Medical Pharmacology at a Glance

Michael J. Neal

• Editore: Wiley-Blackwell
• Anno: 2020
• ISBN:
  9781119548096
• Edizione: 9
• Argomento: Medicina
• Categoria: Farmacologia

The internationally best-selling Medical Pharmacology at a Glance is the ideal companion for all medical and healthcare students, providing a visual overview of pharmacology, and describing the basic principles of drug action, interaction, absorption, and excretion. Clear and accessible chapters organised around common diseases and conditions facilitate efficient clinical learning, and include references to drug classes and side effects, disease pathophysiology, prescribing guidelines, and more.

Now in its ninth edition, this leading guide has been thoroughly updated to reflect current guidelines and drug information. This edition features new and revised illustrations, additional pedagogical tools, and enhanced online content. Widely recognised as both the best introduction to medical pharmacology and the perfect revision tool for USMLE and pharmacology exams, this invaluable guide:

• Covers a wide range of drugs used to treat conditions such as hypertension, anaemias, cancer, and affective disorders
• Explains drug mechanisms and the principles of drug action
• Discusses practical topics including drug misuse, drug indications, and side effects
• Includes a companion website featuring online cases, flashcards, and a list of core drugs

1
Introduction: principles of drug action

Medical pharmacology is the science of chemicals (drugs) that interact with the human body. These interactions are divided into two classes:

• pharmacodynamics – the effects of the drug on the body; and
• pharmacokinetics – the way the body affects the drug with time (i.e. absorption, distribution, metabolism and excretion).

The most common ways in which a drug can produce its effects are shown in the figure. A few drugs (e.g. activated charcoal, osmotic diuretics) act by virtue of their physicochemical properties, and this is called non‐specific drug action. Some drugs act as false substrates or inhibitors for certain transport systems (bottom right) or enzymes (bottom left). However, most drugs produce their effects by acting on specific protein molecules, usually located in the cell membrane. These proteins are called receptors (

), and they normally respond to endogenous chemicals in the body. These chemicals are either synaptic transmitter substances (top left,

) or hormones (top right,

). For example, acetylcholine is a transmitter substance released from motor nerve endings; it activates receptors in skeletal muscle, initiating a sequence of events that results in contraction of the muscle. Chemicals (e.g. acetylcholine) or drugs that activate receptors and produce a response are called agonists (

). Some drugs, called antagonists (

), combine with receptors, but do not activate them. Antagonists reduce the probability of the transmitter substance (or another agonist) combining with the receptor and so reduce or block its action.

The activation of receptors by an agonist or hormone is coupled to the physiological or biochemical responses by transduction mechanisms (lower figure) that often (but not always) involve molecules called ‘second messengers’ (

).

The interaction between a drug and the binding site of the receptor depends on the complementarity of ‘fit’ of the two molecules. The closer the fit and the greater the number of bonds (usually noncovalent), the stronger will be the attractive forces between them, and the higher the affinity of the drug for the receptor. The ability of a drug to combine with one particular type of receptor is called specificity. No drug is truly specific, but many have a relatively selective action on one type of receptor.

Drugs are prescribed to produce a therapeutic effect, but they often produce additional unwanted effects (Chapter 46) that range from the trivial (e.g. slight nausea) to the fatal (e.g. aplastic anaemia).

Receptors

These are protein molecules that are normally activated by transmitters or hormones. Many receptors have now been cloned and their amino acid sequences determined. The four main types of receptor are listed below.

1. Agonist (ligand)‐gated ion channels are made up of protein subunits that form a central pore (e.g. nicotinic receptor, Chapter 6; γ‐aminobutyric acid (GABA) receptor, Chapter 24).
2. G‐protein‐coupled receptors (see below) form a family of receptors with seven membrane‐spanning helices. They are linked (usually) to physiological responses by second messengers.
3. Nuclear receptors for steroid hormones (Chapter 34) and thyroid hormones (Chapter 35) are present in the cell nucleus and regulate transcription and thus protein synthesis.
4. Kinase‐linked receptors are surface receptors that possess (usually) intrinsic tyrosine kinase activity. They include receptors for insulin, cytokines and growth factors (Chapter 36).

Transmitter substances are chemicals released from nerve terminals that diffuse across the synaptic cleft and bind to the receptors. This binding activates the receptors by changing their conformation and triggers a sequence of postsynaptic events resulting in, for example, muscle contraction or glandular secretion. Following its release, the transmitter is inactivated (left of the figure) by either enzymic degradation (e.g. acetylcholine) or reuptake (e.g. norepinephrine [noradrenaline], GABA). Many drugs act by either reducing or enhancing synaptic transmission.

Hormones are chemicals released into the bloodstream; they produce their physiological effects on tissues possessing the necessary specific hormone receptors. Drugs may interact with the endocrine system by inhibiting (e.g. antithyroid drugs, Chapter 35) or increasing (e.g. oral antidiabetic agents, Chapter 36) hormone release. Other drugs interact with hormone receptors, which may be activated (e.g. steroidal anti‐inflammatory drugs, Chapter 33) or blocked (e.g. oestrogen antagonists, Chapter 34). Local hormones (autacoids), such as histamine, serotonin (5‐hydroxytryptamine, 5HT), kinins and prostaglandins, are released in pathological processes. The effects of histamine can sometimes be blocked with antihistamines (Chapter 11), and drugs that block prostaglandin synthesis (e.g. aspirin) are widely used as anti‐inflammatory agents (Chapter 32).

Transport systems

The lipid cell membrane provides a barrier against the transport of hydrophilic molecules into or out of the cell.

Ion channels are ...