5.the best that can reasonably be hoped for in this
individual patient;
6.the patient’s beliefs and goals.
DRUG HISTORY AND THERAPEUTIC PLAN
In the twenty-first century, a reliable drug history involves
questioning the patient (and sometimes family, neighbours,
other physicians, etc.). What prescription tablets, medicines,
drops, contraceptives, creams, suppositories or pessaries are
being taken? What over-the-counter remedies are being used
including herbal or ‘alternative’ therapies? Does the patient
use drugs socially or for ‘life-style’ purposes? Have they suf-
fered from drug-induced allergies or other serious reactions?
Have they been treated for anything similar in the past, and if
so with what, and did it do the job or were there any prob-
lems? Has the patient experienced any problems with anaes-
thesia? Have there been any serious drug reactions among
family members?
The prescriber must be both meticulous and humble, espe-
cially when dealing with an unfamiliar drug. Checking
contraindications, special precautions and doses in a formu-
lary such as the British National Formulary (BNF) (British
Medical Association and Royal Pharmaceutical Society of
Great Britain 2007) is the minimum requirement. The proposed
plan is discussed with the patient, including alternatives,
goals, possible adverse effects, their likelihood and measures
to be taken if these arise. The patient must understand what is
intended and be happy with the means proposed to achieve
these ends. (This will not, of course, be possible in demented
or delirious patients, where discussion will be with any
available family members.) The risks of causing harm must
be minimized. Much of the ‘art’ of medicine lies in the ability
of the prescriber to agree to compromises that are accept-
able to an individual patient, and underlies concordance
(i.e. agreement between patient and prescriber) with a thera-
peutic plan.
Prescriptions must be written clearly and legibly, conform-
ing to legal requirements. Electronic prescribing is currently
being introduced in the UK, so these are changing. Generic
names should generally be used (exceptions are mentioned
later in the book), together with dose, frequency and duration
of treatment, and paper prescriptions signed. It is prudent to
print the prescriber’s name, address and telephone number to
facilitate communication from the pharmacist should a query
arise. Appropriate follow up must be arranged.
FORMULARIES AND RESTRICTED LISTS
Historically, formularies listed the components of mixtures
prescribed until around 1950. The perceived need for hospital
formularies disappeared transiently when such mixtures
were replaced by proprietary products prepared by the
pharmaceutical industry. The BNF summarizes products
licensed in the UK. Because of the bewildering array, includ-
ing many alternatives, many hospital and primary care trusts
have reintroduced formularies that are essentially restricted
lists of the drugs stocked by the institution’s pharmacy, from
which local doctors are encouraged to prescribe. The objec-
tives are to encourage rational prescribing, to simplify pur-
chasing and storage of drugs, and to obtain the ‘best buy’
among alternative preparations. Such formularies have the
advantage of encouraging consistency, and once a decision
has been made with input from local consultant prescribers
they are usually well accepted.SCIENTIFIC BASIS OF USE OF DRUGS IN
HUMANSThe scientific basis of drug action is provided by the discipline
of pharmacology. Clinical pharmacology deals with the effects
of drugs in humans. It entails the study of the interaction of
drugs with their receptors, the transduction (second messen-
ger) systems to which these are linked and the changes that
they bring about in cells, organs and the whole organism.
These processes (what the drug does to the body) are called
‘pharmacodynamics’. The use of drugs in society is encom-
passed by pharmacoepidemiology and pharmacoeconomics –
both highly politicized disciplines!
Man is a mammal and animal studies are essential, but
their predictive value is limited. Modern methods of molecu-
lar and cell biology permit expression of human genes, includ-
ing those that code for receptors and key signal transduction
elements, in cells and in transgenic animals, and are revolu-
tionizing these areas and hopefully improving the relevance
of preclinical pharmacology and toxicology.
Important adverse effects sometimes but not always occur
in other species. Consequently, when new drugs are used to treat
human diseases, considerable uncertainties remain. Early-phase
human studies are usually conducted in healthy volunteers,
except when toxicity is inevitable (e.g. cytotoxic drugs used
for cancer treatment, see Chapter 48).
Basic pharmacologists often use isolated preparations,
where the concentration of drug in the organ bath is controlled
precisely. Such preparations may be stable for minutes to
hours. In therapeutics, drugs are administered to the whole
organism by a route that is as convenient and safe as possible
(usually by mouth), for days if not years. Consequently, the
drug concentration in the vicinity of the receptors is usually
unknown, and long-term effects involving alterations in receptor
density or function, or the activation or modulation of homeo-
static control mechanisms may be of overriding importance.
The processes of absorption, distribution, metabolism and elim-
ination (what the body does to the drug) determine the drug
concentration–time relationships in plasma and at the recep-
tors. These processes comprise ‘pharmacokinetics’. There is
considerable inter-individual variation due to both inherited4 INTRODUCTION TO THERAPEUTICS