This document discusses tetracycline antibiotics. It provides classifications of tetracyclines including their natural/semi-synthetic origins and duration of action. It describes the antibiotics' mechanism of action as reversible binding to the 30S ribosomal subunit, inhibiting protein synthesis. It also covers the antibiotics' spectrum of activity against gram-positive and gram-negative bacteria and atypical pathogens. The document provides dosages and formulations for various tetracycline antibiotics and notes common adverse effects like gastrointestinal issues. It discusses drug interactions and populations where tetracyclines should be used cautiously like children and pregnant/breastfeeding women.

2. 
1.Introduction
2.Classifications
3.Mechanism of action
4.Spectrum of activity
5.Dosages
6.Adverse reactions
7.Drug interactions
8.Use in Special Populations
9.Patient counselling
Objectives

3. 
 Tetracyclines is a group of antibiotics that include
Tetracycline ; it was discovered in 1948 , exhibited
activity against a wide range of microorganisms
including gram-positive and gram-negative bacteria,
Chlortetracycline was the first Tetracycline to be
identified. . Since then five additional tetracyclines
have been isolated or derived (oxytetracycline,
tetracycline, Demeclocycline, Doxycycline and
minocycline ).
1.Introduction

4.  Tetracyclines retain important roles in both human
and veterinary medicine.
 The favorable antimicrobial properties of these
agents and the absence of major adverse side effects
has led to their extensive use in the therapy of
human and animal infections but the emergence of
microbial resistance has limited their effectiveness.

5. 
 They are also inexpensive antibiotics, therefore have
been used extensively in the prophlylaxis and
therapy of human and animal infections also at
subtherapeutic levels in animal feed as growth
promoters.

6.  Doxycycline and minocycline are the most
frequently prescribed .
 The improved understanding of tetracycline
resistance mechanisms has provided opportunities
for the recent discovery of a new generation of
tetracyclines, the GLYCYLCYCLINES.

7. 
2.1 According to source:
 Naturally occurring
 Tetracycline
 Chlortetracycline
 Oxytetracycline
 Demeclocycline
 Semi-synthetic
 Doxycycline
 Lymecycline
 Meclocycline
 Methacycline
 Minocycline
 Rolitetracycline
2.Classifications

8. 2.2.According to duration of action:
 Short-acting (Half-life is 6-8 hrs)
 Tetracycline
 Chlortetracycline
 Oxytetracycline
 Intermediate-acting (Half-life is ~12 hrs)
 Demeclocycline
 Methacycline
 Long-acting (Half-life is 16 hrs or more)
 Doxycycline
 Minocycline
 Tigecycline
 Tigecycline may also be considered a tetracycline
antibiotic, though it is usually classified as a glycylcycline
antibiotic.

9. 
 tetracyclines bind reversibly to the 30S ribosomal
subunit at a position that blocks the binding of the
aminoacyl-tRNA to the acceptor site on the mRNA-
ribosome complex. Protein synthesis is ultimately
inhibited, leading to a bacteriostatic effect .
3.Mechanism of action

10. 
4.Spectrum of activity
 The antimicrobial activity of all the tetracyclines is
essentially the same although some differences in the
relative degree of activity against certain pathogens
do exist among the various agents.
 As an example, minocycline appears to be the most
active of the compounds due to its slight increase in
lipid solubility; Doxycycline follows closely behind.

11. 
 The tetracyclines are considered broad-spectrum
bacteriostatic antibiotics that are used to treat
infection caused by many aerobic gram-positive and
gram-negative bacteria. However, they also have
activity against many atypical pathogens.
 These drugs have little activity against fungi and
viruses .

12. 
 Against N. gonorrhoeae, the 2006 Gonococcal Isolate
Surveillance Project (GISP) report shows that 25.6 percent
of isolates collected in 2006 were resistant to Tetracycline,.
Therefore, use of tetracyclines for the treatment of N.
gonorrhoeae in the US is NOT recommended
by the CDC.

13. 
 Doxycycline is effective for patients with
nongonococcal urethritis caused by Chlamydia
trachomatis; however, recurrent urethritis in patients
previously treated with doxycycline may be the
result of tetracycline-resistant U. urealyticum.
Doxycycline is an alternative agent in the treatment
of genital Chlamydial infections [11].

15. 
Drug Usual Dosing Availability
Demeclocycline Adults: 150 mg four times
daily or 300 mg twice
Daily.
Gonorrhea patients sensitive
to penicillin: initial oral
dose of 600 mg followed by
300 mg every 12 hours
for four days to a total of 3 g
Pediatrics > 8 years: 7-13
mg/kg/day depending
on severity of disease, divided
into two to four doses, not to
exceed dosage of 600 mg
daily.
150, 300 mg tablets
5.Dosages

16. 
Drug Usual Dosing Availability
Doxycycline Adults: 100 mg twice daily for
most infections;
duration of therapy is typically
seven to 10 days,
but duration may depend on
severity of infection
Inhalational anthrax: 100 mg
twice daily for 60 days
Prophylaxis of malaria: 100 mg
daily beginning one
to two days before travel and
continuing for four
weeks after leaving malarious
area.
Dental: 20 mg twice daily at 12-
hour intervals,
usually in the morning and
evening
Pediatrics > 8 years and < 45 kg:
2.2 mg/kg give
twice daily on Day 1, then 2.2
mg/kg daily
If > 45 kg, then use adult dosing
Prophylaxis for malaria: 2 mg/kg
once daily (not to
exceed 100 mg).
50, 75, 100, 150 mg
capsules
75, 100 mg delayed
release capsules
20, 50, 75, 100, 150 mg
tablets
75, 100, 150 mg delayed
release tablets
25 mg/5mL, 50 mg/5mL
Suspension.

17. Drug Usual Dosing Availability
Doxycycline DR Adults: One capsule daily in
the morning on an
empty stomach, preferably at
least one hour prior
to or two hours after meals.
40 mg capsules with 30
mg immediate release and
10 mg delayed release.
Minocycline Adults:
44-54 kg: 45 mg daily
55-77 kg: 65 mg daily
78-102 kg: 90 mg daily
103-125 kg: 115 mg daily
126-136 kg: 135 mg daily
May be taken with or without
food.
45, 65, 90, 115, 135 mg
extended release tablets.

18. Drug Usual Dosing Availability
Minocycline Adults: 200 mg initially
followed by 100 mg every
12 hours or two or four 50 mg
pellet-filled capsules
may be given initially
followed by one 50 mg
capsule 4 times
Pediatrics: 4 mg/kg initially
followed by 2 mg/kg
every 12 hours, not to exceed
the usual adult dose.
50, 100 mg pellet-filled
capsules
50, 75, 100 mg capsules
50, 75, 100 mg tablets

19. Drug Usual Dosing Availability
Tetracycline Adults: 250-500 mg every six
hours or 500-1,000
mg every 12 hours. Duration
of therapy dependent
on type and severity of
infection.
Acne rosacea: 250-1,500 mg
per day
Inflammatory acne vulgaris:
125-250 mg every six
hours then taper to 125-500
mg daily or every
other day.
Pediatrics: 4 mg/kg initially
followed by 2 mg/kg
every 12 hours, not to exceed
the usual adult dose
250, 500 mg capsules

20. 
 Tetracyclines are generally safe drugs, but some
adverse effects can occur.
6.1. Gastrointestinal
Dose-related gastrointestinal side effects are the
most common complaint in patients taking oral
tetracyclines . These include abdominal discomfort,
epigastric pain, nausea, vomiting and anorexia. Food
may decrease these symptoms but also may decrease
the absorption of tetracycline by 50 percent. Food
does not affect the absorption of doxycycline
6.ADVERSE REACTIONS

21. 
Tetracyclines may alter gut flora to cause large
bulky stools and diarrhea. Diarrhea usually subsides
once the agent is stopped. A patient with continued
diarrhea, fever, and a rising white blood count
should be evaluated for antibiotic associated
diarrhea caused by Clostridium difficile. Esophageal
ulcerations and strictures have been reported with
tetracyclines but can be prevented by taking the
drugs with plenty of water and not before bedtime.

22. 
 Allergic and skin reactions:
Hypersensitivity reactions can occur with
tetracyclines but are uncommon. If a patient is
allergic to one tetracycline, they should be
considered allergic to all. Photosensitivity reactions
can occur, ranging from a red rash to blistering on
areas exposed to the sun. These reactions are most
common with demeclocycline but can occur with all
analogues. Photosensitivity can be decreased by
avoiding direct sunlight or wearing protective
clothing with sunscreen.

23. 
 Teeth and bone:
Tetracyclines can cause a brown to yellow discoloration
of the teeth in children under the age of eight that is
sometimes associated with hypoplasia of the enamel. The
darkening effect on the permanent teeth appears to be
dose related and does not occur in adults. These agents
generally should be avoided in children under the age of
eight; however if they must be used, doxycycline may be
the preferred agent. Tetracyclines may also deposit in the
bone likely due to chelate formation with calcium, thus
adding another reason to avoid these agents in children
with developing bone formation.

24. 
 Liver and renal :
Hepatotoxicity with tetracyclines is rare but can be fatal. This
occurs more commonly with tetracycline and minocycline and
less often with doxycycline.
Tetracyclines inhibit protein synthesis and may exacerbate
preexisting renal failure by increasing the azotemia from amino
acid metabolism. Demeclocycline can cause a nephrogenic
diabetes insipidus, a side effect that is used therapeutically to
treat the syndrome of inappropriate antidiuretic hormone
secretion (SIADH). The use of outdated tetracyclines has been
associated with a reversible Fanconi-like syndrome and renal
tubular acidosis; however, current formulations, which do not
contain citric acid as an excipient, have virtually eliminated this
possibility.

25. 
The absorption of tetracyclines can be impaired by
co-administered minerals and antacids (eg, calcium,
magnesium, iron), lanthanum, and dairy including
milk. Tetracyclines can interact with oral isotretinoin,
beta-lactams, and a variety of other drugs
7.DRUG INTERACTIONS

26. Pediatrics:
Use of tetracycline products in children less than
eight years of age is not recommended due to the
potential for tooth discoloration. Safety and
effectiveness of minocycline ER (Solodyn) in children
less than 12 years of age have not been established.
 Pregnancy:
All agents in this class are Pregnancy Category D.
8.Use in Special Populations

27. 
Nursing Mothers:
The American Academy of Pediatrics considers
ciprofloxacin and tetracyclines including doxycycline
to be usually compatible with breastfeeding because
the amount of drug absorbed by infants is small, but
little is known about the safety of long-term use.
Mothers concerned about the use of ciprofloxacin or
doxycycline for antimicrobial prophylaxis should
consider expressing and then discarding breast milk
so that breastfeeding can be resumed when
antimicrobial prophylaxis is completed.

28. 
 Renal Impairment
If renal impairment is present, minocycline doses
may need to be adjusted to avoid
excessive systemic accumulation of the drug and
possible liver toxicity.

29. 
 Take your medicine with a full glass of water. These
medicines are best taken on an empty stomach
(either 1 hour before or 2 hours after meals). unless
manufacturer specify or if stomach upset occurs.
 Avoid exposure to direct sunlight.
 Do not take milk, other dairy products, antacids or
iron within 2 hours of taking these medicines
9.Patient counselling

30. 
 The course of antibiotics should be completed even
if you feel better after a few days, and DO NOT
forget to keep the medicine out of reach of children

31. 
 http://www.uptodate.com
 http://www.micromedexsolutions.com/micromede
x2/librarian?partner=true
 www.clinicalpharmacology.com.
 Toxicology and Applied Pharmacology
References

32. Thanks