some of its effects by activating an enzyme called adenyl cyclase. Also, anesthetic gases do not bind to receptors in the central nervous system. Antacids do not work by interacting with receptors.13 Q. What are drug agonists and antagonists?
14 A. Drugs produce their effects by altering the function of cells and tissues in the body or organisms such as bacteria. Most drugs have an affinity for a target receptor, which is usually a protein on the cell surface. Once a drug binds to a receptor, it can act as either as an agonist (produces a stimulatory response) or an antagonist (sits on the receptor site and prevents an agonist from binding to the receptor; an antagonist does not produce a therapeutic response).For example, epinephrine in low doses as used in dentistry is an agonist that binds to and activates beta‐2 receptors, resulting in vasodilation of systemic arterioles (Becker and Reed 2012). This vasodilation tends to reduce peripheral resistance and therefore diastolic blood pressure. At the same time, the beta‐1 receptors in the heart are activated to increase cardiac output and systolic blood pressure. These two influences cancel each other out regarding mean blood pressure (Becker and Reed 2012).An example of an antagonist is flumazenil (Romazicon®), which is a benzodiazepine receptor antagonist used as rescue medication in the event of benzodiazepine overdose. It will bind the benzodiazepine receptor (BZR) and prevent the benzodiazepine from attaching. Naloxone (Narcan®) is a narcotic receptor antagonist.
15 Q. What is the difference between drug potency and efficacy?
16 A. Potency is the relationship between the dose of a drug and the therapeutic effect; it is the strength of drug required to produce the desired response. Efficacy refers to the ability of a drug to exert an effect. For example, 500 mg of acetaminophen and 200 mg of ibuprofen both produce the same analgesia and have the same efficacy, but ibuprofen is more potent because it requires a lower dosage.
17 Q. What is the TI of a drug?
18 A. The therapeutic index (TI) is the dose range within which the drug is effective without causing adverse events/effects (Tamargo et al. 2015). The TI or ratio equates the blood level at which a drug causes a therapeutic effect compared to the dose that causes death. To determine drug safety, the drug's TI is calculated by dividing LD50 by ED50. The ED50 is the median effective dose, which is the dose required to produce a specific therapeutic response in 50% of patients. The median lethal dose (LD50) refers to the dose of drug that will be lethal in 50% of a group of animals, not humans. Some drugs (e.g., lithium, digoxin) have a narrow TI so that routine blood tests are necessary to assure the plasma drug level is within the therapeutic range.
19 Q. What is an ADR and why is it important to know?
20 A. An adverse drug reaction (ADR) is defined by the World Health Organization (WHO) as any response to a drug that is noxious, unintended, and occurs when a drug is properly prescribed at doses normally used in humans for the prophylaxis, diagnosis, or therapy of disease. Medical errors are not included in this definition. Bisphosphonate‐induced osteonecrosis of the jaws is an ADR. Other examples of ADRs include drug interactions, allergic reactions and irritating adverse effects of a drug such as gastrointestinal problems (nausea, diarrhea). A drug interaction occurs when the effects of one drug are altered by the effects of another drug, resulting in an increase or decrease in the blood levels of the drug. An allergic reaction due to a drug is an abnormal and unwanted response that ranges from a mild rash to life‐threatening anaphylaxis. An allergic reaction does not often happen the first time you take a medication but is much more likely to occur the next time you take that medication (Shamna et al. 2014). ADRs have a great effect on quality of life and continue to be challenging in prevention and treatment because of the increased use of alternative medications and an increase in the elderly population (Coleman and Pontefract 2016; Rieder and Ferro 2015).
21 Q. How does an ADR differ from an adverse effect or allergy?
22 A. An adverse effect is a type of ADR mediated by an immune response and is not the intended therapeutic outcome. It has been suggested to avoid using the term “side effect” and use the term “adverse effect” or “adverse drug reaction” instead (Riedl and Casillas 2003; VA Center for Medication Safety and VHA Pharmacy Benefits Management Strategic Healthcare Group and the Medical Advisory Panel 2006).
23 Q. What is an ADE and is it the same as an ADR?
24 A. An adverse drug event (ADE) is an unfavorable and unintended response to a drug that includes medical errors (e.g., miscalculations, misinterpretation of handwritten prescriptions). The dentist has the responsibility to report any ADE that occurs through the FDA's Adverse Event Reporting System (MedWatch; www.fda.gov/Safety/MedWatch/default.htm) (Mayer et al. 2010). The terms ADE and ADR are often used interchangeably but should not be (Leheny 2017). Adverse drug events are not desired and usually require medical intervention. On the other hand, the majority of ADRs are undesirable but are usually predictable. The majority of cases resolve on their own (Leheny 2017).
25 Q. What is the definition of tolerance?
26 A. Tolerance is the development of resistance to the effects of a drug. Therefore, in order to achieve the desired response, more of the drug must be taken. Overdose is very common. Narcotics and alcohol are common examples of drugs that produce tolerance.
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