As introduced in the previous section, efficacy is the maximal effect produced by a drug. It is related to the ability of a drug to bind with the appropriate receptors to cause a desired effect. It is affected by the route of administration, volume of distribution, and clearance of the drug from the body. Therefore, efficacy of a particular drug can vary among patients depending on drug pharmacokinetics, pharmacodynamics, or both with respect to the individual patient. As the concentration of a drug increases, its effect also increases. However, there is a point when increased drug concentration does not produce any additional effect, which is defined as maximal efficacy. From this dose-response relationship, the value of ED 50 is derived (as stated in Chapter 5, this is the dose at which 50% of patients exhibit the desired effect of the drug). The dose-response relationship is also used to define the lethal dose of medications (again, as stated earlier, LD 50 is the dose that will cause mortality in 50% of the population). This is derived experimentally in rats or mice.

The desired effect of a drug is the effect that treats the patient’s symptoms or disease. In addition to the desired effects, drugs also can produce unwanted effects. When these unwanted effects are mild, they are called side effects and can include a myriad of symptoms such as dry mouth, headache, or nausea. However, these side effects also have the potential to be harmful or toxic and these are known as adverse effects. These adverse effects can be pharmacologic or dose related, meaning that giving an overdose of medication leads to toxic effects. Drugs with a narrow therapeutic index (ratio of LD 50 to ED 50) are more likely to cause adverse effects due to overdose. For example, in anesthesiology, opioid medications (e.g., fentanyl and morphine) are commonly used to treat pain in the perioperative period. Opioids have a dose-related adverse effect of respiratory depression. Therefore, if too high a dose is given to a particular patient, the patient’s respiratory rate will decrease and he or she may stop breathing.

Adverse effects are also related to lack of selectivity of drugs for the desired target. The target may be one organ or system, but the drug has the ability to interact with receptors all over the body, which may produce adverse effects in other organs. One example of this would be β antagonists, which is a drug commonly used in anesthesiology to treat tachycardia and hypertension. β receptors are located all over the body, and blocking all of these receptors may have adverse effects in other systems, such as triggering bronchospasm in patients with reactive airway disease.

Adverse effects can also occur as a result of the metabolism of the drug. If drug breakdown produces a toxic metabolite, this can lead to adverse effects. In an acetaminophen overdose, enzymatic pathways are saturated, and a reactive toxic metabolite is formed, leading to liver injury.

Allergic reactions to drugs are another form of adverse effect, the most severe being anaphylaxis, which is an immediate hypersensitivity reaction. In an anaphylactic reaction, the drug antigen activates the patient’s immune system, causing mast cells to release histamine via an IgE-mediated response. This leads to edema, vasodilation, hypotension, and shock.

When the causes of adverse effects of a drug are not dose related or are unclear, they are called
idiosyncratic reactions and may be due to individual patient characteristics such as metabolism, receptor-drug interaction, immunologic factors, or a combination of multiple factors.