BIO 217 Exam 3

Chemotherapeutic Agents

Chemical agents that are used to treat disease (Used in treatment, relief or prophylaxis of disease)

Kill or inhibit growth of microorganisms, while causing as little damage to the host as possible is known as

selectively toxic

The effectiveness of a drug can be determined by what three things

1.) Therapeutic Index (TI)
2.) Narrow-spectrum
3.) Broad-spectrum

Therapeutic Index (TI) five examples

– Lethal dose / Effective Dose
– Measure of drug effectiveness over side effects
– Higher TI, better chemotherapeutic agent
– Higher TI, fewer side effects (undesirable effects to host)
– Higher TI drugs act against component in microorganism not found in host (Example) Penicillin blocks peptidoglycan synthesis

Narrow-spectrum

effective against limited variety of pathogens

Broad-spectrum

Attacks many different types of pathogens

Classification of Drugs (3)

1) Organisms they attack
2) Source
3) Means of action

organisms they attack

Antibacterial, antifungal, antiviral, etc.

Source

– Natural = isolated from another bacterium or fungi
– Synthetic = Man-made
– Semisynthetic = chemical modification of a natural compound

Means of action

– -cidal = Kill organism
• Some may be static at low concentrations
– -static = Inhibit growth of microorganisms

Course of Antimicrobial Therapy five steps

1.) Administration of drug
2.) Absorption and distribution to body
3.) Action of Drug
4.) Resolution of Infection
5.) Metabolism and Excretion of Drug

administration of the drug (methods. of administration)

info - Microbial load is high during
infection

•Oral
•Intravenous
•Suppository
•Subcutaneous

upon administration, initially serum levels of drug rise, followed later by levels in body _____

tissues

2) Absorption and distribution
to body

serum levels rise followed later by

levels in body tissues

As drug is delivered to site of infection, microbial loads begin to ____

decrease

Action of Drug

Serum and tissue levels peak to ___________ ___________

effective concentrations

Microbial loads decrease due to drug action unless

organism is resistant

Levels of drug or its metabolites begin to increase in

urine

Resolution of Infection

Microbial infection is cleared by drug action and immune system

Metabolism and Excretion of Drug

Levels of drug or its metabolites
continue to increase in _____

urine

Urination removes these ________
from body

chemicals

Kirby-Bauer Method is the standardized method for which test

disk diffusion test

Sensitivity/resistance determined using tables relating
______ diameter with ______ resistance

zone, microbial

Table values plotted, used to determine if effective ________ of drug in body can be reached

concentration

Antibacterial drugs
derived from _____ or
_________ sources

natural or semisynthetic

Streptomyces = _____ bacterium

soil

streptomyces makes up what percent of antibiotics

70%

what are two other organisms that make antibiotics

Penicillium (fungus) & Bacillus

Four Activities of Antibiotics

1) Inhibit cell wall synthesis
2) Destroy or inhibit cell membrane activity
3) Inhibit nucleic acid synthesis
4) Inhibit protein synthesis

what are four drugs that inhibit cell wall synthesis

1.) penecillins
2.) cephalosporins
3.) bacitracin
4.) vancomycin

penecillin comes from a ____ called penicillium

fungus

Have __________ ring in structure

b-lactam

All are derivatives of 6-aminopenicillanic ______

acid

penicllian is bacterio_____

cidal

Natural Penicillin examples

Penicillin G, Penicillin V

Semi-Synthetic Penicillins

Amoxicillin, Ampicillin, Carbenicillin

Penicillinase-Resistant Penicillins

Methicillin, Nafcillin

Natural (Penicillin G) is narrow spectrum meaning

Only effective vs. gram-positive, not gram-negative

natural penicillin is destroyed by _____ and cannot be taken ______

stomach acid, orally

Semi-Synthetic (Amoxicillin) are broad spectrum meaning

More effective vs. gram-negative

semi-synthetic are less susceptible to ______ _____

stomach acid (can take orally)

1) Resembles ______ _____ ____ in peptide bridge of peptidoglycan

last amino acid

penicillin inhibits enzymes that catalyze _________

transpeptidation

it blocks

cell wall synthesis

Cells succumb to osmotic pressure and _____

lyse

Only effective against _______ _______ cells

actively growing

b-lactamases

–Enzymes that break bond in b-lactam ring
–Inactivate antibiotic

what is an example of B-lactamase

Penicillinase
- inactivates penicillin

Gram negatives have
intrinsic resistance meaning penicillin can't cross the _______ ______

outer membrane

what are two side effects of penicillin

1) Toxic at high doses
2) Allergies

Toxic at high doses

Diarrhea, delirium, anemia, irritability

Allergies

–1-5% of adults in US
–IgE overactivity
–Can be fatal

cephalosporins --->

Cephalosporins from which fungus

Cephalosporium

cephalosporins also have a b-lactam ______

ring

Based on __-aminocephalosporanic acid

7

cephalosporins are what to bacteria

bactericidal

cephalosporins are frequently given to patients with _________ allergies

penicillin

Usually names start with cef-, ceph- or kef- examples include

Cefoxitin, Keflex, Omnicef (cefdinir)

bacitracin --->

Bacitracin comes from

bacillus

bacitracin is toxic to _____ and can therefore ony be used _______

the kidney, topically

Blocks dephosphorylation of bactoprenol pyrophosphate

Carries peptidoglycan building blocks from cytoplasm where
their made to periplasmic space where cell wall is synthesized

Vancomycin comes from

streptomycin

vancomycin is a type of ________ antibiotic

glycopeptide

vancomycin given both orally and _______

intravenously

Blocks transpeptidation of peptidoglycan

Specifically binds to terminal D-alanine of peptide bridge

Used as ______ _____ when all other drugs are ineffective

“last resort”

Antibiotics that Destroy or Inhibit
Cell Membrane Activity

Polymixin B

polymixin b comes from

Bacillus polymyxa

polymixin b is toxic to the

kidney (Only administered topically)

Binds to the outer layer of the plasma membrane and destroys the ______ ________ meaning that some molecules leak out and the cell lyses

semi-permeability

Neosporin

Also sold generic as triple antibiotic ointment

Neosporin contains tree antibiotics which are

bacitracin, polymixin B, neomycin

Prevents development of resistance to any

one drug

Used topically for cuts, scrapes or burns (which are toxic to kidneys if ingested)

Bacitracin & polymixin B

Antibiotics that Inhibit Nucleic Acid
Synthesis
most are used in _____ and are not therapeutic

research

all antibiotics that inhibit nucleic acid synthesis are made of

streptomyces

Antibiotics that Inhibit Nucleic Acid
Synthesis are divided into which categories

A) Inhibit DNA Synthesis
B) Inhibit RNA Synthesis

what are two examples that inhibit DNA synthesis

Novobiocin, Mitomycin C

novobiocin

– Bacteriocidal
– Interferes with DNA supercoiling

Mitomycin C is extremely

toxic (never used)

mitomycin crosslinks

two DNA strands

mitomycin alkylates DNA chains meaning

Bases improperly recognized

examples of antibiotics that inhibit RNA synthesis

1) Actinomycin D
2) Rifampin

1) Actinomycin D

– Binds to guanines in DNA
– Blocks RNA polymerase enzyme

2.) Rifampin

– Bacteriostatic
– Binds to and inactivates RNA polymerase

rifampin are useful against mycobacteria meaning

Used in combination with a handful of other antibiotics over months of treatment

antibiotics that bond to 30s ribosomes

1) c
2) Aminoglycosides

Tetracyclines are from

streptomyces

tetracycline has a ____ ring structure

4

tetracyclines are Bacterio______

static

tetracyclines are effective only against ______ ______ bacteria

actively dividing

Binds to 30S ribosome preventing the binding of _______ to _______

tRNA to ribosome

in high doses tetracycline causes

nausea, diarrhea, permanent yellowing of teeth (eardrops)

Aminoglycosides two broad categories

Gentamycin
Streptomycin & Neomycin

Gentamycin

Micromonospora

Streptomycin & Neomycin

from Streptomyces

Aminoglycosides are all bacterio_____

cidal

Mechanism - Cause misreading of mRNA message meaning

the wrong amino acid is incorporated