Monday, December 11, 2017

Old drugs, new uses

Resident’s Name: Brian Darling                                                                     Date: 12/13/17

Article Title: Old drugs, new uses
Author(s): Marcio da Fonseca, Paul Casamassimo
Journal: Pediatric Dentistry
Date: 2011; 33: 67-74
Major Topic: Drugs for pediatric patients
Type of Article: Literature review
Main Purpose: This article reviewed new uses for several medications, methods of action, and concerns for pediatric dental care.
Key Points:  One cannot assume that a certain drug is used only for the indication you learned in school

Drug Class
Original Indications
New Indications
Acetylsalicylic Acid
Antiplatelet therapy
Antiepileptic Drugs
Neurological conditions, psychiatric disorders, pain syndromes, eating disorders
Postmenopausal and steroid-induced osteoporosis
Primary and secondary osteoporosis, hypercalcemia of malignancy, metastatic bone disease in cancer, multiple myeloma
Botulinum toxin
Strabismus, blephatospasm
Hyperhidrosis, cervical dystonias, facial frown lines, spasticity, hyperlacrimiation, bruxism, rhinitis, hemifacial spasm, Tourette’s syndrome, incontinence, salivary secretory disorder, trismus, myofacial pain, headache
Psoriasis, polycythemia vera, cancer, thrombocythemia
Sickle cell disease
Intravenous immunoglobulin
Infections diseases, congenital immunodeficiencies, hypogammaoglobulinemia
Pediatric HIV infections, idiopathic thrombocytopenic purpura, Kawasaki disease, chronic lymphocytic leukemia, prevention of graft-versus-host disease, infections of HSCT, Guillain-Barre syndrome, autoimmune diseases
Juvenile idiopathic arthritis, psoriasis, inflammatory bowel disease, prevention of GVHD in HSCT
Epilepsy, sedation, antiemetic in pregnancy
Leprosy, multiple myeloma, meylodysplastic syndrome, Behcet’s disease, systetmic lupus erythematosus, aphthous ulcers, erythema multiforme, Crohn’s disease, treatment of post-HSCT GVGD

Anti-epileptic Drugs (Anti-seizure medications)
·      Incidence of psychiatric disorders is higher in epileptic patients
·      Most new anti-epileptic drug claims some efficacy for a psychiatric disorder
·      Used to treat:
o   Neurological conditions
o   Psychiatric disorders
o   Pain syndromes
o   Neuropathic pain
o   Essential tremors
o   Psychiatric disorders
o   Pain syndromes
o   Eating disorders
·      Adverse effects
o   Gingival overgrowth
o   Blood dyscrasias
o   Increased oral secretions or dry mouth
o   Behavior change
o   Liver dysfunction

·      Affects body immune’s system in several ways – anti-inflammatory and anticancer properties
·      Dose-limiting neutropenia and thrombocytopenia. Risk of thromboembolism

Intravenous Immunoglobulin
·      Increases platelet count
·      Physiologically and pharmacologically the same as immunoglobulin taken from the human body because it is purified from pooled human plasma from healthy donors
·      More than half of clinical IVIG use of “off-label”
·      ~10% of patients have side effects which are usually transient and self-limited – headache, low-grade fever, muscle, back, and joint pain, nausea, vomiting, abdominal pain
·      Very expensive

·      Increases production of fetal hemoglobin containing erythrocytes, which are less likely to sickle and dilutes the number of sickled cells in circulation and may reduce cell adhesion that contributes to vaso-occlusion
·      Dose-related leukopenia, thrombocytopenia, anemia, and oral mucositis
o   All usually resolve within 1-2 weeks
·      Long-term effects may include teratogenic defects, growth delays, cancer

·      Inhibits dihydrofolate reductase, an enzyme needed for DNA synthesis, repair, and cellular replication
·      Actively proliferating tissues are very sensitive to methotrexate, such as oral mucosa, bone marrow, malignant cells
·      Side effects: mucositis, taste disturbance, nausea, anorexia, headaches, chills, fatigue, pruritus, skin pain, urticarial, alopecia, acute depression, teratogenesis, nephropathy
·      May induce or exacerbate oral lesions like ulcers
·      Opportunistic infections may occur under methotrexate
·      Methotrexate absorption may be reduced with dental drugs of:
o   Nystatin, polymixin B, vancomycin, barbiturates, tranquilizers, NSAIDs, salicylates, penicillins
·      May increase risk of soft tissue necrosis and osteonecrosis when given in combination with radiotherapy

Botulinum Toxin
·      Neurotoxin from Clostridium botulinum, a gram-positive anaerobe, inhibits the release of acetycholine from presynaptic nerve terminals causing local chemodenervation
·      Reduces spasticity in patients with cerebral palsy leading to improvements in gross motor and upper extremity function, gait patterns, and independent ambulation
·      Transient effectiveness

·      Bind strongly to hydroxyapatite crystals and reduce bone resorption by inhibiting cell functions and inducing accelerated osteoclast death
·      Treats primary and secondary osteoporosis
o   Primary osteoporosis: intrinsic skeletal defect seen in osteogenesis imperfect, Marfan syndrome, Ehlers-Danlos syndrome
o   Secondary osteoporosis: sequelae of chronic diseases/conditions
·      Avoid surgical procedures, especially in children being given IV bisphosphonates
·      Insufficient evidence to suggest that implant placement, extraction, and other surgical treatments should be avoided in patients receiving oral bisphosphonates
·      No cases of BRONJ in children to date
·      Ask question about bisphosphonates on medical history because many are taken only every few weeks or months
·      Bisphosphonates may inhibit tooth movement for orthodontics
·      Bisphosphonates may delay tooth eruption

Aspirin (acetylsalicylic acid/ASA)
·      Inhibits COX-1-dependent platelet function (aggregation and vasoconstriction) at low daily doses
·      Also inhibits COX-2-dependent pathophysiologic processes of hyperalgesia and inflammation but requires larger doses to do so
·      Irreversibly inhibits COX-1 and so platelet inhibitory effect lasts entire 8-10 day lifespan of platelet
·      No studies exhibit a causal relationship between Reye Syndrome and aspirin
·      Aspirin has been replaced with acetaminophen often, which bears significant hepatotoxicity potential and may have led to increase in allergic reactions, most notably asthma because it lacks anti-inflammatory activity. Frequent acetaminophen use can cause asthma attacks
·      It is OK to proceed with surgical procedures in patients taking aspirin without any modification of care
·      Anesthesiologists often erroneously defer nasal intubation in patients taking aspirin unless the drug has been stopped for a few days prior to surgery, thus prolonging and complicating dental care under general anesthesia
Assessment of Article:  Level of Evidence/Comments: III

Dental care of the pediatric cancer patient

Article Title: Dental care of the pediatric cancer patient
Author(s): Marcio A. da Fonseca
Journal: Pediatric Dentistry
Date: 2004; 26: 53-57
Major Topic: Dental management of children with cancer
Type of Article: Literature review
Main Purpose: This article aimed to discuss recommendations for dental care of the pediatric oncology patient.
Key Points: It is very important to be knowledgeable about the oral implications of cancer and its treatment because physicians and nurses involved in the patient’s care rarely discuss these issues.
·      Cancer is the leading cause of disease-related death in children <14 years in the USA
·      Cancers incidence is greatest the 1st year of life with a 2nd peak at 2-3 years followed by a decline to age 9 and then an increase through adolescence
·      Boys > girls
·      Most common pediatric cancers: ALL > CNS tumors > sarcomas
·      Radiation therapy
o   Given over several weeks in a series of equal-sized fractions usually spaced by 24 hours to allow repair of normal tissues
·      Acute Lymphoid Leukemia
o   Most common childhood cancer
o   75% of childhood leukemias. Peaks at 4 years
o   Craniofacial manifestations: lymphadenopathy, sore throat, laryngeal pain, gingival bleeding, oral ulceration
o   4 phases of treatment
§  Remission induction: usually 28 days; 3-4 drugs (vincristine, prednisone, L-aspariginase)
§  CNS preventive therapy/prophylaxis because CNS can act as reservoir for leukemic infiltrates (normal chemotherapeutics can’t cross blood-brain barrier). Cranial irradiation and/or weekly intrathecal injection
§  Consolidation or intensification: intensified treatment to minimize drug cross-resistance and minimize remaining leukemic cells.
§  Maintenance: 2.5-3 years to suppress leukemic growth
·      Central Line: indwelling catheter inserted into the right atrium of the heart for obtaining blood samples and administering drugs
o     Antibiotic prophylaxis is NOT needed for these patients
·      Increased bleeding risk in patients with liver tumor or dysfunction
·      Prothrombin time: measures extrinsic pathway
·      Partial thromboplastin time: measures intrinsic pathway
·      Platelet Counts
o   Normal: 140,000-340,000/mL
o   >75,000/mL – no additional support needed
o   40,000-75,000/mL – consider platelet transfusion pre-op and 24 hours post-op
o   <40,000/mL – defer elective treatment; contact physician about emergency treatment (platelet transfusion, bleeding control, hospital admission)  
o   Platelet concentration peaks 45-60 minutes after transfusion
·      Absolute Neutrophil Count (ANC)
o   >2000/ml – no antibiotic needed
o   1000-2000/ml – use clinical judgment about using antibiotics
o   <1000/ml – defer elective treatment and discuss antibiotic coverage with physician if emergency treatment is needed
·      Toothbrushing is OK even though many medical and dental providers think it increases risk of bacteremia and bleeding
o   Patients can brush without bleeding at various platelet levels
o   Good oral hygiene decreases risk of mucositis without increasing risk of septicemia and oral infections
o   Avoid sponges, foam brushes, supersoft brushes because they do not provide effective mechanical cleaning unless the patient has severe mucositis
o   Air dry brushes between uses
o   Use dentifrice without heavy flavoring agents because they can irritate tissues
·      Avoid toothpicks and water-irrigating devices when neutropenic
·      Consider prescribing chlorhexidine for patients with poor oral hygiene or periodontal disease
·      Many pediatric medications have high amounts of sucrose
·      Nystatin should not be prescribed as prophylaxis for Candida infections in immunosuppressed patients
·      Vomiting is a common side effect of cancer treatment. Patients should rinse with tap water or bland solutions to remove gastric acid which is irritating to oral tissues and may cause enamel decalcification  
·      Notify physician of spontaneous gingival bleeding because it may be a sign of internal hemorrhage
·      Patients may experience paresthesia due to leukemic infiltration around peripheral nerves
·      Vincristine and vinblastine can cause pain that mimics irreversible pulpitis but will go away within a few days after stopping the drug.
·      Blood counts start falling 5-7 days after the beginning of each treatment cycle, staying low for approximately 14 days before rising again.
·      No pulpal treatment in primary teeth à only extractions because pulpal and periapical infections can have serious effects on cancer treatment when the patient is immunosuppressed.
·      May perform RCT on nonvitial, symptomatic teeth if there’s at least 7 days before cancer treatment. Extract if this cannot be done.
·      May delay endodontic treatment in neutropenic patients with asymptomatic teeth with periapical involvement  
·      Signs of infection like swelling and purulent exudate may be masked when patient is immunosuppressed.
·      Fixed orthodontic appliances and space maintainers should be removed if patient has poor hygiene.
·      Removable appliances and retainers may be worn if the patient has good hygiene
·      Consider removing gingival tissue if concerned that gingival tissue over partially erupted molars are at risk of pericoronitis
·      Loose primary teeth may be left to exfoliate if the patient does not play with them to avoid bacteremia. Extract loose primary tooth if the patient is not compliant
·      Ideally extract teeth 3 weeks before cancer treatment and at least 4-7 days before of: impacted teeth, root tips, partially erupted third molars, teeth with periodontal pockets >5mm, teeth with acute infections, nonrestorable teeth
·      If medical status of patient does not allow extraction, may consider amputating crown above the gingiva followed by root canal treatment with antimicrobial medicament and then providing antibiotics for 7-10 days.
·      Orthodontic treatment may be started 2 years after disease-free survival. Recommended to use appliances that minimize risk of toot resorption, use lighter forces, terminate treatment earlier than normal, choose simplest method for treatment needs, and do not treat the mandible.

1- Dated article
Assessment of Article:  Level of Evidence/Comments: III