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Role antibiotics and antiinflammatory Mustofa Bagian Farmakologi & Terapi Fakultas Kedokteran UGM

Role antibiotics and antiinflammatory

Mustofa Bagian Farmakologi & Terapi Fakultas Kedokteran UGM

Antibiotic and antimicrobial

Antibiotic : Chemical molecules produced by a microorganism

that kills or inhibits the growth of another microorganism

Antimicrobial agent : Chemical molecules that kills or inhibits the growth of microorganisms

The anti-infective drugs

Anti-infective agents : drugs that

are developed to act selectively on

foreign organisms that have

Anti-infective invaded and infected drugs : the range body. from

  • a. Antibiotics

b. Antifungals

  • c. Antiprotozoals

  • d. Antihelminthics

  • e. Antivirals

  • f. Antimycobacterial

Microbial Sources of Antibiotics

Microbial Sources of Antibiotics

Antibiotic classification base on their chemical sturcture

1.Beta-lactam antibiotics:

  • a. Penicillins

  • b. Inhibitors of beta-lactamases and combined drugs,

  • c. Cephalosporins

  • d. Monobactams

  • e. Tienamycin (carbapenems).

2.Macrolides, azalides, streptogramins, prystinamycines.

3.Linkozamides.

4.Tetracyclines.

5.Aminoglycosides.

6.Chloramphenicols.

7.Glycopeptides.

8.Cyclic polipeptides (polimixins). 9 Oth tibi ti

Antibiotic classification base on their spectrum activity

No antibiotic is effective against all microbes

Broad-spectrum:

Justifiable in life-threatening disease, with unidentified organism

In general more expensive more likely to resistance

More adverse effects than narrow spectrum (increase superinfection)

Narrow spectrum:

Preferable if possible

Dangerous choice in life-threatening disease unless organism (and sensitivities) known

Antibiotic classification base on their activity

1. Bactericidal drugs kill bacteria directly

  • a. Β-lactam antibiotics

  • b. Cephalosporins

  • c. Vancomycin

  • d. Vancomycin

  • e. Aminoglycoside antibiotics

2. Bacteriostatic drugs prevent bacteria from dividing

  • a. Tetracyclines

  • b. Sulfonamides

  • c. Spectinomycin

  • d. Trimethoprim

  • e. Macrolides

  • f. Lincosamides

Modes of antimicrobial action

Modes of antimicrobial action

Principle antibiotics therapy

  • 1. Susceptibility testing

  • 2. Drug concentration in blood

  • 3. Serum bactericidal titers

  • 4. Route of administration

  • 5. Monitoring of therapeutic response

  • 6. Clinical failure of antibiotics therapy

1. Susceptibility testing

The results of susceptibility testing establish the drug sensitivity of hte organism

These results usually predict the MIC of a antibiotics

Choosing of the most effective and the

2. Drug concentration in the blood

least toxic drug, in time administration

The measurement of drug concenctration may be appropriate when using antibiotics with low therapeutic index (aminoglycosides & vancomycin)

It is also appropriate when investigating poor clinicall response to a drug treatment r imen

3. Route of administration

Parenteral administration is prefered in most cases of serious microbacterial infections.

Chloramphenicol, the fluoroquinolones and trimethoprim-sulfamethoxazole may be effective orally.

5. Monitoring of therapeutic response

Therapeutic response should be monitored clinically and microbiologically to detect the development of resistance or superinfection

The duration of therapy depend on the pathogen (fungi or micobacterium), the site of infection (endocarditis & i

t

liti )

d th

t

6. Clinical failure of antimicrobial therapy

Inadequate clinical or microbial response can result from :

laboratory testing error,

problems the drug (incorrect choice, poor tissue penetration, inadeqaute dose)

the patient (poor host defense, undrained abcesses)

the pathogen (resistance or superinfection)

Factors influencing antibiotics use

  • 1. Bacterial versus bacteriostatic actions

  • 2. Drug elimination mechanism

  • 3. Special patients group (pregnancy, neonate and adult patients)

  • 4. Drug interactions

1. Bactericidal versus bacteriostatic actions

For bacteriostatic drugs, the concentration that inhibit growth are much lower than those that kill bacteria.

For bactericidal drugs, there is little difference between the concentration that inhibit growth and those that kill bacteria.

Bactericidal drugs are preferred for the treatment of infections in patients with impaired defense mechanism (immunocompromised patients)

Some bactericidal (aminoglycosides, fluoroquinolones) cause concentration- dependent killing → maximing Cp increase

1. Bactericidal versus bacteriostatic actions (cont. )

Other bactericidal (beta lactam, vancomycin) cause time-dependent killing → their killing is independent of drug concentration and continous only while blood concentration are maintained > MBC.

Inhibition of bacterial growth that continues after antibiotic blood concentration have fallen to low level is called the postantibiotic effect (PAE).

PAE is another factor contribute to the effectivenes of once daily administration of aminoglycosides and clinical efficacy of the fluoroquinolones.

2. Drug elimination mechanism

Change in hepatic and renal function influence pharma-cokinetics of antibiotic & necessite dosage modifications.

In anuria (creatinine Cl < 5mL/min) → ↑ the t1/2 → necessiting major reduction in drug dosage.

Erythromycin, clindamycin, chloramphenicol, rifampicin, ketokonazole no change in dosage in renal failure.

Patients with biliary dysfunction &cirrhosis, reduction in dosage is required for drug undergo hepatic elimination.

Dialysis/hemodialysis decrease the plasma

level → su

lementara

dosees ma

be

3. Special patients group

Antibiotics therapy in special group (preganancy, nonate & elderly) requires special conciderations. Aminoglycosides may cause neurologic and renal damage. Tetracucline casue tooth enamel dysplasia and inhibiton of bone growth. Sulfonamide displaces bilirubin from serum albumin and causes kernicterus in the neonate. Chloramphenicol may cause gray baby syndrome. Other antibiotics should be used with extreme

4. Drug interaction

Interaction sometimes occure between antibiotics and other drugs.

Aminoglycosides with diuretics, vancomycin or cisplatin → enhanced nephrotoxicity & ototoxicity

Sulfonamide with sulfonylurea → hypoglycemic

Sulfonamides with warfarin → ↑hypoprothrombinemia

Dilsufiram-like reactions to ethanol occur with metronidazole, with TMP-SMX & with

4. Drug interaction

(cont. ..

)

Erythromycin inhibits the hepatic metabolism of a number of drugs :

clozapine, lidocaine, loratidine, phenytoin, quinidine, sildenefil, theiphylline and warfarin.

The azole antifungal (ketoconazole) inhibits metabolims of caffeine, carmazepine, cyclosporine, HMG-CoA inhibitor, methadone, oral contraceptives, phenytoin, sildenafil, verapamil and zidovudine.

Rifampicin decreases the effect of digoxin, ketoconalzole, oral contraceptive,

Antimicrobial drugs combination indication

  • 1. Emergency situations

  • 2. To delay resistance

  • 3. Mixed infections

  • 4. To achieve synergistic effects

1. Emergency situations

In seveval infections (sepsis and meningitis), combinations of antimicrobial drugs are used empirically to supress all of the most likely pathogens.

2. To delay resistance

The combined use of drugs is valid when the rapid emergence of resistance impairs the chances for cure.

Combined drug therapy is especially important in the treatment of TBC, malaria, virus infection.

3. Mix infections

Multiple organims may be involved in some infections.

Peritonial infections may be caused by several pathogens → a combiantion drug may be required. Skin infections are often due to mixed

4. To achieve synergistic effect

bacterial, fungal or viral pathogens. The use combination may result in an effect

greater than a single drug.

Examples :

Penicillins + gentamicin in enterococcal endocarditis Penicillin + aminoglycoside in Pseudomonas infections

Mechanism antimicrobial drugs combination

1. Sequential blockade

combination may cause inhibition of 2 or more steps in a metabolic pathway.

Example :

Mechanism antimicrobial drugs combination 1. Sequential blockade • combination may cause inhibition of 2 or more

TMP+SMX

H O H N C N SO 2 NH 2 H OH H P-aminobenzoid Sulfonamides acid
H
O
H
N
C
N
SO 2 NH 2
H
OH
H
P-aminobenzoid
Sulfonamides
acid
Folic acid
H
H 2 C
O
N
C
Dihydropteroate
H
synthase
H N
N
NH
HOOC CH
CH
HOOC CH 2
2
Dihydro folic acid (DHF)
N
H 2 N
OH
N
OCH 3
H 3 CO
OCH 3
DHFReductase
CH 2
N
H 2 N
NH 2
N
Tetrahydro-folic acid
H
H 2 C
N
Trimethorprim
H
H N
N
Human cell
N
H 2 N
OH
N
Synthesis of purine
bases & thymidine
Parasite

Mechanism antimicrobial drugs combination

(cont. ..

)

2. Blockade of drug-inactivating

enzymes

Clavulanic acid, sulbactam and

tazobactam inhibit penicillinases and

are often combined with penicillinase-

sensitive beta-lactam drugs.

3. Enhanced drug uptake

Increase permeability to

aminoglycosides after exposure of

certain bacteria to cell wall-inhibiting

antimicrobacterial (e.g. beta-lactams)

Antimicrobial chemoprophylaxis

General priciples :

  • a. Prophylaxis should always be

directed toward a specific

pathogen (TBC, malaria, influenza,

hepatitis, polio, ect.)

  • b. No resistance should develop

during the period of drug use

  • c. Prophylaxis drug use should be of limited duration

  • d. Conventional therapeutic doses

should be employed

  • e. Prophylaxis should be used only