drugs for bacterial pulmonary infections

Question 1

describe the 4 major categories of penicillins

Answer 1

1. natural penicillins
2. anti-staphylococcal (penicillinase-resistant) penicillins
3. Amino penicillins (Extended spectrum)
4. Anti-pseudomonal

Question 2

MOA of penicillins

Answer 2

beta-lactams that bind to and inhibit transpeptidation of the peptidoglycan in bacterial cell walls (bacteriocidal)

Question 3

what is augmentin?

Answer 3

amoxicillin + clavulanic acid

Question 4

what does augmentin treat?

Answer 4

beta-lactamase producing staph aureus and other anaerobes producing respiratory tract infections

Question 5

what is unasyn?

Answer 5

ampicillin + sulbactam

Question 6

how is unasyn administered

Answer 6

parenteral

Question 7

what is unasyn used for?

Answer 7

amp-resistant H. influenzae
moraxella catarrhalis
mixed G+ and anaerobic infections (CAP)

Question 8

how do Clavulanic acid, Sulbactam and Tazobactam work?

Answer 8

they are suicide inhibitors that irreversibly acetylate the beta-lactamase enzyme

Question 9

when should Penicillin V be given?

Answer 9

1 hour before or 2 hours after meal

Question 10

how does food affect the absorption of penicillins?

Answer 10

generally decreases absorption (except amoxicillin)

gastric juices and decreased pH destroys PCN

Question 11

how are penicillins metabolized?

Answer 11

hepatic enzymes (increased in pts w/ renal impairment)

Question 12

how are the penicillins excreted?

Answer 12

renal tubular secretion (90%)

Question 13

what 2 important things can affect the half life of penicillin?

Answer 13

1. physiological state of the kidneys

2. concomitant therapy w/ drugs that are organic acids (drugs compete w/ penicillin for excretion by the kidneys)

Question 14

if you have a pt w/ renal dysfunction how might you change the way you prescribe penicillins?

Answer 14

increase the dosing interval

Question 15

what are 5 important adverse effects of penicillins?

Answer 15

1. N/V (frequent w/ children)
2. diarrhea after oral dose (killed gut flora)
3. abnormal plasma electrolytes (in hypokalemic pt)
4. renal impairment-dose related (Penicillin G)
5. neurotoxicity w/ large doses (likely in pts w/ reduced renal function)

Question 16

How long do delayed allergic rxns to penicillins take?

Answer 16

2 days (rashes)

Question 17

how long do accelerated pencillin allergic reactions take?

Answer 17

30 mins to 48 hrs (hives, wheezing ,mild laryngeal edema, local inflamm. rxns)

Question 18

what are the symptoms associated with penicillin acute allergic reaction?

Answer 18

anaphylaxis

bronchospasm

Question 19

How do cephalosporins work?

Answer 19

bind to PBPs on bacterial cell membranes and inhibit bacterial cell wall synthesis similar to penicillins

Question 20

Modifications at position 7(R1) of the beta-lactam ring are associated with_________________

Answer 20

alteration in antibacterial activity

Question 21

Substitutions at position 3(R2) of the dihydrothiazine ring are associated with changes in ______________________

Answer 21

the metabolism and pharmacokinetic profile of the drug

Question 22

what were the 3 reasons that cephalosporins were developed?

Answer 22

1. be effective in pt allergic to penicillins
2. to be effective against bacteria that are resistant to penicillins
3. to have a broader spectrum

Question 23

progression from 1st to 3rd generation cephalosporins are marked by what 4 things?

Answer 23

1. broadening in gram negative susceptibility
2. diminished activity against G+ bacteria
3. increased resistance to beta-lactamase inactivation
4. increased capability to enter the CSF

Question 24

what are the 3rd generation cephalosporins used for?

Answer 24

enteric gram-negative organisms
reserved for very serious infections (crosses the BBB)
-H. influenza, Serratia, Pseudomonas (ceftazadime only)

Question 25

whats unique about the 3rd generation cephalosporins?

Answer 25

penetrate the CSF enough to treat meningitis

Question 26

how are the cephalosporins excreted?

Answer 26

renal tubular mechanims

Question 27

what happens to the serum levels of cephalosporins when taken with probenecid?

Answer 27

increased

Question 28

what are the adverse reactions to cephalosporins?

Answer 28

``` hypersensitivity diarrhea & GI distrubance severe pain w/ IM injections Phlebitis from intravenous administration nephrotoxicity at high dosage ```

Question 29

which cephalosporin most commonly causes diarrhea and GI disturbance?

Answer 29

ceftriaxone

Question 30

how do carbapenems work

Answer 30

chemically different than penicillins but still have beta-lactam ring structure (binds to transpeptidase and blocks the cross linking of the cell wall peptidoglycan strands)

Question 31

what is one big advantage of the carbapenems over the penicillins?

Answer 31

carbapenems have high resistance to bacterial beta-lactamase (potent suicide inactivators)

Question 32

which drug has the broadest spectrum of any beta-lactam antibiotic?

Answer 32

imipenem

Question 33

imipenem is administered with what drug?

Answer 33

cilastatin

Question 34

how does cilastatin work?

Answer 34

inhibitor of dehydropeptidase (in brush border of proximal renal tubule) prevents breakdown of imipenem and renal toxicity fixed combination-->primaxin

Question 35

how is imipenem administered?

Answer 35

IV w/ good distribution to body tissues, but not CSF

Question 36

how is imipenem excreted?

Answer 36

both glomerular filtration and active secretion

Question 37

how does probenecid affect the half life of imipenem?

Answer 37

IT DOESNT

Question 38

Which carbapenem is contraindicated in pts w/ CNS seizures?

Answer 38

imipenem

Question 39

what is the typical indication for imipenem-cilastatin combo?

Answer 39

serious infections of aerobic gram-negative bacilli, anaerobes, and staph aureus

Question 40

how do aminoglycosides work?

Answer 40

protein synthesis inhibitor by binding to 30S subunit: 1. block formation of initiation complex 2. cause misreading of the code on mRNA template 3. inhibit translocation

Question 41

what's so great about the aminoglycosides?

Answer 41

broad spectrum of activity | valuable in treating nosocomial infections

Question 42

how do the macrolides work?

Answer 42

binds reversibly to 50s ribosomal subunit and inhibits protein synthesis (bacteriostatic)

Question 43

Name the 3 macrolides?

Answer 43

erythromycin azithromycin clarithromycin

Question 44

which macrolide do you have to make sure that you are reaching the minimal inhibitory concentration?

Answer 44

erythromycin

Question 45

which macrolide diffuses into prostatic fluid and macrophages and is primarily excreted in bile and feces?

Answer 45

erythromycin

Question 46

What are the drugs of choice in legionnaire's disease?

Answer 46

erythromycin, azithromycin

Question 47

what is the most frequent side effect of erythromycin?

Answer 47

GI upset

Question 48

what is an important drug interaction involved with erythromycin?

Answer 48

inhibits cytochrome P450 3A (possible QT elongation in combo w/ other CYP3A inhibitors)

Question 49

which drug causes cholestatic hepatitis and transient deafness?

Answer 49

erythromycin hypersensitivity reaction to estolate form (also contraindicated in pts with liver dysfunction b/c it accumulates in liver)

Question 50

Name this drug: more acid stable than erythromycin, absorption increases w/ food, undergoes rapid first pass metabolism with active primary metabolite, eliminated by kidney and liver.

Answer 50

clarithromycin

Question 51

Name this macrolide: t 1/2 40-68 hours

Answer 51

azithromycin

Question 52

how is the majority of azithromycin excreted?

Answer 52

in bile

Question 53

which macrolide has a major advantage over the others in that it doesn't inhibit any CYP enzymes?

Answer 53

azithromycin

Question 54

how do the quinolones work?

Answer 54

inhibits DNA replication via binding to DNA gyrase and topoisomerase IV (bactericidal)

Question 55

What are 2 ways that resistance is developing to fluroquinolones by less drug getting to the target enzyme?

Answer 55

1. decrease number of porin proteins in the outer membrane (impairing access to intracellular gyrase) 2. decreased intracellular accumulation of drug via efflux pumps

Question 56

what can bind to and negatively affect the absorption of oral fluoroquinolones?

Answer 56

divalent, trivalent cations (iron, zinc supplements)

Question 57

what are the important side effects of fluoroquinolones?

Answer 57

photosensitivity prolongation of QT interval (moxifloxacin) articular cartilage erosion GI upsets

Question 58

how do the tetracyclines work?

Answer 58

inhibit protein synthesis by reversible binding to 30S ribosome (bacteriostatic, MIC must be maintained)

Question 59

how can resistance to tetracyclines develop?

Answer 59

1. increased efflux of tetracycline from cell 2. decreased transport (resistance to one tetracycline provides resistance to all )

Question 60

what are the main indications for tetracyclines?

Answer 60

atypical pneumonias, dental disease

Question 61

what can inhibit the absorption of tetracyclines?

Answer 61

di, trivalent cations

Question 62

how are most tetracyclines removed from the blood?

Answer 62

removed by liver, also undergoes enterohepatic cycling

Question 63

how are tetracyclines distributed?

Answer 63

- wide tissue distribution and cross the placental barrier | - bone and teeth when undergoing calcification (discolors teeth)

Question 64

what are some adverse effects of tetracyclines?

Answer 64

1. GI disturbance (N/V/D, avitaminosis, superinfections) 2. chelation of Ca2+ (discoloration of teeth) 3. depression of bone growth 4. hepatic toxicity 5. photosensitivity (doxycycline)

Question 65

which tetracycline is less likely to cause superinfections?

Answer 65

doxycycline

Question 66

what are the advantages to using doxycycline over other tetracyclines?

Answer 66

1. requires fewer doses (100% bioavailability) 2. less GI disturbance 3. available oral and parenteral 4. no dosage adjustment required for reduced renal function

Question 67

what are the therapeutic uses of tetracyclines?

Answer 67

``` atypical pneumonia (doxycycline) Lyme disease Rickettsial infections periodontal disease acne ```

Question 68

what is first line therapy for nocardiosis?

Answer 68

TMP/SMX

Question 69

none of the cephalosporins work against which bug?

Answer 69

enterococcus

Question 70

what are the adverse effects of imipenem?

Answer 70

SEIZURES (beware w/ renal insufficiency) CNS toxicity allergic reactions expensive!

Question 71

how can resistance to erythromycin develop?

Answer 71

plasmid mediated processes - decreased transport - modification of target by methylases - hydrolysis of drug from hydrolases

Question 72

name of the phenotype that has a gene that encodes methylases that modify the macrolide binding to the ribosome and confers resitance to all 3 macrolides?

Answer 72

MLSb from the erm gene via a plasma mediated process

Question 73

how is erythromycin excreted?

Answer 73

in bile and feces

Question 74

what are the important drug interactions for clarithromycin?

Answer 74

also CYP3A4 inhibit but not as much as erythromycin

Question 75

which macrolide has impaired absorption with food?

Answer 75

azithromycin

Question 76

how is resistance developing against fluorquinolones regarding DNA gyrase binding?

Answer 76

Mutation in QRDR of DNA gyrase enzyme

Question 77

which tetracycline can be given to pts w/ renal dysfunction without adjustment of dose?

Answer 77

doxycycline

Question 78

what patients don't get tetracyclines?

Answer 78

pregnant women and kids under 9 yrs

Question 79

what do the fluoroquinolones treat?

Answer 79

Pneumococcus (levofloxacin, moxifloxacin) Staph Aureus bunch of gram negatives