A brief pharamcological overview about Macrolides, Fluoroquinolones and Broad spectrum antibiotics along with clinical application

1. MACROLIDES,
FLUOROQUINOLONES
AND BROAD SPECTRUM
ANTIBIOTICS

3. MACROLIDES

4. DRUGS
• Erythromycin
• Azithromycin
• Clarithromycin

5. MECHANISM OF ACTION
• Macrolides inhibit bacterial protein
synthesis.
• They bind to the 50S ribosomal subunit of
bacteria, preventing the translocation step in
protein synthesis.
• This leads to inhibition of protein elongation
and ultimately bacteriostatic or bactericidal
activity.

6. ACTIVITY AND CLINICAL USES
Macrolides are wide-spectrum antibiotics
• Gram-positive cocci (not MRSA)
• Atypical organisms (Chlamydia, Mycoplasma, and
Ureaplasma species)
• Legionella pneumophila
• Campylobacter jejuni
• Mycobacterium avium-intracellulare (MAC)
• H. pylori

7. INDICATIONS
• Respiratory tract infections: Community-
acquired pneumonia, acute exacerbations of
chronic bronchitis.
• Skin and soft tissue infections: Cellulitis,
erysipelas.
• Sexually transmitted infections: Chlamydia
trachomatis, Neisseria gonorrhoeae.

8. • Upper respiratory tract infections: Sinusitis,
pharyngitis.
• Pertussis (whooping cough).
• Prophylaxis for endocarditis in certain cases.
• Treatment of Helicobacter pylori infection in
combination with other drugs

9. SIDE EFFECTS
• Macrolides stimulate motilin receptors and
cause gastrointestinal distress
(erythromycin, azithromycin > clarithromycin)
• Macrolides cause reversible deafness at high
doses
• Increased QT interval

10. FLUOROQUINOLONES

11. DRUGS
• Ciprofloxacin
• Levofloxacin
• Moxifloxacin
• Norfloxacin
• Ofloxacin

12. MECHANISMS OF ACTION
• Quinolones are bactericidal
• interfere with DNA synthesis − Inhibit topoisomerase
II (DNA gyrase) and topoisomerase IV (responsible for
separation of replicated DNA during cell division)
• Broad spectrum

13. ACTIVITY AND CLINICAL USES
• Urinary tract infections (UTIs), particularly when
resistant to cotrimoxazole
• Sexually transmitted diseases (STDs)/pelvic
inflammatory diseases (PIDs): chlamydia, gonorrhoea
• Skin, soft tissue, and bone infections by gram-negative
organisms
• Diarrhoea to Shigella, Salmonella, E. coli,
Campylobacter
• Drug-resistant pneumococci (levofloxacin)

14. PHARMACOKINETICS
• Iron, calcium limit their absorption
• Eliminated mainly by kidney by filtration and
active secretion (inhibited by probenecid)
• Reduce dose in renal dysfunction

15. SIDE EFFECTS
• Tendonitis, tendon rupture
• Phototoxicity, rashes
• CNS effects (insomnia, dizziness, headache)
• Contraindicated in pregnancy and in children
(inhibition of chondrogenesis)

16. TETRACYCLINES

17. MECHANISM OF ACTION
• Tetracyclines inhibit bacterial protein
synthesis.
• They bind reversibly to the 30S ribosomal
subunit, preventing the attachment of
aminoacyl-tRNA to the mRNA-ribosome
complex.
• This leads to inhibition of protein elongation.

18. ACTIVITY AND CLINICAL USES
• Bacteriostatic drugs, actively taken up by susceptible
bacteria
• Broad-spectrum antibiotics, with good activity versus
chlamydial and mycoplasmal species, H. pylori (GI
ulcers), Rickettsia, Borrelia burgdorferi, Brucella, Vibrio,
and Treponema

19. INDICATIONS
• Respiratory tract infections: Community-
acquired pneumonia, bronchitis.
• Skin and soft tissue infections: Acne,
cellulitis.
• Sexually transmitted infections: Chlamydia,
gonorrhea, syphilis.
• Tick-borne illnesses: Lyme disease,
ehrlichiosis.

20. • Rickettsial infections: Rocky Mountain
spotted fever, typhus.
• Helicobacter pylori eradication in peptic ulcer
disease.
• Mycoplasma pneumoniae infections.
• Adjunctive therapy for periodontal diseases

21. SPECIFIC DRUGS
• Doxycycline: more activity overall than
tetracycline HCl and has particular usefulness
in prostatitis because it reaches high levels in
prostatic fluid
• Minocycline: in saliva and tears at high
concentrations and used in the
meningococcal carrier state

22. • Tigecycline: used in complicated skin, soft
tissue, and intestinal infections due to
resistant gram + (MRSA, VREF), gram –, and
anaerobes

23. PHARMACOKINETICS
• Kidney for most (↓ dose in renal dysfunction)
• Liver for doxycycline
• Chelators: tetracyclines bind divalent cations
(Ca2+, Mg2+, Fe2+), which ↓ their absorption

24. CONTRAINDICATIONS
• Pregnancy: Tetracyclines can cross the
placenta and harm the developing fetus,
especially during the second half of
pregnancy.
• Severe hepatic impairment: Dose adjustments
may be necessary.
• Known hypersensitivity to tetracyclines

25. ADVERSE EFFECTS
• Gastrointestinal effects: Nausea, vomiting, diarrhea,
and abdominal discomfort are common.
• Photosensitivity: Increased sensitivity to sunlight,
leading to sunburns or exaggerated sunburn reactions
(demeclocycline, doxycycline)
• Tooth discoloration: Tetracyclines can bind to calcium
ions and deposit in developing teeth, resulting in
yellow-gray or brown discoloration.

26. Children under 8 years old: Tetracyclines can affect
tooth and bone development, leading to permanent
discoloration and enamel hypoplasia

27. • Effects on bone growth: Prolonged use in children can
inhibit bone growth and cause skeletal abnormalities.
• Candidiasis: Superinfection with Candida species may
occur due to disruption of the normal flora.
• Vestibular toxicity: Rarely, high doses of certain
tetracyclines can cause dizziness, vertigo, and other
vestibular symptoms (minocycline)

28. CHLORAMPHENICOL

29. MECHANISM OF ACTION
• Inhibits bacterial protein synthesis.
• It binds reversibly to the 50S ribosomal
subunit, preventing the peptidyl transferase
activity necessary for peptide bond formation.
• This leads to inhibition of protein elongation
and ultimately bacteriostatic activity.

30. ACTIVITY AND CLINICAL USES
• Broad spectrum of activity
• Currently a backup drug for infections due to
Salmonella typhi, B. fragilis, Rickettsia, and
possibly in bacterial meningitis

31. INDICATIONS
• Bacterial meningitis.
• Typhoid fever: alternative treatment for
Salmonella typhi infection, high rates of
multidrug-resistant strains.
• Anaerobic infections: Clostridium spp.
• Empiric therapy: In resource-limited
settings, chloramphenicol may be used
as a broad-spectrum empiric treatment.

32. PHARMACOKINETICS
• Orally effective, with good tissue distribution,
including CSF
• Metabolized by hepatic glucuronidation, and
dose reductions are needed in liver
dysfunction and in neonates
• Inhibition of cytochrome P450

33. CONTRAINDICATIONS
Chloramphenicol should be used with caution
and avoided in certain situations:
• Hypersensitivity: Known hypersensitivity
or previous serious adverse reactions to
chloramphenicol.
• Preexisting bone marrow suppression:
Patients with a history of blood
dyscrasias or bone marrow disorders.

34. • Pregnancy and breastfeeding: Use
should be carefully considered due to the
potential risks to the fetus or newborn.
• Neonates and infants : GRAY BABY
SYNDROME, a potentially fatal condition
characterized by abdominal distension,
cardiovascular collapse, and gray
discoloration of the skin.

36. SIDE EFFECTS
• Dose-dependent bone marrow suppression
common; aplastic anaemia rare (1 in 35,000)
• GI disturbances: Nausea, vomiting, and
diarrhea are common, especially with high
doses or prolonged use.
• Neurological effects: Rarely, chloramphenicol
may cause peripheral neuropathy and optic
neuritis.

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