PHARMACOLOGY

OF ANTIBIOTIC

dr.Siti Syarifah, M.Biomed

Faculty of Dentistry
Universitas Sumatera Utara
Medan, 2020
CASE 1

• A 25-year-old female patient presents with localized

periodontitis with a 6 mm pocket along the mesial root of
tooth #14. A decision is made for treatment with gingival
flap surgery.
The patient’s medical history is remarkable for
prosthetic mitral valve placement and for penicillin-
induced angioedema
Q: What antibiotic can you prescribe to the patient?
CASE 2

• A 35-year-old obese female patient present in the office

with a canine fossa abscess associated with the root
remnant of tooth#6. Incision and drainage of the abscess,
extraction of the root remnant, and antibiotics are
scheduled.
Q: What are antibiotics you will prescribe?
BACTERIAL INFECTION IN MOUTH
AREA

• Streptococcus viridans
• Staphylococcus species
• Haemophillus aphrophilus
• Aggregatibacter ( formerly Actinobacillus)
• Cardiobacterium hominis
• Eikenella corrodens
• Kingella kingae
• P.ginggivalis
• Bacteroides fragilis
 Antibiotics

Chemical substances which were originally produced

by micro-organisms (fungi, actinomyces, bacteria) and
either retard the growth of other microorganisms or
result in their death.
 Louis Pasteur was one of the first recognized
physicians who observed that bacteria could be
used to kill other bacteria.
 In 1929 Sir Alexander Fleming a Scottish
bacteriologist, went on a vacation and left a
petri dish of staphylococci bacteria uncovered.
When he returned, he noticed that there was
mold growing on it. Upon further examination,
he saw that the area around the mold had no
bacteria growing. He named the mold
Penicillium, and the chemical produced by the
mold was named penicillin, which is the first
substance recognized as an antibiotic.
 Modern History

• In 1935, Domagk discovers synthetic

antimicrobial chemicals (sulfonamides).
• the late 1940's through the early 1950's,
streptomycin, chloramphenicol, and
tetracycline were discovered and introduced as
antibiotics
 Classification of antibiotics
 Antibiotics are classified several ways.
 On the basis of mechanism of action
 On the basis of spectrum of activity
 On the basis of mode of action
On the basis of mechanism of action:
On the basis of mechanism of action
 On the basis of spectrum activity
 Broad spectrum antibiotics :
› Amoxicillin
› Tetracycline
› cephalosporin
› Chlorampenicol
› Macrolide
› Fluoroquinolone
› Carbapenem
 Short spectrum antibiotics:
› Penicillin-G
› Cloxacillin
› vancomycin
› Bacitracin
› Fluxacillin
› Metronidazole
› Linezolide
› Aminoglikoside
 On the basis of mode of
action
 Bacteriostatic antibiotics
› Tetracycline
› Chlorampenicol
› Erythromycin
› Lincomycin
› Sulfonamide
› Macrolide
› Clindamycin
 Bacteriocidal antibiotics
› Cephalosporin
› Penicillin
› Aminoglycosides
› Cotrimoxazole
› Vancomycin
› Polymixin
ANTIBIOTICS
• Penicillin
• Cephalosporin
• Macrolide
• Aminoglycoside
• Quinolone and fluoroquinolone
• Trimetoprim-Sulfametoxazole
• Tetracycline
• Linezolid
• Clindamycin
• Chloramphenicol
• Metronidazole
ANTIBIOTIC USE IN DENTISTRY

• Penicillin with or without beta-lactamase

inhibitor
• Cephalosporine
• Macrolide
• Clindamycin
• Metronidazole
 Beta-lactam antibiotics

• Antibiotics containing beta-lactam ring

• Classification (based on structure)
• Penicillins
• Cephalosporins
• Carbapenems
• Monobactams
• Beta-lactamase inhibitors
• Beta lactam group target transpeptidase
• Beta lactamase / penicillinase target beta- lactam ring,
hydrolysis produce penisiloat acid
 Penicillin

• Spectrum of Activity
• Gram (+) organisms
• Staph
• Strep
• Pneumococcus
 Several Gram (-)
 Penicillin

• Preparations
• Category 1 (Penicillin G, V)
• Category 2 (Beta lactamase-resistant
synthetics)
• Category 3 (Broader-spectrum
Penicillin, Beta lactamase
sensitive)
• Category 4 (New synthetic broad-
spectrum penicillin)
 Penicillin

• Category 1 Penicillin G, Penicillin V (Narrow spect)

• Gr (+) ,Pneumococcus, Gonococcus, enterococcus, S. Pyogenes, clostridia
• Gr(-) N.meningitidis, spirochetes (syphilis), Leptospira, not effective in Gr (-) rod,
resistant (+)
• IV administered
-Comes in many different forms:
• Benzatine / Potassium Penicillin G
• Reaches blood levels fast/ drops fast
• Procaine Penicillin G
• Reaches blood levels slow/drops slow

• Penicillin V, taken orally

• Penicillin G preferred in inpatient setting
 Penicillin

• Category 2 Beta lactamase-resistant

Synthetics
• Predominantly Gr(+) cocci (anti Beta-lactamase
staphylococcal penicillins)
• Structurally resistant to beta-lactamase,
counterpart of relative hidrophobicity, have a
narrow spectrum of action
• Methicillin Resistant Staphylococcus aureus (MRSA)
• MRSA : resistant to other beta lactam, typically
treated with vancomycin
• Metisilin, nafsilin, iskosazosil
 Penicillin

 Category 3 Broader-spectrum Penicillins

› These have a wider spectrum than other penicillins

› Are effective against organisms affected by the
category 1 & 2 penicillins plus more Gram (-)
organisms such as N.meningitidis, Neisseria
gonorrhoeae, E.colli, H.influenze
› Beta-lactamase sensitive
› Co-administered with beta lactamase inhibitor
 Penicillin

• Category 3 Broader-spectrum Penicillins ( Gr - >>)

• Amoxicillin
• Becoming very popular because:
• Reaches high blood levels
• Better absorption from the stomach even
with presence of food.
Ampicillin
• Anaerob, enterococcus, L.monocytogenes,
E.coli, Salmonela
Effective in UTI, Sinusitis, Otitis, LRTI
 Penicillin

• Category 4
• Also broad in spectrum, chiefly for use againts
Pseudomonas aeruginosa
• They are used when other penicillins (or other antibiotics)
are ineffective
• Beta lactamase sensitive
• Examples:
• Ticarcillin
• Piperacillin
• Carbenicillin
• Mezlocillin
 Penicillin
The action of Penicillins
• BACTERICIDAL effects by interfering with
the ability of susceptible bacteria to
biosynthesize the framework of the cell
wall.
• Beta lactam ring: substrat for one or
several bacterial transpeptidase
• Transpeptidase- beta lactam ring: dead-
end complex
 Penicillin

• The bacterium will have

weakened cell wall, will
swell and then burst from
the osmotic pressure
within the cell.
 Penicillin

Therapeutic Indications of
penicillin:
• The penicillins are indicated
for the treatment of
streptococcal infections,
Staphylococcus
• Syphilis
• Tetanus
 Toxicity of Penicillin
• Allergic reactions are the only real toxicity
• First exposure
• A mild reaction
• Skin rash, itching, etc.
• Second exposure
• Anaphylactic shock
• Asthmatic breathing and drop in BP
 Adverse Effects of
Penicillins
• GI system effects- the major adverse
effects of penicillin therapy involve the
GIT.
• Nausea, vomiting, diarrhea, abdominal
pain, glossitis, stomatitis, gastritis, sore
mouth and furry tongue.
• The reason for some of these effects
(superinfection) is associated with the
loss of bacterial flora.
 Adverse Effects of
Penicillins
• Hypersensitivity reactions- rashes,
pruritus, fever and urticaria
• These indicate mild allergic reaction.
Wheezing and diarrhea may also occur.
• Anaphylaxis can also happen leading to
shock or death. It occurs in 5-10% of
those receiving penicillins.
• Pain and inflammation on injection sites
Routes of administration:

Ticarcillin, carbenicillin, piperacillin, and the combinations of

ampicillin with sulbactam, ticarcillin with clavulanic acid must
be administered intravenously (IV) or intramuscularly (IM).
Penicillin V, amoxicillin, amoxicillin combined with clavulanic
acid, and the indanyl ester of carbenicillin (for treatment of
urinary tract infections) are available only as oral
preparations.
Others are effective by the oral, IV, or IM routes .
Depot forms: Procaine penicillin G and benzathine penicillin G
are administered IM and serve as depot forms. They are slowly
absorbed into the circulation and persist at low levels over a
long time period.
 ABSORPTION

• Absorption of all the beta lactamase-resistant penicillins

(Category 2) is decreased by food in the stomach, because
gastric emptying time is lengthened, and the drugs are
destroyed in the acidic environment. Therefore, they must
be administered 30 to 60 minutes before meals or 2 to 3
hours postprandially.
• Other penicillins are less affected by food.
 Distribution

• The β-lactam antibiotics distribute well throughout the

body.
• All the penicillins cross the placental barrier, but none
has been shown to be teratogenic.
• However, penetration into certain sites, such as bone or
cerebrospinal fluid (CSF), is insufficient for therapy
unless these sites are inflamed
 Excretion

• The primary route of excretion is through the organic

acid (tubular) secretory system of the kidney as well as
by glomerular filtration.
• Patients with impaired renal function must have dosage
regimens adjusted.
• The penicillins are also excreted into breast milk.
INTERACTION

• Probenecid inhibit Penicillin excretion  Blood

level of penicillin increase
 Cephalosporins

• Effective in the treatment of all strains of bacteria

affected by penicillins and some strains resistant
to penicillins, not effective to enterococcus and
L.monocytogenes
• Differ structurally from penicillins by having a six-
membered ring attached to beta-lactam ring, core
structure: 7-aminocefalosporic acid
• Classification: Divided into first-, second-, third-,
and fourth-generation drugs
 Cephalosporins
• First generation Cephalosporins
• Cefazolin (IV), cefadroxil (oral)
• Cephalexin
Beta-lactamase sensitive
• Second generation Cephalosporins
• Cefoxitin
• Cefotetan
• Cefuroxime
• Cefamandole
• More-resistant to beta lactamase
• Use in Community acquired pneumonia (H.influenza, K.pneumonia)
 Cephalosporins

• Third generation Cephalosporins

• Ceftriaxone – meningitis, pneumonia, gonorrhae
• Ceftazidime – Pseudomonas, Pyelonephritis
• Cefotaxime - meningitis
• Cefizoxime, Cefixime (oral)
• Fourth generation Cephalosporins
• Cefepime – Similar to the 3rdgen. compounds, but
more resistant to hydrolysis by some β- lactamases.
Third and fourth generation: hydrophobic, useful against
infection of CNS
 Cephalosporins: Actions

• Exert bactericidal effect

• Have a beta-lactam ring
• Targets the bacterial cell wall, making it
defective and unstable
 Cephalosporins: Uses

• Used to treat infections caused by

bacteria
• Respiratory
• Ear
• Bone/joint
• Genitourinary tract infections
• Used during peri-operative period
 PHARMACOKINETICS

• Excretion is via the kidney and dose

adjustments must be made for impaired
renal function.
 Cephalosporins: Adverse Reactions

• Gastrointestinal reactions
• Nausea; vomiting; diarrhea
• Administration route reactions
• Intramuscularly (local irritation); intravenously
(thrombophlebitis)
 Cephalosporins: Adverse Reactions
(continue)
 Other body system reactions
› Headache; dizziness; malaise; heartburn; fever; nephrotoxicity;
hypersensitivity; aplastic anemia; toxic epidermal necrolysis

 Allergy: Approximately 10% of people allergic

to penicillin are also allergic to cephalosporins
 In contrast, the incidence of allergic
reactions to cephalosporins is one to two
percent in patients not allergic to penicillin
 Cephalosporins: Contraindications and
Precautions
• Contraindicated in patients allergic to
cephalosporins or penicillins
• Used cautiously in patients with:
• Renal disease; hepatic impairment; bleeding disorder
 Cephalosporins: Interactions

Drug Common use Effect of

interaction

Aminoglycosides Anti-infective Increased risk

for
(Gentamicin) nephrotoxicity

Oral Blood thinner Increased

anticoagulants risk for
bleeding
(Coumadin)
• Promoting an optimal response to therapy

• Oral administration: Question patient regarding allergy to

cephalosporins or penicillins
• shake oral suspensions
• Administer around the clock
• Administer orally at least 1 hour before or 2 hours after meals
• If patient experiences GI upset: Administer with food
 β-Lactamase inhibitors
 β-Lactamase inhibitors, such as clavulanic acid,
sulbactam, and tazobactam, contain a β-lactam
ring but, by themselves, do not have significant
antibacterial activity.
 Instead, they bind to and inactivate β--lactamases,
thereby protecting the antibiotics that are
normally substrates for these enzymes. The β--
lactamase inhibitors are therefore formulated in
combination with β-lactamase sensitive
antibiotics.
 Macrolides

• Gr (+), Gr (-)
• Erythromycin: the best known member
• Important in pulmonary infections include Legionnaire’s
disease
• Bacteriostatic, bactericidal in high dose
• Azythromycin, clarithromycin: broader spectrum
Mechanism of action

• The macrolides bind irreversibly to a site on the 50S

subunit of the bacterial ribosome, thus inhibiting the
translocation steps of protein synthesis
• Generally considered to be bacteriostatic, they may be
bactericidal at higher dose
• Erythromycin: This drug is effective against many of
the same organisms as penicillin G. therefore, it is
used in patients who are allergic to the penicillins.
Drug interaction:
• Erythromycin and telithromycin are extensively
metabolized and are known to inhibit the oxidation of a
number of drugs through their interaction with the
cytochrome P450 system .
•Interference with the metabolism of drugs such as
theophylline and carbamazepine has been reported for
clarithromycin
•No interactions have been reported for azithromycin.
 Macrolides

• Gastrointestinal intolerance: This side effect is common

and can lead to poor patient compliance for erythromycin.
Acute cholestatis hepatitis: hypersensitivity reaction
 Macrolides contraindicated in
1. the presence of known allergy to any
macrolide, because cross-sensitivity occurs
2. Caution should be used in patients with hepatic
dysfunction that could alter the metabolism of
the drug
3. in lactating women because of drug excretion
in breast milk
4. in pregnant women because potential adverse
effects on the developing fetus
 CLINDAMYCIN
• The major lincosamide
• Severe anaerobic infections: Bacteroides and other
anaerobs
• However, it is also significantly active against gram-
positive cocci.
• well absorbed by the oral route.
• Penetration into bone occurs even in the absence of
inflammation.
• undergoes extensive oxidative metabolism to inactive
products. The drug is excreted into the bile or urine
by glomerular filtration
Mechanism of Action
METRONIDAZOLE

• Anti amoeba, sensitive from anaerob bacteria

• ES: Metallic taste
 Antibiotics and pregnancy

• group B (i.e., warranting caution with treatment during

pregnancy) contains the following antibiotics: penicillins with
or without beta-lactamase inhibitors, azithromycin,
erythromycin,cephalosporin, metronidazole
• Group C in turn includes clarithromycin, the fluoroquinolones
and the sulfa drugs (cotrimoxazole).
• group D contains the aminoglycosides,
Thank you