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Reversal (Antagonism) of Neuromuscular Blockade

Key Points ▪ Appropriate reversal of a nondepolarizing neuromuscular blockade is essential to avoid adverse patient outcomes. Complete recovery of muscle strength should be present, and the residual effects of neuromuscular blocking drugs (NMBDs) should be fully pharmacologically reversed (or spontaneously recovered). ▪ Sufficient recovery from neuromuscular blockade for tracheal extubation can be confirmed by an adductor pollicis train-of-four (TOF) ratio of at least 0.90 (or…

Pharmacology of Neuromuscular Blocking Drugs

Key Points ▪ Two different populations of nicotinic acetylcholine receptors exist at the mammalian neuromuscular junction. In the adult, the nicotinic acetylcholine receptor at the postsynaptic (muscular) membrane is composed of α 2 βδε subunits, while the fetal (immature) receptor is composed of α 2 βγδ. The presynaptic (neuronal) nicotinic receptor is a pentameric complex composed of α 3 β 2 subunits. Each of the two…

Intravenous Drug Delivery Systems

Key Points ▪ The pharmacokinetics of anesthetic drugs are described by multicompartment models. Accurate intravenous drug delivery requires adjusting the maintenance infusion rates to take into account the accumulation of the drug in the peripheral tissues. ▪ Biophase is the site of action of a drug. Initiation, maintenance, and titration of intravenous anesthetics must account for the delay in equilibration between plasma and the site of…

Nonopioid Pain Medications

Key Points ▪ With a better understanding of pain pathways and mechanisms, it has been recognized that ion channels play an important role in the transduction, transmission, and modulation of nociceptive signals. This opens a new avenue of developing novel therapeutic agents for the treatment of acute or chronic pain, particularly neuropathic pain. ▪ Although the exact mechanism of action remains unclear for many drugs listed…

Opioids

Key Points ▪ Opioids are a vital part of providing the analgesic component of anesthesia and often form the foundation for postoperative pain management. ▪ Opioids suppress pain by targeting multiple sites throughout the nervous system including action in brain, spinal cord, and peripheral nervous systems. ▪ An increased understanding of the molecular pharmacology of opioid receptors and opioid-induced cellular responses allows utilization of innovative techniques…

Intravenous Anesthetics

Key Points ▪ The introduction of thiopental into clinical practice in 1934 marked the beginning of modern intravenous (IV) anesthesia. Today, IV anesthetics are used for induction and maintenance of anesthesia and sedation in a wide variety of circumstances. ▪ The most commonly used IV anesthetic is propofol, an alkylphenol presently formulated in a lipid emulsion. Propofol provides rapid onset and offset with context-sensitive decrement times…

Inhaled Anesthetics: Delivery Systems

Key Points ▪ The modern anesthesia workstation has evolved into a complex device with a number of safety features. However, if there is any possibility that the workstation or the breathing circuit is a potential cause of difficulty with ventilation or oxygenation, ventilating the patient using an oxygen cylinder and a manual ventilation bag is an appropriate decision. When in doubt, ventilate and oxygenate the patient…

Pulmonary Pharmacology and Inhaled Anesthetics

Key Points ▪ Inhaled anesthetics affect every part of physiology of the lungs and their pulmonary pharmacology is complex. ▪ Volatile anesthetics produce bronchodilation through decreases in cytoplasmic ionized calcium concentration and/or a reduction in calcium sensitivity of airway smooth muscle. Volatile anesthetics also attenuate an increase in pulmonary airway resistance induced by chemical and mechanical stimulation. ▪ Inhaled anesthetics reduce the rate of mucous clearance…

Inhaled Anesthetic Uptake, Distribution, Metabolism, and Toxicity

Key Points ▪ The alveolar anesthetic concentration (F A ) or partial pressure (P alv ) is important because it is the driving force determining anesthetic uptake into blood and target tissues in the central nervous system, and it can be monitored as a readout of anesthetic dosage. P alv is influenced by both delivery and uptake of anesthetic gas. ▪ Inhaled anesthetic delivery to patients…

Inhaled Anesthetics: Mechanisms of Action

Key Points ▪ Anesthesia consists of separable and independent components, each of which involves distinct, but possibly overlapping, mechanisms at different sites in the central nervous system. ▪ The potencies of general anesthetics correlate with their solubility in oil, indicating the importance of interactions with predominantly hydrophobic targets. ▪ General anesthetics act by binding directly to amphiphilic cavities in proteins. Binding sites have been identified by…

Basic Principles of Pharmacology

Key Points ▪ Pharmacokinetics describes the relationship between drug dose and drug concentration in plasma or at the site of drug effect over time. For anesthetic drugs, the processes of distribution and elimination (metabolism and excretion) govern this relationship. ▪ The time course of intravenously administered drugs is a function of distribution volume and clearance. Estimates of distribution volumes and clearances, pharmacokinetic parameters, are derived from…

Renal Anatomy, Physiology, Pharmacology, and Evaluation of Function

Key Points ▪ A molecule in the plasma must pass in succession through the endothelial fenestration, glomerular basement membrane (GBM), and epithelial slit diaphragm to cross the filtration barrier and enter the tubular fluid. The capillary endothelium restricts the passage of cells, while the GBM restricts albumin and larger molecules. The negatively charged glycoproteins of the GBM limit the passage of other negatively charged proteins. Thus,…

Hepatic Physiology, Pathophysiology, and Anesthetic Considerations

Key Points ▪ The liver is the largest abdominal organ and carries out a number of vital functions including metabolism and detoxification. ▪ The liver receives approximately 25% of the resting cardiac output. The hepatic artery is responsible for 25% to 30% of the blood supply to the liver while the portal vein is responsible for 70% to 75%. They each deliver 50% of the total…

Gastrointestinal Physiology and Pathophysiology

Key Points ▪ The gastrointestinal (GI) tract forms a long tube from mouth to anus and its main functions are motility, digestion, absorption, excretion, and circulation. Each component of the GI tract has specific functions. ▪ The layers of the GI tract wall are (outermost to innermost): serosa, longitudinal muscle, circular muscle, submucosa, and mucosa. Within the mucosa is (outermost to innermost): muscularis mucosae, lamina propria,…

Cardiac Physiology

Key Points ▪ The cardiac cycle is the sequence of electrical and mechanical events during a single heartbeat. ▪ Cardiac output is determined by the heart rate, myocardial contractility, and preload and afterload. ▪ The majority of cardiomyocytes consist of myofibrils, which are rod-like bundles that form the contractile elements within the cardiomyocyte. ▪ The basic working unit of contraction is the sarcomere. ▪ Gap junctions…

Respiratory Physiology and Pathophysiology

Key Points ▪ Removal of carbon dioxide (CO 2 ) is determined by alveolar ventilation, not by total (minute) ventilation. ▪ Dead space ventilation can be dramatically increased in patients with chronic obstructive pulmonary disease and pulmonary embolism to more than 80% of minute ventilation. ▪ Breathing at small lung volumes increases airway resistance and promotes closure of airways. ▪ Hypoxemia can be caused by alveolar…

Neuromuscular Physiology and Pharmacology

Key Points ▪ The neuromuscular junction contains the distal nerve terminal, Schwann cell, synaptic cleft, and muscle end plate, which together provide an array of receptors and substrates for drug action. Neuromuscular transmission is predominantly dependent on acetylcholine as the natural transmitter. Acetylcholine, when released from the prejunctional nerve terminal, binds to acetylcholine receptors (AChRs) that are present either prejunctionally or postjunctionally within the neuromuscular junction…

Cerebral Physiology and the Effects of Anesthetic Drugs

Key Points ▪ The brain has a high metabolic rate and receives approximately 12% to 15% of cardiac output. Under normal circumstances, cerebral blood flow (CBF) is approximately 50 mL/100 g Gray matter receives 80% and white matter receives 20% of this blood flow. ▪ Approximately 60% of the brain’s energy consumption supports electrophysiologic function. The remainder of the energy consumed by the brain is involved…

Sleep Medicine

Key Points ▪ Sleep is a dynamic neuronal and behavioral state that can be characterized using specific electroencephalographic, electrophysiologic, and behavioral findings. ▪ Characteristics of sleep can be quantified using questionnaires, actigraphy, or respiratory polygraphy. However, polysomnography, including electroencephalogram, electrooculogram, submental electromyogram, and analysis of breathing, is required to describe the cortical characteristics and immediate physiological consequences. ▪ Activation of hypothalamic sleep-promoting pathways including the ventrolateral…

Consciousness, Memory, and Anesthesia

Key Points ▪ Mechanisms of consciousness and memory, and their interruption by general anesthetics, are important scientific problems that have clinical relevance for the practice of anesthesiology. ▪ Consciousness is characterized by both wakefulness (i.e., the brain being aroused) and awareness (i.e., subjective experience). ▪ Anesthetics act at structures in the brainstem, hypothalamus, and basal forebrain that regulate sleep-wake states, which may account for loss of…