Professional Documents
Culture Documents
DR ARUN KUMAR BR
CONTENTS
• Introduction
• Effects of drugs on induce tooth movement
• Non-steroidal anti-inflammatory drugs
• Corticosteroids
• Bisphosphonates
• Acetaminophen
• Effects of systemic factors on induced tooth movement
• Sex hormone
• Relaxin
• Thyroid hormones
• Parathyroid hormone
• Vitamin D
• Conclusion
• Bibliography
• Orthodontic tooth movement is induced by the prolonged application
However, some of these ligands can also cause unwanted side effects,
effects.
Orthodontists often prescribe drugs to manage pain from force application
to biological tissues, manage TMJ problems, and tackle fungal and viral
infections throughout the course of treatment.
A recent review of pharmaceuticals commonly used in orthodontic practice,
provided an insight into the dosage, pharmacological actions and side
effects of these agents .
Apart from these drugs, patients who consume vitamins, minerals, and
other compounds, for the prevention or treatment of various diseases,
can also be found in every orthodontic practice. Some of these drugs
may have profound effects on the short- and long-term outcomes of
orthodontic treatment. However, in many cases little is known on the
nature of this interaction between specific drugs and orthodontic tissue
remodeling, thereby increasing the risk of negative effects.
For example, a recent editorial has raised concern regarding increased use
deficit disorders in children of all ages. In these children, this drug has
movement .
prescription.
• Mode of action
by John Vane, who later received a Nobel Prize for his work.
• Cyclooxygenase (COX) is an enzyme that is responsible for formation of
3. COX-3 is a splice variant of COX-1 which retains intron one and has a
variant (COX-1v).
• COX-2 inhibitors
protective effects are lost and ulcers of the stomach or duodenum and
etoricoxib.
• Classical NSAIDs
• The classical COX inhibitors are not selective (i.e. they inhibit all types of
COX), and the main adverse effects of their use are peptic ulceration and
dyspepsia.
direct irritation of the gastric mucosa (many NSAIDs are acids), and
• Selectivity for COX-2 is the main feature of celecoxib, rofecoxib and other
members of this drug class, but these drugs carry the risk of peptic
ulceration.
• Rofecoxib was taken off the market in 2004 because of these concerns.
reversibly inhibits COX-3, although there is now some doubt about this
thereby may interfere with the perception of pain. Since it has no effect
• COX-2 inhibitors have been found to increase the risk of atherothrombosis even
with short term use. A 2006 analysis of 138 randomised trials and almost 150 000
moderately increased risk of vascular events, mainly due to a twofold increased risk
of myocardial infarction, and also that high dose regimens of some traditional
NSAIDs such as diclofenac and ibuprofen are associated with a similar increase in
• These are most commonly used in orthodontics for the control of pain
isoforms
• COX-1 serves as physiological house keeping function
inhibitors.
Aspirin
• Is acetylsalicylic acid
• One of oldest analgesic - antiinflammatory drug and still used widely
• Rapidly converted in the body to salicylic acid which is responsible for
most of the actions
• Pharmacological action
• Analgesic ,antipyretic, antiinflammatory actions
• Metabolic effects
• Respiration
• Acid base and electrolyte balance
• CVS
• GIT
• Urate excretion
• Blood
• Analgesic action:
• Aspirin and other NSAIDs ↓↓ dull aching pain of low intensity (tooth
ache and head ache)
• Respiration:
• Avoided in diabetics, in those with low cardiac reserve or frank CHF and in juvenile
rheumatoid arthritis
• If given during pregnancy may be responsible for low birth babies, delayed
labour, greater postpartum bleeding and premature closure of ductus arterious are
possible if aspirin is taken at or near term
dose of aspirin
indomethacin
• Has been most common drug for medical closure of patent ductus
piroxicam
• In short term studies , gastric changes with the lower doses were found to be
similar to placebo, but at the higher dose they were intermediate b/w
• Gastric side effect are milder, but ulcer complications (bleeding ,perforation)
strokes
• Banned in India
• Valecoxib
• Etoricoxib
• Cinchona bark was also used to create the anti-malaria drug quinine.
Quinine itself also has antipyretic effects. Efforts to refine and isolate
salicin and salicylic acid took place throughout the middle- and late-19th
century, and was accomplished by Bayer chemist Felix Hoffmann (this
was also done by French chemist Charles Frédéric Gerhardt 40 years
earlier, but he abandoned the work after deciding it was impractical).
• When the cinchona tree became scarce in the 1880s, people began to look
& Co, a subsidiary of Sterling Drug Inc. Panadol was originally available
only by prescription, for the relief of pain and fever, and was advertised
as being "gentle to the stomach," since other analgesic agents of the time
NAPQI).
• Adverse effects
the kidneys. However, some studies have shown that high dose-usage
(greater than 2000 mg per day) does increase the risk of upper
gastrointestinal complications.
• Paracetamol is safe in pregnancy, and does not affect the closure of the fetal
to cause euphoria or alter mood in any way. Paracetamol and NSAIDs have
withdrawal, but, unlike opioid medications, may damage the liver; however,
addiction.
likelihood of causing toxicity. Toxicity can also occur when multiple smaller
doses within 24 hours exceeds these levels, or even with chronic ingestion of
• In children, acute doses above 200 mg/kg could potentially cause toxicity.
This higher threshold is largely due to larger kidneys and livers relative to
liver failure.
Adverse Reactions
• Since NSAIDs are freely available over the counter, patients should be
the orthodontists knowledge. One drug of choice for the patients under
• The widespread use of NSAIDs has meant that the adverse effects of
agents.
• Common ADRs, other than listed above, include: raised liver enzymes,
headache, dizziness (Rossi, 2006).
• Most NSAIDs penetrate poorly into the central nervous system (CNS).
However, the COX enzymes are expressed constitutively in some areas of
the CNS, meaning that even limited penetration may cause adverse effects
such as somnolence and dizziness.
Analgesic /NSAIDs in Dentistry
• Are mainstay for management of acute dental pain.
• Mild-moderate pain with little inflammation paracetamol or low dose
ibuprofen
• Postextraction or acute but short lasting ketorolac, diclofenac, nimesulide/
aspirin
• Patients with H/O asthma or anaphylatoid reaction to aspirin/ other NSAIDs
nimesulide
• Paediatric patients only paracetamol, aspirin, ibuprofen & naproxen have been
adequately evaluated in children. Due to risk of Reye’s syndrome, aspirin
should be avoided unless viral infection can be ruled out.
• Pregnancy paracetamol is safest & low dose of aspirin is second best
• Hypertensive, epileptic, diabetic, ischaemic heart disease and patient on other
drugs for long term regularly should be considered for drug interaction with
NSAIDs and should consult physician.
• Harell and colleagues in 1977, observed the synthesis of PG from
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
has been suggested that the use of over the counter NSAIDs by
movement
during the application of forces did not interfere with the tooth
orthodontic patients.
• Fewer osteoclasts were observed in the pressure side of orthodontically
moved incisors in rats treated with aspirin / ibuprofen. This may be due
to inhibition of PGs , there by reduced bone resportion and teeth moved
less. When PGs injected in the pressure area there was increased tooth
movement noticed. (Yamasaki et al)
• Lee introduced PGs locally and systemically in guinea pigs and observed
a significant in no. of osteoclasts in the pressure side of orthodontic tooth
movement.
• Study by Davidovitch and Shanfeld with cats showed that PGs were
responsible for bone resorption during tooth movement.
• Ibuprofen and aspirin significantly reduced the no. of resorption
lacunae and osteoclasts in the pressure areas of orthodontic tooth
movement, whereas Acetaminophen did not reduce no. 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.
Corticosteroids
• are a class of steroid hormones that are produced in the adrenal cortex.
(Werner, 2005).
remainder has a very high affinity for bone tissue, and is rapidly
Mechanism of action
• In chronic renal failure, the drugs are excreted much slower, and dose
adjustment is required.
• Bisphosphonates have been associated with osteonecrosis of the jaw;
with the mandible twice as frequently affected as the maxilla and most
osteonecrosis risks.
increasing demand for osseous repair that might exceed compromised alveolar
bone capability
• Teeth with grade 3 mobility are strongly associated with periodontal abscesses
and osteonecrosis.
• Monitor for signs and symptoms of later drug accumulation effects and
possible osteonecrosis
Sex steroid
• Sex steroids, also known as gonadal steroids, are steroid hormones that interact
with vertebrate androgen or estrogen receptors. The term sex hormone nearly always
is synonymous with sex steroid.
• Types
• In many contexts, the two main classes of sex steroids are androgens and estrogens,
of which the most important human derivatives are testosterone and estradiol,
respectively. Other contexts will include progestagen as a third class of sex steroids,
distinct from androgens and estrogens. Progesterone is the most important and only
naturally-occurring human progestagen.
• Sex steroids include:
• Androgens:
• testosterone
• androstenedione
• dihydrotestosterone
• dehydroepiandrosterone
• anabolic steroids
• Estrogens:
• estradiol
• estrone
• Progestagens:
• progesterone
• progestins
• The ovaries of sexually-mature females secrete:
• a mixture of estrogens of which 17β-estradiol is the most abundant
(and most potent).
• progesterone.
• Estrogens
• They are primarily responsible.
• development of breasts
• further development of the uterus and vagina
• broadening of the pelvis
• growth of pubic and axillary hair
• increase in adipose (fat) tissue
• participate in the monthly preparation of the body for a possible
pregnancy
• participate in pregnancy if it occurs
• Estrogens also have non-reproductive effects.
• They antagonize the effects of the parathyroid hormone, minimizing the
loss of calcium from bones and thus helping to keep bones strong.
• They promote blood clotting.
• The principal androgen (male sex hormone) is testosterone. This steroid
is manufactured by the interstitial (Leydig) cells of the testes. Secretion
of testosterone increases sharply at puberty and is responsible for the
development of the so-called secondary sexual characteristics (e.g.,
beard) of men.
• Testosterone is also essential for the production of sperm.
• Production of testosterone is controlled by the release of luteinizing
hormone (LH) from the anterior lobe of the pituitary gland, which is in
turn controlled by the release of GnRH from the hypothalamus. LH is
also called interstitial cell stimulating hormone (ICSH).
• Hypothalamus → GnRH→ Pituitary→LH→Testes→Testosterone
• The level of testosterone is under negative-feedback control: a rising
level of testosterone suppresses the release of GnRH from the
hypothalamus. This is exactly parallel to the control of estrogen secretion
in females.
• 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.
• In 2001, Yamashiro & Takano Yamamoto demonstrated an acceleration of
tooth movement in sprayed female rats.
• In 1996, Miyajima & colleagues attributed a female patients 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.
Relaxin
• In humans
• In women relaxin levels rise after ovulation as a result of its production by
the corpus luteum.
• During the first trimester of pregnancy levels rise and additional relaxin is
produced by the decidua.
• T1a and T0a are positively charged and do not cross the membrane; they
Region Effect
Bones
it enhances the release of calcium from the large reservoir contained in the bones.
Bone resorption is the normal destruction of bone by osteoclasts, which are indirectly stimulated by PTH.
Stimulation is indirect since osteoclasts do not have a receptor for PTH; rather, PTH binds to osteoblasts, the cells
Binding stimulates osteoblasts to increase their expression of RANKL, which can bind to osteoclast precursors
containing RANK, a receptor for RANKL. The binding of RANKL to RANK stimulates these precursors to fuse,
Kidney It enhances active reabsorption of calcium from distal tubules and the thick ascending limb.
Intestine
It enhances the absorption of calcium in the intestine by increasing the production of activated vitamin D. Vitamin D
via
kidney activation occurs in the kidney.
PTH up-regulates the enzyme responsible for 1-alpha hydroxylation of 25-hydroxy vitamin D, converting vitamin D to
its active form (1,25-dihydroxy vitamin D).
This actived form of vitamin D affects the absorption of calcium (as Ca2+ ions) by the intestine via calbindin. It enhances
the absorption of calcium in the intestine by increasing the production of activated vitamin D. Vitamin D activation
occurs in the kidney.
PTH up-regulates the enzyme responsible for 1-alpha hydroxylation of 25-hydroxy vitamin D, converting vitamin D to
its active form (1,25-dihydroxy vitamin D). This actived form of vitamin D affects the absorption of calcium (as Ca2+
ions) by the intestine via calbindin.
• Effects on serum phosphate (decrease, with compensation)
• PTH reduces the uptake of phosphate from the proximal tubule of the
• However, PTH also enhances the uptake of phosphate from the intestine
that of calcium. The end result is a small net drop in the serum
concentration of phosphate.
• 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.
• Syndromes
• A high level of PTH in the blood is known as hyperparathyroidism.
• If the cause is in the parathyroid gland it is called primary
hyperparathyroidism. The causes are parathyroid adenoma,
parathyroid hyperplasia and parathyroid cancer. secondary
• If the cause is outside the gland, it is known as hyperparathyroidism.
This can occur in chronic renal failure.
• A low level of PTH in the blood is known as hypoparathyroidism.
Causes include surgical misadventure (eg inadvertent removal during
routine thyroid surgery), autoimmune disorder, and inborn errors of
metabolism.
• In 1970s , animal studies demonstrated that PTH could induce an increase
systemically.
9. Roche JJ, Cisneros GJ, Ais G. The effect of acetaminophen on tooth movement in
rabbits. Angle Orthod 1997;67:231–6.
10. Polat O, Karaman AL. Pain control during fixed appliance therapy. Angle Orthod
2005;75:210–5.
11. Polat O, Kararam AI, Durmus E. Effects of preoperative ibuprofen and naproxan
sodium on orthodontic pain. Angle Orthod 2005;75:656–61.
13. Melo MD, Obeid G. Osteonecrosis of the jaws in patients with a history of
receiving bisphosphonate therapy. J Am Dent Assoc 2005;136:1675-81.