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Pulmonary > Pulmonary Pharmacology > Flashcards

Pulmonary Pharmacology Flashcards

1
Q

Breaking of the Carbon-Nitrogen bond in the ß-lactam ring structure by ßlactamases
(penicillinase) will?

A

Inactivate the penicillin’s antibacterial activity.

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2
Q

To combat the action of the ß-lactamases, combine the ß-lactam with?

A

A ß-lactamase inhibitor, such as Clavulante,

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3
Q

A ß-lactam that is resistant to the specific ß-lactamase?

A

(carbapenem), or use a different class.

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4
Q

Natural penicillins G and V

A

Effective against gram + cocci (sensitive strains of S. pneumococcus).
Ineffective against many Staph aureus strains, which produce the penicillinase-type ß-lactamases.

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5
Q

Antibiotic-associated diarrhea (AAD) can be a problem following oral treatment with?

A

Penicillins, ampicillin in particular, but also augmentin.

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6
Q

penicillin can cause or exacerbate?

A

Hypokalemic alkalosis, because penicillin exists as a non-absorbable anion. To maintain electric neutrality, K+ moves into the tubule in exchange for H+.

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7
Q

The most frequent adverse effect of the penicillins?

A

Allergic reactions

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8
Q

There are three levels of sensitivity reactions to the penicillins?

A

Delayed, accelerated and acute. The accelerated and acute reactions are IgE mediated.

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9
Q

Procaine penicillin G is associated with the highest incidence of?

A

Drug allergy.

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10
Q

A patient considered allergic to one penicillin should be?

A

Considered allergic to all other pencillins.

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11
Q

Cephalosporins were developed to do three things?

A
  1. be effective in the patient allergic to penicillins!
    Less than 10% of PNC allergic patients will be allergic to CEPHS.
  2. to be effective against bacteria that are resistant to penicillins!
  3. to have a broader spectrum!
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12
Q

One of the newest (forth or fifth generation) is important because it is effective in treating methicillin resistant S. aureus and is FDA approved for community acquired bacterial pneumonia

A

cephalosporins (Ceftaroline)

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13
Q

Cephalosporins what can third generation do that fisrt and second cannot?

A

None of the the 1st or 2nd generations enter the CSF, even in the presence of inflammation where 3rd generations do enter CSF.

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14
Q

Ceftriaxone is now drug of choice for?

A

N. gonorrhea–replacing penicillin

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15
Q

Cefotaxime-active against?

A

Ampicillin-resistant H. flu.

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16
Q

IMPORTANT- none of these cephalosporins work against?

A

Enterococci.

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17
Q

Most of the cephs require an adjustment of dosage in patients with compromised?

A

Renal function. Either decrease the dosage or increase the dosage interval. Supplemental dosage needed following hemodialysis except for Ceftiaxone.

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18
Q

Several cephalosporins penetrate into CSF in sufficient concentration to be useful
for the treatment of?

A

Meningitis; Cefotaxime and Ceftriaxone in particular.

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19
Q

Cephalosporins adverse reaction?

A

Nephrotoxicity at high dose.

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20
Q

Carbapenems are a subclass of?

A

ß-lactams.

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21
Q

One big advantage of the Carbapenems?

A

Their high resistance to the bacterial ßlactamase

enzymes.

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22
Q

Carbapenems are potent suicide inactivators of the?

A

ß-lactamase enzymes.

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23
Q

Imipenem is given with?

A

Cilastatin. A preparation has been developed that contains equal amounts of imipenem and cilastatin (PRIMAXIN).

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24
Q

Imipenem has one of the broadest spectrums?

A

ß-lactams.

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25
Q

Imipenem administered?

A

IV, with good distribution to body tissues, but does not

achieve therapeutic levels in the CSF except with inflamed meninges.

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26
Q

Imipenem-cilastatin combination is especially useful for treatment of serious infections?

A

Which aerobic gram-negative bacilli, anaerobes and staph aureus may be involved.

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27
Q

Imipenem has the same adverse effects as the previous ß-lactam?

A

Patients can have similar allergic reactions to Imipenem. Patients who are allergic to other ß-lactam antibiotics may have hypersensitivity reactions when given imipenem.

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28
Q

Imipenem is contraindicated in patient with?

A

CNS seizures.

29
Q

Two newer carbapenems are?

A

Meropenem and Ertapenem.

30
Q

Neither Meropenem and Ertapenem require?

A

Co-administration of cilastatin.!

31
Q

Meropenem is very similar to imipenem but with less?

A

G+ activity, but also with less chance of inducing seizures.

32
Q

Ertapenem has a long?

A

Half life which enables once daily dosing, but is less effective against pseudomonas.!

33
Q

Amikacin is often effective for treatment of infections caused by?

A

Gram-negative strains resistant to gentamicin and tobramycin, including some strains of Pseudomonas aeruginosa and Acinetobacter.

34
Q

Amikacin like other aminoglycosides has limited distribution? and should be combined with?

A

Lungs is limited and when used to treat gram negative
bacilli that cause pneumonia it should be combined with another agent to which the organism is susceptible, such as a ß-lactam.

35
Q

Colistimethate is a generic of?

A

polymyxin E.

36
Q

The polymyxins are used topically in combination

with other antibiotics for treatment of?

A

Infected wounds and otitis externa. Some strains of gram-negative bacilli (particularly Klebsiella, Pseudomonas aeruginosa and Acinetobacter) resistant to all other available antibiotics have been treated with one of the polymyxins; for infections caused by Acinetobacter, sulbactam (in the form
of ampicillin/sulbactam) is often added, though some strains are resistant to it.

37
Q

The polymyxins used systemically are often?

A

Nephrotoxic.

38
Q

Macrolide class.

A

Erythromycin, Clarithromycin, and Azithromycin

39
Q

Macrolide class.

Mechanism of action:

A

Inhibition of protein synthesis by binding 50S ribosomal subunit.

40
Q

Constitutive expression of erm confers cross-resistance to?

A

All three drug types: Erythromycin, Clarithromycin, and Azithromycin

41
Q

Erythromycin crosses?

A

Placenta and is distributed in breast milk and is one of few drugs to diffuse into prostatic fluid and accumulates in macrophages.

42
Q

The spectrum for erythromycin is similar to?

A

Penicillin for gram positives and can be a substitute for penicillin allergic patients.

43
Q

Erythromycin can be used to eliminate the carrier state?

A

Corynebacterium dephtheriae.

44
Q

Most common side effect erythromycin?

A

Epigastric distress can lead to poor patient compliance.

45
Q

Erythromycin can cause two other adverse effects?

A

Chloestatic hepatitis – hypersensitivity reaction to estolate form of the erythromycin
Transient deafness – associated with high doses in geriatric patients

46
Q

Erythromycin is contraindicated in patients with?

A

Hepatic dysfunction – drug accumulates in liver and is a big time inhibitor of the cytochrome p450 system.
May also see QT prolongation.

47
Q

Clarithromycinadvantages to Erythromycin?

A

More acid stable, has better oral absorption, a somewhat longer half-life and increased tissue penetration.

48
Q

Clarithromycin disadvantages?

A

Undergoes first pass metabolism, elimination is by both renal and hepatic mechanisms and if the creatinine clearance is low, will need to make dosage adjustments.

49
Q

Azithromycin advantages?

A

Half life in the range of 40 to 70 hrs.
There is very good concentrations of Azithromycin in neutrophils, macrophages and fibroblasts, which also leads to its wide usage and effectiveness.

50
Q

Fluoroquinolones the most effective for the treatment of pneumococcus.?

A

Levofloxacin and Moxifloxacin

51
Q

Fluoroquinolones selectivity

A

Need 100 to 1000 X more quinolone to inhibit mammalian topo II than bacterial.

52
Q

Quinolone resistance-determining region (QRDR)?

A

Mutations in this region generally result in resistance to the quinolones because of decreased binding of the FQ to the protein.

53
Q

QRDR resistance is not plasmid mediated, but results from?

A

Chromosomal alterations.
Two mechanisms for reduced accumulation:
1. decreased number of porin proteins in the outer membrane, thereby
impairing access of the drugs to the intracellular gyrase.
2. energy-dependent efflux system in the cytoplasmic membrane.

54
Q

Fluoroquinolones affects absorption of oral FQs?

A

Avoid use with antacids, iron or zinc supplements,

multivitamins. Oral FQs should be taken 2hrs before or 4hrs hours following any meal or product containing this cations.

55
Q

Fluoroquinolones accumulate in? making them effective against?

A

Macrophages and polymorphonuclear leukocytes, thus

being effective against intracellular organisms such as Legionella.

56
Q

Levofloxacin and Moxifloxacin prolong the half-time of each drug.

A

Renal failure will prolong the half-time of each drug.

57
Q

Fluoroquinolones to some degree, all FQs may cause?

A

Interval prolongation or with hypokalemia. This caution also applies to patients concurrently taking Class IA or Class III antiarrhythmic agents or patients taking drugs know to increase the Etc. interval (erythromycin, tricyclic antidepressants).

58
Q

Levofloxacin may be more effective for the treatment of?

A

Legionella pneumophila than azithromycin.

59
Q

The FQs also may produce a synergistic activity with combined with?

A

ß-lactams. Thus the FQs have been nicknamed aminoglycosides-lite.

60
Q

Tetracyclines:

Mechanism of Action MOA:

A

MOA of tetracyclines in inhibition of protein synthesis by binding to 30S ribosomal proteins.

61
Q

Tetracyclines binding compared to aminoglycosides?

A

The binding is reversible as opposed to the binding of AMG which is irreversible. This results in the tetracyclines being bacteriostatic in their action.

62
Q

Broad spectrum nature of tetracyclines is shown by?

A

The fact that have activity against gram-positive and gram-negative bacteria (both aerobic and anaerobic species), but also Chlamydia, Rickettsia, and Mycoplasma. Tetracycline is something like a jack of all trades and a master of none when it comes to treating bacterial infections.

63
Q

Tetracycline should not be given with?

A

Milk and dairy products iron containing vitamins or mineral supplements and with antacids.

64
Q

Toxicity Minocycline:

A

Vestibular toxicity: manifested as dizziness, ataxia, nausea, and vomiting. Symptoms occur soon after initial dose and generally disappear in 1-2
days after treatment is stopped.

65
Q

Adverse effect Doxycycline

A

Photosensitivity (doxycycline)– if apparent, can appear within minutes of taking the tetracycline if the patient is exposed to direct sunlight or UV light.

66
Q

tetracycline is used mostly for the

infections with?

A

Atypical organisms.

67
Q

The Sulfonamides will distribute to the?

A

CSF even without inflammation of the meninges. Depressed kidney function causes accumulation of both the parent compounds and its metabolites.

68
Q

Sulfonamides adverse effect?

A

Nephrotoxicity develops as a result of crystalluria.

69
Q

Trimethoprim-sulfamethoxazole TMP/SMX is first line therapy for?

A

Nocardiosis. If the patient is allergic to the TMP/
SMX, desensitization should be performed. If this isn’t possible, a 3rd generation cephalosporin or imipenem or meropenem are alternatives.

Pulmonary (9 decks)

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