Pharmacology of the

Antibiotics

Dr.Ameya Hasamnis [MBBS,MD]

 The anti-infective drugs
 Anti-infective agents are drugs that
are designed to act selectively on
foreign organisms that have invaded
and infected the body
 The anti-infective drugs

Anti-infective drugs - range from

 Antibacterials
 Antifungals
 Antiprotozoals
 Antihelminthics
 Antivirals
 Antimycobacterial
General Mechanisms of Action
of anti-infective agents

The mechanisms are:

 Inhibition the biosynthesis of

bacterial cell WALL

 Inhibition of protein synthesis

 Some change the cell membrane

permeability
 Some inhibit DNA synthesis
 Examples
CELL WALL penicillin,
INHIBITORS cephalosporin,
vancomycin
PROTEIN SYNTHESIS Macrolides,
INHIBITORS aminogylcosides
CELL WALL Ketoconazole
Permeability
DNA SYNTHESIS Quinolones
INHIBITORS
Spectrum of Activity of Anti-infectives

 Narrow spectrum

 Broad-spectrum
Spectrum of Activity of Anti-infectives

 Narrow spectrum anti-infectives

affect only a few bacterial types

 The early penicillin drugs are

examples.
Spectrum of Activity of Anti-infectives

 Broad-spectrum anti-infectives affect

many bacteria.
 Meropenem is an example.
 Because narrow spectrum antibiotics
are selective, they are more active
against single organisms than the
broad spectrum antibiotics.
Spectrum of Activity of Anti-infectives
Anti-infective agents can also be:

 Bacteriostatic
Erythromycin, tetracyclines,
clindamycin, chloramphenicol,
spectinomycin, sulfonamides
 Bactericidal
- Penicillins, Cephalosphorins,
Metronidazole, Aminoglycosides,
Vancomycin, Polymyxin
 Spectrum of Activity of Anti-
infectives
 Anti-infectives that interfere with the
ability of the cell to
reproduce/replicate without killing
them are called BACTERIOSTATIC
drugs.
 Tetracycline is an example.
 Spectrum of Activity of Anti-
infectives
 Antibiotics that can aggressively cause
bacterial death are called
BACTERICIDAL.
 These properties (-cidal and –static) can
also depend on the antibiotic
concentration in the blood.
 (e.g. Erythromycin and Clindamycin may
be bactericidal at higher blood levels)
 Factors That Determine the Likehood Of a
microorganism Causing an Infection:

1. Virulence of the microorganism

2. Number of the microorganism present
3. Resistance of the host
Common Adverse Reactions to
Anti-infective Therapy
The most common adverse effects are
due to the direct action of the drugs
in the following organ system-
Neuro, nephro and GI system
Common Adverse Reactions to
Anti-infective Therapy
1. Nephrotoxicity
 Antibiotics that are metabolized
and excreted in the kidney most
frequently cause kidney damage..
Common Adverse Reactions to
Anti-infective Therapy
2. Gastro-intestinal toxicity
 Direct toxic effect to the cells of the

GI tract can cause nausea, vomiting,

stomach pain and diarrhea.
 Some drugs are toxic to liver cells

and can cause hepatitis or liver

failure.
Common Adverse Reactions to
Anti-infective Therapy
3. CNS toxicity
 When drugs can pass through the

brain barrier and accumulate in the

nervous tissues, they can interfere
with neuronal function.
Common Adverse Reactions to
Anti-infective Therapy
4. Hypersensitivity
 Most protein antibiotics can induce
the body’s immune system to
produce allergic responses.
 Drugs are considered foreign
substances and when taken by the
individual, it encounters the body’s
immune cells.
Common Adverse Reactions to
Anti-infective Therapy
5. Super-infections
 Opportunistic infections that develop

during the course of antibiotic

therapy are called
SUPERINFECTIONS.
 The PENICILLINS
Narrow spectrum penicillins
 Penicillin G
 Penicillin V

Broad Spectrum Penicillins (aminopenicillin)

 Amoxicillin
 Ampicillin
 Bacampicillin

Penicillinase-resistant Penicillin (anti-staphyloccocal penicillins)

 Cloxacillin
 Nafcillin
 Methicillin
 Dicloxacillin
 Oxacillin

Extended-Spectrum penicillins (Anti-pseudomonal penicillins)

 Carbenicillin
 Mezlocillin
 Piperacillin
 Ticacillin

Beta-lactamase inhibitors
 Clavulanic acid
 Sulbactam
 Tazobactam
 Penicillin
Penicillin is a beta-lactam drug,
with a beta-lactam ring.

The group of penicillins is called

beta lactam antibiotics.
 Penicillin
The action of Penicillins

 The penicillin and penicillinase-

resistant penicillins produce
BACTERICIDAL effects by
interfering with the ability of
susceptible bacteria from
biosynthesizing the framework of
the cell wall.
 Penicillin
 Thebacterium will have
weakened cell wall, will
swell and then burst from
the osmotic pressure within
the cell.
 Penicillin
Pharmacokinetics:

Amoxicillin is well absorbed in the

GIT. This in NOT affected by food
intake!!
 Penicillin
Therapeutic Indications of
penicillin
 The penicillins are indicated
for the treatment of
streptococcal infections
 Syphilis
 Tetanus
 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
 THE CEPHALOSPORINS

The cephalosporins
also belong to the
beta-lactam group
of antibiotics
 THE CEPHALOSPORINS

 First Generation cephalosporin

 Second generation cephalosporin

 Third Generation cephalosporin

 Fourth generation cephalosporin

 THE CEPHALOSPORINS
 First Generation cephalosporins- are
largely effective against the same
gram-positive organisms affected by
penicillin.

 Second generation cephalosporins-

are effective against those strains as
well as Haemophilus influenza,
Entreobacter aerogenes and Nesseria
sp. These drugs are less effective
against gram positive bacteria
 THE CEPHALOSPORINS
 Third Generation cephlosporins- are
relatively weak against gram-
positive bacteria but more potent
against gram-negative bacteria, to
include Serratia marcescens.

 Fourth generation cephalosporins-

are developed to fight against the
resistant gram-negative bacteria.
The first drug is cefepime.
 First generation cephalosporins
 cefadroxil
 Cefazolin
 Cephalexin
 Cephalotin
 Cephapirin
 Cephadrine
 Second Generation cephalosporins
 Cefaclor
 Cefamandole
 Cefonizind
 Cefotetan
 Cefoxitin
 Cefmetazole
 Cefprozil
 Cefuroxime
 Third Generation Cephaosporins
 Cefnidir
 Cefixime
 Cefoperazone
 Cefotaxime
 Cefpodoxime
 Ceftazidime
 Ceftibuten
 Moxalactam
 Fourth Generation Cephalosporin
 Cefepime
 Cephalosporin
 The mechanism of action
 The cephalosporins are primarily
BACTERICIDAL.
 They interfere with the cell-wall
building ability of bacteria when they
divide.
 They prevent the bacteria from
biosynthesizing the framework of
their cell wall.
 The weakened cell wall will swell and
burst causing cell death.
 Cephalosporin
 Pharmacokinetics
 Only a few cephalosporins are
administered orally, most are
administered parenterally.
 Their half-lives are short and they
are excreted mainly in the urine.

 Contraindications and Precautions

 The drugs are contraindicated in
patients with known allergies to
cephalosporins and penicillins.
 Cephalosporin
Adverse Effects
 GI system- Nausea, vomiting,
diarrhea, anorexia, abdominal pain
and flatulence are common effects.
 CNS – headache, dizziness, lethargy
and paresthesias have been reported.
 Renal system- nephrotoxicity in
individuals with pre-existing renal
disease
 Hypersensitivity
 Cephalosporin
Drug-Drug interactions
 ALCOHOL- many patients experience a
disulfiram-like reactions when taken
with some specific cephlosporins
( cefamandole, cefoperazone or
moxalactam).
 The patient may experience flushing,
headache, nausea, vomiting and
muscular cramps. This may occur even
up to 72 hours of cephalosporin
discontinuance.
 The Aminoglycosides

The following are the aminoglycosides

1. Gentamycin
2. Tobramycin
3. Amikacin
4. Netilmicin
5. Kanamycin
 The Aminoglycosides

Mechanism of action
 They inhibit protein synthesis in
susceptible strains of gram-
negative bacteria, leading to loss
of functional integrity of the
bacterial cell membrane, which
causes cell death.
 The Aminoglycosides
Therapeutic Use of the Aminoglycosides
 These drugs are used to treat serious
infections caused by gram-NEGATIVE
bacteria.

 These drugs are contraindicated in

known allergies to aminoglycosides, in
patients with renal failure, hepatic
disease, pre-existing hearing loss,
myasthenia gravis, Parkinson’s,
pregnancy and lactation.
 The Aminoglycosides
Adverse Effects of Aminoglycosides
 CNS- irreversible deafness, vestibular
paralysis, confusion, depression,
disorientation, numbness, tingling and
weakness related to drug effects.
 Kidney- renal toxicity, which may
progress to renal failure caused by the
direct toxicity of the aminoglycosides.
 Hema- bone marrow depression
resulting from direct drug effect may
lead to immune suppression and super-
infection.
 Ototoxicity
 The Aminoglycosides

Adverse Effects of Aminoglycosides

 GI system- nausea, vomiting,
diarrhea, weight loss, stomatitis and
hepatic toxicity
 Skin effects- photosensitivity,
purpura, rash, urticaria and
exfoliative dermatitis
 Cardiac- palpitations, hypotension
or hypertension
 The Aminoglycosides

Drug to drug interactions

 Diuretics- increased incidence of
ototoxicity, nephrotoxicity and
neurotoxicity.
 Anesthetics and Neuromusular
blockers- increased neuromuscular
blockage and paralysis may be
possible
 Penicillin- synergistic action
 The Macrolides

The macrolides are

 Azithromycin
 Clarithromycin
 Dirithromycin
 Erythromycin
 The Macrolides
Mechanism of Action of the Macrolides

 They exert their effect by binding

to the bacterial cell ribosomes and
changing or altering protein
production/function

 This will lead to impaired cell

metabolism and division.
 The Macrolides

 Pharmacokinetics
 Erythromycin is destroyed by
the gastric juice, which is
why salts are added to
stabilize the drug.
 Food does not interfere with
the absorption of the
macrolides.
 The Macrolides

Therapeutic Use of Macrolides

 These are indicated for the
treatment of the following
conditions:
 Steptococcal infection,
Mycoplasma infection, Listeria
infection and group A beta
hemolytic strep infection.
 The Macrolides
Contraindications and Precautions in the Use of
Macrolides
 These agents are contraindicated in the
presence of known allergy to any macrolide,
because cross-sensitivity occurs.
 Caution should be used in patients with
hepatic dysfunction that could alter the
metabolism of the drug; in lactating women
because of drug excretion in breast milk and in
pregnant women because potential adverse
effects on the developing fetus.
 The Macrolides

Adverse Effects of Macrolides

 GI system- abdominal cramping, anorexia,
diarrhea, vomiting and
pseudomembranous colitis.
HEPATOTOXICITY can occur if the drug is
taken in high doses with other hepatotoxic
drugs.
 CNS- confusion, abnormal thinking and
uncontrollable emotions.
 Hypersensitivity reactions
 The Lincosamides

These agents are similar to the

Macrolides but are more toxic.

 Clindamycin
 lincomycin
 The Lincosamides

Pharmacodynamics: The Mechanism of

Action of Lincosamides
 These agents penetrate the cell
membrane and bind to the ribosome in
the bacterial cytoplasm to prevent the
protein production
 The Lincosamides

Side effects and Adverse Reactions

 GIT- GI irritation, nausea, vomiting and
stomatitis
 Allergic reactions

Drug Interactions
 Lincomycin and clindamycin are
incompatible with aminophyline,
phenytoin, barbiturates and ampicillin.
 The Tetracyclines
These agents were first isolated from
Streptomyces aureofaciens
The following are the tetracyclines
 Short-acting tetracyclines
 tetracycline
 oxytetracycline
 Intermediate acting tetracyclines
 demeclocycline
 methacycline
 Long acting tetracyclines
 doxycycline
 minocycline
 The Tetracyclines

Pharmacodynamics
 Thetetracyclines inhibit
protein synthesis in
susceptible bacteria
leading to the inability of
the bacteria to multiply.
 The Tetracyclines
Contraindications and Precautions in the use of Tetracyclines
 It is not recommended for use in
pregnancy and lactation because the
drug can affect the bones and teeth,
causing permanent discoloration and
sometimes arrest of growth.

 Tetracyclines are also avoided in

children less than 8 (eight) years of
age because of the potential damage
to the bones and permanent
discoloration of the teeth.
 The Tetracyclines

Adverse Effects of the Tetracycline

 GI system- nausea, vomiting, diarrhea, abdominal
pain, glossitis and dysphagia.
 Fatal hepatotoxicity related to tetracycline’s
irritating effect on the liver cells has been reported.
 Musculoskletal- Tetracyclines have an affinity for
teeth and bones; they accumulate there, leading to
weakening of the bone/teeth and permanent
staining and pitting.
 Skin- photosensitivity and rash are expected .
 Less frequent- bone marrow depression,
hypersensitivity, super infections, pain and
hypertension
 The Tetracyclines

Drug-Drug Interactions
 Penicillin- if taken with tetracyclines, will
decrease the effectiveness of penicillin.
 Oral contraceptives- if taken with
tetracycline, will have decreased
effectiveness.
 Digoxin- digoxin toxicity rises when
tetracyclines are used together
 The Tetracyclines

Drug-Food Interaction
 Dairy products- can complex with
tetracycline and render
unabsorbable.
 Tetracyclines should then be given
on an EMPTY stomach 1 hour before
meals or 2-3 hours after any meal or
other medications.
 The Fluoroquinolones
The fluoroquinolones are broad-spectrum antibiotics.
They are usually manufactured synthetically and
are associated with mild adverse reactions.

The examples are:

1. Nalidixic acid
2. ciprofloxacin
3. ofloxacin
4. norfloxacin
5.Levfofloxacin
6.Sparfloxacin
 The Fluoroquinolones
Pharmacodynamics: Mechanism of
action of the Fluoroquinolones
 These agents enter the bacterial cell
by diffusion through cell channel.
 Once inside they interfere with the
action of DNA enzymes (DNA
gyrase) necessary for the growth
and reproduction of the bacteria.
This will lead to cell death.
 The Fluoroquinolones

 Contraindications and Precautions

Pregnancy and lactation are also
contraindications.
These agents are found to cause
significant damage to the cartilages
such that they are given cautiously to
growing children and adolescents less
than 18 years of age
 The Fluoroquinolones
Adverse Effects of the Fluoroquinolones
 CNS- dizziness, insomnia, headache, and
depression related to possible effects on the
CNS membrane.
 GI system- nausea, vomiting, diarrhea and dry
mouth related to the direct effect on the GIT
 Hema- bone marrow depression related to the
direct effect of the drug on the cells of the
bone marrow that rapidly turn over.
 Other effects- skin reactions, rash, fever and
photosensitivity
 Sulfonamides

The following are the

sulfonamides:
1. Sulfazalazine
2. Sulfamethoxazole
3. Sulfadiazine
4. Sulfixoxazole
 Sulfonamides

Pharmacodynamics
 The sulfa drugs competitively
block the para-amino benzoic
acid to prevent the synthesis
of folic acid in susceptible
bacteria that synthesize their
own folates for the production
of RNA and DNA.
 Sulfonamides

Contraindications and precautions

 These agents are contraindicated to patients

with known allergy to sulfa drugs,
sulfonylureas and thiazide diuretics because
they share similar structures.
 It is not recommended for use in pregnancy
because it can cross the placenta and cause
birth defects and kernicterus.
 Lactating women who take these drugs will
excrete them in the breast milk potentially
causing kernicterus, diarrhea and rash in the
newborn.
 Sulfonamides
Adverse Effects of the Sulfonamides
 GI system- nausea, vomiting, diarrhea, abdominal
pain, anorexia, stomatitis and hepatic injury, which are
all related to the direct irritation of the GIT and death
of normal flora.
 Renal system- crystalluria, hematuria and proteinuria
which can progress to a nephrotic syndrome .
 CNS- headache, dizziness, vertigo, ataxia, convulsions
and depression related to drug effects on the nerves
 Hema- bone marrow depression related to drug effects
on the cells of the bone marrow that turn over rapidly.
 Dermatologic effects- photosensitivity and rash and
hypersensitivity