March 1, 2007
by Marvin Malamed, B.Sc.Phm., C.C.N
Dentists and oral surgeons often encounter problems that do not respond to traditional allopathic therapies, or may require special preparations that are not commercially available. Nutritional deficiencies can affect the integrity of the oral mucosa. Supplementation to replace deficient vitamins, minerals, amino acids, and enzymes, as well as the use of specially-formulated medicated dosage forms can greatly enhance dental care.
Here are just a few examples of dosage forms that can be compounded by prescription to meet the unique needs of dentists and their patients:
* Lip balms for cold sores which contain the natural anti-viral 2-DDG (2-deoxy D-glucose), a glucose derivative which exerts anti-viral activity against herpes simplex and HPV by interfering with the viral replication process. 2-DDG has no known toxicities, and can be incorporated into a variety of topical preparations.
* Electrolyte lozenges to suppress the gag reflex prior to taking an impression or for patients who can not properly perform oral hygiene procedures at home due to a gagging problem1
* Troches or long-acting pilocarpine capsules for dry mouth, which stimulate salivation while avoiding the problems associated with immediate-release pilocarpine products.
* Topical muscle relaxants/pain relievers for temporomandibular joint (TMJ) disorder caused by injury or inflammation of the joint. A topical gel containing an anti-inflammatory and a muscle relaxant can be applied over the affected joint to deliver the medication where it is needed and decrease the risk of adverse side effects such as gastrointestinal irritation and drowsiness that occur when medications are administered orally. Iontophoretic delivery of dexamethasone and lidocaine has improved mandibular function in patients who had concurrent temporomandibular joint capsulitis and disc displacement without reduction.
* “Mucosal bandages,” muco-adhesive bases, and oral pastes to cover ulcerated, infected, or tender areas on the oral mucosa, or to maintain medication contact with the oral mucosa.
Novel formulations of topical anesthetics, including intra-oral anesthetics in plasticized gel or an adherent base, may prevent pain associated with laser and soft tissue procedures; phrenectomies; deep scaling, root planing, and curettage; and prior to extraction of primary teeth, and often eliminate the need for injections. The use of topical anesthetics may improve patient recall, because an aversion to injections in patients with recurrent disease or who have dentinal sensitivity may negatively affect their compliance with treatment plans. Vasoconstrictors can be added to preparations to promote local hemostasis, decrease systemic absorption, and prolong the duration of action.
Approximately 1,700 pediatric dentists responded to a survey conducted by West Virginia University School of Dentistry, and indicated that most pediatric patients (89%) disliked the taste of topical anesthetics. Compounding pharmacies can customize topical anesthetics in a variety of appealing flavours.
In November 2006, Health Canada issued an advisory regarding an association between the local anesthetic benzocaine and a potentially serious blood condition known as methemoglobinemia (MHb). MHb is an uncommon adverse reaction known to be associated with benzocaine. This condition reduces the ability of red blood cells to deliver oxygen throughout the body, which can lead to bluish discoloration of the skin, nausea and fatigue. It can progress to stupor, coma and death. As of November, 2006, Health Canada had received reports of nine cases of suspected MHb associated with the use of benzocaine. None of the reported cases had a fatal outcome. Almost all reported cases of benzocaine-induced MHb were associated with high-concentration preparations (14% to 20% benzocaine). Compounding pharmacies can formulate benzocaine-free topical anesthetics, including combinations such as lidocaine and tetracaine or prilocaine.
TOPICAL MEDICATIONS FOR OROFACIAL NEUROPATHIC PAIN
The most common neuropathic pain syndromes in the orofacial region include trigeminal neuralgia, traumatic neuropathy; trigeminal neuroma; postherpetic neuralgia; diabetic neuropathy; cancer-related neuropathy; neuropathy induced by AIDS; and chronic-continuous trigeminal nociceptor neuropathy. The pain mechanisms that generate these problems are different for each neuropathy, and treatment protocols need to be structured accordingly. Numerous studies have shown that NMDA-receptor antagonists such as ketamine and gabapentin, may be useful in the treatment of neurogenic pain. Cyclobenzaprine, a muscle relaxant, has been used for peripheral application to relieve muscle trismus and spasm.2
Customized oral rinses can be formulated to treat problems such as:
Burning Mouth Syndrome: Burning mouth syndrome (BMS) is characterized by a burning sensation on the tongue or other oral sites, usually in the absence of clinical and laboratory findings. Burning mouth is reported most often by women, especially after menopause. Typically, patients awaken without pain but note increasing symptoms throughout the day and into the evening. Conditions that have been reported in association with BMS include chronic anxiety or depression, various nutritional deficiencies, type 2 diabetes, taste alterations, and changes in salivary function and dry mouth. Recent studies have pointed to dysfunction of several cranial nerves as a possible cause of BMS. Given in low dosages, benzodiazepines, tricyclic antidepressants or anticonvulsants may be effective in treating BMS. The formulation for clonazepam 1mg per 5ml mouthwash was reported in the International Journal of Pharmaceutical Compounding. Topical capsaicin has also been used successfully.3
Gingivitis: Folate mouthwash appears to have an influence on gingival health through local rather than systemic influence. Use of a mouthwash containing folate 5mg/5ml (twice daily for 4 weeks, rinsing for 1 min. before expectorating) reduced gingival inflammation and bleeding in patients with periodontal disease. Folic acid mouthwash and oral tablets both significantly increased folate levels in pregnant women, but only folic acid mouthwash showed a highly significant improvement in gingival health.4 Topical folate has been shown to inhibited gingival hyperplasia to a significantly greater extent than administration of systemic folate or placebo.5
Post-Surgical Bleeding in Anticoagulated Patients: Tranexamic acid is an antifibrinolytic agent, which can be applied topically or used as a mouthwash to prevent post-surgical bleeding in anticoagulated patients after oral surgery or extractions, without discontinuation or dose reduction of anticoagulant therapy.6,7
Coenzyme Q10 for peridontal therapy
Topical application of Coenzyme Q10 (CoQ10) to the periodontal pocket was evaluated with and without subgingival mechanical debridement. Significant improvements in the modified gingival index, bleeding on probing and peptidase activity derived from periodontopathic bacteria were observed only at sites treated with CoQ10. These results suggest that topical application of CoQ10 improves adult periodontitis not only as a sole treatment but also in combination with traditional nonsurgical periodontal therapy.8
Therapy for mucositis caused by chemotherapy or radiation
Patients with cancer are at high risk for numerous oral problems. Cytotoxic chemotherapy, radiation to the head and neck, and immunosuppression prior to bone marrow transplantation commonly cause significant inflammation and painful lesions of the oral and esophageal mucosa which lead to difficulty swallowing and can result in a compromised nutritional status. Oral mucositis is the dose-limiting toxi
city for patients receiving concurrent chemoradiotherapy regimens for tumors of the head and neck area. Dry mouth secondary to radiation can lead to rampant dental caries. Oral rinses can be formulated to prevention mucositis (i.e., glutamine), relieve pain (i.e., morphine), reduce inflammation, or treat superinfections (bacterial, viral, or fungal).9,10
Glutamine is a nutrient for rapidly dividing cells. Administration of glutamine suspension after chemotherapy has resulted in significant amelioration of stomatitis and decreased the duration of mouth pain by 4.5 days when compared to placebo. The severity of oral pain may also be reduced significantly when glutamine is provided with chemotherapy. No toxicity has been observed. Oral glutamine appears to be a safe, simple and useful measure to increase the comfort of children and adults at high risk of developing mouth sores as a consequence of chemotherapy.11-14
Persistent mucosal pain may be helped by topical preparations that provide local protection or anesthesia. For patients with head and neck carcinomas receiving concomitant chemoradiotherapy, morphine mouthwash is a simple and effective treatment to decrease the severity and duration of oral lesions and the duration of functional impairment.15 Also, a three-drug mouthwash containing lidocaine, diphenhydramine and sodium bicarbonate in normal saline has been reported to provide effective symptomatic relief in patients with chemotherapy-induced mucositis.16
Fungal infections of the oral mucosa are common in patients with compromised immune status. Candidiasis usually appears as adherent white plaques but can also present as erythema or angular cheilitis. Amphotericin B and nystatin are potent antifungal agents which are active against most pathogenic fungi like Aspergillus and Candida, and can be formulated as an oral rinse.17 Melaleuca (tea tree oil) rinse has been effective in treating fluconazole-resistant candidiasis in AIDS patients.18
Malignant oral lesions are often associated with anaerobic bacteria that produce a foul odour. The odour can be reduced with a topically applied metronidazole gel.
Relief for aphthous ulcers
Aphthous ulcers affect up to 25% of the general population and three month recurrence rates are as high as 50%.19 Aphthous ulcers may be helped with topical corticosteroids prepared as a mouth rinse or paste, or oral rinses containing a combination of medications to combat the various possible causes of these painful oral lesions.
Patients suffering from recurrent aphthous stomatitis (RAS) may have low levels of vitamin B12. A common cause of vitamin B12 deficiency is low intake of meat or other animal products. Administration of vitamin B12 has led to rapid improvement of RAS and complete recovery within several weeks.19
Zinc promotes wound healing and maintains epithelial integrity. Zinc sulfate in doses of up to 660mg/day produced a significant reduction in frequency of RAS in zinc-deficient patients.20
Licorice can be processed to remove glycyrrhiza, resulting in DGL (deglycyrrhizinated licorice), which does not appear to share the potential metabolic disadvantages (hypertension, hypokalemia, and fluid retention) associated with high doses of licorice. Patients with aphthous ulcers who used DGL mouth wash experienced 50-75% improvement within one day followed by complete healing of the ulcers by third day.21
Application of 5-aminosalicylic acid (5-ASA; mesalamine) 5% cream three times daily for up to 14 days for the treatment of aphthous ulcers shortened healing time and reduced the difficulty in eating. No significant side-effects were reported.22
“Rinse #5” (tetracycline, nystatin, triamcinolone, and 2-deoxy-D-glucose) has been used to reduce pain and promote the healing process.
In summary, dental preparations can be compounded to meet specific patient needs.
Compounding pharmacies can assist dental professionals by providing customized medications including:
* novel dosage forms such as lozenges, freezer pops, intraoralor topical gels, and muco-adhesive pastes, chewable “gummy treats”, and lollipops which are ideal for children or patients who have difficulty swallowing, or when a medication (such as an antifungal or anesthetic) needs to be held in contact with the oral mucosa.
* combinations of medications such as a mouthwash that contains a topical anesthetic, corticosteroid, antifungal, antibiotic, and/or antiviral.
* topical or transdermal gels for those who can not swallow or to minimize the risk of systemic side effects.
* Recently developed anhydrous bases to deliver medication through lipophilic tissues.
Compounding pharmacists are in a unique position to work with both patient and dentist to customize medications that meet specific patient needs and solve medical problems.
Marvin Malamed, B.Sc.Phm., C.C.N., has owned Haber’s Pharmacy (Toronto, ON) for over 16 years. He is a national award winning pharmacist (PCCA’s 2005 Canadian Compounding Pharmacist of the Year), a clinical nutritionist, and a founding member of the Ontario Compounding Association. The Professional Compounding Centers of America has described Marvin as “a community leader in the pharmacy compounding profession.” Under his influence, Haber’s Pharmacy has evolved into a pharmacy with a unique blend of traditional and holistic approaches, always with the focus on solving individual problems. He can be reached by calling 416-656-9800 or by emailing marvin @haberspharmacy.com.
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