Role of drugs in orthodontics

APPLIED PHARMACOLOGY IN
ORTHODONTICS.
www.indiandentalacademy.com

CONTENTS.
Introduction.
Eiocosanides.
NSAID’s.
Effects of NSAID’s on tooth
movement.
Bisphosphonates.
Vitamin-D metabolites.
Hormonal drugs.
Anti-biotics.
Conclusion.
References.

Introduction.
During orthodontic treatment ,often prescribe drugs to manage
pain from force application to biological tissues , manage TMJ
problems and tackle some infections throughout course of
treatment. Apart from these drugs patients who consume
vitamins , minerals, hormonal supplements and other
compounds for the prevention or treatment of various
diseases, can also found in every orthodontic practice.

Introduction.
Some of these drugs may have profound effects on the short
and long term outcomes of orthodontic practice. Hence it is
necessary to review the mechanism of action and effects of
commonly used drugs on tissue remodeling and orthodontic
tooth movement.

Introduction
 DRUG; It is the single active chemical entity present in
a medicine that is used for diagnsis ,
prevention, treatment /cure of a disease.
According to WHO(1966) Drug is any substance
or product that is used to modify or explore
physiological systems or pathological states for the
benefit of the recipient.

1.Pharmacodynamics; What the drug does to the body?
It includes physiological and biochemical effects of drugs and their
mechanism of action at organ system/subcellular/macromolecular
levels.
2.Pharmacokinetics; What the body does to the drug?
It refers to movement of the drug by the body,which includes
absorption, distribution, binding/ localiszation, storage,
biotransformation and excretion of drug
Pharmacology is the science of drugs which deals with the
Interaction of exogenously administered chemical molecules
(drugs) with living systems.
PHARMACOLOGY

Eiocosanides/ autocoids
These are the biologically active derivative of 20 carbon
atom PUFA’s that are released from cell membrane
phospholipids.
There are 2 major lipid derived autocoids.
1.Prostaglandins
2.leukotriens.

Biosynthesis PG’s and LT’s.
Dietary EFA
Membrane phospholipids
Arachidonic acid
Hydro-peroxides
Lipo-oxygenases(LOX)
LEUKOTRIENS(LT’s)
Cyclo-oxygenases
COX1&COX2
PGG2
PGH2
COX1,COX2
PGI-sythetase
(PGI)Prostacyclines PGF1,PGD,PGH2 (TXA)Thromobxane
TXA-synthetase

Most of the tissues are capable of synthesizing PG’s from the dietary
essential fatty acids.
PG’s released due to mechanical,chemical ,thermal &bacterial insults.
Both PGE 2 and PGI 2 are the potent vasodialators & hyperalgesic
agents.PGE2 is also potent pyrogenic substance.
PG’s play important role in inflammatory response.
Prostaglandins(PG’s)

Actions of PG’s.
PGI2 –Regulation of vascular tone as a vasodilator and
exudation at the site of inflammation.
PGI2-Anti-aggregatory,TXA2- aggregation of platelets.
PGE2-mediate bacterial or pyogenic induced fever & malease at
the level of hypothalamus.
PG’s-neuromodulators in the brain by regulating neuronal
exitabilty,sympathetic neurotransmission in periphery.
PGE2 & PGI2-sensitize afferent nerve endings to induce pain
by chemical, mechanical & thermal stimuli.

Effect of PGs on bone & tooth
movement.
Experiments have shown that PG’s may be mediators of
mechanical stress during orthodontic tooth movement.
They stimulate bone resorption,root resorption, decreased
collagen synthesis and increase cyclicAMP.
They stimulate bone resorption by increasing the number of
osteoclasts and activating already existinng osteoclasts.
Am J Orthod Dentofacial Orthop1995; 108: 380-8

Effect of PGs on bone & tooth
movement.
 A lower concentration of PGE2 0.1-1microgram appears to be
effective in enhancing tooth movement.
 Higher concentration leads to root resorption.
 Systemic adminstration is reported to have better effect than
local adminstation.
Am J Orthod Dentofacial Orthop1995; 108: 380-8www.indiandentalacademy.com

Leukotrienes(LT’s)
Leukotrienes are the metabolites of Arachodonic acid,they
are produced when arachdonic acid is metabolized by the
enzyme lipo-oxygenase.
It is produced by limited number of tissues,mainly by LTB4
neutrophils,LTC4 & LTD4-cysteinyl – LTs by macrophages.

Leukotrienes(LT’s)
Actions;
 LTC4&LTD4 injected i.v. it rises BP fallowed by more
prolonged fall in BP.
 It increases capillary permeability –leads edema formation.
 Important mediators of inflammation, produced at the site
of inflammation& causes exudation of plasma.

Leukotrienes(LTs).
It sensitizes afferent carrying pain impulses,causes pain and
tendorness at the site of inflammation.
It constricts smooth muscle,important mediator in allergic asthma.
Effects on bone and tooth movement.
LTs important mediators of orthodontic tooth movement.
It stimulates bone resorption.This role is clearly demonstrated
when inhibitors of LTs synthesis are used in experiment model.
Quintessence .Int 2001;32:365-371.

Analgesics.
 Analgesic is a drug that selectively relives pain by
acting on the CNS or peripheral pain mechanisms,
without significantly altering consciousness'.
1.Opiod /narcotic/morphine like analgesics
2.Non-opiod /non-narcotics /NSAID’S
TYPES OF ANALGESICS

Classification of
NSAID’S
A..Non-selective COX inhibitors(conventional NSAID’s)
1.Salisylates; Asprin
2.Proprionic acid derivatives ;Ibuprofen,Naproxen,Ketoprofen,Flurbiprofen.
3.Anthranilic acid derivatives; Mephenamic acid
4.Aryl-acetic acid derivatives; Diclofenac.
5.Oxicam derivatives; Piroxicam,Tenoxicam.
6.Pyrrolo-pyrrole derivatives; Keterolac
7.Indole derivative; Indomethacin.
8.Pyrazolan derivatives; Phenylbutazone,Oxyfenbutazone.

Classification of
NSAID’s
B.Preferential COX-2 inhibtors.
1.Nimesulide,2.Meloxicam,3.Nabumetone.
C.Selective COX-2 inhibitors
1.Celicoxib,2.Roficoxib,3.Valdicoxib,4.Etoricoxib
D.Analgesic-antipyretic with poor anti-inflammatory action.
1.Para-aminophenol derivative; Paracetamol(Acetaminophen)
2.Pyrazolone derivatives ;Metamizole(Dipyrone),Propiphenazone.
3.Benzoxacaine derivative ;Nefopam.

Analgesic property
 NSAID’s donot affect the tenderness induced
by direct application of PG’s, but block the pain
sensitizing mechanism induced by bradykinins,
TNF’s,IL’s .etc.

Antpyretic Action
NSAID’s reduce body temperature in
fever,but donot cause hypothermia
in normothermic individuals.NSAID’s
block the pyrogenic actions of
IL’s,TNF’s,IF’s which induce PG
production in hypothalamus.

ASPIRIN
Aspirin is acetylsaicylic acid ,it rapidly converted in the body to
salicylic acid.
Mechanism action
The analgesic action is mainly due to obtunding
of peripheral pain receptors and prevention of PG
mediated sensitization of nerve endings.
Aspirin resets the hypothalamic thermostat and
rapidly reduces fever by promoting heat loss
by sweating,cutanious vasodilation.

Actions of Aspirin.
Analgesic,antipyretic and anti-inflammtory.
Increase in cellular metabolism,especially in skelital muscles,
due to uncoupling of oxidative phsphorylation –incerased heat
production .
It stimulates the respiration ,Further increase in salicylate
level causes respiratoy depression.
Produces significant change in acid-base and
electrolyte balance.

Actions of Aspirin
GIT; Aspirin and released salicylic acid irritate gastric
mucosa-cause epigastric distress,nausea,vomiting.
Blood; It irreversibly inhibits TXA2 synthesis by the
platelates.Thus inerfere with the platelet aggrigation
and prolongs BT.

Adverse effects of
Aspirin.

Contraindications
Hypersensitivity
Gastric ulcers.
Diabetic individuals .
Pregnant and lactating womens.
Bleeding disorders.
Hemolytic anemia.
Chronic liver disorders.
PRECAUTION ; Aspirin should be stopped 1week before
elective surgery and Dental extractions.

Uses of Aspirin
1.Analgesic for head ache,orofacial pains,mayalgia,joint
pain,neuralgeias. Dose; 0.3-0.6g,6-8hourly
2.Acute rheumatic fever.
3.Rheumatoid arthritis . Dose; 3-5g/day.
4.Ostoarthritis.
5.Postmayocardial infraction and post-stroke patients.

Ibuprofen.
Proprionic acid derivative.
MOA; Inhibition of PG synthesis at the site of injury.
Anti-inflamtory actions similar to aspirin.
Ibuprofen and all its congeners are better tolerated than
aspirin.Side effects are milder.
Adverse reactions –Gastric discmfort,nausea and vomiting
CNS side effects-head ache,dizziness,blurring of vision,
tinnitus and depression.
 Dose;400-600mg TDS.
 Ketoprofen ;50-100mg BID, Naproxen; 250mg BID.www.indiandentalacademy.com

Uses of ibuprofen.
Analgesic and anti-pyretic.
Rheumatic arthritis, osteoarthritis.
Musculo-skeletal disorders.
Soft tissue injuries.
Extractions and fractures-to reduce post-operative swelling
and inflammation.
Ibuprofen 400mg+codeine 60mg ,used to relieve severe pains.

Anthranilic acid
derivative
Mephenamic acid(Fenamate)
-Analgesic,Antipyretic and Anti-inflammtory drug.
-MOA:It inhibits COX as well as antagonises certain actions of PG’s.
-Peripheral and central analgesic actions.
-Oral absoption is slow but almost complete.
-Adverse Rxns: Diarrhoea, epigastric distress,rarely haemolytic
anaemia.
-Used primarily as a analgesic in muscle, joint and soft
tissue
where strong anti-inflammatory action is not reqired.-Dose:250-500mg TDS www.indiandentalacademy.com

DICLOFENAC SODIUM
 Aryl –acetic acid derivative.
 Analgesic, antipyretic and anti-inflammatory drug.
 MOA: It inhibit PG synthesis and has short lasting
anti-platelet action.
 It is well absorbed orally, 99% protein bound,metabolized,
because of its good tissue penetrability ,concentration in
joints and other site of inflammaton is maintained for
longer period of therapeutic effect.
 Uses: Post-traumatic and post-operative conditions,
tooth ache,osteoarthritis,rhuematoid arthritis;bursitis.
Dose :100mg BID, 50mg TID. www.indiandentalacademy.com

Piroxicam
 Oxicam derivative
 It is a long –acting NSAID with potent anti-
inflammatory,
good analgesic,anti-pyretic actions. MOA :It is reversible inhibitor of COX,It lowres PG
concentration
of synovial fluid and inhibits platelet aggregation prolongs the
bleeding time. Absorbs rapidly and completely by oral route,99% plasma
proteinbound,largely metabolized in the liver.
 Ad.Rxns : Heart burns,nausea and
anerexia,rashes. Used in cases of RA,OA,Ankylozing spondelytis,acute
gout,musculo-skeletal injuries.
Dose: 20mg BD for two days, followed by 20mg daily OD.www.indiandentalacademy.com

KETOROLAC-Pyrrolo-pyrrole derivative
NSAID with potent analgesic and anti-inflammatory activity.
Most effective in postoprative pain.
Act by inhibition of PG synthesis and relieves pain by
peripheral mechanism.
Rapidly absorbed after oral and i.m. route.
Ad.Rxn: Nausea,abdominal pain,dyspepsia,ulceration,head ache,
dizziness,nervousness,pruritis,fluid retention.
Frequently used in postoperative,dental and musculoskelital pain,
pain due to bony metastasis and migraine.
Dose :10-20mg 6hourly oral route. 15-30mg i.m. 6hourly.www.indiandentalacademy.com

Indomethacin
 It is a potent anti-inflammatory drug with prominent
antipyretic action.
 It is a highly potent inhibitor of PG synthesis and suppress the
neutrophil motility.
 Well absorbed orally,90% protein bound to plasma proteins,
partly metabolized by the liver .
 Ad.Rxn: High incidence of GIT&CNS side effects-anerexia,
nausea,gastric irritation,gastric bleeding,frontal head ache,
dizziness,mental confussion,hallucination,depression and
psychosis,leukopenia,rashes & hypersensitiviy.www.indiandentalacademy.com

Indomethacin
Contraindications : In machinary operators,drivers,
Psychiatric patients,renal disease,bleeding disorders,
children,pregnancy.
Dose: 25-50mg BD
Uses : Ankylosing spondylitis.
Destructive arthropathies.
Psoriac arthritis.
Acute gout.
Malignancy associated fever.
Medical closure of PDA.

Preferential COX-2
Inhibitors.
NSAID is a relativevely weak inhibitor of PG Synthesis and
anti-inflammatory action may be exerted by reduced generation
of superoxide by neutrophils,inhibiton of PAFsynthesis and
TNF release,free radicle scavanging,inhibition of metalloprotease
activity in cartilage.
1.Nimesulide, 2.Meloxicam and
3.Nabumetone
Nimesulide:

It completely absorbed from oral route,99% plasma bound,
extensively metabolized in the liver and excreted in urine.
Ad.Rxns : GIT symptoms like epigastralgia,heart burn,
nausea, skin rashes.
Contraindications: In childrens below 4 years,known to cause
haematuria,fulminent hepatic failure.
Dose: 100mg BD.
Nimesulide

 Prodrug-generates an active metabolite(6-MNA).
 Rlatively more potent COX-2 than COX-1 inhibitor.
 Analgesic ,antipyretic and anti-inflammatory actions.
 Used in cases of RA,OA and soft tissue injuries.
 Lower incidence of gastric errosions,bleeding dueto
COX inhibitor produced in tissues after absorption.
 Dose: 500mg tab. OD
Nabumetone.

Selective COX-2 inhibitors.
 Selective COX-2 inhibitors cause little gastric mucosal damage,peptic
ulcer lower than other NSAID’s.
 They donot depress TXA2 production by the platelets,don’t inhibit
platelet aggregation or prolonged BT.But they can reduce PGI2
production by vascular endothelium.
Celecoxib.
 Anti-inflammatory,analgesic and antipyretic actions.
 Slowly absorbed ,97% plasma protein bound metabolized primarily by
liver.
 Dose: 100-200mg BD.
 Used in osteo and rheaumatoid arthritis.
1.Celecoxib, 2.Valdecoxib , 3.Etoricoxib &4.Rofecoxib.

Valdecoxib
Simlar actions ,efficiency & tolerability like Celecoxib.
Dose :10mg OD in ostoarthritis and rheaumatoid cases.
20mg BD in Dental or postoperative pain.
Etoricoxib
Highly selective COX-2 inhibitor, similar actions & like Valdecoxib.
Dose :60-120mg OD.
Roficoxib.
Highly selective COX2 inhibitor commoly used forRA,OA,dental,

Para-amino phenol
derivatives.
1.Phenacetin and 2.Paracetamol(Acetaminophen)
Phenacetin.
 Introduced in 1887 was extensively used as analgesic-antipyretic.
 Banned because it was implicated in analgesic abuse neuropathy.
Paracetamol(Acetaminophen)
 It is a de-ethylated active metabolite of phenacetin,
 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.
 Minimal gastric irritation , low incidence of gastric errosion,bleeding.
 Anti-pyretic doses of paracetamol is safe and well tolerated. www.indiandentalacademy.com

Paracetamol.
Well absorbed from oral route,only about 1/3 is protein bound in
plasma and unifom distribution in the body.
It is conjugated with glucuronic acid and sulfate and is excreted
in urine rapidly.Plasma t1/2 is 2-3hrs.
Adverse reactions:
Nausea,rashes occurs rarely,anlagesic neuropathy(long term use).
Acute paracetamol poisening-seen in small children having low
hepatic glucuronide conjugating ability.

Paracetamol.
 Treatment of paracetamol poisening: Induce vomiting or gastric
lavage.Activated charcoal given to prevent further absorption.
 Antidote; N-acetycysteine i.v. infusion or given orally,it replineshes
hepatic glutathione and prevents binding of toxic metabolite to
other cellular constituents.
 DOSAGE ;500mg-1g, total daily dose should not exceed
2.5gm in adults.
In childrens 1-3 years , 80-160mg, tds.
4-8 years , 240-320mg,tds.
9-12years , 300-600mg.tds.

Effect of NSAID’s on tooth
movement.
Most commonly used medications used in
orthodontics,for control of pain following mechanical
force application to tooth.
Mechanism ;PG’s a product of arachdonic acid
metabolism,are local harmone like agents produced
by mammal cells,osteoblasts after cell injury.These
20 carbon atom EFA molecules are important role as
mediator of inflammatory response, which facilitates
tooth movement.Inhibition of this inflammatory
reaction slowing of the tooth movement.
Orthod Craniofacial Res 9,2006/163-171

movement.
Recent research demonstrated the molecular mechanisms
behind the inhibition of tooth movement by NSAID’s,the levels
of Matix Mettallo-proteinnases(MMPs)-9 and (MMPs)-2 were
found to be increased, along with elevated colagenase
activity,followed by a reduction in procollagen synthesis which
are essential for bone and periodontal remodelling.
The whole process is controlled by inhibition of COX activity,
leading to altered vascular and extra vascular matrix
remodelling,causing a reduction in the pace of the tooth
movement.

Acetylsalicylic acid and the related compounds ,their action results
from inhibition of cyclooxygenase activity ,which converts USF’s in cell
membrane to prostaglandins.
Clinical experience shows that orthodontic tooth movement is very
slow in patients undergoing longterm acetylsalicylic therapy
Salicylate therapy decreases bone resorption by inhibition of
PG’s synthesis and may affect differentiation of osteoclasts from
their precursors.
There fore, it is recommended that patients undergoing orthodontic
treatment ,should not advised take aspirin & related compounds for
longer period during orthodontic treatment.
Effect of NSAID’s on
tooth movement.
Quintessence Int 2001;32:365-371.www.indiandentalacademy.com

An interesting recent development seen in prescriptions of a specific
COX-2 inhibitor,rofecoxib,a drug with no effect on PGE2 synthesis.
These drugs selectively block the COX2 enzyme, and impede the
production of PG’s that cause pain and swelling.
Because they selectively block COX2 enzyme not COX1 enzyme, it
was suggested that rofecoxib can be safely employed during
orthodontic mechanotherapy,without causing negative effcts on
tooth movement.
This drug no more prescribed due to risk of cardiovascular events.
movement.

Acetaminophen(paracetamol),a weak COX-1 and COX-2 inhibitor that
also reduces urinary prostaglandin levels after systemic adminstration,
has shown no effect on orthodontic tooth movement in guinea pigs
and rabbits.
Comparative studies and clinical experience shown that acetaminophen
is effective for controlling pain and discomfort associated with the
Orthodontic treatment.
movement.
JCO / Feb.2007;73-78

Effects of NSAID’s on tooth
movement.
A recent study reported that nabumetone ,a belonging
to NSAID group , reduces the amount of root resoption
along control of pain from intrusive orthodontic forces,
without affecting the pace of tooth movement.
J Endod 2005; 31:61-6

Flourides.
 Flouride is a one the trace element that affect had tissue
metabolism.
Actions;
 Flouride increases bone mass,mineral density and because
of these skeletal actions ,it has been used in treatment of
metabolic bone diseases,osteoporosis.
 Even a very active caries treatment with sodium flouride during
othodontic treatment may delay orthodontic tooth
movement and the time of orthodontic treatment.
 Sodium flouride,it has been shown to inhibit the osteoclastic
activity and reduce number of active osteoclasts.www.indiandentalacademy.com

Bisphosphonates
These groups of drugs high affinity for calcified tissues, potent
blockers of bone resorption.
They have commonly used in treatment of hypercalcemia,osteoporosis
and metabolic bone diseases that causes bone resorption.
Increases ostoblastic differentiations and inhibit osteoclast recruitment
and activity.
Similar structure to pyrophosphoste,which modulates mineralization by
binding to hydroxyappatite crystals of bone and prevents growth and
resorption.
Quintessence Int.2001;32:365-371www.indiandentalacademy.com

Classification
1st
generation; Alkyl side chain.
- Etidronate.
2nd
generation-Amino-bisphosphonate
- Aledronate.
-Pamidronate.
3rd
generation-Cyclic-side chains.
-Resedronate.
Quitessence Int. 2006;37:103-107www.indiandentalacademy.com

Mechanism of Action
Bisphosphonates have strong chemical affinity to the solid-phase
surface of calcium phosphate , this causes inhibition of
hydroxyapatite aggrigation,dissolution and crystal formation.
Bisphosphonates causes raise in intra-cellular calcium levels
in an osteoclast like cell line.
Reduction of osteoclastic activity,prevention of osteoclastic
development from hematopoietic precussors and production
of an osteoclast inhibitory factor.
Quintessece Int.2006;37:103-107

Effects BPN’s on bone and tooth movement.
Studies have shown that BPN’s can inhibit orthodontic tooth movement
and delay the orthodontic treatment.
Topical application of BPN’s could be helpful anchoring and retaining
teeth under orthodontic treatment.
A significant potential side-effect of BPN’s is the development of osteo-
necrosis in the mandible or maxllia,particularly related to i.v.theraphy
or high dose,longterm,oral usage.This adverse effect due to death of
osteoclasts along with bone related capillary inhibition, decreasing
microcirculation to the maxilla or mandible.
Am J Orthod Dentofacial Orthop 2007;131:321-6.www.indiandentalacademy.com

Echistatin and RGD peptides.
Another approach made recently local injection of echistatin and RGD
(Arginine-glycine-aspartic acid) peptides on rats to prevent tooth
movement, there by enhancing anchorage.
Dolce et al. made the first attempt this aspect,reported that ELVAX-40
a non-biodegradable,non-inflammatory,sustained release polymer used
to deliver integrin inhibitors like echistatin and RGD peptides agents,to
reduce tooth movement at a local level.
Recent research has demonstrated decrease in root resorption
following orthodontic force application after adminstration
of echistatin.
Am J Orthod Dentofacial Orthop 2006;129:252-260www.indiandentalacademy.com

Vitamin-D
Vitamin D is collective name given to anti-rachitic substances
synthesized in the body and found in dietary sources activated
by uv radiation.
7-DEHYDROCHOLESTEROL
CHOLECALCIFEROL (Vit D3)
CALCIFEDIOL (25-OH-D3)
CALCITRIOL (1,25 (OH) 2 D3)
s(Sythesized in skin)
ERGOSTEROL
(yeast,bread,milk)
CALCIFEROL (Vit D2)
25-OH-D2
1,25 (OH)2 D2
(Active forms)
(Active form)
UV light
Liver microsomes
Kidney,mitochondria.
Sythesis of vitamin-DSYNTHESIS OF VITAMIN-D

Vitamin D.
Actions
 Vitamin D and its active metabolite,which is 1,25 2(OH) D3, together
with
Parathyroid hormone and caclitonin,regulates the amount of calcium
and phosphorus levels.
 It promotes intestinal calcium and phosphorus absorption and
promotes calcium release from the skeletal system to blood circulation.
Increases bone mass and thus reduces fractures in osteoporotic
patients.
Uses.
 Used in prophylaxis(400 IU/day) & treatment of rickets (3000-4000www.indiandentalacademy.com

Effects of vitamin-D on bone
and
tooth movement.
Some auther consider vitamin D3 to be a bone resorption-promoting
agent because stimulatory effects on osteoclasts.
Vitamin D receptors have been demonstrated not only in osteoblasts
but also in osteoclast precussors and in active osteoclasts.
In 1988, Collins and Sinclair demonstrated that intraligamentary
injections of vitamin-D metabolite,1,25-dihydroxy cholecalciferol
caused in increase in the no of osteoclasts and amount tooth
movement during canine retraction with light forces.
In 2004 Kale and colleagues ,observed that the local application
of vitamin enhanced the rate of tooth movements in rats due the
well balanced bone turnover induced by vitamin-D.www.indiandentalacademy.com

Stimulatory action of vitamin-D on osteoblasts can help stabilize
orthodontic tooth movement.
In 1976 study by Bran and colleagues,treated rats with vitamin-D
showed increased bone formation on pressure side of the PDL
after application of othodontic forces.
In 2004, kawakaami observed an increase in the mineral appositional
rate on alveolar bone after orthodontic force application, they
suggested that local application of vitamin-D could intensify the
reestablishment of supporting alveolar bone ,after orthodontic
treatment.
Effects of vitamin-D on bone
and tooth movement.
JCO,2007; vol.XLI ,No.2:73-78.www.indiandentalacademy.com

Estrogens
Estrogens is considered to be most important hormone to affect bone
metabolism in women.
It controls bone remodeling during reproductive life, and maintenance
of maximum bone mass after menarche.
Estrogens on bone tissue results in decrease the rate of bone resorption.
Estrogen inhibit the production of various cytokines, mainly interleuki-1(IL-1),
(TNF-a ) tumour necrosis factor-a, and interleukin-6(IL-6),which are involved in
bone resorption by stimulating osteoclast formation and osteoclastic bone
resorption.

Estrogens.
According to population based study,deficiency in estrogen seems
to be responsible for the secondary hyperparathyroidism found in
postmenopausal women,they also inhibit osteoblasts responsiveness
to parathyroid harmone.
Estrogens do not have any anabolic effects on bone tissue,they directly
stimulate the bone forming activity of osteoblasts.

Effect of estrogens on
tooth movement.
Studies have shown that ,Estrogens decreases the velocity
of tooth movement. Oral contraceptive, taken for long
periods of time ,can influence the rate of tooth movement.
Androgens also inhibit bone resorption and modulate the
growth of the muscular system, may affect the length
and results of the Orthodontic treatment.
Quitessence Int.2001;32:365-371www.indiandentalacademy.com

Thyroid harmones.
Thyroid harmones are recommended for the treatment Hypothyroidism
and used after thyroidectomy in substitutive therapy.
Thyroxin adminstration lead to increased bone remodelling ,increased
bone resorptive activity, and reduced bone density.
Effects on bone tissue may related to the augmentation of interleukin-1
(IL-1B), production that thyroid harmones induce at low concentrations,
cytokine stimulate osteoclast formation and osteoclastic bone
resorption.
The skeletal actions of thyroid harmones,it seems possible for
the speed of orthodontic tooth movement increased in patients
undergoing such medication.

Thyroid harmones.
Low-dosage and short-term thyroxin administrations are reported to
lower the frequency of “force induced” root resorption.
Decrease in resorption may be correlated to a change in bone
remodeling process and a reinforcement of the protection of the
cementum and dentin to“force induced” osteoclastic resorption.
Angle Orthod 1994;64:395-9www.indiandentalacademy.com

Relaxin.
Relaxin has been known as a pregnancy hormone.It is released
just before child birth to loosen the pubic symphysis,so that
the relaxed suture will allow widening of the birth canal for parturition.
Other actions ,include the regulation of vasotonus, plasma osmolarity,
angiogenesis , collagen turnover , and renal function.
Relaxin influence on soft tissue remodelling and several mediators
that stimulate osteoclasts formation.
In 2005 ,Liu and colleagues showed that the adminstation of relaxin
might accelerate the early stages of orthodontic tooth movements in
rats.
JCO,2007;vol.XLI:No.2;73-78.www.indiandentalacademy.com

Effects of Relaxin on bone
and tooth movement.
Stewart and collegues used gingival injections of relaxin to relieve
rotational memory in the connective tissues of maxillary lateral
incisors that had been orthodontically rotated.
In 2000,Nicozis and colleagues suggested that relaxin might be used
as an adjutant to orthodontic therapy,during or after tooth movement,
for promotion of stability; for rapid remodeling of gingival tissue
during extraction space closure; for orthopedic expansion in
non-growing patients, by reducing the tension of the stretched
soft tissue envelope, particularly the expanded palatal mucosa,
after orthognathic surgery.
JCO,2007;vol.XLI:No.2;73-78.www.indiandentalacademy.com

Calcitonin.
Calcitonin is a peptide harmone secreted by thyroid in respons to
hypocalcemia .It is produced by parafollicular ‘C’cells of thyroid.
Synthesis and secretion of calcitonin is regulated by plasma calcium
concentration.rise in plasma calcium increases,while fall in plasma
calcium decreases calcitonin release.
Calcitonin inhibits proximal tubular calcium and phosphate
reabsorption by direct action on kidney.
Calcitonin is used in the treatment of hypercalcemia, osteoporosis and
paget’s disease of bone. www.indiandentalacademy.com

Effects of calcitonin on bone
and tooth
movement.
Cacitonin inhibits bone resorption by direct action on osteoclasts
-decreasing their ruffled surface which forms contact with
resorptive pit . It also stimulates the activity of osteoblasts.
Because of its physiological role, it is considered to inhibit the
tooth movement, consequently delay in orthodontic treatment
can be expected.
Quintessence Int.2001;32:365-371

Parathyroid Harmone(PTH).
Parathyroid harmone produced by parathyroid glands to regulate
serum calcium concentration.
In kidneys,PTH increases renal calcium resorption and stimulates
the excretion of urinary phosphate.
In bone,PTH can induce a rapid release of calcium,but also mediates
longer term changes by acting directly on osteoblasts & indirectly on
osteoclasts.
PTH affects osteoblasts’ cellular metabolic activity, gene transcriptional
activity, and multiple protease secretion.
Its effects on osteoclasts occur through the production of RANK-L, a
protein plays a crucial role in osteoclast formation and activity.www.indiandentalacademy.com

Effects of PTH on tooth
movement.
In 1970s ,animal studies demonstrated that PTH could induce an
increase in bone turnover that would accelerate orthodontic tooth
movement.
More recently ,observed an increased rate of tooth movements in
rats treated with PTH,whether adminstered sytemically or locally.
These results indicate that orthodontists should take note of
patients being treated with PTH-for example,in cases of severe
osteoporosis.
JCO,2007;vol.XLI,No.2:73-78

Corticosteroids.
The adrenal cortex secretes steroid harmones which have gluco-
coticoids, mineralo-corticoid and weakly androgenic activities.
The corticoids are 21 carbon compounds having
cyclopentanoperhydro-
-phenantherene(steroid) nucleus,they are synthesized in adrenal cortical
cells from cholesterol.
Adrenal-steroidogenesis takes place under the influence of ACTH which
makes more cholesterol available for conversion to pregenenolone an
induces steroidogenic enzymes.

Classification of
corticosteroids
GLUCO-COTICOIDS
1. Short acting ; -hyrocotisone (cortisol)
(t1/2 <12 hr) -cortisone.
2. Intermediate acting; -Prednisolone.
(t1/2 12-36 hr) -Methyl prednisolone.
-Triamcilonolone.
3. Long acting ; -Dexamethasone.
(t1/2 > 36 hr) -Betamethasone.
MINERALO-CORTICOIDS
-Desoxy corticosterone acetate(DOCA)
-Fludrocortisone.
-Aldosterone.

Actions of glucocorticoids.
Carbohyrate and protein metabolism;
Promotes glycogen deposition in liver and promoting
gluconeogenesis.They also cause protein breakdown and
amino acid mobilization from peripheral tissues.
Fat metabolism;
Corticosteroids promotes lipolysis.
Calcium metabolism;
They inhibit intestinal absorption and enhance renal excretion
of calcium, which leads to loss of calcium from indirectly due to
loss of osteoid.

CVS;
GC’s restrict capillary permiability,maintain tone of arterioles and
myocardial contractility.
Skeletal muscles;
Optimal level of corticosteroids is needed for normal muscular
activity..Hypocortism-weakness due to hypodynamic circulation.
Excess gluco-corticoid action-muscle wasting & myopathy-
weakness.

Inflammatory responses;
 GC’s causes reduction of cappillary permiability,local exudation ,
cellular infiltration,phagocytic activity and late responses like
cappillary proliferation,collagen deposition ,increased fibroblastic
activity and ultimmately scar formation.
GC’s interferes production of PG’s & several mediators of
inflammation like LT’s,PAF,TNF-a and cytokins.
Immunologic responses;
 They suppress all type of hypersensitivity and allergic phenomenon
due to suppression of leucocytes at the site contact with the antigen.

Actions of mineralocorticoids.
Enancement of Na+ reabsorption in DCT of kidney associated with the
increased K+ and H+ excretion.
Execessive action leads to Na+ and water retention,edema,progressive
rise in BP,hypokalaemia and alkalosis.
Mineralocoticoid defficiency results in progressive Na+ loss-dilutional
Natraemia-cellular dehydration-decreased blood volume.

Pharmacokinetics.
All natural and synthetiic corticoids are absorbed by oral route.
Hydrocortisone 90% bound to plasma protein- transcortin and albumin.
Metabolised primarily by hepatic microsomal enzymes.
Metabolites are excreted in urine.
Adverse reactions.
Cushing syndrome,cutanious atrophy,hyperglycaemia,muscular weakness,
susceptibility to infections,delayed wound healing,peptic ulceration,
osteoporosis,growth retardation,adrenal insufficiency.
fetal abnormalities; cleft palate.

Contraindications.
Peptic ulcers.
Diabetes mellitus.
Hypertension.
Viral and fungal infections.
Tuberculosisis.osteoporosis.
Herpes simplex keratitis.
Psychosis.
Epilepsy.
CHF.
Renal failure.

Uses of corticosteroids.
Medical conditions like arthritis,allergic,blood,renal,collagen neoplastic
diseases.
Recurrent oral ulcers.
Oral lesions like pemphigus,errosive lichen planus.
Intra-articular hyrocortisone injections in TMJ to relieve refractory pain.
Prophylatic supplementary corticoid to cover dental procedure-in
patients who have been on long term corticosteroid therapy.

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

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 no
indication of bone formation. A more extensive retention may be
required.
Effects of corticosteroids on bone
and tooth movement.
Quintessence Int.2001;32:365-371www.indiandentalacademy.com

Immunosuppressant Drugs.
Patients with chronic renal failure or kidney transplants and on
immunosuppressant drugs ,which might encounter some difficulty
during orthodontic treatment.
Drug consumed for prevention of graft rejection (cyclosporin A)
produce severe gingival hyperplasia,making orthodontic treatment,
and maintainace of oral hyegine difficult.
Ortthod Craniofacial Res 9,2006;163-
171. www.indiandentalacademy.com

Immunosuppressant Drugs.
Treatment should be started or resumed once good oral hyegine
and after surgical removal of excecssive gingival tissues.
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 not recommended, due to
improper fit.
Ortthod Craniofacial Res 9,2006;163-171.

Immunomodulatory drugs.
Most of these drugs used for treatment Rheumatoid arthritis
includes
Immunomodulatory agents- Leflunomide.
TNFantagonists- Etanercept, Infliximab, Adalimumbab.
Interleukin antagonists- Anakinra.
Immunomodulatory drugs – modulates nuclear factor kappa-B,
tyrosine kinases in signaling pathway, interleukin-6.MMPs,
and PGE2, all of which are essential for the bone remodeling
process.
Ortthod Craniofacial Res 9,2006;163-171.www.indiandentalacademy.com

Immunomodulatory drugs.
TNF alpha antagonists- block TNFalpha in inflammatory cytokinins released
by activated monocytes ,macrophages and T-lymphocytes ,which are essential
for inflammatory responses following force application.
Interleukin antagonists- inhibits IL-1, produced by monocytes ,macrophages
and some specialized cells,which are important for the inflammatory response
and IL-6 and COX-2.
These drugs will influence the inflammatory response following force application
reducing the pace of tooth movement and bone remodeling.
Orthod Craniofacial Res 9,2006/163-171www.indiandentalacademy.com

Cytotoxic
drugs(chemotherapy)
These are used for the treatment of childhood cancers, threre are
every chances of observing disturbences in dental as well as
general body growth and development ,due to adverse effects of
chemotherapeutic agents and radiotherapy.
It is clearly stated that patients who had been on chemotherapy
with Busulfan /cyclophosphamide, belongs to risk group, for
orthodontic treatment.
These drugs are known to produce damage to precursor cells
involved in bone remodelling process there by comlpicating
tooth movement. Semin orthod 2004; 10:266-76

Anticovulsants.
Seizure disorders ,the most common serious chronic neurologic
conditions,are charecterised by sudden involuntary time limited
alteration in neurological function result from abnormal electrical
discharge of cerebral neurons.
Commonly used drugs for treatment these conditions are
Valproric acid (sodium valporate) - Absence seizures,myoclonic seizures.
Phenytoin –Tonic clonic seizures,status epilepticus,Trigiminal neuralgia.
Gabapentin- Diabetic neuropathy,post-herpatic neuralgia.www.indiandentalacademy.com

Anticonvulsants.
Valporic acid-
 It has a potential to induce gingival bleeding even with minor tauma,
making orthodontic maneuvers difficult.
 Fetal abnormalities .
Phenytoin-
 It induces gingival hyperplasia due overgrowth of gingival collagen
fiberes, which involves the interdental papilla,making application of
orthodontic mechanics and difficulty in maintaing oral hyegine.
 Used during pregnancy-can produce fetal hydontion syndrome
charecterised by hyppoplastic phalanges,cleft palate,hare lip and
microcephaly.
 Osteomalacia and megaloblastic anaemia.
Orthod Craniofacial Res 9, 2006/ 163-171.www.indiandentalacademy.com

Anticonvulsants.
Gabapentin;
Gabapentin produces xerostomia,making oral hygiene
maintenance difficult during orthodontic treatment.
In these cases, clinician should be aware of possible
difficulties encounter 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.
Orthod Craniofacial Res 9, 2006/ 163-171.

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.

Alcohol abuse.
In such cases the synthesis of PTH is increased ,tipping
the balance of cellular function towards the enhanced
resoption of mineralized tissues ,including root resorption
in order to maintain normal levels of calcium in blood.
Davidovitch et al. have found that chronic alcoholics receiving
orthodontic treatment are high risk of developing severe root
resorption during course of orthodontic treatment.
Orthod Craniofacial Res 9, 2006/ 163-171.

Effects of drugs on induced tooth movement.
Effects on bone Metabolism. Effects on Tooth Movement.
NSAIDs
Aspirin. Decreases bone resorption. Decreases tooth movement.
Diclolofenac. ” ”
Ibuprofen. ” ”
Indomethacin. ” ”
Celecoxib. Decreases bone resorption(in vitro) No influence.
Acetaminophen. Unproven. No influence.
CRTICOSTEROIDS Increases bone resorption (chronic use) Increases Tooth movement.
BISPHOSPHONATES Decreases bone resorption Decreases tooth movement.

Effect of systemic factors on induced tooth movement.
Effects on bone metabolism Effects on tooth movement
Estrogens decreases bone resorption decreases tooth movement.
Androgens decreases bone resorption unproven.
Relaxin increases bone resorption increases tooth movement.
Thyroid hormones increases rate of bone remodeling increases tooth movement.
increases bone resorption, decreases root resorption.
Parathyroid hormone increases bone resorption increases tooth movement.
Viamin –D increases rate of bone remodeling increases tooth movement.
increases bone resorption www.indiandentalacademy.com

,to be continued…

Antibiotic
s
DEFINITIONS :
Chemotherapy : It is the treatment of systemic infection / malignancy with
specific drugs that have selective toxicity for the infecting organism /
malignant cell with no / minimal effects on the host cells.
Antibiotic agent : Chemical substances produced by microorganisms,which
selectively suppress the growth of or kill other micro-organisms in dilute
solutions, to produce antimicrobial action.
Antimicrobial agent : Substances that will suppress the growth / multiplication
of microorganisms. antimicrobial agents may be antibacterial, antiviral /
antifungal.

A) Mechanism of action :
1. Inhibit cell wall synthesis
• Penicillins
• Cephalosporins
• Vancomycin
• Bacitracin
2. Cause leakage from cell membranes
• Polypeptides – Polymyxins, colistin, Bacitracin
• Polyenes – Amphotericin B, Nystatin
CLASSIFICATION OF ANTIMICROBIAL DRUGS

3. Inhibit protein synthesis
• Tetracyclines
• Chloramphenicol
• Erthromycin,
• Clindamycin
• Linezolid
3. Cause misreading of m-RNA code and affect permeability
Aminoglycosides
Streptomycin
Gentamicin

5. Inhibit DNA gyrase .
• Fluoroquinolones – Ciprofloxacin
5. Interfere with DNA function.
• Rifampin
• Metronidozole
5. Interfere with DNA synthesis .
• Idoxuridine
• Acyclovir
• Zidovudine
5. Interfere with intermediary metabolism.
Sulfonamides PAS
Sulfones Ethambutol

1. Narrow spectrum
• Penicillin G
• Streptomycin
• Erythromycin
2. Broad spectrum
• Tetracyclines
• Chloramphenicol
b) Spectrum of
activity

1. Primarily bacteriostatic
• Sulfonamides
• Tetracyclines
• Chloramphenicol
• Erythromycin
• Ethambutol
2. Primarily bacteriocidal
• Penicillin's
• Aminoglycosides
• Polypeptides
• Rifampin
• Cotrimoxazole
• Cephalosporins
• Vancomycin
• Nalidixic acid
• Ciprofloxacin
c) Type of
action

Penicillins
Most important antibiotics first extracted from the mould PENICILLIUM
NOTATUM
First used in 1941 clinically and was a miracle drug with a least toxic effect.
BETA LACTAM ANTIBIOTICS

1. Natural penicillins.
• Penicillin G (benzyle penicillin)
• Procaine penicillin G
• Benzathine penicillin G
2. Acid resistant penicillins.
• Phenoxymethyl penicillin (pencillin V)
• Phenoxyethylpenicillin (phenethecillin)
3. Penicillianse – resistant penicillins.
• Acid labile – methecillin, nafcillin, cloxacillin, dicloxacillin
CLASSIFICATION OF
PENICILLINS

CLASSIFICATION OF
PENICILLINS
4. Extended spectrum penicillins.
a) Amino penicillins; - Ampicillin ,
-Amoxicillin,
- Becampicillin.
b) Carboxypenicillins: - Carbenicillin,
- Ticarcillin.
c) Ureidopenicillins: - Piperacillin,
- Mezlocillin.
5.Betalactamase inhibitors; -Clavulanic acid,
-Sublactam.

Bactericidal drug effective mainly against multiplying organisms.
Penicillin binding to this proteins are bacterial enzymes on the cell wall
are responsible for synthesis and cross linkage of peptidoglycans in the
cell wall.
Penicillins bind to these proteins and inactivate them, thereby
preventing the synthesis and cross linkage.
This weakens bacterial cell wall and makes organism vulnerable to
damage.
As the cell wall synthesis occurs during the growth phase the antibiotic
is more effective against actively multiplying organisms.
Mechanism of
action.

About 1/3 of drug is activated on oral administration.
Absorbed from the duodenum.
Because of the inadequate absorption the oral dose should be 4/5
times larger than the intramuscular dose.
As food interferes with its absorption PnG should be given orally
atleast 30 min after food or 2 to 3 hours before food.
B. Pencillin in aqucous solution is rapidly absorbed after SC or IM
administration.
Absorption,fate &excretion.

Widely distributed in the body and significant amounts appear in liver,
bile, kidney, joint fluid and intestine.
PnG is excreted mainly by the kidney but in small part in the bile and
other routes.
50% drug is eliminated in urine with in first hour.
Preparation and dose :
PnG inj 0.5-5 MU i.m or i.v 6-12 hours
Procaine pencillin inj 0.5, 1 MU dry powder in vial
Penidure 0.6, 1.2, 2.4 MU as dry powder in vial
Fortifide PP inj 3+1 lac U vial

a) Miscellaneous reactions :
• Nausea and vomiting on oral PnG
• Sterile inflammatory reaction at the site of IM inj.
• Prolonged IV administration may cause thrombophlebitis
• Accidental IV administration of procaine PP cause anxiety, mental
disturbances paraesthesia and convulsions
a) Intolerance :
• Major problem with PnG includes idiosyncratic, anaphylactic and allergic
reactions
ADVERSE REACTIONS
:

1. Periapical abcess.
2. Periodontal abcess.
3. Pericocoronitis.
4. Acute supporative pulpits.
5. Acute necrotising ulcerative gingivitis.
6. Cellulitis.
7. Diptheria.
8. Prophylaxis against endocarditis.
Uses of penicillins.

Similar antibacterial spectrum like benzylpenicillin.
More active against resistant staphylococci
Less inactivated by the gastric acid.
Plasma levels achieved is 2 to 5 times higher than
benzylpenicillin.
50-70% is bond to plasma proteins.
25% of drug is eliminated in urine
Administered in the dose of 250 –500 mg at 4-8 hours intervals,
atleast 30 min before food.
Uses; Streptococcal pharyngitis,sinusitis,otitis media,prophylaxis.
Potassium phenoxymethyl penicillin (penicillin V)

Methicillin
Effective in staphylococci
It is given IM or IV (slow) in the dose of 1 gm every 4-6 hours.
Haematuria, albuminuria and reversible interstitial nephritis
are the special adverse effects of methicillin.
Cloxacillin
 Weaker antibacterial activity.
 Incompletely but depedably absorbed from oral route.Distrubuted
 through out the body, but highest s concentration in kidney and liver.
30% excreted in urine.
 dose; 0.25-0.5g orally every 6hrs.
Pencillinase resistant penicillin's :

Ampicillin – amino penicillin.
• Antibacterial activity is similar to that of PnG that is more effective than
PnG against a variety of gram-ve bacteria
• Drug is effective against H.influenzae strep.viridans, N.gonorrhea,
Salmonella, shigellae, Klebsilla and enterococci.
Absorption, fate and excretion :
• Oral absorption is incomplete but adequate
• Food interferes with absorption
• Partly excreted in bile and partly by kidney
Extended spectrum pencillins :

Dose : 0.5-2 gm oral/IM or IV depending on severity of infection every 6 hours
Children : 25-50 mg/kg/day
- 250, 500 mg caps.
USES :
• Prophylaxis against endocarditis.
• Respiratory tract infections.
• Aerobic and anaerobic infections.
• Gonorrhoea
• Typhoid fever.
• Septicaemias.
Ampicilli
n.

Adverse effects :
• Diarrhoea is frequent
• Skin rashes is more common
• Unabsorbed drug irritates lower interstines
• Patient with history of hypersensitivity to PnG should not be given
ampicillin.
Ampicillin

This is a semisynthetic penicillin .
(amino-p-hydroxy-benzylpencillin)
Antibacterial spectrum is similar to ampicillin but less effective.
Oral absorption is better; food does not interfere; higher and more
sustained blood levels are produced.
It is less protein bound and urinary excretion is higher than that of
ampicillin.
Incidence of diarrhea is less.
AMOXYCILLIN

Dose : 0.25-1 g TDS oral;
250, 500 mg cap, 125 mg/5ml dry syr, 500 mg/vial inj.
Uses;
Prophylaxis against local wound infection.
Prophylaxis against SBE.
Periapical abcess,osteomylitis.
Extractions and minor surgical procedures.
AMOXYCILLIN

CARBENICILLIN
It is a carboxypenicillin,actively against pseudomonas aeurginosa and
proteus which are not inhibited by penicillin-G and aminopenicillins.
Carbenicillin is neither penicillin resistant nor acid resistant. it is inactive
orally and rapidly excreted in urine.
Adverse effects; Fluid retention, CCF in patients with renal and cardiac
dysfunctions, bleeding tendencies due disturbs in platelet functions.
Uses; Infection caused by pseudomonas,burns,septicaemia,
Oro-dental infections.
Dose: it is used with a sodium salt in a dose of1-2g i.m. or 1.5g i.v
every 4-6 hrs.

CLAVULANIC ACID
• Obtained from STREPTOMYCES CLAVULIGERUS
• It has betalactam ring – no antibacterial activity,it inhibits betalctamase
produced by both gram positive and gram negative bacteria .
•It permeates the outer layers of cell wall of gram-ve bacteria and inhibits
periplsamically located beta lactamase.
•Adverse effects; GI intolerence, hepato-toxicity.
BETA LACTAMASE INHIBITORS

Pharmacokinetics :
• Oral absorption- rapid
• Bioavailability-60%
• Distribution similar that of amoxicillin
• Excretion-tubular secretion
Uses :
• Amoxicillin+clavulanic acid (augmentin) -dental infections
CLAVULANIC ACID

Semisnythetic betalactamase inhibitor.
Related chemically in activity to clavulanic acid .
Progressive inhibitor ,highly active against betalactamase.
2-3 times < potent.
Oral absorption- inconsistent,preferably im/iv.
Sulbactam+ ampicillin=Dicapen.
1g+ 0.5g per vial im/iv 6-8hourly.
1g+500mg tab.
SULBACTAM

Adverse effects :
• Pain-thrombophebitis
• Rashes and diarrhoea
Uses :
• Mixed aerobic-anaerobic infections
• Gonorrhoea
• Skin/soft tissue infections
SULBACTAM

Cephalosporium acremonium was the first source.
They contain 7 amino cephalosporonic acid nucleus.
Structurally they contain betalactam and didhydro thiazine rings.
Mechanism of action :
Act by inhibiting bacterial cell wall synthesis and
are bactericidal.
Cephalosporins.

Classified according to its antibacterial activity.
First generation cephalosporins
•Good activity against gram +ve bacteria. (except enterococci).
•Most oral cavity anaerobes are sensitive.
Parental Oral
CEPHALOTHIN CEPHALEXIN
CEFAZOLIN CEPHRADINE
CEFADROXIL
Classificatio
n

Cephalaxin and Cephadroxil :
•Useful in treating community acquired, respiratory and urinary tract
infections and in surgical prophylaxis.
•Not choice for systemic infections.
Cefazolin :
•For antimicrobial prophylaxis in most surgical procedures.
•Given only IM / IV.
•Dose: Oral 0.25 - 1g 6-8 hrly
Children : 25-100mg/kg/day

Increased activity against gram –ve organism.
More active against anaerobes.
Parenteral Oral
CEFUROXIME CEFACLOR
CEFOXITIN CEFUROXIME AXETIL
Cefaclor and cefuroxime axetil retains significant by oral route.
More active against H. influenzae, E coli.
Dose : 250mg, 125mg, 125mg/5ml syr. and
50 mg /ml ped. drops.
Second generation
cephalosporins :

•They highly augmented against gram –ve enterobacter and pseudomonas.
•Highly resistant to β-lactamase from gram –ve bacteria.
•Less active on gram +ve cocci
Parenteral Oral
CEFOTAXIME CEFIXIME
CEFTIZOXIME CEFDINIR
CEFTRIAXONE CEFTIBUTEN
CEFTAZIDIME
CEFOPERAZONE
Dose : 100, 200 mg tab/cap.
Third generation cephalosporins :

Developed in 1990 similar to that of 3rd
generation.
Highly resistant to β-lactamases.
Active against many bacteria resistant to earlier drugs.
It has high potency and extended spectrum.
Effective in many serious infections.
Parenteral
CEFEPINE, CEFPIROME
USES :
Serious and resistant hospital acquired infections.
Septicaemia,
Lower respiratory tract infection.
Dose : 1-2g IM / IV 12 hrly.
CEFROM, CEFORTH – 1g inj.
Fourth generation cephalosporins :

Local reactions – cause pain (IM) and cause thrombophlebitis
(IV) .
Allergy – skin rashes .
Super infection.
Nephrotoxicity .
CNS toxicity .
Blood toxicity .
Intolerance to alcohol .
Cross reactivity with penicillin.
Adverse reactions of
cephalosporins.

Alternatives to pencicillins.
RTI, UTI and soft tissue infection
Penicillinase producing staph infection.
Septicaemias.
Surgical prophylaxis
Meningitis, gonorrhoea
Typhoid
Mixed aerobic and anaerobic infections
Infection by odd organism or hospital infections
Prophylactic treatment in neutropenic patients.
Uses of cephalosporins

They are called macrolides because they contain a many
membered lactone ring to which are attached one or more deoxy
sugars.
Clarithromycin differs from erythromycin only by methylation
of the hydroxyl group at the 6 position, and Azithromycin by the
addition of a methyl substituted nitrogen atom into the lactone ring.
MACROLIDES

Erythromycin.
Erythromycin was isolated from Streptomyces erythreus and widely
employed mainly an alternative to penicillin.
Mechanism of action:
Erythromycin acts by inhibiting bacterial protein synthesis.It combines
with 50s ribosome sub unit and interferes with ‘translocation’ .
Antibacerial action;
Baceriostatic in low concentration and bactericidal at high concentration.
Effective against gram positive bacteria.
It is more active in alkaline medium due to non-ionised form of the drug
is favoured at higher pH.

Pharmacokinetics :
 Erythromycin base - acid labile
 Given with enteric coated - incomplete absorption
 Its acid stable esters are better absorbed
 Widely distributed in the body ,enter into abcesses.
 Metabolised in liver
 Excreted through kidney and bile.
 Dose: 250-500mg ,6 hourly (max.4g/day)
Children- 30-60mg /kg/day.
 Erythromycin estolate(lauryl sulphate); Relative acid stable and
better absorbed after oral adminstration.
Erythromyci
n.

Adverse effects :
 GIT – epigastric pain
 On high doses – hearing impairment.
 Hypersensitivity reactions – rare
Uses :
 Aerobic and anaerobic infectios of dental origin.
 Peridontal/peiapical abcess, ANUG,pericoronitis ,cellulitis.
 Post-extraction infections .
 Prophylaxis to cover dental procedures.
 Penicillin resistant infections
Erythromyci
n

Semisynthetic - long acting stable macrolide
Antibacterial spectrum similar to erythromycin
Better enteral absorption and tissue penetration.
Better gastic tolerability.
Used for oro-dental infections.
Dose - 150-300mg BD
Children - 2.5-5mg/kg BD
50mg kid tab,150 mg tab
ROXITHROMYCIN

This differs chemically from other macrolide group in that lactone
ring contains nitrogen atom.
It is new azilide congener of erythromycin has an expanded spectrum .
Less active against gram +ve organisms
Pharmacokinetics :
Rapidly absorbed and distributed through out the body
Drug is highly concentrated in cells
Excreted unchanged – bile
AZITHROMYCIN

• Prophylaxis against SBE.
• Alternative to erythromycin.
 Respiratory infections.
 Strep and Staph skin and soft tissue infections
• Dose : 500mg once daily for 3days
100,250,500mg tab, are available.
Uses of azithromycin.

It is lincosamide antibiotic having similar action (macrolide 50s)
Semisynthetic derivative of Lincomycin
Bacteriostatic – low conc
Bacteriocidal – high conc
Most active against gram+ve cocci, C.diphtheriae, Actinomyces
Highly active against – anaerobes (B fragilis)
Pharmacokinetics :
Oral absorption – good
Distribution – skeletal and soft tissues.
Excreted in urine and bile.
CLINDAMYCIN

Adverse effects :
 Rashes
 Urticaria
 Abdominal pain
 Superinfection
 Enterocolitis
 Diarrhoea
Uses :
 Anaerobic and mixed infections
 Doses : 150-300 mg caps QID orally.
200-600mg I.v. 8 hourly

 Tetracyclines are napthacene derivatives.
 Obtained from Actinomycetes.
 The napthacene nucleus is made up by fusion of 4 partially unsaturated
cyclohexane radicals and hence the name tetracyclines.
 ‘Broad spectrum antibiotic’- affecting wide range of micro-organisms.
 All tetracyclines are bitter solids which are weakly water soluble,but their
hydrochlorides are more soluble.
Tetracyclines.

Group I Group II Group III
Tetracycline. Demeclocycline Doxycycline.
Oxytetracycline. minocycline.
Tetracyclines to inhibit bacterial protein synthesis by binding to the 30 S
bacterial ribosome and preventing the access of aminoacyl tRNA to the
acceptor (A) sites on the mRNA- ribosome complex.
Classification.

Pharmacokinetics :
 Incompletely absorbed from GIT,better absorption with empty stomach,
doxy-cycline and minocycline absorbed irrespective of food.
 Tetracyclines have chelating property-form insoluble and unabsorbabl
complexes with calcium and other metals.
 They cross the placenta and enter fetal circulation and amniotic fluid
widely distributed in liver ,bone marrow and spleen.
 They accumulate in dentine and enamel of unerupted developing teeth.

GIT-epigastric burning, nausea, vomiting,diarrhoea
Hepatoxicity.
Renal toxicity.
Thrombophlebitis.
Hypersensitivity Reactions .
Superinfection.
Antianabolic effect- reduce protein synthesis .(negative nitrogen balance).
Phototoxicity.
Incresed intracranial pressure in infants.
Adverse effects :

Bone and teeth;
 Tetracyclines have chelating property, calcium –tetracyline chelate gets
deposited in developing teeth and bone .
 When given from mid-pregnancy to 5 months of extra-uterine life,the
decidous teeths are affected; brown discolouration ,illformed teeth ,
more susceptable to caries.
 Tetracyline given between 3months and 6 years of age affect the crown
of anterior teeth.
 Prolonged use of tetracycline during late pregnancy or childhood can
cause temporary supression of bone growth.
Adverse effects :

Dose :
Tetracycline-250 mg ,qid.
Mino-cycline 100mg ,bid.
Doxy-cycline 100mg, od.
Local drug delivary systems in peridontal pockets.
Actisite- tetracycline fiberes (25% of tetracycline).
Atridox- 10% doxycycline.
Periocline-2% minocycline.

Not to be used in pregnancy, lactation and in children.
Avoided in patients on diuretics.
Used cautiously in renal and hepatic insufficiency.
Beyond expiry date should not be used.
Do not mix injectable Tc with Pn- inactivation occurs.
Precautions

Uses of tetracyclines.
Chronic periodontis.
Refractory periodontis.
Juvenile periodontis.
Mixed infections.
In periodontal diseases tetracyclines suppress the activity of collagenase
enzymes derived from neutrophils,fibroblasts that contribute to the
gingival inflammation and scavanging free radicals.

Synthetic antimicrobials having a quinolone structure that are active
primarily against gram –ve bacteria.
The FQs inhibit the enzyme bacterial DNA gyrase, which nicks
double stranded DNA.
The DNA gyrase consists of two A and two B subunits; A subunit
carries out nicking of DNA, B subunit introduces –ve supercoils and
then a subunit reseals the strands.
Quinolones.

First generation FQs :
• Norfloxacin
• Ofloxacin
• Ciprofloxacin
• Pefloxacin
Second generation FQs :
• Lomefloxacin
• Levofloxacin
• Sparfloxacin
• Gatifloxacin
• Moxifloxacin
Classification

1st
generation FQ’sactive against broad range micro-organisms,especially
aerobic gram -negative bacilli.
Rapid bactericidal activity and high potency.
Relatively long post antibiotic effect on enterobacteriaceae pseudomonas
and staphalococus.
Low frequency of mutational resistance.
Active against many β lactam and amino glycoside resistant bacteria.
Less active at acidic pH.
Phramocokinetics :
Rapidly absorbed on oral, food delays absorption.
High tissue penetration, concentration in lung sputum, muscle, bone.
Ciprofloxacin

Adverse effects :
 GIT – Nausea, vomiting, bad taste, anorexia, diarrhoea is infrequent.
 CNS- Dizziness, headache, restlessness, anxiety, insomnia and seizures.
 Skin/hypersensitivity – rashes, pruritis, urticaria.
 Tendonitis and tendon rupture
Uses.
 Gram -ve septicaemias
 Typhoid.
 Bone and soft tissue infections.
 Periapical abscess. Bacterial gastroenteritis
 Dose; 250, 500,750 mg tab, 200mg/100 ml IV infusion..
Ciprofloxacin

It is the prototype nitroimidazole and found to be highly active
amoebicide.
Broad spectrum cidal activity against protozoa and anaerobic bacteria's .
Metronidazole is selectively toxic to anaerobic microorganisms.
Metronidazole has been found to inhibit cell mediated immunity and
cause radiosensitization.
Effective against many anaerobic periodontal pathogens like
Fusobacterium, Bact.fragalis,Prevotella ,Veillionella, Bact.melanogenicus,
Campylobacter, etc.
METRONIDAZOLE

Mechanism of action;
After entering cell by diffusion,its nitro group is reduced by certain redox
proteins of anaerobs to highly reactive nitro radical which interfere
with the DNA function,
Pharmacokinetics :
 Completely absorbed from the small intestine.
 Widely distributed in the body ,saliva ,GCF and other secretions.
 It is metabolized in liver primarily by oxidation and glucuronide conjugation, and
excreted in urine.
 Anorexia, nausea, metallic taste and abdominal cramps are the most common.
METRONIDAZOLE

Amoebiasis anaerobic bacterial infections, pseudomembranous enterocolits.
helicobacter pylori gastritis/peptic ulcer,worm infestations.
Extensively used in oro-dental anaerobic infections like periodontis,acute
apical infections.
Drug of choice in cases of Acute necrotising ulcerative gingivitis (ANUG).
Dose ; METROGYL 200, 400 mg tab ,5-7 days.
Metronidazole gel- for local application.
Uses :

Dental procedures which requires
prophylaxis against SBE.
Dental Extractions.
Pridontal procedures,flap surgery,curretage,scaling,root planing,
Probing and recall maintainance.
Dental implant placement and reimplatation of avulsed teeth.
Endodontic procedures & Apesectomy.
Sub-gingival placement of anti-biotic fibers & gingival retraction
cords.
Initial placement of orthodontic bands but not brackets.
Prophylaxis cleaning of implants/teeth where bleeding is
anticipated.

Antibiotic prophylatic regimen
Situation Antibiotic Regimen
Standard
prophylaxis
Amoxicillin Adult – 2gm children 50mg/kg PO, 1 hr
before.
Cannot use oral
medication
Ampicillin Adult – 2gm, children 50 mg/kg IM/IV.
30 min before.
Allergic to
pencillin
Clindamycin Adult – 600mg ,children 20 mg/kg PO,
1 hr before
Cephalexin /
cefadroxil
Adult – 2gm ,children 50 mg/kg PO, 1
hr before
Azithromycin or
clarithromycin
Adult – 500mg children 15 mg/kg PO,
1 hr before
Allergic Pn,
cannot use oral
medication
Clindamycin Adult – 600mg children 15 mg/kg IV 1
hr before
Cefazolin Adult 1 gm, children 25 mg/kg IM /
IV30 min beforewww.indiandentalacademy.com

Conclusion.
Orthodontists have long observed that teeth move at different
rates ,and individuals have differing responses to treatment.
some of the differences are caused by change in bone
remodeling induced by drugs and systemic factors.
All the drugs reviewed have the therapeutic effects, as well as
side effects that influences the cells targeted by orthodontic
forces.

Conclusion.
There fore it is imperative that the orthodontist need to pay
attention to drug consumption , history of each every patient,
before and during course of orthodontic treatment .So 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.

References.
1.Essentials of Medical pharmacology- KD Tripathi.
2.Phamacology and ppharmacotherapy-R.S .Sathoshkar.
3.Clinical phamacology –Laurence and Bennet.
4.Essentials of pharmacology for dentistry-KD. Tripathi.
5.Am J Ortod Dentofacial Orthop 2004;125:310-5.
6. Am J Ortod Dentofacial Orthop 2006;129:402-6.

References.
12.Quintessence Int 2001;32:365-371.
13.Orthod Craniofacial Res 9,2006;163-171.
14.JCO, 2007;vol XLI ,No.2:73-78.

Role of drugs in orthodontics

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