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Multisystem Pharm > Antibiotics I > Flashcards

Antibiotics I Flashcards

1
Q

What does bacteriostatic mean?

A

Stops growth or replication of microorganism

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2
Q

What does bactericidal mean?

A

KILL (the microorganism)

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3
Q

Drop the MIC aka drop the ___________

A

Minimal inhibitory concentration (the smallest amount needed to have its effect)

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4
Q

What is the Post-antibiotic effect (PAE)?

A

The PAE is when the antibiotic has bactericidal activity after its concentration falls below the MIC. This can occur if the antibiotic accumulates in the tissue or the bacteria itself.

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5
Q

When can a superinfection occur?

A

When you are undergoing antimicrobial therapy that is getting rid of your normal happy oral/gut flora, you can get a super duper infection. Wahh.

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6
Q

When we talk about pharmacokinetics we talk about the LADME process. Wtf is the LADME process?

A

LADME=

  1. Liberation: release of drug from dosage form
  2. Absorption: drug goes from site of admin to blood
  3. Distribution: drug goes to tissues
  4. Metabolism: drug is transformed into easily eliminated products
  5. Excretion: get rid of the drug or metabolite
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7
Q

What is the one-compartment model?

A

Drugs rapidly equilibrate with the tissue and there is linear elimination over time.

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8
Q

What is the two-compartment model?

A

Drugs slowly equilibrate with the tissue. There is a distribution phase where the drug moves between central compartment and tissue compartment and elimination phase where you guessed it, elimination happens.

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9
Q

What is the relationship between the % of antibiotic bound to protein and its antimicrobial activity?

A

Inverse. More protein bounded drug, less bacteria fighting power

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10
Q

What are some of the predictors of efficacy of antibiotics? (factors that define certain antibiotics)

A
  1. Concentration dependent killing: more drug=more killing
  2. Time-dependent killing: want to max the amount of above MIC exposure.
  3. Area under the curve concentration/time curve: PAE, so basically the drug is still doing its job when it is in the tissue and you don’t need to focus on keeping concentrations above MIC.
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11
Q

What are some examples of Concentration dependent antibiotics with some PAE

A
  1. Aminoglycosides
  2. Daptomycin
  3. Quinolones
  4. Ketolides
    My AMIGO likes QUINOA with a DAP of HIGH CONCENTRATION KETONES.
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12
Q

What are some examples of Time dependent antibiotics with minimal PAE

A
  1. Beta-lactams (penicillins, carbapenems, cephalosporins)

2. Vancomycin (some)

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13
Q

What are some examples of Time dependent killing and moderate to long PAE

A
  1. Chloramphenicol
  2. Clindamycin
  3. Tetracycline
  4. Oxazolidines
  5. Streptogramins
  6. Glycopeptides
  7. Macrolides
  8. Sulfonamides

GMC COSTS a lot of PAE and time

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14
Q

When we compare mammalian cells to the bacterial cells, there are two differences we should keep in mind. Out of all the differences that exist, guess the two I’m thinking of.

A
  1. We have no cell wall

2. We don’t use D amino acids ever

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15
Q

Whats the difference between gram positive and gram negative?

A

Gram positive: cell wall made of peptidoglycan

Gram negative: periplasmic cell wall made of peptidoglycan with another cell membrane with lipopolysaccaride (LPS) sticking out of it.

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16
Q

What kind of antibiotics work on inhibiting the cell wall biosynthesis?

A

Beta lactams, which includes:

  1. Penicillins
  2. Cephalosporins
  3. Monolactams
  4. Carbapenems

Glycopeptides (Vancomycin, Teicoplanin)

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17
Q

How to beta lactams do their job in inhibiting cell wall biosynthesis?

A

They inhibit the enzyme transpeptidase. This enzyme is usually used to make peptidoglycan polymer crosslinks between D-Ala-D-Ala subunit and glycine. The shared 4 sided beta-lactam ring structure allows the antibiotic to bind to the enzyme and keep it from doing its real job.

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18
Q

What is the significance of penicillin binding protein (PBPs)?

A

These are all the proteins that penicillins will bind to (apparently its not just the transpeptidase we just learned about). In order for the beta-lactam to be effective it must inhibits many other PBPs

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19
Q

What are the 4 types of penicillin?

A
  1. G: naturally occurring, acid labile and V: synthetic, acid stable. Both cover Gram +
  2. Penicillinase-resistant
  3. Extended range: covers gram - as well
  4. Antipsuedomonal
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20
Q

Penicillins have 2 named rings in their structure

A
  1. B-lactam ring (4 sides)

2. Thiazolidine ring (5 sides)

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21
Q

What can you do to absorb the penicillin slower?

A

Inject with procaine or benzathine.

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22
Q

Where does penicillinase (the enzyme produced by bacteria to destroy our antibiotics) usually strike the antibiotic?

A

Right in the beta-lactam ring (specially between the nitrogen and the carbonyl in case you were curious). What a jerk.

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23
Q

What are two examples of penicillinase-resistant penicillins

A
  1. Nafcillin

2. Cloxacillin (+improved ½ life)

24
Q

What are examples of extended range penicillins

A
  1. Ampicillin
  2. Amoxicillin

i AM EXTENDED RANGE

25
Q

What modification occurs in extended range penicillins

A

Different R groups off of the beta-lactam ring. Makes them orally available

26
Q

What are examples of anti-pseudomonal penicillins?

A
  1. Ticarcillin (IV)

2. Ureidopenicillin (brand new!)

27
Q

Why are cephalosporins so special?

A

Now the structure we are dealing with is:

  1. Beta lactam ring
  2. Cephalosporin (6 sided) ring Instead of just being able to substitute R groups on the B-lactam ring, we can put R groups on the cephalosporin ring now too!

So many more options!

28
Q

1st generation cephalosporins

A

Narrow spectrum Gram +. These are used mainly prophylactically for surgery since there is resistance.

  1. Cefazolin (IV/IM)
  2. Cephalexin (Oral)
  3. Cephradine (Oral/IV/IM)
  4. Cefadroxil (Oral)
29
Q

2nd generation cephalosporins

A

Less active against gram +, more against gram -. Used for intestinal anaerobes mostly

  1. Cefoxitin: B. fragilis
  2. Cefuroximine
  3. Cefaclor: H.flu
    * She listed about 9 drugs here and talked about the above 3 briefly. Not about to memorize them all.
30
Q

3rd generation cephalosporins

A 
Has broader spectrum and location of action: Used against pneumonias, Klebsiella, Enterobacter, Proteus and Haemophilus
Works in the:
1. CNS
2. Lung
3. Bone
4. Urinary tract
31
Q

Examples of 3rd generation cephalosporins

A
  1. Ceftriaxone

2. Ceftaroline fosamil: new drug for MRSA infections

32
Q

4th generation cephalosporins

A

More active against gram - and used with beta lactamase organisms
Example: cefepime

33
Q

Carbapenems. Structure? Resistance?

A
  1. B-lactam ring

2. DIFFERENT 5 sided ring Resistant to B-lactamases

34
Q

Examples of carbapenems

A
  1. Imipenem
  2. Meropenem
  3. Ertapenem
  4. Doripenem
35
Q

Tell me about imipenem

A
  1. Broad spectrum
  2. no cross resistance from other antibiotics
  3. cross allergenicity with penicillin and nephrotoxicity
  4. hydrolyzed by renal tubules dipeptidase
36
Q

Tell me about meropenem

A
  1. NOT hydrolyzed by renal tubule dipeptidase

2. Reduced nephrotoxicity

37
Q

Ertapenem

A
  1. Longer ½ life

2. 1 a day dosing

38
Q

Doripenem

A
  1. MIC similar to imipenem but no nephrotoxicity

2. Drug interaction with valproate causes seizures

39
Q

Monobactams Structure?

A

ONLY ONE RING OMG

40
Q

What is the main monobactam that we need to know and what’s so special about it?

A

Aztreonam

  1. Good against gram - aerobes, not for gram +
  2. Available as inhaled solution to treat P. aeruginosa in CF patients
  3. low cross allergenicity with penicillin
  4. Cross the placenta but safe during pregnancy
41
Q

Bad side effects of penicillin

A
  1. Allergic rxn
  2. Hemolytic anemia (due to some b-lactams inhibiting vitamin K, leading to platelet dysfunction)
  3. Nephritis
  4. Seizures (esp with people with renal failure that can’t clear the drug)
42
Q

Explain how penicillin allergy occurs

A
  1. The b-lactam ring on the penicillin opens up
  2. This new structure attaches to the lysine residue on proteins
  3. This makes the antigen that causes an allergic rxn
43
Q

What are the different types of penicillin allergies?

A
  1. Immediate type 1: you’re about the die (anaphylaxis, bronchospasm, IgE mediated). Avoid all penicillin, cephalosporin and carbapenem
  2. Delayed, non-utricarial rash: not IgE mediated red rash. Most can take cephalosporins
  3. Idiopathic: often in mono patients. can take b-lactams after disease ends
  4. Non-allergic: diarrhea/nausea usually due to loss of normal gut flora
44
Q

Side effects of cephalosporins?

A
  1. Thrombophlebitis: vit K deficiency
  2. Diarrhea
  3. Allergic reaction: cross allergenicity with penicillins (similar structure)
  4. Hemolytic anemia
  5. Nephrotoxicity
45
Q

Why should you not drink alcohol when taking 2nd generation cephalosporins?

A

Because it inhibits aldehyde dehydrogenase, which leads to a build up of acetaldehyde (metabolite of ethanol)

46
Q

Where are b-lactams cleared?

A

Mostly the kidney

47
Q

Mechanism of b-lactam resistance?

A
  1. B-lactamses
  2. Decreased affinity of penicillin binding protein for bacteria
  3. Decreased membrane permeability (gram -)
  4. Energy dependent efflux pumps
48
Q

Glycopeptides include:

A
  1. Vancomycin

2. Teicoplanin

49
Q

How do glycopeptides work?

A

They bind to the D-Ala-D-Ala substrate on the cell wall and prevent transpeptidases from binding. Because these drugs are so BIG they can not fit through the pores of gram negative bacteria to get to the cell wall, so they work on GRAM POSITIVE ONLY

50
Q

Side effects of vancomycin

A
  1. When given too fast, can cause exfoliative dermatitis that is directly toxic to mast cells. Give this drug IV, NOT IM
  2. Nephrotoxicity
  3. Ototoxicity
51
Q

Does Teicoplanin have the same side effects as vancomycin?

A

No

  1. Only a skin rash
  2. Can be given IM
  3. Less nephrotoxicity
  4. No ototoxicity
52
Q

Lipopeptides are antibiotics that inhibits cell membrane structure. Name two types

A
  1. Daptomycin

2. Polymixins A and B

53
Q

How does daptomycin work?

A

Its a big sucker that can insert itself into the cell membrane and then cause ion leakage/depolarization of the cell.

54
Q

Does daptomycin work on gram negatives?

A

No because it is so big it can’t fit through the pores. This drugs is reserved from drug resistance bacteria.

55
Q

How is daptomycin administered

A

IV because it is directly toxic to muscle so can’t do IM

56
Q

What are polymyxins A and B usually used for?

A

Skin infections (topical)

Multisystem Pharm (9 decks)

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