tetracycline drug reporting-2

8/10/2019 Tetracycline Drug Reporting-2

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TETRACYCLINES

Alduheza, Shynne B.

Banaa, Mae Anne S.


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I. DOXYCYCLINE

((4S,4aR,5S,5aR,6R,12aS)-4-(dimethylamino)-

3,5,10,12,12a-pentahydroxy- 6-methyl- 1,11-dioxo- 1,4,4a,5,5a,6,11,12a-octahydrotetracene- 2-carboxamide orC22H24N2O8)

Doxin (Biofemme), Vibramycin (Pfizer)


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II.CHEMISTRY and STABILITY

Pharmacologyprotein synthesis inhibitor

bacteriostatic

high lipid solubility and low affinity forcalcium binding

highly stable in normal human serum

Categorized as a long acting tetracycline


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III. MECHANISM OF ACTION

inhibits bacterial protein synthesis bybinding to the 30S ribosomal subunit, therebyblocking access of the amino acyl-tRNA to themRNA-ribosome complex at the receptor site.

entry is mediated both by passive diffusion andby an energy-dependent transport proteinunique to the bacterial inner cytoplasmic

membrane


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SPECTRUM

gram-positiveand

gram-negative Bacillus anthracis, Staph.aureus,Listeria

monocytogens, Mycoplasmapneumoniae,Neisseria

gonorrhoea,Haemophilus influenzae

44% of strains of Streptococcus pyogenesand 74% of Streptococcus faecalis have

been found resistant to tetracyclines active against the asexual erythrocytic forms of

Plasmodium falciparum but not against thegametocytic form of this organism.


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IV. PHARMACOKINETICS

IVa. 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.


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IVb. Distribution liver, kidney, spleen, 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. Elimination/Excretion partially inactivated in GI tract by chelate

formation. via urine (23%) and feces (30%); Plasma

half-life:15-25 hr. 30-42% is excreted unchanged in the urine


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V. USES

It is a drug of choice in infections caused by:

Mycoplasma: PneumoniaRickettsiae: Rocky mountain spotted fever

and Reckettsial poxChlamydia :Trachoma & PsittachosisVibrio : CholeraBacillus anthracis:Anthrax

Spirochetes: Lyme disease

it is use in a regimen for treatment of gastric ulcercaused by Helicobacer pylori

Used with Aminoglycoosides for plague, tularemia,bruceloosis

D l


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Dental:

1. reduce bacteria associated with periodontaldisease

2. adjunct to scaling and root planning to promoteattachment level gain and reduce pocket depthin adult periodontis

Others:

1. gram-negative: chancroid, tularemia, plague,cholera

2. gram-positive: chlamydial infections, lymedisease, relapsing fever


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VI. CAUTION

Adverse Drug Events

A. Gastrointestinal Adverse Effects anorexia, diarrhea, nausea, vomitting

B. Bone structures and teeth

Fluorescence,discoloration of the teeth

C. Liver toxicity

Hepatic toxicity leading to hepatic necrosis

D. Others: Anemia,arthralgia, myalgia,headache, benign

intracranial hypertension, tinnitus,dyspnea,tachycardia,asthma, anaphylaxis, anaphylactic shock


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Precautions and Contraindications

Known hypersensitivity to tetracyclines or toany component of the product.

Patients who are pregnant, breastfeeding,infants and children below 8 yrs old (except for

use as an alternative treatment for inhalationalanthrax post-exposure)

Patients with myasthenia gravis

Patients with systemic lupus erythematosus


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Pediatric

doxycycline forms a stable calcium complex in any

bone-forming tissue. 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 permanentdiscoloration of the teeth (yellow-gray-brown). Doxycycline, therefore, should not be used in these

groups of patients unless other drugs are notavailable, are not likely to be effective or are

contraindicated.


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Pregnancy

It should not be used in pregnant women unless, inthe judgment of the physician. (Pregnancycategory D)

Results of animal studies indicate that tetracyclinescross the placenta, are found in fetal tissues and canhave toxic effects on the developing fetus (oftenrelated to retardation of skeletal development).

Evidence of embryotoxicity has also been noted inanimals treated early in pregnancy.

Doxycycline should be avoided in nursing mothers


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Chronic toxicity

Chronic toxicity of doxycycline was evaluated in rats atoral doses up to 500 mg/kg/day for 18 months.Findings revealed no adverse effects on growth,food consumption, or survival.

Yellow ultraviolet fluorescence of bone, teeth

and/or kidneys was seen in rats at all levels. Chronic studies in dogs at oral doses up to 100

mg/kg/day for one year showed some functional andhistopathological changes in the liver. However,effects were reversible after cessation of exposure tothe material.


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Acute toxicity

Acute overdosage with tetracyclines is extremely rare,and if it occurs, no specific treatment is required. Anygastrointestinal upset should be treatedsymptomatically. As tetracyclines form insolublecomplexes with cations, antacids may be administered

in appropriate circumstances.

Dialysis does not alter serum t1/2 and thus would notbe of benefit in treating cases of overdosage.


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Drug Interactions

anticoagulants: prolongation of prothrombin time

penicillins: interfere bactericidal action ofpenicillins

antacids: impaired doxycycline absorption

alcohol, barbiturates, anticonvulsants:decrease half-life of doxycycline

methoxyflurane: fatal renal toxicity

oral contraceptives: less effectivity ofcontraceptives, increase breakthrough bleeding


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Atovaquone: may decrease plasma concentrationof 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, colestipol,cholestyramine and kaolin-pectin: decreasedoxycycline absorption

Laboratory Test Interactions: False elevationsof urinary catecholamine levels may occur due tointerference with the fluorescence test.

h i l d f


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Pharmaceutical dosage forms

Capsules, delayed release capsules, oral suspension, syrup,tablet, IV

Adult: First day, 100 mg q12hMaintenance: 100-200 mg/day, depending on severity of

infection

Children over 8 years (45 kg or less): first day,4.4 mg/kg in 1-

2 doses; then 2.2-4.4 mg/kg/day in divided dose dependingon severity of infection

Children over 45 kg should receive the adult dose.

Adminstration

oral, intravenous

Preparation

100 mg caps


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VII. Clinical Studies Done

Two randomized phase III clinical trials evaluatinganti-inflammatory dose doxycycline (40-mgdoxycycline, USP capsules) administered once daily fortreatment of rosacea

Phase 3 Methodology: In two phase III, parallel-group,

multicenter, randomized, double-blind, placebo-controlled studies (studies 301 and 302), patientsreceived 40-mg of controlled-release doxycycline (n =269) or placebo (n = 268) for 16 weeks. The primaryefficacy end point was the mean change from baseline

in facial inflammatory lesion count.

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Rationale: to evaluate the efficacy and safety ofonce-daily anti-inflammatory dose doxycyclinefor the treatment of rosacea

Results: The mean lesion count at baseline wasapproximately 20 in each study arm. At week16, the mean change from baseline in lesioncount in the active-treatment groups was -11.8in study 301 and -9.5 in study 302 comparedwith -5.9 and -4.3, respectively, in the placebogroups (P < .001 for both comparisons). Anti-

inflammatory dose doxycycline was welltolerated; the most common adverse eventswere nasopharyngitis (4.8%), diarrhea (4.4%),and headache (4.4%).


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tetracycline drug reporting-2

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