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Antibiotics - classes Flashcards

1
Q

2 major beta lactams (and thus cell wall synthesis inhibitors)

A

Penicillin and cephalosporins

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2
Q

What does a beta lactam do to a bacteria (MOA)

A

Cell wall inhibitor. Prevents the cell wall from forming properly. But the bacteria must be actively dividing and growing in order for this group to work

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3
Q

How do beta lactams differ from each other

A

The R group (functional group) on the 6-aminopenicillanic acid - garage of the house:)

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4
Q

What is the MOA for penicillin

A

Interferes with transpeptidation cross-linkage (cell wall cannot connect properly). Which eventually will lead to cell lysis

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5
Q

What other ways to penicillins target bacteria

A
  1. Penicillin binding proteins
  2. Inhibition of transpeptidase
  3. Production of autolysins
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6
Q

How do penicillin binding proteins work

A

Penicillin inactivates proteins on the bacteria cell membrane that are involved with cell wall synthesis (these proteins can cause resistance if the bacteria starts to alter them)

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7
Q

How do the autolysins play a role in bacterial cell destruction

A

Penicillins prevent transpeptidase from linking, but the bacteria still produces enzymes that normal break down and rebuild the cell wall (autolysis). Thus the autolysins continue to produce even after the penicillin as interfered with the cell wall link which leads to faster cell lysis.

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8
Q

What type of bacteria do beta lactams work well on

A

Gram + streptococcus

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9
Q

What is the biggest clinical application of beta lactams

A

Pneumonia (streptococcus pneumonia)

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10
Q

What other types of bacteria can penicillin be used against

A
  1. Limited gram (-). Neisseria group
  2. Syphilis - spirochetes
  3. Anaerobes: oral only!!
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11
Q

What are the natural penicillins

A

Penicillin V

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12
Q

What are the extended spectrum penicillins

A
  1. Ampicillin

2. Amoxicillin

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13
Q

What factors contribute to the antibacterial spectrum of a penicillin

A
  1. Ability to cross the peptidoglycan cell wall to reach PBP

2. Size, charge, and lipophilic nature of ABX

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14
Q

What is meant by extended spectrum penicillins

A

Means that some ABX that are in the penicillin group are more effective against gram (-) bacteria. Ampicillin/amoxicillin

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15
Q

What is the clinical use of the extended spectrum penicillins (amox/amp)

A

Respiratory infections and prophylactically by dentists for patients with abnormal heart valves.

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16
Q

Types of penicillins (full spectrum)

A
  1. Natural
  2. antistaphylococcal
  3. Extended-spectrum
  4. Antipseudomonal
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17
Q

What drugs does penicillin have a synergistic effect with

A
  1. clauvonic acid - inhibitor of beta lactamase, which means the penicillin can still do its job
  2. aminoglycosides - penicillin helps facilitate the entry of other drugs
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18
Q

How do you determine the route of administration with penicillins

A

Stability of the drug in stomach acid and the severity of the infection

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19
Q

Routes of administration of beta lactams

A

IM/IV/Oral. Penicillin can only be given orally

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20
Q

Absorption characteristics of penicillins

A

Incompletely absorbed, which means they will reach the intestines. However, amoxicillin is almost completely absorbed which is not effective in treating bugs that affect the lower GI tract

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21
Q

Distribution of penicillins

A
  1. Distribute well
  2. Penicillins cross the placental barrier
  3. Poor bone and CSF penetration
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22
Q

How are penicillins excreted

A

Tubular secretion in the kidneys

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23
Q

Adverse reactions of penicillins

A
  1. hypersensitivity - metabolite penicilloic acid, creates an immune reaction
  2. Diarrhea
  3. Nephritis
  4. Neurotoxicity - seizures
  5. Hematologic toxicities
  6. High Na+/K+ levels
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24
Q

Which beta lactam is more resistant to Beta lactamases

A

Cephalosporins

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25
How are cephalosporins classified
1,2,3,4 generation based on their bacterial susceptibility patterns and resistance to beta lactamases
26
First generation
Best for gram +: Staph, strep, and a few gram (-): e-coli, proteus
27
Second generation
Mostly gram +. Greater activity against gram (-) and some neisseria
28
Third generation
Increased activity against gram (-). Very good against meningitis. Very prone to bacterial resistance
29
Fourth generation
Wide spectrum across both gram +/-. Cefepime is the only one approved in the US. Very good against Staphaureus
30
What is the MOA for cephalosporins
Same as penicillins. Inhibits cell wall synthesis
31
Route of administration for cephalosporins
Mostly IV/IM, poor oral absorption
32
Distribution of cephalosporins
1. Distribute very well in all body fluids 2. Very little CSF distribution (except ceftriaxone) 3. All cross the placenta
33
Antibacterial spectrum for cephalosporins
Almost exclusively gram +/-, with a few select anaerobes.
34
Elimination of cephalosporins
1. Tubular secretion in kidney | 2. Ceftriaxone is exception in that it is secreted by liver bile (good choice in pts with poor kidney function).
35
Adverse effects of cephalosporins
1. Allergic reactions 2. Stevens-johnson syndrome 3. Similar penicillin reactions
36
What groups of ABX are involved in protein synthesis inhibition
1. Tetracyclines 2. Aminoglycosides 3. Macrolides
37
How do ABX that target protein synthesis work
They diffuse through the cell wall and into the bacteria cell, then bind to the 50 or 30S ribosome of the bacteria. High levels of drug may induce toxic affects to human ribosomes (even though they are slightly different than bacteria)
38
What is the chemical makeup of tetracycline
4 fuse rings with double bonds. Substitutions in these rings is what makes up variations of these drugs
39
MOA of tetracycline
ABX diffusions/and is transported into the bacterial cytoplasm where it binds reversibly to 30S ribosome, which blocks synthesis
40
Antibacterial spectrum of tetracyclines
BROAD SPECTRUM! bacteriostatic ABX. Effective against +/- and many unique diseases like rocky mtn spotted fever, mycoplasmas, lyme disease, cholera
41
Absorption of tetracyclines
1. Adequately, but incompletely absorbed after oral ingestion (cannot take with dairy) 2. Doxycyline is preferred oral tetracycline 3. Antiacids negate the effect of tetracyclines
42
Distribution of tetracyclines
1. Distribute and concentrate in the liver, kidney, spleen, skin and in tissues undergo ing calcification 2. Penetrate to most body fluids 3. All enter CSF, but not at therapeutic levels
43
Elimination of tetracyclines
All end up in the liver, and the parent or metabolites of the drug are excreted in the bile
44
Adverse effects of tetracyclines
1. Gastric upset 2. Stunts bone growth in children 3. Fatal hepatotoxicity 4. Phototoxicity - severe sunburn can occur when pts are on this 5. Inner ear issues
45
MOA for aminoglycosides
Susceptible gram (-) bacteria allow ABX to diffuse through porin channels which are carried through cytoplasm by 02 dependent transporter. They then bind to 30S, inhibits protein synthesis. BACTERICIDAL!!
46
Antibacterial spectrum of aminoglycosides
1. Very effective in treating AEROBIC gram (-) bacteria | 2. Often combined as a synergist (vancomycin, penicillin)
47
Why are aminoglycosides effective only against aerobic organisms
Because they must use the 02 to transport through the bacterial cell to the ribosome.
48
Routes of (and characteristics) of administration of aminoglycosides
1. Poor oral absorption 2. Must be given parenterally 3. Can be given once a day (due to concentration dependent bactericidal qualities)
49
What is the bactericidal effect of aminoglycosides dependent on
Concentration and time dependent. The greater the amount of ABX the higher the rate of bacteria cell death
50
Distribution of aminoglycosides
Same as other aminoglycosides. Diverse distribution, in CSF but at very low levels, etc
51
Elimination of aminoglycosides
Metabolism does not occur in the host, all are excreted rapidly in the urine
52
Adverse effects of aminoglycosides
1. Ototoxicity!!! 2. Nephrotoxicity 3. Paralysis 4. Skin rash
53
MOA of macrolides
ABX binds irreversibly to the 50S ribosome, which inhibits the translocation step of protein synthesis
54
Are macrolides bacteriostatic or bacteriocidal
Considered to be mostly bacteriostatic
55
Antibacterial spectrum of macrolides
WIDE USE 1. Gram + (rods/cocci) 2. Gram - (rods/cocci) 3. Spirochete 4. Mycoplasma 5. Chlamydia
56
What is erythromycin used for
Effective against same things as penicillin G. Can be used as a substitute in pts that are allergic to Pen G
57
Types of things you can treat with macrolides
1. syphillis 2. corynebacterium diphtheria 3. Legionnaires disease 4. Mycoplasmal pneumonia 5. Chlamydia
58
Administration of macrolides
1. Erythromycin is destroyed by gastric acid, needs enteric coat 2. All are adequately absorbed 3. Must be careful with food (differs among drugs in this group)
59
Distribution of macrolides
1. Erythromycin distributes well in fluids and in the prostate (very few drugs do this) 2. All concentrate in the liver 3. Some of these drugs can concentrate in neutrophils, macrophages and fibroblasts
60
Elimination of macrolides
Extensively metabolized by the liver. Interact with Cytochrome p450 which blocks the metabolism of other drugs
61
Adverse effects of macrolides
1. Gastric distress 2. Jaundice 3. Ototoxicity 4. contraindicated in pts with hepatic dysfunction
62
MOA of quinolones
Enter through aquaporins, then once inside cell they inhibit DNA replication by interfering with DNA gyrase. Bacteriocidal!!! Are DOSE dependent- the more you give the more you kill
63
Antimicrobial spectrum of quinolones
Effective against gram (-). GI tract (enterobacteria), urinary tract, resistant respiratory infections. Have some uses in gram (+), mycoplasma, and mycobacteria
64
What are fluoroquinolones good for prophylactically
UTI post surgically
65
What are 2nd and 3rd generation quinolones good for treating
Chlamydia and mycoplasma (as well as gram -)
66
Examples of quinolones
1. Ciprofloxacin 2. Norfloxacin 3. Levofloxacin - better against gram -
67
Absorption of quinolones
Only 35-70% of norfloxacin absorbed. All other quinolone are 85-95% absorbed. Longest 1/2 lives. Do not give with Al or Mg
68
Elimination of quinolones
Through the kidneys (except moxifloxacin - liver
69
Distribution of quinolones
Distribute well into all tissues and body fluids. Levels are high in bone and urine (prostate tissue). Low CSF penetration. Accumulate in macrophages and leukocytes (active against legionella)
70
Adverse reactions of quinolones
1. GI 2. CNS effects 3. Phototoxicity 4. CT problems
71
MOA of sulfonamides
Inhibits cells metabolism and are therefore bacteriostatic drugs (inhibits PABA)
72
Antibacterial spectrum of sulfonamides
Selective enterobacteria of urinary tract
73
Absorption of sulfonamides
Well absorbed in the SI
74
Distribution of sulfonamides
Bind to albumin, but distribute to water and CSF. Can pass placental barrier
75
Metabolism of sulfonamides
In the liver
76
Excretion of sulfonamides
Kidney
77
Adverse effects of sulfonamides
1. Crystalluria 2. Hypersensitivity 3. Hemopoietic disturbances

Pharmacology 2 (8 decks)

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