Significance of interactions

When used as intended within the licensed doses, dental LA cartridges, with or without a vasoconstrictor, have very few reports of clinically relevant interactions. The documented interactions may also not be relevant in a general dental practice setting.

Where there is potential for a clinically relevant interaction in a general dental setting, the risk can typically be managed by limiting the administered dose.

Specific recommendations

See our page for guidance on specific recommendations for medicines that interact with dental LA cartridges:

Dental LA cartridges

Anaesthetic cartridges contain an LA and, usually, a vasoconstrictor (adrenaline or felypressin). Since LA alone has a short duration of action, adding a vasoconstrictor improves the depth and duration of anaesthesia. It also reduces bleeding during procedures and the likelihood of systemic absorption of the LA, reducing the risk of systemic side effects.

Lidocaine is the most widely used dental LA and is available with and without adrenaline.

Other available preparations include:

• articaine with adrenaline
• mepivacaine with and without adrenaline
• prilocaine with felypressin

Manageable influencers of interactions

The drug’s dosage and administration method can affect the likelihood of a clinically relevant interaction.

Dosage

Many drug-drug interactions are dose-related, and as doses of LA used in dentistry are small, the clinical significance of reactions is reduced. Interactions listed in the Summary of Product Characteristics (SPCs) and the BNF are often associated with non-dental indications which require far higher dosages than those used in general dental practice. Keeping doses within the licensed directions for dentistry will help limit any potential for interaction.

For example, if lidocaine is being used as an antiarrhythmic, it is administered at an intravenous dose of 1,750mg over 24 hours. This would be equivalent to injecting almost forty 2.2ml lidocaine-containing cartridges intravenously.

Route of administration

Drug interactions are unlikely without systemic drug absorption (absorption into the bloodstream). Correct administration of LA leads to very low blood concentrations, which minimises the interaction risk compared to direct intravascular administration. An aspirating syringe will help avoid accidental intravenous administration.

The injection technique may influence the risk of interactions. In general dental practice, LA preparations can be administered using various methods, including infiltration, regional block, and intraligamentary injection.

Infiltration and regional block anaesthesia

Infiltration and regional block anaesthesia are not associated with significant systemic absorption unless inadvertent intravascular administration occurs. Even then, in the unlikely event of a full cartridge of adrenaline-containing LA being injected intravascularly, the blood concentrations of adrenaline are unlikely to exceed those naturally produced by the body under stressful situations or when performing light physical exercise.

Intraligamentary anaesthesia

Traditional intraligamentary injection can lead to rapid adrenaline absorption into the systemic circulation. Modern Single-Tooth Anaesthesia (STA) systems offer computer-controlled delivery and pressure sensing, allowing for slower absorption and reduced risks of adrenaline blood level peaks.

The volumes used in the intraligamentary technique are very small (around 0.2ml to 0.4ml). Therefore, the blood adrenaline levels reached are unlikely to result in clinically significant interactions. However, caution is required if more than one tooth is being anaesthetised by intraligamentary injection, as higher adrenaline levels may be achieved.

Sources of interaction information

The BNF and manufacturer SPCs, available from the electronic medicines compendium (eMC) or Medicines and Healthcare products Regulatory Agency (MHRA) website, are the most accessible resources providing interaction information.

However, these resources do not consider the significance of the interaction in the dental setting. Therefore, if taken as written, dental treatment could be unnecessarily limited.

SPCs are produced and updated by the manufacturers, who are legally obligated to include specific information about medicines. This includes cautions, contraindications, adverse effects, and interactions with other medications.

Possible limitations of SPCs

There are several factors which should be considered when reviewing interaction information in SPCs.

Date of last update

The information in an SPC may not have been updated since a product was first licensed. Therefore, it may not reflect current understanding or research carried out post-licensing.

For example, hyperthyroidism can cause cardiovascular changes, which present like an adrenaline overdose. It was thought that thyroid hormones or levothyroxine could interact with adrenaline and cause these effects. However, research has shown this does not occur.

Theoretical interactions

Described interactions may be theoretical or extrapolated from other knowledge of other interactions and not be observed in practice.

For example, the lidocaine SPC states there may be an increased risk of ventricular arrhythmia with antipsychotics or other medicines, which may affect QT interval. However, neither the BNF nor specialist interaction resources recognise lidocaine as a drug which may cause QT prolongation.

Real-life usage

Conditions in which clinical trials are performed may not reflect real-life drug usage.

For example, in studies observing the effects of tricyclic antidepressants (TCAs) on adrenaline, TCAs were administered for less than a week. When a drug is taken long-term, continual stimulation of receptors reduces their number, so larger doses are needed to stimulate a response. This is known as downregulation. The trial conditions mean downregulation could not have yet occurred. Therefore, the effect of adrenaline on the heart may have been exaggerated compared to someone taking a long-term daily TCA.

Types of drug interaction

Most drug interactions can be divided into two categories: pharmacodynamic and pharmacokinetic. Our page on understanding drug interactions discusses different mechanisms of drug interactions.

Pharmacokinetic interactions

A pharmacokinetic interaction is when one drug alters another drug’s absorption, distribution, metabolism, or excretion.

For example, erythromycin inhibits the liver enzyme CYP3A4, which is partially responsible for lidocaine metabolism. Erythromycin could be expected to increase lidocaine blood levels. However, lidocaine is also metabolised by CYP1A2, which erythromycin does not affect. This alternate pathway helps limit the inhibitory effect of erythromycin, meaning a dose adjustment of lidocaine would not be needed.

Pharmacodynamic interactions

Pharmacodynamic interactions occur when drugs have additive or opposing pharmacological effects, leading to a reduced or enhanced effect. The likelihood and severity of such interactions will depend on individual patient circumstances.

For example, adrenaline causes vasoconstriction via alpha receptors and vasodilation via beta receptors. Non-selective beta blockers affect beta receptors all over the body, preventing the vasodilatory effect. This leaves the vasoconstrictive effect of adrenaline on alpha receptors unopposed and can result in a dangerous increase in blood pressure with systemic administration of high doses.

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