What are the most common adverse drug reactions in dental practice?

This summary is based on the article published in Anesthesia Progress: Adverse Drug Reactions in Dental Practice (Spring 2014)

Daniel E. Becker, DDS

Context

Adverse reactions may occur with any of the medications prescribed or administered in dental practice. Most of these reactions are somewhat predictable based on the pharmacodynamic properties of the drug. Others, such as allergic and pseudoallergic reactions, are less common and unrelated to normal drug action.

Purpose of the Article

To review the most common adverse reactions that are unrelated to drug allergy.

Key Messages

Sedatives, Opioids, and General Anesthetics

• Respiratory depression is the most significant side effect of all drug classes used for procedural sedation and general anesthesia.
• Respiratory depression proceeds in a dose-response manner, and the intensity is further increased when the various classes are used in combination. Minimal to moderate sedation carries little risk for clinically significant respiratory depression, but deep sedation and general anesthesia introduce substantial risk for both respiratory depression and airway obstruction.
• Potent inhalation anesthetics depress tidal volume while generally increasing respiratory rate; their net influence on minute ventilation varies. In contrast, the intravenous sedatives and opioids usually depress both tidal volume and respiratory rate. Benzodiazepines produce the least intensity of respiratory depression, but this increases when they are combined with other drugs or high doses are administered.
• In addition to respiratory influences, these drug classes may also lower arterial blood pressure and heart rate. With doses and combinations intended for general anesthesia the risk for hypotension may become more substantial.
• Benzodiazepines and propofol produce anterograde amnesia when administered at sedative dosages.⁵ This is an inability to recall events that occur while conscious but under the influence of a medication.

Antihistamines and Antiemetics

• These are commonly used in regimens for procedural sedation but also are indicated for minor allergic reactions and nausea or vomiting. They may potentiate respiratory depression produced by opioids and other sedatives.
• Drugs having central anticholinergic actions should probably be avoided in elderly patients, particularly those having evidence of dementia.⁶
• High doses of anticholinergic drugs can result in a ‘‘central anticholinergic syndrome’’ that includes delirium and combativeness.
• During lengthy treatment under sedation it is important to not exceed conventionally suggested doses for these agents.
• Acute dystonias generally present as spasms of the tongue, facial, and neck muscles, whereas akathisia presents as a subjective feeling of restlessness and a compelling need to move about. These behaviors may be mistaken for agitation, and their distinction is critical to avoid an inclination to further sedate the patient.
• Like other phenothiazine as well as butyrophenone derivatives, promethazine has antagonist actions on vascular alpha receptors, which increases risk for postural hypotension, especially in the elderly.

Local Anesthetics

• Local anesthetic concentrations of 2% or 3% carry little risk, but 4% articaine and prilocaine formulations most certainly introduce added risk. Haas and Lennon first reported an increased incidence of paresthesias in Canada following the introduction of articaine in the mid- 1980s.⁹
• As local anesthetics are absorbed from the injection site, their concentration in the bloodstream rises and the peripheral and central nervous systems are depressed in a dose-dependent manner.⁸
• At higher serum concentrations, convulsive seizures occur and are the initial life-threatening consequence of local anesthetic overdose.
• Although all local anesthetics carry similar risk for central nervous system toxicity, it should be noted that bupivacaine exhibits greater potential for direct cardiac toxicity than other agents.^8,13

Vasoconstrictors: Epinephrine and Levonordefrin

• Vasoconstrictors are combined with local anesthetics to provide hemostasis in the operative field and to delay anesthetic absorption.
• Despite the popularity of epinephrine 1 : 100,000, concentrations greater than 1 : 200,000 (5 lg/mL) offer little if any advantage. Greater concentrations do not provide better onset or duration for inferior alveolar nerve block.^19,20 Nor do higher concentrations reduce local anesthetic serum concentrations.²¹

Analgesics

Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

• The most frequent adverse effects of nonsteroidal anti-inflammatory drugs (NSAIDs) relate to their gastrointestinal (GI) toxicity: mucosal erosion and ulceration.
• Patients receiving antithrombotic therapy with either antiplatelet or anticoagulant drugs are at risk for more significant bleeding from NSAID-induced mucosal injury.
• Although non-aspirin NSAIDs all prolong bleeding times to some degree, this does not correlate with significant clinical bleeding following minor surgical procedures.²⁴
• Prostaglandins play an essential role in renal perfusion, and their inhibition is believed to account for reported cases of nephrotoxicity following chronic NSAID use.
• NSAIDs must never be prescribed for patients having compromised or questionable renal function.

Acetaminophen

• Hepatotoxicity is the principal adverse effect associated with excessive acetaminophen dosages.
• Hepatic injury from acetaminophen is due mainly to a single toxic metabolite, N-acetyl-p-benzoquinone imine, which is formed by oxidation of the drug.

Opioids

• Respiratory depression is a significant side effect of opioids included in sedation and anesthesia regimens but is rarely a concern at the conventional doses prescribed for postoperative pain.
• Analgesic doses are more commonly associated with constipation and nausea.
• Patients consuming opioids regularly for more than a week can develop some degree of dependence. This may require gradual tapering of the dosage to avoid withdrawal symptoms, which can be confused as an exacerbation of their painful condition. However, this does not mean the patient has become addicted.^29,30
• Following repeated administration, patients develop tolerance to opioids. This is to say that greater doses are required to produce the same intensity of effect formerly provided by a smaller dose.

Antibiotics

Opportunistic Yeast Infection

• Candida albicans is a fungus also referred to as yeast because of its manner of growth.
• Overgrowth is ordinarily prevented by resident bacteria, but this control may be lost when patients are immunocompromised or treated with antibiotics.

Antibiotic-Associated Diarrhea

• In general, diarrhea is related to an imbalance in the normal intestinal flora favoring opportunists. Current evidence suggests that probiotics are indeed effective and should be suggested for particularly frail patients or those who have experienced diarrhea with antibiotic regimens in the past.³²

C difficile Disease

• C difficile is an anaerobic, spore-forming bacillus and is not regarded as a normal component of intestinal flora.
• Actual consequences of C difficile infection range from diarrhea to pseudomembranous colitis.
• In a patient who normally tolerates antibiotics but experiences diarrhea that is florid (3 unformed stools per day for 2 days) and complains of abdominal pain, C difficile infection should be suspected.

References

List of references (PDF)