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Pulmonary Physiology

This chapter describes the physiology of the respiratory system by detailing the control systems and mechanisms of air movement into and out of the lungs that allow oxygen and carbon dioxide to exchange with blood. Emphasis is placed on those systems where the molecular physiology is understood as these systems constitute targets for the actions of drugs on the respiratory system, both beneficial and harmful. Pulmonary…

Cardiopulmonary Resuscitation

The objective of cardiopulmonary resuscitation CPR) in the critically ill patient is optimization of both oxygen delivery (D o 2 ) and aerobic metabolism. Shock is defined as dysoxia, or an abnormality in tissue oxygenation. The variables altering the clinical state of shock include D o 2 , tissue uptake of oxygen (V̇ o 2 ), and the tissue metabolic rate of oxygen (MR o 2…

Antiarrhythmic Drugs

Historical Perspective The heart, and more specifically the heartbeat, has throughout history served as an indicator of well-being and disease, both to the physician and to the patient. Through one's own heartbeat, one can feel the physiologic manifestations of joy, thrills, fear, and passion; the rigors of a sprint or long-distance run; the instantaneous effects of medications, recreational drugs, or toxins; the adrenaline of a rollercoaster…

Antihypertensive Drugs and Vasodilators

There are probably more than 1 billion people worldwide with raised blood pressure. It is one of the most common chronic medical conditions internationally (US National Center for Health Statistics, 2005), and occurs almost twice as often in African-Americans than in whites. The incidence of hypertension increases with age, with a slightly greater incidence in men than in women. In the United States, hypertension affects about…

Vasopressors and Inotropes

This chapter reviews the pharmacology of vasopressors and inotropes used commonly in acute care settings and comparable new drugs with promising clinical potential. It focuses on the pharmacodynamic properties of the drugs to a greater degree than their pharmacokinetic properties because most of these drugs have short half-lives, are administered by continuous infusion, and are titrated to clinical effect. Relying on landmark studies from the past…

Cardiovascular Physiology: Integrative Function

A thorough understanding of the basic principles of cardiovascular physiology is essential for effective and safe patient management in the perioperative period. This information provides a theoretical rationale for the use of drugs, intravenous infusions, and other therapeutic measures to maintain and optimize vital organ function. The primary role of the circulation is to provide sufficient blood flow to satisfy the metabolic demands of body tissues.…

Cardiovascular Physiology: Cellular and Molecular Regulation

The human heart beats billions of times during the course of a normal life span, with each beat representing the amalgamation of electrical, biochemical, and mechanical events that occur over milliseconds. This chapter reviews the cellular and molecular processes that initiate and maintain blood pressure and blood flow to provide a framework for understanding concepts central to pharmacologic manipulation of the cardiovascular system. Historical Perspective Although…

Neuromuscular Blockers and Reversal Drugs

Historical Perspective The nondepolarizing neuromuscular blocking agent (NMBA) d-tubocurarine has been used for 500 years as a paralyzing poison. In the 16th century, Sir Walter Raleigh reported that hunters in South America were using darts and arrows dipped in curare to paralyze their living targets. Curare, the poison of the plant Strychnos toxifera , and its active component, d-tubocurarine, were isolated in the 1930s. d-Tubocurarine was…

Neuromuscular Physiology and Pharmacology

The neuromuscular junction (NMJ) is among the most studied of all synapses and serves as a prototype for understanding communication between neurons and effector cells within the central and peripheral nervous systems. Complete understanding of the development and function of the NMJ in normal and pathologic states continues to evolve. The introduction of new and powerful research techniques has revealed detailed information about the mechanics of…

Local Anesthetics

Historical Perspective Cocaine, the first local anesthetic, was isolated from leaves of the coca plant, Erythroxylum coca, by Albert Niemann in 1860. The medicinal use of coca had long been a tradition of Andean cultures but it was only after chemical isolation that it became readily available in Europe. Its pharmacologic properties after oral ingestion were investigated and described by Sigmund Freud in his publication Über…

Nonopioid Analgesics

The term nonopioid analgesics seems to imply a motley group of agents self-consciously trying to establish their parity with their famously potent cousins: the opioid family. With contemporary understanding of the complexities of both acute and chronic pain, the importance of a multimodal approach to pain management pharmacotherapy has emerged, and the former outcasts have slowly been incorporated into the armamentarium of the anesthesiologist. With the…

Nonintravenous Opioids

Historical Perspective The use of opium for treating pain dates back to at least ancient Egypt, but the modern opioid era began in 1804 when German pharmacist Friedrich Wilhelm Sertürner discovered the naturally occurring opioid morphine. Morphine and opium were widely sold over the counter in liquid, pill, and powder forms throughout the 19th century, and in 1898 the Bayer Company released the first semisynthetic opioid,…

Intravenous Opioid Agonists and Antagonists

Historical Perspective The white “latex” juice of the poppy plant is the source of more than 20 opiate alkaloids. Opium, a word derived from the Greek word for juice, is the brownish residue observed after the poppy's juice is desiccated. Opiate is the older term classically used in pharmacology to mean a drug derived from opium. Opioid, a more modern term, is used to designate all…

Nociceptive Physiology

Systems Physiology Management of Perioperative Pain Despite significant progress in our mechanistic understanding of the nociceptive system, inadequately treated perioperative pain remains a significant problem. A third of patients undergoing surgery continue to suffer from moderate to severe pain, resulting in personal suffering, protracted recovery including persistent pain after surgery, delayed hospital discharge, and increased morbidity and mortality. Improving the management of postoperative pain remains an…

Thermoregulation : Normal Physiology, Anesthetic Effects, and Perioperative Considerations

Core body temperature is highly regulated in humans by the autonomic nervous system and the hypothalamus. General anesthesia, neuraxial anesthesia and analgesia, and drugs such as opioids all reduce the ability of the hypothalamus to regulate core temperature. Thus without intervention, hypothermia (and, less commonly, hyperthermia) is a common consequence of anesthetic management. In this chapter, we review normal thermoregulation, the mechanisms responsible for anesthesia-related hypothermia…

Autonomic Nervous System Pharmacology

The autonomic nervous system (ANS) maintains homeostasis by integrating signals from peripheral and central sensors to modulate organ perfusion and function. Autonomic “tone” maintains cardiac muscle, visceral organs, and vascular smooth muscle in a state of intermediate function. From this state, rapid increases or decreases in autonomic outflow can adjust blood flow and organ activity in response to the environment. The rapidity of the ANS response…

Autonomic Nervous System: Physiology

Historical Considerations A specialized taxonomy of the autonomic nervous system (ANS) has been developing since the time of Galen ( ad 130–200). In the early 1900s, Langley first referred to the ANS. He used the term sympathetic nervous system (SNS) as described by Willis in 1665, and introduced the second division as the parasympathetic nervous system (PNS) in 1921. Although Langley initially described only the visceral…

Drugs for Neuropsychiatric Disorders

Historical Perspective In 2016, 395 million prescriptions for drugs used in the treatment of mental health were dispensed in the United States. A further 387 million prescriptions were dispensed for other neurologic disorders. Combining these two therapeutic classes, neuropharmacologic agents represent the most prescribed family of drugs, exceeding antihypertensives (721 million), antinociceptives (460 million), antibacterials (270 million), lipid regulators (264 million), and diabetes treatments (224 million).…

Pharmacology of Inhaled Anesthetics

This chapter focuses on the pharmacology of the inhaled anesthetics, including their mechanisms of action and clinical effects (pharmacodynamics). Related pharmacokinetic principles of inhaled anesthetics are covered in Chapter 3 . Historical Perspective Discovery of Inhaled Anesthetics The German physician and botanist Valerius Cordus (1515–1544) described a method for preparing ether by combining sulfuric acid with alcohol, which he called oleum dulci vitrioli or “sweet oil…

Pharmacology of Intravenous Anesthetics

History of Intravenous Anesthesia The concept of blood delivery of medication can be traced to the middle of the 17th century soon after Harvey described the function of the vascular system. Not only did Sir Christopher Wren study blood transfusions in dogs, but he also experimented with intravenous delivery of injected opium solution into these animals via a feather quill. In the mid-19th century, technologic advancements…