Role of Drugs in Orthodontics / Orthodontic Courses by Indian Dental Academy

ROLE OF DRUGS IN
ORTHODONTICS.
www.indiandentalacademy.com
INDIAN DENTAL ACADEMY

Leader in continuing dental education

CONTENTS.
Introduction.
Eiocosanides.
NSAIDs.
Effects of NSAIDs on tooth movement.
Bisphosphonates.
Vitamin-D metabolites.
Hormonal drugs.
Anti-biotics.
Local anesthetics.
Conclusion.
References.

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.
Divisions of pharmacology;
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 refferes to movement of the drug by the body,which includes
absorption,distribution,binding/localiszation,storage,biotransformation
and excretion of the drug.

Pharmacology is the science of drugs which deals with the
Interaction of exogenously administered chemical molecules
(drugs) with living systems.
PHARMACOLOGY

EICOSANOIDS

These are the biologically active derivative of 20 carbon atom PUFAs
that are released from cell membrane phospholipids.They are major
lipid derived autocoids.

Most of the tissues are capable of synthesizing PGs from the dietary
essential fatty acids.

PGs 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.

PGs play important role in inflammatory response.

Prostaglandins
Biosynthesis PGs and LTs.
Dietary EFA
Membrane phospholipids
Arachidonic acid
Hydro-peroxides
Lipo-oxygenases(LOX)
LEUKOTRIENS(LTs)
Cyclo-oxygenases
COX1&COX2
PGG2
PGH2
COX1,COX2
PGI-sythetase
(PGI)Prostacyclines PGF1,PGD,PGH2 (TXA)Thromobxane
TXA-synthetase
Pharmacological actions of PGs.
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.

PGs-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.

PGI2-regulation of gastric mucous production.
PGE2-increase mucous producton,decrease acid secretion.
Effect of PGs on bone & tooth
movement.
Experiments have shown that PGs 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 inceasing the number of
osteoclasts and activating already existinng osteoclasts.
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 tohave better effect than
local adminstation.

AmJOrthodDentofacialOrthop1995; 108: 380-8
Leukotrienes(LTs)
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.
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 /NSAIDS
TYPES OF ANALGESICS
Classification of NSAIDS
A..Non-selective COX inhibitors(conventional NSAIDs)
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 NSAIDs
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.
NSAIDs and prostaglandin(PG)
synthesis inhibition.
Most of the NSAIDs acts by inhibiton of prostaglandin
synthesis.Prostaglandins(PGs), Prostacyclines(PGI-2) and
thromboxanes A2(TXA2) are produced from arachodonic acid
metabolism by the enzyme cyclo-oxygenase.
Benifitial actions due to PG synthesis inhibition
Analgesia; prevention of pain nerve ending sensation.

Antipyresis.
Anti-inflamatory.
Antithrmbotic.
Analgesic property
PGs induce hyperalgesia by affecting the trnsuducing
property of free nerve endings-stimuli that normally
donot elicit pain.
NSAIDs donot affect the tenderness induced
by direct application of PGs,but block the pain
sensitizing mechanism induced by bradykinins,
TNFs,ILs .etc.
Antpyretic Action
NSAIDs reduce body temperature in
fever,but donot cause hypothermia
in normothermic individuals.NSAIDs
block the pyrogenic actions of
ILs,TNFs,IFs 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.
Pharmacological actions of Aspirin.
1.Analgesic,antipyretic and anti-inflammtory.
2.Increase in cellular metabolism,especially in skelital muscles,
due to uncoupling of oxidative phsphorylation incerased heat
production .There is increased utilization of glucose-decrease in
blood sugar especially in diabetics and liver glycogen depleted.
3.It stimulates the respiration ,hyperventilation is prominent
In salicylate poisening.Further increase in salicylate level
causes respiratoy depression.
4.Produces significant change in acid-base and electrolyte
balance.
Actions of Aspirin
5.GIT; Aspirin and released salicylic acid irritate gastric
mucosa-cause epigastric distress,nausea,vomiting.
6.Blood; It irreversibly inhibits TXA2 synthesis by the
Platelates.Thus inerfere with the platelet aggrigation
and prolongs BT.
Adverse effects of Aspirin.
Adverse effects of Aspirin.
Nausea,vomiting,epigastric distress,gastric mucosal
damage and peptic ulceration.
Hypersensitivity and idiosyncrasy.
Salicylism-dizziness,tinnitus,vertigo,reversible impairment
of hearing and vision,exitement,mental confusion,hyperventilation.
In children having viral infection(varicella,inffluenza) causes
Reyes sysndrome.
Prolonged BT.
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.
Management of salicylate poisening
Hospitalization.
Gastric lavage.
Correct hyperthermia,dehydration/overhydration,
hypokalamia,acid-base imbalance,ketosis.
Increase elimination by alkalization,peritonial
dialysis.
Vitamin-K,blood transfusion.
Uses of Aspirin
1.Analgesic for head ache,orofacial pains,maylgia,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.
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 PGs.
-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
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-opeerative conditions,
tooth ache,osteoarthritis,rhuematoid arthritis;bursitis.
Dose :100mg BID, 50mg TID.
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,acte gout,
musculo-skeletal injuries. Dose: 20mg BD for two days,
followed by 20mg daily OD.
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.
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 in to inactive products.
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,lekopenia,rashes & hypersensitiviy.
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.

PYRAZOLONE DERIVATIVES;
Metamizol: Potent and promtly acting analgesic and antipyretic but
poor anti-inflamatory.,
It canbe given orally, i.m./i.v ,but causes gastric irritation,pain at the
injection site,rarely causes fall in BP by i.v. route.
Few cases of agranulocytosis were reported.It is banned in
USA,Europe countries.
Dose: 0.5 -1.5g oral/i.m/i.v.
Propiphenazone : Similar actions like metamizol,better tolerated.
Agranulocytosis has not been reported.
Dose :300-600mg TDS .
Propiphenazone 150mg +paracetamol 250 mg tabs.

1.Metamizol and 2. Propiphenazone
Preferential COX-2 Inhibitors.
Nimesulide:
NSAID is a relativevely weak inhibitor of PGSynthesis and
anti-inflammatory action may be exerted by reduced generation
of superoxide by neutrophils,inhibiton of PAFsynthesis and
TNF release,free radicle scavanging,inhibitionmetalloprotease
activity in cartilage.

It completely absorbed from oral route,99% plasma bound,
extensively metabolized 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.

1.Nimesulide, 2.Meloxicam and 3.Nabumetone
Meloxicam.
Meloxicam is newer congener of piroxicam COX-2 : COX-1
selectively ratio about 10.
Similar actions like Nimesulide.
Gastic side effects are milder.
More efficient than the piroxicam in cases of osteo-arthritis and
rheumatoid arthritis.
Dose: 7.5-15mg OD.
Nabumetone;
Prodrug-generates an active metabolite(6-MNA).
Rlatively more potent COX-2 than COX-1 inhiitor.
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

Selective COX-2 inhibitors.

Selective COX-2 inhibitors cause little gastric mucosal damage,peptic
ulcer lower than other NSAIDs.
They donot depress TXA2 production by theplatelets,dont 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
CYP 2C9.
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 &uses likeVadecoxib.
Dose :60-120mg OD.
Roficoxib.
Highly seiective COX2 inhibitor commoly used forRA,OA,dental,
post-operative and musculoskeletal pain.
It has been banned worldwide because of higher incidece of MI
and stroke after long term use.

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,come in
common use in since 1950.
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 acive on cox in brain.
Minimal gastric irritation , low incidence of gastric errosion,
bleeding.
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:
Anti-pyretic doses of paracetamol is safe and well tolerated.
Nausea,rashes occurs rarely,anlagesic neuropathy(long term use).
Acute paracetamol poisening-seen in small children having low
hepatic glucuronide conjugating ability.
Larger dose-extensive liver damage-liver failure.
Haemlytic anemia-G6PD individuals.

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 NSAIDs on tooth movement.
Most commonly used medications used in
orthodontics,for control of pain following mechanical
force application to tooth.
Mechanism ;PGs aproduct 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
Effect of NSAIDs on tooth movement.
Recent research demonstrated the molecular mechanisms
behind the inhibition of tooth movement by NSAIDs,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 extravascular matix
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 USFs 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
PGs 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 periods
during orthodontic treatment.
Effect of NSAIDs on tooth
movement.
Quintessence Int 2001;32:365-371.
An interesting recent development seen in prescriptions of a specific
COX-2 inhibitor,rofecoxib,a drug with no effect onPGE2 synthesis.
These drugs selectively block the COX2 enzyme, and impede the
production of PGs 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.
Effect of NSAIDs on tooth
movement.
Am J Orthod Dentofcial Orthop;125:310-5.
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;32:365-371
Classification
1
st
generation; Alkyl side chain.
- Etidronate.

2
nd
generation-Amino-bisphosphonate
- Aledronate.
-Pamidronate.

3
rd
generation-Cyclic-side chains.
-Resedronate.
Quitessence Int. 2006;37:103-107
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 BPNs on bone and tooth movement.
Studies have shown that BPNs can inhibit orthodontic tooth movement
and delay the orthodontic treatment.
Topical application of BPNs could be helpful anchoring and retaining
teeth under orthodontic treatment.

A significant potential side-effect of BPNs 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.
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 echastatin.
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-D
SYNTHESIS OF VITAMIN-D
Vitamin D3.
Vitamin D and its active metabolite,which is 1,25 2(OH) D3, together with
Parathyroid hormone and cacitonin,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.

Vitamin D3 -can inhibit orthodontic 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.

Used in prophylaxis(400 IU/day) & treatment of rickets (3000-4000 IU/day) ,
osteoporosis and hypoparathyroidism.
Hormonal drugs
Estrogens and androgens.
Thyroid harmones.
Calcitonin.
Corticosteroids.
Estrogens
Estrogens is considered tobe most important harmone to affect bone
metabolism in women.

It controls bone remodeling during reproductive life,and it seems acquisition
and maintenance of maximum bone mass after menarche.

The beneficial effect of estrogens on bone tissue results from the decrease
the rate of bone resorption.

Estrogen inhibit the production of various cytokines, mainly interleuki-1(IL-1),
(TNF-a)tumer 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 osteoblsts.

Uses; -contraceptives.
-regulation of menorrhea.
-treatment of amenorrhea.
-postmenopausal syndrome.
-osteoporosis.
Effect of estrogens on tooth
movement.
Studies have shown that ,Estrogens decreases the velocity of tooth
movement. Oral contraceptive,which are taken by youger women for
long periods of time ,can influence the rate of tooth movement.It is
recomeded that one need to give special attention during orthodontic
treatment.

Anrogens 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;32:365-371
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 toforce induced osteoclstic resorption.

Quitessence Int 2001;32:365-371
Calcitonin.
Calcitinin is a peptide harmone secreted by thyroid in respons to
hypocalcemia .It is produced by parafollicular Ccells 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
pagets disease of bone.

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.
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.

The normal rate of secretion of the two principal corticosteroids in man
1.Hydrocartisone and 2.Aldosterone.
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; coticosteroids 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; GCs restrict cappillary 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.
Actions of glucocorticoids.
CNS; Mild euphoria,anxiety or depression.
Stomach; Secretion of gastric acid and pepsin is increased-may aggravate
peptic ulcer.
Lymphyoid tissue; Enhance the rate of distruction of lymphyoid cells.

Inflammatory responses; GCs 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.
GCs interferes production of PGs & several mediators of inflammation
like LTs,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,
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.
Antibiotics
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.
Antibacterial agent : substances that destroy or suppress
the growth / multiplication of bacteria. They are classified
as antibiotic or synthetic agents.
1) Identification of the causative organism :
Isolated from pus, blood or tissue.
Situations in which cultures should be done are
a) The patient has received treatment for 3 days without improvement.
b) Infection is a postoperative wound infection.
c) Recurrent infection
d) Actinomycosis is suspected
e) Osteomyelitis is present
PRINCIPLES FOR CHOOSING THE APPROPRIATE ANTIBIOTIC.
2. Determination of antibiotic sensitivity :
Not responded to initial antibiotic therapy.
Antibiotic sensitivity can be done by 2 methods :
1) Disc diffusion method (Kibby-Bauer)
2) Agar-or broth dilution tests
3. Use of specific, Narrow spectrum antibiotic :
Narrowest antibacterial spectrum should be chosen. Penicillin, a
cephalosporin and a tetracycline.
Penicillin should be used
There are 2 reasons for this :
i) Specific narrow-spectrum antibiotics frequently are more effective against
specific groups of susceptible microorganisms than are broad-spectrum
agents.
ii) Narrow spectrum antibiotics produce less alteration of the normal
microflora, thereby reducing the incidence of superinfection. www.indiandentalacademy.com
4. Use of a least toxic antibiotic :
Antibiotics are utilized to kill living bacteria, also kill or injure
human cells.
Antibiotics can be highly toxic.
Odontogenic infections sensitive to penicillin and
chloramphenicol.
5. Use of a bactericidal rather than a bacteriostatic drug :
Bacteriostatic drugs exert their influence by inhibiting growth and
reproduction of the bacteria, usually by inhibiting protein synthesis. Growth
is slowed, the host defenses can now cure the infection.
The advantages of bactericidal drugs are :
a) Less reliance on host resistance.
b) Antibiotic itself kills the bacteria.
c) Works faster than bacteriostatic drugs
d) There is greater flexibility with dosage intervals.
e) To kill all pathogens.
6. Use of the antibiotic with a proven history of success :
Penicillin has a proven track recorded.
New drug, is haste to use it.
Choice of newer drug should be made only when :
Effective against bacteria, against which no other AMA is effective.
More active at lower concentration
Less toxic / less severe side effects
Less expensive.
Because :
The drug fails to reach its target.
The drug is inactivated
The target is altered (Davies 1994; Nikaido, 1994: Spratt, 1994)
7. Cost of the antibiotic :
It is difficult to place a price tag on health.
Surgeon should consider the cost of the antibiotic.
Parenteral antibiotics given in the hospital cost more.
Pinciples of antibiotic adminstration.

1) Proper dose : Peak concentration should be 3 to 4 times.
Eg : cephalexin vs penicillinase
2) Proper time interval :
Plasma half-life
Dosage interval therapeutic use is 4 times
At 5 times 95% of the drug has been excreted.
Eg : Cefazolin
3) Proper route of administration :
Parentral administration will produce the necessary serum level of antibiotics.
Oral route also results in the most variable absorption.
For maximum absorption is taken in fasting stage.
4) Consistency in regard to route of administration :
When treating a serious, established infections, parenteral antibiotic therapy is
frequently the method of choice.
Discontinue the parenteral route immediately and start the oral route.
Important to maintain peak blood levels.
Antibiotic has been given for 5 or 6 days.
Switching from the parenteral to the oral route on the 2
nd
or 3
rd
day of antibiotic
therapy, recurrence of the infection is more likely.
5) Combination antibiotic therapy :
The rationale for the use of 2 or more drugs together is to minimize
the emergence of antibiotic resistant microorganisms
to increase the certainty of a successful clinical outcome
to treat mixed bacterial infections
to prevent suprainfection
to treat severe infections of unknown etiology
to decrease toxicity without decreasing efficacy
Examples :
1) Isoniazid + ethambutol + streptomycin in treatment of tuberculosis.
With one exception, combinations of antibiotics are not used in the dental
office.
The exception is use of penicillin G + streptomycin before dental procedures
in patients at high risk of developing bacterial endocarditis.
Rules :
1) 2 bactericidal drugs produce, supraadditive effects, not antagonism.
2) The combination of a bacteriostatic and a bactericidal drug generally results
in diminished effects.
3) 2 bacteriostatic drugs are never inhibitory.
Results :
1) Indifference when the effect is equal to the single most active drug or
equal to the arithematic sum of the two use is not justified.
2) Antagonism : when the combined drug effect is less than the
algebraic sum of the effects on the individual drugs in the mixture.
Bactericidal drugs require dividing organisms without an intact cell
wall ; bacteriostatic drugs inhibit cell replication. The end result is
that there are less number of bacteria available for bactericidal drug.
3) Synergism : ability of two antibiotics acting together to markedly
increases the rate of bactericidal action compared to either drug
alone.
CAUSES OF FAILURE IN TREATMENT OF INFECTION :
Inadequate surgical treatment
Depressed host defenses
Presence of foreign body
Antibiotic problems
- Drug not reaching infection
- Dose not adequate
- Wrong bacterial diagnosis
- Wrong antibiotic
During treatment normal host bacteria that are susceptible to the drugs are
eliminated.
In the normal state, these bacteria live in peaceful coexistence with the host
and by their physical presence prevent bacteria capable of producing
disease from growing in large numbers.
The normal flora acts as a defense mechanisms, but when the indigenous
flora is altered, the pathogenic bacteria resistant to an antibiotic may cause a
secondary infection, or SUPERINFECTION.
Example is of CANDIDIASIS with the use of PENICILLIN, which eliminates
the gram-positive cocci (seen after long term high dose penicillin therapy).
3. Superinfection and recurrent infection :
1) Operative procedure must have a risk of significant bacterial
contamination and a high incidence of infection.
2) The organism most likely to cause the infection must be known.
3) The antibiotic susceptibility of the causative organism must be
known.
4) To be effective and to minimize adverse effects, the antibiotic must
be in the tissue at the time of contamination (operation), and it must
be continued for no more than 4 hours after cessation of
contamination.
5) The drugs must be given in dosages sufficient to reach 4 times or
MIC of the causative organisms.
Principles for the use of prophylactic
antibiotics :
Dental procedures which reqires
Endocardtis Prophylaxis.
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 before
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
4. Cause misreading of m-RNA code and affect permeability
Aminoglycosides
o Streptomycin
o Gentamicin

5. Inhibit DNA gyrase .
Fluoroquinolones Ciprofloxacin
6. Interfere with DNA function.
Rifampin
Metronidozole
7. Interfere with DNA synthesis .
Idoxuridine
Acyclovir
Zidovudine
8. Interfere with intermediary metabolism.
Sulfonamides PAS
Sulfones Ethambutol
1. Sulfonamides and related drugs
Sulfadiazine and others
Sulfones Dapsone (DDS), Paraaminosalicylic acid (PAS).
2. Diaminopyrimidines
Trimethoprim
Pyrimethamine
3. Quinolones
Nalidixic acid
Norfloxacin
Ciprofloxacin etc
B) Chemical structure
4. -lactam antibiotics
Penicillins
Cephalosporins
Monobactams
Carbapenems
5. Tetracyclines
Oxytetracycline
Doxycycline etc
6. Nitrobenzene derivative
Chloramphenicol

7. Aminoglycosides
Streptomycin
Gentamicin
Neomycin etc
8. Macrolide antibiotics
Erythromycin
Roxithromycin
Azithromycin etc
9. Polypeptide antibiotics
Polymyxin-B
Colistin
Bacitracin
Tyrothricin
10. Glycopeptides
Vancomycin
Teicoplanin
11. Oxazolidinone
Linezolid
12. Nitrofuran derivatives
Nitrofurantoin
Furazolidone
13. Nitroimidozoles
Metronidozole
Tinidazole
14. Nicotinic acid derivatives
Isoniazid
Pyrazinamide
Ethionamide
15. Polyene antibiotics
Nystatin
Amphotericin-B
Hamycin
16. Azole derivatives
Miconazole
Clotrimazole
Ketoconazole
fluconazole
D) Spectrum of activity
1. Narrow spectrum
Penicillin G
Streptomycin
Erythromycin
2. Broad spectrum
Tetracyclines
Chloramphenicol www.indiandentalacademy.com
1. Primarily bacteriostatic
Sulfonamides
Tetracyclines
Chloramphenicol
Erythromycin
Ethambutol
2. Primarily bacteriocidal
Penicillins
Aminoglycosides
Polypeptides
Rifampin
Cotrimoxazole
Cephalosporins
Vancomycin
Nalidixic acid
Ciprofloxacin
E) Type of action
1. Fungi
Pencillin
Cephalosporin
Griseofulvin
2. Bacteria
Polymyxin B
Colistin
Bacitracin
Tyrothricin
Aztreonam
3. Actinomycetes
Aminoglycosides
Tetracyclines
Chloramphenicol
Macrolides
Polyenes
F) Antibiotics are obtained from
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
Acid resistant flucloxacillin
CLASSIFICATION OF
PENICILLINS

Bactericidal drug effective mainly against multiplying organisms.
Pencilline requires cell wall that contains peptidoglycans.
Peptidoglycan is heteropolymeric component of cell wall provides rigid
mechanical, crosslinked lattice like structure.
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.
Peak plasma level of 8 to 10 units per ml is reached with in 15 to 30
min and drug disappears from plasma with in 3-6 hours.
Absorption,fate &excretion.
Widely distributed in the body and significant amounts appear in liver,
bile, kidney, jointfluid and interstine.
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
ADVERSE REACTIONS :
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
b) Intolerance :
Major problem with PnG includes idiosyncratic, anaphylactic and allergic
reactions
Other allergic reactions are
Skin rashes
Serum sickness
Renal disturbance
Hemolytic disturbance
Anaphylaxis
Jarisch herxheimer reaction
Super infection
Hyperkalemia
Acute non allergic reaction
Uses :
PnG is the drug of choice for infections
1. Streptococcal infections
2. Pneumococcal infections
3. Meningococcal infections
4. Gonorrhoea
5. Syphilis
6. Diphtheria
7. Tetanus and gas gangrene
8. Prophylactic uses
SEMI SYNTHETIC PENCILLINS
The major drawbacks of benzyl pencillin are :
1. Inactivation by the gastric hydrochloric acid
2. Short duration of action
3. Poor penetration into CSF
4. Activity mainly against gram +ve organism
5. Possibility of anaphylaxis
Attempts therefore have been made to synthesize pencillin free from such drawbacks.
P.chrysogenum produces natural penicillins which produce the 6 amino-penicillanic acid
(6-APA) nucleus.
The attachment of side chains are inhibited and instead various organic radicals can be
substituted.
Thus a variety of semisynthetic resins are produced.

1. Potassium phenoxymethyl penicillin (penicillin V)
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
Available as 60 & 125 mg tablets.
Administered in the dose of 250 500 mg at 4-8 hours intervals,
atleast 30 min before food.
This can be used in less serious infections (pneumocci and
streptococci).
I) Acid resistant pencillins :
Dose : infants 60 mg, children 125-250 mg given 6 hourly
CRYSTAPEN-V, KAYPEN, PENIVORAL 65, 130, 125, 250 mg tablets
125 mg/5 ml dry ser

2. Potassium phenoxyethyl penicillin and
3. Azidocillin
Both have similar properties to penicillin V and no difference in the antibacterial
effect
1. Methicillin
1. Effective in staphylococci
2. It is given IM or IV (slow) in the dose of 1 gm every 4-6 hours.
3. Haematuria, albuminuria and reversible interstitial nephritis are the
special adverse effect of methicillin.
2. Cloxacillin
1. Weaker antibacterial activity.
2. Distrubuted thro out the body, but highest s concentration in kidney and
liver. 30% excreted in urine.
3. Oral dose for adults 2-4 gm divided into 4 portions children 50-
100mg/kg/day.
4. IM adults 2-12 gm/day, children 100-300 mg/kg/day every 4-6 hours.
BIOCLOX, KLOX, CLOCILIN 0.25, 0.5 gm cap, 0.5 gm/vial.
II) Pencillinase resistant pencillins :
Oxacillin, Dicloxacillin, Flucloxacillin are other isoxazolyl penicillins, similar to
cloxacillin, but not marketed in India.
Nafcillin :
More active than methicillin and cloxacillin but less active than PnG
80% of drug bonds with plasma proteins excreted by liver in patients with renal
failure.
Dose is similar to cloxacillin.
III) Extended spectrum pencillins :
1. Amino pencillins
1. Ampicillin
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
Dose : 0.5-2 gm oral/IM or IV depending on severity of infection every 6 hours
Children : 25-50 mg/kg/day
AMPILIN, ROSCILLIAN, BIOCILIN 250, 500 mg cap 100mg/ml ped drops, 250
mg/ml dry syr, 1 gm/vial inj.
USES :
Urinary tract infections
Respiratory tract infections
Meningitis
Gonorrhoea
Typhoid fever
Septicaemias
SBE
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.

This is a semisynthetic penicillin .
(amino-p-hydroxy-benzylpencillin)
Antibacterial spectrum is similar to ampicillin but less effective than
ampicillin for shigellosis.
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 diarrhoea is less.
AMOXYCILLIN
Dose : 0.25-1 g TDS oral;
250, 500 mg cap, 125 mg/5ml dry syr, 500 mg/vial inj.

USES :
Typhoid
Bronchitis
Urinary infection
SBE
Gonorrhoea
The Carboxypenicillins, the Ureidopenicillins and the Amidino penicillins are considered
extended spectrum penicillins, because they inhibit a wide variety of aerobic gram-ve
bacilli.
They are ineffective against most strains of staph. Aureus
1. Highly active against anaerobes.
2.Most useful in infections caused by other gram-ve rods.
3.Act synergistically with amino glycoside antibiotics, particularly enterobacteriacea.
4.Much less active than penicillin G against gram+ve organisms.
5.The CNS penetration is about 10% of their serum levels and hence not recommended
for the treatment of meningeal infections.
Carboxyl penciillins :
Has similar spectrum as other penicillin
Weaker antibacterial activity than ampicillin
Active against pseudomonas, proteus
< Salmonella , E coli Enterobacter
Inactive against klebsiella and gram ve cocci
Acid labile and has to be given by parenteral route only
Peak plasma level is 2hours and excreted in urine
CARBENICILLIN
Dose : 1-2g im/iv 4-6hours
Adverse effects :
Cause congestive heart failure
Bleeding disorders-impaired platelet function
Uses :
Pseudomonas ,burns, UTI and septicemia
PYOPEN,CARBELIN 1g,5g per vial
UREIDOPENICILLINS PIPERACILLIN ( PIPRIL)
AMIDINOCILLIN MECILLINAM
Has similar indications of carbenicillin
CLAVULANIC ACID
Obtained from STREPTOMYCES CLAVULIGERUS
Betalactam ring no antibacterial activity
Suicide inhibitor inactivated after binding to enzyme
Permeates the outer layers of cell wall of gram-ve bacteria
BETA LACTAMASE INHIBITORS
Pharmacokinetics :
Oral absorption- rapid
Bioavailability-60%
Distribution similar that of amoxicillin
Excretion-tubular secretion
Uses :
Amoxicillin+clavulanic acid (augmentin)
Ticarcillin+clavulanic acid (timentin)
Staph aureus,H influenza, gonorrhoea and E coli
Adverse effects :
Poor g.i. tolerance
Hepatotoxicity
AUGMENTIN, AMONATE, ENHANCIN
250+125mg tab 1-2tab TDS
250+50mg vial im/iv 6-8 hourly

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.
SULBACIN, AMPITUM .
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

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 was synthesis and are
bactericidal.
New derivatives are much more resistant than the older
cephalosporins

CEPHALOSPORINS
Classification
Classified according to its antibacterial activity.
First generation cephalosporin
Good activity against gram +ve bacteria. (except enterococci).
Most oral cavity anaerobes are sensitive.
Parental Oral
CEPHALOTHIN CEPHALEXIN
CEFAZOLIN CEPHRADINE
CEFADROXIL
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
IM 0.25g 8 hrly (mild cases) 1g 6 hrly (severe cases).
Drops cephaxin 125mg/5ml syrup.
100mg /ml ped. drops.
SPORIDEX, CEPHAXIN, CEPHACILLIN, CEFADROX, DROXYL
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.
KEFLOR, CEFTUM, CEFOGEN, FUROXIL.
Second generation cephalosporins :
They highly augmented against gram ve enterobacter and pseudomonas.
Highly resistant to -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.
100mg/5ml syr., 50mg/ml susp. CESPAN, CEFOPROX, PROCADAX,
CEPODEM, ORFIX.
Third generation cephalosporins :
Developed in 1990 similar to that of 3
rd
generation.
Highly resistant to -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 :
Cephalosporins are and should not be used where an equally effective,
alternative antibiotic expensive is available.
None of them is effective against infections by enterococci.
None of them is agent of choice of anaerobic infections.
Except for cefotaxine, ceftriazone, the CNS penetration of cephalosporins is
poor.
General features of cephalosporins
Most of them given by oral route
IM can cause pain so IV is given.
Mainly excreted by kidney.
Dosage is altered in patients with renal insufficiency.
Most cephalosporins penetrate CSF so useful for the treatment of meningitis.
Guiding principle for the use of 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 :

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
Other beta lactum antibiotics
CARBEPENEMS
Imipenem
More active against wide variety of bacteria (Bactericidal).
Is combined with clistatin, that inhibits the degradation of imipenem
Not absorbed orally.
Drug is hydrolysed rapidly by dipeptidase found in proximal renal tubule.
Nausea, vomiting and seizures are its adverse reaction.
Patients allergic to other beta lactam have hypersensitive reaction to
imipenem.
Uses :
UTI, RTI, skin, soft tissue infection, bone and joint infection
Dose : 0.5gm IV 6 hrly.
AZTREONAM :
Is a novel -lactum antibiotic which in the other ring is missing.
(hence monobactam)
Inhibits gram-ve enteric bacilli, H influenza and gram +ve cocci.
Resistant to gram ve -lactamases.
Uses :
UTI, GI tract infection
Dose : 0.5 2 g IM/IV 6-12 hrly.
MONOBACTAMS
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
Antibacterial activity :
Narrow spectrum antibiotic
Bacteriostatic but bactericidal at higher conc
Effective against penicillin resistant staphylococci
Active against gram+ve cocci and bacilli
Pharmacokinetics :
Erythromycin base - acid labile
Given with enteric coated - incomplete absorption
Its acid stable esters are better absorbed
Widely distributed in body
Metabolised in liver
Excreted through kidney and bile
Dose :
Adults 250 - 500mg 6hrly
Children 30 60mg/kg/day
Erythromycin base - ERYSAFE 250 mg tab
EROMED - 333mg tab, 125/5ml susp
Erythromycin stearate
ERYTHROCIN 250,500mg tab
100mg/5ml susp
100mg/ml ped drops
Adverse effects :
GIT epigastric pain
On high doses hearing impairment
Hypersensitivity reactions rare
Uses :
Substitute for penicillin
Whooping cough
Chancroid
Penicillin resistant infections

Semisynthetic - long acting stable macrolide
Antibacterial spectrum similar to erythromycin
Dose - 150-300mg BD
Children - 2.5-5mg/kg BD
ROXID, ROXIBID 150,300mg tab
50mg kid tab,150 mg tab
ROXITHROMYCIN

This differs chemically from other macrolide group in that lactone ring
contains nitrogen atom
More active than erythromycin
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
Uses :
Chlamydial infection
Respiratory infection
Strep and Staph skin and soft tissue infections
Dose :
500mg once daily for 3days
Children above 6months 10mg/kg
AZITHRAL 250,500mg 250mg/5ml syr
AZIWIN 100,250,500mg tab 200mg/5ml liq
AZITHRAL 500mg inj
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.
CLINDAMYCIN
Adverse effects :
Rashes
Urticaria
Abdominal pain
Superinfection
Enterocolitis
Diarrhoea
Uses :
Anaerobic and mixed infections
Doses : 150-300 mg QID oral ; 200-600mg I.v. 8 hourly
DALCAP, CLINCIN, DALCIN, 150, 300 mg cap, 300mg/2ml and 600
mg/4ml inj.

It is tricyclic glycopeptide.
Antibacterial activity highly effective against gram positive cocci.
It is bactericidal in action.
Pharmacokinetics :
Absorbed poorly after oral administration.
Parenteral therapy should be given only I.V. never I.M.
90% eliminated by glomerular filtration.
Uses :
Staphylococcal infections .
Endocarditis .
Penicillin resistant pneumococcal infections.
Serious infections empyema, pneumonia, osteomyelitis and soft tissue
abscesses.
VANCOMYCIN
Adverse effects :
Hypersensitivity reactions skin rashes and anaphylaxis
Thrombophelebitis on I.V. pain on I.M.
Red-man syndrome rapid I.V. infusion can cause Chills, fever rashes
erythematous or urticarial reactions, flushing, tachycardia, and
hypotension.
Ototoxicity and nephrotoxicity.
Dose :
Given orally 125-500 mg 6 hrly.
VANCOGEN, VANCOLED 150mg tab, 500 mg/vial inj, 0.5, 1.0 g inj.

Tetracyclines are napthacene derivatives.
The napthacene nucleus is made up by fusion of 4
partially unsaturated cyclohexane radicals and hence the
name tetracyclines.
Tetracyclines are bacteriostatic.
TETRACYCLINES
On the basis of chronology of development, convenience of
description, divided into 3 groups.
Group I Group II
Tetracycline Demeclocyline
Oxytetracycline Methacycline
Group III
Doxycycline
Minocycline
Tetracyclines are thought 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.
Antimicrobial activity :
Gram+ve and ve cocci are sensitive
Gram+ve bacilli are inhibited
Entero bactereae are highly resistant
Spirochetes and Borrelia are quite sensitive
All rickettsiae and chlamydiae are highly sensitive
Pharmacokinetics :
Incompletely absorbed from GIT
Absorption is impaired by iron or zinc salts[due to chelation of cations]
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 teeth
Primarily excreted in urine through kidney
Adverse effects :
GIT-epigastric burning, nausea, vomiting,diarrhoea
Hepatoxicity
Renal toxicity
Effects on teeth-Orthophosphate complex
Thrombophlebitis
Hypersensitivity Reactions
Superinfection
Antianabolic effect
Dose :
Tetracycline 1-2g per day in adults
Children over 8yrs -25 to 50mg /kg daily in 2 to4 divided doses
Doxycyline 100mg,12hrs first day followed by 100mg once a day
Children over 8yrs 4-5mg /kg/day divided into 2 equal doses during first
24hrs
TERRAMYCIN, RESTECLIN-250,500mg cap,50mg/ml in10ml vial inj
DOXT, NOVADOX, TETRADOX-100mg cap.
Precautions :
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
Uses :
Mixed infections
Venereal diseases
Atypical Pneumonia, Cholera, Brucellosis, Plague,Rickettsial infections
Alternate to Pn/Ap, Ciprofloxacin,Azithromycin
Other situations UTI,amoebiasis, chronic lung disease
CHLORAMPHENICOL
It is unique among natural compounds because it contains a
NITROBENZENE moiety and is a derivative of DICHLOROCETIC
ACID.
It acts by inhibiting protein synthesis (by binding reversibly to
the 50s ribosomal subunit).
Antimicrobial activity :
Broad spectrum antibiotic
Active against Salmonella,H influenzae, Klebsieilla
Less active gram+ve cocci, spirochetes
Inactive against Entamoeba and Plasmodia, Pseudomonas, Viruses and
Fungi
Pharmacokinetics
Rapidly and completely absorbed on oral adminstration.
Chloramphenicol is eliminated by conversion into active metabolite
Glucoronid, then excreted in urine
Dose :
Oral 250 -500mg 6hrly
Children 25 50mg /kg/day
PARAXIN 250, 500mg cap, 1% eye oint, 0.5% eye drops, 5% ears drops
Adverse effects :
Bone marrow depression
Hypersensitivity reactions
Irritative effects
Superinfections
Gray baby syndrome
Uses :
Typhoid fever(S.typhi)
Bacterial meningitis (H.influenzae)
Anaerobic infections
Rickettsial disease(eg.Rocky mountain spotted fever)
Brucellosis
UTI
Aminoglycosides, which are aminoglycosidic are bactericidal inhibitors of
protein synthesis.
These are a group of natural and semisynthetic antibiotic having
polybasic amino groups.
The aminoglycosides consist of 2 or more aminosugars joined in
glycosidic linkage to a hexose nucleus, which is usually in a central
position.
They inhibit protein synthesis and decrease the fidelity of translation of
RNA at the ribosome.
Used against aerobic gram negative bacteria.
The ones commonly used are Streptomycin, Gentamicin, Amikacin,
Neomycin.
AMINOGLYCOSIDES
Pharmacokinetics :
Poorly absorbed from the GIT on oral.
Absorbed rapidly from the I.M. sites of injection.
Largely are excluded from mast cells from the CNS, and from the eye.
Excreted almost entirely by a glomerular filtration.
Adverse effects :
Ototoxicity
Vestibular and auditory dysfunction are more common
Nephrotoxicity
Neuromuscular blockade
CNS effects
STREPTOMYCIN
Adverse effects :
Anaphylaxis is very rare.
Auditory disturbances are less common.
Streptomycin has the lowest nephrotoxicity.
Hypersensitivity reactions are rare ; rashes ; eosinophilia.
Topical use is contraindicated
Superinfections are not significant.
Paresthesias are occasional.
AMBISTRYN-S : 0.75, 1g dry powder per vial for inj.
Acute infections : 1g I.m. BD for 7-10 days.
Tuberculosis : 1g or 0.75g I.m. OD or twice weekly for 30-60 days.

Preparation and dosage :
Streptomycin sulfate injection 0.5 to 1.0 gm of the base daily by deep
intramuscular injection.
Therapeutic uses :
Bacterial endocarditis streptomycin and penicillin have a synergistic
bactericidal effect. Gentamicin is more popular.
Tuberculosis
15mg/kg per day I.M. for 2-3 months, then 2 or 3 times a week thereafter.
Tularemia
Plague
Brucellosis
Preparation and dosage :
The properties of Gentamicin are as same described for Streptomycin.
There are following differences :
1) It is more potent
2) It has a broader spectrum of action
3) It is ineffective against M. tuberculosis, strep. Pyogenes and strep. pneumonia.
4) It is relatively more nephrotoxic.
Dose : I.M. or slow I.V dose of 2-5 mg/kg/day in 3 divided doses.
1-5 mg/day intrathecally
0.3% cream, ointment or eyedrops.
GARAMYCIN, GENTASPORIN 20, 60, 80, 240 mg per vial inj ; 0.3% eye / ear drops,
0.1% skin cream.
GENTAMICIN
Uses :
Preventing and treating respiratory infections
Urinary tract infections
Pneumonia
Meningitis
Pertinitis
Meningitis
Gram positive infections : enterococcal endocarditis
Sepsis
Topical applications

Used because of its specture of activity.
Kanamycin sulfate is available for injection and oral use.
The parenteral dose is 15mg/kg per day (2 to 4 equally divided doses.
Adverse reactions :
Curariform action on skeletal muscles.
Respiratory and cardiac arrest
KANAMYCIN, KANCIN, KANAMAC 0.5, 1g inj i.m. BD-TDS
KANAMYCIN

It is a broad-spectrum antibiotic.
Gram negative species that are highly sensitive are e.coli, enterobacter aerogences,
klebsiella pneumoniae and proteus vulgaris.
Gram positive microorganisms that are inhibited include staph. aureus, E. faecalis, M.
tuberculosis.
Oral dose : 1g 4-6 hrly.
Ointments : 5mg / gm
Therapuetic uses :
1) On topical application to the skin and eye.
NEOMYCIN SULPHATE, NEBASULF, NEOSPORIN 350, 500, mg tab, 0.3% skin oint,
0.5% skin cream, eye oint.
NEOMYCIN.

This antibiotics is identical with neomycin.
Use is restricted to topical application and oral administration for local
action on GIT only.
Too toxic for systemic administration.
Uses :
Staphylococcal skin infections
SOFRAMYCIN, 1% skin cream, 0.5% eye drops or oint.
FRAMYCETIN
SULFONAMIDES
First antimicrobial agents (AMAs) effective against pyogenic
bacterial infections.
Is a generic name for derivatives of PARA-AMINOBENZENE
SULFONAMIDE. They contain a sulfonamido (SO
2
NH
2
) group.
Classification :
Classified according to their therapeutic utility
1) Treatment of systemic infections depending upon their duration of action
a) Short acting sulfonamides eg. Sulfadiazine, Sulfafurazone,
Sulfamethizole
b) Intermediate acting sulfonamides eg. Sulfaremethoxazole
c) Long-acting sulfonamides eg. Sulfadimethoxine, Sulfarmethoxine
2) Treatment of bowel eg. Sulfasalazine
3) Those use topically eg. Mafenide hydrochloride
Synthesize their own folic acid of which PABA is a constituent. (Woods and
Fildes 1940)
Sulfonadies, being structural analogues of PABA, inhibit bacterial folate
synthetase FA is not formed and a number of essential metabolic reactions
suffer.
Sulfonamides competitively inhibit the union of PABA.
Being chemically similar to PABA, the sulfonamide may itself get
incorporated to form an altered folate which is metabolically injurious.
Human cells also require FA but they utilize preformed FA supplied in diet
and are unaffected by sulfonamides.
Evidents in favour of sulfonamides are :
a) PABA, in small quantities, antagonizes the antibacterial action of
sulfonamides.
b) Only those microbes which synthesize their own FA, and cannot take it from
the medium are susceptible to sulfonamides.
Pus and tissue extracts contain purines and thymidine which decrease
bacterial requirement for FA and antagonize sulfonamide action. Pus is also
rich in PABA.
Effective against a variety of gram positive and gram negative organisms
and certain chlamydia BACTERIOSTATIC.
Pharmacokinetics :
Sulfonamides are rapidly and nearly completely absorbed from
g.I.t.
They highly protein bound members and are long acting.
Widely distributed in the body
Are excreted mainly by the kidney
Adverse effects :
Urinary tract crystallurea, albuminurea, hematuria.
Hematopoietic system acute hemolytic anemia
Hypersensitivity reaction - Rashes, Steven Johnson syndrome
Uses :
UTI
Marcoidosis
Toxoplasmosis
Acute bacillary dysentry
Meningococcal meningitis
Ulcerative colitis
Chancroid
Trachoma and inclusion conjunctivitis
Used in prophylaxis
SULFADIAZINE, SULFUNO, SULFAMYLON, 0.5 g. tab 1% cream
Uses :
UTI
Marcoidosis
Toxoplasmosis
Acute bacillary dysentry
Meningococcal meningitis
Ulcerative colitis
Chancroid
Trachoma and inclusion conjunctivitis
Used in prophylaxis
SULFADIAZINE, SULFUNO, SULFAMYLON, 0.5 g. tab 1% cream

Trimethoperim is a pyrimidine derivative, either bacteriostatic/bactericidal.
The fixed dose combination of trimethoprim and sulfamethoxazole is called
cotrimoxazole.
Trimethoprim acts by inhibiting the enzyme dihydrofolate reductase,
necessary to convert dihydrofolate to tetrahydrofolic acid.
Sulfonamide act by inhibiting the corporation of PABA into dehydrofolate by
parasites.
A combination of trimethoprim and sulfonamide, therefore acts sequentially in
the same metabolic pathway in synthesis of nucleotides.
Individually both are bacteriostatic but combined becomes bacterocidal.
COTRIMOXAZOLE
Antibacterial spectra of both overlaps considerably but more effective against
Salmonella typhi, Serratia, Klebsiella, enterobacter, Vcholerae, E coli, H. influenczae,
Gonococci and Menigococci.
Pharmocokinetics :
Concentration ratio is 20:1 in blood tissues.
Trimethoprim is more absorbed rapidly than sulfamethaxazole.
70% of oral dose is excreted in urine.
Dose :
The ratio of drug is given in 1:5 (TM-SM)
Septran, Sepmax, Ciplin.
80 +400mg tab 2 BD for 2 days then 1 BD.
20 +100 mg ped tab
160 + 800 mg per 3ml for I.M, inj
ULTROX AND TRIGLOBE FORTE,
90 +410 mg, 180 +820 mg tabs
Adverse effects :
Nausea, vomiting, skinrashes, glossities, stomatities, anemia, leucopenia,
thrombocytopenia, aplastic anemia and megaloblastosis.
Uses :
UTI, RTI.
Typhoid.
Bacterial diarrhoeas.
Chancroid.
Granuloma ingunale
Alternative to penicillin.
Pneumocystis carinii.
QUINOLONES
These are entirely synthetic antimicrobials having a quinolone structure
that are active primarily against gram ve bacteria.
These are quinolone antimicrobials having one or more fluorine
substitutions.
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.
First generation FQs :
Norfloxacin Ofloxacin
Ciprofloxacin Pefloxacin
Second generation FQs :
Lomefloxacin Levofloxacin
Sparfloxacin Gatifloxacin
Moxifloxacin
CIPROFLOXACIN
First generation FQ active against a broad range of bacteria especially gram
ve aerobic bacilli.
Highly susceptible :
E coli, shigella, N meningitis, K pneumoniae, Proteus, H influenza, Enterobacter,
V. cholerae, S. typhi, N gonorrhoea.
Moderately susceptible :
Staph aureus, brucella, M. tuberculosis
Microbiological features :
Rapid bactericidal activity and high potency.
Relatively long post antibiotic effect on enterobacteriaceae pseudomonas
and staph.
Low frequency of mutational resistance.
Low protective intestinal streptococci and anaerobes are spared.
Active against many 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.
Excreted primarily in urine.
Adverse effects :
GIT Nausea, vomiting, bad taste, anorexia, diarrhoea is infrequent.
CNS- Dizziness, headache, restlessness, anxiety, insomnia and seizures
are rare.
Skin/hypersensitivity rashes, pruritis, urticaria.
Tendonitis and tendon rupture
Uses :
UTI
Gonorrhoea
Chancroid
Bacterial gastroenteritis
Gr-ve septicaemias
Prophylaxis
Typhoid
Bone, soft tissue, wound infection.
RTI
Tuberculosis
Meningitis
Conjunctivitis
CIFRAN, CIPLOX, CIPROBID, CIPROLET
250, 500,750 mg tab, 200mg/100 ml IV infusion 3mg/ml eye drops.
NORFLOXACIN
It is less potent than ciprofloxacin.
It attains lower concentration in tissues.
It is metabolized as well as excreted unchanged in urine.
USES :
UTI and Genital infections.
Bacterial diarrhoea.
(not recommended for respiratory / any other systemic infection).
NORBACTIN, NORFLOX, UROFLOX
200, 400, 800 mg tab, 3mg/ml eyedrops.
Intermediate between Cirpro and Nor in activity against Gr-ve bacteria
More potent for Gr +ve organisms
Good activity against chlamydia, alternative drug for nonspecific urethritis and atypical
pneumonia.
Inhibits M tuberculosis.
Highly active against M. leprae.
Used in multidrug regimens.
Relatively lipid soluble
Oral bioavailability is high.
Food does not interfere.
Excreted largely unchanged in urine(dose reduced in renal failure)
OFLOXACIN
Uses :
Chronic bronchitis, respiratory/ENT infection.
Gonorrhoea
Nongonococcal urethritis.
ZENFLOX, OFLOX
100, 200, 400 mg tab, 200 mg/100IV infusion 5mg/5ml susp.

It is levoisomer of ofloxacin having improved activity against strep
pneumoniae and some other gram +ve and ve bacteria.
Anaerobes are moderately susceptible.
Oral bioavailability is nearly 100%
Excreted unchanged and single daily dose is sufficient
LEVOFLOXACIN
Oral and IV doses are similar.
Theophylline, Warfarin, Cyclosporine has been found to remain unchanged during
levofloxacin treatment.
The primary indication of this is
Community acquired pneumonia
Chronic bronchitis
Sinusitis,
Pyelonephritis and
Soft/skin tissue infection as well.
TAVANIC, GIEVO, 500mg tab, 500 mg/100 ml inj.

Another 2
nd
generation FQ has excellent activity against strep. Pneumonia
and many atypical respiratory pathogens including chlamydia pneumonia and
other anaerobes.
Uses :
Community acquired pneumonia
Chronic bronchitis.
Upper/lower RTI
UTI and gonorrhoea.
T1/2 is 8 hr
GATIFLOXACIN
Adverse effects :
Tachycardia
CNS effects and swelling over face are other side effects.
It is contraindicated in hypokalemia and other drugs than can prolong QT.
Dose :
400 mg on 1 day followed by 200-400 mg OD.
MYGAT, GATIQIN, GAITY
200, 400 mg tab, 400 mg/200 ml inj
MOXIFLOXACIN :
It is long acting 2
nd
generation FQ having high activity against strep
pneumonia, other Gr +ve bacteria
Primarily used for pneumonias, bronchitis, sinusitis, and otitis media
Side effects : similar to other FQ
CI in patients predisposed to seizures.
MOXIF 400 mg tab,
Dose 400 mg OD
ANTIFUNGAL ANTIBIOTICS
These drugs used for superficial and deep fungal infections
1. Nystatin.
2. Amphotericin B
NYSTATIN
Antifungal activity :
Candida, Histoplasma, Blastomycoses, Trichophyton and Microsporum
audouini are sensitive.
It produces TOXITICTY an parenteral administration. It is used in infections
caused by CANDIDA. It can be fungistatic or fungicidal depending upon its
concentration.
It combines with the cell membrane of the yeast and interferes with vital
cellular processes like respiration and glucose utilisation.
Adverse reactions : Uncommon.
Preparations and dosage :
Nystatin suspension contains 100,000 units of nystatin per ml. Oral topical
application is usually made 3 times a day.
Therapeutic uses :
It is effective in treatment of localized candidiasis of vagina, mouth, skin,
GIT.
Antifungal activity :
It inhibits the growth of Histoplasma capsulatum, Cryptococcus neofarmans,
blastomyces dermatitis, candida glabrata, coccidiodes immitis.
It binds to sterol moiety (ergosterol) in the membrane of the fungi and forms pores.
These pores increase the permeability of the membrane, allowing the leakage of
variety of small molecules.
Pharmacokinetics :
It is poorly absorbed from gut after topical applications.
The I.M. injection is painful.
Therefore, I.V. route is used for systemic infections. only 5% of the drug is found in
urine after 24 hours.
AMPHOTERICIN -B
Uses :
Mucormcycosis, aspergillosis, candidal esopharyngitis, blastomycosis,
cyptococcosis, sporotrichosis, phycomycosis, amduramycosis.
Dosage :
3% in the lotion form.
0.1 mg/ml I.V. in 5% dextrose should be used.
MYCOL 50 mg vial.
FUNGIZONE OTIC 3% ear drops
TRIAZOLES
Presently the most extensively used antifungal drugs.
Four triazoles are currently available three are entirely topical, while
ketoconazole is used both orally and topically.
The triazoles have broad spectrum antifungal activity covering
dermatophytes, Candida, other fungi involved in deep mycosis.
The mechanism of action of triazoles is the same. They inhibit the fungal
cytochrome P450 enzyme and thus impair ergosterol synthesis leading to a
cascade of membrane abnormalities in the fungus.

Effective in the topical treatment. Esp, athletes foot, otomycosis and oral
cutaneous candidiasis. A 7 day course is generally used.
Clotrimazole is well tolerated by most patients. Local irritation and burning
sensation occurs in some.
No systemic toxicity is seen after topical use.
SURFAZ, CLOTRIN, CLODERM, 1% lotion, cream, powder 100mg tab.
CLOTRIMAZOLE

First oral effective broad spectrum antifungal drug.
The oral absorption of KTZ is facilitated by gastric acidity, more soluble in
lower pH.
Hepatic metabolism is extensive metabolites are excreted in urine.
The usual dose is 200 mg OD or BD
FUNAZOLE, KETOVATE, FUNGICIDE, 200mg tab, 2% oint, cream,
shampoo.
Adverse effects :
Nausea and vomiting loss of appetite, headache, paresthesia, rashes,
hair loss.
KETACONAZOLE

It is the prototype nitroimidazole and found to be highly active amoebicide.
Antiprotozoal activity :
Broad spectrum cidal activity against protozoa and anaerobic bacteria such as
B fragilis, Fusobacterium.
Metronidazole is selectively toxic to anaerobic microorganisms.
Metronidazole has been found to inhibit cell mediated immunity and cause
radiosensitization.
METRONIDAZOLE
Pharmacokinetics :
Completely absorbed from the small intestine.
Widely distributed in the body
It is metabolized in liver primarily by oxidation and glucuronide conjugation, and
Excreted in urine.
Adverse effects :
Anorexia, nausea, metallic taste and abdominal cramps are the most common.
Headache, glossitis, dryness of mouth, dizziness, rashes and transient
neutropenia.
Prolonged administration may cause peripheral neuropathy and CNS effects
Seizures have followed by high doses.
Thrombophebitis of injected vein.
Contraindications :
In neurological disease, blood dyscrasias, first trimester of pregnancy,
chronic alcoholism.
Amoebiasis
Giardiasis
Trichomonas vaginitis.
Anaerobic bacterial infections
Pseudomembranous enterocolits.
Ulcerative gingivitis
Helicobacter pylori gastritis/peptic ulcer
Guinea worm infestation.
FLAGYL, METROGYL, METRON, ALDEZOLE 200, 400 mg tab, 200 mg/5ml susp.
Uses :
TINIDAZOLE
It is an equally efficacious congener of metronidazole, similar to it in
every way except.
Metabolism is slower.
Incidence of side effects is lower.
Metallic taste, nausea, rashes
TINIBA, TRIDAZOLE, 300, 500, 1000 mg tab, 800 mg/400 ml I.V.
Local anasthetics.
DEFINITON.
Loss of sensation in a circumscribed area of the
body caused by a depression of excitation in nerve
endings or an inhibition of the conduction process
in peripheral nerves

-(Grune & Straton-1976)
REGIONAL ANALGESIA: loss of pain sensation over a
portion of the anatomy without loss of consciousness

REGIONAL ANESTHESIA: it applies not only to loss of
pain sensation over a specific area of anatomy without
loss of consciousness but also to the interruption of all
other sensations, including temperature, pressure and
motor function.

ESTERS:
Benzoic acid esters:
Benzocaine
Cocaine
Para-amino benzoic esters:
Tetracaine
Chlorprocaine
Procaine
Propoxycaine

AMIDES:
Articaine
Bupivacaine
Etidocaine
Lidocaine
Mepivacaine
Prilocaine
QUINOLINE:
Centbucridine

BASED ON CHEMICAL STRUCTURE
Ester:
Amide:

R COOR N
R NHCOR N
1 2
R
R
3
4
2 1
R
R
3
4
R Lipophilic aromatic residue.
R Aliphatic intermediate connector.
R , R Alkyl groups
1
2
3 4
STRUCTURES OF AMIDES AND
ESTERS
Based on duration of action
Short Intermediate
Long
eg: Lidocaine HCl 2%,
Mepivacaine HCl 3%
eg: Lidocaine HCl 2%
+ epinephrine 1:1,00,000
eg: Bupivacaine HCl 0.5% +
epinephrine 1:2,00,000,
Etidocaine
MODE OF ACTION OF LOCAL ANESTHETIC
Local anesthetic agents interfere with excitation process in a
nerve membrane in one or more of the following ways:
Altering basic resting potential
Altering the threshold potential
Decreasing the rate of depolarization
Prolonging the rate of repolarization

THEORIES OF MECHANISM OF ACTION OF L.A

Ca
2+
DISPLACEMENT THEORY (Goldman-1966)

SURFACE CHARGE THEORY (Wei-1969)

ACETYLCHOLINE THEORY (Dett barn-1967)

MEMBRANE EXPANSION THEORY (Lee-1976)

SPECIFIC RECEPTOR THEORY (Strichartz-1987)

ACETYL CHOLINE THEORY
MEMBRANE EXPANSION THEORY
SPECIFIC RECEPTOR THEORY
RNHOH + HCl RNHCl + H2O
Weak strong acid water
Base acid salt
RNHCl RNH
+
+ CI-

CHEMICAL REACTON OF LA
EFFECT OF PH

Basic environment (higher pH)
RNH+ > RN + H+

Acidic environment (low pH)
RNH+ < RN + H+
RNH+ displaces calcium ions for the sodium channel receptor site.
which causes
Binding of the local anesthetic molecules to this receptor site
which produce
Blockade of sodium channel
and
Decrease in sodium conduction
which leads to
Depression of the rate of electrical depolarization
and
Failure to achieve the threshold potential level

Lack of development of propagated action potentials
called
Conduction blockade
INDIVIDUAL LOCAL ANESTHETIC AGENTS
Drug pka ph Conc
used
Onset life
Procaine 9.1 5-6.5
3.5-5.5
2-4% 6-10 min hr
Propoxycaine - - 0.4% 2-3 min -
Lidocaine 7.9 6.5
5-5.5
2% 2-3 min 1.6 hr
Mepivacaine 7.6 4.5
3-3.5
3%
2%
1.5-2
min
1.9 hr
Prilocaine 7.9 4.5
3-4
4% 2-4 min 1.6 hr
Articaine 7.8 4.4-5.2 4% 2-3 min 1.25 hrs
Bupivacaine 8.1 4.5-6 :3-4.5 0.5% 6-10 min 2.7 hr
Etidocaine 7.7 4.5
3-3.5
1.5% 1.5 3-
min
2.6 hr
UPTAKE
Oral route :
Hepatic first pass effect. 72% Lignocaine.
Topical route:
Tracheal mucosa. (lignocaine. Adrenaline, fumazenil).
Pharyngeal mucosa.
Esophageal or bladder mucosa.
Skin or oral mucosal.
Injection:
Activity depends on:
Vascularity of the tissue.
Vasoactivity of the drug.
IV caution. ( used in treatment of ventricular dyrhythmias).
DISTRIBUTION.
High conc seen in well purfused organs such as brain, kidney, lungs,
heart.
Level of drug in blood depend on:
Rate at which drug is absorbed into CVS.
Rate at which drug is distribute from vasculature to tissue.
Elimination of drug through excretion.

BIOTRANSFORMATION.
Esters:
Pseudocholinesterase.
Succinylcholine.
Atypical pseudo cholinesterase.
PABA (cause allergic reactions).
Amides:
More complicated.
Hepatic microsomal enzymes.
Liver function and perfusion play an important role.
Intermediate products cause complications.
Prilocaine metabolite: orthotoluidine
- methhemoglobinemia.
Lilocaine metabolites: monoethyl glycine xylidide & xylidide
- sedation
EXCRETION.
Kidneys are the primary
excretory organs.
Less % of parent molecules
of ester anesthetics.
Large% of unchanged amide
parent molecules.
Renal impairment causes
accumulation of drug and its
metabolites causing toxity.
SYSTEMIC ACTIONS.
CNS.
CVS.
LOCAL TISSUE TOXICITY.
RESPIRATORY SYSTEM.
MISCELLANEOUS.
Neuromuscular blockade.
Drug interactions.
Malignant hyperthermia.
CNS-Pathophysiology
Local anesthetics cross blood-brain barrier, producing CNS depression as
level rises
eg. LIDOCAINE
Blood Level Action Produced
< .5 ug/ml - no adverse CNS effects
0.5-4 ug/ml - anticonvulsant
4.5-7.5 ug/ml - agitation,irritability (pre - convulsant)
> 7.5 ug/ml - tonic-clonic seizures
Analgesia.
Mood elevation.
CVS-Pathophysiology
Local anesthetics exert a lesser effect on the cardiovascular
system
eg. LIDOCAINE
Blood Level Action Produced
1.8-5 ug/ml - treat PVCs, tachycardia
5-10 ug/ml - cardiac depression
>10 ug/ml - severe depression,
bradycardia, vasodilatation, arrest

MINIMAL TO MODERATE OVERDOSE.
SIGNS
Talkativeness
Excitability
Apprehension
Slurred speech
Stutter( Muscular twitching / tremors )
Euphoria
Dysarthria
Nystagmus
Sweating
Nausea/vomiting
Failure to follow commands / reason
Elevated BP
Elevated heart rate
Elevated resp rate
SYMPTOMS:
Light-headed and dizzy
Restless
Nervous
Numbness
Nervousness
Sensation of twitching (before actual
twitching is observed)
Metallic taste
Visual disturbances
Auditory disturbances
Drowsy and disoriented
Losing consciousness
MODERATE TO HIGH OVER DOSE.
Generalized tonic-clonic seizure activity
followed by
Generalized CNS depression
Depressed BP, heart rate
Depressed respiratory rate
LOCAL TISSUE TOXICITY.
RESPIRATORY SYSTEM.
MISCELLANEOUS.
Neuromuscular blockade.
Drug interactions.
Potentiates the action the action of CNS depressants.
Prolongs the action of succinlycholine.
Malignant hyperthermia.
Thachycardia, tachypnea, cyanosis, unstable BP,
Respiratory and metabolic acidosis, fever.
Muscle rigidity and death
FACTORS AFFECT THE REACTION OF LOCAL
ANESTHETICS
pKa:
Local anesthetics have two forms, ionized and nonionized. The nonionized
form can cross the nerve membranes and block the sodium channels.
So, the more nonionized presented, the faster the onset action.
pH influence:
Usually at range 7.6 8.9
Decrease in pH shifts equilibrium toward the ionized form, delaying the onset
action.
Lipid solubility:
All local anesthetics have weak bases. Increasing the lipid solubility leads to
faster nerve penetration, block sodium channels, and speed up the onset of
action.
Protein binding:
The more tightly local anesthetics bind to the protein, the longer the duration of onset
action.

Vasodilation:
Vasodilator activity of a local anesthetic leads to a faster absorption and slower
duration of action
Vasoconstrictor is a substance used to keep the anesthetic solution in place at a
longer period and prolongs the action of the drug
vasoconstrictor delays the absorption which slows down the absorption into the
bloodstream
Vasoconstrictor used the naturally hormone called epinephrine (adrenaline).
Epinephrine decreases vasodilator.
VASOCONSTRICTORS
Decrease blood flow
Lower anesthetic blood levels
Decrease the risk of toxicity
Increases duration of action
Decrease bleeding
EPINEPHRINE
Most potent and widely used vasoconstrictor in dentistry
Source: 80% of medullary secretion, also available as a synthetic
MOA- both and , with being predominate
Systemic Effects of Epinephrine
Myocardium - heart rate & cardiac output
Pacemaker - risk of dysrhythmias
Coronary Artery-Dilation of coronary artery
B P- systolic pressure, effect on diastolic pressure is dose related
Cardiovascular -Decrease cardiac efficiency
SYRINGE
NEEDLE
ANESTHETIC SOLUTION
TOPICAL ANESTHETICS
Minimize sensation of needle penetrating the soft tissue.
Used in greater concentration than LA in order to penetrate the mucous
membrane.
Benzocaine
14-20% liquid, gel
Onset 30 seconds

Longer duration than the others

Lower toxicity potential than the
others
Best one for Pedo although some
children say it feels hot

Lidocaine
5% ointment, gel, liquid

10% metered spray

Onset 3-5 minutes
RECOMMENDATIONS
For the administration of local dental anesthesia, dentists should select
aspirating syringes that meet the standards of the ADA.
1. Short needles may be used for any injection in which the thickness of
soft tissue is less than 20 mm
2. Long needle for a deeper injection into soft tissue.
3. Any 23- through 30-gauge needle may be used for intraoral injections
since blood can be aspirated through all of them; however, aspiration can
be more difficult when smaller gauge needles are used.
4. An extra-short, 30-gauge is appropriate for infiltration injections.
5. Needles should not be bent or inserted to their hub for injections to avoid
needle breakage.


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