What is Pharmacology?
- the study of how drugs effect a
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
What the body does to drug
What the drug does to body
The study of the use of drugs
Identifying crude materials as drugs
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
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.
What the body does to the
- 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
*Chemical name- propranolol
competent scientific body- USAN, BAN
Ex-Meperidine (USA) & Pethidine( UK, India)
*Proprietary name ( Brand name) accepted by
manufacturer & is his property or trademark
ALTOL, ATECOR, BETACARD, ATEN,
ATCARDIL, ATEN, LONOL, TENOLOL,
Oral absorption (enteral route)
1) safe, convenient, economical
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
Routes of administration other than oral route termed as parenteral
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
1) pain on injection
2) abscess and inflammation at the site of injection
3) sterile procedure required for injection
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
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
Few n mild
Excessive CNS depression
Decreased motor coordination,
Impaired intellectual functions
- 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
Drug taken longer then 4 months
Higher doses have been used
Drug stopped suddenly
Short acting BZD has been used
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
Narrow angle glaucoma
Non benzodiazepine anxiolytic
Devoid of hypnotic, anticonvulsant, or muscle relaxant properties.
not involve GABA ergic neurons
Equieffective to diazepam
Not effect automobile driving performace
-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
-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
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
Dried latex from the seed capsules of certain types of
poppy (Papaver somniferum).
Psychological have been recognized for over 6000
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
Mid-19th century, the use of pure alkaloids began to
prevail over the use of the cruder opium.
1.Natural opium alkaloids - Morphine, Codeine
2.Semisynthetic opiates - Diacetylmorphine(Heroin),
many others like- Hydromorphone, Oxymorphone,
Hydrocodeine, Oxycodone, are not used in India
3. Synthetic opioids- Pethidine, Fentanyl, Methadone,
Dextroprpxyphene, Tramadol, Ethoheptazine
*Source- natural opium alkaloid
milky exudate of unripe capsules of poppy
plant, papaver somniferum
a) Phenanthrene group- Morphine, Codeine
b) Benzylisoquinoline group- Papaverine,
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
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
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
2. sedation and slep
3. pre-anaesthetic medication
4. acute LVF
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
- 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
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
synthetic, analgesic, resp depressant, emetic, antitussive,
constipating and biliary action similar to morphine
- used in opioid dependence mechanism
coupled to guanine
regulatory proteins (Gproteins)
Narcotic Analgesics in Dentistry
opioids used in dentistry are primarily those used for oral
administration such as codeine, hydrocodone, oxycodone, and
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
combinations of opioids such as codeine and aspirin or
acetaminophen are commonly employed
e.g Oxycodone (related to codeine - but 6-fold more
(Percocet -- contains acetaminophen)
-- contains ASA)
Comments related to use of narcotic
analgesics in dentistry
other CNS depressants will increase the degree of respiratory depression
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.
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
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
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.
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
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
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 :
Specific narrow-spectrum antibiotics frequently are more
microorganisms than are broad-spectrum agents.
ii) Narrow spectrum antibiotics produce less alteration of the
normal microflora, thereby reducing the incidence of
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.
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
• More active at lower concentration
• Less toxic / less severe side effects
• Less expensive.
• The drug fails to reach it’s target.
• The drug is inactivated
• The target is altered (Davies 1994; Nikaido, 1994: Spratt,
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 :
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
• 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
• 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
5) Combination antibiotic therapy :
The rationale for the use of 2 or more drugs together is to
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
1) Isoniazid + ethambutol + streptomycin in treatment of
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
1) 2 bactericidal drugs produce, supraadditive effects, not
2) The combination of a bacteriostatic and a bactericidal drug
generally results in diminished effects.
3) 2 bacteriostatic drugs are never inhibitory.
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
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
Adds nothing to therapeutic efficacy and may even reduce it
ii) Increase antibiotic toxicity and allergy.
iii) Increase the likelihood of superinfection
iv) Discourages specific etiologic diagnosis and promote false
v) Encourage inadequate doses, particularly with fixed dose
vi) Increased cost
vii) Emergence of resistant bacterial strains
viii)Increase the environmental spread of antibiotic resistant
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
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
Example is of CANDIDIASIS with the use of PENICILLIN,
which eliminates the gram-positive cocci (seen after long term
high dose penicillin therapy).
Prevention of infection
Decreased patient morbidity
Decreased patient mortality
Decreased hospital stay
Decreased medical costs
Decreased total antibiotic usage
Decreased number of resistant bacteria
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
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
3) The antibiotic susceptibility of the causative organism must
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
CLASSIFICATION OF ANTIMICROBIAL DRUGS
A) Mechanism of action :
1. Inhibit cell wall synthesis
2. Cause leakage from cell membranes
Polypeptides – Polymyxins, colistin, Bacitracin
Polyenes – Amphotericin B, Nystatin
3. Inhibit protein synthesis
3. Cause misreading of m-RNA code and affect permeability
5. Inhibit DNA gyrase
Fluoroquinolones – Ciprofloxacin
5. Interfere with DNA function
5. Interfere with DNA synthesis
5. Interfere with intermediary metabolism
B) Chemical structure
1. Sulfonamides and related drugs
Sulfadiazine and others
Sulfones – Dapsone (DDS), Paraaminosalicylic acid
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
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
VIII. Antibiotic prophylaxis is usually effective
IX. Bactericidal agents are always superior to
X. Antimicrobial are effective in chronic infectious
XI. Antibiotics are safe and nontoxic
XII. Antibiotic dosage are established for most
XIII. Infection require a complete course of therapy
BETA LACTAM ANTIBIOTICS
Most important antibiotics first extracted from the mould
First used in 1941 clinically and was a miracle drug with a
least toxic effect.
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
• 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.
• 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
• 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
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
c) Other allergic reactions are
Jarisch herxheimer reaction
Acute non allergic reaction
PnG is the drug of choice for infections
1. Streptococcal infections
2. Pneumococcal infections
3. Meningococcal infections
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
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
Dose : infants 60 mg, children 125-250 mg given 6 hourly
CRYSTAPEN-V, KAYPEN, PENIVORAL 65, 130, 125, 250 mg
125 mg/5 ml dry ser
2. Potassium phenoxyethyl penicillin and
Both have similar properties to penicillin V and no difference in
the antibacterial effect
II) Pencillinase resistant pencillins :
1. Effective in staphylococci
2. It is given IM or IV (slow) in the dose of 1 gm every 4-6
3. Haematuria, albuminuria and reversible interstitial nephritis
are the special adverse effect of methicillin.
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
4. IM adults 2-12 gm/day, children 100-300 mg/kg/day every
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.
More active than methicillin and cloxacillin but less active than
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
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.
• Urinary tract infections
• Respiratory tract infections
• Typhoid fever
• Bacillary dysentry
Adverse effects :
• Diarrhoea is frequent
• Skin rashes is more common
• Unabsorbed drug irritates lower interstines
• Patient with history of hypersensitivity to PnG should not
be given ampicillin.
• This is a semisynthetic penicillin
• 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
• Incidence of diarrhoea is less
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
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
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
Adverse effects :
• Cause congestive heart failure
• Bleeding disorders-impaired platelet function
• Pseudomonas ,burns, UTI and septicemia
• PYOPEN,CARBELIN 1g,5g per vial
UREIDOPENICILLINS –PIPERACILLIN ( PIPRIL)
AMIDINOCILLIN – MECILLINAM
Has similar indications of carbenicillin
BETA LACTAMASE INHIBITORS
•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
Oral absorption- rapid
Distribution similar that of amoxicillin
Amoxicillin+clavulanic acid (augmentin)
Ticarcillin+clavulanic acid (timentin)
Staph aureus,H influenza, gonorrhoea and E coli
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
New derivatives are much more resistant than the older
Classified according to its antibacterial activity.
First generation cephalosporin
•Good activity against gram +ve bacteria. (except enterococci).
•Most oral cavity anaerobes are sensitive.
Cephalaxin and Cephadroxil :
•Useful in treating community acquired, respiratory and urinary
tract infections and in surgical prophylaxis.
•Not choice for systemic infections.
•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.
Second generation cephalosporins :
Increased activity against gram –ve organism.
More active against anaerobes.
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
•Highly resistant to β-lactamase from gram –ve bacteria.
•Less active on gram +ve cocci
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.
Serious and resistant hospital acquired infections.
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
Adverse reactions :
Local reactions –
Allergy – skin rashes
Intolerance to alcohol
Cross reactivity with penicillin
Alternatives to pencicillins.
RTI, UTI and soft tissue infection
Penicillinase producing staph infection.
Mixed aerobic and anaerobic infections
Infection by odd organism or hospital infections
Prophylactic treatment in neutropenic patients.
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
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
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
This differs chemically from other macrolide group in that
lactone ring contains nitrogen atom
More active than erythromycin
Less active against gram +ve organisms
Rapidly absorbed and distributed through out the body
Drug is highly concentrated in cells
Excreted unchanged – bile
Strep and Staph skin and soft tissue infections
500mg once daily for 3days
Children above 6months 10mg/kg
AZITHRAL 250,500mg 250mg/5ml syr
AZIWIN 100,250,500mg tab 200mg/5ml liq
It is lincosamide antibiotic having similar action (macrolide
Semisynthetic derivative of Lincomycin
Bacteriostatic – low conc
Bacteriocidal – high conc
Highly active against – anaerobes (B fragilis)
Oral absorption – good
Distribution – skeletal and soft tissues
Excreted in urine
Tetracyclines are napthacene derivatives.
The napthacene nucleus is made up by fusion of 4 partially
unsaturated cyclohexane radicals and hence the name
Tetracyclines are bacteriostatic.
On the basis of chronology of development, convenience
of description, divided into 3 groups.
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)
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
Incompletely absorbed from GIT
Absorption is impaired by iron or zinc salts[due to chelation of
They cross the placenta and enter fetal circulation and amniotic
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
Tetracycline – 1-2g per day in adults
Children over 8yrs -25 to 50mg /kg daily in 2 to4 divided
Doxycyline – 100mg,12hrs first day followed by 100mg once
Children over 8yrs – 4-5mg /kg/day divided into 2 equal doses
during first 24hrs
in10ml vial inj
DOXT, NOVADOX, TETRADOX-100mg cap.
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
Atypical Pneumonia, Cholera, Brucellosis, Plague,Rickettsial
Alternate to Pn/Ap, Ciprofloxacin,Azithromycin
Other situations –UTI,amoebiasis, chronic lung disease
These are entirely synthetic antimicrobials having a
quinolone structure that are active primarily against gram –
These are quinolone antimicrobials having one or more
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 :
Second generation FQs :
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
Active against many β lactam and amino glycoside resistant
Less active at acidic pH.
Rapidly absorbed on oral, food delays absorption.
High tissue penetration, concentration in lung sputum,
Excreted primarily in urine.
CIFRAN, CIPLOX, CIPROBID, CIPROLET
250, 500,750 mg tab, 200mg/100 ml IV infusion 3mg/ml eye drops.
It is less potent than cipro
It attains lower concentration in tissues.
It is metabolized as well as excreted unchanged in urine.
UTI and Genital infections.
(not recommended for respiratory / any other systemic infection).
NORBACTIN, NORFLOX, UROFLOX
200, 400, 800 mg tab, 3mg/ml eyedrops.
Intermediate between Cirpro and Nor in activity against Gr-ve
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)
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
Soft/skin tissue infection as well.
TAVANIC, GIEVO, 500mg tab, 500 mg/100 ml inj.
Another 2nd generation FQ has excellent activity against strep.
Pneumonia and many atypical respiratory pathogens including
chlamydia pneumonia and other anaerobes.
Community acquired pneumonia
UTI and gonorrhoea.
T1/2 is 8 hr
Adverse effect :
CNS effects and swelling over face are other side effects.
It is contraindicated in hypokalemia and other drugs than can
400 mg on 1 day followed by 200-400 mg OD.
MYGAT, GATIQIN, GAITY
200, 400 mg tab, 400 mg/200 ml inj
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
Side effects : similar to other FQ
CI in patients predisposed to seizures.
MOXIF 400 mg tab,
Dose – 400 mg OD
ANTIAMOEBIC AND OTHER ANTIPROTOZOAL
It is the prototype nitroimidazole and found to be highly
Antiprotozoal activity :
Broad spectrum cidal activity against protozoa and
anaerobic bacteria such as B fragilis, Fusobacterium.
Metronidazole has been found to inhibit cell mediated
immunity and cause radiosensitization.
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
Looseness of stool is occasional,
Headache, glossitis, dryness of mouth, dizziness, rashes and
Prolonged administration may cause peripheral neuropathy and
Seizures have followed by high doses.
Thrombophebitis of injected vein.
In neurological disease, blood dyscrasias, first trimester of
pregnancy, chronic alcoholism.
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
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
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
Low potency, short duration
Intermediate potency and duration
High potency, long duration
Coca leaves from the genus Erythroxylum
Erythroxylum contains high concentration of alkaloid up to
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
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
After the fall of the Inca empire, coca consumption spread
widely to the population
More physicians began to do research of cocaine in the clinic
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
Freud, Halsted, and Koller became addicted to the drug
Side Effects of Cocaine and 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
In 1898, Professor Heinrich
Braun introduced procaine as the
first derivative of cocaine, also
known as the first synthetic local
Trade name is Novocaine®
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
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
In 1940, the first modern local anesthetic
agent was lidocaine, trade name
It developed as a derivative of xylidine
Lidocaine relieves pain during the dental
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.
--Amide link b/t intermediate --Ester link b/t intermediate chain and chain and aromatic
--Metabolized in liver and very
--Metabolized in plasma through soluble in the
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
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
The trick the anesthetic molecule must play is getting from one side of the
membrane to the other.
The mechanism of local anesthetics connects with the ion channels, nerve, and
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
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
All local anesthetics have weak bases. Increasing the lipid solubility leads to
faster nerve penetration, block sodium channels, and speed up the onset of
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.
Usually at range 7.6 – 8.9
Decrease in pH shifts equilibrium toward the ionized form, delaying the
Lower pH, solution more acidic, gives slower onset of action
Factors Affect the Reaction of Local Anesthetics
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
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 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
---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
The doses are not considered lethal.
Some common toxic effects:
---shivering or twitching
--hypotension (low blood pressure) --numbness
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
--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
--most toxic local anesthetic drug
--Identical pKa and same conc. with lidocaine
--Almost same duration as lidocaine
--Less toxic in higher doses than lidocaine b/c small vasodilatory activity
--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
atropine as a prototype
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
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
Obstructive or paralytic GI or GU disease
Common adverse effects
Hyperthermia in children
Tachycardia with atropine
Sedation/confusion with scopolamine
- Dentoalveolar surgery: pressure with sterile cotton
> 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
Hemostatic Agents (con’t)
- 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)
- epinephrine (epinephrine solution and dry cotton pellets
impregnated with racemic epinephrine are available for
- tetrahydrozoline (0.5%) and oxymetazoline (0.5%)
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.