This presentation was used to conduct theory class of BSN 1st year

1. Antimicrobial agents:
Specific Drugs
Dr. Pravin Prasad
M.B.B.S., MD Clinical Pharmacology
Lecturer, Lumbini Medical College
20 February, 2019 (8 Falgun 2075), Wednesday

2. By the end of the class BSN 1st year
students will be able to:
Classify AMAs that act by inhibiting:
Folate synthesis
Cell wall synthesis
Explain the mechanism of action of cotrimoxazole
and penicillin
List the uses and adverse effect of cotrimoxazole
and penicillin

3. Folate synthesis inhibitors AMAs
First effective AMA to be used systematically in
man
Limited role because of:
High toxicity
Development of resistance drugs
Availability of safer drugs
Primarily bacteriostatic
Acts on both gram positive and gram negative

4. Folate synthesis inhibitors
Classification
Short acting Sulfixazole, sulfadiazine
Intermediate acting Sulfamethoxazole
Long acting Sulfamethoxypyridazine,
sulfadoxine
Special purpose drugs Sulfasalazine, silver
sulfadiazine

5. Folate synthesis inhibitors
Uses:
Urinary tract infection
Topically: burn dressing, bacterial conjunctivitis
Toxoplasmosis, Malaria
Ulcerative colitis, rheumatoid arthritis

6. Folate synthesis inhibitors
Adverse effects:
Hypersensitivity reaction
Haemolytic anaemia
Kernicterus
•Contraindicated: Pregnancy, infant
Kidney damage (precipitated in acidic urine)
•Can be avoided by drinking plenty of water and
alkalinizing the urine

7. Folate synthesis inhibitors:
Cotrimoxazole
Combination of trimethoprim and
sulfamethoxazole
Less chance of resistance if used in combination
Individual drugs- bacteriostatic
•Combination- bactericidal
Ratio of drugs 1:5 (T:S)

8. Folate synthesis inhibitors:
Cotrimoxazole
Sequential block in the
formation of
tetrahydrofolic acid
Required for nucleic
acid synthesis
Resistance if
dihydrofolate reductase
enzyme is altered
p-aminobenzoic acid
Dihydrofolic acid
Tetrahydrofolic acid
Dihydropteroic
synthase
Dihydrofolate
reductase
S
T

9. Folate synthesis inhibitors:
Cotrimoxazole
Uses:
Urinary tract infection
•Uncomplicated UTI
•Chronic or recurrent
UTI
•Bacterial prostatitis
Pneumocystis jiroveci
infection
Chancroid
Bacterial gastro-
enteritis
•Shigella
•E. coli
Sinusitis, otitis media,
bronchitis

10. Folate synthesis inhibitors:
Cotrimoxazole
Adverse effects:
Hypersensitivity reaction
Megaloblastic anaemia (in patients with folate
deficiency)
Uraemia in renal disease patients
Anaemia, granulocytopenia

11. Cell wall synthesis inhibitors AMAs
Broad group:
Beta lactams, Monobactams, Carbapenems,
Glycopeptides, Others
Penicillin belongs to beta lactam group

12. Penicillin: Classification
Natural: Penicillin G (Benzyl penicillin)
Semi-synthetic
Acid resistant: Penicillin V
Penicillinase resistant: Methicillin, Cloxacillin
Aminopenicillin: Ampicillin, Amoxicillin
Antipseudomonal penicillin: Carbenicillin,
Ticarcillin, Piperacillin

13. Penicillin: Mechanism of Action
Enters gram positive
bacteria through porin
channels
Binds to
transpeptidase enzyme
(Penicillin binding
proteins, PBPs)
Gets inhibited

14. Penicillin: Mechanism of Action
Transpeptidation
reaction cannot occur
No cross linking of
polymers
Weak cell wall formed
Lysis of cell occurs

15. Penicillin: Mechanism of Resistance
Resistance develops by:
Change in porin structure
Altered structure of PBPs
Production of penicillinase (beta lactamase)
•Thus combined with beta lactamase inhibitors
like clavulanic acid, sulbactam, tazobactam

16. Penicillin: Uses
Treatment of:
Syphilis
Anthrax, Actinomycosis, Listeria infections
Meningococcal meningitis
Streptococcal infections
•Pharyngitis, otitis media, Scarlet fever and
Rheumatic fever
•Subacute bacterial endocarditis

17. Penicillin: Uses
Prophylactic uses:
Rheumatic fever
•Benzathine penicillin
Infective endocarditis
•Benzyl penicillin
•Prior to procedures like dental extraction,
endoscopies, etc.

18. Penicillin: Adverse effects
Hypersensitivity reaction
Nurses should avoid touching preparation of
penicillin directly
Jarisch Herxheimer reaction in syphilis
Local adverse effects: pain at injection site,
thrombophlebitis

19. Conclusion