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ANTIBIOTIC & SYNTHETIC ANTIMICROBIAL AGENTS

Antibiotic
A drug used to treat bacterial infections. Antibiotics have no
effect on viral infections. Originally, an antibiotic was a
substance produced by one microorganism that selectively
inhibits the growth of another. Synthetic antibiotics, usually
chemically related to natural antibiotics, have since been
produced that accomplish comparable tasks.
In 1926, Alexander Fleming discovered penicillin, a substance
produced by fungi that appeared able to inhibit bacterial growth. In
1939, Edward Chain and Howard Florey further studied penicillin and
later carried out trials of penicillin on humans (with what were
deemed fatal bacterial infections). Fleming, Florey and Chain shared
the Nobel Prize in 1945 for their work which ushered in the era of
antibiotics.
Another antibiotic, for example, is tetracycline, a broad-spectrum
agent effective against a wide variety of bacteria
including Hemophilus influenzae, Streptococcus pneumoniae,
Mycoplasma pneumoniae, Chlamydia psittaci, Chlamydia
trachomatis, Neisseria gonorrhoea, and many others. The first drug of
the tetracycline family, chlortetracycline, was introduced in 1948.
GENERAL MECHANISMS OF ACTION OF ANTI
MICROBIAL AGENTS:
1.Other interfere with biosynthesis of bacterial cell wall.
2. Some inhibits protein synthesis

3.Some change the cell membrane permeability


4. Some inhibit DNA synthesis

PENICILLINS
STRUCTURE:
A beta-lactam drug, with beta-lactam ring.(beta
lactam antibiotics)
THE ACTION OF PENICILLINS:

Penicillin and penicillinase-resistant penicillins


produce bactericidal affects by interfering with the
ability of susceptible bacteria from biosynthesizing
the framework of the cell wall.
Bacterium will have weakened cell wall, will swell
and then burst from osmotic pressure within the
cell.
THERAPEUTIC INDICATIONS:
Indicated for treatment of streptococcal infections
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.
Some are associated with the loss of bacterial flora.
Heypersensitivity reactionsrashes,pruritus,fever,mild allergic reactions.
Wheezing and diarrhea mal 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.

CEPHALOSPORINS

1. First Generation
cephalosporins largely
effective against the same
gram-positive organisms
affected by penicillin.
-cefadroxil
-cefazolin
-cephalexin
-cephalotin

-cephapirin
-cephadrine
2. Seond Generation
Cephalosporinseffective against
those strain as well
as Haemophilus
influenza,
Enterobacter
aerogenes and

Nesseria sp. Less


effective against
gram positive
bacteria.
-cefaclor
-cefamandole
-cefonizind
-cefotetan
-cefoxitin
-cefmetazole
-cefprozil
-cefuroxime
3. Third Generation
Cephalosporinsrelatively weak
against grampositive bacteria but
more potent against
gram-negative

bacteria, to include
Serratia
marcescens.
-Cefnidir
-Cefixime
-Cefoperazone
-Cefotaxime
-Cefpodoxime
-Ceftazidime
-Ceftibuten
-Moxalactam
4. Fourth Generation
Cephalosporinsdeveloped to fight
against the resistant
gram-negative
bacteria. The first
drug is cefepime.
-Cefepime

CONTRAINDICATIONS AND PRECAUTIONS


Contraindicated in patients with known
allergies to cephalosporins and penicillins.
ADVERSE EFFECTS
GI systems- Nausea, vomiting, diarrhea,
anorexia,abdominal pain and flatulence are
common effects.
CNS- headache, dizzinedd, lethargy and
paresthesias have been reported.
Renal system- nephrontoxicity in individuals
with pre-existing renal disease.
DRUG-DRUG INTERACTIONS
Aminoglycosides- if given with cephalosporins may
increase the risk of kidney toxicity.
Anti-coagulants- may experience increased bleeding
tendencies.

AMINOGLYCOSIDES
The following are aminoglycosides:
1.

Gentamycin

2.

Tobramycin

3.

Amikacin

4.

Netilmicin

5.

Kanamycin

MECHANISM OF ACTION:
Bactericidal
Inhibit protein synthesis in susceptible strains of gramnegative bacteria, leading to loss of functional integrity
of the bacterial cell membrane, which causes cell
death.
THERAPEUTIC USE OF AMINOGLYCOSIDES
Used to treat serious infections caused by gramnegative bacteria
CONTRAINDICATIONS AND PRECAUTIONS
Contraindicated in known allergies to
aminoglycosides, in patients with renal failure,
hepatic disease, pre-existing hearing loss, myasthenia
gravis, Parkinsons, pregnancy and lactation.
DRUG TO DRUG INTERACTIONS
Diuretics- increased incidence of
ototoxicity, nephrotoxicity and
neurotoxicity.

Anesthetics and Neuromuscular blockersincreased neuromuscular blockage and


paralysis may be possible.
Penicillin- synergistic action.

ADVERSE EFFECTS
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
aminoglycosides.
Hema- bonemarrow depression resulting from
direct drug effect may lead to immune
suppression and superinfection.
GI system- nausea,vomiting, diarrhea,weight
loss of bacterial flora and toxicity to mucus
membrane and liver as the drugs are
metabolized.
Skin effects- photosensitivity, purpura, rash,
urticaria and exfloliative dermatitis.
Cardiac- palpitations, hypotension or
hypertension.

MACROLIDES
The macrolides are
Azithromycin
Clarithromycin
Dirithromycin
Erythromycin
MECHANISM OF ACTION:
Bactericidal and sometimes bacteriostatic
Exert effect by binding to the bacterial cell
ribosomes and changing or altering protein
production/ function
Lead to impared cell metabolism and division
PHARMACOKINETICS
Erythromycin is destroyed by gastric juice,
slats are added to stabilize the drug. Food
does not interfere with the absorption of the
macrolides.
THERAPEUTIC USE:
Indicated for the treatment of : Streptococcal
infection, Mycoplasma infection, Listeria

infection and group A beta haemolytic strep


infection.
CONTRAINDICATIONS AND PRECAUTIONS
Contraindicated in the presence of known
allergy to macrolides because of crosssensitivity.
Cautions in patients with hepatic dysfunction
that could alter the metabolism of the drug.
In lactating women, excretion in breast milk
In potential adverse effects on developing
fetus

LINCOSAMIDES
Similar to the Macrolides but are more toxic
Bactericidal and bacteriostatic depending on
the dose
Examples: Clindamycin and Lincomycin
MECHANISM OF ACTION
penetrate the cell membrane and bind to the
ribosome in the bacterial cytoplasm to prevent the
protein production.
SIDE EFFECTS AND ADVERSE REACTIONS
GIT-GI irritatin , nausea, vomiting and stomatitis.
Allergic reactions.
DRUG INTERACTIONS
Lyncomycin and clindamycin are incompatible with
aminophyline, phenytoin, barbiturates and
ampicillin.

TETRACYCLINE

FLUOROQUINOLONES

SULFONAMIDES
called sulfa drugs that inhibit folic acid
synthesis
folic acid is necessary for the synthesis
of purine and pyrimidine precursors of DNA
and RNA. Humans cannot produce folic acid
and must obtain it from diet. While bacteria
need to manufacture their own folic acid
inside their cell structure.
1. Sulfazalazine
2. Sulfamethoxazole
3. Sulfadiazine
4. Sulfixoxazole

ADVERSE EFFECTS
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 nephritic
syndrome.
CNS- headache, dizziness, vertigo, ataxia,
convulsions and depression related to drug effects
on the nerves.
Hema- bone marrow depression related to the drug
effects on the cells of the bone marrow that turn
over rapidly.

Dermatologic effects- photosensitivity and rash


hypersensitivity.
DRUG-DRUG INTERACTION
Tobultamide,
tolazanide,glyburide,glipizide,acetohexamide or
chlorpropamide (all are oral Anti- Diabetic agents)
can increase the risk of hypoglycaemia if taken with
the sulfa drugs.
How They Work
Antibiotics work by being either bactericidal where they kill
microorgnisms; or by being bacteristatic where they inhibit the
growth of the microorganisms.
An example of a bactericidal antibiotic is Penicillin. This works by
preventing the production of a substance that form the cell wall:
peptidoglycan. This means the cell will continue to grow without
dividing or developing new cell wall. Therefore, the wall gets weaker,
and eventually ruptures (lysis).

Other antibiotics work by inhibiting the protein synthesis or nucleic


acid synthesis. Tetracycline is a bacteristatic antibiotic that binds to
ribosomes in bacteria, this means the cell cannot make proteins and
therefore can't grow.

When choosing antibiotics to treat diseases, it is important to think


carefully. For instance, bacteria have a different type of ribosome
(70S) to humans (80S), therefore they will only work to target the
bacteria and not affect the patient.
Narrow spectrum antibiotics target specific reaction in particular
microorganisms; whereas broad spectrum antibiotics will have an
effect on more general features so affect a wide range of pathogens.
Antibiotic Resistance
Antibiotic resistance arises as a result of natural selection. Since
bacteria reproduce rapidly, resistance can arise quickly. Those
antibiotics resistant will remain after treatment and can continue to
divide.
An example of antibiotic resistance can be seen with Penicillin, some
bacteria can produce an enzyme called Penicillinase which breaks
down Penicillin before it can take effect.
Other mechanisms of resistance include the evolution of a capsule
that is resistant to antibiotic, and cell membranes becoming less
permeable to antibiotic.
Bacteria can spread resistance genes between each other by bacterial
conjugation where two cells join by their pilli and
exchange plasmids which often contain genes for antibiotic
resistance.

Antibiotic resistance is made much worse by the overuse of


antibiotics in medical treatment. Some bacteria are resistant to most
antibiotics (MRSA or mycobacterium-tuberculosis) meaning it is
increasingly difficult to treat infection unless new antibiotics are
developed.

There are four antibiotic resistance can occur:


1. decreased permeability of the antibiotic
2. bacterial enzymes inactivate the antibiotic
3. target site of antibiotic is altered and so binding of antibiotic to
target does not occur. Imagine a key, the antibiotic, does not fit into
the key hole, the target site, because the key hole (target site) has been
altered.
4. the antibiotic is actively transported out of the bacterial cell due to
an efflux pump.

Diagram of how antibiotic resistance genes are transferred among


bacterial cells

Activity Spectrum of Certain Antibiotics and Antimicrobial Drugs

Narrow Spectrum Antibiotics


Drug name:

Prescribed for:

Isoniazid

Tuberculosis

Ethambutol

Tuberculosis

Penicillin V & G

Acintobactor

Vancomycin

MRSA

Cephalosporin 1st generation (

Bacterial Endocarditis

Metroidazole

Infection of the vagina, stomach, skin, joints, and respiratory tract

Penciclovir

Herpes

Augmentin

Lower respiratory tract infection

Broad Spectrum Antibiotics


Drug Name:

Prescribed for:

Erythromycin

Strep throat

Clindamycin

If allergic to penicillin

Rifampin

Tuberculosis

Tetracycline

Acne

Chloramphenizol

Salmonella

Nitrofurantoin

E-coli

Penicillin VK

Ear infection

Ciprofloxacin

Respiratory tract infection

Cephalosporin 4th generation (Cefepime)

bacteremia

Mechanism of action of certain antibiotics


EXAMPLE
Aminoglycosides

Bacitracin

streptomycin
neomycin

Mechanism of
Action
Inhibit protein
synthesis by
binding to a
portion of the
bacterial
ribosome.
Most of them are
bacteriocidal
(cause bacterial
cell death).
Inhibits cell wall
production by
blocking a step in
the process
(recycling of the
membrane lipid
carrier) which is

Beta-lactam antibiotics

penicillins
cephalosporins
carbapenems
monobactams

Cephalosporins

Chloramphenicol

Glycopeptides

vancomycin

needed to add on
new cell wall
subunits.
Group of
antiobiotics which
contain a specific
chemical structure
(a beta-lactam
ring)
Similar to
penicillins in their
mode of action,
but they treat a
broader range of
bacterial
infections.
The have
structural
similarities to
penicillins and
many people with
allergies to
penicillins also
have allergic
reactions to
cephalosporins.
Inhibits protein
synthesis by
binding to a
subunit of
bacterial
ribosomes (50S).
Interferes with cell
wall development
by blocking the

Macrolides

erythromycin

Lincosamides

clindamycin

Penicillins

Quinolones

Rifampin

attachment of
new cell wall
subunits
(muramyl
pentapeptides).
Inhibit protein
synthesis by
binding to a
subunit of the
bacterial
ribosome (50S).
Inhibit protein
synthesis by
binding to a
subunit of the
bacterial
ribosome (50S).
Inhibit formation
of the bacterial
cell wall by
blocking crosslinking of the cell
wall structure.
The cell wall is a
needed protective
casing for the
bacterial cell wall.
Block DNA
synthesis by
inhibiting one of
the enzymes
(DNA gyrase)
needed in this
process.
Inhibits RNA

Tetracyclines

Trimethoprim andSulfonamides

synthesis by
inhibiting one of
the enzymes
(DNA-dependent
RNA polymerase)
needed in this
process. RNA is
needed to make
proteins.
Inhibit protein
synthesis by
binding to the
subunit of the
bacterial
ribosome (30S
subunit).
Blocks cell
metabolism by
inhibiting
enzymes which
are needed in the
biosynthesis of
folic acid which is
a necessary cell
compound.

SOURCES:
http://www.medicinenet.com/script/main/art.asp?articlekey=8121

http://scienceaid.co.uk/biology/micro/antibiotics.html
http://pharmacologydeh-28classof2011.wikispaces.com/AntiInfective+Agents

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