Drugs in orthodontics and applications(2).pptx

Drugs in orthodontics and applications

1. Drugs in orthodontics Presented By – Dr. Princymol.K 1 st yr. PG 1

2. CONTENTS INTRODUCTION. EICOSANIDES. VITAMIN-D. NSAID’S. BISPHOSPHONATES. CORTICOSTERIODS. FLUORIDES. SEX STERIODS. THYROID. CALCITONIN. 2

3. PARATHYROID. IMMUNOSUPPRESSANT DRUGS. ANTI CONVULSANTS DRUGS ANTI CANCER DRUGS ALCOHOL ABUSE CONCLUSION. REFERENCES.

4. DRUG : It is the single active chemical entity present in a medicine that is used for diagnosis , prevention , treatment/cure of a disease. According to WHO (1966)- “Drug is any substance or product that is used or is intended to be used to modify or explore physiological systems or pathological states for the benefit of the recipient .” 4

5. Pharmacology : pharmacology is the science of drugs which deals with interaction of exogenously administered chemical molecules (drugs) with living systems. 5

6. Pharmacodynamics: what the drug does to the body? This includes physiological and biochemical effects of drugs and their mechanism of action at organ system /subcellular / macromolecular levels. 6

7. Pharmacokinetics: What the body does to the drug? This refers to movement of the drug in and alteration of the drug by the body; includes absorption, distribution, biotransformation and excretion of the drug . 7

8. Tooth movement is the key principle behind any orthodontic treatment. Orthodontic tooth movement (OTM) is mainly a biological response towards mechanical force. It is induced by the prolonged application of controlled mechanical force on the tooth, which eventually causes remodeling of the tooth socket by creating pressure and tension zones in the alveolar bone and periodontal ligament. Strains of periodontal cells, bone-related cells, and extracellular matrix play a key role in orthodontic tooth movement (OTM ). 8

9. Various cell-signaling pathways are activated, ultimately leading to stimulation of periodontal ligament metabolism, and localized bone resorption and bone deposition. These interactions are regulated by local factors such as cytokines ( IL-1), and growth factors, as well as by systemic factors such as parathyroid hormone, vitamin D, estrogen, or calcitonin . 9

10. Drugs that alter or interfere with the inflammatory process will therefore have an effect on the tooth movement. Several studies have proposed the effect of short and long term administration of medication on orthodontic tooth movement. Davidovitch et al.(2006) and Yamasaki et al.(1983) concluded in their study that the rate of orthodontic tooth movement can be altered by administrating certain drugs locally or systemically. 10

11. The drugs used in orthodontics can be broadly classified into two major groups, promoter drugs and suppressor agents. Promoter drugs are agents that act with the secondary and primary inflammatory mediators and enhance the tooth movement. Suppressor agents are drugs which reduces bone resorption . 11

12. PROMOTER DRUGS SUPPRESSOR DRUGS Prostaglandins Calcitonin Para thyroid hormone Bisphosphonates Vitamin D corticosteroids L-arginine Estrogens NSAIDS Anti cancer drugs Fluorides 12

13. Eicosanoids/autocoids These are biologically active derivatives of 20 carbon atom polyunsaturated fatty acids (PUFA) that are released from cell membrane phospholipids. There are two major lipid derived autocoids: 1 ) Prostaglandins (PG’s) 2) Leukotrienes (LT’s) 13

14. Biosynthesis of PG’S and LT’S 14

15. ACTIONS OF PG’S PG’s released due to mechanical, chemical, thermal stimuli. PGs play important role in inflammatory reponse . PG’s along with LT’s and other autocoids may mediate vasodilatation and exudation at the site of inflammation. Both PGE2 and PGI2 are the potent vasodilators and hyperalgesic agents. PGE2 is also potent pyrogenic substance . 15

16. PGI2- regulation of vascular tone as a vasodilator and exudation at the site of inflammation. PGE2-mediate bacterial or pyogenic induce fever. PGI2 and PGE2 –Sensitize afferent nerve endings to induce pain by chemical, mechanical and thermal stimuli. 16

17. Effect of PG’S on bone and tooth movement Experiments have shown that PGs mediate the inflammatory reponse in PDL during orthodontic force application facilitating in tooth movement. They stimulate bone resorption, root resorption, decreased collagen synthesis and increases cyclic AMP. They stimulate bone resorption by increasing the number of osteoclasts and activating already existing osteoclasts. 17

18. Chao et al(1988) observed that PGE2 injection increased the number of osteoclasts in pdl membrane. Davidovitch et al(1975) demonstrated in vitro direct effect of PG’s on bone resorption along with increase in CAMP and CGMP levels. Sandy et al (1984) found that inhibition of PG synthesis by flubiprofen, a PG inhibitor, showed inhibition of osteoclast activity and bone resorption. In another study by Gurton et al(2004) found that PGI2 and TXA2 analogs increase the number of multinuclear osteoclasts, osteoclastic bone resorption and rate of OTM. 18

19. 1st human study done by Yamasaki et al (1984 ) and 2nd by Patil AK et al (2005) clearly depicted that orthodontic tooth movement was achieved approximately twice faster if accomplished by local injection of prostaglandins. Ngan et al(1989) observed that PG’s cause hyperalgesia by facilitating pain stimulus and increasing the effects of histamine and bradykinin. The main side effect associated with local injection of PGs is hyperalgesia due to the release of noxious agents. 19

20. leukotrienes Leukotrienes are the metabolites of arachidonic acid, they are produced when arachidonic acid is metabolized by the enzyme lipo-oxygenase . It is produced by limited number of tissues( LTB4 mainly by neutrophils; LTC4 and LTD4-the cysteinyl LTs- mainly by macrophages. 20

21. Actions of LT’s It increases capillary permeability-leads edema formation. Important mediators of inflammation, produced at the site of inflammation and causes exudation of plasma. It sensitizes afferent carrying pain impulses, causes pain and tenderness at the site of inflammation. LTs are the most important mediators of human allergic asthma. 21

22. Effects on bone and tooth movement LTs important mediators of orthodontic tooth movement. They stimulate bone resorption by increasing the number of osteoclasts . 22

23. ANALGESIC Analgesic is a drug that selectively relieves pain by acting in the CNS or on peripheral pain mechanisms, without significantly altering consciousness. Analgesics are divided into two groups: A. Opioid/narcotic/morphine like analgesics. B. Nonopioid/non-narcotic/antipyretic/aspirin-like analgesics or nonsteroidal anti-inflammatory drugs (NSAIDs). 23

24. classification A. NONSELECTIVE COX INHIBITORS: 1. Salicylates: Aspirin. 2. Propionic acid derivative: Ibuprofen, Naproxen, ketoprofen, flurbiprofen. 3. Anthracitic acid derivative : Mephanamic acid. 4. Aryl-acetic acid derivative : Diclofenac. 5.Oxicam derivatives : Piroxicam, tenoxicam. 6. Pyrrolo-pyrrole derivative: Ketorolac 7. Indole derivative: Indomethacin. 8. Pyrazolone derivative : phenylbutazone, Oxyphenbutazone. 24

25. B. PREFERENTIAL COX-2 INHIBITORS: Nimesulide, Meloxicam, Nabumetone. C. SELECTIVE COX-2 INHIBITORS: Celecoxib, Etoricoxib, Parecoxib. 25

26. D. ANALGESIC-ANTIPYRETICS WITH POOR ANTI-INFLAMMATORY ACTION: 1. Paraaminophenol derivative : Paracetamol (Acetaminophen). 2. Pyrazolone derivatives : Metamizol (Dipyrone), Propiphenazone. 3. Benzoxazocine derivative : Nefopam. 26

27. Actions of NSAIDS ANALGESIC PROPERTY : NSAID’s do not affect the tenderness induced by direct application of PGs, but block the pain sensitizing mechanism induced by bradykinin, TNF α , interleukins (ILs). They are more effective against inflammation associated pain, including acute dental/ post extraction pain. 27

28. ANTIPYRETIC ACTION: NSAIDS reduce body temperature in fever, but do not cause hypothermia in normothermic individuals. NSAID’s block the pyrogenic actions of IL’s, TNF’s, IF’s which induce PG production in hypothalamus. 28

29. ANTI INFLAMMATORY ACTION: The most important mechanism of anti-inflammatory action of NSAIDs is considered to be inhibition of PG synthesis at the site of injury. 29

30. Mechanism of action Most NSAID’s act as non-selective inhibitors of the enzyme cyclooxygenase, inhibiting both the cyclooxygenase (COX-1) and (COX-2) isoenzymes. Cyclooxygenase catalyzes the formation of prostaglandins and thromboxane from arachidonic acid. Prostaglandins act as messenger molecules in process of inflammation. This mechanism was elucidated by John vane , who later received a noble prize for his work. 30

31. Pharmacological inhibition of COX can provide relief from the symptoms of inflammation and pain; this is the method of action of well-known drugs such as aspirin and ibuprofen. Currently, three COX isoenzymes are known –COX-1 , COX-2 and COX-3. 31

32. COX-1 is a constitutively expressed enzyme with a house keeping role in regulating many physiological process. One of these is in stomach lining , where prostaglandin serve a protective role, preventing the stomach mucosa from being eroded by its own acid. When non-selective COX-1/COX-2 inhibitors lower stomach prostaglandins levels, these protective effects are lost and ulcers of the stomach or duodenum and potentially internal bleeding can result. 32

33. COX is the enzyme responsible for the synthesis of various prostaglandins. Aspirin and most of the nonsteroidal anti-inflammatory drugs(NSAIDs) inhibit both COX-1 and COX-2 isoforms, thereby decrease prostaglandin and thromboxane synthesis. The anti-inflammatory effect of NSAIDs is mainly due to inhibition of COX-2. 33

34. COX-2 INHIBITORS- The discovery of COX-2 in 1991 by Daniel l. simmons at brigham young university raised the hope of developing an effective NSAID without the gastric problems characteristics of these agents. It was thought that selective inhibition of COX-2 would result in anti-inflammatory action without disrupting gastro protective prostaglandins. 34

35. ASPIRIN Aspirin is acetylsalicylic acid . It is rapidly converted in the body to salicylic acid which is responsible for most of the actions. ACTIONS OF ASPIRIN: Analgesic , antipyretic and anti-inflammatory. GIT - Aspirin released salicylic acid irritate gastric mucosa-cause epigastric distress , nausea and vomiting. Blood- It irreversibly inhibits TXA2 synthesis by the platelets .Thus , it interferes with platelet aggregation and prolongs bleeding time. 35

36. SIDE EFFECTS OF ASPIRIN 36

37. CONTRAINDICATIONS Gastric ulcer. Pregnancy and lactating womens. Bleeding disorders. Chronic liver diseases. Hypersensitivity. PRECAUTIONS- Aspirin should be stopped 1 week before elective surgery and dental extractions. 37

38. USES As analgesic for head ache, orofacial pains, myalgia , joint pain, neuralgia and dysmenorrhea. DOSE-0.3-0.6g as antipyretic. Acute rheumatic fever. Osteoarthritis. 38

39. Effects on tooth movement Clinical experience shows that orthodontic tooth movement is very slow in patients undergoing long-term acetylsalicylic therapy. Salicylate therapy decreases bone resorption by inhibition of PGs’ synthesis and may effect differentiation of osteoclasts from their precursors. Therefore, it is recommended that patients undergoing orthodontic treatment should not be advised to take aspirin and related compounds for longer period during orthodontic treatment. 39

40. ibuprofen Propionic acid derivative. MOA- Inhibition of PG synthesis at the site of injury. Anti-inflammatory actions similar to aspirin. Ibuprofen and all its congeners are better tolerated than aspirin. Side effects are milder. ADVERSE REACTIONS- gastric discomfort- nausea and vomiting. CNS side effects-head ache, dizziness, blurring of vision, tinnitus and depression. 40

41. USES OF IBUPROFEN Analgesic and anti-pyretic. Rheumatic arthritis, osteoarthritis. Musculo-skeletal disorders. Soft tissue injuries. Tooth extraction pain. Suppress swelling and inflammation and are very popular in dentistry. Ibuprofen 400mg+ codeine 60mg, used to relieve severe pains. 41

42. Effects on tooth movement Discomfort and pain after initial separator or arch wire placement are common experiences among orthodontic patients. If NSAIDs were given before the procedure, the body absorbs them before prostaglandin production, and this decreases the inflammatory response. 42

43. Bradley RL et al(2007) have evaluated the efficacy of preoperative analgesic consumption and have found that ibuprofen taken one hour before arch wire or band application decreases the pain levels from two hours after bonding until nighttime. They found that preoperative ibuprofen significantly decreased pain compared with postoperative ibuprofen. 43

44. Kehoe et al (1996) found that ibuprofen significantly inhibited the production of prostaglandin E (PGE) in the periodontal ligament and, subsequently, decreased the rate of tooth movement. Bartzela et al (2009) in their systematic literature review reported that after ibuprofen administration of 30 mg/kg twice a day in rats, the rate of orthodontic tooth movement decreased significantly. 44

45. DICLOFENAC SODIUM Aryl –acetic acid derivative. Analgesic ,antipyretic and anti-inflammatory drug. MOA- It inhibit PG synthesis. USES Toothache, Post-traumatic and post-operative conditions. Osteo-arthritis. Dysmenorrhea. 45

46. KETOROLAC Pyrrolo-pyrrole derivative. NSAID with potent analgesic and anti-inflammatory. Most effective in postoperative pain. Rapidly absorbed after oral and i.m route. ADVERSE REACTION- nausea ,abdominal pain , ulceration, loose stools, drowsiness. Uses -frequently used in postoperative , dental and acute musculoskeletal pain. Dose- 10-20mg 6 hourly oral route. 46

47. Indomethacin Indole derivative It is a potent anti-inflammatory drug with prominent antipyretic action. It is a highly potent inhibitor of PG synthesis. ADVERSE REACTION- High incidence of GIT and CNS side effects –nausea, gastric irritation, gastric bleeding, frontal headache , depression, rashes and hypersensitivity. 47

48. Contraindications: In machinery operators, drivers, psychiatric patients , renal disease, bleeding disorders, children and pregnancy. DOSE- 25-50mg BD. Uses - Malignancy associated fever. Medical closure of PDA. Acute gout. 48

49. Selective COX-2 inhibitors CELECOXIB: Has anti-inflammatory, analgesic & antipyretic actions with low ulcerogenic potential. Tolerability of celecoxib is better than older NSAIDs Slowly absorbed. Abdominal pain, dyspepsia & mild diarrhea are common side effect. 49

50. ROFECOXIB Highly selective COX-2 inhibitor introduced in 1999 had become popular for osteoarthritis, rheumatoid arthritis as well as for dental, post operative pain and acute musculoskeletal pain. This drug was withdrawn worldwide by its manufacturer in September 2004 due to high incidence of myocardial infraction and strokes. Banned in India. 50

51. VALECOXIB Have similar efficacy and tolerability as earlier COX-2 inhibitors. Used in osteo & rheumatoid arthritis, dental, postoperative pain, dysmenorrhea. Severe skin reaction such as Steven Johnson syndrome has reported. 51

52. ETORICOXIB Highly selective COX-2 inhibitors suitable for once a day treatment of osteo & rheumatoid arthritis, acute gouty arthritis, dental, postoperative pain, dysmenorrhea without affecting the platelet function or damaging gastric mucosa. 52

53. Paracetamol Para-amino phenol derivative. Actions - The central action of paracetamol is by raising pain threshold, weak peripheral anti-inflammatory actions. It is a poor inhibitor of PG synthesis in peripheral tissues, but more active on COX in brain. ADVERSE EFFECTS- nausea and rashes. Minimal gastric irritation ,low incidence of gastric erosion and bleeding. 53

54. USES - headache. toothache. dysmenorrhea. musculoskeletal pain. Comparative studies have been demonstrated to determine the effectiveness of acetaminophen in controlling pain and discomfort associated with orthodontic treatment. Roche JJ et al.(1997) reported that acetaminophen has no effect on the rate of tooth movement in rabbits undergoing orthodontic treatment. Generally, studies suggests that paracetamol does not affect orthodontic tooth movement, so it’s safe to use as a choice of pain management in orthodontic treatment 54

55. ANALGESIC/NSAIDS IN DENTISTRY Are mainstay for management of acute dental pain. Mild-moderate pain with little inflammation  paracetamol or low dose ibuprofen Post extraction or acute but short lasting pain  ketorolac, diclofenac, nimesulide/ aspirin Patients with H/O asthma or anaphylatoid reaction to aspirin/ other NSAIDs nimesulide Pediatric patients only paracetamol, aspirin, ibuprofen & naproxen have been adequately evaluated in children. 55

56. In Pregnancy, paracetamol is safest & low dose of aspirin is second best option. Hypertensive, epileptic, diabetic, ischemic heart disease and patient on other drugs for long term regularly should be considered for drug interaction with NSAIDs and should consult physician. 56

57. In 1980, Yamasaki and colleagues found that Indomethacin, non-steroidal COX1 & COX2 inhibitor, reduced bone resorption and orthodontic tooth movement in rats. These authors also demonstrated that the local injection of PG E-1 &E-2 into the submucosa overlying orthodontically treated doubled the rate of the tooth movement, both in monkeys and humans. Because PGs appear to be important in the process of tooth movement, it has been suggested that the use of over the counter NSAIDs by orthodontic patients can significantly alter the efficacy of tooth movement 57

58. Ibuprofen and aspirin significantly reduced the number of resorption lacunae and osteoclasts in the pressure areas of orthodontic tooth movement. Whereas Acetaminophen did not reduce number of resorption lacunae and osteoclasts in the pressure areas of orthodontic tooth movement. Acetaminophen probably does not alter osseous regeneration or dental movement because it acts at CNS level and does not affect the peripheral secretion of PGs. 58

59. 59

60. Vitamin d Vitamin D is a group of fat-soluble prohormones. Several forms of vitamin D have been discovered. The two major forms are vitamin D2 or ergocalciferol, and vitamin D3 or cholecalciferol. Vitamin D3 is produced in skin exposed to sunlight, specifically ultraviolet B radiation. Vitamin D plays an important role in the maintenance of organ systems. 1,25 dihydroxycholecalciferol is the most active hormonal form of vitamin D. 60

61. actions It regulates calcium and phosphate serum levels by promoting their intestinal absorption and reabsorption in the kidneys. Furthermore, it promotes bone deposition and inhibits PTH release. Although, at very high levels it will promote the resorption of bone. It also plays a role in the immune response by promoting immunosuppression. 61

62. Studies on Effects of vitamin d on tooth movement In 1988, Collins and Sinclair demonstrated that intraligamentous injections of a vitamin D metabolite, 1,25dihydroxycholecalciferol, caused an increase in the number of osteoclasts and the amount of tooth movement during canine retraction with light forces in cats. Similar results were observed by Takano-Yamamoto and colleagues in 1992. In 2004, Kale and colleagues observed that local applications of vitamins enhanced the rate of tooth movement in rats. According to them this effect was due to well balanced bone turnover induced by vitamin D. In addition, the stimulatory action of vitamin D on osteoblast can help stabilize orthodontic tooth movement 62

63. Bisphosphonates In pharmacology, bisphosphonates (also called: diphosphonates) is a class of drugs that inhibits osteoclast action and the resorption of bone . Its uses include the prevention and treatment of osteoporosis, osteitis deformans ("Paget's disease of bone"), bone metastasis (with or without hypercalcemia), multiple myeloma and other conditions that feature bone fragility . They act by inhibiting the osteoclastic activity and decreasing the number of osteoclasts. This leads to inhibition of orthodontic tooth movement and hence delays orthodontic treatment. 63

64. CLASSIFICATION First generation BPN- Etidronate Second generation BPN- Pamidronate Alendronate Third generation BPN- Risedronate Zoledronate 64

65. Effect of bpn’s on tooth movement Few studies have been reported on the effect of bisphosphonates in orthodontic tooth movement. All showed a dose-dependent decrease in the rate of OTM, with either topical or systemic administration of bisphosphonates. Sato Y et al(2000) did a study to clarify the effects of bisphosphonates administration on structure and function of osteoclasts in alveolar bone resorption during experimental tooth movement and found that BP significantly impair the osteoclast structure. 65

66. Liu et al(2004) also suggested the inhibitory effect of clodronate on tooth movement and osteoclasts may be due to inhibition of COX-2 dependent PGE2 production and RANKL expression in pdl cells. Liu et al found that local clodronate inhibited root resorption incident to tooth movement and suggested it to be a useful therapeutic adjunct in orthodontic treatment. 66

67. The clinical utility of bisphosphonates resides in their ability to inhibit bone resorption. In orthodontics, undesirable movement of anchor teeth during tooth movement and relapse of moved teeth after treatment are the main cause of unsuccessful results. 67

68. Kim et al(1999) suggested t hat a single systemic administration of bisphosphonate decreases the extent of initial relapse in experimentally moved rat molars via a mechanism involving impairment of the structure and resorptive functions of osteoclasts. In another study by Adachi et al (1994) , found that the topical administration of residronate may be helpful in anchoring and retaining teeth under orthodontic treatment. 68

69. Therefore it is imperative that Bisphosphonate medical screening, patient counseling, informed consent, and changes in treatment planning should be considered for every patient by the orthodontist. SIDE EFFECTS : Long term, use of bisphosphonate are very dangerous. They can cause osteonecrosis, especially in the alveolar bones of maxilla and the mandible. 69

70. PROPOSED ORTHODONTIC RECOMMENDATIONS Zahrowski propose the following recommendations for patients receiving bisphosphonate treatment. These recommendations are to be used for professional guidance and are not to be interpreted as the standard of care. Ask all patients whether they currently take or have ever taken IV or oral bisphosphonates and ask the medical reason for treatment (severe bone disorders, cancers, osteoporosis/osteopenia) on your screening/ medical history form. 70

71. Determine the risk of osteonecrosis and the level of osteoclastic inhibition . Route of administration and reason for bisphosphonate treatment .As, severe bone disorders and cancers has high risk of osteonecrosis and high level of osteoclastic inhibition. Oral bisphosphonate treatment for osteoporosis or osteopenia has a lower risk of osteonecrosis and lower level of osteoclastic inhibition; duration of treatment -(longer duration is associated with more risk) dose and frequency (presume that a higher dose or more frequent administration leads to higher risks). 71

72. Elective surgeries should be avoided (extractions, implants, periodontal surgeries) after IV bisphosphonates. Clinical monitoring should include to see any changes in decreased movement and increased mobility of teeth. Radiographic monitoring should include changes of sclerotic or radiolucent bone surrounding teeth. 72

73. CORTICOSTERIODS are a class of steroid hormones that are produced in the adrenal cortex. Corticosteroids are involved in a wide range of physiologic systems such as stress response, immune response and regulation of inflammation, carbohydrate metabolism, protein catabolism, blood electrolyte levels, and behavior. Glucocorticoids such as cortisol control carbohydrate, fat and protein metabolism and are anti-inflammatory by preventing phospholipid release, decreasing eosinophil action and a number of other mechanisms. Mineralocorticoids such as aldosterone control electrolyte and water levels, mainly by promoting sodium retention in the kidney. 73

74. classification GLUCO-CORTICOIDS- 1.Short acting : Hydrocortisone (t½< 12 hr.) (cortisol) 2.Intermediate acting : -Prednisolone (t½ 12-36hr) -Methyl-prednisolone -Triamcinolone 3.Long acting : -Dexamethasone -Betamethasone 74

75. MINERALO-CORTICOIDS- -Desooxycorticosterone acetate (DOSA) -Fludrocortisone -Aldosterone 75

76. Actions of gluco-corticoids Carbohydrate and protein metabolism : Promotes glycogen deposition in liver and promoting glyconeogenesis. They also cause protein breakdown and amino acid mobilization from peripheral tissues. Fat metabolism: Corticosteroids promotes lipolysis. Calcium metabolism: They inhibit intestinal absorption and enhances renal excretion of calcium, there is also loss of calcium from bone indirectly due to loss of osteoid. 76

77. Inflammatory responses: GC’s causes reduction of capillary permeability , local exudation , cellular infiltration , phagocytic activity. GC’s interferes in production of PG’S and several mediators of inflammation like LT’s , TNF and cytokinins. Immunological responses: They suppress all types of hypersensitivity and allergic phenomenon due to suppression of leukocytes. 77

78. Action of mineralocorticoids Enhancement of sodium reabsorption in DCT of kidney associated with increased K+ and H+ excretion. Excessive action leads to sodium and water retention, edema, progressive rise in BP and hypokalemia. 78

79. Uses Nephrotic syndrome , rheumatic fever, myasthenia gravis. Severe allergic reactions: anaphylaxis, urticaria. Recurrent oral ulcers. Intra-articular hydrocortisone injected in the TMJ to relieve refractory pain. Oral lesions like pemphigus, erosive lichen planus. 79

80. contraindications Peptic ulcer Diabetes mellitus Hypertension Renal failure Viral and fungal infections. 80

81. Effects on tooth movement Evidence indicates that the main effect of corticosteroid on bone tissue is direct inhibition of osteoblastic function and thus decreases total bone formation. Decrease in bone formation is due to elevated PTH levels caused by inhibition of intestinal calcium absorption which is induced by corticosteroids. Corticosteroids increase the rate of tooth movement, and since new bone formation can be difficult in a treated patient, they decrease the stability of tooth movement and stability of orthodontic treatment in general. 81

82. When they are used for longer periods of time, the main side effect is osteoporosis. It has been demonstrated in animal models with this type of osteoporosis that the rate of active tooth movement is greater, but tooth movement is less stable since little bone is present and there is no indication of bone formation. A more extensive retention may be required. 82

83. In 2004 , Kalia and colleagues evaluated the rate of tooth movement in rats during short and long term corticosteroid therapy. They demonstrated that bone remodeling seemed to slow down in acute administrations, whereas the rate of tooth movement increased in chronic treatment. 83

84. This suggest that orthodontic treatment should be postponed in patient undergoing short term corticosteroids whereas, patient with long term corticosteroid therapy treatment can be continued with minimal adverse effect and more extensive retention may be helpful in retaining these teeth if the dentist decides to proceed with the orthodontic treatment. 84

85. Fluorides Fluoride is one of the trace elements having an effect on tissue metabolism. Fluoride increases bone mass and mineral density, and because of the actions, it has been used in the treatment of metabolic bone disease, osteoporosis. Even a very active caries treatment with sodium fluoride during orthodontic treatment may delay orthodontic tooth movement and increase the time of orthodontic treatment. 85

86. Sodium fluoride has been shown to inhibit the osteoclastic activity and reduce the number of active osteoclasts. Foom et al(2007) evaluated the effect of systemic Fluoride intake on root resorption and found that fluoride reduces the size of resorption craters and therefore decreases the orthodontic tooth movement. \ 86

87. SEX STEROID Sex steroids, also known as gonadal steroids, are steroid hormones that interact with vertebrate androgen or estrogen receptors. Estrogen is considered the most important hormone affecting bone metabolism in women. It inhibits the production of cytokines involved in osteoclastic activation & bone resorption, such as IL-1, TNF-a & IL-6. 87

88. Yamashiro & Takano Yamamoto(2001) demonstrated an acceleration of tooth movement in spayed female rats. In 1996, Miyajima & colleagues attributed a female patient’s slow turnover of alveolar bone to her menopausal status and to the estrogen supplement she had been taking for three years. They also suggested that young women taking oral contraceptives might experience a reduced rate of tooth movement, although further studies are required in this area. The inhibitory effect of androgens on bone resorption has been demonstrated, but their influence on orthodontic tooth movement has not been clarified. 88

89. Relaxin Relaxin is a peptide hormone that was first described in 1926 by Frederick Hisaw. In the female, it is produced by the corpus luteum of the ovary, and placenta during pregnancy. In the male, relaxin is produced in the prostrate. Relaxin’s influence on soft tissue remodeling and on several mediators that stimulate osteoclast formation has attracted attention from orthodontic researchers. In 2005, Liu and colleagues showed that the administration of human relaxin might accelerate the early stages of orthodontic tooth movement in rats. 89

90. These authors suggested that relaxin might be used as an adjunct to orthodontic therapy, during or after tooth movement, for promotion of stability, for rapid remodeling of gingival tissue during extraction space closure or for orthopedic expansion in non-growing patients, by reducing the tension of stretched soft tissue envelope, particularly the expanded palatal mucosa, after Orthognathic surgery. 90

91. Thyroid hormone The thyroid hormones, thyroxine (T4) and triiodothyronine (T3), are tyrosine-based hormones produced by the thyroid gland. An important component in the synthesis is iodine. The major form of thyroid hormone in the blood is thyroxine (T4). The ratio of T4 to T3 released in the blood is roughly 20 to 1. Thyroxine is converted to the active T3 (three to four times more potent than T4) within cells by deiodinases (5'-iodinase). 91

92. Thyroid hormones play an essential role in the normal growth and development of vertebrates. They enhance the response to growth hormone, stimulate cartilage growth and differentiation and promote bone maturation and resorption . In bone remodeling, they act directly by stimulating the action of osteoclasts. 92

93. In 1999, Shirazi et al reported that thyroid hormone administration not only increased the rate of tooth movement in rats, but also reduced the extent of root resorption, as seen from scanning electron micrographs. In 1994, Poumpros and colleagues reported a protective effect from thyroxin on root resorptive lesions that had been induced by the application of orthodontic forces. 93

94. Vazquez L. et al(2002) showed that animals treated with thyroid hormones (intraperitoneal or oral) had significantly less force induced root resorptive lesions than were found in a control group. They also suggested that low doses of thyroid hormones may have a protective effect on root surfaces, either during orthodontic treatment or in patients who present spontaneous root resorptive lesions The clinical application of these drugs still need to be clarified. 94

95. The main hormone prescribed to reduce root resorption is L-thyroxine, which increases the resistance of cementum and dentin to clastic activity. Shirazi et al have confirmed this finding through the administration of increased doses of L-thyroxine to rats, which resulted in the reduction of the extent of root resorption . However, the results of the rat studies should be viewed with caution as no human trials on the use of L-thyroxine have been reported till now. 95

96. Calcitonin Calcitonin inhibits bone resorption by direct action on osteoclasts, decreasing their ruffled surface which forms contact with resorptive pit. Because of its physiological role, it is considered to inhibit the tooth movement; consequently, delay in orthodontic treatment can be expected. 96

97. 97

98. Parathyroid hormone Parathyroid hormone (PTH), or parathormone, is secreted by the parathyroid glands as a polypeptide containing 84 amino acids. It acts to increase the concentration of calcium (Ca2+) in the blood. Whereas calcitonin (a hormone produced by the parafollicular cells (C cells of the thyroid gland) acts to decrease calcium concentration. PTH acts to increase the concentration of calcium in the blood by acting upon parathyroid hormone receptor in three parts of the body. 98

99. Effects on serum phosphate PTH reduces the uptake of phosphate from the proximal tubule of the kidney which means more phosphate is excreted through the urine. Slightly more calcium than phosphate is released from the breakdown of bone. And the intestinal absorption of phosphate is decreased . The end result is a drop in the serum concentration of phosphate. 99

100. Feedback regulation Increased calcium concentration in the blood acts (via feedback inhibition) to decrease PTH secretion by the parathyroid glands. This is achieved by the activation of calcium-sensing receptors located on parathyroid cells. 100

101. Soma and colleague (1999) observed an increase rate of tooth movement in rats treated with PTH, whether administered locally or systemically. These results indicate that orthodontists should take note of patients being treated with PTH (osteoporosis). 101

102. Immunosuppressant drugs Patients with chronic renal failure or kidney transplants are on immunosuppressant drugs can encounter some difficulty during orthodontic treatment. Drug consumed for prevention of graft rejection (cyclosporine A) produce severe gingival hyperplasia, making orthodontic treatment and maintenance of oral hygiene difficult. 102

103. Treatment should be started or resumed after surgical removal of excessive gingival tissues once there is good oral hygiene. Whenever possible, fixed appliances should be kept to a minimum period with brackets and avoiding the use of cemented bands. Removable appliances in these cases are not recommended due to improper fit. 103

104. ANTICONVULSANTS DRUGS EPILEPSIES - These are a group of disorders of CNS characterized by paroxysmal cerebral dysrhythmia, manifesting as brief episodes (seizures) of loss or disturbance of consciousness , with or without characteristic body movements(convulsions) sensory or psychiatric phenomena. 104

105. Commonly used drugs are : Valproic acid - Absence seizures , myoclonic seizures. Phenytoin - Tonic clonic seizures, status epilepticus, trigeminal neuralgia. Gabapentin – Diabetic neuropathy, post-herpetic neuralgia. 105

106. Phenytoin -It induces gingival hyperplasia due to overgrowth of gingival collagen fibers, which involve the interdental papilla, making application of orthodontic mechanics and maintaining oral hygiene difficult. If used during pregnancy, it can produce fetal hydantoin syndrome characterized by hypoplastic phalanges, cleft palate, hare lip, microcephaly. 106

107. Valproic acid- Valproic acid has a potential to induce gingival bleeding even with minor trauma, making orthodontic maneuvers difficult. Gabapentin - Gabapentin produces xerostomia , making oral hygiene maintenance difficult during orthodontic treatment. In these cases, clinician should be aware of possible difficulties during Treatment period, and discuss it with the patients and or parents and educate them so that adequate measures to maintain oral hygiene are followed. 107

108. Alcohol abuse Chronic ingestion of large amounts on daily basis may have devastating effects on a number of tissue systems, including skeletal system. Alcoholism may lead to severe complications, such as liver cirrhosis, neuropathies, osteoporosis, and spontaneous bone fractures . Circulating ethanol inhibits the hydroxylation of vitamin D3 in liver, thus impending calcium homeostasis . 108

109. In such cases the synthesis of PTH is increased, tipping the balance of cellular function towards the enhanced resorption of mineralized tissues, including root resorption in order to maintain normal levels of calcium in blood. It was found that chronic alcoholics receiving orthodontic treatment are high risk of developing severe root resorption during course of orthodontic treatment. 109

110. Anticancer drugs There is every chance of observing disturbances in dental as well as general body growth and development due to the adverse effects of the chemotherapeutic agents. It is clearly stated that patients who had been on chemotherapy with busulfan/cyclophosphamide belong to the risk group for orthodontic treatment These drugs are known to produce damage to precursor cells involved in bone remodeling process, thereby complicating tooth movement . 110

111. CONCLUSION Therefore, it is imperative that the orthodontists need to pay attention to drug consumption and history of each and every patient, before and during the course of orthodontic treatment, so that the best treatment strategy (including force control and appointment intervals) can be selected for each case. Acetaminophen, which does not have significant influence on the rate of tooth movement, can be recommended for controlling pain during orthodontic treatment. 111

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117. THANK YOU 117