Review of Pharmacology - 9E (2015)

Review of Pharmacology
immunocompromised patients. Oropharynx, intestine, respiratory and genitourinary tracts
are common sites for the development of new infection. The organisms frequently involved
are Candida albicans, Clostridium difficile, staphylococci, proteus and pseudomonas. Clostridium
difficile superinfection may result in pseudomembranous colitis (most commonly due to third
generation cephalosporins) for which metronidazole is the drug of choice (alternative drug is
vancomycin). Further, due to the loss of commensal flora, there may be decreased formation
of vitamin K leading to enhanced anticoagulant effects of warfarin.
Concentration Dependent Killing (Cdk) and Time Dependent Killing (Tdk)
Chemotherapy A: General Considerations and Non-specific...
Pseudomembranous Colitis
• Most common organism implicated:
Clostridium difficite.
• Most common antimicrobial
implicated: Third generatiion
cephalosporins > Clindamycin
• Treatment of choice: Metronidazole
• Treatment of choice for severe
cases: Vancomycin
Drugs having
• CDK
– Aminoglycosides
– Fluoroquinolones
• TDK
– Beta lactams
– Vancomycin
• Prolonged PAE against
gram –ve bacteria
– Carbapenems
– Tetracyclines
– Chloramphenicol
– Aminoglycosides
– Fluoroquinolones
– Rifampicin
• CDK means that killing effect of a drug is high when ratio of peak concentration to
MIC is more. This type of killing behaviour is exhibited by aminoglycosides and
fluoroquinolones. These drugs produces better action when used as a large single
dose as compared to same daily dose divided into 2-3 portions.
• TDK means antimicrobial action depends on the length of time the concentration
remains above the MIC. This is exhibited by β-lactams and macrolides. For these
drugs multiple daily doses are preferred over single dose.
• Post antibiotic effect (PAE): After exposure of an organism to the antibiotic, its
growth stops. When it is placed in the antibiotic free medium, the growth resumes
but only after a lag period. This signifies that inhibitory effect of antibiotics is present
even when their concentration is below MIC. This period is known as PAE. Most of the
antimicrobials have long PAE (> 1.5 hours) against gram postive bacteria. Carbapenems
and drug affecting protein synthesis (aminoglycosides, chloramphenicol,
tetracyclines) or DNA synthesis (Quinolones, rifampicin) have long PAE against
gram-ve bacteria also. Rifampicin prolongs the PAE of isoniazid. Due to this reason
isoniazid can be given thrice weekly when given in combination with rifampicin in
short course chemotherapy of tuberculosis (it needs to be administered daily if used
alone).
Combined Use of Antibiotics
Though every combination is unique but the general guidelines are that:
• Two bacteriostatic agents often show additive effect.
• Two bactericidal agents are additive if the organism is sensitive to both e.g. isoniazid and
rifampicin in tuberculosis.
• Combination of a bactericidal with a bacteriostatic drug is additive if the organism has
low sensitivity to the cidal drug e.g. streptomycin + tetracycline for brucellosis.
• Combination of bactericidal with bacteriostatic agent is antagonistic if the organism has
high sensitivity to cidal drug e.g. penicillin + tetracycline (or chloramphenicol) for
pneumococci.
Factors Affecting the Choice of an Antimicrobial Agent
1. Age
• Chloramphenicol in new born may cause grey baby syndrome.
• Sulfonamides in new born may cause kernicterus.
• Half life of aminoglycosides is prolonged in the elderly.
• Tetracyclines are contra-indicated in children below 6 years because it accumulates in
the developing teeth and bone.
2. Pregnancy
All antibiotics pose risk to the fetus when used in pregnancy. Penicillins, most cephalosporins
and macrolides (PCM) appear safe.
3. Impaired Host Defenses
Bactericidal drugs are must in immunocompromised patients.
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