Antibiotic Classes and MOA

Question 1

What are the targets for killing a cancer cell?

Answer 1

DNA and Mitotic tubules

Question 2

Do we want to target what we do in cancer cells when trying to kill bacteria?

Answer 2

NO. Because bacterial cells have things in them that our cells don’t and therefore we can target that

Question 3

What are some things we target in bacterial cells?

Answer 3

• Cell wall synthesis
• Transcription and translation
• DNA synthesis and integrity

Question 4

What do bacteriostatic drugs do?

Answer 4

• Inhibits cell growth, does NOT kill the cell

- They slow down the spreading of the bacteria and then the immune system takes over for the rest

Question 5

What do bactericidal drugs do?

Answer 5

Kill bacteria

Question 6

What do bacteriostatic drugs target?

Answer 6

Protein synthesis (except aminoglycosides)

Question 7

What do bactericidal drugs target?

Answer 7

Cell wall synthesis

Question 8

Who should get bacteriostatic drugs?

Answer 8

• Non-immune compromised

- Uncomplicated infections

Question 9

Who should get bactericidal drugs?

Answer 9

Immune compromised (particularly if life threatening infection)

Question 10

How many drugs are bacterial infections usually treated with?

Answer 10

1 drug

Question 11

What is antibiotic synergism and when would you use it?

Answer 11

• Combination therapy (using 2+ antibiotics)
• Can be critical for life-threatening infections
• Infrequently would 2 antibiotics in the same class be used together

Question 12

What is the MIC?

Answer 12

• Minimal inhibitory concentration (minimal effective dose)
• When the curve drops below the MIC you must redose
• how much drug you need to stop the bacteria from growing

Question 13

When are concentration dependent antibiotics most effective?

Answer 13

When they have a high peak concentration

• Highest concentration kills
• Aminoglycosides

Question 14

When are time-dependent antibiotics most effective?

Answer 14

When there is a long exposure to a drug

• Longest duration over MIC kills
• Beta-lactams

Question 15

What makes up the cell wall?

Answer 15

Peptidoglycan

Question 16

Why is peptidoglycan a target for antibiotics?

Answer 16

Three enzymes are needed to build the polymer and all three are targets for antibiotics

Question 17

What is peptidoglycan made of?

Answer 17

Two amino sugars in chain cross-linked to 5 amino acids

Question 18

What are the two sugars in peptidoglycan and which has amino acids attached to it?

Answer 18

NAG and NAM

-NAM has the amino acids on it

Question 19

How are the sugars connected?

Answer 19

They are cross-linked via 5 glycines and this is referred to as TRANSPEPTIDASE ENZYME

Question 20

What is the target for beta lactam drugs?

Answer 20

Transpeptidase enzyme

Question 21

What are three reasons for antibiotic resistance to penicillin?

Answer 21

1. Bacteria developed “penicillinase enzymes”
2. Bacteria have resistant transpeptidase enzymes
3. Bacteria have multiple resistance patterns

Question 22

What is the function of an OAT?

Answer 22

Secretes penicillin drugs into urine, enhancing elimination

Question 23

What is probenicid?

Answer 23

• OAT inhibitor
• Using probenicid with penicillin helps prolong blood and tissue levels of the antibiotics, giving longer duration of efficacy

Question 24

Why would you not want to give probenicid to a patient with a UTI?

Answer 24

Because probenicid keeps the drug away from the urine so its not excreted, but with a UTI we want the drug to go to the urine

Question 25

______ have surpassed the use of oral amino and natural penicillins.

Answer 25

Oral Cephalosporins

Question 26

What are the two most common oral cephalosporins used currently?

Answer 26

Cefdinir and Cefpodoxime (both are 3rd generation)

Question 27

Unless a resistant organism has been previously identified, what two generations of cephalosporins can be started for broad empiric coverage?

Answer 27

3rd or 4th generation

Question 28

What generation are common pre-op antibiotics when viscera are not entered?

Answer 28

1st generation

Question 29

Why is it necessary to use a different beta lactam antibiotic when treating a strept throat infection vs an E. coli UTI?

Answer 29

Because even though all bacteria have the transpeptidase enzyme, different transpeptidase enzymes are found in different bacteria

Question 30

What are processes of the cell wall we target to kill the cell?

Answer 30

1. Transpeptidase (BLs) 2. Transglycosylation (binds NAG-NAM units together) 3. Transamination (binds the peptides to NAM)

Question 31

What is the action of vancomycin?

Answer 31

Inhibits cell wall synthesis - Blocks transglycosylase (binding of NAM and NAG) - Blocks transpeptidase * Bactericidal

Question 32

Does vancomycin treat gram + or -?

Answer 32

Gram + ONLY

Question 33

What route is vancomycin given?

Answer 33

- Poorly absorbed orally | - IV requires monitoring to prevent renal and ototoxcitiy

Question 34

What are the chemical properties of vancomycin?

Answer 34

- Glycopeptide - BIG molecule - Polar - Water soluble

Question 35

What is vancomycin used for?

Answer 35

BIG GUN - Only used for severe or resistant gram positive infections - Sepsis due to strep. pneumo or MRSA

Question 36

What are potential side effects of vancomycin?

Answer 36

- Red man syndrome | - Renal and Oto toxic (too high blood levels of vancomycin can cause dead kidneys and deafness)

Question 37

Is vancomycin a concentration-dependent or time-dependent drug?

Answer 37

Time-dependent * Its efficacy is primarily dependent on Duration of time above the MIC, not the Cpeak * Too high Cpeak is toxic!!!

Question 38

What drug class is daptomycin?

Answer 38

Lipopeptide

Question 39

What is the action of daptomycin?

Answer 39

Toxic to the cell wall and cell membrane - Binds to the membranes and disrupts non-polar permeability - Bactericidal - Won't use unless consulted with infectious disease

Question 40

What is the action of fosfomycin?

Answer 40

It blocks an early step in cell wall synthesis

Question 41

What is fosfomycin a good choice to treat?

Answer 41

Uncomplicated UTI | *Beta-lactam allergies

Question 42

How can we target protein synthesis in bacterial cells without it hurting our own cells?

Answer 42

Human ribosomes (which are responsible for protein synthesis) have 40s and 60s subunits while bacterial ribosomes have 30s and 50s ribosomes

Question 43

What drug classes are protein synthesis inhibitors?

Answer 43

- Tetracyclines (30s bacteriostatic) - Macrolides (50s bacteriostatic) - Aminoglycosides (30s bactericidal) - Lincosamides & Oxazolidinones (50s bacteriostatic)

Question 44

What two drugs in the tetracycline class do we most often use?

Answer 44

- Doxycycline | - Minocycline

Question 45

What is Tigecycline?

Answer 45

A new tetracycline - Only indication is Gram + resistant organisms like MRSA - Never use for UTI - Restricted drug - Not able to order this for uncomplicated cellulitis

Question 46

What is the tetracycline class good for?

Answer 46

-Well distributed in water/urine (UTIs, urethritis)

Question 47

What are tetracyclines not good for?

Answer 47

- Not good for CNS infections as they are too large/polar to cross into CNS (not for meningitis) - Drugs chelate calcium which discolors teeth (don't take with dairy products)

Question 48

What is the most often used macrolide?

Answer 48

Azithromycin (Z-pak)

Question 49

What macrolide is infrequently used?

Answer 49

Erythromycin because it has many drug/drug interactions

Question 50

What are the common aminoglycosides that are used?

Answer 50

- Gentamicin | - Tobramycin

Question 51

What is the action of aminoglycosides?

Answer 51

- Irreversible inhibitors of protein synthesis - Moves into cells via porin channels - Actively transported into cytoplasm - Binds to 30s subunit of ribosome

Question 52

What should you not use aminoglycosides for?

Answer 52

Meningitis (poor CNS penetration)

Question 53

Are aminoglycosides concentration dependent or time dependent?

Answer 53

Concentration, higher concentration = higher kill rate * But higher concentration enhances toxicity risk * Blood levels and kinetics need to be obtained * Oto and nephrotoxic (best to get patient off of these and onto less toxic drugs)

Question 54

What two drugs are sulfonamides (anti folate drugs)

Answer 54

-Trimethoprim -Sulfamethoxazole (if these two are given together its bactrim)

Question 55

What can you NOT use sulfonamides for?

Answer 55

Streptococcus

Question 56

What is the most common use for sulfonamides?

Answer 56

UTI (e. coli)

Question 57

What three drugs are fluoroquinolones?

Answer 57

- Ciprofloxacin - Levofloxacin - Moxifloxacin

Question 58

What is the action of fluoroquinolones?

Answer 58

Inhibit bacterial topoisomerase II

Question 59

What are known complications of fluoroquinolones?

Answer 59

Tendon rupture, skeletal muscle injury, peripheral neuropathy

Question 60

What drug is a nitroimidazole?

Answer 60

Metronidazole

Question 61

What is metronidazole good to treat?

Answer 61

ANAEROBES | -Pelvic, vaginal, and intra-abdominal infections (including STDs, post-operative, perforations)