1.DOXYCYCLINE HISTORY
How was Doxycycline discovered?

Doxycycline was discovered in the late 1950s.

Doxycycline is approved by the Food and Drug Administration (FDA) to treat and protect people who have been exposed to anthrax spores.

2.DOXYCYCLINE FACTS

Doxycycline is a member of a group of Antibiotics called the tetracyclines.

Doxycycline has the ability to inhibit the growth of a wide variety of bacteria and certain other organisms. 

3.ABOUT DOXYCYCLINE MEDICATION

What are antibiotics?

An antibiotic is a drug that kills or slows the growth of bacteria. Antibiotics are one class of "antimicrobials", a larger group, which also includes anti-viral, anti-fungal, and anti-parasitic drugs. They are relatively harmless to the host, and therefore can be used to treat infections. The term originally described only those formulations derived from living organisms, in contradistinction to "chemotherapeutic agents", which were purely synthetic. Nowadays the term "antibiotic" is also applied also to synthetic antimicrobials, such as the sulfonamides.

Antibiotics are labeled as "magic bullets": drugs, which target disease without harming the host. Antibiotics are not effective in viral, fungal and other nonbacterial infections, and individual antibiotics vary widely in their effectiveness on various types of bacteria. Some specific Antibiotics target either gram-negative or gram-positive bacteria, and others are more wide-spectrum Antibiotics.

The effectiveness of individual Antibiotics varies with the location of the infection, the ability of the antibiotic to reach the site of infection, and the ability of the bacteria to resist or inactivate the antibiotic. Some Antibiotics actually kill the bacteria (bactericidal), whereas others merely prevent the bacteria from multiplying (bacteriostatic) so that the host's immune system can overcome them.

Classes of Antibiotics?

There are many ways to classify Antibiotics.

One such classification is by chemical structure:

Aminoglycosides

•   Amikacin
•   Dibekacin
•   Gentamicin
•   Kanamycin
•   Neomycin
•   Netilmicin
•   Paromomycin
•   Sisomycin
•   Streptomycin
•   Tobramycin

Beta-lactam ring antibiotics

Carbapenems

• Ertapenem
• Imipenem
• Meropenem

Cephalosporins and cephamycins

• Cephalexin
• Cefazolin
• Cefuroxime
• Cefadroxil
• Ceftazidime

Penicillins

• Amoxicillin

Monocyclic beta-lactams

Glycopeptide antibiotics

• Vancomycin
• Teicoplanin
• Ramoplanin
• Decaplanin

Oxazolidinones

• Linezolid
• Quinupristin/dalfopristin

Polyketides

Macrolides

• Erythromycin
• Azithromycin
• Clarithromycin
• Roxithromycin

Ketolides

• Telithromycin

Tetracyclines

• Doxycycline
• Oxytetracycline
• Chlortetracycline

Polymyxins

• Polymyxin B
• Colistin

Quinolones (fluoroquinolones)

• Nalidixic acid
• Ciprofloxacin (Cipro)
• Ofloxacin
• Norfloxacin (Norflox)
• Levofloxacin (Levaquin)
• Trovafloxacin (Trovan)

Streptogramins

Sulfonamides

• Prontosil

Other important antibiotics:

• Chloramphenicol
• Clindamycin
• Fusidic acid
• Trimethoprim

Another such classification is by their mechanism of action

Antibiotics, which interfere with cell-wall synthesis

Beta-lactams, including penicillins like Amoxicillin and cephalosporins; mono-lactams, such as Imipenem; vancomycin, bacitracin

Antibiotics that interfere with bacterial protein synthesis 

Antibiotics that bind to the 50S ribosomal unit

Lincosamides/lincosides including clindamycin and lincomycin; chloramphenicol, macrolides

Antibiotics, which interfere the 30S ribosomal unit

Tetracyclines; aminoglycosides including gentamicin

Drugs that inhibit folate synthesis

Sulfonamides and trimethoprim 

Drugs that interfere with DNA synthesis

Metronidazole, quinolones, novobiocin

Drugs that interfere with RNA synthesis

Rifampin (rifampicin)

Drugs that interfere with cell membrane function

Polymyxin B, gramicidin

Antibiotics can also be classified by the organisms against which they are effective, and by the type of infection in which they are useful, which depends on the sensitivities of the organisms that most commonly cause the infection and the concentration of antibiotic obtainable in the affected tissue. 

How does Doxycycline work?

Doxycycline works by preventing bacteria from producing proteins that are essential to them. Without these proteins the bacteria cannot grow, replicate and increase in numbers. Doxycycline therefore stops the spread of the infection and the remaining bacteria eventually die.

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Doxycycline blocks bacterial translation by binding reversibly to the 30S subunit and distorting it in such a way that the anticodons of the charged tRNAs cannot align properly with the codons of the mRNA.

Uses of Doxycycline

Doxycycline is an antibiotic used to treat infections in animals caused by susceptible bacteria.

Examples of these infections include urinary tract infections, respiratory infections, blood-borne infections and wound infections.

Doxycycline is especially useful for treating tick-borne bacterial diseases such as Rocky Mountain spotted fever, ehrlichiosis and water-borne infections such as leptospirosis.

• Rocky Mountain Spotted Fever is a disease transmitted by the organism Rickettsia rickettsii and is transmitted by a tick bite. The spots begin as flat (macular) red (erythematous) patches that may bleed into the skin, causing purplish spots (purpura). The disease is named after its characteristic spots.

Tularemia

• Tularemia is an infection common in wild rodents caused by the organism Francisella tularensis and transmitted to humans by contact with animal tissues or ticks.

Ehrlichiosis

• Ehrlichiosis is a disease transmitted by a tick infected with Ehrlichia organisms. Symptoms include fever, headache and nausea. The disease is treated with Antibiotics and recovery is expected.

Doxycycline is not effective for treating infections caused by a virus or fungus.  

4.DOXYCYCLINE EFFECTIVENESS
When is Doxycycline best taken?

Absorption:

Doxycycline is well absorbed after oral administration. In a single-dose study, concomitant administration of with a 1000 calorie, high-fat, high-protein meal, which included dairy products, in healthy volunteers, resulted in a decrease in the rate and extent of absorption and delay in the time to maximum concentration.

Distribution:
Doxycycline is greater than 90% bound to plasma proteins. Its apparent volume of distribution is variously reported as between 52.6 and 134 L. 4,6

Metabolism:
Major metabolites of Doxycycline have not been identified. However, enzyme inducers such as barbiturates, carbamazepine, and phenytoin decrease the half-life of Doxycycline.

Excretion:
Doxycycline is excreted in the urine and feces as unchanged drug. It is variously reported that between 29% and 55.4% of an administered dose of Doxycycline can be accounted for in the urine by 72 hours. 5,6 Half-life averaged 18 hours in subjects receiving a single 20 mg Doxycycline dose. 

5.DOXYCYCLINE EFFECTS ON SPECIAL POPULATION
How do different people react to Doxycycline?

Geriatric : Doxycycline pharmacokinetics have not been evaluated in geriatric patients.

Pediatric : Doxycycline pharmacokinetics have not been evaluated in pediatric patients.

Gender: Doxycycline pharmacokinetics were compared in 9 men and 11 women under fed and fasted conditions. While female subjects had a higher rate (Cmax) and extent of absorption (AUC), these differences are thought to be due to differences in body weight/lean body mass. Differences in other pharmacokinetic parameters were not significant.

Race : Differences in Doxycycline pharmacokinetics among racial groups have not been evaluated.

6.DOXYCYCLINE EFFECTS ON MEDICAL CONDITIONS
How does Doxycycline affect your existing condition/ailment?

Renal Insufficiency : Studies have shown no significant difference in serum half-life of Doxycycline in patients with normal and severely impaired renal function. Hemodialysis does not alter the half-life of Doxycycline.

Hepatic Insufficiency : Doxycycline pharmacokinetics have not been evaluated in patients with hepatic insufficiency.

7.OTHER/ALTERNATE USES OF DOXYCYCLINE
(What else does Doxycycline treat?

Doxycycline can also be used to treat some bacteria caused sexually transmitted diseases. 

8.ADVERSE/SIDE EFFECTS of DOXYCYCLINE
(What are the side effects of Doxycycline?)

In clinical trials of adult patients with periodontal disease 213 patients received 20 mg BID over a 9-12 month period. The most frequent adverse reactions occurring in studies involving treatment with a bioequivalent form of Doxycycline tablets or capsules or placebo are listed below:

Incidence (%) of Adverse Reactions in Clinical Trials of Doxycycline (Tablets or Capsules, 20mg ) (Bioequivalent to Doxycycline vs. Placebo)
Adverse Reaction	Doxycycline 20 mg BID (n=213)	Placebo (n=215)
Headache	55 (26%)	56 (26%)
Common Cold	47 (22%)	46 (21%)
Flu Symptoms	24 (11%)	40 (19%)
Tooth Ache	14 (7%)	28 (13%)
Periodontal Abscess	8 (4%)	21 (10%)
Tooth Disorder	13 (6%)	19 (9%)
Nausea	17 (8%)	12 (6%)
Sinusitis	7 (3%)	18 (8%)
Injury	11 (5%)	18 (8%)
Dyspepsia	13 (6%)	5 (2%)
Sore Throat	11 (5%)	13 (6%)
Joint Pain	12 (6%)	8 (4%)
Diarrhea	12 (6%)	8 (4%)
Sinus Congestion	11 (5%)	11 (5%)
Coughing	9 (4%)	11 (5%)
Sinus Headache	8 (4%)	8 (4%)
Rash	8 (4%)	6 (3%)
Back Pain	7 (3%)	8 (4%)
Back Ache	4 (2%)	9 (4%)
Menstrual Cramp	9 (4%)	5 (2%)
Acid Indigestion	8 (4%)	7 (3%)
Pain	8 (4%)	5 (2%)
Infection	4 (2%)	6 (3%)
Gum Pain	1 (<1%)	6 (3%)
Bronchitis	7 (3%)	5 (2%)
Muscle Pain	2 (1%)	6 (3%)

Gastrointestinal : anorexia, nausea, vomiting, diarrhea, glossitis, dysphagia, enterocolitis, and inflammatory lesions (with vaginal candidiasis) in the anogenital region. Hepatotoxicity has been reported rarely. Rare instances of esophagitis and esophageal ulcerations have been reported in patients receiving the capsule forms of the drugs in the tetracycline class. Most of these patients took medications immediately before going to bed.

Skin : maculopapular and erythematous rashes. Exfoliative dermatitis has been reported but is uncommon. Photosensitivity is discussed above.

Renal toxicity : Rise in BUN has been reported and is apparently dose related.

Hypersensitivity reactions : urticaria, angioneurotic edema, anaphylaxis, anaphylactoid purpura, serum sickness, pericarditis, and exacerbation of systemic lupus erythematosus.

Blood : Hemolytic anemia, thrombocytopenia, neutropenia, and eosinophilia have been reported.