1. Chemotherapeutic Agents
Antibiotics
Synthetic Drugs

2. History Ancient remedies Ehrlich Domagk Fleming
________ in egyptian times
Quinine
Ehrlich
Salvarsan
Domagk
Dyes led to discovery of sulfa drugs
Fleming
________________ mold

3. Properties of Antimicrobial Agents
Selective Toxicity

4. Spectrum of Activity
Narrow
Broad

5. Drug Mechanisms of Action
Inhibition of Cell Wall Synthesis
Bacterial peptidoglycan
Bacterial mycolic acid
Fungal β-glucans
Disruption of Cell Membrane Function
Bacterial membrane proteins - polymyxins
Fungal ergosterol

6. Drug Mechanisms of Action
Inhibition of Protein Synthesis
70S vs 80S protein synthesis (bacteria)
Inhibition of Nucleic Acid Synthesis
Unique bacterial or viral enzymes may be affected
Antimetabolites
Essential biochemical pathways are blocked, mostly bacteria, e.g. Folate synthesis inhibition by sulfa drugs

7. Side Effects Toxicity Allergy Disruption of Microflora
Accumulation in kidneys
Liver metabolism
Allergy
Disruption of Microflora

8. Resistance to Drugs Chromosomal mutations
Plasmid borne resistance genes

9. Mechanisms of Drug Resistance
Mutations in Target molecules
Ribosome alterations
Alterations in membrane permeability
Transport pumps exclude drugs
Enzyme development
Penicillinases (β lactamase)

10. Mechanisms of Drug Resistance
Enzyme Activity Changes
PABA binding much greater than sulfa drug binding
Alterations in Anabolic Pathways
Uptake of folic acid rather than synthesis

11. Generations of Drugs First/Second/Third Line Drugs Cross Resistance
Used as evolving resistances limit the usefulness of original drugs
Cross Resistance
Similar drugs are all broken down by the resistant microbe, e.g. β lactamase effects

12. Limiting Drug Resistance
Effective Drug Concentrations
Simultaneous Drug Administration
Synergism
Antagonism
Restricting Drug Prescriptions

13. Determining Microbial Sensitivities
Disk Diffusion Method
Dilution Method

14. Ideal Antimicrobial Attributes
Solubility
Selective toxicity
Stable toxicity level
Allergenicity
Tissue stability
Resistance Acquisition
Shelf Life
Cost

15. Antibacterials — Cell Wall Target
Penicillins
Natural
Semisynthetic
Many Gram +ve’s but Staphylococcus is mostly resistant
Safe, but allergies in 1-5% of adults

16. Antibacterials — Cell Wall Target
Cephalosporins
Work similarly to penicillins
Safe but more expensive
Carbapenems
Work like penicillins, more stable
Broader spectrum
Still effective against Staphylococcus

17. Antibacterials — Cell Membrane Target
Polymyxins
Topical use only
Injure bacterial plasma membrane
Used for Pseudomonas dermatitis

18. Antibacterials — Protein Synthesis Inhibition
Aminoglycosides (*mycin)
Streptomycin original
Toxicity, deafness
Chromosomal mutation causing resistance
Tetracyclines (Aureomycin)
Soluble
Good for obligate intracellulars
Cause tooth discoloration in children / fetal bone malformations
Chloramphenicol
Tocicity makes it a drug of last choice in U.S.A.
Macrolides (Erythromycin)
Legionnaire’s disease
Bacteriostatic, may be used with other drugs
Low toxicity

19. Antibacterials — Nucleic Acid Synthesis Inhibition
Rifampin
Blocks RNA transcription
Red colored, v. soluble
Used against M. tuberculosis, N. meningitidis
Many negative interactions with other meds.
Quinolones
Inhibit DNA gyrase
Used in traveller’s diarrhea, anthrax

20. Antibacterials — Antimetabolites
Sulfonamides
Block folate synthesis
Isoniazid
Interferes with vitamin B conversions
Ethambutol
Similar to Isoniazid, often used together
Nitrofurans
Interfere with KREbs cycle/ETC
Used in UTIs
Veterinary topical agent

21. Antifungals Imidazoles (Clotrimazole) Polyenes (Amphotericin B)
Disrupt ergosterol synthesis
Some cross-reactivity with cholesterols
Mostly for cutaneous and superficial conditions
Ketoconazole – safe for oral administration
Polyenes (Amphotericin B)
Ergosterol targeted
Systemic infections only, severe side effects
Griseofulvin
Impairs mitotic spindle formation
Oral admin, for cutaneous and superficial mycoses

22. Antifungals Flucytosine Tolnaftate/ Terbinafine (Lamisil)
Nucleoside analog
Tolnaftate/ Terbinafine (Lamisil)
Topicals, unclear mech. of action
Superficial and cutaneous mycoses

23. Antivirals Nucleotide analogs Ribavirin anti-influenza, anti-herpes
Zidovudine (AZT) anti-HIV
Acyclovir anti-herpes

24. Antivirals Amantidine/Rimantidine Interferons Immunoenhancers
Prevents Influenza A virus penetration
Ataxia/insomnia in many elderly
Interferons
Promote release of antiviral proteins in uninfected cells
Immunoenhancers
T lymphocyte stimulators

25. Antiprotozoan Drugs Quinine/derivatives Metronidazole Pyrimethamine
Malaria
Metronidazole
Trichomonas/Giardia
Pyrimethamine
Toxoplasmosis
Suramin
Trypanosoma

26. Antihelminthic Drugs Niclosamide Mebendazole Piperazine Tapeworms
Affect CHO synthesis in worms
Mebendazole
Roundworms
Blocks glucose uptake
Piperazine
Neurotoxin
Pinworms and Ascaris
Can cause convulsions in children