CHEMOTHERAPY

TERMINOLOGIES
CHEMOTHERAPY: treatment of infectious
diseases or malignancy with drugs which
destroy microorganisms or cancer cells
prefrentially with minimal damage to host
tissue
Antimicrobial agents: drugs that acts against
microorganisms
Antibiotic: drugs acts against bacteria
Bacteriostatic: inhibits the growth of bacteria
Bactericidal: kills the bacteria
chemoprophylaxis
Administration of antimicrobial agents to
prevent infection
Indication:
◦ Prior to surgical procedures
◦ To prevent endocarditis
◦ In organ transplantation
◦ To prevent infection in immunocompromised
pts
Classification
Based on target microorganism
◦ Antibacterial:-penicillins, aminoglycosides
◦ Antiviral:-acyclovir , zidovudine
◦ Antifungal:-Amphotericin B
◦ Antihelmentic:- mebendaozle
◦ Antiprotozoal :-chloroquine, metronidazole

Spectrum of activity
◦ Broad spectrum: tetracyclines, chloramphenicol
◦ Narrow spectrum: penicillin, streptomycin
Based on mechanism of action
◦ Inhibit cell wall synthesis:
 penicillin, vancomycin, cephalosporins, bacitracin
◦ Affect cell membrane function:
 amphotericin B, nystatin, polymixin
◦ Inhibits protein synthesis:
 chloramphenicol, erythromycins
◦ Inhibit DNA gyrase:
 fluoroquinilones
 ◦ Drugs that alter the protein synthesis , by misreading
mRNA :
 aminoglycosides, gentamycin
◦ Inhibits DNA synthesis:
 antiretroviral drugs(zidovudine), acyclovir
◦ Interferes with metabolism :
 sulfonamides,
◦ Interfres with DNA function :
 rifampicin , metronidazole
Based on action
◦ Bacteriostatic:- chloramphenicol, sulphoneamides,
clindamycin, erythromycin
◦ Bactericidal: penicillin, cephalosporins, aminoglycosides,
rifampicin
Based on chemical structure
◦ Beta lactam : penicilin, cephalosporins
◦ Quinolones: norfloxacin, ciprofloxacin,ofloxacin
◦ Sulphonamides: sulfadiazine, dapsone
◦ Tetracyclines:- oxytertracycline, doxytetracycline
◦ Aminoglycosides: streptomycin gentamycin
◦ Macrolides: azithromycin, erythromycin
◦ Nitrobenzene derivatives: chloramphenicol
◦ Diaminopyrimidines: trimethoprin, pyrimethamine
◦ Azole derivatives: miconazole, clotrimazole,
ketaconazole
◦ Polypeptide antibiotics: polymixin B, bacitracin, colistin
◦ Glyycopeptides: vancomycin, teicoplanin
◦ Nitroimidazoles: metronidazoles, tinidazole
◦ Nicotinic acid derivatives:- isoniazid, pyrazinamide,
ethionamide
◦ Polyene antibiotics: nystatin, amphotericin B
Beta Lactam Antibiotics: Penicillin
Group of antibiotics having beta lactam ring
Mechanism of action: inhibits cell wall
synthesis. Bacterial cell wall is synthesised of
peptidoglycan structure..Glycan chains cross
linked by peptides. The glycan chains ( N-acetyl
-muramic acid and N acetyl glucosamine) are
cross linked by transpeptidases. Penicillin inhibits
transpeptidase , thus cross linking does not
occur results in formation of cell wall deficient
bacterial forms – leads to bacterial lysis.
Classification
◦ Natural penicillin: penicillin G, benzathine
penicillin
◦ Semisynthetic penicillins:
 Acid resistant penicillin: penicillin V( phenoxypenicillin)
 Penicillinase resistant penicillins: methicillin, cloxacillin
◦ Synthetic penicillins
 Aminipenicillin: ampicillin, amoxicillin
 Carboxypenicillins: carbenicillin, ticarcillin
 Ureidopenicillins: piperacillin, mezlocillin
Beta lactamse inhibitors : clavulanic acid, sublactam
PENCILLIN -G
Benzyl penicillin
Narrow spectrum antibiotics
Acts against primarily to gram positive bacteria
, and few gram negative bacteria
◦ Eg: streptococci, staph.aureus, clostridia,
cornybacterium , bacillus anthracis,- are sensitive
◦ Nisseria gonorrhoeae, nisseria meningitis are midly
sensitive
◦ Mycobacterium tuberculosis, chlamydiae, protozoa,
fungi , viruses- are non sensitive to penicillin G
Penicillinase:- inactivate the penicillin by opening the beta
lactam ring.

Pharmacokinetics:
◦ Penicillin is acid liable , hence destroyed by gastric acid.
◦ IV/IM route of administration
◦ Rapid absorption in IM ( 30mins)
◦ Metabolized in liver and readily excreted in urine
◦ Poorly crosses BBB

Preparations
◦ Sodium penicillin G: 0.5-5MU im/iv , 6-12 hourly
◦ Procaine penicillinG :- inj.0.5-1MU in IM 12-24hourly
◦ Benzathine penicillin G:- 0.6-2.4MU in IM every 2-3 weeks
(chemoprophylaxitic)
Therapeutic uses
◦ Pneumococcal infection: pneumonia, meningitis
◦ Streptococcal infection: otitis media, pharyngitis,
rheumatic fever
◦ Meningococal meningitis
◦ Syphillis
◦ Diptheria
◦ Tetanus, gas gangrene
◦ Rat bite fever, anthrax, leptosporosis
◦ Anaerobic Periodontal infections
Prophylatic uses: Rheumatic fever 1.2million
units once a month
Adverse effects
◦ skin rashes
◦ Utricaria
◦ Fever
◦ Dermatitis,
◦ Bronchospasm,
◦ Angioedema,
◦ Joint pains,
◦ Anaphylatic shock
Phenoxypenicillin ( penicillin V)
Semi synthetic penicillin
Acid stable : hence used in oral
administration
T ½ -30-60 min
Dose: 250-500mgin adults, 60mg in infants,
125-250 mg in children- orally
Used in staphylococcal infections :
pharyngitis, sinusitis, minor n=pneumococal
infections , prophylactic in rheumatic fever
Ampicillin
 More sensitive to all organisms sensitive to
penicillin G and gram negative organisms
( H.influenzae, salmonella ,shigella, Ecoli)
Administrated in oral route/IV/IM
Absorption is incomplete but adequate
Food interferes with absorption
Excreted partly in bile and kidney
Dosage:- 0.5-2g oral/iv/im TID, 25-50mg
/kg/day in children
Uses:
◦ Urinary tract infections
◦ Respiratory infections’meningitis
◦ Gonorrhorea
◦ Bacillary dysentery
◦ Typhoid fever
◦ Subacute bacterial endocarditis
◦ Septicemias
 Adverse effects: diarrhoea, skin rashes ,
hypersentivity reactions
Contraindicated : hypersentivity to PnG,
AMOXICILLIN
Most commonly used antibiotic
Similar to ampicillin in all aspects
Oral absorption is better , high plasma
concentration , more sustained action
Less active against shigella , and
H.influenzae
Dosage: - 250-500mg cap , 125mg/5ml
dry syrup, 250/500mg in injection IV/IM
Beta lactamase inhibitors
Clavulanic acid and sublactam :- binds to
beta lactamase
In combination with beta lactum
antibiotics
Cephalosporins
Cephalosporins
Semisynthetic antibiotic sysnthesied from
cephalosporin C, obtained from fungus
cephalosporium
Contains beta lactam ring fused to
dihydrothiazine ring
MECHANISM OF ACTION
 Peptidoglycan layer is important for cell
wall structural integrity
 The final step in synthesis of
petidoglycan(Transpeptidation) is
fascillitated by transpeptidases(pencillin
binding proteins)
 Cephalosporins competitively inhibit PBP
and disrupt synthesis of peptidoglycan
 These are bactericidal agents
Classification of cephalosporin
Firstgeneration: - cephalexin, cephradine,
cefadroxil

Second generation: - cefuroxime, cefoxitin,

cefaclor, cefuroxime axetil

Third generation: -cefotaxime, ceftizoxime,

ceftriaxone, cefoperazone, cefixime,

Fourth generation:- cefepime, cefpirome

pharmacokinetics
Except 1st and some of 2nd generation,all cephalosporins
are adminstered parentrally
Well distributed in body fluids
 Crosses placenta and secreted in breast milk.
 Therapeutic levels in CSF are achieved only with 3 rd
generation cephalosporins
 20-30% bound to plasma proteins
 80-90% excreted unchanged in urine
 Elimination occurs through tubular secretion/glomerular
filtration
 Cefoperazone and ceftriaxone are excreted through bile
(can be administered in renal insufficiency)
First generation
Drug
◦ Cefadroxil Cefazolin Cephalexin Cephradine
Spectrum
◦ Active against gram positive Cocci: strep.pneumonia,
S.pyogenes
◦ Moderately active against a few gram negativebacillic
: E.coli,P.mirabilis,K.pneumonia
◦ No activity against: Enterococci , B.fragilis
THERAPEUTIC USES
 Pharyngitis
 Tonsilitis
 Otitis
 Pneumonia
 UTI
 Skin infections
 Bone infections (cefazolin)
 Surgical prophylaxis (cefazolin is drug of
choice )
dosage

Cefadroxil Oral 500mg-1g (bid)

 Cefazolin parentral 0.25g/8hour ,
1g/6hrs
Cephalexin Oral 250mg-500mg/6houly,
25-100mg/kg/day in children
Cephradine Oral :-250mg-500mg/6hrs,
parental :- 0.5g-1g in IV/ IM
Second generation
Drugs :-Cefaclor Cefuroxime Cefoxitin
 spectrum:-Streptococcus pneumonia
Strep.pyogens N.Gonorrhoeae E.Coli
Pneumonia H.influenzae Proteus mirabilis
Dosage
◦ Cefaclor 250-500 mg/8 hour
◦ Cefuroxime 750mg-1.5 G/8hour
◦ Cefoxitin 1-2 G /6-8 hour
THERAPEUTIC USES
 Upper RTI (weaker effect)
 Pneumonia
 UTI
 Skin infections
 Bone infections
Gonorrhea
 Surgical prophylaxis(cefuroxime 1.5 G 1hour
prior )
 Meningitis (cefuroxime ; but less effective than
3rd generation )
Third generation
Drugs: Cefotaxime Ceftriaxone Ceftazidime
Spectrum
◦ Inferior activity to gram + cocci Enhanced
activity against gram –ve organism Including
N.Gonorrhea Enterobacter E.Coli K.Pneumonia
And Pseudomonas aeruginosa
• dosage
• Cefotaxime 1-2 G 6-12 hourly in IV/IM
◦ Ceftriaxone 1-4 G/24 hours
◦ Ceftazidime 1-2 G 8-12 hourly
THERAPEUTIC USES
 Gonorrhea(single dose of ceftriaxone;1st
line drug)
 Meningitis ( good penetration in CSF)
 Sepsis
 Typhoid (4G ceftriaxone/day for 2 days,
then 2G/day for 2 days)
 Surgical prophylaxis
 UTI
 Intra-abdominal infections
Forth generation
More balanced spectra With greater
resistance to beta lactamases. Modest
activity against anaerobes
 drugs : Cefipime Cefpirome
Upper RTI , Pneumonia , UTI ,Skin
infections Intra abdominal infections ,
Febrile neutropenia.,septicemia,
bacteraemia
Cefipime 1-2 g(bid ) iv , 8-12 hourly
Adverse effects
Pain after iminjection ,
thromphophlebotos
Diarrhoea
Hypersensitivity reaction:- rashes,
anaphylaxis angioedema asthma, utricaria
Nephrotoxicity
Neutropenia, thrombocytopenia
Bleeding
Aminoglycosides
Aminoglycosides
Aminoglycosides are a group of
bactericidal antibiotics, which act by
inhibiting bacterial protein synthesis.
Structurally related amino sugars attached
by glycosidic linkages
Mechanism of action
Interfereswith bacterial protein synthesis
by binding to the 30S ribosomal subunit.
 Rapidly bactericidal.
classification
Aminoglycosides
◦ Mycin :- Streptomycin Kanamycin Neomycin
Hygromycin B Spectinomycin Paromomycin

◦ Micin :-Amikacin Gentamicin Verdamicin

Astromicin
Pharmacokinetics
 Polar compounds
 Not absorbed orally
 Given intramuscularly or intravenously for
systemic effects
 Limited tissue penetration
 Do not readily cross the blood-brain barrier
 Plasma levels are affected by changes in renal
function
 Excretion is directly proportional to creatinine
clearance
Therapeutic uses
Gram –ve bacillary infection – septicaemia, pelvic &
abdominal sepsis
 Bacterial endocarditis – enterococcal, streptococcal
or staphylococcal injection of heart valves
 Pneumonias, Tuberculosis
 Plague, Brucellosis
 Topical – Neomycin, Framycetin.
 Infections of conjunctiva or external ear
 To sterilize the bowel of patients who receive
immunosuppressive therapy, before surgery & in
hepatic coma
Adverse effects
Nephrotoxicity
Otoxicity
Neromuscular blockade (reduces Ach
release)
Hypersensitivity reactions
GI disturbances.
Dosage
Streptomycin:-
◦ 0.75-1g in im 7-10days
◦ 0.75-1g in im , OD or twice weekly for 30-60
days in TB
• Gentamicin :-20-240mg in im/iv, 0.3%
drops, 0.1% skin creams
• Amikacin: 100-500mg in im/iv(2ml
ampoule)
• Neomycin:-0.25-1g QID orally, 0.3-0.5%
topically
TETRACYCLINES
TETRACYCLINES
Tetracylines are group of broad spectrum
antibiotics compounds that having common
four cyclic ring structure
Gram-positive and gram-negative cocci -
S.pneumoniae,N.gonorrhoeae
Gram-negative bacilli -V.cholerae, H.
influenzae
Gram-positive bacilli- B.anthracis, Listeria
mycoplasma, Rickettsiae
CLASSIFICATION OF
TETRACYCLINES

Short Acting(t1/2= 6-12 hrs) : -

◦ Tetracycline
◦ Oxytetracycline
Intermediate Acting(t1/2= 16-18 hrs)
◦ Demeclocycline
◦ Methacycline
 Long Acting(t1/2= 18-24hrs) :-
◦ doxycycline
◦ Minocycline
Mechanism of action
Tetracyclines

actively taken up by susceptible bacteria

bind reversibly to 30s ribosomal subunit

Prevent binding of aminoacyl tRNA to mRNA-

ribosome complex

Prevent the addition of amino acid to the growing

peptide chain

Inhibit bacteria protein synthesis (Bacteriostatic)

drug Route of absorption Half life dosage
administration

Chlortetracycline, oral incomplete 6-12 hrs 250-500mg

tetracyclines, QID
oxydetracyclines

Demeclocycline, oral Partial 16-18 300-500 mg BD

methacycline

Doxyciline, oral high 18-24 100mg-BD or

minocycline OD
Therapeutic uses
Lyme disease: caused by a Spirochete
 Granuloma inguinale
 Acne: Low doses of tetracyclines are used
 Malaria
 Amoebiasis
 Syndrome of inappropriate ADH secretion
 Leprosy
Chlamydial infections:-
◦ Lymphogranuloma venereum, Psittacosis
 Cholera : fluid and electrolyte replacement.
 Brucellosis
 Plague: Doxycycline is highly effective.
 Anthrax and leptospirosis
Rickettsial infections:
◦ Epidemic typhus,
◦ Rocky mountain spotted fever, scrub typhus,
rickettsial pox and Q fever.
• Mycoplasma pneumoniae infections
Adverse effects
Gastrointestinal:
◦ GI irritation manifestated as nausea, vomiting,
epigastric distress, abdominal discomfort and
diarrhoea.
Phototoxicity:
◦ it is particularly seen with demeclocycline and
doxycycline.
 Hepatotoxicity:
◦ more likely to occur in pregnantwomen.
Renal toxicity:
◦ demeclocycline may produce nephrogenic diabetes
insipidus.
Effects on bones and teeth:
◦ permanent brownish discolouration of deciduous teeth
and affect linear growth of bones.
CNS : May cause increased intracranial pressure
(pseudotumour cerebri) in infants.
 Hypersensitivity reactions:
◦ skin rashes, fever, urticaria, exfoliative dematitis, etc.
Superinfection:
◦ causes alteration of the gut flora, pseudomembranous
colitis, diarrhoea, fever, abdominal pain and stool
mixed with blood and mucus
Interaction
Tetracyclines should not be used during
pregnancy, lactation and in children.
 Should be avoided in patients on
diuretics.
 Do not mix injectable teracyclines with
pencillin inactivation occur
 Do not inject tetracycline i.m or
intrathecally.
 Quinolones
and
Fluroquinolones
Quinolones and Fluroquinolones
Quinolones: Nalidixic acid
Inhibits DNA gyrase enzyme and
interferes with the replication of Bacterial
DNA.
Bacteriostatic effect
Fluroquinolones are synthetic derivatives
of quinolones. These are fluorinated
analogues of nalidixic acid .these are
bactericidal in action
MOA :
◦ inhibits bacterial DNA synthesis , by
inhibiting DNA gyrase- gram negative
bacteria
◦ blocks DNA replication –inhibition of
topoisomerase IV – prevents seperation of
DNA – in gram positive bacteria
Classification
1st generation
◦ nalidixic acid
◦ cinoxacin
Gram- but not Pseudomonas species
2nd generation
◦ Norfloxacin
◦ ciprofloxacin
◦ enoxacin
◦ ofloxacin
Gram- (including Pseudomonas species), some
Gram+ (S. aureus) and some atypicals
3rd generation
◦ levofloxacin
◦ moxifloxacin
◦ Gemifloxacin
Gram- (including Pseudomonas species), some
Gram+ (S. aureus) on with extended Gram+ and
atypical coverage
4th generation
◦ trovafloxacin :- Gram- (including Pseudomonas
species), some Gram+ (S. aureus) on with extended
Gram+ and atypical coverage with broad anaerobic
coverage
 Pharmacokinetics
DRUG ROUTE BIOAVAILIB T1/2 DOSAGE
ILITY
NORFLOXACIN ORAL, 35-45% 4-6hrs 200-800mg , 3mg/ml
topical drops
LEVOFLOXACIN ORAL , IV, 100 8 hrs 500mg OD,
TOPICAL 500mg/100ml in iv

OFLOXACIN ORAL , IV, 85-95 5-8hrs 100-400mg orally,

TOPICAL 200mg/100ml in Iv
infusion
CIPROFLOXACIN ORAL , IV, 60-80 3-5hrs 500 -750 mg tab,
TOPICAL 500mg /100ml in iv
infusion ,
MOXIFLOXACIN ORAL , 90% 12hrs 400mg OD
IV,TOPICAL
Uses
Urinary tract infections
Bacterial diarrhoea
Typhoid fever
Gonococcal infection
MDR tuberculosis
Mycobacterial infections
Respiratory infections
Conjunctivitis
Adverse Effects
GI disturbance : nausea , vomitting ,
abdominal discomfort
Headache, dizziness insomnia, confusion,
hallucinations , convulsions
Hypersensitivity reactions
Tenosynovitis, tendon and cartilage
damage
Contraindicated in pregancy
Chloramphenicol
Chloramphenicol
Broad spectrum antibiotics obtained from
streptomyces venezuelae
Chemically contains nitrobenzene ring
MOA;
◦ Binds reversibly to 50 s ribosome subunit-
prevents formation of peptide bond- inhibit
protein synthesis
◦ At high doses inhibits mammaian protein
synthesis
Bacteriostatic in action
Spectrum:- gram positive , gram negative
bacteria , and rickettsiae, chlamydia,
mycoplasm, spirochetes,
Pharmacokinetics :-
◦ administrated orally, parentrally, topically
◦ Rapidly absorbed in gut
◦ Activated by pancreatic lipases, metabolised in
liver by glucuronide conjugation reaction
◦ Excreted in urine, breast milk
◦ Crosses BBB and placental barries
DOSAGE :
◦ 250-500mg capsules /6 hourly,
◦ 25-50mg/kg/day
◦ 1% eye oinments,0.5% drops
◦ Chloramphenicol palmitate: 125mg/5ml oral suspension

USES
◦ Typhoid fever
◦ Bacterial meningitis
◦ Anaerobic infections ;-abscesses
◦ Rickettsial infection
◦ Eye and ear infections
◦ brucellosis
Adverse effects
Hypersentivity reactions : skin rashes ,
angioedema, drug fever
Bone marrow supression
Nausea vomitting diarrhoea
Teratogenic effect – gray baby syndrome
Macrolides
Erythromycin – natural macrolide
obtained from streptomyces erythreus
Azithromycin, clarithromycin ,
roxithromycin, are semisynthetic
derivatives of erythromycin
MOA: inhibits protein synthesis , by
binding to 50 S ribosomal subunit
Bacteriostatic in action – but bactericidal
at high doses
Erythromycin
Natural macrolides
Short acting -6hrs
Acid labile- enteric coated tablets
Narrow spectrum
Incomplete absorption, metabolised in
liver, excreted in urine
Dosage :250-500mg-orally QID
Azithromycin
Semisynthetic
Long acting
Administrated orally , acid stable , food
interacts with food absorption,
Expanded spectrum antibiotics
Dosage :- 500mg OD