Antimicrobial Pharmacology Flashcards
1
Q
How are bacterial cell wall inhibitors classified?
A
Penicillins
Cephalosporins
Carbapenems
Others
2
Q
What is the process of cell wall synthesis in bacteria?
A
- starts with 2 major proteins - NAM and NAG ( N - acetylmuramic acid and N-acetylglucosamine).
- Very long chains of these proteins are bound together to make a train.
- In order to make a wall, 2 trains need to be bound together by 2 chains of amino acids.
- Penicillin-binding protein cleaves off 2 end units, binds the amino acid chains together tightly, and keeps doing that over and over again until two very long trains are hooked together to make a strong cell wall for the bacteria.
3
Q
What is the mechanism of action of the cell wall synthesis inhibitors?
A
- They stop the production of the cell wall - hence cell wall synthesis inhibitors.
- Beta-lactam antibiotics are given.
- Beta-lactam ring binds to the penicillin-binding protein and prevents the cross-linking of NAM and NAG chains to each other.
- This does not affect the pre-existing bacteria but when the bacteria try to divide, the new cell cannot build a new wall.
- Spheroplast = bacteria without a cell wall. It cannot infect the body, it autocatalyzes and dies.
4
Q
What are the mechanisms of antibiotic resistance?
A
- B-lactamase-mediated resistance
- Penicillin-binding protein-mediated resistance
- Porin-mediated resistance
5
Q
What is B-lactamase mediated resistance?
A
- Beta-lactamases are enzymes within the bacteria that break down the beta-lactam ring.
- They break down the antibiotic that is killing them.
- This affects many antibiotics with beta-lactam rings in their structure - penicillins, cephalosporins, some cephamycins, and other carbapenems.
- produced mainly by gram + bacteria ( can also be from gram -).
- secreted in presence of antibiotics.
6
Q
What can be done to counteract the beta-lactamase activity?
A
- With penicillin-based beta-lactamases, we can counter it with certain types of inhibitors of these enzymes.
- Clavulanic acid is an example of a beta-lactamase inhibitor.
- Pair clavulanic acid with amoxicillin
- Tazobactam with piperacillin
- Ampicillin with Sulbactam
7
Q
What is penicillin-binding protein-mediated resistance?
A
- Penicillin-binding protein that is resistant to the effects of beta-lactam activity.
- Naked DNA from resistant bacteria gets incorporated into the cell.
- The host DNA is now changed. When host DNA produces a new penicillin-binding protein, it’s slightly different - enough to be resistant to the beta-lactam antibiotic but is still able to produce a cell wall.
- Reduced affinity to the new beta-lactam antibiotic.
8
Q
What is porin-mediated resistance?
A
- Porins are water-filled channels.
- Tubular structure seen in cell walls.
- Antibiotics travel through the porins to get into the bacteria.
- If bacteria has adapted and makes fewer porins you’ll have less ability for the antibiotic to get in.
- seen in Pseudomonas aeruginosa.
trick = P for porins and P for Pseudomonas.
9
Q
What are the 5 different types of penicillins?
A
- Natural Penicillins
- beta-lactamase resistant penicillins
- Aminopenicillins
- Carboxypenicillins
- Ureidopenicillins
10
Q
What are the types, structures, and indications of natural penicillin?
A
Types:
- Several different types
- Penicillin G is the most common
- Also K, N, V
Structures:
Indications:
- Penicillin G is used in strp throat and necrotizing enterocollitis.
- These agents are used in syphilis, leptospiralis, and in gonorrhea.
Given IM or IV.
Focus mostly on gram + organisms.
- Penicillin V - used more commonly in strp throat, otitis media in children, cellulitis and in rheumatic fever.
- Is acid stable - can survive the gut and therefore can be given orally.
11
Q
What is the pharmacology of beta-lactamase-resistant penicillin?
A
- Methicillin, Oxacillin, Cloxacillin
- Cloxacillin used in skin infections, cellulitis, impetigo, some pneumonias, septic arthritis, otitis.
- Safe in pregnancies
- Staph that produce beta-lactamase can be treated with cloxacillin.
- Long R chain present in cloxacillin - prevents beta lactamase from binding to it,
Methicillin:
- not used as much anymore
- Important = lot of resistance to this drug.
- MRSA - big problem in hospitals.
- Methicillin is liked to interstitial nephritis.
Nafcillin:
- Associated with neutropoenia.
12
Q
What is the pharmacology of aminopenicillins?
A
- Ampicillin and amoxicillin
- Wide spectrum antibiotics but can still be susceptible to beta lactamases.
- can be give IM or IV.
- Indications: bacterial meningitis, endocarditis, GI infections like salmonella, genitourinary tract, used in catheter-based infections.
- Also used in bacterial endocarditis prophylaxis.
- Ampicillin can by enhanced with an additional agent (sulbactam) to protect it from the effects of the beta-lactamase.
- In enterococcal infections we use aminoglycosides in combination with ampicillin or amoxicillin - gentamycin + ampicillin (common type of regimen for complicated infections).
13
Q
What are the pharmacological features of ureidopenicillin?
A
- Pipercillin is an intensive care unit kind of drug.
- Broad-spectrum agent
- Very good gram-negative coverage but it also has some good gram-positive coverage as well.
- Pair this with a beta-lactamase inhibitor.
- Pipercillin + Tazobactam
- Pseudomonas seen in wet infections
- Intubated patients in ICU - complicated infections involving areas like a wet mucosa = wet infection - pipercillin is used to treat it.
- Lacks strong activity against staph aureus
Indications:
- pipercillin tazobactam used in neutropenic sepsis
14
Q
How are cephalosporins classified?
A
- Cephalosporins are divided into generations
- 1st generation (fal,fad,faz)
- 2nd generation (fam,fur,fac)
- 3rd generation
- 4th generation (cefepime)
- 5th generation
- Unclassified
15
Q
What are the 1st generation cephalosporins?
A
- Cefazolin, Cefalotin, Cefalexin, Cefadroxil
- Cefazolin - excellent coverage against gram + organisms.
- Used in surgical infections, for skin infections,
- Not effective against gram negative bacteria - not good for urinary tract infection.
16
Q
What is the mechanism of action of 2nd generation Cephalosporins?
A
- Cefuroxime, Cefaclor, Cefamandole , Cefotetan, Cefoxitina
- Effective against gram - bacteria
17
Q
What are the uses of 2nd gen cephalosporins?
A
- Effective against gram - bacteria.
- Used in respiratory infections.
- Cefuroxime works against gram-bacteria such as Haemophilus Influenzae.
18
Q
What are the mechanisms of action of 3rd gen cephalosporins?
A
- Ceftriaxone, Cefoperazone, Cefotaxime, Ceftazidime, Ceftributen, Cefixime, cefpodoxime, cefoperazone + sulbactam
- Effective against gram - bacteria, less effective against gram + bacteria
- some like Cefotaxime will work against organisms that are resistant to penicillins.
- We only use these types in serious infections.
19
Q
What is the mechanism of action and uses of 4th gen cephalosporins?
A
- Cefepime
- Zwitterions - 2 different charges on the same molecule.
- More resistant to beta-lactamase producing organisms
20
Q
What is the pharmacology of Penems?
A
Penems - can be sulfapenems and carbapenems
- Sulfapenems - e.g., Faropenem
- Orally active unsaturated b-lactam antibiotic.
- Resistant to many different forms of extended-spectrum beta-lactamases.
- better chemical stability than most agents.
- Effective in TB
- Carbapenems = Imipenem, Meropenem
- Imipenem - powerful
- Contains b-lactam ring but has low susceptibility to penicillinase.
- It is susceptible to a kidney enzyme called dehydropeptidase so it must be administered along with an inhibitor called cilastatin.
- wide-ranging agent = used against all kinds of organisms
- gram + cocci, gram - rods, anaerobic infections, used against pseudomonas and Acinetobacter species.
-Pneumosepsis, bleeding gut
21
Q
What are the structure, uses, and spectrum of activity of imipenem, doripenem, and meropenem?
A
- Carbapenems = Imipenem, Meropenem
- Imipenem - powerful
- Contains b-lactam ring but has low susceptibility to penicillinase.
- It is susceptible to a kidney enzyme called dehydropeptidase so it must be administered along with an inhibitor called cilastatin.
- wide-ranging agent = used against all kinds of organisms
- gram + cocci, gram - rods, anaerobic infections, used against pseudomonas and Acinetobacter species.
-Pneumosepsis, bleeding gut
22
Q
What are the pharmacological features and indications of vancomycin?
A
- Vancomycin = bacterial glycoprotein - binds to peptidoglycan in the cell wall.
- Binds to alanine terminal - stops cell wall synthesis.
- downside = if cell wall has an altered alanine terminal on its NAG, it will not allow vancomycin to bind - decreased affinity to vancomycin = Vancomycin-resistant.
- Vancomycin is limited to serious infections only.
- Powerful agent - has some side effects :
- Large molecule - doesn’t cross BBB.
- Often used intrathecally in serious spinal infection (severe spinal or central meningitis)
- Can use the drug orally in certain conditions - doesn’t pass the gut barrier (stays in the gut) - used in gut infections - Enterococcus mediated infections.
- Vancomycin-Resistant cocci (VRE)
23
Q
What are the toxicity issues of Vancomycin?
A
- Red man syndrome
- Severe cutaneous reaction where you have tremendous flushing (bright red) due to histamine release.
- Other side effects include:
phlebitis, ototoxicity, nephrotoxicity.
24
Q
What is the structure and indications of Teicoplanin?
A
- Has a complicated structure
- Used in prophylaxis (not really used in a lot of clinical practice)
- used to treat MRSA and methicillin-resistant enterococcus faecalis.
- Also used in the treatment of pseudomembranous colitis and in clostridium difficile diarrhea.
25
Q
What is Bacitracin?
A
- Intra-cellular agent
- Used as a prophylactic measurement in wards
- It is a bacterophenol inhibitor ( aka dolichol-11. It is a lipid in the cell wall of the bacteria. By inhibiting the bacterophenol pathway, you can inhibit the growth of the new bacteria)
- Used in the topical treatment of certain types of infections and in decontamination syndromes.
- Used in staph colonization in the skin and used in particularly bad superficial infections.
- When bacitracin is taken Intravenously or parenterally it can cause nephrotoxicity
- Prefer to use it on the surface of the skin
26
Q
What are the bacterial protein synthesis inhibitors?
A
Classification:
1. Narrow spectrum agents that act on the 50S subunit - Linezolid, lincosamides
- Broad-spectrum agents that act on the 50S subunit- macrolides, chloramphenicol
- Broad-spectrum agents that act on 30S subunit -tetracyclines, aminoglycosides
