19 Basic principles of pharmacology
Additive Effect: Occurs when a second drug with properties similar to the first is added to produce an effect equal to the algebraic sum of the effects of the two individual drugs. Shorthand often used is 1 + 1 = 2.
Agonists: Drugs such as dopamine that attach and activate specific receptors.
Antagonists: Drugs such as naloxone (Narcan) that attach to a specific receptor and do not activate the receptor, but prevent an agonist or body chemical such as a neurotransmitter from stimulating the receptor.
Competitive Antagonist: When the concentration of the antagonist is higher than the agonist concentration resulting in reversal or antagonism of the agonist. Examples include naloxone (Narcan) reversing fentanyl or flumazenil (Romazicon) reversing midazolam (Versed). Shorthand often used is 1 + 1 = 0.
Cross Tolerance: Tolerance to a drug because of an existing tolerance to a similar drug. An example of cross tolerance is a patient who has developed a tolerance to morphine due to repeated administration will also require higher doses of all other opioids as well.
Efficacy of a Drug: Refers to the maximum effect that can be produced by a drug.
Hyperreactivity: An abnormal reaction to an unusually low dose of a drug. For example, patients with Addison disease, myxedema, or dystrophia myotonica have hyperreactivity to unusually low doses of barbiturates.
Hypersensitivity (Anaphylaxis): A drug-induced antigen-antibody reaction. The particular hypersensitivity reaction can be either an immediate (anaphylactic) or a delayed reaction. Hypersensitivity reactions can occur with succinylcholine, antibiotics, and many other drugs that are administered in the PACU (see Chapter 18).
Hyporeactivity: An indication that a person needs excessively large doses of a drug to obtain a therapeutic or desired effect.
Idiosyncrasy: An adverse drug reaction that occurs in a small number of persons and has no correlation to dosage or of type of therapy. Postoperative liver dysfunction following halothane administration is an example.
Pharmacodynamics: The study of the mechanisms of action of drugs and other biochemical and physiologic effects on the body.
Pharmacokinetics: The study of the movement of drugs throughout the body, including the processes of absorption, distribution, biotransformation or metabolism, and excretion.
Potency of a Drug: The dose necessary of a particular drug to produce a specific effect that is designated as the effective dose (ED). When that effect is achieved in a particular percentage of patients, it is quantified as ED50 for 50% of the patients and ED95 for 95% of the patients who show an effect to the drug.
Potentiation: The enhancement of the action of one drug by a second drug that has no detectable action of its own. Shorthand commonly used is 1 + 0 = 3.
Receptors: The portion on or in a cell, usually a protein complex, at which attachment of drugs leads to a physiologic response. The receptors are selective in that they recognize and bind only to specific pharmacologic or physiologic agents.
Synergistic Effect: Addition of a second drug to a drug with properties similar to the first that results in an effect greater than the algebraic sum of the effects of the two individual drugs. Shorthand often used is 1 + 1 = 3.
Tachyphylaxis: An acute drug tolerance—for example, succinylcholine administered by intravenous drip. Over time, a higher drip rate is needed to achieve the necessary response.
Tolerance: A type of hyporeactivity that is acquired during chronic exposure to a drug in which unusually large doses are needed to reach a desired effect. A prime example is a person who has become dependent on opioids and needs larger than normal doses to elicit the desired therapeutic response.
A thorough understanding of the pharmacology of the drugs used in perianesthesia care is necessary to ensure the best outcomes in surgical patients. Anesthesia care continues to evolve, and the judicious use of a number of selective, potent drugs in various combinations represents the cornerstone of current practice. Consequently, a comprehensive review of the principles and concepts of pharmacology is presented in this chapter. The specific actions and uses of drugs related to perianesthesia care are discussed in the physiology chapters in Section II, as are the concepts of anesthetic agents in the chapters in Section III. The pharmacology of individual drugs can be best understood in relation to the physiologic functions they affect and their common clinical applications.
A significant portion of this chapter is dedicated to an overview of drug interactions, because modern anesthesia care requires balancing the administration of multiple drugs throughout the perianesthesia period. These drugs include anesthesia-related agents, the patient’s existing medications, including herbal agents, and other over-the-counter preparations.1 Clinically, at least 10% of the patients for perianesthesia are taking some form of herbal preparation.2 Consequently, knowledge of the principles of pharmacology becomes a meaningful and useful tool in the delivery of nursing care to the patient in the postanesthesia care unit (PACU).
Drug responses
Pharmacokinetic actions
Systemic absorption by various routes of administration
Oral route of administration
When a drug is administered orally, it is absorbed in the small intestine, which has a large surface area. A drug must be lipid soluble to cross the gastrointestinal lining. After such absorption, the drug passes to the liver by way of the portal veins before it can enter the systemic circulation. The liver extracts and metabolizes some of the drug in a process termed the first-pass hepatic effect. The drugs that are particularly subject to this effect are agents such as propranolol, metoprolol, verapamil, chlorpromazine, and morphine; therefore these drugs are administered in much higher doses orally than intravenously.3
Sublingual route of administration
The sublingual route of administration has several important advantages over the oral route, because the sublingual route bypasses the first-pass hepatic effect. This route can be particularly favorable in the PACU for drugs such as nitroglycerin. A nitroglycerin tablet can be placed sublingually in an intubated as well as a cooperative awake patient.4
Subcutaneous and intramuscular routes of administration
These routes of administration require simple diffusion from the site of injection into the systemic circulation and are dependent on blood flow to the injection site. Consequently, these administration routes can result in variations in absorption particularly in the PACU when patients are hypothermic and hypotensive and usually have some peripheral vasoconstriction. Subcutaneous absorption is slow and is reserved for drugs such as insulin or hormones, for which a slow, continuous absorption is advantageous. Intramuscular injections produce a more rapid action and are a common practice in the PACU. In addition, if a patient with a hypothermic condition in the PACU is administered a drug either subcutaneously or intramuscularly, absorption can be delayed. However, when the patient undergoes rewarming, a significant amount of the drug can be rapidly liberated from the injection site, thus causing a large concentration of the drug in the systemic circulation and an exaggerated effect.3
Intravenous route of administration
This route of administration facilitates the delivery of a desired concentration of a drug in a rapid and precise fashion by single bolus injection or continuous infusion. In the PACU, because patients have an intravenous line, it is the most popular means of drug administration.
Aerosolized medications to the respiratory tract
The aerosolized route of administration facilitates direct delivery from inhaled aerosols to a targeted organ, which reduces the systematic drug exposure and side effects. Many aerosol delivery devices can be used for administration of bronchoactive inhaled aerosols. The most commonly used method of administration in the PACU is the aerosolized nebulizer, in which a specific amount of drug is administered in a solution of normal saline and is nebulized with a ventilator or oxygen delivery devices. Other devices for delivery of the drug either orally or nasally via inhalation are the metered dose inhaler (MDI) with or without a holding chamber or spacer device, the small volume nebulizer (SVN), and the dry powder inhaler (DPI). The MDI, SVN, and the DPI devices deliver approximately the same percentage of the drug to the target organ, the lungs, with the MDI increasing the patient flow rates better than the SVN and the DPI.4
Drug distribution
A drug’s distribution in the body is envisioned as entering various defined compartments. A compartment represents a theoretic space. A mathematic model can be used to describe the pharmacokinetics of the disposition of a drug. A two-compartment model is usually used in depiction of a central compartment and a peripheral compartment. The central compartment includes plasma and blood cells and highly perfused tissues such as the heart, lungs, brain, liver, and kidneys. The peripheral compartment represents all other fluids and tissues in the body. With this two-compartment model, a drug can be introduced into the central compartment, move into the peripheral compartment, and then return to the central compartment where removal from the body occurs. The two-compartment model is constructed with the serum concentration versus time and is called the plasma concentration curve. From this curve, the distribution and elimination half-times and other kinetic parameters of the drug can be calculated. A drug like propofol will rapidly distribute into the brain when given intravenously, causing a rapid onset of sedation. It also quickly redistributes from the tissues into the blood, resulting in a short duration of action.5
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