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Common Mechanisms of Disease-2 > Anti Bacterials - Swepman > Flashcards

Anti Bacterials - Swepman Flashcards

1
Q

What are the 4 mechanisms of anti-bacterial drugs?

A
  1. Inhibition of cell wall synthesis
  2. Inhibition of protein synthesis
  3. Inhibition of folic acid biosynthetic pathways
  4. Inhibition of Dna/Rna Synthesis
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2
Q

What are the 4 ways that bacteria can become resistant against anti-bacterial drugs?

A
  1. Alteration of receptor targets (Penacillin binding proteins and methylation of ribosomes)
  2. Decreased entry or efflux (Porins or efflux pumps)
  3. Alterations in metabolic pathways (Sulfa Drugs)
  4. Inactivate the drug (ionization)
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3
Q

How do penicillins work ?

A

Penacillins inhibit cell wall synthesis by interfering with the formation of the peptidoglycan later and are bactericidal. they bind to transpeptidase enzyne that is responsible for cross linking of n-acetyl muramic acid and N-acetyl glucosamine.

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4
Q

What is another term for the peptidase enzyme that penacillins bind to ?

A

Penicillin binding proteins (PBP’s)

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5
Q

What is a key aspect of penacillin’s efficacy?

A

Its ability to permeate the bacterial cell wall. And bind to PCP’s

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6
Q

What do gram negative bacteria do to prevent binding to PBP’s ?

A

They can alter their porin composition

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7
Q

What will B-Lactamase cause bacterial resistance to ?

A

Penacillins because they cleave the Beta-Lactam ring structure and are located in the periplasmic space. (Hence gram - Bacteria)

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8
Q

What are the 4 ways bacteria become resistant to penicillin

A
  • Modify their PBP’s
  • Pump the drugs back outside of the cells.
  • Cleave the B-Lactam ring (B-Lactamase in periplasmic space of G(-) )
  • Alter their porins
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9
Q

What drugs bind to the 30S subunit of the bacterial ribosome?

A

Tetracyclines and Aminoglycosides

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10
Q

What drugs bind to the 50S ribosomal subunit ?

A

Chloramphenicol
Macrolides
Clindamycin

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11
Q

What drugs prevent DNA-Directed RNA Polymerase

A

Rifampin

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12
Q

What drugs bind to DNA Gyrase?

A

Quinolones

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13
Q

Cell wall synthesis

A 
B Lactams ( Penicillins and cephalosporins) 
Vancomycin
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14
Q

Which drugs are Folic Acid Inhibitors ?

A

Trimethoprim

Sulfonamides

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15
Q

What happens when you give a drug like penicillin with a drug like tetracycline ?

A

Penicillins inhibit cell wall synthesis. For them to work the bacterial cell must be growing and dividing. If you give it with a drug like tetracycline which prevents bacterial growth pharmacologic antagonism will ensue.

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16
Q

Whats happens when a PBC bind to penicillin ?

A

It inhibits cell wall synthesis and blocks transpeptidation of peptidoglycan and also activates autolytic enzymes in the cell.

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17
Q

What is something about penicillin that is bad for girls?

A

It will decrease intestinal flora that will impare enterohepatic circulation of estrogenic compounds. She needs other contraceptives because estrogen birth control pills wont do much

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18
Q

What might you want to prescribe with penicillins ?

A

A beta lactimase inhibitor to prevent the penici

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19
Q

What are the aminopenacillins?

A

Ampicillin and amoxicillin Both can be taken on an empty stomach

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20
Q

What are the penicillinase resistant penicillins and why are they good?

A

Dicloxacillin, methicillin, oxacillin, and nafcillin. These hace a side group that profect them from bacterial B-Lactamase

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21
Q

How are cephalosporins like penicillins?

A

Both have B-Lactam ring. Cephalosporins are Ph stable so can be taken with or without food.

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22
Q

What are the antipseudomonial penicillins and what do they do?

A

Carbenicillin, ticarcillin, mezlocillin, and piperacillin. Usually given perentally, (Carbenicillin PO) but they only reach therapeutic levels in the UG tract. They are used to treat Prostate and urinary tract infections.

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23
Q

Do irreversible B Lactamase inhibitor have any microbial activity at all ?

A

No they can only complement the activity of a drug that is degraded by B-Lactamase.

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24
Q

What B Lactamase goes with Ticarcillin & Amoxicillin?

A

Clavulanic acid

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25
Q

What B lactamase goes with Ampicillin ?

A

Sulbactam

26
Q

What are adverse reaction involved in treating patients with cephalosporins ?

A

Because of their chemical structural similarities between cephalosporins and penicillins there is a possibility that penicillin- allergic patients may also be hypersensitive to cephalosporins.
They are excreted by the kidney so renal toxicity is possible. GI irritation is common bu can be circumvented by taking the medication with food.
-If given parentally it can cause seizures

27
Q

Carbapenems (imipenem/cilastatin, doripenem, ertapenem, meropenem)

A

Bactercidal inhibitor of cell wall synthesis ( Liek penicillins and carbapenems) but unlike penicillins and cephalosporins carbapenems have a different stereochemical structure in their B lactam ring that resists B-Lactamases

28
Q

What do (telavancin, vancomycin) do?

A

block cross-linking of peptidoglycan by binding D-Ala-D-Ala, telavancin disrupts membrane potential and changes in cell permeability because of lipophilic side chain

29
Q

What does Cycloserine do ?

A

inhibits cell wall synthesis in Gram + and – but usualy used for Mycobacterium tuberculosis

30
Q

What does Polymyxin B do ?

A

bactericidal to Gram – bacilli (but not Proteus), increases membrane permeability

31
Q

How do protein synthesis inhibitors work ?

A

They target pathways associated with bacterial but not human protein synthesis. These drugs

32
Q

How do amonoglycosides work ?

A

( Amikacin, Gentamycin, Kanamycin, metilmicin, streptomycin, tobramycin, and neomycin ) These drugs bind to the bacterial 30 S ribosomas subunits interferind with protein synthesis in atleast three ways.

33
Q

What are the ways that aminoglycosides inhibit protein synthesis by binding to 30S ribosomal subunits ?

A
  1. Interfere formation of the initiation complex
  2. Aminoglycosides misread mRNA and miscode amino acids in the growing peptide chain
  3. Aminoglycosides cause ribosomes to separate from mRNA. Causing a blockade of the movement of a ribosome
34
Q

What drugs inhibit the 50 S ribosomal subunit ?

A

Chloramphenicol
Macrolides
Clindamycin

35
Q

What drugs bind to the 30 S ribosomal subunit ?

A

Tetracycline and Aminoglycosides

36
Q

How are aminoglycosides absorbed?

A

They are too water soluble to ba absorbed orally. Therefor they are given parentally. However they can accumulate in the inner ear and renal cortex which will cause the side effects.

37
Q

What is the post-antibiotic effect ?

A

The number of bacteria in the cell will continue to decline even after the antibiotic plasma concentration has declined.

38
Q

What are teracyclines ?

A

Teracyclines inhibit protein synthesis through reversible binding to bacterial 30S ribosomal subunits thus preventing incoming amino acids and interfering with peptide growth.
**They are

39
Q

How do bacteria resistance to Teracyclines develop ?

A

Resistance is mediated by efflux pumps and ribosomal protection.

40
Q

Describe the pharmacokinetics of tetracyclines.

A

Gastric absorption of tetracyclines may be ihibited by chealtion to divalent cations or to bile acid resins. As a result it is best to administer tetracyclines on an empty stomach.
** Doxycycline is metabolized hepatically and excreted in the feces so it is safest option in patients with renal dysfunction .

41
Q

How do Gram + bacteria develop resistance to tetracyclines ?

A

They actively pump the drugs out of the cells via efflux pumps.

42
Q

What is chloramphenicol ?

A

Chloramphenicol is bacteriostatic. At the molecular level chloramphenicol binds to the 50 S subunit and blocks linkage of incoming amino acids to the growing peptide chain by interfering with the enzyme peptidyl transferase

43
Q

How are cloramphenicols metabolized ?

A

Glucouridation. In infants as well as adults with hepatic disease there will be hepatic accumulation

44
Q

What are Lincosamides ?

A

Clindamycin- which interrupts protein synthesis by binding to 50S ribosomal subunits and preventing translocation of incoming amino acids from the ribosomal A site to the P site.

45
Q

What are macrolide?

A

Drugs like erythromycin. They inhibit protein synthesis by binding to the same site on prokaryotic ribosomal 50 S subunit as clindamucin and chloramphenicol bind. Macrolides precent translocation of amino acids from the A site to the P site.

46
Q

How do organisms become resistant to macrolides?

A

Alter their permeability to micro lids
Methylation of bacterial 50 S ribosomal subinits
They develop

47
Q

How do Ketolides work ?

A

Telithromycin- as with macrocodes, telithromycin inhibits protein synthesis by inhibiting the 50 S ribosomal subunit by binding to two separate domains. This is adventageous because for a tumor to develop resistance there would have to be two separate mutations

48
Q

How does Retapamulin work ?

A

It is available as a topical ointment, retapamulin is structurally considered to be a peluromutilin antibiotic. It binds to the 50S ribosomal subunit and inhibits peptidyl transferase and blocks the P site.

49
Q

How does Muciprocin work ?

A

This antibiotic inhibits the tRNA that transports isoleucine

50
Q

What is a drug you could give orally for a patient who you were worried B Lactamase would degrade the penacillin ?

A

Dicloxicillin

51
Q

What Penicillins can not be degraded by B Lactamase ?

A

Dicloxocillin, Methicillin, Oxacillin, Natcillin

52
Q

What is a penicillin drug that can be given orally and only reaches effective concentration in the urinary tract. Used for urinary infections

A

Carbenicillin

53
Q

How are cephalosporins and penicillins similiar, how are they different ?

A

Cephalosporins have a B Lactam backbone but are very pH stable and can be taken on an empty stomach

54
Q

Are carbapenems B Lactam Drugs ?

A

Yes like penicillins and cephalosporins they are B-Lactam drugs, However, Carbapenems are resistant to B Lactamase

55
Q

How to Telavancin and Vancomycin work ?

A

These drugs interfere with cell wall synthesis by blocking polymerization and cross linking of the peptidoglycan by binding to the D-Ala D-Ala portion walls.

56
Q

How does Cycloserine work ?

A

It inhibits cell wall synthesis in gram + and Gram - bacteria but is reserved for treating Tuberculosis

57
Q

How does Polymyxin B work ?

A

It is a cationic detergent that disrupts lipoproteins in bacterial cell walls. Thus, increasing membrane permeability

58
Q

What are the drug classes that inhibit protein synthesis ?

A

Aminoglycosides, macrolides, and tetracyclines)

59
Q

What is a bactericidal drug ?

A

An antimicrobial drug that can eradicate an infection in the absence of host defense mechanisms, it will kill the bacteria

60
Q

What is a bacteriostatic drug ?

A

An antimicrobial drug that inhibits antimicrobial growth but requires host defence mechanisms to eradicate the infection

Common Mechanisms of Disease-2 (24 decks)

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