Antibacterials 4

Question 1

Route of administration of vancomycin:

Answer 1

slow IV infusion

Question 2

Adverse effects of Vancomcyin

Answer 2

• Red man/red neck syndrome which is a infusion related flushing over the face so just need to slow the infusion rate (not allergenic)
• ototoxicity
• nephrotoxicity

Question 3

What is the clinical use of daptomycin

Answer 3

Created because bacteria became resistant to vancomycin → used tot rest resistant gram positive organisms include VRE and VRSA

Question 4

Daptomycin cannot be used to treat ____________

Answer 4

Pneumonia; surfactant inactivates it

Question 5

Mechanism of action of daptomycin

Answer 5

Unique: binds to cell membrane via Calcium dependent insertion of lipid tail → depolarization → K efflux → cell death

Unique mechanism allows for ↓ resistance against daptomycin

Question 6

Adverse effects of daptomycin

Answer 6

Constipation, nausea, headache, insomnia

Also causes ↑ creatine phosphokinases which makes them at higher risk for myopathies

Question 7

It is recommended to discontinue coadminstiation of _________ when taking daptomycin

Answer 7

Statins (due to ↑ creatine phosphokinases)

Question 8

What is bacitracin used to treat and is there risk of resistance?

Answer 8

Gram positive organisms;
No cross resistance due to having a unique mechanism

Acts at late stage of cell wall synthesis

Question 9

What is an adverse effect of bacitracin ?

Answer 9

Marked nephrotoxicity so must be given topically

Question 10

Mechanism of action of fosfomycin and what kind of bacteria is it used against

Answer 10

Inhibits enolpyruvate transferase in the early stage of cell wall synthesis
Gram positive and gram negative

Question 11

What condition is fosfomycin used to treat

Answer 11

Uncomplicated lower UTI’s

Question 12

Protein synthesis inhibitors are mostly bacterio_________ and they target the bacterial ribosome _____S.

Answer 12

Static;

70S ( mammalian are 80S)

Question 13

Drugs that are in the class of tetracyclines (3)

Answer 13

Doxycycline, minocycline, tetracycline

Question 14

Mechanism of action of tetracycline and

Answer 14

Enter via passive diffusion and energy dependent transport which is unique to bacterial inner cytoplasmic membrane
Bind reversibly to 30S subunit of the ribosome and prevents attached of tRNA

Question 15

Tetracyclines bind to ________

Answer 15

30S subunit of the ribosome

Question 16

Tetracyclines are especially effective in treating conditions caused by __________ organisms

Answer 16

Intracellular organisms

Question 17

What are the 3 main mechanisms of tetracycline resistance (plasmid encoded)

Answer 17

• impaired influx or ↑ efflux by active (plasmid encoded) protein pump
• production of proteins that interfere with binding to the ribosome
• enzymatic inactivation

Question 18

What are the conditions that tetracyclines are used to treat

Answer 18

• most common: severe acne and rosacea
• empiric therapy of community acquired pneumonia (outpatients)
• atypical pneuma (mycoplasma, chlamydia and legionella)
• treat syphillis patients who are allergic to penicillin for

Question 19

________ decreases the GI absorption of tetracyclines

Answer 19

Calcium and other divalent and trivalent cations which will chelate the tetracyclines

Question 20

What type of things should patients who are taking tetracyline avoid?

Answer 20

Milk/diary (calcium)

Antacids (magnesium)

Question 21

____________ is a tetracycline that is lipid soluble and is preferred by parenteral administration

Answer 21

Doxycycline

Question 22

_________ is a tetracyline that is used for STD’s and prostatitis

Answer 22

Doxycycline

Question 23

Where can tetracyclines concentrate?

Answer 23

Liver, kidneys, spleen, and skin

Question 24

Tetracyclines are primary excreted in the urine except for _______ which is excreted primarily by _______

Answer 24

Doxycycline; bile

Question 25

What are some adverse effects of tetracycline

Answer 25

- Gastric effects/ super infections - discoloration and hypoplasia of teeth (calcium) - stunning of growth (teratogenic in pregnancy and should not be given to kids under 8 years old) - photosensitization - dizziness, vertigo (esp with doxycline and minocycline)

Question 26

Example of a glycylcycline drug and what is important about this family of drugs

Answer 26

Tigecycline | Similar to tetracyclines but with less resistance

Question 27

Route of administration of glycylcyclines

Answer 27

IV

Question 28

Primary route of elimination of glycylcyclines

Answer 28

Biliary/fecal

Question 29

What are the aminoglycoside drugs (5)

Answer 29

``` Amikacin Gentamicin Tobramycin Streptomycin Neomycin ```

Question 30

Aminoglycoside s are bateri______

Answer 30

Bactericidal; | Associated with serious toxicities

Question 31

Which class of protein synthesis inhibitors are bactericidal?

Answer 31

Aminoglycosides

Question 32

What is the difference between concentration dependent killing and time dependent killing of antibiotics

Answer 32

Concentration dependent: the amount of organisms that are killed is based on how high the peak concentration is Time dependent: the amount of organisms killed is dependent on how long the drug concentration stayed above the MIC

Question 33

Unique pharmacodynamic features of amnioglycosides that allow it to be only given once daily

Answer 33

Post antibiotic effect + concentration dependent killing

Question 34

What is the mechanism of action of aminoglycosides

Answer 34

- passive diffuses across membranes of gram NEGATIVE - actively transported (O2 dependent) across cytoplasmic membrane - covalently binds to 30S subunit and causes irreversible inhibition of the initiation complex → misreading of mRNA and blockade of translocation

Question 35

What are some of the consequences of the irreversible inhibition of the initiation complex in aminoglycoside

Answer 35

Misreading of mRNA and blockade of translocation

Question 36

Aminoglycosides are most active against _______ bacteria

Answer 36

Aerobic gram negative

Question 37

3 principle mechanisms of aminoglycoside resistance

Answer 37

- Plasmid associated synthesis of enzymes that modify and inactivate drugs by: acetylation, phosphorylation and adenylation - ↓ accumulation of the drug - mutation can alter or delete the receptor protein on the 30S subunit

Question 38

_____________ (an aminoglycoside) is used for bowel surgery and hepatic encephalopathy

Answer 38

Neomycin

Question 39

What is aminoglycosides used to treat

Answer 39

Used mostly in combination - empiric therapy for serious infections such as septicemia, nocosomial RTI, complicated UTI’s, endocarditis, etc Once the organism is identified, aminoglycosides are usually discontinued to favor less toxic drugs

Question 40

Aminoglycosides are given ______ except for _______

Answer 40

Parenteral; neomycin which is given topically

Question 41

High levels of aminoglycosides are seen in _____ and _____

Answer 41

Renal cortex and inner ear

Question 42

Adverse effects of aminoglycosides

Answer 42

- ototoxicity - nephrotoxicity - neuromuscular blockade in patients who have neuromuscular conditions such as Myasthenia

Question 43

In what conditions are aminoglycosides contraindicated with

Answer 43

Myasthenia gravis (and other similarly conditions) and pregnancy

Question 44

What drugs are used to treat hepatic encephalopathy and explain why

Answer 44

- oral neomycin - lactulose - oral vancomycin - oral metronidazole - rifaximin Drugs that are poorly metabolized in the gut are used to treat this and the encephalopathy is due to the ↑ NH4 (ammonia)

Question 45

Mechanism of action of how lactulose treats hepatic encephalopathy

Answer 45

Acidified the gut lumen which favors NH4 → NH3 and thus plasma ammonia concentrations are ↓ When lactulose is degraded by the intestinal bacteria, lactic acid is produced

Question 46

Effects of lactulose

Answer 46

- treat hepatic encephalopathy - prebiotic: suppression of urase producing organisms - osmotically active laxative

Question 47

Macrolide family drugs: ( 4)

Answer 47

Erythromycin Clarithromycin Azithromycin Telithromycin

Question 48

Macrolide are bacterio________ and are mainly used to treat gram ______ bacteria

Answer 48

Bacteriostatic; gram positive

Question 49

mechanism of action of macrolide

Answer 49

Reversibly binds 23S rRNA of the 50S subunit and blocks translocation

Question 50

3 Mechanisms of resistance for macrolides

Answer 50

- reduced membrane permeability or active efflux - production of esterase that hydrolyze drugs (by enterobacteriase) - modification of ribosomal binding site by either mutation or methylation

Question 51

Macrolide drugs that have complete cross resistance: | 3

Answer 51

Erythromycin, azithromycin, clarithromycin

Question 52

Macrolides are most active against gram _________ bacteria

Answer 52

Positive

Question 53

Clinical applications for Macrolides

Answer 53

- community acquired pneumonia outpatient (combine with β lactam for inpatients) - atypcial pneumonia - upper respiratory tract and soft tissue infection

Question 54

_________ is the drug of choice for whooping cough

Answer 54

Erythromycin

Question 55

Macrolides is a common substitute for someone with ______ allergy

Answer 55

Pencillin

Question 56

Compare the pharmacokinetics of the macrolide drugs

Answer 56

Clarithromycin, azithromycin and telithromycin have improved oral absorption, longer half life, ↑ bioavailability, and broader spectrum than erythromycin

Question 57

__________, __________, and _________ are CYP 450 ___________ .

Answer 57

Erythromycin, clarithromycin, telithromycin | Inhibitors

Question 58

_________ is a macrolide drug that does NOT inhibit CYP 450

Answer 58

Azithromycin

Question 59

Contraindications for macrolides:

Answer 59

- statins (macrolides inhibit CYP 450) | - do not use telithromycin for minor illnesses because it can cause fatal hepatotoxicity