Drugs in endodontics and
operative dentistry

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INDIAN DENTAL ACADEMY
Leader in continuing dental education
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CONTENTS


INTRODUCTION



DEFINITIONS



PHARMACODYNAMICS



PHARMACOKINETICS



DRUG NOMENCLATURE



ROUTES OF DRU...
ABSORPTION
KINETICS OF ELIMINATION
FACTORS MODIFYING DRUG
ACTION
DRUGS IN ENDODONTICS
- ANTIANXIETY DRUGS
- ANALGESICS
* O...
Introduction

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What is Pharmacology?
- the study of how drugs effect a
biological system

What is a drug?
- any chemical agent which
effe...
What is Pharmacology ?
The study of how drugs effect biological systems

Pharmacokinetics
What the body does to drug

Phar...
Pharmacodynamics
What the drug does to the body
Physiological and biochemical effects of drug
and their mechanism of actio...
Pharmacodynamics
Dose response curve…...

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Pharmacokinetics
What the body does to the drug


Movement of the drug in and alteration of the
drug by the body; include...
Pharmacokinetics
What the body does to the
drug
t1/2 (Half-Life)
- the time required for the plasma concentration of a dru...
Drug Nomenclature
*Chemical name- propranolol
1-(isopropylamino)-3-(1-naphthyloxy) propranolol
*Nonproprietary name
compet...
Routes of Drug Administration
I) LOCAL ROUTES
1) Topical
2) Deeper tissues
3) Arterial supply
II) SYSTEMIC ROUTES
1) Oral
...
Oral absorption (enteral route)
Advantages
1) safe, convenient, economical
2)Self medication
3)drug withdrawl
Disadvantage...
Parenteral route
Routes of administration other than oral route termed as parenteral
Advantages
1)Absorption rapid & quick...
Anti anxiety drugs


Anxiety- it is an emotional state, unpleasant in
nature, associated with uneasiness, discomfort
and ...


Antianxiety- these are ill defined group of mild CNS
depressants which are aimed to control the symptoms of
anxiety, pr...
Oral benzodiazepines


Classification-

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Pharmacological actions


Preparation-1960



Pharmacodynamics-

1)
2)
3)
4)
5)
6)

Antianxiety
Sedative-hypnotic
Antico...




With short half lives- 10-20 hrs (Triazolam at 2.6 to 4 hrs)
With long half lives (lorazepam 10-20 hrs) 50 hrs or m...
PSYCHIC AND PHYSICAL DEPENDENCE
- Tremor, anorexia, sweating, agitation, and insomnia
- Tachycardia, hypertension, visual,...
Non benzodiazepine anxiolytic

-

BUSPIRONE
Devoid of hypnotic, anticonvulsant, or muscle relaxant properties.
not involv...
Benzodiazepine antagonists
Flumazenil
-competetive antagonist of BZD receptor used to
reverse BZD induced CNS depression
-...
Pharmacology of pain
Two components of pain
-Pain perception, and Pain reaction
Pain perception is the reasonably objectiv...


Analgesics-relieve pain without loss of
consciouness

Opiates-products obtained from opium poppy
Opioid analgesics- nat...
OPIUM
 Dried latex from the seed capsules of certain types of
poppy (Papaver somniferum).
 Psychological have been recog...
Classification
1.Natural opium alkaloids - Morphine, Codeine
2.Semisynthetic opiates - Diacetylmorphine(Heroin),
Pholcodei...
Morphine
*Source- natural opium alkaloid
milky exudate of unripe capsules of poppy
plant, papaver somniferum
a) Phenanthre...
Pharmacological actions


1) Analgesia- visceral, pain of trauma
- elevates pain threshold
- alters emotional reaction to...
11) CVS- hypotension at toxic dose
Absorption, fate and excretionPreparation and dose
1. tincture opium – 0.3 to 2 ml by m...
Other opioid analgesics
*Codeine: phenanthrene alkaloid, antitussive
- less potent to morphine
- spasmogenic effect, nause...
3. Euphoria, dysphoria, and vomitting
4. depression of foetal respiration
5. resp. depression, coma,convulsion
6. addictio...
OPIOID RECEPTORS


inhibition of
neurotransmission via
presynaptic and
postsynaptic actions



coupled to guanine
nucleo...
Narcotic Analgesics in Dentistry



opioids used in dentistry are primarily those used for oral
administration such as co...
Comments related to use of narcotic
analgesics in dentistry


DRUG INTERACTIONS



other CNS depressants will increase t...
CLASSIFICATION
(Acc. to Tripathi)
A. Analgesic and antiinflammatory :
Salicylates

Aspirin, Salicylamide, Benorylate, Difl...
B. Analgesic but poor antiinflammatory:
Paraaminophenol derivative

Paracetamol (Acetaminophen)

Pyrazolone derivatives

M...
Aryl propionic acid

Ibuprofen, naproxen, flurbiprofen, ketoprofen,
fenoprofen, oxaproxin.

Anthranilic acid (fenamates)
E...
MECHANISM OF ACTION
Odontogenic pain
Noxious stimuli
Disease process
+
Surgical intervention

Acute pain
Tissue destructio...
Beneficial actions due to PG
Synthesis inhibition
 Analgesia
 Antipyresis
 Antiinflammatory
 Antithrombotic
 Closure ...
COMMON PROPERTIES OF ALL NSAIDS

Analgesia
Anaphylactoid
reactions

Antipyresis
Antiinflammatory

Renal effects

Dysmenorr...
SALICYLATES
Aspirin (prototype)

Pharmacological actions

• Analgesic (0.3-1.5 g/day)
• Antipyretic
• Respiration
• GIT
• ...
Pharmacokinetics
 80% bound to plasma proteins.
 Volume distribution 0.17 L/kg.
 Plasma t ½ = 15-20 min.
 Release sali...
Adverse effects

Salicylism : dizziness, tinnitus, vertigo, reversible impairment of
hearing & vision, excitement & mental...
Contraindications :
 Sensitivity, peptic ulcers, bleeding tendency, chicken pox
or influenza.
 Chronic liver disease
 D...
Interactions :
 Warfarin, naproxen, sulfonylureas,
phenytoin and methotrexate.
 Oral anticoagulants.
 Uric acid
 Probe...
Uses :

Patent ductus
arteriosus

Analgesic

Pregnancy induced
hypertension and
preeclampsia

Antipyretic

Acute rheumatic...
PYRAZOLONES
Phenylbutazone
Pharmacokinetics
 98% bound to plasma proteins.
 Plasma t ½ = 60 hrs.
 Dose 100-200 mg BD/TD...
PYRAZOLONES
Phenylbutazone
Pharmacokinetics
 98% bound to plasma proteins.
 Plasma t ½ = 60 hrs.
 Dose 100-200 mg BD/TD...
Interactions :
 Sulfonamides, tolbutamide,
imipramine & methotrexate

warfarin,

 Anticoagulants
 Phenytoin & tolbutami...
Sioril, phenabid

 Oxyphenbutazone
 Metamizol (Dipyrone) : 0.5-1.5 g

Analgin, novalgin

 Propiphenazone : 300-600 mg T...
Adverse effects

Interactions :
 Furosemide
 Thiazides, furosemide, β
blockers, ACE inhibitors
 Warfarin

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Uses :

P L
Psoriatic
arthritis

Rheumatoid
arthritis
Ankylosing
spondylitis

Acute gout

Malignancy
asso. fever

Acu. E...
PROPIONIC ACID DERIVATIVES
Pharmacokinetics
 90-99% bound to plasma proteins.

Drug

Plasma t ½

Ibuprofen
Naproxen

2 hr...
Adverse effects

Interactions :
 Anticoagulants
 Furosemide, thiazides &
β blockers

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Uses :
Antipyretic
Analgesic
Dysmenorrhoea

ANTHRANILIC ACID DERIVATIVE (Fenamate)
Mephenamic acid
Pharmacokinetics
 High...
Adverse effects

L

Uses :

Osteoarthritis

Analgesic
Rheumatoid
arthritis

Dysmenorrhoea
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Med...
ARYL-ACETIC ACID DERIVATIVES
Diclofenac sodium :
Pharmacokinetics
 99% bound to plasma proteins.
 Plasma t ½ = 2 hrs
 5...
Uses :
Ankylosing
spondylitis

Osteoarthritis

Rheumatoid
arthritis

Bursitis

Dysmenorrhoea

Post-traumatic / post-op
inf...
OXICAM DERIVATIVES
Piroxicam
Pharmacokinetics
 99% bound to plasma proteins.
 Plasma t ½ = 2 days
 20 mg BD / 20 mg OD
...
Uses :

P L

Ankylosing
spondylitis

Osteoarthritis

Rheumatoid
arthritis

Dysmenorrhoea
Dentistry

Acute gout
Episiotom...
PYRROLO-PYRROLE DERIVATIVE
Ketorolac :
Pharmacokinetics
 Highly bound to plasma proteins.
 Plasma t ½ = 5-7 hrs
 10-20 ...
Uses :
Renal colic

Bony
metastasis

Migraine

Post-op / acute
musculoskeletal pain
(15-30 mg i.m. / 4-6 hrs

Ketorol, tor...
Adverse effects

Uses :
Sports injuries

Dental surgery

ENT disorders
Bursitis
Low backache

Dysmenorrhoea
Post-op
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PARA-AMINO PHENOL DERIVATIVES
•

Phenacetin 1887

•

Paracetamol (acetaminophen) 1950

Actions
Pharmacokinetics
 1/3 boun...
Adverse effects

Analgesic nephropathy
Acute paracetamol poisoning
 150 mg/kg
 Fatality > 250 mg/kg
 Early manifestatio...
 Mechanism of toxicity
 Treatment –
• Gastric lavage
• N-acetylcysteine 150 mg/kg / i.v./ 15 min / 20 hrs
• 75 mg/kg / o...
BENZOXAZOCINE DERIVATIVE
Nefopam
30-60 mg TDS oral
20 mg i.m. 6 hrly
Nefomax

CHOICE OF NSAIDS
• Mild to moderate pain – p...
• Exacerbation

of

rheumatoid

arthritis,

ankylosing

spondylitis, acute gout, acute rheumatic fever – aspirin,
indometh...
Analgesics after certain endodontic procedures

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PAIN MANAGEMENT STRATEGY

D

3

iagnosis
efinitive Rx
rugs

Definitive treatment :

Drug :

•Pulpotomy, pulpectomy

•Pretr...
Flexible analgesic prescription plan
Mild
pain

Aspirin like drugs
indicated
Ibuprofen 200 mg

Moderate
pain

NSAIDs (alon...
ADVANCES
Selective cox-2 inhibitors :
Celecoxib, rofecoxib, valdecoxib, etoricoxib, meloxicam,
diisopropyl flurophosphate...
Valdecoxib
Dose – 10-20 mg OD
Commercial name – Valed, Valus, Vorth, Bextra
Banned –7 April 2005.
Other drugs banned by FD...
ANTIBIOTICS

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Antimicrobial agent : substances that will suppress the growth /
multiplication of microorganisms. antimicrobial agents ma...
Principles of appropriate antibiotic use :
1. Presence of infection : If a patient has infection.
•

Local signs and sympt...
3. Surgical Drainage and incision :
•Treatment of deep tissue infections – surgical drainage
•If unreleased – vascularity ...
PRINCIPLES FOR CHOOSING THE APPROPRIATE
ANTIBIOTIC
1) Identification of the causative organism :
Isolated from pus, blood ...
2. Determination of antibiotic sensitivity :
Not responded to initial antibiotic therapy.
Antibiotic sensitivity can be do...
3. Use of specific, Narrow spectrum antibiotic :
Narrowest antibacterial spectrum should be chosen. Penicillin,
a cephalos...
4. Use of a least toxic antibiotic :
•

Antibiotics are utilized to kill living bacteria, also kill or
injure human cells....
5. Use of a bactericidal rather than a bacteriostatic drug :
•

Bacteriostatic drugs exert their influence by inhibiting
g...
Choice of newer drug should be made only when :
• Effective against bacteria, against which no other AMA is
effective.
• M...
PRINCIPLES OF ANTIBIOTIC ADMINISTRATION
1) Proper dose :
•

Peak concentration should be 3 to 4 times.

Eg : cephalexin vs...
3) Proper route of administration :
• Parentral administration will produce the necessary serum level of
antibiotics.
• Or...
5) Combination antibiotic therapy :
The rationale for the use of 2 or more drugs together is to
minimize
•

the emergence ...
Examples :
1) Isoniazid + ethambutol + streptomycin in treatment of
tuberculosis.
With one exception, combinations of anti...
Results :
1) Indifference when the effect is equal to the single most active
drug or equal to the arithematic sum of the t...
Disadvantages :
i)

Adds nothing to therapeutic efficacy and may even reduce it
(antagonism).

ii) Increase antibiotic tox...
MONITORING THE PATIENT
1. Response to treatment :
•

Noticeable response first 24 to 48 hours.

•

If the end of the 3rd d...
CAUSES OF FAILURE IN TREATMENT OF INFECTION :
• Inadequate surgical treatment
• Depressed host defenses
• Presence of fore...
2. Development of adverse reactions :
•

Adverse reactions occur all too commonly.

•

15 to 20 percent of hospitalized pa...
3. Superinfection and recurrent infection :
•

During treatment normal host bacteria that are susceptible to
the drugs are...
PROPHYLACTIC ANTIBIOTICS
Advantages :
•

Prevention of infection

•

Decreased patient morbidity

•

Decreased patient mor...
Disadvantages :
1) No reduction of infection, despite prophylaxis
2) Development of increased number of resistant bacteria...
Principles for the use of prophylactic antibiotics :
1) Operative procedure must have a risk of significant bacterial
cont...
CLASSIFICATION OF ANTIMICROBIAL DRUGS
A) Mechanism of action :
1. Inhibit cell wall synthesis
•

Penicillins

•

Cephalosp...
3. Inhibit protein synthesis
•

Tetracyclines

•

Chloramphenicol

•

Erthromycin,

•

Clindamycin

•

Linezolid

3. Cause...
5. Inhibit DNA gyrase
•

Fluoroquinolones – Ciprofloxacin

5. Interfere with DNA function
•

Rifampin

•

Metronidozole

5...
B) Chemical structure
1. Sulfonamides and related drugs
•

Sulfadiazine and others

•

Sulfones – Dapsone (DDS), Paraamino...
4. β-lactam antibiotics
•

Penicillins

•

Cephalosporins

•

Monobactams

•

Carbapenems

4. Tetracyclines
•

Oxytetracyc...
7. Aminoglycosides
•

Streptomycin

•

Gentamicin

•

Neomycin etc

7. Macrolide antibiotics
•

Erythromycin

•

Roxithrom...
10. Glycopeptides
•

Vancomycin

•

Teicoplanin

10. Oxazolidinone
•

Linezolid

10. Nitrofuran derivatives
•

Nitrofurant...
14. Nicotinic acid derivatives
•

Isoniazid

•

Pyrazinamide

•

Ethionamide

14. Polyene antibiotics
•

Nystatin

•

Amph...
17. Others
•

Rifampin

•

Lincomycin

•

Clindamycin

•

Spectinomycin

•

Sod. fusidate

•

Cycloserine

•

Viomycin

•
...
C) Type of organisms against which primarily active
1. Antibacterial
•

Penicillins

•

Aminoglycosides

•

Erythromycin e...
4. Antiprotozoal
•

Chloroquine

•

Pyrimethamine

•

Metronidazole

•

Diloxanide etc

4. Anthelmintic
•

Mebendazole

•
...
D) Spectrum of activity
1. Narrow spectrum
•

Penicillin G

•

Streptomycin

•

Erythromycin

2. Broad spectrum
•

Tetracy...
E) Type of action
1. Primarily bacteriostatic

2. Primarily bactericidal

•

Sulfonamides

•

Penicillins

•

Tetracycline...
F) Antibiotics are obtained from
1. Fungi

3. Actinomycetes

•

Pencillin

•

Aminoglycosides

•

Cephalosporin

•

Tetrac...
Misconception about antibiotics








Improper choice- drug, dosage, duration of therapy
Ignorance of Microbial b...
Myths in antibiotic theapy









I. Antibiotic cure patients
II. Antibiotics are substitute for surgical drainag...










VIII. Antibiotic prophylaxis is usually effective
IX. Bactericidal agents are always superior to
bacterios...
BETA LACTAM ANTIBIOTICS
Pencillins
Most important antibiotics first extracted from the mould
PENICILLIUM NOTATUM
First use...
CLASSIFICATION OF PENICILLINS
1. Natural penicillin
•

Penicillin G (benzyle penicillin)

•

Procaine penicillin G

•

Ben...
4. Penicillins effective against gram positive and some gramnegative organisms
•

Ampecillin

•

Ampoxycillin

•

Talampic...
BENZYL PENICILLIN (PENCILLIN G)
• PnG is a narrow spectrum antibiotic; activity is limited primarily
to gram positive bact...
Mechanism of action :
• Bactericidal drug effective mainly against multiplying
organisms.
• Pencilline requires cell wall ...
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Absorption fate and excretion :
• About 1/3 of drug is activated on oral administration.
• Absorbed from the duodenum.
• B...
• Widely distributed in the body and significant amounts
appear in liver, bile, kidney, jointfluid and interstine.
• PnG i...
ADVERSE REACTIONS :
a) Miscellaneous reactions :
•

Nausea and vomiting on oral PnG

•

Sterile inflammatory reaction at t...
c) Other allergic reactions are
•

Skin rashes

•

Serum sickness

•

Renal disturbance

•

Hemolytic disturbance

•

Anap...
Uses :
PnG is the drug of choice for infections
1. Streptococcal infections
2. Pneumococcal infections
3. Meningococcal in...
SEMI SYNTHETIC PENCILLINS
The major drawbacks of benzyl pencillin are :
1. Inactivation by the gastric hydrochloric acid
2...
I) Acid resistant pencillins :
1. Potassium phenoxymethyl penicillin (penicillin V)
•

Similar antibacterial spectrum like...
Dose : infants 60 mg, children 125-250 mg given 6 hourly
CRYSTAPEN-V, KAYPEN, PENIVORAL 65, 130, 125, 250 mg
tablets
125 m...
II) Pencillinase resistant pencillins :
1. Methicillin
1. Effective in staphylococci
2. It is given IM or IV (slow) in the...
Oxacillin, Dicloxacillin, Flucloxacillin are other isoxazolyl
penicillins, similar to cloxacillin, but not marketed in Ind...
III) Extended spectrum pencillins :
1. Amino pencillins
1. Ampicillin –
•

Antibacterial activity is similar to that of Pn...
Dose : 0.5-2 gm oral/IM or IV depending on severity of infection
every 6 hours
Children : 25-50 mg/kg/day
AMPILIN, ROSCILL...
Adverse effects :
• Diarrhoea is frequent
• Skin rashes is more common
• Unabsorbed drug irritates lower interstines
• Pat...
AMOXYCILLIN :
• This is a semisynthetic penicillin
• (amino-p-hydroxy-benzylpencillin)
• Antibacterial spectrum is similar...
Dose : 0.25-1 g TDS oral;
AMOXYLIN, NOVAMOX, SYNAMOX, MOX, AMOXIL 250,
500 mg cap, 125 mg/5ml dry syr, 500 mg/vial inj.

U...
Carboxy penciillins :
The Carboxypenicillins, the Ureidopenicillins and the Amidino
penicillins are considered extended sp...
CARBENICILLIN
•

Has similar spectrum as other penicillin

•

Weaker antibacterial activity than ampicillin

•

Active aga...
Dose : 1-2g im/iv

4-6hours

Adverse effects :
• Cause congestive heart failure
• Bleeding disorders-impaired platelet fun...
UREIDOPENICILLINS –PIPERACILLIN ( PIPRIL)
AMIDINOCILLIN – MECILLINAM
Has similar indications of carbenicillin

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BETA LACTAMASE INHIBITORS
•CLAVULANIC ACID
•Obtained from STREPTOMYCES CLAVULIGERUS
•Betalactam ring – no antibacterial ac...
Pharmacokinetics :
•

Oral absorption- rapid

•

Bioavailability-60%

•

Distribution similar that of amoxicillin

•

Excr...
Adverse effects :
• Poor g.i. tolerance
• Hepatotoxicity
AUGMENTIN, AMONATE, ENHANCIN
• 250+125mg tab 1-2tab TDS
• 250+50m...
SULBACTAM
•

Semisnythetic betalactamase inhibitor

•

Related chemically in activity to clavulanic acid

•

Progressive

...
Adverse effects :
• Pain-thrombophebitis
• Rashes and diarrhoea
Uses :
• Mixed aerobic-anaerobic infections
• Gonorrhoea
•...
CEPHALOSPORINS
Cephalosporium acremonium was the first source.
They contain 7 amino cephalosporonic acid nucleus.
Structur...
Classification
Classified according to its antibacterial activity.
First generation cephalosporin
•Good activity against g...
Cephalaxin and Cephadroxil :
•Useful in treating community acquired, respiratory and urinary
tract infections and in surgi...
Second generation cephalosporins :
Increased activity against gram –ve organism.
More active against anaerobes.
Parenteral...
Third generation cephalosporin :
•They highly augmented against gram –ve enterobacter and
pseudomonas.
•Highly resistant t...
Fourth generation cephalosporins :
Developed in 1990 similar to that of 3rd generation.
Highly resistant to β-lactamases.
...
Guiding principle for the use of cephalosporins :
•Cephalosporins are expensive and should not be used where an
equally ef...
Adverse reactions :
•

Local reactions –
thrombophlebitis (IV)

•

Allergy – skin rashes

•

Super infection

•

Nephrotox...
Uses :
•

Alternatives to pencicillins.

•

RTI, UTI and soft tissue infection

•

Penicillinase producing staph infection...
MACROLIDES
They are called macrolides because they contain a
many membered lactone ring to which are attached one or
more ...
Antibacterial activity :
 Narrow spectrum antibiotic
 Bacteriostatic but bactericidal at higher conc
 Effective against...
Dose :
 Adults 250 - 500mg 6hrly
 Children 30 – 60mg/kg/day
 Erythromycin base - ERYSAFE 250 mg tab
 EROMED - 333mg ta...
Adverse effects :
 GIT – epigastric pain
 On high doses – hearing impairment
 Hypersensitivity reactions – rare
Uses :
...
ROXITHROMYCIN
 Semisynthetic - long acting stable macrolide
 Antibacterial spectrum similar to erythromycin
Dose - 150-3...
AZITHROMYCIN
 This differs chemically from other macrolide group in that
lactone ring contains nitrogen atom
 More activ...
Uses :
 Chlamydial infection
 Respiratory infection
 Strep and Staph skin and soft tissue infections
Doses :
 500mg on...
CLINDAMYCIN
 It is lincosamide antibiotic having similar action (macrolide
50s)
 Semisynthetic derivative of Lincomycin
...
Adverse effects :
 Rashes
 Urticaria
 Abdominal pain
 Superinfection
 Enterocolitis
 Diarrhoea
Uses :
 Anaerobic an...
TETRACYCLINES
 Tetracyclines are napthacene derivatives.
 The napthacene nucleus is made up by fusion of 4 partially
uns...
On the basis of chronology of development, convenience
of description, divided into 3 groups.
Group I

Group II

Tetracycl...
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Antimicrobial activity :
 Gram+ve and –ve cocci are sensitive
 Gram+ve bacilli are inhibited
 Entero bactereae are high...
Adverse effects :
 GIT-epigastric burning, nausea, vomiting,diarrhoea
 Hepatoxicity
 Renal toxicity
 Effects on teeth-...
Dose :
 Tetracycline – 1-2g per day in adults
 Children over 8yrs -25 to 50mg /kg daily in 2 to4 divided
doses
 Doxycyl...
Precaution :
 Not to be used in pregnancy, lactation and in children
 Avoided in patients on diuretics
 Used cautiously...
QUINOLONES
 These are entirely synthetic antimicrobials having a
quinolone structure that are active primarily against gr...
Mechanism of action :
 The FQs inhibit the enzyme bacterial DNA gyrase, which nicks
double stranded DNA.
 The DNA gyrase...
CIPROFLOXACIN
First generation FQ active against a broad range of bacteria
especially gram –ve aerobic bacilli.
Highly sus...
Microbiological features :
 Rapid bactericidal activity and high potency.
 Relatively long post antibiotic effect on ent...
Adverse effect :
 GIT – Nausea, vomiting, bad taste, anorexia, diarrhoea is
infrequent.
 CNS- Dizziness, headache, restl...
CIFRAN, CIPLOX, CIPROBID, CIPROLET
250, 500,750 mg tab, 200mg/100 ml IV infusion 3mg/ml eye drops.
NORFLOXACIN
 It is les...
OFLOXACIN
Intermediate between Cirpro and Nor in activity against Gr-ve
bacteria
 More potent for Gr +ve organisms
 Good...
Uses :
 Chronic bronchitis, respiratory/ENT infection.
 Gonorrhoea
 Nongonococcal urethritis.
 ZENFLOX, OFLOX
 100, 2...
LEVOFLOXACIN
 It is levoisomer of ofloxacin having improved activity against
strep pneumoniae and some other gram +ve and...
 Oral and IV doses are similar.
 Theophylline, Warfarin, Cyclosporine has been found to
remain unchanged during levoflox...
GATIFLOXACIN
Another 2nd generation FQ has excellent activity against strep.
Pneumonia and many atypical respiratory patho...
Adverse effect :
 Tachycardia
 CNS effects and swelling over face are other side effects.
 It is contraindicated in hyp...
MOXIFLOXACIN :
 It is long acting 2nd generation FQ having high activity
against strep pneumonia, other Gr +ve bacteria
...
ANTIAMOEBIC AND OTHER ANTIPROTOZOAL
DRUGS
METRONIDAZOLE :
 It is the prototype nitroimidazole and found to be highly
acti...
Pharmacokinetics :
 Completely absorbed from the small intestine.
 Widely distributed in the body
 It is metabolized in...
 Looseness of stool is occasional,
 Headache, glossitis, dryness of mouth, dizziness, rashes and
transient neutropenia.
...
Uses :
 Amoebiasis
 Giardiasis
 Trichomonas vaginitis.
 Anaerobic bacterial infections
 Pseudomembranous enterocolits...
TINIDAZOLE
 It is an equally efficacious congener of metronidazole, similar
to it in every way except.
 Metabolism is sl...
Role of antibiotics in endodontics
(jr of Dent 26 (2001) 539-48)
I ENDODONTICS AND THERAPEUTIC ANTIBIOTICS
1) Adjunct to o...
What are local anesthetics?


Local anesthetic: are agents which block
conduction impulses in nerves. When applied
locall...
Classification
INJECTABLE
Low potency, short duration
Procaine
Chloroprocaine
Intermediate potency and duration
Lidocaine ...
History











Coca leaves from the genus Erythroxylum
Erythroxylum contains high concentration of alkaloid up t...
History (cont.)








Spanish conquistadors and explorers witnessed the
consumption of coca in South America
Spaniar...
Cocaine Addiction










More physicians began to do research of cocaine in the clinic
trials.
The physician Sigmu...
Side Effects of Cocaine and Solutions
Minor:
 Addiction
 Intoxication
Severe:
 Death

Solutions:
 Used nitrous oxide g...
Procaine replaced
cocaine




In 1898, Professor Heinrich
Braun introduced procaine as the
first derivative of cocaine, ...
Lidocaine











In 1940, the first modern local anesthetic
agent was lidocaine, trade name
Xylocaine®
It develo...
Differences of Esters and Amides
All local anesthetics are weak bases. Chemical structure of local anesthetics have
an ami...
Structures of Amides and Esters






The amine end is hydrophilic (soluble in water), anesthetic molecule dissolve in
...
Mechanism










The mechanism of local anesthetics connects with the ion channels, nerve, and
depolarization.
Loc...
Factors Affect the Reaction of Local Anesthetics
Lipid solubility








All local anesthetics have weak bases. Incre...
Factors Affect the Reaction of Local Anesthetics
(cont.)
Vasodilation
 Vasoconstrictor is a substance used to keep the an...
Toxicity
Toxicity is the peak circulation levels of local anesthetics
 Levels of local anesthetic concentration administe...
Factors of circulation levels










Factors of circulation levels are the rates of absorption,
distribution, and ...
Three special drugs used in dental anesthesia



Bupivicaine (Marcaine®

--Produce very long acting anesthetic effect to ...
Conclusion
Anesthetic

pKa

Onset

Duration (with
Epinephrine)
in minutes

Max Dose
(with
Epinephrine)

Procaine

9.1

Slo...
Antimuscarinic drugs


Natural alkaloids (and derivatives)





Synthetic quaternary ammonium drugs






Atropine...
Pharmacologic effects:
atropine as a prototype
Dose
(mg)
Effects
0.5 Slight cardiac slowing; some dryness of
mouth; inhibi...
Therapeutic uses
Antisialogogues for dentistry

Drug

Dose (mg)

Atropine sulfate
0.4-1.2
(Sal-Tropine)
Scopolamine HBr
0....
Therapeutic uses (cont.)










Bradycardia: atropine
Ocular examination: topical antimuscarinics
Bronchial as...
Clinical considerations


Contraindications/precautions






Angle-closure glaucoma
Obstructive or paralytic GI or G...
Hemostatic Agents


Local measures


Dressings
- Dentoalveolar surgery: pressure with sterile cotton
gauze
> soft tissue...
Hemostatic Agents (con’t)


Clotting factors
- topically applied thrombin, NOT INTRAVENOUSLY (Severe
thrombosis and death...
Hemostatic agents (cont’d)


•

Vasoconstrictor
- epinephrine (epinephrine solution and dry cotton pellets
impregnated wi...
Desensitizing agents









Fluorides
Silver nitrate
Strontium chloride
Formalin
Sodium monoflurophosphate
Sodiu...











Calcium hydroxide
Zinc chloride
Sodium sulphate + barium chloride
Sodium carbonate + calcium chloride...
CONCLUSION

www.indiandentalacademy.com
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Drugs in endodontics /certified fixed orthodontic courses by Indian dental academy

  1. 1. Drugs in endodontics and operative dentistry www.indiandentalacademy.com
  2. 2. INDIAN DENTAL ACADEMY Leader in continuing dental education www.indiandentalacademy.com www.indiandentalacademy.com
  3. 3. CONTENTS  INTRODUCTION  DEFINITIONS  PHARMACODYNAMICS  PHARMACOKINETICS  DRUG NOMENCLATURE  ROUTES OF DRUG ADMINISTRATION www.indiandentalacademy.com
  4. 4. ABSORPTION KINETICS OF ELIMINATION FACTORS MODIFYING DRUG ACTION DRUGS IN ENDODONTICS - ANTIANXIETY DRUGS - ANALGESICS * Opioid Analgesics * Non Opioid Analgesics -ANTIBIOTICS IN ENDODONTICS - LOCAL ANAESTHETICS DRUGS IN OPERATIVE DENTISTRY - ANTI SIALOGOUGES - STYPTICS - DESENSITIZING AGENTS  www.indiandentalacademy.com
  5. 5. Introduction www.indiandentalacademy.com
  6. 6. What is Pharmacology? - the study of how drugs effect a biological system What is a drug? - any chemical agent which effects any biological process WHO 1966, “Drug is any substance or product that is used or intended to be used to modify or explore physiological systems or pathological states for the benefit of the recipient” www.indiandentalacademy.com
  7. 7. What is Pharmacology ? The study of how drugs effect biological systems Pharmacokinetics What the body does to drug Pharmacodynamics What the drug does to body Pharmacology Pharmacotherapeutics The study of the use of drugs Pharmacocognosy Identifying crude materials as drugs Toxicology www.indiandentalacademy.com
  8. 8. Pharmacodynamics What the drug does to the body Physiological and biochemical effects of drug and their mechanism of action at organ system or subcellular or macromolecular level Ex- adrenaline-adrenoreceptors- G-protein mediated cell membrane bound adenyl cyclase-intracellular 3,5 AMP-cardiac stimulation-hepatic glycogenolysishyperglycemia  www.indiandentalacademy.com
  9. 9. Pharmacodynamics Dose response curve…... www.indiandentalacademy.com
  10. 10. Pharmacokinetics What the body does to the drug  Movement of the drug in and alteration of the drug by the body; includes absorption, distribution, binding or localization or storage, biotransformation and excretion of the drug.  Pharmacodynamic agents  Chemotherapeutic agents www.indiandentalacademy.com
  11. 11. Pharmacokinetics What the body does to the drug t1/2 (Half-Life) - the time required for the plasma concentration of a drug to be reduced by 50% ED50 (effective dose) - The dose of a drug that is effective for 50% of the population exposed to the drug LD50 (lethal dose) - the dose at which death occurs in 50% of subjects www.indiandentalacademy.com
  12. 12. Drug Nomenclature *Chemical name- propranolol 1-(isopropylamino)-3-(1-naphthyloxy) propranolol *Nonproprietary name competent scientific body- USAN, BAN Ex-Meperidine (USA) & Pethidine( UK, India) *Proprietary name ( Brand name) accepted by manufacturer & is his property or trademark Ex- Atenolol ALTOL, ATECOR, BETACARD, ATEN, ATCARDIL, ATEN, LONOL, TENOLOL, TENORMIN www.indiandentalacademy.com
  13. 13. Routes of Drug Administration I) LOCAL ROUTES 1) Topical 2) Deeper tissues 3) Arterial supply II) SYSTEMIC ROUTES 1) Oral 2) Sublingual or buccal 3) Rectal 4) Cutaneous 5) Inhalation 6) Nasal 7) Parenteral - subcutaneous - Intramascular - intravenous - intradermal injection www.indiandentalacademy.com
  14. 14. Oral absorption (enteral route) Advantages 1) safe, convenient, economical 2)Self medication 3)drug withdrawl Disadvantages 1)Slow onset 2) Bitter taste 3) Nausea and vomitting 4) Inactivated by gastric enzymes 5) Not possible in unconscious patient Enteric coated pills and tablets- cellulose acetate or gluten cant destoy by acid juice of stomach, alkaline intestinal juice removes the coatings www.indiandentalacademy.com
  15. 15. Parenteral route Routes of administration other than oral route termed as parenteral Advantages 1)Absorption rapid & quick 2) Accurate dose can be given 3) Drug enters in active form to circulation 4) Useful in emergency 5) Useful in unconscious patient Disadvantages 1) pain on injection 2) abscess and inflammation at the site of injection 3) sterile procedure required for injection 4) expensive 5) self medication is not possible  www.indiandentalacademy.com
  16. 16. Anti anxiety drugs  Anxiety- it is an emotional state, unpleasant in nature, associated with uneasiness, discomfort and concern or fear about some defined or undefined future threat. www.indiandentalacademy.com
  17. 17.  Antianxiety- these are ill defined group of mild CNS depressants which are aimed to control the symptoms of anxiety, produce a restful state of mind without interfering with normal mental or physical functions.  Sedatives- the drug that subdues the excitement and calms the subject without inducing sleep though drowsiness may be produced  Hypnotic- a drug that induces and or maintains sleep similar to normal arousable sleep www.indiandentalacademy.com
  18. 18. Oral benzodiazepines  Classification- www.indiandentalacademy.com
  19. 19. Pharmacological actions  Preparation-1960  Pharmacodynamics- 1) 2) 3) 4) 5) 6) Antianxiety Sedative-hypnotic Anticonvulsant Amnesic Skeletal muscle relaxant Induce anterograde amnesia Mechanism of action-facilitates inhibitory action of gamma aminobutyric acid (GABA) www.indiandentalacademy.com
  20. 20.    With short half lives- 10-20 hrs (Triazolam at 2.6 to 4 hrs) With long half lives (lorazepam 10-20 hrs) 50 hrs or more to eliminate Bzd biotransformed in the liver to active metabolite have the potential for a long duration of action ADVERSE REACTIONSse Few n mild Excessive CNS depression Drowsiness Somnolence Decreased motor coordination, Impaired intellectual functions other are - CNS depressant synergism - Release of anxiety bound hostility - acute overdosage - excerberation of porphyria  www.indiandentalacademy.com
  21. 21. PSYCHIC AND PHYSICAL DEPENDENCE - Tremor, anorexia, sweating, agitation, and insomnia - Tachycardia, hypertension, visual, tactile, auditory or gustatory hallucinations - paresthesias, photophobia, Abdominal muscular pain depersonization and psychosis BENZODIAZEPINE WIHDRAWL 1) Drug taken longer then 4 months 2) Higher doses have been used 3) Drug stopped suddenly 4) Short acting BZD has been used DRUG INTERACTIONS Cimetidine, Ranitidine, increase blood levels of triazolam and midazolam possibly decreasing their liver metabolism rates All CNS depressants are synergistic with BZD for respiratory depression CONTRAINDICATIONS 1) Allergic patients 2) Narrow angle glaucoma 3) Porphyrism THERAPEUTIC USES www.indiandentalacademy.com
  22. 22. Non benzodiazepine anxiolytic  - BUSPIRONE Devoid of hypnotic, anticonvulsant, or muscle relaxant properties. not involve GABA ergic neurons Equieffective to diazepam Not effect automobile driving performace Adverse effects Dizzinesss Headache Insomnia GIT upset www.indiandentalacademy.com
  23. 23. Benzodiazepine antagonists Flumazenil -competetive antagonist of BZD receptor used to reverse BZD induced CNS depression -commonly given IV also well absorbed orally -Eliminaion half life is 1 hr i.e. less than midazolam and less than diazepam or its metabolite- Rebound CNS depression  ADVERSE EFFECTS -Nausea and vomitting -physical abstinence syndrome Dose- 0.2 mg IV followed by 0.1 to 0.2 mgmin until patient awakens for BZD overdose antagonism www.indiandentalacademy.com
  24. 24. Pharmacology of pain Two components of pain -Pain perception, and Pain reaction Pain perception is the reasonably objective component of the pain phenomenon  Pain reaction is the emotional response to the percieved injury and its painful manifestation www.indiandentalacademy.com
  25. 25.  Analgesics-relieve pain without loss of consciouness Opiates-products obtained from opium poppy Opioid analgesics- naturally occuring, semisynthetic and synthetic drugs which have a morphine like action i.e relief of pain and depression of CNS Narcotic analgesics-old term for opioid analgesics www.indiandentalacademy.com
  26. 26. OPIUM  Dried latex from the seed capsules of certain types of poppy (Papaver somniferum).  Psychological have been recognized for over 6000 years.  Name derived from the Greek name for juice.  First undisputed reference to “poppy juice” dates to Greek medicine, 300 B.C.  In the 18th century, the drinking of “Laudanum” was socially acceptable in Europe, particularly among the artistic in-crowd.  Mid-19th century, the use of pure alkaloids began to prevail over the use of the cruder opium. www.indiandentalacademy.com
  27. 27. Classification 1.Natural opium alkaloids - Morphine, Codeine 2.Semisynthetic opiates - Diacetylmorphine(Heroin), Pholcodeine many others like- Hydromorphone, Oxymorphone, Hydrocodeine, Oxycodone, are not used in India 3. Synthetic opioids- Pethidine, Fentanyl, Methadone, Dextroprpxyphene, Tramadol, Ethoheptazine www.indiandentalacademy.com
  28. 28. Morphine *Source- natural opium alkaloid milky exudate of unripe capsules of poppy plant, papaver somniferum a) Phenanthrene group- Morphine, Codeine and Thebaine. b) Benzylisoquinoline group- Papaverine, Noscapine, Narcine www.indiandentalacademy.com
  29. 29. Pharmacological actions  1) Analgesia- visceral, pain of trauma - elevates pain threshold - alters emotional reaction to pain - produce sleep which also elevates threshold 2) CNS- euphoria- dysphoria- sleep 3) Respiration- depression 4) Pupil- miosis 5) Emetic action- stimulates and inhibits 6) Antitussive effect-suppress 7) ADH secretion-decrease urinary output 8) GIT- decreases peristalitic propulsive movement-spasm-increases water absorption- dry feces- constipation 9) Biliary tract- spasm of sphincter of oddi-increase intrabiliary pressure 10) Other smooth musclesIncreases tone of detrusor muscle, vesicle spehincter contracted increases tone of ureter and decreases its peristalisis constriction of bronchi www.indiandentalacademy.com
  30. 30. 11) CVS- hypotension at toxic dose Absorption, fate and excretionPreparation and dose 1. tincture opium – 0.3 to 2 ml by mouth 2. morphine sulphate3. morphine hydrochloride 8 to 20 mg by mouth or by injection Adverse reactions 1.Dysphoria, mental clouding 2.Nausea, vomiting, rashes 3. Tremor, delirium, and skin rashes 4. acute morphine poisoning- resp. depression, pin point pupil, cyanosis, reduced body temp, hypotension, shock and coma 5. Depression of foetal respiration 6. Tolerance and drug dpendenance Therapeutic uses 1.analgesic 2. sedation and slep 3. pre-anaesthetic medication 4. acute LVF 5. Diarrhoeae www.indiandentalacademy.com 6. As antitussive
  31. 31. Other opioid analgesics *Codeine: phenanthrene alkaloid, antitussive - less potent to morphine - spasmogenic effect, nausea,vomitting, miosis, addiction are less *Papaverine: benzylisoquinoline alkaloid - predominant relaxant on smooth muscles *Noscapine: benzylisoquinoline, antitussive *Heroin (DiacetylMorphine); semisynthetic, more potent than morphine because it produce euphoria, capable of producing severe addiction *Apomorphine: semisynthetic, emetic *pethidine; synthetic -analgesic - spasmogenic on smooth muscle, and sphincter - nausea and vomitting - sedation and euphoria - respiratry depression does not produce miosis and antitussive effect as is produced by morphine Adverse reactions; 1. local irritation on parenteral administration 2. dry mouth, nausea,and vomitting www.indiandentalacademy.com
  32. 32. 3. Euphoria, dysphoria, and vomitting 4. depression of foetal respiration 5. resp. depression, coma,convulsion 6. addiction and tolerance Preparation and dose 1.pethindine hydrochloride tablets- 25 to 100 mg 2. pethidine hydrochloride injection- 25 to 100 mg by sc, im, and 25 to 50 mg by iv Methadone synthetic, analgesic, resp depressant, emetic, antitussive, constipating and biliary action similar to morphine - used in opioid dependence mechanism www.indiandentalacademy.com
  33. 33. OPIOID RECEPTORS  inhibition of neurotransmission via presynaptic and postsynaptic actions  coupled to guanine nucleotide-binding regulatory proteins (Gproteins) www.indiandentalacademy.com
  34. 34. Narcotic Analgesics in Dentistry  opioids used in dentistry are primarily those used for oral administration such as codeine, hydrocodone, oxycodone, and pentazocine.  employed exclusively for pain relief  opioid drugs are NOT anti-inflammatory and much of the pain produced by dental procedures is due to inflammation. Therefore, antiinflammatory drugs such as aspirin, ibuprofen, etc. should be used first to relieve pain - then move to opioids if pain relief is not sufficient.  combinations of opioids such as codeine and aspirin or acetaminophen are commonly employed e.g Oxycodone (related to codeine - but 6-fold more potent) (Percocet -- contains acetaminophen) (Percodan www.indiandentalacademy.com -- contains ASA)   
  35. 35. Comments related to use of narcotic analgesics in dentistry  DRUG INTERACTIONS  other CNS depressants will increase the degree of respiratory depression with opioids  opioids and phenothiazines produce at least additive CNS depression. This combination may also increase orthostatic hypotension, as can opioids and tricyclic antidepressants.  respiratory acidosis caused by large doses of opioid agonists may increase entry of local anaesthetics into the CNS  well documented interaction between meperidine and MAO inhibitors severe and immediate reactions - include excitation, rigidity, hypertension, and sometimes death. www.indiandentalacademy.com
  36. 36. CLASSIFICATION (Acc. to Tripathi) A. Analgesic and antiinflammatory : Salicylates Aspirin, Salicylamide, Benorylate, Diflunisal Pyrazolone derivatives Phenylbutazone, oxyphenbutazone Indole derivatives Indomethacin, sulindac Propionic acid derivatives Ibuprofen,Naproxen, Ketoprofen, Fenoprofen, Flurbiprofen. Anthranilic acid derivative Mephenamic acid Aryl-acetic acid derivatives Diclofenac, Tolmetin Oxicam derivatives Piroxicam, Tenoxicam, Meloxicam. Pyrrolo-pyrrole derivative Ketorolac. Sulfonanilide derivative NImesulide Alkanones www.indiandentalacademy.com Nabumetone
  37. 37. B. Analgesic but poor antiinflammatory: Paraaminophenol derivative Paracetamol (Acetaminophen) Pyrazolone derivatives Metamizol (Dipyrone), propiphenazone Benzoxazocine derivative Nefopam Acc. to Goodman and Gillman A. Non selective Cox inhibitor Salicylic acid derivatives Aspirin, sodium salicylate, choline magnesium trisalicylate, salsalate, diflunisal, salfasalazine, olsalazine. Para amino derivatives Acetaminophen Indole & indene acetic acid Indomethacin, sulindac Heteroaryl acetic acid Tolmetin, diclofenac, www.indiandentalacademy.com ketorolac.
  38. 38. Aryl propionic acid Ibuprofen, naproxen, flurbiprofen, ketoprofen, fenoprofen, oxaproxin. Anthranilic acid (fenamates) Enolic acid Mefenamic acid, meclofenamic acid Oxicams (piroxicam, Meloxicam) Alkanones Nabumetone. B. Selective cox-2 inhibitor Diaryl substituted furanones Diaryl substituted Pyrazoles Indole acetic acid Sulfonanilides Rofecoxib Celecoxib Etodolac Nimesulide www.indiandentalacademy.com
  39. 39. MECHANISM OF ACTION Odontogenic pain Noxious stimuli Disease process + Surgical intervention Acute pain Tissue destruction or injury Cellular destruction Release / synthesis of histamine / prostaglandin / bradykinin + Peripheral nociceptor / free nerve endings PAIN www.indiandentalacademy.com
  40. 40. Beneficial actions due to PG Synthesis inhibition  Analgesia  Antipyresis  Antiinflammatory  Antithrombotic  Closure of ductus arteriosus Shared toxicities due to PG synthesis inhibition  Gastric mucosal damage  Bleeding  Limitation of renal blood flow  Delay / prolongation of labour  Asthma & anaphylactoid reactions www.indiandentalacademy.com
  41. 41. COMMON PROPERTIES OF ALL NSAIDS Analgesia Anaphylactoid reactions Antipyresis Antiinflammatory Renal effects Dysmenorrhoea Gastric mucosal damage Parturition Ductus arteriosus closure www.indiandentalacademy.com Antiplatelet aggregatory
  42. 42. SALICYLATES Aspirin (prototype) Pharmacological actions • Analgesic (0.3-1.5 g/day) • Antipyretic • Respiration • GIT • Antiinflammatory (3-6 g/day or 100mg/kg/day) • Immunological effect • Uricosuric effect • CVS • Blood • Endocrines  <2g/day  • Metabolic effect 2-5 g/day • Local actions  > 5g/day www.indiandentalacademy.com
  43. 43. Pharmacokinetics  80% bound to plasma proteins.  Volume distribution 0.17 L/kg.  Plasma t ½ = 15-20 min.  Release salicylic acid (t ½) = 3-5 hrs.  Antiinflammatory doses (t ½) = 8-12 hrs. (30 hrs in poisoning) www.indiandentalacademy.com
  44. 44. Adverse effects Salicylism : dizziness, tinnitus, vertigo, reversible impairment of hearing & vision, excitement & mental confusion, hyperventilation & electrolyte imbalance. www.indiandentalacademy.com Acute salicylate poisoning : fatal dose-15-30g , > 50 mg/dl.
  45. 45. Contraindications :  Sensitivity, peptic ulcers, bleeding tendency, chicken pox or influenza.  Chronic liver disease  Diabetics, low cardiac reserve or frank CHF, juvenile rheumatoid arthritis. Precautions :  Stopped 1 week before elective surgery.  During pregnancy  Avoided by breast feeding mothers.  G-6-PD deficient individuals www.indiandentalacademy.com
  46. 46. Interactions :  Warfarin, naproxen, sulfonylureas, phenytoin and methotrexate.  Oral anticoagulants.  Uric acid  Probenecid  Methotrexate.  Furosemide and thiazides  Spironolactone. www.indiandentalacademy.com  Protein bound iodine levels.
  47. 47. Uses : Patent ductus arteriosus Analgesic Pregnancy induced hypertension and preeclampsia Antipyretic Acute rheumatic fever (4-6 g) Postmyocardial infarction & poststroke patients Delay labour Rheumatoid arthritis (3-5 g) Osteoarthritis www.indiandentalacademy.com * Aspirin, dispirin, colosprin
  48. 48. PYRAZOLONES Phenylbutazone Pharmacokinetics  98% bound to plasma proteins.  Plasma t ½ = 60 hrs.  Dose 100-200 mg BD/TDS Adverse effects  Bone marrow depression  Agranulocytosis  Stevens-Johnson syndrome www.indiandentalacademy.com
  49. 49. PYRAZOLONES Phenylbutazone Pharmacokinetics  98% bound to plasma proteins.  Plasma t ½ = 60 hrs.  Dose 100-200 mg BD/TDS Adverse effects  Bone marrow depression  Agranulocytosis  Stevens-Johnson syndrome www.indiandentalacademy.com
  50. 50. Interactions :  Sulfonamides, tolbutamide, imipramine & methotrexate warfarin,  Anticoagulants  Phenytoin & tolbutamide P L Uses : Rheumatic fever Severe cases Acute gout Ankylosing spondylitis Zolandin www.indiandentalacademy.com Rheumatoid arthritis
  51. 51. Sioril, phenabid  Oxyphenbutazone  Metamizol (Dipyrone) : 0.5-1.5 g Analgin, novalgin  Propiphenazone : 300-600 mg TDS Saridon, anafebrin INDOLE DERIVATIVES Indomethacin Pharmacokinetics  90% bound to plasma proteins.  Plasma t ½ = 2-5 hrs.  Dose 25-50mg BD/QID www.indiandentalacademy.com
  52. 52. Adverse effects Interactions :  Furosemide  Thiazides, furosemide, β blockers, ACE inhibitors  Warfarin www.indiandentalacademy.com
  53. 53. Uses : P L Psoriatic arthritis Rheumatoid arthritis Ankylosing spondylitis Acute gout Malignancy asso. fever Acu. Exa. destructive arthropathies Patent ductus arteriosus closure (0.1/0.2 mg/kg/12 hrly Indicin, indocap www.indiandentalacademy.com
  54. 54. PROPIONIC ACID DERIVATIVES Pharmacokinetics  90-99% bound to plasma proteins. Drug Plasma t ½ Ibuprofen Naproxen 2 hr 12-16 hr Ketoprofen Fenoprofen 2-3 hr 2-4 hr Dosage 400-800 mg TDS Brufen, emflam 250 mg BD/TDS Xenobid, naxid 100 mg BD/TDS Ketofen 300-600 mg TDS Arflur www.indiandentalacademy.com Flurbiprofen 4-6 hr 50 mg BD/QID Flurofen
  55. 55. Adverse effects Interactions :  Anticoagulants  Furosemide, thiazides & β blockers www.indiandentalacademy.com
  56. 56. Uses : Antipyretic Analgesic Dysmenorrhoea ANTHRANILIC ACID DERIVATIVE (Fenamate) Mephenamic acid Pharmacokinetics  Highly bound to plasma proteins.  Plasma t ½ = 2-4 hrs  250-500 mg TDS www.indiandentalacademy.com
  57. 57. Adverse effects L Uses : Osteoarthritis Analgesic Rheumatoid arthritis Dysmenorrhoea www.indiandentalacademy.com Medol, meftal, ponstan
  58. 58. ARYL-ACETIC ACID DERIVATIVES Diclofenac sodium : Pharmacokinetics  99% bound to plasma proteins.  Plasma t ½ = 2 hrs  50 mg TDS/BD, 75 mg i.m. Adverse effects www.indiandentalacademy.com
  59. 59. Uses : Ankylosing spondylitis Osteoarthritis Rheumatoid arthritis Bursitis Dysmenorrhoea Post-traumatic / post-op inflammatory condition Voveran, diclonac, movonac Tolmetin : 400-600 mg TDS www.indiandentalacademy.com
  60. 60. OXICAM DERIVATIVES Piroxicam Pharmacokinetics  99% bound to plasma proteins.  Plasma t ½ = 2 days  20 mg BD / 20 mg OD Adverse effects www.indiandentalacademy.com
  61. 61. Uses : P L Ankylosing spondylitis Osteoarthritis Rheumatoid arthritis Dysmenorrhoea Dentistry Acute gout Episiotomy Musculoskeletal injuries Dolonex, pirox, piricam, toldin Tenoxicam : 20 mg OD Meloxicam : 7.5-15 mg/day (rheumatoid & osteo-arthritis) www.indiandentalacademy.com www.indiandentalacademy.com Melflam, Meloxi
  62. 62. PYRROLO-PYRROLE DERIVATIVE Ketorolac : Pharmacokinetics  Highly bound to plasma proteins.  Plasma t ½ = 5-7 hrs  10-20 mg / 6 hrly (orally) Adverse effects www.indiandentalacademy.com
  63. 63. Uses : Renal colic Bony metastasis Migraine Post-op / acute musculoskeletal pain (15-30 mg i.m. / 4-6 hrs Ketorol, torolac SULFONANILIDE DERIVATIVE Nimesulide : Pharmacokinetics  99% bound to plasma proteins.  Plasma t ½ = 2-5 hrs  100 mg BD www.indiandentalacademy.com
  64. 64. Adverse effects Uses : Sports injuries Dental surgery ENT disorders Bursitis Low backache Dysmenorrhoea Post-op www.indiandentalacademy.com pain/osteoarthritis Nimulid, nimodol
  65. 65. PARA-AMINO PHENOL DERIVATIVES • Phenacetin 1887 • Paracetamol (acetaminophen) 1950 Actions Pharmacokinetics  1/3 bound to plasma proteins.  Plasma t ½ = 2-3 hrs  3-5 hrs (orally)  0.5-1g TDS  Infants - 50 mg  Children 1-3 yrs- 80-160 mg 4-8 yrs 240-320 mg www.indiandentalacademy.com 9-12 yrs 300-600 mg
  66. 66. Adverse effects Analgesic nephropathy Acute paracetamol poisoning  150 mg/kg  Fatality > 250 mg/kg  Early manifestations / 12-18 hrs / 2 days www.indiandentalacademy.com
  67. 67.  Mechanism of toxicity  Treatment – • Gastric lavage • N-acetylcysteine 150 mg/kg / i.v./ 15 min / 20 hrs • 75 mg/kg / orally / 4-6 hrs / 2-3 days Uses : ‘Over the counter’ analgesic Antipyretic Dysmenorrhoea Musculoskeletal pain Crocin, metacin, paracin www.indiandentalacademy.com
  68. 68. BENZOXAZOCINE DERIVATIVE Nefopam 30-60 mg TDS oral 20 mg i.m. 6 hrly Nefomax CHOICE OF NSAIDS • Mild to moderate pain – paracetamol, ibuprofen • Acute musculoskeletal, osteoarthritic, injury associated inflammation – ibuprofen, diclofenac, piroxicam • Post-op / acute / short lasting painful condition – ketorolac, nefopam www.indiandentalacademy.com
  69. 69. • Exacerbation of rheumatoid arthritis, ankylosing spondylitis, acute gout, acute rheumatic fever – aspirin, indomethacin, naproxen, piroxicam • Asthma or anaphylactoid reactions to aspirin – nimesulide www.indiandentalacademy.com
  70. 70. Analgesics after certain endodontic procedures www.indiandentalacademy.com
  71. 71. PAIN MANAGEMENT STRATEGY D 3 iagnosis efinitive Rx rugs Definitive treatment : Drug : •Pulpotomy, pulpectomy •Pretreat with NSAIDs •Extraction •Prescribe by clock •Incision & drainage •Long acting LA •Flexible prescription plan www.indiandentalacademy.com
  72. 72. Flexible analgesic prescription plan Mild pain Aspirin like drugs indicated Ibuprofen 200 mg Moderate pain NSAIDs (alone max.effective dose) OR NSAID + acetaminophen Aspirin like drugs contra indicated Acetaminophen 600-1000mg Acetaminophen 600-1000 mg + codine 60 mg Ibuprofen 400 mg/4 hrly and equivalent of acetaminophen 600 mg / codine 60 mg 4 hrly Severe pain NSAID (max. dose) & Acetaminophen 1000 mg with acetaminophen / oxycodone equivalent of oxycodone 10 www.indiandentalacademy.com 10 mg combination mg
  73. 73. ADVANCES Selective cox-2 inhibitors : Celecoxib, rofecoxib, valdecoxib, etoricoxib, meloxicam, diisopropyl flurophosphate. Action Celecoxib P© L© Use-osteoarthritis, rheumatoid arthritis Dose – 200 mg / day OD or 100 mg BD. Commercial names – Celebrex, Celib, Celfast, Celact etc. Banned – July 2001 Rofecoxib P© L© Dose – 12.5 mg OD (max. dose 25 mg) Commercial name – Vioxx, Dolib MD, Roff, Rofaday www.indiandentalacademy.com Banned – September 2004
  74. 74. Valdecoxib Dose – 10-20 mg OD Commercial name – Valed, Valus, Vorth, Bextra Banned –7 April 2005. Other drugs banned by FDA  Benoxaprofen  Phynylbutazone  Oxyphenbutazone  Saprofen  Piroxicam www.indiandentalacademy.com
  75. 75. ANTIBIOTICS www.indiandentalacademy.com
  76. 76. 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. Antibiotic agent : against life (greek-anti means against and biosis means life). Chemical substances produced by microorganisms that have the capacity in dilute solutions, to produce antimicrobial action. www.indiandentalacademy.com
  77. 77. Principles of appropriate antibiotic use : 1. Presence of infection : If a patient has infection. • Local signs and symptoms • Systemic signs and symptoms • Other disease conditions having some of the same signs and symptoms. 2. State of host defenses : • Final outcome of a bacterial insult. • It is important to understand that infections are ultimately cured by the host, NOT by antibiotics. • Antibiotics can only help • Control of infection www.indiandentalacademy.com
  78. 78. 3. Surgical Drainage and incision : •Treatment of deep tissue infections – surgical drainage •If unreleased – vascularity of the tissue and prevents host defense substance for getting to the area. •Odontogenic infection 4. The decision to use antibiotic therapy : •Intact host defenses may not require antibiotic therapy. •Severe conditions can be treated. •In all instances of infection. www.indiandentalacademy.com
  79. 79. PRINCIPLES FOR CHOOSING THE APPROPRIATE ANTIBIOTIC 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 www.indiandentalacademy.com e) Osteomyelitis is present
  80. 80. 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 www.indiandentalacademy.com
  81. 81. 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
  82. 82. 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 chloramphenicol. www.indiandentalacademy.com to penicillin and
  83. 83. 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. www.indiandentalacademy.com
  84. 84. 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 it’s 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. www.indiandentalacademy.com
  85. 85. PRINCIPLES OF ANTIBIOTIC ADMINISTRATION 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 www.indiandentalacademy.com
  86. 86. 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 3rd www.indiandentalacademy.com day of antibiotic therapy, recurrence of the infection is more likely.
  87. 87. 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 • www.indiandentalacademy.com to decrease toxicity without decreasing efficacy
  88. 88. 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. www.indiandentalacademy.com 3) 2 bacteriostatic drugs are never inhibitory.
  89. 89. 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 algebric 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. www.indiandentalacademy.com
  90. 90. Disadvantages : i) Adds nothing to therapeutic efficacy and may even reduce it (antagonism). ii) Increase antibiotic toxicity and allergy. iii) Increase the likelihood of superinfection iv) Discourages specific etiologic diagnosis and promote false security. v) Encourage inadequate doses, particularly with fixed dose combination therapy. vi) Increased cost vii) Emergence of resistant bacterial strains viii)Increase the environmental spread of antibiotic resistant www.indiandentalacademy.com bacteria.
  91. 91. MONITORING THE PATIENT 1. Response to treatment : • Noticeable response first 24 to 48 hours. • If the end of the 3rd day, no improvement is noted, the patient must be carefully reevaluated. Several questions should be considered : a) Have the route of administration and the dose of the antibiotic been adequate ? b) Is the patient taking the antibiotic as prescribed ? c) Have the physician’s orders on the chart been understood and carried out ? d) Was the initial choice of the antibiotic correct ? many of times, the combination of SURGICAL and NATURAL www.indiandentalacademy.com HOST DEFENSES has resulted in resolution of the infection.
  92. 92. 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 www.indiandentalacademy.com
  93. 93. 2. Development of adverse reactions : • Adverse reactions occur all too commonly. • 15 to 20 percent of hospitalized patients receiving antibiotics experience and adverse reactions. • Hypersensitivity (type I) reactions occur with all antibiotics – penicillins and cephalosporins • Less severe reactions – edema, urticaria and itching are delayed reactions. • Anaphylactic reactions is not difficult, but treatment must be rapid and intense. • Treatment is to discontinue the causative antibiotic, restore fluid and electrolyte balance. • The usual choice is oral vancomycin, but metronidazole may www.indiandentalacademy.com be used also.
  94. 94. 3. Superinfection and recurrent infection : • 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 www.indiandentalacademy.com high dose penicillin therapy).
  95. 95. PROPHYLACTIC ANTIBIOTICS Advantages : • Prevention of infection • Decreased patient morbidity • Decreased patient mortality • Decreased hospital stay • Decreased medical costs • Decreased total antibiotic usage • Decreased number of resistant bacteria www.indiandentalacademy.com
  96. 96. Disadvantages : 1) No reduction of infection, despite prophylaxis 2) Development of increased number of resistant bacteria 3) Delayed onset of infection 4) Adverse effect on surgical technique Note : Effective is a short-term administration of a narrowspectrum antibiotic. www.indiandentalacademy.com
  97. 97. Principles for the use of prophylactic antibiotics : 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 thewww.indiandentalacademy.com causative organisms.
  98. 98. CLASSIFICATION OF ANTIMICROBIAL DRUGS 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 www.indiandentalacademy.com
  99. 99. 3. Inhibit protein synthesis • Tetracyclines • Chloramphenicol • Erthromycin, • Clindamycin • Linezolid 3. Cause misreading of m-RNA code and affect permeability • Aminoglycosides o Streptomycin o Gentamicin www.indiandentalacademy.com
  100. 100. 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 Sulfones PAS www.indiandentalacademy.com Ethambutol
  101. 101. B) Chemical structure 1. Sulfonamides and related drugs • Sulfadiazine and others • Sulfones – Dapsone (DDS), Paraaminosalicylic acid (PAS). 2. Diaminopyrimidines • Trimethoprim • Pyrimethamine 3. Quinolones • Nalidixic acid • Norfloxacin • www.indiandentalacademy.com Ciprofloxacin etc
  102. 102. 4. β-lactam antibiotics • Penicillins • Cephalosporins • Monobactams • Carbapenems 4. Tetracyclines • Oxytetracycline • Doxycycline etc 4. Nitrobenzene derivative • Chloramphenicol www.indiandentalacademy.com
  103. 103. 7. Aminoglycosides • Streptomycin • Gentamicin • Neomycin etc 7. Macrolide antibiotics • Erythromycin • Roxithromycin • Azithromycin etc 7. Polypeptide antibiotics • Polymyxin-B • Colistin • Bacitracin • Tyrothricin www.indiandentalacademy.com
  104. 104. 10. Glycopeptides • Vancomycin • Teicoplanin 10. Oxazolidinone • Linezolid 10. Nitrofuran derivatives • Nitrofurantoin • Furazolidone 10. Nitroimidozoles • Metronidozole • Tinidazole www.indiandentalacademy.com
  105. 105. 14. Nicotinic acid derivatives • Isoniazid • Pyrazinamide • Ethionamide 14. Polyene antibiotics • Nystatin • Amphotericin-B • Hamycin 14. Azole derivatives • Miconazole • Clotrimazole • Ketoconazole • fluconazole www.indiandentalacademy.com
  106. 106. 17. Others • Rifampin • Lincomycin • Clindamycin • Spectinomycin • Sod. fusidate • Cycloserine • Viomycin • Ethambutol • Thiacetazone • Clofazimine • Griseofulvin www.indiandentalacademy.com
  107. 107. C) Type of organisms against which primarily active 1. Antibacterial • Penicillins • Aminoglycosides • Erythromycin etc 2. Antifungal • Griseofulvin • Amphotericin B • Ketoconazole 3. Antiviral • Idoxuridine • Acyclovir • Amantadine • Zidovudine etc www.indiandentalacademy.com
  108. 108. 4. Antiprotozoal • Chloroquine • Pyrimethamine • Metronidazole • Diloxanide etc 4. Anthelmintic • Mebendazole • Pyrantel • Niclosamide • Diethyl carbamazine etc www.indiandentalacademy.com
  109. 109. D) Spectrum of activity 1. Narrow spectrum • Penicillin G • Streptomycin • Erythromycin 2. Broad spectrum • Tetracyclines • Chloramphenicol www.indiandentalacademy.com
  110. 110. E) Type of action 1. Primarily bacteriostatic 2. Primarily bactericidal • Sulfonamides • Penicillins • Tetracyclines • Aminoglycosides • Chloramphenicol • Polypeptides • Erythromycin • Rifampin • Ethambutol • Cotrimoxazole • Cephalosporins • Vancomycin • Nalidixic acid • Ciprofloxacin www.indiandentalacademy.com
  111. 111. F) Antibiotics are obtained from 1. Fungi 3. Actinomycetes • Pencillin • Aminoglycosides • Cephalosporin • Tetracyclines • Griseofulvin • Chloramphenicol • Macrolides • Polyenes 2. Bacteria • Polymyxin B • Colistin • Bacitracin • Tyrothricin • Aztreonam www.indiandentalacademy.com
  112. 112. Misconception about antibiotics        Improper choice- drug, dosage, duration of therapy Ignorance of Microbial biology Antibiotics- “safe & do no harm” Antibiotics prophylaxis commonly successful To mask poor surgical procedure “ I don’t know what else to do syndrome” Malpractice negligence suit www.indiandentalacademy.com
  113. 113. Myths in antibiotic theapy        I. Antibiotic cure patients II. Antibiotics are substitute for surgical drainage III. The most important decision is which antibiotic use IV. Antibiotic therapy is a science and not an art V. Culture and sensitivity are required VI. Antibiotics increase host defence to infection VII. Multiple antibiotics are superior to a single antibiotic www.indiandentalacademy.com
  114. 114.       VIII. Antibiotic prophylaxis is usually effective IX. Bactericidal agents are always superior to bacteriostatic agent X. Antimicrobial are effective in chronic infectious diseases XI. Antibiotics are safe and nontoxic XII. Antibiotic dosage are established for most infections XIII. Infection require a complete course of therapy www.indiandentalacademy.com
  115. 115. BETA LACTAM ANTIBIOTICS Pencillins 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. www.indiandentalacademy.com
  116. 116. CLASSIFICATION OF PENICILLINS 1. Natural penicillin • Penicillin G (benzyle penicillin) • Procaine penicillin G • Benzathine penicillin G 2. Acid resistant penicillin • Phenoxymethyl penicillin (pencillin V) • Phenoxyethylpenicillin (phenethecillin) 3. Penicillianse – resistant penicillins • Acid labile – methecillin, nafcillin, cloxacillin, dicloxacillin • Acid resistant – flucloxacillin www.indiandentalacademy.com
  117. 117. 4. Penicillins effective against gram positive and some gramnegative organisms • Ampecillin • Ampoxycillin • Talampicillin 4. Extended spectrum penicillins • Carboxypenicillins – carbenicillin, ticarcillin • Ureidopencillins – piperacillin, mezlocillin • Amidino pencillins – mecillinam, pivmecillinam 4. Penicillins with betalactamase inhibitors • Amoxycillin – clavulanic acid (Augmentin) • www.indiandentalacademy.com Ticarcillin – clavulanic acid (Timentin)
  118. 118. BENZYL PENICILLIN (PENCILLIN G) • PnG is a narrow spectrum antibiotic; activity is limited primarily to gram positive bacteria • Is available in the form of water soluble sodium and potassium salts • This salts in a dry state are stable at room temperature for years. The aqueous solution however requires refrigeration and deteriorates considerably with in 72 hours. Antibactrial activity • Most potent AMA, inhibits the growth of susceptible organism. • Mainly gram +ve, gram –ve cocci and some gram +ve bacilli with exception of enterococci. • Cocci – Highly sensitive – Streptococci, Pneumococci, Staph. aureus, N. gonorrhoeae, N. meningitis • Bacilli – B. anthracis, Corynebacterium diphtheriae, clostridium tetany and spirocheteswww.indiandentalacademy.com • Actinomyces israelii is moderately sensitive
  119. 119. Mechanism of action : • 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 www.indiandentalacademy.com actively multiplying effective against organisms.
  120. 120. www.indiandentalacademy.com
  121. 121. Absorption fate and excretion : • 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. www.indiandentalacademy.com
  122. 122. • 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 www.indiandentalacademy.com
  123. 123. 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 a) Intolerance : • Major problem with PnG includes anaphylactic and allergic reactions www.indiandentalacademy.com idiosyncratic,
  124. 124. c) Other allergic reactions are • Skin rashes • Serum sickness • Renal disturbance • Hemolytic disturbance • Anaphylaxis • Jarisch herxheimer reaction • Super infection • Hyperkalemia • Acute non allergic reaction www.indiandentalacademy.com
  125. 125. 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 www.indiandentalacademy.com
  126. 126. 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. www.indiandentalacademy.com Thus a variety of semisynthetic resins are produced.
  127. 127. I) Acid resistant pencillins : 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 www.indiandentalacademy.com and streptococci).
  128. 128. 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 www.indiandentalacademy.com
  129. 129. II) Pencillinase resistant pencillins : 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. www.indiandentalacademy.com BIOCLOX, KLOX, CLOCILIN 0.25, 0.5 gm cap, 0.5 gm/vial.
  130. 130. 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. www.indiandentalacademy.com
  131. 131. 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 www.indiandentalacademy.com
  132. 132. 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 • Bacillary dysentry • Septicaemias • www.indiandentalacademy.com
  133. 133. 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. www.indiandentalacademy.com
  134. 134. AMOXYCILLIN : • 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 bond and urinary excretion is higher than that of ampicillin. • Incidence of diarrhoea is less www.indiandentalacademy.com
  135. 135. Dose : 0.25-1 g TDS oral; AMOXYLIN, NOVAMOX, SYNAMOX, MOX, AMOXIL 250, 500 mg cap, 125 mg/5ml dry syr, 500 mg/vial inj. USES : • Typhoid • Bronchitis • Urinary infection • SBE • Gonorrhoea www.indiandentalacademy.com
  136. 136. Carboxy penciillins : 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 They have following properties : 1. Highly active against anaerobes 2. Most useful in infections caused by other gram-ve rods 3. Act synergistically with amino particularly enterobacteriacea. glycoside antibiotics, 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 www.indiandentalacademy.com infections.
  137. 137. CARBENICILLIN • 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 www.indiandentalacademy.com
  138. 138. 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 www.indiandentalacademy.com
  139. 139. UREIDOPENICILLINS –PIPERACILLIN ( PIPRIL) AMIDINOCILLIN – MECILLINAM Has similar indications of carbenicillin www.indiandentalacademy.com
  140. 140. BETA LACTAMASE INHIBITORS •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 www.indiandentalacademy.com
  141. 141. 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 www.indiandentalacademy.com
  142. 142. Adverse effects : • Poor g.i. tolerance • Hepatotoxicity AUGMENTIN, AMONATE, ENHANCIN • 250+125mg tab 1-2tab TDS • 250+50mg vial im/iv 6-8 hourly www.indiandentalacademy.com
  143. 143. SULBACTAM • 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 www.indiandentalacademy.com
  144. 144. Adverse effects : • Pain-thrombophebitis • Rashes and diarrhoea Uses : • Mixed aerobic-anaerobic infections • Gonorrhoea • Skin/soft tissue infections www.indiandentalacademy.com
  145. 145. CEPHALOSPORINS 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 www.indiandentalacademy.com
  146. 146. 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 www.indiandentalacademy.com
  147. 147. 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, DROXYL CEPHAXIN, CEPHACILLIN, www.indiandentalacademy.com CEFADROX,
  148. 148. Second generation cephalosporins : 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. www.indiandentalacademy.com
  149. 149. Third generation cephalosporin : •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. 100mg/5ml syr., 50mg/ml susp. CESPAN, CEFOPROX, www.indiandentalacademy.com PROCADAX, CEPODEM, ORFIX.
  150. 150. Fourth 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. www.indiandentalacademy.com CEFROM, CEFORTH – 1g inj.
  151. 151. Guiding principle for the use of cephalosporins : •Cephalosporins are expensive and should not be used where an equally effective, alternative antibiotic 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 www.indiandentalacademy.com meningitis.
  152. 152. Adverse reactions : • Local reactions – thrombophlebitis (IV) • Allergy – skin rashes • Super infection • Nephrotoxicity • CNS toxicity • Blood toxicity • Intolerance to alcohol • Cross reactivity with penicillin cause pain www.indiandentalacademy.com (IM) and cause
  153. 153. Uses : • 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. www.indiandentalacademy.com
  154. 154. MACROLIDES 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. www.indiandentalacademy.com
  155. 155. 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 www.indiandentalacademy.com  Excreted through kidney and bile
  156. 156. 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 www.indiandentalacademy.com
  157. 157. Adverse effects :  GIT – epigastric pain  On high doses – hearing impairment  Hypersensitivity reactions – rare Uses :  Substitute for penicillin  Whooping cough  Chancroid  Penicillin resistant infections www.indiandentalacademy.com
  158. 158. ROXITHROMYCIN  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 www.indiandentalacademy.com
  159. 159. AZITHROMYCIN  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 www.indiandentalacademy.com
  160. 160. Uses :  Chlamydial infection  Respiratory infection  Strep and Staph skin and soft tissue infections Doses :  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 500mgwww.indiandentalacademy.com inj
  161. 161. CLINDAMYCIN  It is lincosamide antibiotic having similar action (macrolide 50s)  Semisynthetic derivative of Lincomycin  Bacteriostatic – low conc  Bacteriocidal – high conc  Most active Actinomyces against gram+ve cocci,  Highly active against – anaerobes (B fragilis) Pharmacokinetics :  Oral absorption – good  Distribution – skeletal and soft tissues  Excreted in urine www.indiandentalacademy.com C.diphtheriae,
  162. 162. 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.www.indiandentalacademy.com
  163. 163. TETRACYCLINES  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. www.indiandentalacademy.com
  164. 164. 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 Mechanism of action : 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) www.indiandentalacademy.com sites on the mRNA ribosome complex.
  165. 165. www.indiandentalacademy.com
  166. 166. 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 inwww.indiandentalacademy.com urine through kidney
  167. 167. Adverse effects :  GIT-epigastric burning, nausea, vomiting,diarrhoea  Hepatoxicity  Renal toxicity  Effects on teeth-Orthophosphate complex  Thrombophlebitis  Hypersensitivity Reactions  Superinfection  Antianabolic effect www.indiandentalacademy.com
  168. 168. 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 in10ml vial inj www.indiandentalacademy.com  DOXT, NOVADOX, TETRADOX-100mg cap. cap,50mg/ml
  169. 169. Precaution :  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 www.indiandentalacademy.com
  170. 170. 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. www.indiandentalacademy.com
  171. 171. Mechanism of action :  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 www.indiandentalacademy.com
  172. 172. 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 www.indiandentalacademy.com
  173. 173. 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 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. www.indiandentalacademy.com  Excreted primarily in urine.
  174. 174. Adverse effect :  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  Typhoid  Gonorrhoea  Bone, soft tissue, wound infection.  Chancroid  RTI  Bacterial gastroenteritis  Tuberculosis  Meningitis  Gr-ve septicaemias  Prophylaxis  Conjunctivitis www.indiandentalacademy.com
  175. 175. CIFRAN, CIPLOX, CIPROBID, CIPROLET 250, 500,750 mg tab, 200mg/100 ml IV infusion 3mg/ml eye drops. NORFLOXACIN  It is less potent than cipro  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 www.indiandentalacademy.com  200, 400, 800 mg tab, 3mg/ml eyedrops.
  176. 176. OFLOXACIN 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. www.indiandentalacademy.com  Excreted largely unchanged in urine(dose reduced in renal failure)
  177. 177. Uses :  Chronic bronchitis, respiratory/ENT infection.  Gonorrhoea  Nongonococcal urethritis.  ZENFLOX, OFLOX  100, 200, 400 mg tab, 200 mg/100IV infusion 5mg/5ml susp. www.indiandentalacademy.com
  178. 178. LEVOFLOXACIN  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 www.indiandentalacademy.com
  179. 179.  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. www.indiandentalacademy.com
  180. 180. GATIFLOXACIN Another 2nd 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 www.indiandentalacademy.com
  181. 181. Adverse effect :  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 www.indiandentalacademy.com
  182. 182. MOXIFLOXACIN :  It is long acting 2nd 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 www.indiandentalacademy.com
  183. 183. ANTIAMOEBIC AND OTHER ANTIPROTOZOAL DRUGS METRONIDAZOLE :  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 microorganisms. selectively toxic to anaerobic  Metronidazole has been found to inhibit cell mediated www.indiandentalacademy.com immunity and cause radiosensitization.
  184. 184. 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 : Side effects relatively frequent but mostly not serious,  Anorexia, nausea, metallic taste and abdominal cramps are the most common. www.indiandentalacademy.com
  185. 185.  Looseness of stool is occasional,  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. www.indiandentalacademy.com
  186. 186. Uses :  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. www.indiandentalacademy.com
  187. 187. 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. www.indiandentalacademy.com
  188. 188. Role of antibiotics in endodontics (jr of Dent 26 (2001) 539-48) I ENDODONTICS AND THERAPEUTIC ANTIBIOTICS 1) Adjunct to operative treatment 2) Contingency treatment 3) Antibiotics at Obturation 4) Antibiotics for perio-endo lesion 5) which antibiotic II TOPICAL ANTIBIOTICS AND ENDODONTICS 1) Pulpitis 2) Pulp capping 3) Root canal therapy 4) Flare- ups 5) Perio endo lesion 6) Tooth avulsion www.indiandentalacademy.com III ANTIBIOTIC PROPHYLAXIS AND ENDODONTICS
  189. 189. What are local anesthetics?  Local anesthetic: are agents which block conduction impulses in nerves. When applied locally, they produce loss of sensation in the desired area. www.indiandentalacademy.com
  190. 190. Classification INJECTABLE Low potency, short duration Procaine Chloroprocaine Intermediate potency and duration Lidocaine (Lignocaine) Prilocaine High potency, long duration Tetracaine Bupivacaine Ropivacaine Dibucaine  SURFACE ANAESTHETIC Soluble Cocaine Lidocaine Tetracine Insoluble Benzocaine Butylaminobenzoate Oxyethazine www.indiandentalacademy.com
  191. 191. History       Coca leaves from the genus Erythroxylum Erythroxylum contains high concentration of alkaloid up to 0.7-1.8% Alkaloid has natural nitrogen bases found in the coca leaves, also known as cocaine Genus Erythroxylum discovered in South America, Venezuela, Bolivia, and Peru since pre-Columbian periods Earliest cultivation and use of the coca leaf went back to about 700 BC in Bolivia and Andes regions New discoveries showed humans used coca more than 5,000 years ago in Ecuador www.indiandentalacademy.com
  192. 192. History (cont.)     Spanish conquistadors and explorers witnessed the consumption of coca in South America Spaniards, such as Alfred Buhler, hypothesized a tribe in the Negro River area called Arhuaco was the original discoverers of the properties and functions of the drugs. In 1571, Pedro Pizarro, a conquistador of Inca, observed nobles and high rank officials of the Inca empire consumed the coca plant. After the fall of the Inca empire, coca consumption spread widely to the population www.indiandentalacademy.com
  193. 193. Cocaine Addiction      More physicians began to do research of cocaine in the clinic trials. The physician Sigmund Freud used the stimulant effect of cocaine to treat the morphine addiction in patients An ophthalmologist Carl Koller realized the importance of the alkaloid’s anesthetic effect on mucous membranes In 1884, he used the first local anesthetic on a patient with glaucoma Freud, Halsted, and Koller became addicted to the drug through self-experimentation www.indiandentalacademy.com
  194. 194. Side Effects of Cocaine and Solutions Minor:  Addiction  Intoxication Severe:  Death Solutions:  Used nitrous oxide gases and ether for minor surgery in dentistry  Give a low concentration of cocaine; it slows down the release of the drug into the bloodstream causing little side effects www.indiandentalacademy.com
  195. 195. Procaine replaced cocaine   In 1898, Professor Heinrich Braun introduced procaine as the first derivative of cocaine, also known as the first synthetic local anesthetic drug Trade name is Novocaine® Novocaine Problems Took too long to set (i.e. to produce the desired anesthetic result)  Wore off too quickly, not nearly as potent as cocaine  Classified as an ester; esters have high potential to cause allergic reactions  Caused high conc. of adrenaline resulted in increasing heart rate, make people feel nervous Most dentists preferred not to used any local anesthetic at all that time; they used nitrous oxide gas. Today, procaine is not even available for dental procedures.  www.indiandentalacademy.com
  196. 196. Lidocaine       In 1940, the first modern local anesthetic agent was lidocaine, trade name Xylocaine® It developed as a derivative of xylidine Lidocaine relieves pain during the dental surgeries Belongs to the amide class, cause little allergenic reaction; it’s hypoallergenic Sets on quickly and produces a desired anesthesia effect for several hours It’s accepted broadly as the local anesthetic in United States today www.indiandentalacademy.com
  197. 197. Differences of Esters and Amides All local anesthetics are weak bases. Chemical structure of local anesthetics have an amine group on one end connect to an aromatic ring on the other and an amine group on the right side. The amine end is hydrophilic (soluble in water), and the aromatic end is lipophilic (soluble in lipids)  Two classes of local anesthetics are amino amides and amino esters. Amides: Esters: --Amide link b/t intermediate --Ester link b/t intermediate chain and chain and aromatic ring aromatic ring --Metabolized in liver and very --Metabolized in plasma through soluble in the solution pseudocholinesterases and not stable in the solution --Cause allergic reactions  www.indiandentalacademy.com
  198. 198. Structures of Amides and Esters    The amine end is hydrophilic (soluble in water), anesthetic molecule dissolve in water in which it is delivered from the dentist’s syringe into the patient’s tissue. It’s also responsible for the solution to remain on either side of the nerve membrane. The aromatic end is lipophilic (soluble in lipids). Because nerve cell is made of lipid bilayer it is possible for anesthetic molecule to penetrate through the nerve membrane. The trick the anesthetic molecule must play is getting from one side of the membrane to the other. www.indiandentalacademy.com
  199. 199. Mechanism      The mechanism of local anesthetics connects with the ion channels, nerve, and depolarization. Local anesthetics block the conduction in peripheral nerves that inhibited the nerve to excited and created anesthesia. The anesthetic is a reversible reaction. It binds and activates the sodium channels. The sodium influx through these channels and depolarizes the nerve cell membranes. It also created high impulses along the way. As a result, the nerve loses depolarization and the capacity to create the impulse, the patient loses sensation in the area supplied by the nerve. www.indiandentalacademy.com
  200. 200. Factors Affect the Reaction of Local Anesthetics 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. The more tightly local anesthetics bind to the protein, the longer the duration of onset action. 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.  Lower pH, solution more acidic, gives slower onset of action www.indiandentalacademy.com
  201. 201. Factors Affect the Reaction of Local Anesthetics (cont.) Vasodilation  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  Lower vasodilator activity of a local anesthetic leads to a slower absorption and longer duration of action  Vasoconstrictor used the naturally hormone called epinephrine (adrenaline). Epinephrine decreases vasodilator. Side effects of epinephrine  Epinephrine circulates the heart, causes the heart beat stronger and faster, and makes people feel nervous. www.indiandentalacademy.com
  202. 202. Toxicity Toxicity is the peak circulation levels of local anesthetics  Levels of local anesthetic concentration administered to patients are varied according to age, weight, and health.  Maximum dose for an individual is usually between 70mg to 500mg  The amount of dose also varied based on the type of solution used and the presence of vasoconstrictor Example: ---For adult whose weight is 150lbs and up, maximum dose Articaine and lidocaine is about 500mg ---For children, the dosage reduced to about 1/3 to ½ depending on their weight. The doses are not considered lethal.  Some common toxic effects: --light headedness ---shivering or twitching --hypotension (low blood pressure) --numbness www.indiandentalacademy.com --seizures
  203. 203. Factors of circulation levels      Factors of circulation levels are the rates of absorption, distribution, and metabolism. Absorption depends on the speed of administration and levels of the doses. Distribution allows absorption to occur in three phases. First, the drug occurs at highly vascular tissues in the lungs and kidneys. Then it appears less in vascular muscle and fat. Then the drug is metabolized. Metabolism involves in the chemical structure based on two classes, amide and ester as discussed earlier. Decreasing the potential toxicity resulted in rapid metabolism. www.indiandentalacademy.com
  204. 204. Three special drugs used in dental anesthesia  Bupivicaine (Marcaine® --Produce very long acting anesthetic effect to delay the post operative pain from the surgery for as long as possible --0.5% solution with vasoconstrictor --toxicity showed by the pKa is very basic --Onset time is longer than other drugs b/c most of the radicals (about 80%) bind to sodium channel proteins effectively --most toxic local anesthetic drug  Prilocaine (Citanest®) --Identical pKa and same conc. with lidocaine --Almost same duration as lidocaine --Less toxic in higher doses than lidocaine b/c small vasodilatory activity  Articaine (Septocaine®) --newest local anesthetic drug approved by FDA in 2000 --Same pKa and toxicity as lidocaine, but its half life is less than about ¼ of lidocaine --Used with vasoconstrictor. --Enters blood barrier smoothly --The drug is widely used in most nations today www.indiandentalacademy.com
  205. 205. Conclusion Anesthetic pKa Onset Duration (with Epinephrine) in minutes Max Dose (with Epinephrine) Procaine 9.1 Slow 45 - 90 8mg/kg – 10mg/kg Lidocaine 7.9 Rapid 120 - 240 4.5mg/kg – 7mg/kg Bupivacaine 8.1 Slow 4 hours – 8 hours 2.5mg/kg – 3mg/kg Prilocaine 7.9 Medium 90 - 360 5mg/kg – 7.5mg/kg Articaine 7.8 Rapid 140 - 270 4.0mg/kg – 7mg/kg www.indiandentalacademy.com
  206. 206. Antimuscarinic drugs  Natural alkaloids (and derivatives)    Synthetic quaternary ammonium drugs     Atropine (Sal-Tropine) Scopolamine (Scopace, Transderm-Scop) Glycopyrrolate (Robinul) Propantheline (Pro-Banthine) Ipratropium (Atrovent) Other synthetic drugs   Benztropine (Cogentin) Tolterodine (Detrol) www.indiandentalacademy.com
  207. 207. Pharmacologic effects: atropine as a prototype Dose (mg) Effects 0.5 Slight cardiac slowing; some dryness of mouth; inhibition of sweating 1.0 Dryness of mouth; thirst, mild tachycardia; mild pupillary dilation 2.0 Tachycardia; palpitation; marked dryness of mouth; dilated pupils; some blurring of vision 5.0 All above more marked; difficulty in speaking, swallowing; headache; fatigue; dry, hot skin; urinary, GI inhibition 10+ All above more marked; ataxia; www.indiandentalacademy.com excitement; delirium; coma
  208. 208. Therapeutic uses Antisialogogues for dentistry Drug Dose (mg) Atropine sulfate 0.4-1.2 (Sal-Tropine) Scopolamine HBr 0.4-0.8 (Scopace) Glycopyrrolate 1-2 (Robinul) Propantheline Br 7.5-30 (Pro-Banthine) www.indiandentalacademy.com Onset time 0.5-1 hr 0.5-1 hr 0.5-0.75 hr 0.5-0.75 hr
  209. 209. Therapeutic uses (cont.)          Bradycardia: atropine Ocular examination: topical antimuscarinics Bronchial asthma: ipratropium aerosol GI hyperactivity: numerous antimuscarinics Hyperactive urinary bladder: tolterodine Meniere’s disease: scopolamine Motion sickness: scopolamine Parkinson’s disease: benztropine, others Anticholinesterase poisoning: atropine www.indiandentalacademy.com
  210. 210. Clinical considerations  Contraindications/precautions     Angle-closure glaucoma Obstructive or paralytic GI or GU disease Myasthenia gravis Common adverse effects      Xerostomia Hyperthermia in children Tachycardia with atropine Sedation/confusion with scopolamine Mydriasis, cycloplegia www.indiandentalacademy.com
  211. 211. Hemostatic Agents  Local measures  Dressings - Dentoalveolar surgery: pressure with sterile cotton gauze > soft tissue bleeding: clamping with hemostats, ligation, electrocautery, or application of microfibrillar collagen or collagen sheets > bleeding from bone structure: a collagen plug or gelatin sponge may be inserted within the extraction socket www.indiandentalacademy.com
  212. 212. Hemostatic Agents (con’t)  Clotting factors - topically applied thrombin, NOT INTRAVENOUSLY (Severe thrombosis and death may occur). - fibrin glue  Astringents and styptics: Used in our restorative clinic for bleeding control prior to impressions and placements of subgingival restorations. Mechanism of action: denatures blood and tissue proteins, which then agglutinate and form plugs that occlude the capillary orifices. -Nephrostat-active ingredient is 25% aluminum chloride -Viscostat-active ingredient is 20% ferric sulfate www.indiandentalacademy.com
  213. 213. Hemostatic agents (cont’d)  • Vasoconstrictor - epinephrine (epinephrine solution and dry cotton pellets impregnated with racemic epinephrine are available for topical application) - tetrahydrozoline (0.5%) and oxymetazoline (0.5%) Systemic measures  Platelet disorders (patients with a platelet count of less than 50,000/mm3 are at risk for surgical or other trauma) - platelet transfusion - aspirin therapy precaution: pts. On aspirin therapy should consult with their physician regarding reducing or discontinuing use 4-7 days prior to surgery. www.indiandentalacademy.com
  214. 214. Desensitizing agents         Fluorides Silver nitrate Strontium chloride Formalin Sodium monoflurophosphate Sodium silicofluoride Calcium hypophosphate Corticosteroids www.indiandentalacademy.com
  215. 215.           Calcium hydroxide Zinc chloride Sodium sulphate + barium chloride Sodium carbonate + calcium chloride Sodium fluoride & Iontophoresis Sodium citrate Potassium nitrate Stannous fluoride Potassium oxalate Glutaraldehyde www.indiandentalacademy.com
  216. 216. CONCLUSION www.indiandentalacademy.com
  217. 217. Thank you www.indiandentalacademy.com Leader in continuing dental education

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