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TETRACYCLINES

Alduheza, Shynne B.
Banaña, Mae Anne S.

I. DOXYCYCLINE
• ((4S,4aR,5S,5aR,6R,12aS)-4-(dimethylamino)3,5,10,12,12a-pentahydroxy- 6-methyl- 1,11dioxo- 1,4,4a,5,5a,6,11,12aoctahydrotetracene- 2-carboxamide or
C22H24N2O8)

• Doxin (Biofemme), Vibramycin (Pfizer)

CHEMISTRY and STABILITY • Pharmacology – protein synthesis inhibitor – bacteriostatic – high lipid solubility and low affinity for calcium binding – highly stable in normal human serum – Categorized as a long acting tetracycline .II.

III. • entry is mediated both by passive diffusion and by an energy-dependent transport protein unique to the bacterial inner cytoplasmic membrane . thereby blocking access of the amino acyl-tRNA to the mRNA-ribosome complex at the receptor site. MECHANISM OF ACTION • inhibits bacterial protein synthesis by binding to the 30S ribosomal subunit.

Staph.aureus.Listeria monocytogens.Haemophilus influenzae • 44% of strains of Streptococcus pyogenes and 74% of Streptococcus faecalis have been found resistant to tetracyclines • active against the asexual erythrocytic forms of Plasmodium falciparum but not against the gametocytic form of this organism. Mycoplasma pneumoniae. .Neisseria gonorrhoea.SPECTRUM • gram-positive and gram-negative • Bacillus anthracis.

Absorption • readily and almost completely absorbed from the GI tract (90-100%) after oral administration • food and milk products may decrease absorption • time to peak plasma concentration: 2 hr. PHARMACOKINETICS IVa. .IV.

Elimination/Excretion • partially inactivated in GI tract by chelate formation. • via urine (23%) and feces (30%). • 30-42% is excreted unchanged in the urine .IVb. kidney. Distribution • liver. skin • bind to tissues undergoing calcification or to tumors having a high calcium content • cross the placental barrier and concentrate in fetal bone and dentition • 80-90% bound to serum proteins IVc. Plasma half-life: 15-25 hr. spleen.

bruceloosis .V. USES • It is a drug of choice in infections caused by: Mycoplasma: Pneumonia Rickettsiae: Rocky mountain spotted fever and Reckettsial pox Chlamydia :Trachoma & Psittachosis Vibrio : Cholera Bacillus anthracis:Anthrax Spirochetes: Lyme disease • it is use in a regimen for treatment of gastric ulcer caused by Helicobacer pylori • Used with Aminoglycoosides for plague. tularemia.

gram-positive: chlamydial infections. adjunct to scaling and root planning to promote attachment level gain and reduce pocket depth in adult periodontis • Others: 1. plague. tularemia. cholera 2.• Dental: 1. lyme disease. reduce bacteria associated with periodontal disease 2. relapsing fever . gram-negative: chancroid.

Liver toxicity • Hepatic toxicity leading to hepatic necrosis D.discoloration of the teeth C. tachycardia. vomitting B. anaphylactic shock .asthma.headache. myalgia. Others: • Anemia.VI.arthralgia. anaphylaxis. Bone structures and teeth • Fluorescence. Gastrointestinal Adverse Effects • anorexia. diarrhea. nausea. CAUTION Adverse Drug Events A. tinnitus. benign intracranial hypertension.dyspnea.

infants and children below 8 yrs old (except for use as an alternative treatment for inhalational anthrax post-exposure) • Patients with myasthenia gravis • Patients with systemic lupus erythematosus . • Patients who are pregnant.Precautions and Contraindications • Known hypersensitivity to tetracyclines or to any component of the product. breastfeeding.

• Doxycycline. are not likely to be effective or are contraindicated. • A decrease in the fibula growth rate • Use of tetracycline class during tooth development (last half of pregnancy. infancy and childhood to the age of 8 years) may cause permanent discoloration of the teeth (yellow-gray-brown). should not be used in these groups of patients unless other drugs are not available.Pediatric • doxycycline forms a stable calcium complex in any bone-forming tissue. . therefore.

(Pregnancy category D) • Results of animal studies indicate that tetracyclines cross the placenta. Evidence of embryotoxicity has also been noted in animals treated early in pregnancy.Pregnancy • It should not be used in pregnant women unless. • Doxycycline should be avoided in nursing mothers . are found in fetal tissues and can have toxic effects on the developing fetus (often related to retardation of skeletal development). in the judgment of the physician.

Chronic toxicity • Chronic toxicity of doxycycline was evaluated in rats at oral doses up to 500 mg/kg/day for 18 months. • Chronic studies in dogs at oral doses up to 100 mg/kg/day for one year showed some functional and histopathological changes in the liver. • Yellow ultraviolet fluorescence of bone. . Findings revealed no adverse effects on growth. or survival. effects were reversible after cessation of exposure to the material. However. teeth and/or kidneys was seen in rats at all levels. food consumption.

antacids may be administered in appropriate circumstances. . Any gastrointestinal upset should be treated symptomatically.Acute toxicity • Acute overdosage with tetracyclines is extremely rare. As tetracyclines form insoluble complexes with cations. no specific treatment is required. • Dialysis does not alter serum t1/2 and thus would not be of benefit in treating cases of overdosage. and if it occurs.

anticonvulsants: decrease half-life of doxycycline • methoxyflurane: fatal renal toxicity • oral contraceptives: less effectivity of contraceptives. barbiturates. increase breakthrough bleeding .Drug Interactions • anticoagulants: prolongation of prothrombin time • penicillins: interfere bactericidal action of penicillins • antacids: impaired doxycycline absorption • alcohol.

cholestyramine and kaolin-pectin: decrease doxycycline absorption • Laboratory Test Interactions: False elevations of urinary catecholamine levels may occur due to interference with the fluorescence test. colestipol. .• Atovaquone: may decrease plasma concentration of atovquone • Ciclosporin: increased plasma concentration of ciclosporin • Ergot alkaloids and methotrexate: increased toxic effects • Isotretinoin: may result in pseudomotor cerebri (benign intracranial hypertension) • Sodium bicarbonate.

Adminstration • oral. then 2. 100 mg q12h Maintenance: 100-200 mg/day.4 mg/kg/day in divided dose depending on severity of infection Children over 45 kg should receive the adult dose. depending on severity of infection Children over 8 years (45 kg or less): first day. tablet. syrup.2-4.Pharmaceutical dosage forms • Capsules. IV Adult: First day. intravenous Preparation • 100 mg caps .4 mg/kg in 12 doses.4. delayed release capsules. oral suspension.

USP capsules) administered once daily for treatment of rosacea • Phase 3 • Methodology: In two phase III. patients received 40-mg of controlled-release doxycycline (n = 269) or placebo (n = 268) for 16 weeks. .VII. randomized. multicenter. The primary efficacy end point was the mean change from baseline in facial inflammatory lesion count. parallel-group. Clinical Studies Done • Two randomized phase III clinical trials evaluating anti-inflammatory dose doxycycline (40-mg doxycycline. placebocontrolled studies (studies 301 and 302). double-blind.

• Rationale: to evaluate the efficacy and safety of once-daily anti-inflammatory dose doxycycline for the treatment of rosacea • Results: The mean lesion count at baseline was approximately 20 in each study arm. At week 16.4%). and headache (4.8%).4%). respectively. the mean change from baseline in lesion count in the active-treatment groups was -11. in the placebo groups (P < . the most common adverse events were nasopharyngitis (4.8 in study 301 and -9.001 for both comparisons).3. .5 in study 302 compared with -5. Antiinflammatory dose doxycycline was well tolerated. diarrhea (4.9 and -4.

nih.html .nlm.gov/medlineplus/drugin fo/meds/a682063.Sources: • Lippincott’s Illustrated Reviews Pharmacology (5th edition) • PDR Nurse’s Drug Handbook (2003 edition) • http://www.