**Four Powerhouses Against Bacteria:** These antibiotics are warriors against a wide range of bacteria (broad-spectrum) but work in unique ways: * **Tetracyclines (e.g., Doxycycline):** These classics inhibit protein synthesis by binding to a bacterial ribosome subunit, halting growth. They're known for being inexpensive and effective against many common infections. * **Macrolides (e.g., Azithromycin):** Another broad-spectrum group, macrolides also block protein synthesis but at a different ribosomal site. They're popular for respiratory infections and offer convenient dosing options like single-dose packs. * **Chloramphenicol:** This powerful broad-spectrum antibiotic disrupts protein synthesis too. However, due to rare but serious side effects, it's reserved for severe infections where other options fail. * **Clindamycin:** This lincomycin antibiotic works differently, inhibiting protein chain elongation. It's useful against some bacteria resistant to other antibiotics and for treating serious infections like bone infections. **Remember:** * These are just highlights. Each drug has its own specifics regarding spectrum, strengths, and side effects. * Always consult a healthcare professional for diagnosis and antibiotic selection.

1. Tetracyclines and
Macrolides Antibiotics
B.Pharm 6th semester

2. Introduction to Tetracyclines:
Definition and historical background: Tetracyclines are a class of antibiotics
derived from Streptomyces bacteria. They were first discovered in the 1940s and
have since become widely used in medicine.
Classification and structure: Tetracyclines are classified based on their chemical
structure into various subgroups, including tetracycline, doxycycline, minocycline,
and others. They share a common core structure and belong to the broader group
of polyketides.
Mechanism of Action:
Inhibition of bacterial protein synthesis: Tetracyclines inhibit protein synthesis in
bacteria by binding to the 30S ribosomal subunit, thereby preventing the attachment
of aminoacyl-tRNA to the mRNA-ribosome complex.
Binding to the 30S ribosomal subunit: Tetracyclines bind reversibly to the 30S
ribosomal subunit of bacteria, interfering with the elongation of the polypeptide
chain during protein synthesis.

3. MOA of TETRACYCLINES

4. 1.Spectrum of Activity:
1. Broad-spectrum antibiotic coverage: Tetracyclines exhibit broad-spectrum
activity against a wide range of bacteria, including both Gram-positive and Gram-
negative species.
2. Effective against both Gram-positive and Gram-negative bacteria:
Tetracyclines are effective against many bacterial pathogens, including
Staphylococcus aureus, Streptococcus pneumoniae, Escherichia coli, and
Chlamydia trachomatis.
2.Indications for Use:
1. Treatment of various bacterial infections: Tetracyclines are used to treat a
variety of bacterial infections, including respiratory tract infections, urinary tract
infections, and skin infections.
2. Specific diseases targeted: Tetracyclines are also used to treat specific diseases
such as acne vulgaris, Lyme disease, and sexually transmitted infections like
chlamydia and gonorrhea.

5. Stereochemistry of
Tetracyclines
Carbon atoms 4, 4a, 5,
5a, 6, and 12a are
potentially chiral,
depending on
substitution
Classifications
Of Tetracyclines

6. Tetracyclines Dosage
Forms

7. Tetracyclic Nucleus: The core structure of tetracyclines is a four-ring system where each ring is six-
membered. This tetracyclic backbone is crucial for antibacterial activity1.
Ring A Modifications:
C-1 and C-3: These positions are involved in keto-enol tautomerism. Modifications here usually result
in a loss of antibacterial activity1.
C-2: The carboxamide moiety at this position is important. Large substitutions can disrupt the keto-
enol equilibrium and reduce activity1.
C-4: Typically has a dimethyl-amino group. Altering this group can lead to a loss of activity1.
Ring B and C: Changes in these rings are tolerated as long as the keto-enol systems remain intact and
conjugated with the phenolic D-ring1.
Ring D: Needs to be aromatic, and its phenolic nature is imperative for activity1.
Other Positions:
C-4a: The α-hydrogen here is necessary for antibacterial activity1.
C-5 and C-5a: Alkylation at C-5 usually leads to a loss of activity. However, oxytetracycline, with a
hydroxyl group at C-5, is an exception and is quite potent1

8. Adverse Effects:
1. Common side effects: Common side effects
of tetracyclines include gastrointestinal
disturbances (e.g., nausea, vomiting, diarrhea),
photosensitivity, and rash.
2. Rare but serious adverse reactions: Rare
but serious adverse reactions include
hepatotoxicity, nephrotoxicity, and potentially
life-threatening allergic reactions.

9. 1.Drug Interactions:
1. Interaction with other medications: Tetracyclines may interact with other
medications, such as antacids, dairy products, and certain vitamins, reducing their
absorption or efficacy.
2. Importance of avoiding concomitant use with certain drugs: Concomitant use
of tetracyclines with drugs like oral contraceptives or anticoagulants may reduce
their effectiveness, necessitating caution and potential dosage adjustments.
Contraindications

10. Clinical Considerations:
•Dosing regimens and administration routes: Tetracyclines are typically administered
orally, although intravenous formulations are available for certain indications. Dosing
regimens vary depending on the specific tetracycline and the type and severity of
infection.
•Monitoring for therapeutic efficacy and adverse effects during treatment: Patients
should be monitored for both therapeutic efficacy (resolution of infection) and adverse
effects (e.g., liver and kidney function tests, monitoring for signs of superinfection).

11. Pharmacokinetics:
1. Absorption, distribution, metabolism, and
excretion: Tetracyclines are well-absorbed orally
and widely distributed in body tissues. They
undergo hepatic metabolism and are primarily
excreted through the kidneys.
2. Factors affecting absorption and
bioavailability: Absorption of tetracyclines can be
affected by food, calcium-containing products, and
certain medications. They have variable
bioavailability and may require dose adjustments
in patients with renal impairment.

12. Macrolide antibiotics

13. Structure of Macrolides
Antibiotics

16. MOA Of Macrolides antibiotics

19. Chloramphenicol
1. Chloramphenicol is a broad-spectrum antibiotic first discovered in 1947, prized for its efficacy against
various bacterial infections.
2. It inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit, making it a bacteriostatic
agent.
3. Despite its effectiveness, chloramphenicol carries risks of serious adverse effects, including aplastic
anemia, limiting its use to specific cases.
4. It remains a vital antibiotic in treating typhoid fever, bacterial meningitis, and certain other infections,
especially in areas with limited antibiotic options.
5. Chloramphenicol resistance has emerged due to widespread use and misuse, prompting caution in its
administration to prevent further resistance development.
6. Continuous surveillance and prudent use strategies are essential to preserve chloramphenicol's utility
while minimizing the risk of adverse effects and antibiotic resistance.

20. Structure of
Chloramphenicol
MOA

24. Synthesis of Chloramphenicol

25. Uses Of Chloramphenicol

26. Clindamycin
Clindamycin is an older antibiotic that is used to treat
bacterial infections including pneumonia, strep throat,
osteomyelitis, and endocarditis. It was first synthesized in
1966 by Barney J. Magerlein*, Robert D.

27. 1. Chloramphenicol exhibits a narrow spectrum targeting anaerobic bacteria,
gram-positive cocci and bacilli, and select gram-negative bacilli.
2. Clindamycin, while related, displays activity against protozoans, with off-
label applications in treating toxoplasmosis, malaria, and babesiosis.
• Good G-I absorption
• Does Not Cross BBB
• Increases Bone Penetration

29. Brand Names Medicines
Of Clindamycin

30. Thank you

31. References:-
Ruiz NM, Rámirez-Ronda CH. Tetracyclines, macrolides, lincosamides & chloramphenicol. Bol Asoc
Med P R. 1990 Jan;82(1):8-17. PMID: 2180420.
Smilack JD, Wilson WR, Cockerill FR 3rd. Tetracyclines, chloramphenicol, erythromycin,
clindamycin, and metronidazole. Mayo Clin Proc. 1991 Dec;66(12):1270-80. doi: 10.1016/s0025-
6196(12)62479-3. PMID: 1749296.
https://www.slideshare.net/slideshow/tetracyclines-aminoglycosides-chloramphenicol-macrolides/103702471
Scholar, Eric M, and William B Pratt, 'Bacteriostatic Inhibitors of Protein Synthesis:
Chloramphenicol, Macrolides, Clindamycin, Spectinomycin, Tetracyclines and Streptogramins', The
Antimicrobial Drugs (New York, NY, 2000; online edn, Oxford Academic, 31 Oct. 2023),
https://doi.org/10.1093/oso/9780195125283.003.0006, accessed 28 Apr. 2024.