Drugs in Endodontics and Operative Dentistry: An Overview

Drugs in endodontics and
operative dentistry

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INDIAN DENTAL ACADEMY
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CONTENTS


INTRODUCTION



DEFINITIONS



PHARMACODYNAMICS



PHARMACOKINETICS



DRUG NOMENCLATURE



ROUTES OF DRUG ADMINISTRATION

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



Introduction


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”

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


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



Pharmacodynamics
Dose response curve…...


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

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

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

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

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

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



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.




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

Oral benzodiazepines


Classification-


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)






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



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

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


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

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



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

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.

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

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



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


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
6. As antitussive

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

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


OPIOID RECEPTORS


inhibition of
neurotransmission via
presynaptic and
postsynaptic actions



coupled to guanine
nucleotide-binding
regulatory proteins (Gproteins)

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)






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.


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


Nabumetone

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,

ketorolac.

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


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

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


COMMON PROPERTIES OF ALL NSAIDS

Analgesia
Anaphylactoid
reactions

Antipyresis
Antiinflammatory

Renal effects

Dysmenorrhoea

Gastric mucosal
damage
Parturition

Ductus
arteriosus
closure


Antiplatelet
aggregatory

SALICYLATES
Aspirin (prototype)


• 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


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)

Adverse effects

Salicylism : dizziness, tinnitus, vertigo, reversible impairment of
hearing & vision, excitement & mental confusion,
hyperventilation & electrolyte imbalance.
Acute salicylate poisoning : fatal dose-15-30g , > 50 mg/dl.

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

Interactions :
 Warfarin, naproxen, sulfonylureas,
phenytoin and methotrexate.
 Oral anticoagulants.
 Uric acid
 Probenecid
 Methotrexate.
 Furosemide and thiazides
 Spironolactone.

 Protein bound iodine levels.

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

* Aspirin, dispirin, colosprin

PYRAZOLONES
Phenylbutazone
Pharmacokinetics
 Plasma t ½ = 60 hrs.
 Dose 100-200 mg BD/TDS
Adverse effects
 Bone marrow
depression
 Agranulocytosis
 Stevens-Johnson
syndrome


Interactions :
 Sulfonamides, tolbutamide,
imipramine & methotrexate

warfarin,

 Anticoagulants
 Phenytoin & tolbutamide
P L

Uses :

Rheumatic
fever

Severe
cases

Acute gout
Ankylosing
spondylitis
Zolandin


Rheumatoid
arthritis

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

Adverse effects

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


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

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
Flurbiprofen 4-6 hr
50 mg BD/QID
Flurofen

Adverse effects

Interactions :
 Anticoagulants
 Furosemide, thiazides &
β blockers


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


Adverse effects

L

Uses :

Osteoarthritis

Analgesic
Rheumatoid
arthritis

Dysmenorrhoea
Medol, meftal, ponstan

ARYL-ACETIC ACID DERIVATIVES
Diclofenac sodium :
Pharmacokinetics
 Plasma t ½ = 2 hrs
 50 mg TDS/BD, 75 mg i.m.
Adverse effects


Uses :
Ankylosing
spondylitis

Osteoarthritis

Rheumatoid
arthritis

Bursitis

Dysmenorrhoea

Post-traumatic / post-op
inflammatory condition

Voveran, diclonac, movonac

Tolmetin : 400-600 mg TDS

OXICAM DERIVATIVES
Piroxicam
Pharmacokinetics
 Plasma t ½ = 2 days
 20 mg BD / 20 mg OD
Adverse effects


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)

Melflam, Meloxi

PYRROLO-PYRROLE DERIVATIVE
Ketorolac :
Pharmacokinetics
 Highly bound to plasma proteins.
 10-20 mg / 6 hrly (orally)
Adverse effects


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
 100 mg BD


Adverse effects

Uses :
Sports injuries

Dental surgery

ENT disorders
Bursitis
Low backache

Dysmenorrhoea
Post-op
pain/osteoarthritis

Nimulid, nimodol

PARA-AMINO PHENOL DERIVATIVES
•

Phenacetin 1887

•

Paracetamol (acetaminophen) 1950

Actions
Pharmacokinetics
 1/3 bound to plasma proteins.
 3-5 hrs (orally)
 0.5-1g TDS
 Infants - 50 mg
 Children 1-3 yrs- 80-160 mg
4-8 yrs 240-320 mg

9-12 yrs 300-600 mg

Adverse effects

Analgesic nephropathy
Acute paracetamol poisoning
 150 mg/kg
 Fatality > 250 mg/kg
 Early manifestations / 12-18 hrs / 2 days

 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

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


• Exacerbation

of

rheumatoid

arthritis,

ankylosing

spondylitis, acute gout, acute rheumatic fever – aspirin,
indomethacin, naproxen, piroxicam
• Asthma or anaphylactoid reactions to aspirin – nimesulide


Analgesics after certain endodontic procedures


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

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
10 mg combination
mg

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

Banned – September 2004

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


ANTIBIOTICS


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.

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

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.

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
e) Osteomyelitis is present

2. Determination of antibiotic sensitivity :
Not responded to initial antibiotic therapy.
Antibiotic sensitivity can be done by 2 methods :
1) Disc –diffusion method (Kibby-Bauer)
2) Agar-or broth dilution tests


3. Use of specific, Narrow spectrum antibiotic :
Narrowest antibacterial spectrum should be chosen. Penicillin,
a cephalosporin and a tetracycline.
Penicillin should be used
There are 2 reasons for this :
i)

Specific narrow-spectrum antibiotics frequently are more
effective

against

specific

groups

of

susceptible

microorganisms than are broad-spectrum agents.
ii) Narrow spectrum antibiotics produce less alteration of the
normal microflora, thereby reducing the incidence of
superinfection.


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.

to

penicillin

and

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.

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.

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

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
day of antibiotic therapy, recurrence of the infection is more
likely.

5) Combination antibiotic therapy :
The rationale for the use of 2 or more drugs together is to
minimize
•

the emergence of antibiotic resistant microorganisms

•

to increase the certainty of a successful clinical outcome

•

to treat mixed bacterial infections

•

to prevent suprainfection

•

to treat severe infections of unknown etiology

•

to decrease toxicity without decreasing efficacy

Examples :
1) Isoniazid + ethambutol + streptomycin in treatment of
tuberculosis.
With one exception, combinations of antibiotics are not used in
the dental office.
The exception is use of penicillin G + streptomycin before
dental procedures in patients at high risk of developing
bacterial endocarditis.
Rules :
1) 2 bactericidal drugs produce, supraadditive effects, not
antagonism.
2) The combination of a bacteriostatic and a bactericidal drug
generally results in diminished effects.
3) 2 bacteriostatic drugs are never inhibitory.

Results :
1) Indifference when the effect is equal to the single most active
drug or equal to the arithematic sum of the two use is not
justified.
2) Antagonism : when the combined drug effect is less than the
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

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
bacteria.

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
HOST DEFENSES has resulted in resolution of the infection.

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


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
be used also.

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
high dose penicillin therapy).

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

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.

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.

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

3. Inhibit protein synthesis
•

Tetracyclines

•

Chloramphenicol

•

Erthromycin,

•

Clindamycin

•

Linezolid

3. Cause misreading of m-RNA code and affect permeability
•

Aminoglycosides
o

Streptomycin

o

Gentamicin

5. Inhibit DNA gyrase
•

Fluoroquinolones – Ciprofloxacin

5. Interfere with DNA function
•

Rifampin

•

Metronidozole

5. Interfere with DNA synthesis
•

Idoxuridine

•

Acyclovir

•

Zidovudine

5. Interfere with intermediary metabolism
Sulfonamides
Sulfones

PAS

Ethambutol

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

•

Ciprofloxacin etc

4. β-lactam antibiotics
•

Penicillins

•

Cephalosporins

•

Monobactams

•

Carbapenems

4. Tetracyclines
•

Oxytetracycline

•

Doxycycline etc

4. Nitrobenzene derivative
•

Chloramphenicol

7. Aminoglycosides
•

Streptomycin

•

Gentamicin

•

Neomycin etc

7. Macrolide antibiotics
•

Erythromycin

•

Roxithromycin

•

Azithromycin etc

7. Polypeptide antibiotics
•

Polymyxin-B

•

Colistin

•

Bacitracin

•

Tyrothricin


10. Glycopeptides
•

Vancomycin

•

Teicoplanin

10. Oxazolidinone
•

Linezolid

10. Nitrofuran derivatives
•

Nitrofurantoin

•

Furazolidone

10. Nitroimidozoles
•

Metronidozole

•

Tinidazole


14. Nicotinic acid derivatives
•

Isoniazid

•

Pyrazinamide

•

Ethionamide

14. Polyene antibiotics
•

Nystatin

•

Amphotericin-B

•

Hamycin

14. Azole derivatives
•

Miconazole

•

Clotrimazole

•

Ketoconazole

•

fluconazole


17. Others
•

Rifampin

•

Lincomycin

•

Clindamycin

•

Spectinomycin

•

Sod. fusidate

•

Cycloserine

•

Viomycin

•

Ethambutol

•

Thiacetazone

•

Clofazimine

•

Griseofulvin


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


4. Antiprotozoal
•

Chloroquine

•

Pyrimethamine

•

Metronidazole

•

Diloxanide etc

4. Anthelmintic
•

Mebendazole

•

Pyrantel

•

Niclosamide

•

Diethyl carbamazine etc

D) Spectrum of activity
1. Narrow spectrum
•

Penicillin G

•

Streptomycin

•

Erythromycin

2. Broad spectrum
•

Tetracyclines

•

Chloramphenicol


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


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


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


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











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


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.


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

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)

•

Ticarcillin – clavulanic acid (Timentin)

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

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.

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.


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

ADVERSE REACTIONS :
a) Miscellaneous reactions :
•

Nausea and vomiting on oral PnG

•

Sterile inflammatory reaction at the site of IM inj.

•

Prolonged IV administration may cause thrombophlebitis

•

Accidental IV administration of procaine PP cause anxiety,
mental disturbances paraesthesia and convulsions

a) Intolerance :
•

Major problem with PnG includes
anaphylactic and allergic reactions

idiosyncratic,

c) Other allergic reactions are
•

Skin rashes

•

Serum sickness

•

Renal disturbance

•

Hemolytic disturbance

•

Anaphylaxis

•

Jarisch herxheimer reaction

•

Super infection

•

Hyperkalemia

•

Acute non allergic reaction

Uses :
PnG is the drug of choice for infections
1. Streptococcal infections
2. Pneumococcal infections
3. Meningococcal infections
4. Gonorrhoea
5. Syphilis
6. Diphtheria
7. Tetanus and gas gangrene
8. Prophylactic uses

SEMI SYNTHETIC PENCILLINS
The major drawbacks of benzyl pencillin are :
1. Inactivation by the gastric hydrochloric acid
2. Short duration of action
3. Poor penetration into CSF
4. Activity mainly against gram +ve organism
5. Possibility of anaphylaxis
Attempts therefore have been made to synthesize pencillin free
from such drawbacks.
P.chrysogenum produces natural penicillins which produce the 6
amino-penicillanic acid (6-APA) nucleus.
The attachment of side chains are inhibited and instead various
organic radicals can be substituted.
Thus a variety of semisynthetic resins are produced.

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
and streptococci).

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

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.

BIOCLOX, KLOX, CLOCILIN 0.25, 0.5 gm cap, 0.5 gm/vial.

Oxacillin, Dicloxacillin, Flucloxacillin are other isoxazolyl
penicillins, similar to cloxacillin, but not marketed in India.
Nafcillin :
More active than methicillin and cloxacillin but less active than
PnG
80% of drug bonds with plasma proteins excreted by liver in
patients with renal failure.
Dose is similar to cloxacillin.

III) Extended spectrum pencillins :
1. Amino pencillins
1. Ampicillin –
•

Antibacterial activity is similar to that of PnG that is more
effective than PnG against a variety of gram-ve bacteria

•

Drug is effective against H.influenzae strep.viridans,
N.gonorrhea, Salmonella, shigellae, Klebsilla and
enterococci.

Absorption, fate and excretion :
•

Oral absorption is incomplete but adequate

•

Food interferes with absorption

•

Partly excreted in bile and partly by kidney

Dose : 0.5-2 gm oral/IM or IV depending on severity of infection
every 6 hours
Children : 25-50 mg/kg/day
AMPILIN, ROSCILLIAN, BIOCILIN – 250, 500 mg cap
100mg/ml ped drops, 250 mg/ml dry syr, 1 gm/vial inj.
USES :
• Urinary tract infections
• Respiratory tract infections
• Meningitis
• Gonorrhoea
• Typhoid fever
• Bacillary dysentry
• Septicaemias
•


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.

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

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

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
infections.

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

Dose : 1-2g im/iv

4-6hours

Adverse effects :
• Cause congestive heart failure
• Bleeding disorders-impaired platelet function
Uses :
• Pseudomonas ,burns, UTI and septicemia
• PYOPEN,CARBELIN 1g,5g per vial

UREIDOPENICILLINS –PIPERACILLIN ( PIPRIL)
AMIDINOCILLIN – MECILLINAM
Has similar indications of carbenicillin


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


Pharmacokinetics :
•

Oral absorption- rapid

•

Bioavailability-60%

•

Distribution similar that of amoxicillin

•

Excretion-tubular secretion

Uses :
•

Amoxicillin+clavulanic acid (augmentin)

•

Ticarcillin+clavulanic acid (timentin)

•

Staph aureus,H influenza, gonorrhoea and E coli

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

im/iv 6-8 hourly

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

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

CEPHALOSPORINS
Cephalosporium acremonium was the first source.
They contain 7 amino cephalosporonic acid nucleus.
Structurally they contain betalactam and didhydro thiazine rings.
Act by inhibiting bacterial cell was synthesis and are
bactericidal.
New derivatives are much more resistant than the older
cephalosporins


Classification
Classified according to its antibacterial activity.
First generation cephalosporin
•Good activity against gram +ve bacteria. (except enterococci).
•Most oral cavity anaerobes are sensitive.
Parental

Oral

CEPHALOTHIN

CEPHALEXIN

CEFAZOLIN

CEPHRADINE
CEFADROXIL

Cephalaxin and Cephadroxil :
•Useful in treating community acquired, respiratory and urinary
tract infections and in surgical prophylaxis.
•Not choice for systemic infections.
Cefazolin :
•For antimicrobial prophylaxis in most surgical procedures.
•Given only IM / IV.
•Dose: Oral 0.25 - 1g 6-8 hrly
Children : 25-100mg/kg/day
IM – 0.25g 8 hrly (mild cases) 1g 6 hrly (severe cases).
Drops – cephaxin 125mg/5ml syrup.
100mg /ml ped. drops.
SPORIDEX,
DROXYL

CEPHAXIN,

CEPHACILLIN,


CEFADROX,

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.

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,
PROCADAX, CEPODEM, ORFIX.

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.

CEFROM, CEFORTH – 1g inj.

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
meningitis.

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


(IM)

and

cause

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.

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.

Antibacterial activity :
 Narrow spectrum antibiotic
 Bacteriostatic but bactericidal at higher conc
 Effective against penicillin resistant staphylococci
 Active against gram+ve cocci and bacilli
Pharmacokinetics :
 Erythromycin base - acid labile
 Given with enteric coated - incomplete absorption
 Its acid stable esters are better absorbed
 Widely distributed in body
 Metabolised in liver
 Excreted through kidney and bile

Dose :
 Adults 250 - 500mg 6hrly
 Children 30 – 60mg/kg/day
 Erythromycin base - ERYSAFE 250 mg tab
 EROMED - 333mg tab, 125/5ml susp
 Erythromycin stearate
 ERYTHROCIN – 250,500mg tab
100mg/5ml susp
100mg/ml ped drops

Adverse effects :
 GIT – epigastric pain
 On high doses – hearing impairment
 Hypersensitivity reactions – rare
Uses :
 Substitute for penicillin
 Whooping cough
 Chancroid
 Penicillin resistant infections

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

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

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

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


C.diphtheriae,

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

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.


On the basis of chronology of development, convenience
of description, divided into 3 groups.
Group I

Group II

Tetracycline

Demeclocyline

Oxytetracycline

Methacycline
Group III
Doxycycline
Minocycline

Tetracyclines are thought to inhibit bacterial protein
synthesis by binding to the 30 S bacterial ribosome and
preventing the access of aminoacyl tRNA to the acceptor (A)
sites on the mRNA ribosome complex.

Antimicrobial activity :
 Gram+ve and –ve cocci are sensitive
 Gram+ve bacilli are inhibited
 Entero bactereae are highly resistant
 Spirochetes and Borrelia are quite sensitive
 All rickettsiae and chlamydiae are highly sensitive
Pharmacokinetics :
 Incompletely absorbed from GIT
 Absorption is impaired by iron or zinc salts[due to chelation of
cations]
 They cross the placenta and enter fetal circulation and amniotic
fluid
 Widely distributed in liver ,bone marrow and spleen
 They accumulate in dentine and enamel of unerupted teeth
 Primarily excreted inwww.indiandentalacademy.com
urine through kidney

Adverse effects :
 GIT-epigastric burning, nausea, vomiting,diarrhoea
 Hepatoxicity
 Renal toxicity
 Effects on teeth-Orthophosphate complex
 Thrombophlebitis
 Hypersensitivity Reactions
 Superinfection
 Antianabolic effect

Dose :
 Tetracycline – 1-2g per day in adults
 Children over 8yrs -25 to 50mg /kg daily in 2 to4 divided
doses
 Doxycyline – 100mg,12hrs first day followed by 100mg once
a day
 Children over 8yrs – 4-5mg /kg/day divided into 2 equal doses
during first 24hrs
 TERRAMYCIN,

RESTECLIN-250,500mg

in10ml vial inj
 DOXT, NOVADOX, TETRADOX-100mg cap.

cap,50mg/ml

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

QUINOLONES
 These are entirely synthetic antimicrobials having a
quinolone structure that are active primarily against gram –
ve bacteria.
 These are quinolone antimicrobials having one or more
fluorine substitutions.


 The FQs inhibit the enzyme bacterial DNA gyrase, which nicks
double stranded DNA.
 The DNA gyrase consists of two A and two B subunits; A
subunit carries out nicking of DNA, B subunit introduces –ve
supercoils and then a subunit reseals the strands.
First generation FQs :
Norfloxacin

Ofloxacin

Ciprofloxacin

Pefloxacin

Second generation FQs :
Lomefloxacin

Levofloxacin

Sparfloxacin

Gatifloxacin

Moxifloxacin


CIPROFLOXACIN
First generation FQ active against a broad range of bacteria
especially gram –ve aerobic bacilli.
Highly susceptible :
E coli, shigella, N meningitis, K pneumoniae, Proteus, H
influenza, Enterobacter, V. cholerae, S. typhi, N gonorrhoea.
Moderately susceptible :
Staph aureus, brucella, M. tuberculosis

Microbiological features :
 Rapid bactericidal activity and high potency.
 Relatively long post antibiotic effect on enterobacteriaceae
pseudomonas and staph.
 Low frequency of mutational resistance.
 Low protective intestinal streptococci and anaerobes are
spared.
 Active against many 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.

 Excreted primarily in urine.

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


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

 200, 400, 800 mg tab, 3mg/ml eyedrops.

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.

 Excreted largely unchanged in urine(dose reduced in renal failure)

Uses :
 Chronic bronchitis, respiratory/ENT infection.
 Gonorrhoea
 Nongonococcal urethritis.
 ZENFLOX, OFLOX
 100, 200, 400 mg tab, 200 mg/100IV infusion 5mg/5ml susp.


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


 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.

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


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

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

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
immunity and cause radiosensitization.

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.

 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.

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.

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.

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
III ANTIBIOTIC PROPHYLAXIS AND ENDODONTICS

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.


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


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


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


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

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


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.



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

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



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.


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.


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


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.


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

--seizures

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.


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


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


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)

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;
excitement; delirium; coma

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

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

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

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

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

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.

Desensitizing agents









Fluorides
Silver nitrate
Strontium chloride
Formalin
Sodium monoflurophosphate
Sodium silicofluoride
Calcium hypophosphate
Corticosteroids












Calcium hydroxide
Zinc chloride
Sodium sulphate + barium chloride
Sodium carbonate + calcium chloride
Sodium fluoride & Iontophoresis
Sodium citrate
Potassium nitrate
Stannous fluoride
Potassium oxalate
Glutaraldehyde

CONCLUSION


Thank you
Leader in continuing dental education

Drugs in Endodontics and Operative Dentistry: An Overview

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