Drugs
Taufik Nur Yahya, MD
Resident
Div. Of Thoracic And Cardiovascular Surgery
Faculty Of Medicine, Airlangga University/Soetomo General Hospital
Antimicrobial Drugs
Chemicals used to treat microbial infections
Before antimicrobials, large number of people died from
common illnesses
Now many illnesses easily treated with antimicrobials
However, many antimicrobial drugs are becoming less
useful
Antimicrobial Drugs
Chemotherapeutic agent = Antimicrobial drug
Different types of antimicrobial drugs:
Antibacterial drugs
Antifungal drugs
Antiprotozoan drugs
Antihelminthic drugs
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Drug
Bacteria
1.
2.
3.
4.
Antimicrobial Action
Bacteriostatic: inhibit growth of
microorganisms
Bactericidal: Kill microorganisms
All antibiotics require the immune system to
work properly
Spectrum of Activity
Antimicrobial medications vary with respect to the range
of microorganisms they kill or inhibit
Some kill only limited range : Narrow-spectrum
antimicrobial
While others kill wide range of microorganisms: Broadspectrum antimicrobial
Adverse Effects
1. Allergic Reactions: some people develop
hypersensitivities to antimicrobials
2. Toxic Effects: some antimicrobials toxic at high
concentrations or cause adverse effects
3. Suppression of normal flora: when normal flora killed,
other pathogens may be able to grow to high numbers
Resistance to Antimicrobials
Some microorganisms inherently resistant to effects of a
particular drug
Other previously sensitive microorganisms can develop
resistance through spontaneous mutations or acquisition
of new genes
Mechanisms of action of
Antibacterial Drugs
1.
2.
3.
4.
5.
Figure 20.2
Lactam Drugs
Some bacteria produce -lactamase- enzyme that breaks
the critical b-lactam ring
-lactam drugs include: penicillins and cephalosporins
Penicillins (Benzylpenicillin)
Acid-labile.
Gram+ bacteria.
So, take phenoxymethylpenicillin.
Large Vd, but penetration into brain: poor, except
when the meninges are inflammed.
Broad spectrum penicillins: amoxicillin and
ampicillin are more hydrophillic and therefore,
are active against gram- bacteria.
Penicillins (Benzylpenicillin)
Penicillinase-resistant penicillins Flucloxacillin
Indicated in infections caused by penicillinase-producing penresistant staphlococci.
Has an isoxazolyl group at R1 sterically hinders access of the
enzyme to the -lactam ring.
Less effective than benzylpen.
So, should be used only for pen-resistant infections.
Broad-Spectrum Penicillins
Ampicillin and amoxicillin very active against non--lactamase-producing
gram+ bacteria.
Because they diffuse readily into Gram- bacteria, also very active against many
strains of E. coli, H. influenzae, and Salmonella typhimurium.
Many baterial -lactamases are inhibited by clavulaic acid amoxicillin (coamoxiclav) antibiotic is effective against penicillinase-producing organisms.
Cephalosporins
Vancomycin
Antibacterial Drugs
that Inhibit
Cell Wall Synthesis
Aminoglycosides
Aminoglycosides
Rifampicin resistance develops quickly alone; so, with TB, combine with
isoniazid, ethambutol, and pyrazinamide for the 1st 2 mos of treatment,
followed by another 4 mos with rifampicin and isoniazid.
Macrolides
Very safe drugs.
Ususally given orally.
Erythromycin and clarithomycin
Effective against gram- bact and can be used as an alt to pen-sensitive
patients, esp in infections caused by streptococci, staphylococci,
pneumococci, and clostridia.
Erythromycin in high doses, may cause nausea and vomiting (less so with
clarithromycin and azithromycin).
Azithromycin very long t1/2 (~40-60 hr) and a single dose is as effective in
treating chlamydial non-specific urethritis as tretracycline admin over 7
days,
Tetracyclines
Broad-spectrum.
Penetrate microorganisms well.
Sensitive organisms accumulate it through partly passive
Chloramphenicol
Broad-spectrum.
Serious side-effects: bone marrow aplasia,
Antibacterial
Drugs that Inhibit
Protein Synthesis
Sulphonamides
Figure 5.7
Figure 20.13
5-Nitroimidazoles
Wide-spectrum
Metronidazole against anaerobic bacteria and protozoan
infections.
Tinidazole longer duration of action.
Diffuses into the organism where the nitro group is
reduced chemically reactive intermediates are formed
that inhibit DNA synthesis and/or damage DNA.
Antibacterial Drugs in
Surgery
Definition
Prophylactic antibiotic treatment
The use of antibiotics before, during, or after a diagnostic, therapeutic, or
surgical procedure to prevent infectious complications
Common Principles
Ideally, an antimicrobial agent for surgical prophylaxis should
(1)prevent surgical site infection (SSI),
(2)prevent SSI-related morbidity and mortality,
(3)reduce the duration and cost of health care (when the costs
associated with the management of SSI are considered, the costeffectiveness of prophylaxis becomes evident),
(4)produce no adverse effects, and
(5)have no adverse consequences for the microbial flora of the
patient or the hospital
Timing
The antimicrobial agent should be started within 60 minutes before surgical incision
Figure 21.10
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