Contraindications to vasoconstrictors in dentistry: Part III. Pharmacologic interactions.

This article discusses the relative contraindications to the use of vasoconstrictor in patients currently medicated with tricyclic antidepressants, monoamine oxidase inhibitors, phenothiazines and beta-blockers. It reviews drug interactions and emphasizes potential detrimental systemic effects that epinephrine contained in local anesthetics can have when administered concomitantly with these drugs. Finally, special considerations are expressed concerning patients who abuse illicit drugs such as cocaine.     

Adverse drug interactions in dental practice: interactions involving antibiotics. Part II of a series

BACKGROUND: The prudent use of antibiotics is an integral part of dental practice. While these agents generally are considered safe in the dental setting, their use can result in interactions that can lead to serious morbidity in dental patients. METHODS: The faculty of a symposium entitled "Adverse Drug Interactions in Dentistry: Separating the Myths From the Facts" did an extensive literature review on drug interactions. Through this, they were able to establish a significance rating of alleged adverse drug interactions as they relate to dentistry, based on their scientific documentation and severity of effect. The author of this article focused on antibiotics. RESULTS: Most of the reported drug interactions discussed in this article are well-documented by clinical studies. It is particularly important that dentists be aware of the potentially serious and life-threatening interactions of the antibiotics erythromycin, clarithromycin and metronidazole, and of the antifungal agents ketoconazole and itraconazole, with a host of other drugs whose metabolism is impaired by these antimicrobial agents. In contrast, the alleged ability of commonly employed antibiotics to reduce the effectiveness of oral contraceptive agents is not adequately supported by clinical research. It still is recommended, however, that clinicians discuss this possible interaction with their patients, as it might represent a relatively rare event that cannot be discerned in clinical trials. CONCLUSIONS: Potentially serious adverse drug interactions can occur between antimicrobial agents used in dental practice and other drugs patients are taking for a variety of medical conditions. CLINICAL IMPLICATIONS: It is important that dentists stay abreast of potential drug interactions involving antibiotics to avoid serious morbidity among their patients.     

Adverse drug interactions in dental practice: interactions associated with local anesthetics, sedatives and anxiolytics. Part IV of a series

BACKGROUND: This article is the fourth in a five-part series based on a 1998 International Association for Dental Research symposium entitled "Adverse Drug Interactions in Dentistry: Separating the Myths From the Facts." The symposium evaluated the significance of various drug interactions associated with dental therapeutics. METHODS: Local anesthesia and preoperative oral sedative/anxiolytic therapy often are indicated for routine oral surgery and restorative dentistry. The author conducted a literature review of the drug interactions associated with the use of local anesthetics and sedatives. The quality of the information used to document these interactions and the severity of the possible adverse outcome were assessed using a significance rating scale for dental drug interactions. RESULTS: Many of the frequently described drug interactions were found to be poorly documented in the dental and medical literature. Others were determined not to be relevant to current dental practice. The use of local anesthetics, sedatives or anxiolytic agents in combination with other central nervous system depressant agents or in combination with drugs that inhibit their metabolism was associated with a few serious adverse drug interactions or complications. CONCLUSIONS: The adverse drug interactions associated with the use of local anesthetics and oral sedative/anxiolytic agents in general practice vary in significance. An understanding of possible adverse drug interactions in dentistry may help practitioners avoid and prevent these complications.     

Vasoconstrictors: indications and precautions

Vasoconstrictors are useful additives to local anesthetic solutions. They can enhance the duration and quality of the anesthetic block while also decreasing surgical blood loss. Precautions must be taken, however, when using vasoconstrictors with certain patients, especially those with cardiovascular disease. Several drug interactions must also be considered before administration of a local anesthetic with a vasoconstrictor, and special care must be taken when injecting such preparations in patients on nonspecific beta-adrenergic blockers, tricyclic antidepressants, catechol-O-methyltransferase inhibitors, cocaine, and certain general anesthetics. Lastly, in the patient with true sulfite allergy, local anesthetics without a vasoconstrictor should be used.     

Emergencies evolving from local anesthesia

Local anesthesia is without doubt the most frequently used drug in dentistry and in medicine. In spite of records of safety set by using these drugs, there is evidence to adverse reactions ranging from 2.5%-11%. Most of the reactions originate from the autonomic system. A recent, well-planned study indicates that adverse reactions are highly correlated to the medical status of the patient: the higher the medical risk, the greater the chance to experience an adverse reaction. This study also found that adverse reactions highly correlated to the concentration of adrenalin. Another recent study found a direct relationship between adverse reactions and the level of anxiety experienced by the patient and to the dental procedure. Most of the reactions in this study occurred either immediately at injection time and within 2 hours following the injection. Since the beginning of last century, vasoconstrictors have been added to local anesthesia solutions in order to reduce toxicity and prologue activity of the LA. However, today it is commonly agreed that this addition to local anesthesia should not be administered to cardiac patients especially those suffering from refractory dysrhythmias, angina pectoris, post myocardial infarction (6 months) and uncontrolled hypertension. Other contraindications to vasoconstrictors are endocrine disorders such as hyperthyroidism, hyperfunction of the medullary adrenal (pheochromocytoma) and uncontrolled diabetes mellitus. Cross reactivity of local anesthetic solutions can occur with MAO inhibitors, non specific beta adrenergic blockers, tricyclic antidepressants, phenothiazides and cocaine abusers. Noradrenaline added to local anesthetics as a vasoconstrictor has been described as a trigger to a great increase in blood pressure and therefore has been forbidden for use in many countries. This paper describes 4 cases of severe complications following the injections of local anesthesia of which three ended in fatality.     

Drug interactions and vasoconstrictors used in local anesthetic solutions

This study examined widely advertised interactions between sympathomimetic amine vasoconstrictors currently used in dental local anesthetic solutions and MAO inhibitors (phenelzine, 5 mg/kg), phenothiazines (chlorpromazine, 2 mg/kg), and tricyclic antidepressants (desipramine, 2 mg/kg). Twelve greyhound dogs premedicated with morphine and anesthetized with urethane and alpha-chloralose were prepared for physiologic recordings. During a control period, the dogs received bolus injections of epinephrine, norepinephrine, and levonordefrin sufficient to construct log-linear dose-response curves for each agent. Commercial anesthetic solutions, with and without the vasoconstrictors, were also used. The dose-response curves were then reproduced 1 hour after the administration of a drug interactant. Cardiovascular responses were not influenced by the coadministration of local anesthetics or by the prior administration of phenelzine. Chlorpromazine ameliorated pressor responses to norepinephrine and levonordephrin and reversed the hypertensive effect of high-dose epinephrine. Desipramine significantly increased vasoconstrictor potencies, particularly those of levonordefrin and norepinephrine, which were multiplied more than sixfold.     

Migraine drug therapy: dental implications

Triptan drugs continue to constitute the major pharmacotherapeutic interventional agents for migraine therapy. Interactions of dental drugs with migraine medications are limited, but their seriousness dictates that dentists be aware of the use of ergot alkaloids, triptans, or other migraine drugs. While many migraine sufferers avoid dental therapy dur ing migraine attacks, the practitioner who is treating a patient who has taken migraine medications must carefully monitor the cardiovascular status of the patient, which may affect the use of vasoconstrictors. Macrolide antibiotics and azole antifungals represent additional drug groups that are prescribed by dentists but which may potentiate the adverse effects of migraine drugs. Migraine patients prefer agents that offer rapid onset of relief and total relief within a couple hours of drug administration; they also prefer therapy that prevents recurrences and does not require "rescue" medications, and, of course, a lack of adverse effects and interactions with other medications. Currently, no single drug or class of drugs offers this ideal combination of actions in all patients.     

Drug therapy for the pregnant dental patient

Providing needed dental treatment, managing oral infection, and controlling pain are essential functions of dentists for helping patients maintain overall health during pregnancy. Medications commonly required for dental care consist of local anesthetics and associated vasoconstrictors, centrally and peripherally acting analgesics, sedative and anxiolytic agents, and antibiotics. Therapeutic drugs routinely used in dental practice are selected because of their known safety and effectiveness. However, for a pregnant patient requiring dental care, the agents routinely prescribed should be reevaluated for potential risks to the mother and/or fetus. The decision to administer a specific drug requires that the benefits outweigh the potential risks of the drug therapy. This article reviews and updates the recommendations for using dental therapeutic agents, thereby enabling general practitioners to select the safest drugs when treating pregnant dental patients.     

Geriatric pharmacology for the dentist. An overview

The information presented in this article suggests that the drug responses of the elderly may be greater than those in the young or essentially the same. We have presented evidence that the pharmacokinetics in the elderly would probably tend toward prolonging the half-life and delaying the clearance of many drugs. Pharmacodynamic changes are more ambiguous, increasing sensitivity to some drugs and decreasing sensitivity to others. Compliance errors, from whatever cause, lead to unpredictable intake of drugs. Psychosocioeconomic factors contribute to compliance errors and no doubt also lead to increased intake of combination of drugs. Multiple diseases are common among the elderly, but it is not clear how disease states, per se, affect drug responses unless the specifically diseased organ is focally important in the handling of drugs. Alterations in perception of pain and in reflex and immune competence will produce changes in all directions. Use of multiple drugs almost certainly will create an environment favorable to drug interactions and adverse reactions. What is the dentist to do with these conflicting effects of aging in drug therapy? There are a few, and only a few, rules that can be said to have a solid basis in fact. Elderly patients seem to be more sensitive to the depressant effects of drugs. It is wise, therefore, to reduce the dosage of such drugs as the benzodiazepines, general anesthetics, analgesics, and sedative-hypnotics in the elderly. Old people are apparently more sensitive to certain drugs, for example, the neuromuscular blocking drugs. It would be wise to reduce the dosage of these for the older patient. The geriatric person appears to be less sensitive to pain; it would be wise to prescribe analgesics for such patients in lower doses. Elderly patients are known to have lost some of their reflex ability to maintain homeostasis. This should be taken into consideration when drugs that affect blood pressure, heart rate, and smooth muscle tone are used. Elderly patients are almost certain to be taking multiple medications. Drug interactions, as well as adverse drug reactions (which are exaggerated in the elderly), are likely to occur in this polypharmaceutical setting. It is critical that the dentist be continually informed of the pharmacologic status of each patient and be aware of the likelihood of interactions between drugs prescribed by the dentist, drugs-prescribed by the physician, and drugs that are self-administered.     

Sulfite, asthma and vasoconstrictors

The use of vasoconstrictors in dentistry has always been a topic of controversy for the medically compromised patient. Over the past few years, dentists have been warned not to use local anesthetics with vasoconstrictors in asthmatic patients. In this article, the authors question the rationale behind these recommendations and explain why the warning should be restricted to steroid-dependent asthmatic patients.     

Adverse drug interactions in dental practice: interactions associated with analgesics, Part III in a series

BACKGROUND: Numerous reports of drug interactions exist, yet not all are valid in or pertinent to dentistry. This article provides an overview of drug interactions with analgesics and identifies those that are clinically relevant. METHODS: The author reviewed reports of drug interactions involving nonsteroidal anti-inflammatory drugs, or NSAIDs (including aspirin), acetaminophen and opioids to determine the interactions' validity and clinical relevance. Consistent with the practice followed in other articles in this series, the author determined the significance of the proposed interaction by gauging its reported severity and the quality of the documentation. RESULTS AND CONCLUSIONS: NSAIDs should not be taken by patients taking high-dose methotrexate, anticoagulants or alcohol. They should be avoided in elderly or renally impaired patients taking digoxin, and avoided over the long term in those taking other NSAIDs. It is possible that NSAIDs should not be given to patients taking lithium, but future studies should be conducted to confirm this. Use of NSAIDs likely is appropriate in the short term with patients taking antihypertensives, unless they have severe congestive heart disease. Aspirin should not be given to patients taking oral hypoglycemics, valproic acid or carbonic anhydrase inhibitors. Acetaminophen may be given in the short term to any patient with a healthy liver, but it should not be given to a patient who has stopped drinking alcohol after chronic intake. Opioids should not be combined with alcohol, and meperidine must be avoided in the patient who has taken monoamine oxidase inhibitors in the previous 14 days. CLINICAL IMPLICATIONS: Drug interactions with analgesics are often reported, but only a small number have clinical relevance in dentistry. Awareness of the significance of these interactions will allow dentists to prescribe analgesics optimally and minimize the potential for adverse reactions.     

Adrenergic regulation of capsaicin-sensitive neurons in dental pulp

Alpha adrenergic agonists (e.g. vasoconstrictors) represent one of the most commonly used drug classes in dentistry. Although adrenergic agonists have potent vascular effects, recent studies suggest that capsaicin-sensitive nociceptors may express adrenoceptors, suggesting that these drugs may directly modulate the function of an important class of pain-signaling neurons in peripheral tissues. In this study, we tested the hypothesis that adrenergic agonists inhibit activation of peripheral terminals of capsaicin-sensitive fibers innervating dental pulp. Pretreatment with epinephrine or clonidine significantly inhibited capsaicin-evoked release of immunoreactive calcitonin gene-related peptide from superfused bovine dental pulp. These studies suggest that adrenergic agonists may reduce postoperative pain in part via a direct inhibition of capsaicin-sensitive nociceptors. This finding may lead to the development of selective, peripherally acting, adrenergic analgesics. Moreover, because neuropeptide release alters blood flow, it is possible that the vascular effects of these drugs are caused by both vasoconstriction and inhibition of peripheral neuropeptide release.     

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Demystifying medical complexities

Although dentists often fear treating medically complex patients, in many cases this fear may be based not on scientific facts but rather on a "mythology" of the dangers of dentistry. Dentistry is a remarkably safe profession, even for most medically complex patients. The myths of endocarditis, artificial joint infections, local anesthetics and vasoconstrictors, dental surgery in anticoagulated patients and patients on antiplatelet drugs, and antibiotic interference with oral contraceptives are discussed. Although dental treatment is not usually a risk factor for endocarditis, practitioners should consult the 1997 American Heart Association statement for recommendations for endocarditis prevention. Most artificial joint patients should not receive antibiotic prophylaxis. Local anesthetics and vasoconstrictors can be used safely in most medically complex patients. Neither continuous anticoagulation nor antiplatelet medications should be withdrawn for dental surgery. Scientific studies have failed to document an interaction between antibiotics used in dentistry and oral contraceptives.     

An update on local anesthetics in dentistry

Local anesthetics are the most commonly used drugs in dentistry. This article provides a brief update on the pharmacology, adverse effects and clinical applications of these drugs, as well as the role of vasoconstrictors.     

Adverse drug reactions to local anesthesia

A dentist's ability to safely administer regional anesthesia is essential for dental practice. Local anesthetic solutions used in the United States for dental anesthesia are formulated with several components. The contents of a standard local anesthetic cartridge may include an amide or ester local anesthetic drug, an adrenergic vasoconstrictor, and an antioxidant. In susceptible patients, any of these components may induce systemic, dose-dependent adverse reactions. Although extremely rare, allergic reactions may also occur. Signs and symptoms of the various adverse reactions associated with local anesthetics are quite distinctive, permitting rapid diagnosis and treatment. Serious reactions are extremely infrequent and, when treated properly, unlikely to result in significant morbidity or mortality.     

Comparative efficiency of local anesthetics from the group of complex amides during therapeutic stomatological interventions

The efficiency of infiltration, conduction, and intraligamental anesthesia with different drugs for dental interventions was evaluated in 331 patients without concomitant somatic diseases. The efficiency of local anesthesia depends primarily on the drug; other essential factors are the route of this drug administration and type of intervention in the oral cavity. The most effective of the studied anesthetics was 4% artisane with epinephrine 1:100,000; 3% prolocaine with epinephrine 1:100,000 ranked second. These anesthetics maximally realized their effects at intraligamental injection during the treatment of caries and periodontitis.     

Managing patients with local anesthetic complications using alternative methods

This article discusses various alternative methods of treating the patient who encounters problems with local anesthetics. Those alternative methods include: acupuncture, hypnosis, sedation, general anesthesia, and antihistamines as a substitute for local anesthetics with more of a focus in using antihistamines as an effective local anesthetic agent. Although not frequently encountered in the clinical setting, allergic reactions to local anesthetics do occur. Various surveys indicate the number of deaths attributed to local anesthesia range from 1:1,500,000 to 1:4,000,000, with oral surgery offices having higher mortality rates than general dentistry offices. This occurs despite clinicians' attention to patient medical histories, aspiration of the local anesthetic syringe during injections, and minimizing the dosage of local anesthetic solutions. Generally speaking, local anesthetics can be divided into two groups: ester of benzoic and aminobenzoic derivatives (cocaine, benzocaine, procaine, tetracaine, butacaine, etc.) or amide-derivatives of xylidine and toluidine groups (lidocaine, mepivacaine, prilocaine a.k.a. Citanest, etc.). Adverse effects include allergic or toxic reactions, as well as negative effects of any vasoconstrictors contained within the local anesthetic solution. This article will concentrate on how to successfully manage patients who have previously encountered allergic reactions.     

Emergencies evolving from local anesthesia in the pediatric dental clinic: prevention and treatment

A wide range of drugs and dental materials may be used when providing treatment to children. Routine medical and dental history may not provide all the necessary information to prevent allergic reactions, since young patients may be exposed to some of these drugs for the first time in the dental chair. The dentist should be prepared through training to reduce and at the same manage unwanted side effects. This article focuses on the possible adverse reactions following injection of local anesthetics; mainly, allergic and toxic side effects. Signs and symptoms are described and differential diagnosis is considered. The limited and absolute contraindication for administering some common local anesthetics is presented and local anesthetic drug interactions and toxicity relevant to pediatric patients are reviewed.