Antibiotics (PHARM)

Question 1

What are the four antibiotics mechanisms of target?

Answer 1

1. Cell wall synthesis
2. DNA replication
3. Protein synthesis 50S and 30S ribosome
4. Antimetabolites

Question 2

Targets synthesis of bacterial wall

Answer 2

-B-lactams (penicillins, cephalosporins, carbapenems)
-Vancomycin

Question 3

Targets Protein synthesis

Answer 3

-Aminoglycosides
-Macrolides
-Tetracycline
-Clindamycin
-Erythromycin

Question 4

Targets Nucleic acid synthesis

Answer 4

-Metronidazole
-Fluoroqinolones (ciprofloxacin)
-Rifampin

Question 5

Targets Synthesis of essential metabolites/folic metabolism

Answer 5

-Sulfamethoxazole/trimethoprim

Question 6

Mechanisms of antimicrobial resistance, Beta Lactamase

Answer 6

-Bacteria produce beta lactamase enzyme that cleaves beta lactam ring and this inactivates the antibiotics

-Clavulanic acid is a beta lactam that inactivates beta-lactamase and can renew abx sensitivity

-ESBL producing organisms such as E.Coli tend to be multi-drug resistant

Question 7

Common infections in the community and their common pathogens?

Answer 7

-Meninges/brain: Streptococcus pneumonia (+), Haemophilus influenzae (-)

-Eye infection: Staphylococcus aureus (+), Neisseria gonorrhoea, Chlamydia trachomatis

-Otitis Media: Streptococcus pneumonia (+)

-Sinusitis: Streptococcus pneumonia (+),Haemophilus influenzae(-)

-Upper respiratory infections (Pharyngitis and Bronchitis): Haemophilus influenzae (-), Streptococcus pyogenes

-Pneumonia (community acquired): Streptococcus pneumonia, Haemophilus influenzae, Staphylococcus aureus

-Skin infections: Staphylococcus aureus (+), streptococcus pyogenes

-UTI: E. coli (-), staphylococcus saprophytic, pseudomonas aeruginosa

-Prostatitis: E. coli

-GI infections: H. Pylori, food poisoning (eg. Salmonella, clostridium, shigella)

-STI: Neisseria gonorrhoea, Chlamydia trachomatis, treponema pallidum, ureaplasma urealyticum, haemophilus ducreyi

Question 8

What are some atypical pathogens in pneumonia?

Answer 8

-Atypical: mycoplasma pneumonia, legionella pneumophila, chlamydia pneumoniae

-TB: Mycobacterium tuberculosis

Question 9

MOA of Beta Lactam-Penicillins

Answer 9

-Names: penicillin, amoxicillin +/- clavulanic acid, cloxacillin, ampicillin

MOA:
-bactericidal, time dependent killing
-covers wide range of gm - and +, some oral anaerobes
-inhibits cell wall synthesis by blocking peptidoglycan cross linking which weakens the cell wall leading to death of bacteria

Common use:
-Penicillin: drug of choice for S. pneumonia or Group A strep
-Amoxicillin and Ampicillin: drug of choice of upper respiratory tract infection, UTI
-Amox+Clav: Staph or strep in high risk
-Cloxicillin: drug of choice for Staph (MSSA)W

Question 10

MOA of Cephalosporins

Answer 10

5 generations based on antibacterial action of Gm (-) or (+)
-Names: cephalexin, cefazolin, cefuroxime, cefprozil, cefoxitin, cefixime, ceftriaxone, ceftazidime, cefotazime, cefepime, ceftolozane

MOA:
-bactericidal, time dependent killing
-inhibits cell wall synthesis by blocking peptidoglycan cross linking which weakens the cell wall leading to death of bacteria
-More resistant to beta lactase
-No coverage for ESBL and LAME (listeria, atypical, MRSA, enterococci)

Question 11

MOA of Sulphonamides or Antifolates

Answer 11

Name: sulfamethoxazole (+trimethoprim)
-Gram - and + range

MOA:
-inhibits bacterial ability to make thymidine
-sulfamethoxazole bacteristatic
-Trimethoprim bactericidal
-concentration dependent killing, combined to prevent resistance

-Really bad allergy: SJS and bone marrow suppression or sulfa allergies

Question 12

MOA of Macrolides

Answer 12

Names: erythromycin (1st gen), azithromycin and clarithromycin (2nd gen)

MOA:
-Inhibit bacterial protein synthesis by biding to the 50S ribosome
-Bacteriostatic, high concentration bacteriocidal
-Time dependent killing

S/E: GI upset and QT prolongation, highly protein bound will cause many interactions

Question 13

MOA of tetracyclines

Answer 13

Names: tetracyline, doxycycline, minocycline

MOA:
-Inhibit protein synthesis 30 s ribosome
-Bacteriostatis, both concentration and time dependent killing
-Gram + and -

-S/E: strong affinity to calcium (tooth discolouration) and retard skeletal development in pregnancy

Question 14

MOA of Fluoroquinolones

Answer 14

Names: Ciprofloxacin, levofloxacin, moxifloxacin, norfloxacin

MOA:
-Inhibits DNA replication, induces double strand breaks
-Bactericidal, concentration dependent killing
-Gm - and +, pseudomonas

-S/E: rare tendon rupture, retinal detachment, articular damage in kids, chelates with mineral (ca, fe, Al, Mg)

Question 15

MOA of Metronidazole

Answer 15

MOA:
-Interferes with DNA replication by production of free radicals damaging to DNA
-Bactericidal, concentration dependent killing
-Antibacterial, amebicidal, trichomonacidal (uses intra abdominal infection, bacterial vaginosis, c.difficile)
-no gm - or + coverage
-Covers most anaerobes: clostridia, lung anaerobes

Question 16

MOA of Clindamycin-Lincosamides

Answer 16

MOA:
-Inhibition of protein synthesis at 50s ribosome
-coverage only gm + and anaerobes but resistance to gm + so only used for anaerobes coverage
-alternative for erythro or cloxacillin or metronidazole
-Bacteriostatic, time dependent killing

-S/E: rare pseudomembranous colitis, c.diff

Question 17

MOA Nitrofurantoin

Answer 17

MOA:
-Multiple action via breakdown into reactive compounds that inhibit ribosomal proteins, cell wall synthesis DNA and RNA process
-bactericidal, concentration dependent killing
-Requires renal concentration into urine crcl>30 ml/min
-Avoid if suspected pyelonephritis or prostatitis
-minimal effect on gut flora

S/E: long term use pulmonary fibrosis/toxicity, rare SJS, darkens urine