Equine Pharmacology

Cynthia Cole, Bradford Bentz, Lara Maxwell, Cynthia Cole, Bradford Bentz, Lara Maxwell

• Publisher: Wiley-Blackwell
• Year: 2014
• ISBN:
  9781118845158
• Edition: 1
• Topic: Medicine
• Subtopic: Equine Veterinary Science

Equine Pharmacology combines highly practical therapeutic guidance with reliable scientific background information to provide a clinically relevant resource. Taking a body systems approach to the subject, the book offers the equine clinician fast access to drug options for a given disease, with additional information available for reference as needed. Logically organized to lead the reader through the clinical decision-making process, Equine Pharmacology is a user-friendly reference for pharmacological informationon the horse. The book begins with a general review section presenting the principles of antimicrobials, anesthesia, analgesics, anti-parasitics, foals, fluid therapy, and drug and medication control programs. The remainder of the book is devoted to a body systems approach to therapeutics, allowing the reader to search by affected system or specific disease to find detailed advice on drug therapy. Equine Pharmacology is an invaluable addition to the practice library for any clinician treating equine patients.

SECTION II
Therapeutics: A Systems Approach

CHAPTER 10
Clinical pharmacology of the respiratory system

Melissa R. Mazan¹ and Michelle L. Ceresia²

¹ Tufts University, North Grafton, MA, USA

² MCPHS University, Boston, MA, USA

Respiratory anatomy as it pertains to clinical pharmacology

The respiratory system is commonly divided into two sections, the upper respiratory tract (URT) and the lower respiratory tract (LRT). The lung has the privilege of having an extremely large surface area and, in fact, contacts more of the outside environment than does any other epithelial surface of the body. Although the respiratory system has other important functions, such as producing sounds, the vital functions of the respiratory system include the conduction of air, the exchange of oxygen and carbon dioxide, and protecting the respiratory surfaces from infection and exposure to noxious elements.

Upper respiratory tract (URT)

The horse, being an obligate nose breather, lacks an oropharyngeal component, and therefore, the URT is composed of the nasopharynx and the larynx. Cell types found in the URT include pseudostratified epithelium at the proximal portion, progressing to columnar, ciliated, and goblet cells in the more distal portions. Deposition of systemically administered drugs to the URT is not complex, resembling the delivery of such medications to any other simple tissue.

Lower respiratory tract (LRT)

The LRT consists of a conducting system, comprised of the trachea, bronchi, and bronchioles, and the respiratory portion, comprised of the respiratory bronchioles, alveolar ducts, and alveoli. The cells of the LRT change to reflect the functional needs of the respiratory system as air traverses from the trachea to the alveoli. More proximal portions of the LRT, including the trachea and the bronchi, are well endowed with goblet cells to produce mucus and ciliated cells to move the mucus and its entrapped particulates along the well-named mucociliary escalator. This epithelium gives way to a simple squamous epithelium in the alveoli—the type I and type II alveolar epithelium. The alveolar type I cells are thin and simple, ideally suited for the exchange of gases. The alveolar type II cells are much larger and specialize in producing surfactant. The gas exchange surface also includes the endothelial cells lining the capillaries that accompany the alveoli and the basement membrane in which the basal lamina is shared between the epithelium and the endothelium.

Anatomy of the pleura

Each lung occupies a pleural cavity lined by a serous membrane that folds back upon itself to envelope the lung. The external layer is termed the parietal pleura, and the layer that adheres to the lung is called the visceral pleura. The production of a small amount of pleural fluid prevents friction between the two layers.

Respiratory tract defense system

The respiratory tract defense system is comprised of anatomical barriers, as well as the innate and adaptive immune systems. The horse's nose provides the first obstacle to foreign particles. The ornate scrollwork of the turbinates, as well as hairs that line the proximal portion of the nasal passages, physically removes large particulates. Moving more distally, there are mucus production and the cilia that serve to sweep the mucus and its engulfed debris proximally until it is ejected from the respiratory system. The innate immune system includes such nonspecific defenses as antimicrobial peptides, complement, and reactive oxygen species that are produced by phagocytic cells. Macrophages, located in the alveoli and within the interstitium, can phagocytize foreign material, including bacteria, to remove it from the body. Another important component of the lung's defense system is the cough. Triggered by irritants, such as chemical vapors, high air flows, and particulates, it helps the lungs expel noxious material. As with other organs, the lung mounts both cellular and humoral adaptive immune responses with lymphoid tissue distributed throughout the system and foci in the nares, larynx, and bronchioles. The nasopharynx, for example, is responsible for the production of IgA, one of the first lines of defense against an inhaled pathogen.

Considerations for distribution of drugs to the respiratory system

The anatomy of the respiratory system becomes important when we consider which drugs to use in targeting a particular infection or disease. Many studies in humans and other animals and now a series of studies in horses have shown that serum antimicrobial concentrations are not good indicators of drug concentrations in the lung [1, 2]. Moreover, drug concentrations in one section of the lung, for instance, the pulmonary epithelial lining fluid (PELF), may not reflect concentrations achieved in the parenchyma or even the bronchial epithelium. Nevertheless, the PELF concentration is the best indicator of a drug's penetration into the respiratory system. Beyond the anatomy of the respiratory system, drug-specific factors, including protein binding and tissue penetration, also affect the disposition of drugs to the lungs.

The means by which the horse has acquired a respiratory tract infection has important implications for treatment. Many infections are acquired by inhalation, for example, pneumonia secondary to esophageal obstruction or “shipping fever” pneumonia associated with high levels of particulates and microbes in the air during long-distance transport. Blood-borne pneumonia is less common in adult horses but relatively frequent in foals with septicemia. These distinctions help to determine if the infection is systemic, making it is necessary to consider drug distribution to the rest of the body, or if the infection is localized to the lung, and therefore, the lung is the primary target.

When treating infections of the LRT, it is important to consider where the infection is located—in the airway, in the interstitium, or in the alveolar space itself, as these spaces are anatomically and physiologically very different. Somewhat counterintuitively, distribution of systemically administered drugs is actually greater to the airways than to the alveolar space. This is because delivery of an antimicrobial to the airway is a relatively simple process of diffusion from the capillaries to the bronchial mucosa. In contrast, although the capillary endothelium is quite permeable, the alveolar epithelium is well supplied with zonula occludens, which prevent many substances, including many antimicrobials, from crossing the alveolar barrier. This is commonly termed the blood–bronchial barrier.

The disease state itself also strongly affects drug penetration into the respiratory system. Inflammation, which routinely accompanies infection, causes vasodilation that enhances drug delivery. However, inflammation can also increase the thickness of important barriers, such as the alveolar epithelium that will impair drug delivery. Other factors that enhance the penetration of drugs to the lung include high lipophilicity, low protein binding and ionization, and a relatively basic pKa. These characteristics improve passive diffusion through any membrane, but are particularly important in the face of the tight junctions that predominate in the lung [3].

Infectious diseases of the LRT

Bacterial pneumonia

There are two major presentations of bacterial infections in the lungs: juvenile bronchopneumonia and adult pneumonia/pleuropneumonia; the latter is also known as “shipping fever” pleuropneumonia. Juvenile bronchopneumonia is quite common in foals less than 8 months old, whereas pneumonia/pleuropneumonia occurs with much less frequency in adult horses. Nevertheless, both the juvenile and adult forms share important similarities: they are most common secondary to physiologic stressors, such as shipping in adults and weaning in foals, viral URT infections, and/or crowded housing. Other risk factors in adult horses include racing and general anesthesia. In both juveniles and adults, the bacterial population is frequently mixed; however, Streptococcus equi subsp. zooepidemicus (Strep. zoo.) will almost always be present. When we consider that risk factors, such as long-distance transport, strenuous exercise, and viral respiratory diseases, all suppress the immune system and that Strep. zoo. is resistant to phagocytosis by both macrophages and neutrophils and causes alveolar macrophage dysfunction and death, the combination of the presence of the bacterium and those risk factors often creates a perfect storm for the development of disease.

Epidemiology and etiology

Adult pneumonia most commonly occurs after an incident that impairs airway defenses, such as long-distance travel, anesthesia, and racing, or that provokes aspiration of oropharyngeal contents, such as esophageal obstruction. Prior viral infection is also an important risk factor. Pleuropneumonia is most often an extension of pneumonia that was either untreated or inadequately treated. In the USA, pleuropneumonia is more common in the late winter and spring in the northeast, when horses are returning from winter stays in Florida, and in the autumn in the south, when horses are making the reverse trip [4]. Juvenile pneumonia is most likely also a result of inhaled microbes or aspiration of oropharyngeal contents but is seen most commonly in the 3–6-month age group, when maternal antibodies are waning and the foal does not yet have its own full complement of antibodies. Adult and juvenile pneumonia and pleuropneumonia in adults all have moderate to good prognoses with prompt and appropriate treatme...