A science of treating diseases with the help of
The term gradually came in to use in reference to
treatment of infections, infestations, and cancers.
• Treatment of systemic/topical infection with
drugs that have selective toxicity for an invading
pathogens with out harming the host cells.
• Due to analogy between the pathogenic organism
and malignant cells the treatment of neoplastic
diseases with drugs is also called as Chemotherapy
• 1877 – Louis Pasteur – “LIFE DESTROYS LIFE”Bacteria prevented growth of anthrax bacillus in
• 1891 – Paul Erlich (FATHER OF MODERN
CHEMOTHERAPY- NOBEL 1909) - methylene blue
inhibited growth of bacteria
• 1928 – Alexander Fleming: The fungus
penicillium notatum could inhibit staphylococci in
a culture plate
• 1938 – Domagk – Prontosil – a dye inhibited
micro-organisms – sulfonamides- sulfanilamide
• 1941 – Penicillin – Fleming, Florey, Chain- Nobel
• Obtain MO (Antibiotics)
• Antimicorbials Syn in Lab,
• Semisenthetic antibiotics
Mechanism of Action
• Antibiotic action can be split into 2
STATIC - implications
NO KILLING EFFECT – long period of treatment
Infection MAY NOT BE totally eradicated
ORGANISMS MAY REMAIN IN A DORMANT STAGE
MAY MULTIPLY LATER
E.g. chloramphenicol for enteric fever
• COMBINATION – static drug may reduce the rate of growth – a
cidal agent cannot work effectively.
CIDAL - IMPLICATIONS
Infection totally eradicated
Less chances of relapse
Example : ENTERIC FEVER (TYPHOID)
Cotrimoxazole, Ampi/amoxicillin, Ciprofloxacin, Ceftriaxone
• CIDAL drugs produce rapid effect – shortening of length of
treatment – tuberculosis (streptomycin, INH, rifampicin,
• Bacteriostatic Drugs arrest the growth and
replication of bacteria and limits the spread of
• Bacteriostatic antibiotics hamper the growth
of bacteria by interfering with bacterial:
• Macrolids ,Broad spectrum antibiotics ,Sulfanamides
• Trimethroprim, Clindamycin, Ethambutol
• Bacteriocidal kill or irrverisible damage the
• Microbe death is usually achieved by
disruption of the bacterial cell membrane
leading to lysis.
Fluroquinolones, Vancomycin, Polymixins
Rifampicin, INH, Bacitracin
Spectrum of activity
• Spectrum = range of micro-organisms
• Narrow spectrum
• Penicillin G (Benzyl penicillin) Mainly Gm +ve
• Aminoglycosides, Metronidazole – Mainly Gm
• Broad Spectrum Antibiotics: (BSA)
• TETRACYCLINES, CHLORAMPHENICOL
• Broader than NARROW SPECTRUM
• Narrower than BROAD SPECTRUM
Extended spectrum penicillins
II and III generation cephalosporins
Sulfa drugs, trimethoprim
• Usually it take advantage of the biochemical
and physiological differences that exist betn
MO and human beings.
Envelope by rigid cell wall
Flexible plasma membrane
Sub cellular organs absent
Ill- defined nucleus
Well defined nucleus
Energy metabolism bounded to cell
Located in mitochondria
Division -- fission
Ribosomes-70s– 30s & 50s
80s– 60s & 40s
• To make broaden spectrum activity
(Pulmonary, Aerobic, anaerobic)
• Increase antibacterial activity (Synergism)
• To prevent resistance (TB, leprosy)
• To reduce duration of therapy (MDT, leprosy)
• Reduce adverse effects
1. As result of mutation or by plasmid mediated
2. Producing an enzyme that inactivate antibiotic
Acetyl transferase, phosphotrans, adenyltransferase (aminoglycosides)
3. Decreased bacterial permeability or active efflux of drug.
4. An appearance of alternative pathway
5. Decreased affinity for target : Penicillin binding proteins
Prevention of drug resistance
Prefer rapidly acting selective spectrum
Combination of AMAs whenever prolong
Factors affecting choice of
– Chloramphenicol – Gray baby syndrome
– Half life amino glycosides is prolonged in elderly
– Tetracyclines – CI in below 6 years it accumulates in developing bone
All antibiotics produce risk to the fetus . Penicillins, Macrolids &
Impaired host defenses
– Bactericidal drugs are must in immunocompromised patients
• Renal function:
CI in renal disease
Dose reduction in renal failure
• Liver function
CI in liver disease
Dose reduction in liver failure
•Sulfonamide were the first antimicrobial agents effective against
pyogenic bacterial infections
•GELMO 1908 – Synthesized
•Prontosil was first drug active in vivo
•In liver it converting to Sulfonamide
•These are synthetic agents(Antimicrobials)
•Originally, sulfonamides were synthesized in Germany as azodyes.
Gerhard Domagk (1895-1964)
German bacteriologist and pathologist who was awarded
the 1939 Nobel Prize for Physiology or Medicine for his
discovery (announced in 1932) of the antibacterial
effects of Prontosil, the first of the sulfonamide drugs.
The process of discovery for sulfonamides
inactive (in vitro)
• The antimicrobial containing a sulfonamido (sulfanilamide, SO4NH2)
group are called sulfonamides.
• Structurally related to p-aminobenzoic acid (PABA).
SINCE THEN :
* 5000 SYNTHESISED.
* 150 MARKETED.
* 20 IN COMMON USE.
• This group is also present in other non-antibacterial compounds like
Mechanism of action
• Folic acid - synthesized from PABA, pteridine and
• All sulfonamides are analogs of PABA.
• SA compete with this substrate for the bacterial
enzyme, dihydropteroate synthetase.
• All sulfa drugs are bacteriostatic.
Both G+ & G- bacteria, nocardia,
chlamydia trachomatis, some
protozoa, some enteric bacteria (E coli,
klebsiella, salmonella, shigella, &
Sulfonamides stimulate rickettsiae in
• Absorbed rapidly from the gastrointestinal tract (except topically
Peak plasma levels are achieved in 2-6hrs.
• widely distributed and pass through BBB as well as placental barrier.
• Never administered SC & IM (Very painful)
• Metabolized as acetylated conjugates in liver.
Acetylated metabolites are inactive and low soluble in acidic urine,
leads to ppt. of crystaluria and renal toxicity.
• Excreted through the glomerular filtration in urine.
COMBINATION OF : Fixed dose combination
SULPHAMETHAXAZOLE : TRIMETHOPRIM.
400 mg. 800mg
80 mg. 160mg
M. A. O.
D. H. F. R. THFA
- SEQUENTIAL BLOCK.
- Broad spectrum bactericidal combination.
- Delays the development of bacterial resistance
STD DS tablet BD for 7-10days
– Chancoroid- Haemophilus ducreyi
(Chancoroiod – highly infectious nonsyphilitic venereal ulcer)
– Lymphomagranuloma – Chalamydia
– Gonorrhoea- Neisseria gonorrhoea
• Prophylactic DS tablet OD
• Curative – DS 4 times a day for 2-3 week
Sulfadiazine + Pyrimethamine
• 1st line Acute Toxoplasmosis
• Folinic acid 10mg each day to minimize bone marrow
• IV cotrimoxazole - 80mg Trimetho + 500mg
Sulfamethoxazole in 5ml diluted in 125ml of
5% dextrose infusion over period 60-90min
• Preferred for moderate to severe
– Pneumocytis carinii-pneumonia
– Thyoid fever
– Gram –ve bacterial sepsis
Sulfadoxine + Pyrimethamine
• Sequential block in protozoal folic acid synthesis
• Clinical curative for choloro qunine resistance P.
Falciparum (1500mg sulfadoxine+ 75mg Pyri)
sulfadoxine 500mg + Pyrimethamine 25mg (1:20)
• Pyrimethamine + sulfadoxine in toxoplasmosis
Oral non absorbable
Poorly absorbed by GIT
5 Aminosalicyclic acid + sulfapyridine
Anti inflammatory activity
Anti bacterial agent
Carrier moiety for 5AMA
to reach bowel
Sodium sulfacetamide- 10%, 20%, 30%
• Ophthalmic solution or ointment – conjunctivitis
Prevent bacterial colonization and infection
of burn wounds,
For prevention of infection of burn wounds
Crystalluria and renal toxicityAdequate intake of water
By making urine alkaline
Hemolytic and aplastic anemia (G6PD def.)
• Kernicterus in neonates– Sulfonamides displace bilirubin from protein binding
– Free bilirubin gets diposited in basal anglia, subthalamic
nuclei - toxic encephalopathy
– Avoided in neonates & pregnancy (last trimi)
• GI Nausea, vomiting, diarrhea, pancreatitis