Chapter 1 Clinical pharmacology

The use of drugs¹ to increase human happiness by elimination or suppression of diseases and symptoms and to improve the quality of life in other ways is a serious matter and involves not only technical, but also psychosocial considerations. Overall, the major benefits of modern drugs are on quality of life (measured with difficulty), and exceed those on quantity of life (measured with ease).² In some situations we can attempt both objectives.

Medicines are part of our way of life from birth, when we may enter the world with the aid of drugs, to death, where drugs assist (most of) us to depart with minimal distress and perhaps even with a remnant of dignity. In between these events we regulate our fertility, often, with drugs. We tend to take such usages for granted.

But during the intervals remaining, an average family experiences illness on 1 day in 4 and between the ages of 20 and 45 years a lower-middle-class man experiences approximately one life-endangering illness, 20 disabling (temporarily) illnesses, 200 non-disabling illnesses and 1000 symptomatic episodes: the average person in the USA can expect to have about 12 years of bad health in an average lifespan,³ and medicines play a major role: ‘At any time, 40–50% of adults [UK] are taking a prescribed medicine.’⁴

Over the centuries humans have sought relief from discomfort in ‘remedies’ concocted from parts of plants, animals and other sources; numerous formularies attest to their numbers and complexity. Gradually, a more critical view emerged, recognising the need for proper investigation of medications. In 1690, John Locke⁵ was moved to write, ‘we should be able to tell beforehand that rhubarb will purge, hemlock kill, and opium make a man sleep …’.

Yet it was only in the early years of the 20th century that we began to see the use of specific chemical substances to achieve particular biological effects; that is, the exact science of drug action, which is pharmacology. Subsequently the discipline underwent a major expansion resulting from technology that allowed the understanding of molecular action and the capacity to exploit this. The potential consequences for drug therapy are enormous. All cellular mechanisms (normal and pathological), in their immense complexity, are, in principle, identifiable. What seems almost an infinite number of substances, transmitters, local hormones, cell growth factors, can be made, modified and tested to provide agonists, partial agonists, inverse agonists and antagonists. Moreover, the unravelling of the human genome opens the way for interference with disease processes in ways that were never thought possible before now.

Increasingly large numbers of substances will deserve to be investigated and used for altering physiology to the advantage of humans. With all these developments, and their potential for good, comes capacity for harm, whether inherent in the substances themselves or resulting from human misapplication. Successful use of the power conferred (by biotechnology in particular) requires understanding of the growing evidence base of the true consequences of interference. The temporary celebrity of new drugs is not a new phenomenon. Jean Nicholas Corvisart⁶ (1755–1821) reputedly expressed the issue in the dictum: ‘Here is a new remedy; take it fast, as long as it still works’.

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