Pharmacology Week 4

Question 1

ID Cellular targets of drug therapy

Answer 1

Cell wall/membrane, ribosomes, nucleus

Question 2

Methods of bacterial resistance to ribosomal inhibitors

Answer 2

Change shape of binding site

Question 3

Methods of bacterial resistance to enzyme inhibitors

Answer 3

2 drugs inhibit enzymes along same biochem pathway, effects are greater than additive

Question 4

Antagonistic effects

Answer 4

• change shape of enzyme

- make more enzyme

Question 5

Methods of bacterial resistance to intracellular drugs

Answer 5

• active efflux
• prevent entry
• make enzymes to attack drug

Question 6

Mechanism and basis of selective toxicity of antibiotics targeting cell wall

Answer 6

Cell wall synthesis inhibited in actively dividing cells: weaken and destroy cell
ST: human cells lack cell wall

Question 7

Mechanism and basis of selective toxicity of antibiotics targeting ribosomes

Answer 7

• Bind to 50S or 30S subunit, A or P site, inhibits protein synthesis
• Generally bacteriostatic (slow division) not bactericidal
• ST: structurally diff from human

Question 8

Mechanism and basis of selective toxicity of transcription inhibitors

Answer 8

• RNA polymerase inhibitors form complex with enzyme, block action
• ST: structurally different

Question 9

Mechanism and basis of selective toxicity of DNA synthesis inhibition

Answer 9

• DNA gyrase inhibitors prevent resealing step of relaxing supercoiled DNA: leads to fragmented DNA
• bactericidal
• Topoisonerase IV inhibitors interfere with DNA synthesis b/c required to separate DNA into daughter cells in division
• ST: structurally different

Question 10

Mechanism and basis of selective toxicity of purine synthesis inhibitors

Answer 10

• Competitive inhibition of 2 steps: dihydropteroate synthase and dihydrofolate reductase (DHFR)
• ST: humans can acquire THF from diet, bacteria no

Question 11

Mechanism and basis of selective toxicity of glucan synthase inhibitors

Answer 11

• Glucan impt for cell wall rigidity in fungi, without weak -> lyse
• ST: humans no cell wall

Question 12

Mechanism and basis of selective toxicity of ergosterol inhibitors

Answer 12

• antifungal, destabilizes cell membrane -> leakage
• some inhibit enzymes (squalene epoxidase*, CP450), some directly bind ergosterol
• ST: humans have cholesterol instead of ergosterol
• inhibition also causes toxic squalene buildup (dual mechanism)

Question 13

Describe with example how drugs act synergistically

Answer 13

• Complementary action: effects >additive
• consecutive enzymes in pathway
• ex. Trimethoprim + sulfamethoxazole

Question 14

Describe with example how drugs act antagonistically

Answer 14

• drugs in combination oppose each other
• ex. Penicillin + tetracycline
• cell wall synth inhibitor (dividing) + protein synth inhibitor (bacteriostatic)

Question 15

Examples of bacterial cell wall synthesis inhibitors

Answer 15

Penicillins (**amoxicillin)
Cephalosporins (cephalexin)
Glycopeptides (Vancomycin)

Question 16

Examples of inhibitors of protein synthesis

Answer 16

Macrolides (**Azithromycin)
Oxolidinones (linesolid)
Linosamides (clindamycin)

Question 17

Example of DNA gyrase inhibitors

Answer 17

Flouroquinolones (ciprofloxacin)

Question 18

Example of Purine synthesis inhibitors

Answer 18

1. Dihydropteroate synthesis inhibitor: Sulfonamides (Sulfametholxazole =SMX)
2. DHFR inhibitors: Trimethoprim =TMP
3. *Septra is combination of SMX and TMP

Question 19

Examples of inhibitors of RNA synthesis

Answer 19

Rifamycins (Rifampin)

Question 20

Examples of fungi cell wall synthesis inhibitors

Answer 20

-echinocandins (caspofungin)

Question 21

Examples of fungi cell membrane disruptors

Answer 21

1. Bind erogosterol: Polyenes (Nystatin)

2. Reduce ergosterol synthesis: Azoles (fluconazole) and Allylamines (Terbinafine)