مادة االدوية

المرحلة الثالثة

محمد غدير حاتم. م. م

2016-2017

ANTIMICROBIAL DRUGS

Antimicrobial drugs

Lecture 5

50 S INHIBITORS: CHLORAMPHENICOL MACROLIDES CLINDAMYCIN / LINCOMYCIN

Macrolides

Erythromycin, Azithromycin

Clarithromycin

• it contain Macrocyclin lacton .

• Erythromycin used as alternative to penicillin in patient

with allergic to penicillin.

- Low to mild dose = bacteriostatic

- high doses = bactericidal

MECHANISMS OF ACTION OF

ANTIBACTERIAL DRUGS

Macrolids Reversibly binds to 50S.

Macrolide inhibit bacterial protein synthesis by binding reversibly to 50S ribosomal subunit and inhibit RNA dependent protein synthesis. Prevents continuation of

protein synthesis.

It consider bacterostatic and may be cidal at high dose

Erythromycin • Erythromycin :effective against many of the same

MO as Penicillin group so used as an alternative

- Absorption:

• incompletely but adequately absorbed from intestine

- inactivated by gastric acid , so it is given as enteric coated tab. or as cap.

- food impair absorption.

- Higher concentration can be achieved by I.V administration

• Distribution

-diffuse into intracellular fluids , not enter CSF & brain

-protein binding is 70-80%

-cross placenta and milk

• Elimination

.erythromycin : t1\2 is 1.6 hr

-metabolized by liver and excreted by bile, urine .

• Dosage

1-2 gm\day in divided dose i.e 6 hourly

30-50 mg\ Kg\ day for children (can be doubled in sever infection)

Clarithromycin

-absorbed rapidly from GIT

-hepatic first pass metabolism reduces bioavailability to 50%

-can be given with or without food

-peak conc. Occurs 2hr after administration

-have higher intracellular conc.

-protein binding is 40-70%.

-more active against Gram (+) pathogens, than Erythromycin

Elimination :

- t 1\2: 3-7 hr

- Excreted by urine

- Dosage : 250 mg \twice daily (double in sever infection)

7.5 mg\Kg\twice daily for children

Azithromycin

- more active than erythromycin against several Gram (-)

pathogens

- Given orally , absorbed rapidly.

- 50% protein binding.

- Distributed widely (except brain ,CSF)

- Should not be given with food (Should be administered 1

hour before or 2 hours after meals; aluminum and

magnesium delay absorption and reduce peak serum

concentrations

- Can be given I.V

- extensive tissue distribution and high drug conc. Within

cells (maintains high concentrations for prolonged periods

into a number of tissues (lungs, tonsil, cervix))

• Elimination

--mainly by liver

-12% by urine

- long half-life allows once daily oral

administration and shortening of treatment in

many cases

-Does not inactivate cytochrome p450 enzymes

and free of the drug interactions that occur

with erythromycin and clarithromycin

Therapeutic uses of macrolides

• Drug of choice for mycoplasma pneumonia

• Chlamydial infection

• Diphtheria

• Syphilis

• Streptococcal (alternative to P)

• Staphylococcal

Adverse effect macrolides

1- large dose cause epigastic pain , increase GIT motility

2- ototoxicity : transient deafness

3-Contraindication in patient with hepatic dysfunction

4- drug interaction : its enzyme inhibitor so it inhibit

metabolism of number drugs which lead to toxic

accumulation of drug like Warfarin

Therapeutic uses in

dentistry • Erythromycin has a long and successful history of

use against acute orofacial infections, particularly

in β-lactam–allergic patients.

• Its spectrum of activity is good to excellent

against gram-positive aerobic/facultative cocci

(streptococci, somestaphylococci).

Cont.

• Azithromycin has been observed to be effective

against oral spirochetes and pigmented anaerobes.

In the management of acute periapical abscesses,

azithromycin,500 mg/day for 3 days, has shown

comparable efficacy to amoxicillin/clavulanic

acid, 625 mg three times daily for 5 to 10 days.

• Macrolides are also useful for endocarditis

prophylaxis.

Cont.

• Clarithromycin is most active against gram-

positive anaerobes (Actinomyces,

Propionibacterium, Lactobacillus),

• whereas erythromycin is more active than

azithromycin for these organisms.

• Azithromycin has the best activity against gram-

negative anaerobes (Fusobacterium, Prevotella,

Porphyromonas,

Cont.

• Azithromycin may be more active against

streptococci and staphylococci than erythromycin

and clarithromycin and has much less propensity

for drug interactions.

• Prolonged use of erythromycin and possibly other

macrolides may lead to superinfection with gram-

negative enteric bacilli.