8. Principles of Chemotherapy

Question 1

What is chemotherapy for infectious diseases?

Answer 1

Use of synthetic, semi-synthetic and naturally occuring chemicals that selectively inhibit specific organisms causing infectious diseases

Question 2

Chemotherapy of infecitous diseases generally depends on _________?

Answer 2

Selective toxicity

Question 3

What are the 4 mechanisms of chemotherapy action?

Answer 3

1. Antimetabolites
2. Inhibitors of cell wall synthesis
3. Inhibitors of protein synthesis
4. Inhibitors of nucleic acid synthesis

Question 4

How do antimetabolites work?

Answer 4

Compete with substrate for binding to specific enzymes involved in given metabolic pathway

Question 5

What is the significance of inhibitors of cell wall synthesis ?

Answer 5

Human cells do not have cell walls like bacteria and fungi.

Allows for very specific targeting for chemotherapy

Question 6

What is the mechanism of inhibitors of protein synthesis?

Answer 6

Inhibited protein synthesis slows cellular growth.

Question 7

Inhibitors of nucleic acid synthesis are often used in treating what kinds of condition?

Answer 7

Cancer

Viral infection

Question 8

What are key laboratory methods in diagnosing infections?

Answer 8

1. Gram stain
2. Disk diffusion
3. Empiric Therapy

Question 9

What is disk diffusion laboratory diagnosis?

Answer 9

Grow microorganism on plate with several disks of different antibiotics.

Shows which antibiotics are effective against the microorganism

Question 10

What is empiric therapy?

Answer 10

Initiation of treatment prior to determination of a firm diagnosis.

Used in emergency situation

Question 11

What are 3 key features of Gram + bacteria?

Answer 11

Thick layer of murein (peptidoglycan)

Hydrophilic molecules can readil diffuse

Retain Stain

Question 12

What are 3 key features of Gram - bacteria?

Answer 12

Thin layer of murein (peptidoglcan)

Passage of hydrophilic molecules hindered

Lose stain

Question 13

What is susceptibility?

Answer 13

Minimum concentration (MIC) of antibiotic to inhibit growth of organism in vitro

Question 14

The concentration of antibiotic in the blood should exceed the MIC by how much to ensure successful treatment?

Answer 14

Exceed by a factor of 2 - 4 fold

Question 15

What is a narrow spectrum chemtherapeutic?

Answer 15

A chemotherapeutic agent acting only on a single or limited group of microorganisms

i.e. isoniazid

Question 16

What is an extended spectrum chemotherpeutic?

Answer 16

Agents that are effective against gram + and a singificant number of gram - bacteria

i.e. Ampicillin

Question 17

What is a broad spectrum chemotherapeutic?

Answer 17

Agent that affects wide variety of microorganisms

i.e. tetracylcline and chloramphenicol

Question 18

What is a therapeutic index?

Answer 18

An index used to assess the safety of a drug.

TI = TD₅₀/ED₅₀

Question 19

How does a wide therapeutic index drug’s dynamic differ from a narrow therapeutic index drug’s dynamic?

Answer 19

A wide TI drug has a wide range of doses it can give while still being safe. There is a large gap between the effective dose and toxic dose.

A narrow TI drug has a narrow range of doses it can give while still being safe. There is a narrow gap between the effective dose and toxic dose.

Wide TI drug is safer than narrow TI drug

Question 20

What precaution must be taken when administering a narrow TI drug?

Answer 20

Check peak and blood levels 30 misn before and after drug administration

Question 21

Define bacteriostatic drug

Answer 21

Bacteriostatic drugs arrest growth and replication of bacteria at serum levels achievable in patient.

Leave viable organisms to begin second cycle

Question 22

What do bacteriostatic drugs tend to target in bacteria?

Answer 22

Target metabolic pathways that are necessary for bacterial growth but not survival.

Inhibitors of protein synthesis and antimetabolites

Question 23

Define bactericidal drugs

Answer 23

Drugs that kill bacteria.

Question 24

What conditions indicate the use of bactericidal drugs rather than bacteriostatic drugs?

Answer 24

Septicemia or serious infection in patients with impaired host defense

Question 25

What to bactericidal drugs tend to target in bacteria?

Answer 25

Target metabolic pathways essential for bacterial survival Cell wall synthesis inhibitors Inhibitors of nucleic acid synthesis

Question 26

What is the only inhibitor of protein synthesis that is bactericidal?

Answer 26

Aminoglycosides

Question 27

Penicillin uses what mechanism of chemotherapy action?

Answer 27

Inhibitor of cell wall synthesis

Question 28

Cephalosporin uses what mechanism of chemotherapy action?

Answer 28

Cell wall synthesis

Question 29

What are the 4 bacteriostatic inhibitors of protein synthesis antibiotics?

Answer 29

Chloramphenicol Clindamycin Macrolides-erythromycin Tetracycline

Question 30

What are 2 bacteriostatic antimetabolite antibiotics?

Answer 30

Sulfonamide Trimethoprim

Question 31

When do we use a combinatoin of antimicrobial drugs?

Answer 31

Against organisms resistant to single drug therapy Severe infection of uncertain etiology or polymicrobial infection

Question 32

What 3 bacteria are resistant to single drug therapy?

Answer 32

Pseudomonas Group D streptococci Tuberculosis

Question 33

What are 4 adverse effecs of antibiotic therapy?

Answer 33

Drug-drug interactions Allergic reactions Superinfections GI disturbances

Question 34

Two or more drugs administered in therapeutic dosages at hte same time or in close sequence has what 3 possible outcomes (drug to drug interactions)?

Answer 34

1. May act independetly 2. May interact to increase or decrease the magnitude or duration of action of one or more drugs 3. May interact to cause an unexpeceted reaction

Question 35

What kinds of antibiotic allergic reactions can occur?

Answer 35

Substantial morbidity and mortality T cell mediated delayed hypersensitivity IgE mediated immediate hypersensitivity Cross allergy between beta-lactam antibacterial agents

Question 36

What are someclassic GI disturbances from antibiotics?

Answer 36

Nausea, retching, vomiting Diarrhea Abdominal cramping Pseudomembranous colitis

Question 37

What are the mechanisms of drug resistance?

Answer 37

Treatment with an antibacterial agent affects resistance patterns: 1. Genetic mutation causes resistance 2. Gene transfer facilitates the spread of resistance

Question 38

How do you decrease drug resistance?

Answer 38

1. Only use when there is a well established need for antibiotics 2. Select based on susceptibility tests 3. Adequate doses for adequate duration

Question 39

What is antibacterial prophylaxis?

Answer 39

Administration of a single effective drug to PREVENT infection by a specific organism or to eradicate it soon after it has been established

Question 40

What are the two purposes of antibacterial prophylaxis?

Answer 40

To protect healthy persons from infection by a specific microorganism to which they have been exposed To prevent secondary bacterial infection in patients who are ill with other diseases

Question 41

When must we do SBE (subacute bacterial endocarditis) prophylaxis?

Answer 41

All dental procedures that involve manipulation of gingival tissue or PA region of teeth or perforation of oral mucosa in patients that have reaosnable risk of endocaditis