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 DEFINITION OF TERMS
• Antibiosis: The killing action of one living organism by
another organism.
• Antibiotic: Was initially used to describe any organism
that was able to kill other microorganisms.
•Today it is used to describe any chemical agent that could
kill microorganisms. Most antibiotics are now synthesized
or modified from other antobiotics.
 THE WAY ANTIBIOTICS ACT
1. Inhibition of cell wall synthesis e.g. penicillin, bacitracin, vancomycin and the
cephalosporins.
2. Damage cell membrane permeability e.g colistin, nystatin, chlorhexidine,
savlon, polymyxins, and amphotericin.
3. Prevent proper translation of the genetic code and inhibit formation of
proteins (inhibitions of protein synthesis) act on messenger RNA: ofloxacin,
ciprofloxacin (Quinolones), erythromycin and chloramphenicol.
The aminoglycosides such as gentamicin, streptomycin, clindamycin,
oleandomycin, kanamyun, neomycin and clindeparomycin, also belongs to
this group.
4. Inhibit essential metabolites (antimetabolities) e.g. sulphonamides, sulphones,
PAS (Para aminosalicylic acid) trimethoprim, pyrimethamine and prognanil.
 USE OF ANTIBIOTICS

a. Prophylactic - e.g Flagyl in abdominal surgery, bacitracin on skin

after surgery, neomycin and penicillin to prevent endocarditis in
rheumatic fever patients and people going for tooth extraction.
b. Therapeutic: For treating infections.
 BACTERIOSTATIC DRUGS

- Inhibit cell replication.

- If withdrawn, cell will begin to grow
again.
Examples: Sulphonamides
Chloramphenicol
Erythromycin
 BACTERICIDAL DRUGS

- Cause cell death and lysis. If withdrawn, cells

cannot grow.
Examples: Penicillin
Streptomycin
  
BACTERIOSTATIC AND BACTERICIDAL
EFFECTS OF ANTIBIOTICS
 CLASSIFICATION OF ANTIBIOTICS
1. Antimetabolites
- Sulphonamides: Sulphadimidine, Sulphathiazole, etc
- pyrimethamine
- Sulphones
- trimethoprim
- PAS- para-amino salicylic acid
- Proguanil
2. Inhibitors of cell wall synthesis
-The penicillins and the cephalosporins act at same points (carboxypeptidase, transpeptidase)
- Vancomycin
- Ristocetin
- bacitracin
- cycloserine
- Cephalosporins, Carbapenems
 CLASSIFICATION OF ANTIBIOTICS (CTD)
 3. Antibiotics that act on cell membrane
- Colicins
- Amphotericin
- Gramicidin
- Tyrocidin
- Chlorhexidine
- Savlon
- Salicylanamide
- The polymyxins
- The Colistins
- Nystatin
 CLASSIFICATION OF ANTIBIOTICS (CTD)
4. Antibiotics affecting Ribosome function
Chloramphenicol
Erythromycin
Oleandomycin
Carbomycin
Lincomycin
Clindamycin
5. Aminoglycosides- Streptomycin
- Neomycin
- Kanamycin
- Paromomycin
- Gentamicin
6. The tetracyclines: Tetracycline, Oxytetracycline, Doxycycline, etc.
 PENICILLINS
Note that it has only one side chain (R) and a 5-member nucleus
and a thiazolidine ring
Mechanism of action
Inhibits cell wall synthesis leading to osmotic lysis and death. This
is bactericidal action
 CEPHALOSPORINS
CORE STRUCTURE OF THE CEPHALOSPORINS
 These differ from the penicillins in which the nucleus is a five-member ring with
only one side chain (R1).  
- A group of compounds isolated from fungi. They have the same mechanism of
action as the penicillins.
- Also has similar structure with the characteristic β-lactam ring
 FEATURES OF CEPHALOSPORINS

First generation: cephalothin, cephapirin, cephradine,

cefazolin
Second generation: cefamandole, cefuroxime,
cefoxitin, cefonicid, cefotetan
Third generation: ceftotaxime, ceftrizoxime,
ceftriaxone, maxalactam, cefoperazone ceftrazidime.
 CARBAPEMENS
New highly effective antibiotic agents used for the treatment of severe
or high-risk bacterial infections.
It has three side chains,while cephalosporins have two side chains.

Used for the treatment of serious multidrug resistant Gm-ve and Gm-
+ve infections
 EXAMPLES
Imipenem
Meropenem
Ertapenem
Doripenem
Panipenem/Betamipron
Biapenem
Tebipenem
They differ as to the route of administration, number of daily
doses required and whether or not they require combination
therapy with other drugs
 SULPHONAMIDES
 
- Structural analogs of para-amino-benzoic acid (PABA)
-To be a true sulphonamide, the structure must be similar to that of PABA, and its
action must be inhibited by the latter.
-They block folic acid synthesis. Folic acid is used in the body for the synthesis of:
a. Amino acids
Methionine
Thymine
hydroxymethyl cytosine
IUPAC name
b. Purines
DNA 4-Aminobenzoic acid

RNA
 STRUCTURE OF SULPHONAMIDES
Sulphonamides

NH2 R1 varies among the sulphonamides.

R1

SO2 N

Sulphonamides R1

1. Sulphadiazine (most active)

N Benzene
group

2. Sulphathiazole N

Imidazole
grp
N

\
3 Sulphopyridine Benzene group

N
 MODE OF ACTION OF SULPHONAMIDES

- Arrest cell growth

- This is done by inhibition of folic acid synthesis
- Folic acid is required for growth by both mammalian
and bacterial cells
- Mammalian cells cannot synthesise it , as it is absorded
as cofactor
 OTHER SULPHONAMIDES

PARA AMINO SALICYLIC ACID (PAS) & DAPSONE: used for

treating Myco. leprae

TRIMETHOPRIM & CHLORGUANIDE: Are anti-malaria agents

 TETRACYCLINES
General formula

Vibramyan (doxycycline) is a long-acting tetracycline

SIDE CHAINS OF THE TETRACYCLINES
The tetracylines R1 R2 R3
Tetracycline H CH3 H
Chlortetracyline cl CH3 H Aureomycin
Oxytetracyline H CH3 OH Terromycin
dimethylchlortetracyline cl H H
 MODE OF ACTION

A Tetracycline binds A site of the bacterial

ribosomes
And so blocks binding of aa + RNA to the
mRNA – ribosme complex
Inhibits binding , to the acceptor site ,
thus terminates protein synthesis by the
bacteria
 ANTIBIOTICS THAT AFFECT MEMBRANE
PERMEABILITY
Colicins A, E, K, Ia, Ib, Q
Polyene antibiotics: amphotecicin B, nystatin ( treatment
of fungal infections)
The polymyxins: polimyxin B, Colistin (Polimyxin E )-
Treatment of urinary tract and fungal infections
Monocyclic polypeptides: Gramicidin, Tyrothricin,
Chlorhexidine Savlon & Salicylanamide – Some of
them are antiseptics
 CHLORAMPHENICOL

- Only active on 70s ribosomes - Binds to the 50s

ribosome
- Inhibits transpeptidase enzyme function and prevents
peptide bond formation
 AMINOGLYCOSIDES
- Structure
- Polycatinonic compounds composed of aminosugars connected
by glycosidic linkages
 MODE OF ACTION

THEY ARE ALL BACRTERICIDAL and Include:

Streptomycin
Gentamicin
Neomycin
Kanamycin
Spectinomycin
They are all very active against Gram negative bacteria
They cause misreading of the genetic code at the ribosomal site of
protein synthesis by bacteria
 CHEMOTHERAPY OF MALARIA I

1.Chloroquine (CQ)
• This was one time a very effective 4-amino-quinoline
both for malaria treatment and prophylaxis.
• It was first used in the 1940s with few side effects when
taken in the dose prescribed and it was relatively cheap.
• Presently it is not useful as antimalarial in most country
of the world because of its toxicity and the parasites are
now resistant
• May have some use in the treatment of COVID-19
 CHEMOTHERAPY OF MALARIA II
2. Proguanil: It has a biguanide chain attached at one end to a chlorophenyl
ring and is very close in structure to pyrimethamine.
It is a folate antagonist that destroys the malarial parasite by binding to the
enzyme dihydrofolate reductase
3. Malarone: Malarone is a combination of proguanil and atovaquone.
When combined with proguanil, there is a synergistic effect and the
combination is at the present time a very effective antimalarial drug.
4. Maloprim: This is a combination of dapsone and pyrimethamine. Resistance
to this drug is now widespread and its use is no longer recommended.
5. Lapdab: This is combination of dapsone and chlorproguanil. Its use has
been reduced due to the serious complications of severe haemolysis and
anaemia requiring transfusion.
 CHEMOTHERAPY OF MALARIA III
6. Fansidar : This is a combination drug containing sulphadoxine and
pyrimethamine in ratio 20:1 in each tablet. It acts by interfering with folate
metabolism. Resistance to Fansidar is now widespread and clinical confidence
now dropping.
7. Mefloquine (Lariam): First introduced in 1971, this quinoline methanol
derivative is related structurally to quinine. It was effective against malaria
resistant to other forms of treatment when first introduced and because of its
long half life was a good prophylactic, but widespread resistance has now
developed.
8. Halofantrin (Halfan): This belongs to a class of compound called the
phenanthrene-methanols. It has been associated with neuropsychiatric
disturbances and arrythmias. It is contraindicated during pregnancy and is
not advised in women who are breastfeeding.
 CHEMOTHERAPY OF MALARIA IV

9. Coartem: This is a combination of Lumefantrin and

Artemether. It has proven very effective. However
anecdotal experiences are showing early parasitaemic
recrudescence
10. Artemisinins: This is derived from a Chinese herbal
remedy and covers a group of products. The two most
widely used are artesunate and artemether
 CHEMOTHERAPY OF MALARIA V
Classification of combination therapies
a. Artemisinin based combinations
o Artesunate+ amodiaquine
o Artesunate + mefloquine for areas with low transmission
o Co-artemether (Artemether 20mg + Lumefantrine 120mg/tablets
o Sulphamedoxine-pyrimethamine (SP) + Artemether or Artesunate
b. SP based combinations
o SP + CQ as separate tablets
o SP + Amodiaquine as separate tablets
o SP + Quinine
o SP + Mefloquine