L 1-2 Intro to Chemotherapy

Question 1

What is the function of TNF-alpha

Answer 1

Produced by macrophages
Causes fever, cachexia, apoptosis, inflammation, inhibits growth of tumors and viral replication
An acute phase reaction protein

Question 2

What are some of the differences between human and bacterial cells that are used for treatment?

Answer 2

Cell wall

50s/30s ribosomes–remember however that human mitochondria have similar ribosomes that may be affected

Question 3

What are the major groups of drug mechanisms that are used against bacteria?

Answer 3

ICWS
50s/30s protein synth inhibitors
DNA synth inhibition–DNA gyrase or polymerase

Question 4

What are ways drug resistance can be acquired by bacteria?

Answer 4

Spontaneous mutations that are then passed vertically to progeny
Horizontal transmission by:
1) Transformation: uptake of free DNA, colon common location because many dead/dying bac., mech for penicillin resistance in Pneumococci & Neisseria
2) Transduction: bacteriophage mediated, important for Staph. aureus
3) Conjugation: sex-pilus, primarily g(-), Shigella, Enterobacteriaceae

Question 5

Mechanism of Action and Resistance for:

Macrolides

Answer 5

MOA: 50s translocation
MOR: methyltransferases alter binding site

Question 6

Mechanism of Action and Resistance for:

Chloramphenicol

Answer 6

MOA: 50s transpeptidation
MOR: inactivating acetyltransferases

Question 7

Mechanism of Action and Resistance for:

Aminoglycosides

Answer 7

MOA: 30s, blocks initiation, elicits premature termination, incorporates incorrect AA
MOR: acetyl, phosphoryl, adenylyl conjugation

Question 8

Mechanism of Action and Resistance for:

Tetracyclines

Answer 8

MOA: 30s, prevent binding of incoming charged tRNA
MOR: pump out

Question 9

Mechanism of Action and Resistance for:

Fluoroquinolones

Answer 9

MOA: inhibiting topoisomerase
MOR: change in sensitivity of TI, pump out

Question 10

Mechanism of Action and Resistance for:

Rifampin

Answer 10

MOA: inhibits DNA dependent RNA polymerase
MOR: change in enzyme

Question 11

Mechanism of Action and Resistance for:

Sulfonamides

Answer 11

MOA: inhibition of folic acid synth
MOR: decrease sensitivity of target enzymes, increased formation of PABA, use of exogenous folate

Question 12

Mechanism of Action and Resistance for:

Beta Lactams

Answer 12

MOA: inhibition of cell wall synth
MOR: penicillinase, modification of PBP’s, change of porins

Question 13

Mechanism of Action and Resistance for:

Vancomycin

Answer 13

MOA: inhibition of peptidoglycan chain elongation
MOR: change in pentapeptide, D-ala D-ala lactate

Question 14

Name the bactericidal agents

Answer 14

Aminoglycosides
Bacitracin
Beta-lactams
Daptomycin
Isoniazid
Ketolides
Metronidazole
Polymyxins
Pyrazinamide
Quinolones
Rifampin
Tigecycline
Vancomycin

Question 15

Name the bacteriostatic

Answer 15

Chloramphenicol
Clindamycin
Ethambutol
Macrolides
Nitrofurantoin
Novobiocin
Oxazolidinones
Sulfonamides
Tetracyclines
Trimethoprim

Question 16

Difference between concentration and time dependent bacteriocidal agents

Answer 16

Concentration dependent: increased conc leads to increased killing
Time: changes in conc. have an effect early on, but in the long run rates of death are the same, therefore time is the factor that matters

Question 17

How do penicillins and aminoglycosides work synergistically?

Answer 17

Penicillins increase the uptake of aminoglycosides making the overall effect more than just the sum of the two individually

Question 18

How do bacteriocidal and -static agents interact when given together?

Answer 18

-cidal agents often require the cells to be actively growing in order to work, therefore -static agents can inhibit the effects of -cidals

Question 19

What are the superinfections that can result from the use of broad spectrum antibiotics?

Answer 19

Intestinal candidiasis: treated with Nystatin
Staph Enterocolitis: life-threatening
Pseudomembranous colitis: C. difficile overgrowth, treated by metronidazole or vancomycin

All caused by killing the normal flora that otherwise is protective

Question 20

How does inflammation change the volume of distribution of the drugs in the body?

Answer 20

Inflammation increases the permeability of the capillaries including in the BBB thereby increasing penetration into the CNS and increasing the volume of distribution