way in which substances move across the phospholipid bilayer membranes. The vast majority of drugs can be absorbed through this mechanism. In passive diffusion, a drug moves from a high concentration site to a low concentration site without requiring any energy input.

Some relatively large molecule drugs cross cell membranes by passive diffusion via transmembrane proteins that act as carriers, thus facilitating their passage. The drugs still move from the side of high concentration to the side of low concentration without the need for energy. This type of passive diffusion is called facilitated diffusion. As the number of membrane carrier proteins is limited, facilitated diffusion can be subject to saturation and thus inhibited. Some of the cephalosporin antibiotics (such as cephalexin) are absorbed across the intestinal epithelial cells using facilitated diffusion.

Active transport

Some drugs, such as levodopa (used to treat Parkinson’s disease), fluorouracil (anti-cancer drug) and iron salts, are absorbed by active transport. In contrast to passive diffusion, active transport needs specific membrane proteins to act as carriers. As there is a limited number of carrier proteins, the process of active transport can be saturated when the drug concentration reaches a certain level. This absorption process needs energy and can move drugs against a concentration gradient, from lower to higher concentration.

Endocytosis

Endocytosis is another way for drugs to be absorbed. In this process, drugs are engulfed by invaginated cell membrane to form a drug-filled vesicle. They are then transported into the cell, or across epithelial or enterocytic cells, by pinching off the drug-filled vesicle. Endocytosis is an energy-consuming process.

This absorption mechanism only plays a minor role in the transportation of drugs generally, but it is important for some large molecules, particularly for those with high polarity, that cannot pass through the hydrophobic plasma or cell membrane by passive diffusion, such as proteins. Vitamin B12 is an example of a drug that is absorbed across the gut wall, through endocytosis.

Factors affecting drug absorption and drug bioavailability

Many factors can affect the absorption process. It is important to understand these effects, as changes in a drug’s absorption will also cause changes in its bioavailability, and consequently influence its effectiveness or even cause toxicity. Table 1.3 lists some of the most common factors that can significantly affect the absorption of drugs.

Table 1.3: Factors influencing drug absorption

Factors	Influence on drug absorption	Example
Blood flow to the absorption site	•Abundant blood flow to the absorption site will facilitate drug absorption.	•Digoxin bioavailability is increased when gastrointestinal blood flow is increased. Another example is that increased skin temperature increases...

Table of contents

• Title Page
• Copyright
• Contents
• Acknowledgements
• List of contributors
• List of reviewers
• Introduction
• 1. How the body affects drugs
• 2. How drugs affect the body
• 3. Types of adverse drug reactions and interactions
• 4. Understanding and using the British National Formulary
• 5. Adherence
• 6. Pharmacological case studies: Pregnancy and breastfeeding
• 7. Pharmacological case studies: Children
• 8. Pharmacological case studies: Sexual health and contraception
• 9. Pharmacological case studies: Stable angina
• 10. Pharmacological case studies: Hypertension
• 11. Pharmacological case studies: Heart failure
• 12. Pharmacological case studies: Chronic obstructive pulmonary disease (COPD)
• 13. Pharmacological case studies: Neurological disorders
• 14. Pharmacological case studies: Gastrointestinal disorders
• 15. Pharmacological case studies: Urinary incontinence in adults
• 16. Pharmacological case studies: Diabetes
• 17. Pharmacological case studies: Mental health illness
• 18. Pharmacological case studies: Eye problems
• 19. Pharmacological case studies: Complex health needs and polypharmacy
• 20. Pharmacological case studies: Frailty
• 21. Pharmacological case studies: Palliative care
• 22. Insights into professional prescribing
• Glossary
• List of abbreviations
• Index