Principles of Antimicrobial Chemotherapy and 16,17 Cancer Chemotherapy

Question 1

Describe how the “disk diffusion” test evaluates antibiotic resistance and sensitivity.

Answer 1

Disks containing antibiotics are placed on culture dishes with microorganism. If there is a zone of inhibition of growth around a disk, then the microorganism is sensitive to that antibiotic. If the organism grows freely around that disk, then it is resistant to that antibiotic.

Question 2

Apply 3 bactericidal to a clinically-relevant case scenario.

Answer 2

Bactericidal: bacitracin, beta-lactams (inhibit cell wall synthesis), quinolones (disrupt DNA synthesis), aminoglycosides, polymyxins, rifampin (disrupt RNA synthesis)

Question 3

beta-lactams

Answer 3

inhibit cell wall synthesis

Question 4

quinolones

Answer 4

disrupt DNA synthesis

Question 5

rifampin

Answer 5

(disrupt RNA synthesis)

Question 6

Apply 3 bacteriostatic anti-microbials to a clinically-relevant case scenario.

Answer 6

tetracyclines (inhibit protein synthesis), sulfonamides (antimetabolite), trimethoprim (antimetabolite), chloramphenicol, macrolides, novobiocin, clindamycin (inhibit protein synthesis).

Question 7

Apply 4 disadvantages of using antibiotic therapy to a clinically-relevant case scenario.

Answer 7

1. Risk of toxic or allergic reactions.
2. Possible antagonism of antimicrobial effects.
3. Increased risk of superinfection.
4. Selection of drug resistant bacteria.
5. Cost

Question 8

Apply 3 situations in which antibiotics are used prophylactically to a clinically-relevant case scenario.

Answer 8

1. Surgery: cardiac, peripheral vascular, orthopedia, GI.
2. Bacterial endocarditis: congenital/valvular heart disease and prosthetic heart valves.
3. Neutropenia: lowering of WBCs.

Question 9

Apply 2 conditions where antibiotics are not appropriate to a clinically-relevant case scenario.

Answer 9

1. Untreatable infection: some viral infections.
2. Fever of unknown origin: may not be due to infection.
3. Improper dosage.

Question 10

Draw a diagram demonstrating the importance of rapid and frequent chemotherapy treatments in a fast-growing neoplasia.

Answer 10

Chemotherapy must be given to achieve a fractional cell kill in a log fashion (1-log kills = 90%, 2-log kill = 99% of cells). To ensure therapy is successful, want 2-5 log kills. If the frequency of treatment is lower than the growth rate of the neoplasia, then the treatments will not be able to reduce the neoplastic cell population (top graph)

Question 11

Apply p-glycoprotein as an energy-dependent efflux pump for anti-tumor agents to a clinically-relevant case scenario.

Answer 11

The MDR1 gene encodes cell surface p-glycoprotein that is involved in drug efflux (ATP dependent). This allows the development of a multidrug resistant phenotype because certain classes of drugs are moved by this glycoprotein.

Overexpression of multidrug resistance protein (MRP), another transporter increases resistance to:
Anthracyclines, vinca alkaloids.

Question 12

Apply three types of cells possibly reduced during myelosuppression and a symptom of each to a clinically-relevant case scenario.

Answer 12

Myelosuppression: bone marrow suppression. Results in low platelet, WBC (leukopenia) and RBC (anemia) counts.
Leukopenia: fever, sore throat, cough or shortness of breath, nasal congestion, burning during urination, shaking chills, redness/swelling/warmth at site of injury.
Anemia: fatigue, dizziness, headaches, irritability, shortness of breath, increase heart/breath rate.
Thrombocytopenia: bruise easily, bleed longer than usual after minor cuts/scrapes, bleeding nose/gums, develop ecchymyoses/petechiae, serious internal bleeding.

Question 13

Apply three serotonin antagonists given as anti-nausea agents in cancer patients to a clinically-relevant case scenario.

Answer 13

1. Dolasetron 2. Granisetron 3. Ondansetron

First-line antiemetics: most effective in treating nausea and vomiting but are expensive.

Question 14

Describe the relationship between the CTZ and vomiting center and give two receptors in the VC.

Answer 14

The vestibular apparatus sends projections to the chemoreceptor trigger zone (CTZ). CTZ and vomiting center (VM) are located in the medulla.
D2 receptors: Dopamine
5-HT3 receptors: Seratonin

Question 15

Apply three antidopaminergics given as anti-nausea agents in cancer patients to a clinically-relevant case scenario.

Answer 15

1. Prochlorperazine 2. Fluphenazine 3. Chlorpromazine

Second line drugs: treat mild to moderate nausea and vomiting. Selectively depress CTZ, VM to lesser extent.