Endocrinology: Basic and Clinical Principles, Second
Edition aims to provide a comprehensive knowledge
base for the applied and clinical science of
endocrinology. The challenge in its presentation was
to produce a volume that was timely, provided integration
of basic science with physiologic and clinical principles,
and yet was limited to 500 pages. This length
makes the volume suitable as a text; and the timeliness
we have striven for allows the book to serve as an offthe-
People who pursue careers in Internal Medicine are drawn to
the specialty by a love of patients, mechanisms, discovery,
education, and therapeutics. We love hearing the stories told
to us by our patients, linking signs and symptoms to pathophysiology,
solving the diagnostic dilemmas, and proposing
strategies to prevent and treat illness. It is not surprising
given these tendencies that internists prefer to continue their
life-long learning through problem solving.
This book is offered as a companion to the remarkable
17th edition of Harrison’s Principles of Internal Medicine.
Clinical pharmacology comprises all aspects of the scientific study of drugs in man. Its objective is to optimise drug therapy and it is justified in so far as it is of practical use.
Over recent years pharmacology has undergone great expansion resulting from technology that allows the understanding of molecular action and the capacity to exploit this. The potential consequences for therapeutics are enormous. All cellular mechanisms (normal and pathological), in their immense complexity are, in principle, identifiable.
Five years have passed since the first edition of
Principles of Clinical Pharmacology was published. The
second edition remains focused on the principles
underlying the clinical use and contemporary development
of pharmaceuticals. However, recent advances in
the areas of pharmacogenetics, membrane transport,
and biotechnology and in our understanding of the
pathways of drug metabolism, mechanisms of enzyme
induction, and adverse drug reactions have warranted
the preparation of this new edition.
Functional magnetic resonance imaging (fMRI) represents one of the
most advanced and enlightening functional imaging techniques that
has ever been developed. The past ten years (1990–2000) of scientific
research has been designated the decade of the brain and has led to
numerous technological developments and the establishment of fundamental
clinical protocols to understand brain functions. The next
decade, the beginning of the 21st century, will continue the great
momentum of brain research.
For otolaryngology–head and neck surgeons in training as
residents and fellows, it is a difficult task to keep up with
all of the advances in the basic and clinical sciences that
impact the medical and surgical practice of their specialty.
It is also pertinent to the practice of otolaryngology–head
and neck surgery for interested medical students and lecturers
in medical school faculties who teach students and
resident physicians to have a reference book that clearly
presents the basic principles.
Psychiatrists and diverse other mental health and broader healthcare professionals
are faced with many challenges in effectively evaluating and treating
persons with psychiatric illnesses and substance use disorders. Resources are
often stretched thin, especially for those with the most serious and disabling
conditions, and many people who would benefit from treatment are untreated,
undertreated, or treated only after extended delays for complex reasons.
Clinicians clearly have difficulties and barriers in their efforts to provide
comprehensive, efficacious, and timely treatment.
Deliberate and accidental self-poisoning Principles of treatment Poison-specific measures General measures Specific poisonings: cyanide, methanol, ethylene glycol, hydrocarbons, volatile solvents, heavy metals, herbicides and pesticides, biological substances (overdose of medicinal drugs is dealt with under individual agents) Incapacitating agents: drugs used for torture
drugs, and psychotropic drugs is increasing. Repeated episodes are not rare.1 Prescribed drugs are used in over 75% of episodes but teenagers tend to favour nonprescribed analgesics available by direct sale, e.g.
Antiepilepsy drugs: principles of management; withdrawal of therapy; pregnancy; teratogenic effects; epilepsy in children; status epilepticus • Individual drugs: carbamazepine, phenytoin, sodium valproate, lamotrigine, vigabatrin, gabapentin, clonazepam, topiramate, levetiracetam. • Parkinsonism Objectives of therapy Drug therapy; problems of long-term treatment • Other disorders of movement • Tetanus
cortical neurons simultaneously (primary generalised seizure). Bromide (1857) was the first drug to be used for the treatment of epilepsy, but it is now obsolete.
Harrison's Internal Medicine Chapter 5. Principles of Clinical Pharmacology
Principles of Clinical Pharmacology: Introduction
Drugs are the cornerstone of modern therapeutics. Nevertheless, it is well recognized among physicians and among the lay community that the outcome of drug therapy varies widely among individuals. While this variability has been perceived as an unpredictable, and therefore inevitable, accompaniment of drug therapy, this is not the case.
Principles of Pharmacokinetics The processes of absorption, distribution, metabolism, and excretion— collectively termed drug disposition—determine the concentration of drug delivered to target effector molecules.
When a drug is administered orally, subcutaneously, intramuscularly, rectally, sublingually, or directly into desired sites of action, the amount of drug actually entering the systemic circulation may be less than with the intravenous route (Fig. 5-2A ).
Clinical Implications of Altered Bioavailability Some drugs undergo near-complete presystemic metabolism and thus cannot be administered orally. Nitroglycerin cannot be used orally because it is completely extracted prior to reaching the systemic circulation. The drug is therefore used by the sublingual or transdermal routes, which bypass presystemic metabolism.
Some drugs with very extensive presystemic metabolism can still be administered by the oral route, using much higher doses than those required intravenously.
Clinical Implications of Drug Distribution Digoxin accesses its cardiac site of action slowly, over a distribution phase of several hours. Thus, after an intravenous dose, plasma levels fall, but those at the site of action increase over hours. Only when distribution is near-complete does the concentration of digoxin in plasma reflect pharmacologic effect. For this reason, there should be a 6–8 h wait after administration before plasma levels of digoxin are measured as a guide to therapy.
Therapeutic Interventions Based on Genetic Risk for Disease Specific treatments are now available for an increasing number of genetic disorders, whether identified through population-based screening or directed testing (Table 64-2). Although the strategies for therapeutic interventions are best developed for childhood hereditary metabolic diseases, these principles are making their way into the diagnosis and management of adult-onset disorders. Hereditary hemochromatosis illustrates many of the issues raised by the availability of genetic screening in the adult population.
Principles of Vaccine Use
Route of Administration
Microbes differ in their routes of infection, patterns of transmission, and predispositions for certain age groups. The route of vaccine administration (oral, intranasal, intradermal, transdermal, subcutaneous, or intramuscular) takes these factors into account in order to maximize protection and minimize adverse events. Vaccine development is more a pragmatic undertaking than an exact science, guided only in part by immunologic principles and shaped largely by the results of clinical trials.
Principles of Dose Selection The desired goal of therapy with any drug is to maximize the likelihood of a beneficial effect while minimizing the risk of adverse effects. Previous experience with the drug, in controlled clinical trials or in postmarketing use, defines the relationships between dose (or plasma concentration) and these dual effects and provides a starting point for initiation of drug therapy.
Figure 5-1 illustrates the relationships among dose, plasma concentrations, efficacy, and adverse effects and carries with it several important implications:
Principles of Genetic Variation and Human Traits (See also Chaps. 62 and 64) Variants in the human genome resulting in variation in level of expression or function of molecules important for pharmacokinetics and pharmacodynamics are increasingly recognized. These may be mutations (very rare variants, often associated with disease) or polymorphisms, variants that are much more common in a population. Variants may occur at a single nucleotide [known as single nucleotide polymorphism (SNP)] or involve insertion or deletion of one or more nucleotides.
Inherited mitochondrial disorders are transmitted in a matrilineal fashion; all children from an affected mother will inherit the disease, but it will not be transmitted from an affected father to his children (Fig. 62-11D ). Alterations in the mtDNA affecting enzymes required for oxidative phosphorylation lead to reduction of ATP supply, generation of free radicals, and induction of apoptosis. Several syndromic disorders arising from mutations in the mitochondrial genome are known in humans and they affect both protein-coding and tRNA genes (Table 62-1 and Table 62-5).
Current recommendations also include influenza vaccine for routine annual administration to individuals with chronic illness at any age, to persons living in the same household as chronically ill individuals, and to all adults 50 years of age. Polyvalent pneumococcal polysaccharide vaccine is similarly recommended for adults ≥65 years of age and for all chronically ill persons.
This fourth revised edition of “Technical Basis of Radiation Therapy: Practical Clinical
Applications”, edited by S. H. Levitt, J. A. Purdy, C. A. Perez, and S. Vijaykumar, continues
this publication’s outstanding excellence in the definition of the technical advances for
radiation therapy. The previous three editions were milestones in the definition of new
technologies and how they would be applied in clinical practice.