Aminoglycosides

Question 1

Aminoglycoside Examples

Answer 1

Streptomycin
Gentamicin
Tobramycin
Amikacin

Question 2

Aminoglycoside MOA

Answer 2

inhibit protein synthesis by inhibiting 30S subunit of bacterial ribosome

inhibit protein synthesis

Question 3

Resistance to Aminoglycosides

Answer 3

Mutation or methylation of 16S rRNA-binding site
Enzymatic destruction of the drug
Lack of permeability to the drug molecule –> drug cannot get into the organism
Active efflux (or lack of active transport)

CHANGE to BINDING SITE

Question 4

Aminoglycoside Spectrum

Answer 4

aerobic gnb bacilli

Question 5

Aminoglycosides are synergistic with….

Answer 5

penicillins for enterococci and streptococci

Question 6

Streptomycin can be used for…

Answer 6

• TB

Question 7

Aminoglycoside Route of Admin

Answer 7

• IV/IM

Question 8

Aminoglycosides absorbtion

Answer 8

Penetrate tissues relatively poorly; not CNS

Question 9

Aminoglycoside Adverse Effects

Answer 9

Nephrotoxicity
Ototoxicity
Neuromuscular blockade
Allergies rare

Question 10

Aminoglycosides Drug Interactions

Answer 10

Other nephrotoxic drugs
Other ototoxic drugs
Neuromuscular blocking agents

Question 11

Fluoroquinolone Examples

Answer 11

• Ciprofloxacin
• Levofloxacin
• Moxifloxacin

Question 12

Fluoroquinone MOA

Answer 12

• inhibit DNA gyrase or topoisomerase II & IV
  Bacteriocidal; concentration dependent killing

Inhibit DNA replication

Question 13

Fluoroquinone Resistance

Answer 13

alteration of the A or B subunit of DNA gyrase

-
Mutation in ParC or ParE of topoisomerase IV
Change in outer membrane permeability –> cannot get in to act at DNA
Efflux pumps

Question 14

In general, fluoroquinones spectrum is

Answer 14

highly active against gnb, Haemophilus sp, neisseriae, chlamydiae, etc

Question 15

Ciprofloxacin Spectrum

Answer 15

most active against .P aeruginosa

Question 16

Levofloxacin Spectrum

Answer 16

activity against S. pneumoniae –> gram positive cocci

Question 17

Moxifloxacin Spectrum

Answer 17

activity against anaerobes

Question 18

Fluoroquinone Uses

Answer 18

urinary tract infections, STIs due to chlaymdia, lower respiratory tract infections, enteritis/travellers diarrhea, drug resistant mycobacterial infections

Question 19

Fluroquinones Elimination

Answer 19

Ciprofloxacin and levofloxacin – renal elimination; moxifloxacin has a biliary pathway

Question 20

Adverse Effects of Fluoroquinolones

Answer 20

Nausea, vomiting, diarrhea
Insomnia, headache and dizziness
Other CNS effects including seizures
Skin rashes
Impaired liver function
-
Tendinitis/tendon rupture –> tends to occur more in elderly (can occur I. young) –> risk factors –> age over 60, being on corticosteroids, and female –> Counsel –> If develop tenderness, stop and see healthcare professional right away
-
Prolongation of QTc interval
Hypo/hyperglycemia
C. difficile
Peripheral neuropathy –> tingling, prickling,

Question 21

Drug Interactions of Fluoroquinolones

Answer 21

Bind di and tri-valent cations –> Mg, Ca, Zinc, Iron –> Lower serum inf
QTc prolongation
CYP 1A2 inhibition can result in increased levels of many drugs ( e.g. clozapine, duloxetine, methotrexate, quinapril, rasagiline, ropinirole, varenicline,etc)
Increased INR with warfarin

Question 22

Fluroquinolones exception uses… C.I.

Answer 22

Many toxicities
Many have been removed from the market
Reserve for resistant organisms and situations where you cannot use the DOC

Not used in children <18 years of age ( some exceptions)

Exceptions –> Pseudomonas, resistant infections
–> Cystic Fibrosis in Children –> Seen

Question 23

Sulfamethoxazole MOA

Answer 23

structural analogue of PABA; competitively inhibits dihydrofolic acid synthesis

Inhibit folic acid synthesis

Question 24

Trimethoprim MOA

Answer 24

binds to dihydrofolate reductase therefore inhibiting the reduction of dihydrofolic acid to tetrahydrofolic acid

• Inhibit folic acid synthesis

Question 25

Sulfamthoxazole and Trimethoprim mainly found as....

Answer 25

Most commonly combined as TMP/SMX or co-trimoxazole

Question 26

Sulfonamides and Trimethoprim Killing Mechanism

Answer 26

Bacteriostatic but together bacteriocidal

Question 27

Sulfonamides and Trimethoprim Resistance

Answer 27

ability of cell to use preformed folic acid (don’t have to make it)

Question 28

Sulfonamides and Trimethoprim Spectrum

Answer 28

Spectrum – wide spectrum of gp, gn, chlamydiae, nocardiae and protozoa No activity against anaerobes Staphylococci – including MRSA Streptococcus pneumonia; NOT Group A Strep S. maltophilia Moraxella H. influenza Enterobacteriaciae Brucella Pneumocystis jirovecii

Question 29

Sulfonamides and trimethoprim Uses

Answer 29

Urinary tract infections Skin and soft tissue infections- MRSA PJP --> can be seen in other immunocompromised states but mainly HIV Many others

Question 30

Drug Interactions of TMP/SMX

Answer 30

2C9 inhibitor; 3A4 substrate – increased levels of carvedilol, digoxin, phenytoin Increased INR and bleeding with warfarin Hypoglycemic agents – increased risk of hypoglycemia

Question 31

Contraindications of TMP/SMX

Answer 31

CI in first and 3rd trimester of pregnancy Caution in renal dysfunction  excaberates higher K+ levels, hypoglycemic risk

Question 32

Metronidazole MOA

Answer 32

unknown but possible inhibition of nucleic acid synthesis and disruption of DNA

Question 33

Metronidazole Resistance

Answer 33

--> Do not know --> Susceptibility testing is extremely difficult

Question 34

Metronidazole Spectrum

Answer 34

anaerobes including C. difficile Protozoa – trichomonas, Giardia (diarhhea from drinking H2O out of streams), etc Propionibacterium are resistant --> acne --> Not used in this situation

Question 35

Metronidazole Adverse Effects

Answer 35

gi Metallic taste Headache Dark urine Peripheral neuropathy --> usually not until later (weeks, often not used for long durations) Disulfiram-like reaction with alcohol (N, V, D, Headache, Chest Pain) Insomnia Stomatitis  mouth sores

Question 36

Metronidazole Drug Interactions

Answer 36

Alcohol – disulfiram reaction Warfarin – increased INR and bleeding

Question 37

Linezolid MOA and KIlling

Answer 37

MOA – inhibits protein synthesis Usually bacteriostatic; bactericidal against Streptococci

Question 38

LInezolid Spectrum

Answer 38

Streptococci, Enterococci (including VRE), Staphylococci (including MRSA)

Question 39

Linezolid is reserved for....

Answer 39

multi-drug resistant organisms

Question 40

Linezolid Adverse Effects

Answer 40

Headache Nausea, vomiting diarrhea Rash Increased LFT’s Myelosuppression (Bone Marrow) --> Causes neutropenia, low platelets, anemia --> dose and duration dependnent Optic/peripheral neuropathy --> nerve damage in eye --> Sight problems Lactic acidosis Decreased seizure threshold

Question 41

Linezolid Drug Interactions

Answer 41

Increased serotonin syndrome risk with SSRIs and MAOIs (other drugs that cause serotonin syndrome) Rifampin decreases linezolid levels