Microbial antagonism.

Antibiotics.
Drug susceptibility test.
 Study Outline

Microbial relathionship
The Development of Chemotherapy
General Characteristics of Antimicrobial Drugs
Mechanisms of Action of Antimicrobial Agents
Antibacterial Drugs
Determining the Level of Antimicrobial Activity
Drug Resistance
Antiviral Drugs
 Microbial Relationships

Symbiosis
Commensalism
Mutualism
Competition
Parasitism
Antagonism
 Definitions
Symbiosis
Two organisms that live together

Commensalism
A symbiotic relationship between two organisms
One microorganism benefits
One microorganism is unaffected
 Definitions
Mutualism
A symbiotic relationship between two organisms
Both organisms benefit from relationship
 Opportunistic Pathogen
Opportunists (Opportunistic pathogens)
Under proper conditions mutualistic organisms may
be come pathogens
Examples
E. coli in large intestine relatively harmless
E. coli in other parts causes disease
Urinary bladder cystitis
CSF - meningitis
Staphylococcus aureus normal inhabitant of skin
Cut or wound allow bacteria to cause disease
Abscess
Immunocompromised individuals
Pneumocystis jiroveci pnuemonia
 Definitions
Parasitism
A symbiotic relationship between two organisms
One organism benefits (bacteriophague, etc)
One organism is harmed (bacteria)
 Antagonism

The inhibition of one microbial species by another.

Competition among microorganisms

For Nutrients
By Production of toxins
By Production of enzymes that degrade the cell walls of other
organisms.
Production of antibiotics
 Microbial Antagonism
Example
Mouth
Streptococci produce compounds that prevent growth of G+
and G- cocci

Large intestine
E. coli produce bacterocins
Proteins inhibit growth of other bacteria
Inhibits Shigella and Salmonella
 Microbial Antagonism
Examples
Vagina
Normal flora maintain pH of 3.5 4.5
Acid pH inhibits growth of Candida albicans
Antibiotics, excessive douching pH rises to neutral
Candida albicans overgrowth causes vaginitis (yeast)
 Study Outline

The Development of Chemotherapy

 Antimicrobial Drugs
Chemotherapeutic agent=Antimicrobial drug
An anti-microbial is a substance that kills or
inhibits the growth of microorganisms (bacteria,
fungi, or protozoans).
Different types of antimicrobial drugs:
Antibacterial drugs
Antifungal drugs
Antiprotozoan drugs
Antihelminthic drugs
Antiviral drugs
 Antibiotic
Antibiotics are generally used to treat bacterial infections

The term antibiotic originally described only those

formulations derived from living organisms, but is now
applied also to synthetic antimicrobials, such as the
sulfonamides.
 The Development of
Chemotherapy
Early 20th century
1904: Ehrlich found that the dye trypan red was
effective against Trypanosoma (sleeping sickness)
Arspheniamine (Salvarsan) against syphilis
Quinine against malaria
Various dyes (including gentian violet); disinfectants;
heavy metals were tried as antimicrobial
chemotherapeutic agents
 The Development of
Chemotherapy
Sulfa drugs:
1927: Domagk discovered that the dye Prontosil Red
was effective against staphilococcal and
streptococcal infections

Penicillin
Produced by Penicillium notatum
Discovered in 1928 by Fleming
Method of mass production developed in late 1930s -
early 1940s by Chain and Florey
 The Development of
Chemotherapy
Streptomycin
Produced by Streptomyces griseus
Discovered in 1944 by Waksman after screening
10,000 soil isolates
Following its discovery was the discovery of other
antibiotics produced by soil microbes, including
chloramphenicol, neomycin, terramycin, and
tetracyclin by the early 1950s
Drug Discovery
Features of Antimicrobial Drugs
Most modern antibiotics come from species of
microorganisms that live in the soil

To commercially produce antibiotics:

1. Select bacteria and grow in broth
2. When maximum antibiotic concentration reached, extract from
medium
3. Purify
4. Chemical alter to make it more stable
 Study Outline

General Characteristics of
Antimicrobial Drugs
 General Characteristics of
Antimicrobial Drugs
Selective toxicity
Narrow-Spectrum
Broad Spectrum
Cidal vs Static
Therapeutic dose
Toxic Dose
Therapeutic Index
Side Effects
Minimal Inhibitory Concentration
Minimal Bactericidal Concentration
 Selective Toxicity

Cause greater harm to microorganisms than to

host.
 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: Broad-

spectrum antimicrobial
 Antimicrobial Action

Bacteriostatic: inhibit growth of microorganisms

Bactericidal: kill microorganisms

 Effects of Combining Drugs

Combinations are sometimes used to fight

infections
Synergistic: action of one drug enhances the activity
of another or vice versa.
Antagonistic: activity of one drug interferes with the
action of another.
 Adverse Effects
1. Allergic Reactions: some people develop
hypersensitivities to antimicrobial drugs
2. Toxic Effects: some antimicrobial drug are
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
 Principles

Treatment vs prophylaxis

Prophylaxis - antimicrobial agents are administered to

prevent infection

Treatment - antimicrobial agents are administered to

cure existing or suspected infection
 Study Outline

Mechanisms of Action of Antimicrobial

Agents. Antibacterial Drugs.
The Action of Antimicrobial Drugs
Q&A

This bacterium is
lysing because an
antibiotic disrupted
its cell wall. Why
doesnt the antibiotic
lyse human cells?
 Mechanism of action of antibiotics

Mechanism of action include:

Inhibition of cell wall synthesis
Inhibition of protein synthesis
Inhibition of nucleic acid
synthesis
Interference with cell
membrane integrity
Inhibition of metabolic
pathways
Inhibitors of Cell Wall Synthesis

Penicillin
Cephalosporins
Vancomycin
Bacitracin
Isoniazid (INH)
Ethambutol
 Inhibition of Cell wall synthesis

Bacteria cell wall unique in

construction
Contains peptidoglycan

Antimicrobials that interfere with the

synthesis of cell wall do not interfere
with eukaryotic cell
Due to the lack of cell wall in animal
cells

These drugs have very high

therapeutic index
Low toxicity with high effectiveness
 Inhibition of Cell wall synthesis

The weakness in the cell

wall causes the cell to
lyze.
1. Penicillins and cephalosporins
Part of group of drugs called
lactams
Have shared chemical structure
called -lactam ring

Competitively inhibits function of

penicillin-binding proteins
Inhibits peptide bridge formation
between glycan molecules
This causes the cell wall to develop
weak points at the growth sites and
become fragile.
 Penicillin
Natural penicillins

Semisynthetic penicillins

Extended-spectrum penicillins
The Structure of Penicillins

Figure 20.6
Retention of Penicillin G

Figure 20.7
 b-Lactam Drugs

Some bacteria produce b-lactamase- enzyme

(ex. penicillinase) that breaks the critical b-lactam
ring

b-lactam drugs include: penicillins and

cephalosporins
The Effect of Penicillinase on
Penicillins

Figure 20.8
 b-Lactam Antibiotics
To avoid the destruction of b-
lactam AB it is recomended:

Penicillin
Penicilinase-resistant penicillins
Penicillins + b-lactamase inhibitors
Carbapenems
Substitute a C for a S, add a double
bond
Monobactam
Single ring

Figure 20.6a
Inhibitors of Cell Wall Synthesis

Penicillin
Cephalosporins
Vancomycin
Bacitracin
Isoniazid (INH)
Ethambutol
The Cephalosporins (generalized)
*Not effective vs. Enterococcus or Listeria

1st Generation Gram (+)

- Cephalexin, Cefazolin
Decreasing Gram (+) and Increasing
2nd Generation Gram (-)
- Cefoxitin, Cefuroxime, Cefotetan

Gram (-), but also pseudomonads

3rd Generation
- Cefotaxime, Ceftriaxone, Ceftazidime

Gram (+) and Gram (-)

4th Generation
- Cefepime
Inhibitors of Cell Wall Synthesis

Penicillin
Cephalosporins
Vancomycin
Bacitracin
Isoniazid (INH)
Ethambutol
 3. Inhibitors of Cell Wall Synthesis

Polypeptide antibiotics
Vancomycin
Glycopeptide
Important "last line" against antibiotic-resistant
S. aureus

Bacitracin
Topical application
Against gram-positives
 Vancomycin

Inhibits formation of glycan chains

Inhibits formation of peptidoglycans and cell wall
construction
Does not cross lipid membrane of Gram -
Gram - organisms innately resistant
Important in treating infections caused by
penicillin resistant Gram + organisms
Must be given intravenously due to poor
absorption from intestinal tract
 Bacitracin

Interferes with transport of peptidoglycan precursors

across cytoplasmic membrane
Toxicity limits use to topical applications
Common ingredient in non-prescription first-aid
ointments
Inhibitors of Cell Wall Synthesis

Penicillin
Cephalosporins
Vancomycin
Bacitracin
Isoniazid (INH)
Ethambutol
 4. Inhibitors of Cell Wall Synthesis

Antimycobacterial antibiotics

Isoniazid (INH)
Inhibits mycolic acid synthesis

Ethambutol
Inhibits incorporation of mycolic acid
 Mechanism of action -2

Mechanism of action include:

Inhibition of cell wall synthesis
Inhibition of protein
synthesis
Inhibition of nucleic acid
synthesis
Interference with cell
membrane integrity
Inhibition of metabolic
pathways
Antibacterial
Drugs that Inhibit
Protein Synthesis
 Inhibitors of Protein Synthesis
Inhibition of protein synthesis
Structure of prokaryotic ribosome acts as target for many
antimicrobials of this class
Differences in prokaryotic and eukaryotic ribosomes responsible for
selective toxicity
 1. Inhibitors of Protein Synthesis

Chloramphenicol
Aminoglycosides
Tetracyclines
Macrolides
Streptogramins
Oxazolidinones

Figure 20.10
 Inhibitors of Protein Synthesis

Chloramphenicol
Broad spectrum
Binds 50S subunit; inhibits peptide bond formation

Figure 20.10
 Chloramphenicol
Broad-spectrum.

Serious side-effects: bone marrow aplasia, suppression of

RBCs, WBCs, encephalopathy, optic neuritis.

So, periodic blood counts required, esp in high doses.

Inhibits the actions of other drugs and may increase the

actions of phenytoin, sulphonlureas, and warfarin.

Neonates cannot met the drug rapidly accum grey

baby syndrome (pallor, abdominal distension, vomiting,
and collapse).
 Inhibitors of Protein Synthesis

Chloramphenicol
Aminoglycosides
Tetracyclines
Macrolides
Streptogramins
Oxazolidinones

Figure 20.10
 Aminoglycosides

Streptomycin, neomycin, gentamycin

Broad spectrum
Changes shape of 30S subunit

Against many gram- and some gram+.

Very toxic.
Most important adverse side-effect: VIIIth cranial n.
(ototoxicity) and kidney damage.
 Aminoglycosides
Irreversibly binds to 30S
ribosomal subunit
Causes distortion and
malfunction of ribosome
Blocks initiation translation
Causes misreading of
mRNA
Not effective against
anaerobes, enterococci and
streptococci
Often used in synergistic
combination with -lactam
drugs
Allows aminoglycosides to
enter cells that are often
resistant
 Aminoglycosides

Gentamicin used for acute, life-threatening gram-

infections.
Amikacin used for bact that are gent-resistant.
Netilmicin less toxic than gentamicin.
Neomycin too toxic for parenteral use. Used for
topically for skin infections and orally for sterilizing bowel
before surgery.
Streptomycin active against Mycobacterium
tuberculosis. But becouse of its ototoxicity, rifampicin
replaces.
Rifampicin resistance develops quickly alone; so, with
TB, combine with isoniazid, ethambutol, and
pyrazinamide for the 1st 2 line of treatment.
 Inhibitors of Protein Synthesis

Chloramphenicol
Aminoglycosides
Tetracyclines
Macrolides
Streptogramins
Oxazolidinones

Figure 20.10
 Tetracyclines
Broad spectrum
Interferes with tRNA attachment

Figure 20.11
 Tetracyclines
Reversibly bind 30S ribosomal
subunit
Blocks attachment of tRNA to
ribosome
Prevents continuation of protein
synthesis
Effective against certain Gram +
and Gram -
Newer tetracyclines such as
doxycycline have longer half-life
Allows for less frequent dosing
Can cause discoloration of teeth
if taken as young child
 Inhibitors of Protein Synthesis

Chloramphenicol
Aminoglycosides
Tetracyclines
Macrolides
Streptogramins
Oxazolidinones

Figure 20.10
 Macrolides
Gram-positives
Binds 50S; prevents translocation

Figure 20.12
 Macrolids
Reversibly binds to 50S
ribosome
Prevents continuation of
protein synthesis
Effective against variety of
Gram + organisms and those
responsible for atypical
pneumonia
Often drug of choice for
patients allergic to penicillin
Macrolids include
Erythromycin, clarithromycin
and azithromycin
 Macrolides
Very safe drugs. Ususally given orally.
Erythromycin and clarithomycin
Effective against gram- bact and can be used as an alt to penicilline
sensitive patients, ex. in infections caused by streptococci,
staphylococci, pneumococci, and clostridia.
Dont cross the Brain Biological Barrier ineffective against
meningitis.
Resistance.
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.
 Inhibitors of Protein Synthesis

Chloramphenicol
Aminoglycosides
Tetracyclines
Macrolides
Streptogramins
Oxazolidinones

Figure 20.10
 Streptogramins. Oxazolidonses

Streptogramins
Gram-positives
Binds 50S subunit; inhibits translation

Oxazolidinones
Linezolid
Gram-positives
Binds 50S subunit; prevents formation of 70S ribosome
 3. Mechanism of action
Mechanism of action include:
Inhibition of cell wall synthesis
Inhibition of protein synthesis
Inhibition of nucleic acid
synthesis
Interference with cell
membrane integrity
Inhibition of metabolic
pathways
 Inhibitors of Nucleic Acid Synthesis
Rifamycin
block prokaryotic DNA-dependent RNA polymerase from
initiating transcription
Inhibits RNA synthesis
Antituberculosis
Quinolones and fluoroquinolones
inhibit enzymes that maintain the supercoiling of closed
circular DNA
Nalidixic acid: Urinary infections
Ciprofloxacin
Inhibits DNA gyrase
Urinary tract infections
Antibacterial Drugs that Inhibit
Nucleic Acids
 Rifamycins
Block prokaryotic RNA polymerase
Effective against many Gram + and some Gram - as
well as members of genus Mycobacterium
Primarily used to treat tuberculosis and Hansens
disease as well as preventing meningitis after
exposure to N. meningitidis
Resistance due to mutation coding RNA polymerase
Resistance develops rapidly
 Quinolones
Inhibit DNA gyrase.
Effective against Gram + and Gram -
Nalidixic acid used only for UTIs.
Ciprofloxin effective against both gram- and gram+ bacteria.

Well-absorbed both orally and i.v.

Eliminated largely unchanged by the kidneys.
Side-effects (headache, vomiting, nausea) are rare; but
convulsions may occur.
 4. Mechanism of action

Mechanism of action include:

Inhibition of cell wall synthesis
Inhibition of protein synthesis
Inhibition of nucleic acid
synthesis
Interference with cell
membrane integrity
Inhibition of metabolic
pathways
 Injury to the Plasma Membrane

Polymyxin B
Combined with bacitracin and neomycin in
over-the-counter preparation
binds to membrane of G- bacteria and alters
permeability
This leads to leakage of cellular contents and cell death
These drugs also bind to eukaryotic cells to some extent,
which limits their use to topical applications
 5. Mechanism of action

Mechanism of action include:

Inhibition of cell wall synthesis
Inhibition of protein synthesis
Inhibition of nucleic acid
synthesis
Interference with cell
membrane integrity
Inhibition of metabolic
pathways
 Competitive Inhibitors

Sulfonamides (sulfa drugs)

Inhibit folic acid synthesis
Broad spectrum

Figure 5.7b
 Sulphonamides
Sulfadiazine well-absorbed orally. Used to treat
UTIs.
But many strains of E. coli are resistant.
So, use less toxic drugs instead.
Adverse effects: allergic reactions, skin rashes,
fever.

Trimethoprin used for UTIs and Resp TIs

Co-trimoxazole (trimethoprin + sulfamethoxazole)
used mostly for pneumonia, neocarditis, and
toxoplasmosis.
 Trimethoprim
Inhibits folic acid production
Interferes with activity of enzyme following enzyme inhibited
by sulfonamides
Often used synergistically with sulfonamide
Most common mechanism of resistance is plasmid
encoded alternative enzyme
Genes encoding resistant to sulfonamide and trimethoprim
are often carried on same plasmid
 Attributes of an ideal
antimicrobial agent
1. Solubility in body fluids
2. Selectively toxic
3. Toxicity not easily altered
4. Not allergenic
- Therapeutic index: effective to toxic dose ratio
5. Stability in body
6. Resistance not easily acquired
7. Long shelf life
8. Reasonable cost

* There is no perfect drug.

 Study Outline

Drug Resistance
 Antibiotic resistance
Antibiotic resistance is a type of drug
resistance where a microorganism is able to
survive exposure to an antibiotic.

The prevalence of antibiotic resistant bacteria is

a result of antibiotic use both within human
medicine and veterinary medicine.
Antibiotics and Animal Feed

Clinical Focus, p. 577

Resistance to Antimicrobial Drugs
Drug resistance limits use of ALL known
antimicrobials
Penicillin G: first introduced, only 3% of bacteria
resistant
Now, over 90% are resistant
 Antibiotic Resistance
Misuse of antibiotics selects for resistance mutants.
Misuse includes
Using outdated or weakened antibiotics
Using antibiotics for the common cold and other
inappropriate conditions
Using antibiotics in animal feed
Failing complete the prescribed regimen
Using someone else's leftover prescription
 How do Bacteria Become
Resistant?
1. Spontaneous Mutation: happen as cells
replicate
Within a population, there will be some bacteria with
acquired resistance. The drug then eliminate the
sensitive organisms, while the resistant ones
proliferate.

2. Gene Transfer or Transferred resistance:

Usually spread through conjugative transfer of
R plasmid (may be virally mediated).
 RESISTANCE TO
ANTIMICROBIAL DRUGS
 Natural & acquired resistance
Natural resistance
Chromosomic genetic support
Affect almost all species strains
Existed before antibiotic use (Enterobacter sp. - amoxicillin)

Acquired resistance (mutation)

Chromosomic, plasmidic or transposon genetic support
Affects a fraction of strains
Increased with antibiotic use
(extended spectrum beta-lactamase producing E. coli)
 Different acquired resistances
Acquired to a population of strains in a given
species
Extremely frequent in nosocomial infections

Acquired under treatment; specific strain,

specific patient
Relatively uncommon except for certain species
(e.g., Enterobacter, Pseudomonas, Mycobacterium)
 Antibiotic Resistance
A variety of mutations can lead to antibiotic
resistance
Mechanisms of antibiotic resistance
1. Enzymatic destruction of drug
2. Prevention of penetration of drug
3. Alteration of drug's target site
4. Rapid ejection of the drug

Resistance genes are often on plasmids or

transposons that can be transferred between
bacteria
Resistance to Antibiotics

Figure 20.20
 Mechanisms of resistance
Drug inactivating enzymes
Some organisms produce enzymes that chemically
modify drug
Penicillinase breaks -lactam ring of penicillin
antibiotics

Alteration of target molecule

Minor structural changes in antibiotic target can
prevent binding
Changes in ribosomal RNA prevent macrolids from
binding to ribosomal subunits
Antibiotic Resistance

Figure 20.21
 Study Outline

Determining the Level of

Antimicrobial Activity
 Antimicrobial susceptibility tests
Minimum inhibitory concentration [MIC]
The smallest concentration of antibiotic that inhibits the
growth of organism
Liquid media (dilution) allows MIC estimation
Solid media (diffusion)
Disk diffusion (Kirby-Bauer)
E-tests
Allows MIC estimation
Beta lactamase production: quick screening method
 Minimum Inhibitory Concentration (MIC) :

Principle:

The tube dilution test is the standard method for

determining levels of resistance to an antibiotic.

Serial dilutions of the antibiotic are made in a liquid

medium which is inoculated with a standardized number of
organisms and incubated for a prescribed time.

The lowest concentration of antibiotic preventing

appearance of turbidity is considered to be the minimal
inhibitory concentration (MIC).
 Different concentrations of Gentamycin in Nutrient broth:
Conc. in mcg/ml
0.1 0.2 0.4 0.8 1.6 3.1

Gentamicin, generally considered a bacteriocidal antibiotic, for this

bacterium, has an MIC of 0.8 mcg/ml
 Different concentrations of Tetracycline in Nutrient broth:
Conc. in mcg/ml
0.1 0.2 0.4 0.8 1.6 3.1 6.3 12.5

Tetracycline, generally considered a bacteriostatic antibiotic, for this

bacterium, has an MIC of 1.6 mcg/ml
 Minimal Inhibitory Concentration (MIC)
vs.
Minimal Bactericidal Concentration (MBC)
32 ug/ml 16 ug/ml 8 ug/ml 4 ug/ml 2 ug/ml 1 ug/ml

Sub-culture to agar medium

MIC = 8 ug/ml
MBC = 16 ug/ml
The Disk-Diffusion Method

Figure 20.17
 Disk-diffusion Method (Kirby-Bauer Method):

The disk-diffusion method (Kirby-Bauer) is more suitable

for routine testing in a clinical laboratory where a large
number of isolates are tested for susceptibility to numerous
antibiotics.
An agar plate is uniformly inoculated with the test organism
A paper disk impregnated with a fixed concentration of an
antibiotic is placed on the agar surface.
Growth of the organism and diffusion of the antibiotic
commence simultaneously resulting in a circular zone of
inhibition in which the amount of antibiotic exceeds
inhibitory concentrations.
The diameter of the inhibition zone is a function of the
amount of drug in the disk and susceptibility of the
microorganism.
 This test must be rigorously standardized since zone size is also
dependent on:
inoculum size,
medium composition,
temperature of incubation,
excess moisture and
thickness of the agar.

Zone diameter can be correlated with susceptibility as measured by the

dilution method.
Further correlations using zone diameter allow the designation of an
organism as "susceptible", "intermediate", or "resistant" to
concentrations of an antibiotic which can be attained in the blood or
other body fluids of patients requiring chemotherapy.
 Using a dispenser, antibiotic-impregnated disks are placed onto the agar
surface.
As the bacteria on the lawn grow, they are inhibited to varying degrees by
the antibiotic diffusing from the disk.
 SUSCEPTIBILITY OF BACTERIAL
TO ANTIMICROBIAL DRUG

Conventional disc diffusion

method
Kirby-Bauer disc diffusion
routinely used to qualitatively
determine susceptibility
Standard concentration of
strain uniformly spread of Clear zone of inhibition
standard media
around disc reflects
Discs impregnated with specific susceptibility
concentration of antibiotic
placed on plate and incubated Based on size of zone
organism can be described
as susceptible or resistant
 Kirby-Bauer disc testing
Antibiotic-impregnated discs placed on an agar plate at the
interface between test organism and susceptible control
organism
Resulting zones of inhibition compared, use of controls
Susceptibility is inferred (standard tables)
The E Test

Figure 20.18
 ANTIMICROBIAL
SUSCEPTIBILITY TESTING

Probably the most widely

used testing method is
the disk-diffusion method,
also known as the Kirby-
Bauer test.
 Study Outline

Antiviral drugs
 Antiviral Drugs
Very few antiviral drugs approved for use in US
Effective against a very limited group of
diseases
Targets for antiviral drugs are various points of
viral reproduction
 Drugs that Prevent the Virus from
Entering or Leaving the Host Cells

Amantadine interferes with replication of

influenza A by inhibiting the transmembrane M2
protein that is essential for uncoating the virus.

Zanamivir inhibits both influenza A and B

neuraminadase. Decr duration of symptoms if
given within 48 hr of the onset of symptoms.
Prophylactic in healthy adults.
Drugs that Inhibit Nucleic Acid Synthesis
Nucleoside and Nucleotide Analogs

Acyclovir - used to treat genital herpes

Cidofovir - used for treatment of cytomegalovirus
infections of the eye
Lamivudine - used to treat Hepatitis B
 Antiretrovirals
Currently implies a drug used to treat HIV
Tenofovir- nucleotide reverse transcriptase inhibitor
Zidovudine- nucleoside analog inhibits RT of HIV and
is only used orally for AIDS.
- Severe adverse effects: anemia, neutropenia, myalgia,
nausea, and headaches.
Stavudine, didanosine, zalcitabine among other NRTIs.
Nevirapine, efavirenz Non nucleoside RTIs - denature
RT.
 Other enzyme inhibitors
Zanamivir (Relenza) and Oseltamivir phosphate
(Tamiflu)- inhibitors of the enzyme
neuominidase
Used to treat influenza

Indinavir- protease inhibitors. Inhibit the

synthesis of essential viral proteins (e.g., RT) by
viral-specific proteases.
 Interferons
Cells infected by a virus often produce
interferon, which inhibits further spread of the
infection
Alpha-interferon - drug for treatment of viral
hepatitis infections