The macrolides are a group of closely related

compounds characterized by a macrocyclic

lactone ring (usually containing 14 or 16 atoms)
to which deoxy sugars are attached. The
prototype drug, erythromycin, which consists of
two sugar moieties attached to a 14-atom lactone
ring, was obtained in 1952 from Streptomyces
erythreus . Clarithromycin and azithromycin
are semisynthetic derivatives of erythromycin.
Classification of Macrolides:
They are antibiotics and bacteriostatic in
nature.
Natural: Erythromycin
Semi-synthetic: Azithromycin,
Clarithromycin, Roxithromycin.

“Triple Therapy”:
PPI+Clarithromycin+Amoxicillin,--H pylorie
 Mechanism of action: They are protein
synthesis inhibitors.
 They are bacteriostatic in nature, inhibit protein

synthesis by binding reversibly to 50s ribosomal

subunit of sensitive microorganisms.
 It is believed that they inhibit the translocation

step wherein a newly synthesized peptidyl tRNA

molecule moves from the acceptor site on the
ribosome to the peptidyl (donor) site.
***It can be bactericidal at higher doses.
 Erythromycin Azithromycin

Nature 14 membered lactone 15 membered lactone

ring, natural antibiotic. ring, semi-synthetic
From streptomyces derivative of
erythreus. erythromycin.
Plasma half life 1.6 hrs (+_) >20 hrs. 11 – 14 hrs
for 500 mg capsule,
68 hrs for repeated
dose.
Bioavailability 30 – 65% at 250 mg 38% at 250 mg
(oral) depending on its capsule (oral)
bases
Plasma protein 70-80% ( more for 51%
binding estolate base: 96%)
Peak plasma 0.3 to 1.9 µg/ml, 04 hrs 0.4 µg/ml after 500
conc. after a single dose of mg oral dose.
500mg.
Dose: 250 -500 mg, 06 hourly 500 mg/day

Route of Oral tablet, Powder for Tablet, oral

administration: I/V suspension, powder
for I/V
Route of Biliary and renal Biliary and
Elimination: renal
It inhibits cytochrome P450
Drug Does not
enzymes. Increase
interaction: concentration of anticoagulants, inhibit hepatic
theophyline, methyl
enzymes.
prednisolone

Indications: It is not active against most It is very active

aerobic enteric gram ‘-’ bacilli, against gram ‘-’
organisms like, H
Mycoplasma pneumonia, influenza, M
Legionnaires’ disease, pneumoniae, N
Chlamydia infection, gonorrhoeae and
Diptheria, pertusis, M avium-
Indications: streptococcal infection, Intracellulare. It is
staphylococcal used in community
infection, Prophylaxis acquired pneumonia.
or prevention of recurrent Effective also
attack of rheumatic erythromycin sensetive
fever, skin infection. organisms.

Side effects: Abdominal discomfort, Headache,

arrhythmia, convulsion, palpitation, diarrhea,
Angiodema, cholst. Abdominal discomfort,
jaundice, rarely Hearing problem,
pancreatitis others same as
erythromycin.
Contra- Known hypersensitivity, It can cross placenta
indication liver disease, Myasthenia and reach the fetous,
gravis, Heart disease so pregnancy and
(arrhythmia), Pregnancy others are as
erythromycin.
 Ketolides are semisynthetic 14-membered-
ring macrolides, differing from
erythromycin by substitution of a 3-keto
group for the neutral sugar L-cladinose.

 Telithromycin is approved for limited

clinical use.
Tetracyclines
 These antibiotics are broad spectrum and
bacteriostatic in nature.

 Natural: Oxytetracycline, Chlortetracycline,

Demeclocycline.

 Semi-synthetic: Methacycline, Doxycycline, Minocycline,

Tetracycline (semi-synthetically) comes from
chlortetracycline. Tigecycline, a semi-synthetic derivative
of minocycline
Mechanism of action:
They inhibit bacterial protein synthesis at 30s
ribosomal subunit. They prevent access of
aminoacyl tRNA to the acceptor site on the
mRNA-ribosome complex. This prevents the
addition of amiono acids to the growing peptide
chain. The sensitive microorganisms have an
energy dependent active transport process, which
concentrates tetracyclines intracellularly.
 Therapeutic indications:
 1. Rickettsial infections: Typhus fever, Rocky-mountain
spotted fever, Q fever.
 2. Mycoplasma infection: mycoplasma pneumonia.
 3. Chlamydia infection: lymphogranuloma venerum,
Chlamydia pneumonia, psittacosis, Inclusion conjunctivitis,
Trachoma.
 4. In combination to eradicate Helicobacter Pylori.
 5. In combination to eradicate Entamoeba Histolytica
(amebiasis), and Plasmodium falciparum (malaria)
 6. Non-specific urethritis:
 7. Gonorrhoea, 8. Lyme disease.
 9. Bacillary infection: Brucellosis, Tularemia, Cholera,
Travellers diarrhea.
 10. Acne.
 11. Intestinal diseases.
 Adverse effects: 1. GIT: Epigastric pain and
distress, diarrhea and nausea.
 2. Hepatic toxicity: Jaundice
 3. Effects on Teeth: Brown discoloration of teeth
and enamel dysplasia (dental hypoplasia) till 08
years of children.
 5. Effects on bone: It forms tetracycline-ca++
orthophosphate complex, chelating Ca, inhibits
bone growth.
 6. Hypersensitivity reactions: Drug fever, skin rash.
 7. Renal Toxicity: Tetracyclines may aggravate uremia in
patients with renal disease by inhibiting protein synthesis
and provoking a catabolic effect. Doxycycline produces less
effect.
 8. Phototoxicity
 9. Vestibular reactions: Dizziness, Vertigo, Nausea
 Contra-indications: 1. Pregnancy, 2. Children
below 8 years, 3. Nursing mother, 4.
Hepatic/Liver diseases. 5. Kidney disease.
Properties Tetracycline/ Doxycycline
Oxytetracycline
Half life 6-12 hrs 16-18 hrs
Absorption 60-70 % (oral) 95% (oral)
Dose 250-500 mg/ 04 100-200 mg/ once
times daily or twice daily
Route Oral, parenteral, Oral and parenteral
Topical (eye)
Food Interfere Does not
absorption
Route of Renal, breast Renal, mainly through
excretion milk bile (feces)

Drug interactions Ca, Fe, antacids ↓ Barbiturate and

absorption of Phenytoin,
tetracyclines. Carbamazepine, chronic
alcohol ↓ half life from
16 to only 07 hrs.
 Nucleic acid synthesis inhibitors
-- Quinolones and
Fluoroquinolones
 Quinolones and Fluoroquinolones:

 The important quinolones are synthetic fluoronated

analogs of Nalidixic acid.

 Second Group: Ciprofloxacin, lomefloxacin,

levofloxacin, Ofloxacin, Pefloxacin.

 Third Group: Gatifloxacin, gemifloxacin,

moxifloxacin.
Mechanism of actions: They block bacterial DNA
synthesis by inhibiting bacterial topoisomerase II
(DNA Gyrase) and topoisomerase IV.

Inhibition of DNA gyrase prevents the relaxation of

positively supercoiled DNA that is required for
Normal transcription and replication.

Inhibition of topoisomerase IV interferes with

separation of replicated chromosomal DNA into the
respective daughter cells during cell division.
 Advantage of Fluorinated quinolones:
 1. Fluoroquinolones are 60 times potent than

quinolones.
 2. They become broad spectrum.
 3. Adverse effects are less.
 4. They become bactericidal.
 5.
Therapeutic indications:
UTI, Respiratory tract infection, Typhoid fever,
Soft Tissue infection, Joint infection, Gonorrhea,
Pneumonia caused by Chlamydia,
mycoplasma, legionella. Bacterial diarrhea
caused by Shigella and salmonella. Anthrax,
Septicemia, Prostatitis. Tuberculosis. Atypical
mycobacterial infections.
 Adverse Effects:
 1. GIT: nausea, GIT upset, epigastric pain.
 2. Hypersensitivity reactions:
 3. Neurotoxicity: Headache, dizziness, convulsions.
 4. May damage growing cartilage and produce

arthropathy.
 5. Tendinitis.
 6. long term use may cause nephrotoxicity and

convulsion.
 7. Hypoglycemia caused by gatifloxacin.
 Contraindications: 1. History of Epilepsy.
2. Children below 12 years. 3. Pregnancy 4. Kidney
disease.

 Pharmacokinetic data of Ciprofloxacin:

 Half life: 03-05 hrs, Bioavailability: 60-70% (oral), Dose: 500
mg/twice daily, Excretion: Renal and other routes also. Route
of administration: Oral and Parenteral. Drug interactions: It is
an enzyme inhibitor, increase the effect of warferin,
theophylline, sulphonylureas. Antacids and other cations
decrease absorption of ciprofloxacin.