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Doxycycline Pharmacology : Uses, MOA, Dose, Interactions and Side effects

Reading time: 5 minutes, 32 seconds

Doxycycline is a tetracycline antibiotic that is active against susceptible gram-negative and gram-positive microorganisms

Class and Category

Chemical class: Oxytetracycline derivative

Therapeutic class: Antibiotic

Pregnancy category: D

Doxycycline is a broad and medium spectrum antibiotic that belongs to a class of tetracycline. Other important members on tetracycline-class are; tetracycline and oxytetracycline.

The drug is a bacteriostatic drug

Doxycycline has a more activity overall than tetracycline HCl and has particular usefulness in prostatitis because it reaches high levels in prostatic fluid

Indications of Doxycycline

It is indicated for infectious diseases caused by susceptible gram-positive and gram-negative organisms.

These indications include

enterobacter aerogenes, Shigella species, Acinetobacter species,

  • Skin infections ie acne vulgaris
  • Ophthalmic infections due to trachoma, staphylococci and gonococci strains
  • Urinary tract infections by Klebsiella species or Escherichia coli,
  • Rickettsial infections ie Rocky mountain spotted fever, Recrudescent epidemic typhus, Scrub typhus, Q fever,
  • Epididymoorchitis caused by C. trachomatis
  • Murine typhus,
  • Lymphogranuloma vernerum,
  • Psittacosis, tularemia,
  • Brucellosis in conjunction with streptomycin
  • Doxycycline may also be used in the treatment of gonorrhea, syphilis, and yaws caused by treponema pallidum, and anthrax, listeriosis due to Listeria monocytogenes in the cases where the patient is allergic to penicillin.
  • Acute bacterial rhinosinusitis
  • Respiratory tract infections
  • Periodontal disease,
  • Inflammatory lesions due to rosacea
  • Chlamydia trachomatis
  • Prophylaxis of malaria due to plasmodium falciparum in short term travelers to areas with chloroquine or pyrimethamine sulfadoxine resistant strain.
  • Intestinal amebiasis
  • Infective endocarditis
  • Purulent cellulitis from community-acquired MRSA

Mechanism of action of Doxycycline

Doxycycline exerts a bacteriostatic effect against a wide variety of gram-positive and gram-negative organisms. The drug is more lipophilic than other tetracyclines, making it pass more easily through the bacterial lipid bilayer, where it binds reversibly to 30S ribosomal subunits.

Doxycycline like tetracyclines binds to the 30S subunit of bacterial ribosomes and prevents binding of the aminoacyl-tRNA to the ribosome acceptor site which is the messenger RNA, thereby inhibiting protein synthesis and bacterial growth. Doxycycline may block the dissociation of peptidyl t-RNA from ribosomes causing RNA-dependent protein synthesis to arrest.

Dosage and administration

For initial treatment of acne, 100 mg daily dose is used. The dosage must be reduced as soon as possible to a maintenance dose of 50 mg daily.

In children between 12-8 years, the dosage is 200mg on the first day and a maintenance dose of 100mg per day but if the infection is severe a maintenance dose of 200mg per day can be used.

For acne vulgaris use 50mg daily for 6-2 weeks.

STI s the dose is 100 mg twice a day for 7 days.

For chloroquine-resistant malaria, the dose is 200mg/day for 7 days but for malaria prophylaxis the usual dose is 100 mg 1-2 days before expected travel and continued daily till four weeks after the visit to malaria-endemic areas.

For scrub typhus the dose is 200 mg STAT

Prevention of leptospirosis the dose is 200mg once a weak

Rocky mountain fever treatment the dose is 100 mg twice a day for at least 7 days

Capsules are taken twice a day on the first day then one capsule a day after food because absorption is reduced by food.

The tablets should not be chewed and should be administered with plenty of fluids to reduce the risk of esophageal irritation.

When administered intravenously it should be given via a slow intravenous infusion over 1-2 hours.

Medication should be continued for at least 24 to 48 hours after the fever and other symptoms have disappeared.

Doxycycline is given once daily,

Instruct patient not to take doxycycline just before bed because it may not dissolve properly when she’s recumbent and may cause esophageal burning and ulceration

Pharmacokinetics

It is almost completely absorbed following oral intake.

Peak serum time is between 1.5 to 4 hours,

Bioavailability is reduced at high Ph.

It is protein-bound in 90%

The drug is metabolized in the liver.

The medication has a half-life of 15-25 hours

It is excreted in urine and feces.

Side effects and special precautions

The side effects of doxycycline are as follows;

The most common unwanted effect is gastrointestinal upset (Nausea, diarrhea) and symptoms that result from the damage to the natural bacterial gut flora allowing colonization by pathogenic organisms, including Candida fungi and a direct mucosal irritant action of the drug.

Overgrowth of Candida Albicans in the mouth causes soreness, soreness, and thrush which may extend to the trachea and bronchi.

Overgrowth of the candida Albicans in the bowels extend in pruritus ani and there may be an overgrowth of resistant coliform organisms such as pseudomonas species and Proteus species causing diarrhea.

The most serious suprainfection I by resistant staphylococci, causing fulminating enteritis with dehydration and occasionally death; this complication is rare except after abdominal surgery especially gastrectomy.

Hypersensitivity reactions (including rash, exfoliative dermatitis, Stevens-Johnson syndrome, urticaria, angioedema, anaphylaxis, pericarditis);

Discoloration and damage of the teeth and bones of the fetus if the mother takes tetracyclines after the fifth month of pregnancy, and of children.

Phototoxicity

Contraindications of Doxycycline

Doxycycline is contraindicated in pregnancy and in children aged below 12 years.

Avoid giving doxycycline to breastfeeding women because of the risk of enamel hypoplasia, inhibited linear skeletal growth,

The ability to chelate Ca2+ accounts for the propensity of tetracycline to accumulate in growing teeth and bones. As a result, there occurs an irreversible yellow-brown discoloration of teeth and a reversible inhibition of bone growth.

Because of these adverse effects, tetracycline should not be given after the second month of pregnancy and not prescribed to children aged.

Doses of anticoagulants may need to be reduced when doxycycline is used,

As preparations containing aluminum, iron, and calcium or magnesium decrease the absorption of tetracycline,

Do not give the patients who are receiving antacid therapy, milk or calcium-containing foods. This is because tetracyclines form insoluble complexes with plurivalent cations (e.g., Ca2+, Mg2+, Al3+, Fe2+/3+) resulting in their inactivation; that is, absorbability, antibacterial activity, and local irritant action are abolished.

Potentially hepatotoxic drugs should not be given together with doxycycline.

Drug Interactions

Antacids that contain aluminum, calcium, magnesium, or zinc; calcium supplements; choline and magnesium salicylates; iron salts;

Laxatives that contain magnesium decrease the absorption of doxycycline and effects

Barbiturates, carbamazepine, and phenytoin increase the clearance and decrease the effects of doxycycline

Cholestyramine and colestipol decrease doxycycline absorption

Doxycycline, when used together with digoxin, increases the bioavailability of digoxin, possibly leading to digitalis toxicity

Isotretinoin increases the risk of intracranial hypertension

Oral anticoagulants use is associated with the possibility of increased hypoprothrombinemic effects of these drugs

Oral contraceptives use is associated with decreased effectiveness of estrogen-containing oral contraceptives and increased risk of breakthrough bleeding

Concurrent use with penicillin may result in inhibited bactericidal action

Pentane use is associated with the possibility of increased risk of fatal renal toxicity

Sodium bicarbonate alters the absorption of doxycycline from increased gastric pH


Post References

  • Science direct, BNF, NCBI

  • Revised on: 2021-06-24 09:33:30