Phae: Antimicrobial Drugs

Front 1

What are antimicrobial agents?

Back 1

Agents that kill or inhibit growth of microorganisms

Front 2

What is bacteriocidal? What is bacteriostatic?

Back 2

Kills bacteria

Inhibits bacterial growth / replication

Front 3

What are 2 types of susceptibility tests?

Back 3

1. Diffusion tests
2. Dilution tests
   (A) MIC (min. inhibitory concentration)
   (B) MBC (min. bactericidal concentration)

Front 4

What are the steps for antimicrobial therapy?

Back 4

1. Prophylaxis
2. With established infection:
   (A) Wait-and-see approach
   (B) Empirical therapy for immunocompromised / severely ill patients using full course of currently effective antimicrobial agents or broad spectrum of single agent or combination therapy
   (C) Definitive therapy: full course with narrow-spectrum, low-toxicity regimen

Front 5

What is selective toxicity?

Back 5

Concentration of active agent at infected site:

• Sufficient level to be toxic to offending microorganism
• Min. level to be toxic to normal human cells

Front 6

What are the 5 basis of drug action?

Back 6

1. Differences in cell structure
2. Inhibition of biosynthetic pathways
3. Inhibition of protein biosynthesis
4. Selective toxicity based on anatomical environment
5. Interference with life cycle

Front 7

What is an example of drugs that use the difference in cell structure?

Back 7

1. Antifungal agents: target cell membranes
2. Antibacterial agents: target cell walls

Front 8

What is an example of an antifungal agent that targets cell membranes? What is the MoA?

Back 8

-azoles (ketoconazole / itraconazole)

⊖ fungal microsomal cytochrome p450 enzyme → impairs growth of ergosterol for membrane → inhibits growth

Front 9

When is ketoconazole specifically used? What are SE?

Back 9

Oral use for superficial & systemic mycoses

• Dose-dependent nausea, anorexia, vomiting
• ⊖ steroid biosynthesis → corticosteroid suppression
• Hepatotoxicity in 5-10% of patients

Itraconazole causes less DDI

Front 10

What are 2 types of antibacterial agents that targets the cell wall?

Back 10

1. β-lactams
2. Glycopeptides

Front 11

What is the MoA of β-lactams?

Back 11

Binds to penicillin binding protein (PBP) → ⊖ synthesis of peptidoglycan layer of cell wall

Front 12

What are 2 types of β-lactams?

Back 12

1. Penicillins
2. Cephalosporins

Front 13

Which organisms are penicillins effective against?

Back 13

G+ve cocci/bacilli, G-ve cocci; does not cross BBB but can treat meningitis when meninges are inflamed

Front 14

Which organisms are cephalosporins effective against?

Back 14

Broad-spectrum against G+ve / G-ve bacteria

• Cefotaxime: active against Pseudomonas
• Cross BBB: effective in G-ve bacteria induced meningitis

Front 15

What is an example of a glycopeptide?

Back 15

Vancomycin

Front 16

What is the MoA of vancomycin? Which organisms is vancomycin effective against?

Back 16

⊖ proper cell wall synthesis in Gram +ve bacteria

• Active against G+ve cocci, some G-ve bacilli & MRSA

Front 17

What are some SE of vancomycin?

Back 17

May damage kidney & ear

Front 18

What are 2 biosynthetic pathways that are inhibited by antimicrobial drugs?

Back 18

1. Inhibition of folic acid pathway
2. Inhibition of DNA topoisomerase

Front 19

What are 3 antimicrobial drugs that inhibit the folic acid pathway?

Back 19

1. Sulfonamides: sulfamethoxazole
2. Trimethoprim
3. Sulphonamide + trimethoprim = cotrimoxazole

Front 20

When is trimethoprim used?

Back 20

Simple & recurrent UTIs

Front 21

When / for what is cotrimoxazole used? (3)

Back 21

• Urinary tract, respiratory, GI infections (excluding Pseudomonas)
• Typhoid & paratyphoid infections
• Bacillary dysentery by amoxycillin-resistant Shigella strains

Front 22

What is an example of an antimicrobial drug with MoA that inhibits DNA topoisomerase?

Back 22

Quinolones: ciprofloxacin / ofloxacin / levofloxacin

Front 23

What organisms are quinolones effective against? (3)

Back 23

• Broad spectrum, G-ve bacilli & cocci (Neisseria species)
• Good activity against MRSA
• Poor activity against Streptococci, Pneumococci

Front 24

When are quinolones used?

Back 24

• Urinary tract & systemic G-ve infections
• GI & abdominal infections

Front 25

How do antimicrobial agents inhibit protein biosynthesis?

Back 25

Interference with ribosome function

Front 26

What are 4 types of antimicrobial agents that inhibit protein biosynthesis?

Back 26

1. Tetracyclines (4 rings)
2. Aminoglycosides (2+ amino sugar units)
3. Chloramphenicol (nitrobenzene nucleus)
4. Macrolides (14-membered ring)

Front 27

What is the MoA of tetracyclines?

Back 27

Competes with tRNA for A site → prevents docking of tRNA with A site

Front 28

What are 2 examples of tetracyclines?

Back 28

* Doxycycline
* Minocycline

Front 29

What are the side effects of doxycycline and minocycline? (3)

Back 29

Skin rashes, GI upsets, brown staining of growing teeth

Front 30

What is the MoA of aminoglycosides?

Back 30

Binds to bacterial 30S subunit → alter codon → misreading of message

Front 31

What are 3 examples of aminoglycosides?

Back 31

• Gentamicin
• Neomycin (topical)
• Streptomycin (prototype)

Front 32

When are aminoglycosides used?

Back 32

• Active against aerobic G-ve & some G+ve
• Use with penicillin for Streptococcal infections

Front 33

What are some SE of aminoglycosides?

Back 33

Ototoxicity, nephrotoxicity

Front 34

What is the MoA of chloramphenicol?

Back 34

⊖ transpeptidation via transferase

• Higher affinity to bacterial transferase in 50S subunit

Front 35

When is chloramphenicol used?

Back 35

• Broad-spectrum
• Reserved for serious infections:
  (A) H. influenzae resistant to other drugs
  (B) Meningitis patients allergic to penicillins

Front 36

What is the MoA of macrolides?

Back 36

Binds to bacterial 50S subunit → prevent translocation of tRNA-peptide

Front 37

What is an example of a macrolide?

Back 37

Erythromycin

Front 38

When are macrolides used? (2)

Back 38

• Active against G+ve cocci
• Used for Streptococcal infections in penicillin allergic patients

Front 39

What are the SE of macrolides?

Back 39

Epigastric discomfort, nausea, vomiting

Front 40

What are 3 types of antimicrobial drugs that have a selective toxicity based on anatomical environment?

Back 40

1. Antiprotozoal metronidazole: acts at anaerobic situation
2. Antihelminthic pyrantel: retention in gut lumen
3. Antibacterial quinolones: excretion into renal tubular fluid

Front 41

When is metronidazole used?

Back 41

Active against anaerobic protozoal parasites & anaerobic bacteria

Front 42

What is the MoA of pyrantel? When is pyrantel used?

Back 42

• Induces marked & persistent activation of N receptor → spastic paralysis of worm
• Selectivity: poorly absorbed from GI tract

Front 43

When are quinolones used?

Back 43

Active secretion by kidney to treat UTIs

Front 44

What are 2 antimicrobial agents that work via interference with the life cycle?

Back 44

1. Life cycle of DNA virus: acyclovir
2. Life cycle of RNA retroviruses: zidovudine (azidothymidine)

Front 45

What is the MoA of acyclovir?

Back 45

• Phosphorylated only by virus-specific form of thymidine kinase
• Active form inhibits DNA polymerase → impairs nucleic acid synthesis of DNA virus

Front 46

When is acyclovir used?

Back 46

Infections of herpesviruses, topical for herpes infections in eyes

Front 47

What is the MoA of zidovudine?

Back 47

Activated triphosphate form → ⊖ viral DNA-dependent DNA polymerase (reverse transcriptase only in RNA retrovirus) → DNA chain termination

Front 48

What are 3 purposes of development of better penicillin antibiotics?

Back 48

1. To ↑ acid stability and duration of action
2. To generate resistance to bacterial β-lactamases
3. To alter the spectrum of antibacterial activity

Front 49

What are 2 situations in which combination therapy is used?

Back 49

1. Best guess therapy in severe abdominal infection
2. Anti-TB combinations

Front 50

What are 4 types of β-lactam antibacterial agents?

Back 50

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

Front 51

What are some properties of penicillin G / benzylpenicillin that were improved on by other types of penicillin?

Back 51

1. Acid unstable - not stable for oral penicillins
   Phenoxymethylpenicillin (penicillin V): acid stable, used orally
2. Short duration of action (30 min)
   Cloxacillin & flucloxacillin: longer half-life, acid-stable

Front 52

What is the effect of β-lactamase on penicillin G?

Back 52

Hydrolyzes β-lactam ring to form penicilloic acid

Front 53

What produces β-lactamase?

Back 53

Staphylococcal sp; formation of this enzyme is inducible by penicillins

Front 54

What drugs are used to treat Staphylococcal infections?

Back 54

1. Cloxacillin & flucloxacillin: widely used against β-lactamase-producing Staphylococci sp.
2. Vancomycin: for MRSA

Front 55

What is clavulanic acid?

Back 55

• β-lactamase inhibitor (irreversibly binds)
• Little antibacterial activity of its own
• Used concurrently with antibacterial agents

Front 56

What bacteria is penicillin G effective against?

Back 56

G+ve cocci sp., G-ve cocci sp., G+ve bacilli sp.

Front 57

What are 2 examples of broad-spectrum antibiotics? How are they given? What must they be used in conjunction with?

Back 57

Ampicillin, amoxycillin

• Broader - can be used against G-ve bacilli sp.
• Can be used orally
• Hydrolyzed by β-lactamase when used against Staphylococci sp. ∴ must be combined with β-lactamase inhibitor

Front 58

What are 2 examples of antipseudomonal penicillins? How are they given?

Back 58

Piperacillin, ticarcillin

• Active against pseudomonads
• Not given orally - injection

Front 59

When is best guess therapy most often used?

Back 59

Peritonitis / intra-abdominal sepsis

Front 60

What are 2 infecting organisms causing peritonitis / intra-abdominal sepsis?

Back 60

1. Bacteroides fragilis (anaerobe)
2. E. coli (facultative anaerobe)

Front 61

What are the 3 drugs used for combination therapy treating peritonitis / intra-abdominal sepsis?

Back 61

1. Gentamicin: for aerobic G-ve rods
2. Metronidazole: for anaerobes
3. Ampicillin: for enterococci

Front 62

What are common causes of TB?

Back 62

Mycobacterial sp., M. tuberculosis

Front 63

What drugs are used in combination therapy for treatment of TB?

Back 63

Isoniazid, rifampin, pyrazinamid, ethambutol

Front 64

What is the MoA of isoniazid?

Back 64

⊖ biosynthesis of mycolic acids (for mycobacterial cell wall)

Front 65

What is the MoA of rifampin?

Back 65

⊖ DNA-dependent RNA polymerase in prokaryotes → ⊖ RNA production, transcription, translation in mycobacteria

Front 66

What is the MoA of pyrazinamide?

Back 66

Exhibits activity only at acidic pH

Targets mycobacterial fatty acid synthase I gene (for mycolic acid biosynthesis)

Front 67

What is the MoA of ethambutol?

Back 67

Blocks arabinosyl transferase involved in cell wall biosynthesis of mycobacteria

Front 68

What are 3 advantages of combination therapy?

Back 68

• Ensure activity (synergism)
• Minimize adverse effects
• ↓ incidence of resistance development

Front 69

How can penicillin cause allergies?

Back 69

β-lactam ring opened products act as antigenic haptens causing allergic reactions

Front 70

What are the S/Sx of penicillin allergies?

Back 70

Skin rashes, fever, bronchospasm, rare acute anaphylactic shock

∵ cross reactions amongst different penicillins or between penicillins & cephalosporins

Front 71

How can penicillin allergies be managed?

Back 71

History of previous allergy to penicillins, intradermal sensitivity test, use alternative antibacterial agents

Front 72

What are some adverse effects of chloramphenicol?

Back 72

1. Severe depression of bone marow → dose-related blood cell disorders, aplastic anemia
2. "Grey baby syndrome" in newborns

Front 73

What are the S/Sx of Grey baby syndrome?

Back 73

Vomiting, diarrhea, flaccidity, low temp, ashen-grey color

∵ low levels of liver metabolizing enzymes

Front 74

What is an adverse effect of clindamycin?

Back 74

Pseudomembranous colitis (acute inflammation in colon caused by cytotoxin B from C. difficile)

• Normal fecal flora becomes antibiotic resistant pathogenic organism after using antibiotics

Front 75

What is the treatment for pseudomembranous colitis?

Back 75

Vancomycin

Front 76

What are 3 ways in which resistance to antibacterial agents occur?

Back 76

1. Does not reach target
   e.g. inactive/ineffective transporter
   e.g. efflux protein
2. Inactivated
   e.g. β-lactamase inactivates β-lactam antibiotics
3. Target is altered
   e.g. PBPs → penicillin resistance
   e.g. ribosomal mutation → streptomycin resistance