Presentation about History, Resistance, Mechanism of Action, Mode of Action, Types, Classification, Therapeutic uses, Adverse effects, Contraindication, Doses of two broad classes of Antibiotics- Tetracyclines and Quinolones

1. Introduction To Tetracyclines And
Quinolones
Prepared By:
Tareq Tareq,
B.Pharm Student,
International Islamic University Chittagong,
Bangladesh.

2. Tetracyclines are a group of broad-
spectrum antibiotics
They are natural product derived from
Streptomyces sp
Tetracyclines are so named for their four
(tetra) hydrocarbon rings

3. The general usefulness of Tetracyclines
has been reduced with the onset of
antibiotic resistance. Despite this, they
remain the treatment of choice for some
specific indications

4. - Source: Streptomyces grasius, a soil
organism
- Spectrum: Broad spectrum of activity i.e.,
active against both gm(+) and gm(-)
bacteria
- Mode of action: Bacteriostatic in nature
- Mechanism of ACTION: Protein synthesis
inhibition

5. The development of the tetracycline
antibiotics was the result of a systemic
screening of soil specimens collected from
many parts of the world for antibiotic-
producing microorganisms. The first of
these compounds chlortetracycline was
introduced in 1948 followed by
oxytetracycline and tetracycline in 1950
and 1952 respectively.

6. Tetracyclines are of three types:
1. Natural Tetracycline: (Short acting)
- Chlortetracycline (S.aureofaciens )
- Oxytetracycline (S. rimosus )
- Demeclocycline (S. aureofaciens )

7. 2. Semisynthetic Tetracycline: (long acting)
-Doxycyclicline
- Methecycline
- Minocycline
3. Both natural and semisynthetic:
-Tetracycline :
Natural from S. grasius
Semisynthetic from Chlortetracycline

8. Tetracycline
Enters into bacteria by
-passive diffusion
-Active transport
Binds reversibly to receptor on the 30s ribosomal subunit
Block the binding of charged aminoacyl tRNA to the ‘A’ site of the ribosome
mRNA complex
(-) addition of aminoacid in growing peptide chain
(-) Protein synthesis
(-) Bacterial growth & multiplication
Note: At high conc. they can inhibit protein synthesis of mammal cell

9. >>The drug is not actively transported into
the cell
>>The drug leaves the cell so rapidly that
the required conc. Of the drug is not
maintained
>>Enzymatic inactivation of tetracycline
>>Production of protein that interferes
binding of tetracycline to ribosome

10.  Drug of first choice
●Rickettsial infection
-Rocky mountain spotted fever
-Typhus
-Rickettsialpox
●Mycoplasma infection
-Mycoplasma pneumonia
●Borrelia infection
-Lyme disease
-Relapsing fever
●Vibrio infection
-Cholera
●Plague, brucellois ( with aminoglycoside)

11.  Drug of second choice
●Diarrhoea
●Dysentery
●Mixed bacterial infection e.g. respiratory tract infection
●Acne
●SIADH (Syndrome of inappropriate ADH secretion)
●Leptospiral infection
●Tularemia (An acute plague like infectious disease
Caused by Francisella tularensis transmitted to the human by
the bite of an infected tick or other blood sucking insect
●Weils disease

12.  A) Organ/ system toxicity
●GIT
-Nausea
-Vomiting
-Diarrhoea
-Alteration of intestinal flora
● Hepatotoxicity
●Nephrotoxicity (due to inhibition of protein synthesis)
-Renal tubular acidosis
-Nephrogenic diabetes insipidus
-Fanconis syndrome
● Bony stucture and teeth:
-Discoloration and hypoplasia of teeth
●Vestibular toxicity:
-Dizziness
-Vertigo

13.  B) Super infection:
-Candida or resistant staphylococci
 C) Hypersensitivity:
-Urticaria
-Anaphylaxix
-Angioedema

14. ●Pregnancy and lactation
●Young children ( up to 8 years)
●Renal failure
●History of hypersensitivity

15. ● Indications:
-treatment of Spirochaetal infection.
-treatment of Non-Specific-Urethritis.
-treatment of Clostridial wound infection and Anthrax.
●Contraindication:
-Renal impairment
-Pregnancy & breast feeding
-SLE (Systemic lupus eryyhematosus)
●Side effects:
-Local irritation after intramuscular injection.
-Gastrointestinal:-anorexia, nausea, vomiting.
-Renal toxicity.
-Hypersensitivity reactions: Urticaria.
-Blood: Hemolytic anemia, thrombocytopenia, neutropenia

16. ●Dose:
250-500 mg every 6 hours
●Market preparations: ( Bangladesh)
-Renamycin® (Renata)
-Oxecylin® (ACME)
-Oxycap® (Globe Pharma)

17. ●Indications:
-Treatment of chronic adult periodontitis.
-Chronic prostatitis
-Brucellosis
●Contraindication:
-Renal impairment
-Pregnancy & breast feeding
-SLE (Systemic lupus eryyhematosus)
●Side effects:
-Watery diarrhea
-Bloody stools
-photosensitivity, rash

18. ●Dose:
-By mouth 200 mg on first day, then 100 mg daily
-In severe infections 200 mg daily for 4 days
●Market preparations:
-Doxin (Opsoni)
-Doxy-A (ACME)
-Servidoxyne (Novartis)

19. ●Indications:
-Tetracycline's primary use is for the treatment of acne
vulgaris and rosacea.
-It is also used to treat a very wide range of infections.
●Contraindication:
-Renal impairment
-Pregnancy & breast feeding
-SLE (Systemic lupus eryyhematosus)
●Side effects:
-Superinfection
-Enamel dysplasia
-Impairment in bone growth

20. ●Dose:
-By mouth 250 mg every 6 hours
-Increased in severe infections to 500 mg every 6-8 hours
●Market preparations:
-Jmycin (Jayson)
-Tetracycline (Opsonin)
-Tetracyn (Renata)
-Tetrax (Square)

21. The quinolones are family of synthetic
broad spectrum antibacterial drugs
Quinolones exert their antibacterial effect
by preventing bacterial DNA from
unwinding and duplicating
The majority of quinolones in clinical use
belong to the subset fluroquinolones

22. The first generation of quinolones began
with the introduction of nalidixic acid in
1962 for treatment of urinary tract
infections in humans. Nalidixic acid was
discovered by George Lesher and
coworkers in a distillate during an attempt
at chloroquine synthesis.

23. A) First generation:
●Non flurinated quinolone
●Narrow spectrum
-Nalidixic acid
B) Second generation:
● Flurinated quinolones, 6o times more active then nalidixic acid
●Broad spectrum
●Not effective against anaerobes and community acquired pneumonia
caused by Streptococcus pneumoniae
-Ciprofloxacin
-Enoxacin
-Lomefloxacin
-Acrosoxzacin
-Norfloxacin
-Ofloxacin

24. C) Third generation:
●Broad spectrum
●Effective against anaerobes and community acquired pneumonia
caused by Streptococcus pneumoniae
-Sparfloxacin
-Levofloxacin
D) Fourth generation:
●More effective against anaerobes and community acquired
pneumonia caused by Streptococcus pneumoniae
-Moxifloxacin
-Trovafloxacin

25. Mechanism of action:
-Inhibit bacterial DNA synthesis by
inhibiting DNA gyrase and topo-isomerase
IV resulting to rapid cell death
-Post antibiotic effect: lasts 1 to 2
hours, increases with increasing
concentration

26. Quinolone
Enter into cell via passive diffusion
(-) Rejoining of DNA
(-) Supercoiling of DNA
Cell death
Note: Quinolone (-) human DNA gyrase only at much
higher conc. i.e., 100-1000 µ gm/ml

27. ●Chromosomal:
-Alter target enzymes: DNA gyrase and
topoisomerase IV
-Decreased drug penetration:
Pseudomonas, E. coli
●Plasmid: seen in some K. pneumoniae and E.
coli
●Mutations in both target enzymes are needed
to produce significant resistance

28. ●Urinary tract infections
●Gastrointestinal infections
-Enteric fever
-Bacillary dysentery
-Septicaemia
●Respiratory tract infections (but not in
pneumococcal pneumonia
●Gynecological infection
●Intra-abdominal infection
●Severe systemic infection

29. -Tendon inflammation
-Arthralgia
-Myalgia
-Hypersensitivity reactions (sometimes
involving blood cells
-Photosensitivity
-Nausea, Vomiting

30. -Epilepsy
-myasthenia gravis
-Pregnant and lactating women
-Children

31. ●Indications:
-In complicated UTI
●Contraindication:
-Hypersensitivity to drug
-Porphyria
-Liver disease
-Renal impairment
●Side effects:
-Psychosis
-Cranial nerve palsy
-Metabolic acidosis

32. ●Dose:
By mouth 1g every 6hours for 7 days
●Market preparations:
-Naligram® (ACME)
-Nebactil® (Beximco)
-Utirex® (Opsonin)

33. ●Indications:
- Nosocomial pneumonia
- Intra-abdominal infections
-Uncomplicated/complicated UTI
-Anthrax exposure and prophylaxis
●Contraindications:
-Pregnant and lactating women
-myasthenia gravis
-Hypersensitivity
●Side effects:
-CNS toxicity
-GIT upset
-Hypersensitivity

34. ●Dose
By mouth,
-In RTI 250-500 mg every 12 hours
-In pseudomonal lower RTI 750 mg twice daily
-In UTI 250-500 mg twice daily
●Market preparations:
-Beuflox (Incepta)
-Cipro-A (ACME)
-Flontin (Renata)
-Neofloxin XR (Beximco)

35. ●Indications:
-Treatment of bronchitis due to H. inflenzae
-UTI
●Contraindications:
-Pregnant and lactating women
-myasthenia gravis
-Hypersensitivity
●Side effects:
-Phototoxicity
-CNS toxicity
-GIT upset
-Hypersensitivity

36. ●Dose:
400 mg once daily
●Market preparations:
-Lomeflox (Aristopharma)
-Mexio (Square)
-Namicin (Nipa)

37. ●Indications:
-UTI
-Lower RTI
-Gonorrhea
-Cervicitis
●Contraindications:
-Hepatic and renal impairment
-History of psychiatric illness
●Side effects:
-Hypersensitivity reactions (sometimes
involving blood cells)
-Photosensitivity
-Nausea, Vomiting

38. ●Dose:
By mouth,
-UTI: 200-400 mg daily in the morning. Increased
up to 400 mg twice daily for upper UTI
-Chronic prostatitis 200 mg twice daily for 28 days
-Lower RTI 400 mg daily in the morning
●Market preparations:
-Oflacin (Drug Intl.)
-Rutix (Square)

39. ●Indications:
-Chronic bronchitis and CAP
- Nosocomial pneumonia
-SSTIs
-Intra-abdominal infections
●Contraindications:
-Renal impairment
-Pregnant and lactating women
-Children
●Side effects:
-Asthenia
-Rarely tremor
-Anxiety
-Tachycardia
-Hypotension
-Hypoglycemia

40. ●Dose:
Oral,
-Acute sinusitis: 500mg daily for 10-14 days
- -Exacerbation of chronic bronchitis: 250-500 mg daily for 7-
10 days
- -Community acquired pneumonia: 500 mg once or twice
daily for 7-14 days
●Market preparations:
-Evo (Beximco)
-Exolev (Novartis)
-Levoking (Renata)
-Trevox (Square)

41. ●Indications:
-Chronic bronchitis
-Bacterial conjuctivitis
-Sinusitis
●Contraindications:
-Should be avoided in patients with existing QT prolongation
●side effects:
-CNS toxicity
-GIT upset
-Hypersensitivity

42. ●Dose:
Adult dose is 400 mg daily
●Market preparations:
-Maximox (Orion)
-Odycin (Beximco)
-Optimox (aristopharma)