L71 – Drugs Used in the Treatment of Pulmonary Infections Flashcards Preview

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Flashcards in L71 – Drugs Used in the Treatment of Pulmonary Infections Deck (92):
1

Symptom of tonsilitis?

Local infection of tonsils = red, swollen with exudate on the surface

2

What are some upper respiratory tract infections?

Pharyngitis
Tonsilitis
Sinusitis and otitis media

3

What is acute bronchitis? Symptoms? Pathogen?

Inflammation of bronchi

fever, cough, wheezing and "noisy chest“

Respiratory syncytial virus (RSV), parainfluenza virus, adenovirus

4

What is acute BRONCHIOlitis? Symptoms? Pathogen?

Inflammation and narrowing of terminal bronchioles

fever first and followed by
respiratory distress and wheezing

RSV, parainfluenza virus

5

Some general symptoms of pneumonia? Type of pathogens?

fever, respiratory distress and cyanosis

Primary community-acquired: bacterial infections are more prominent

6

Name all the classes of antibiotics used to treat primary community-acquired pneumonia (bacteria)?

- B-lactams:
1) Cephalosporins (3rd gen)
2) Penicillins +/- B-lactamase inhibitor

- Macrolides

- Tetracyclines

- Fluoroquinolones

7

When is Fluoroquinolone used for primary community -acquired pneumonia?

For severe gram -ve bacterial infection

8

Give the bacterial component target for all classes of antibiotics used for primary comminity=acquired pneumonia?

B-lactams - cell wall peptidoglycan synthesis

Tetrcyclines - 30s inhibitor

Fluoroquinolones - Nucleic acid synthesis

Macrolides - 50s inhibitor

9

Is B-lactams bactericidal or static?

Bactericidal

10

What is the MoA of B-lactams?

Cross bacteria cell wall > bind to penicillin-binding-protein > inhibit these transpeptidase enzymes > cannot make peptidoglycan cross links between NAM subunits

Activate autolysins in bacteria to destroy existing cell wall > cell burst through osmotic pressure

11

Compare the entry of B-lactams in gram +ve and-ve bacteria?

Gram +ve: no outer membrane, no porin channel >> antibiotics go in by diffusion >> less resistance

Gram -ve: if porin channel is impaired >> antibiotic cannot go in

12

What are some resistance mechanisms specific for gram -ve bacteria against B-lactams?

1. Loss of porins
2. Efflux pump

13

What are some resistance mechanisms used by both gram+ve and -ve bacteria?

Altered/ Modified PBP, penicillin binding protein (e.g. mecA)


B-lactamase

14

What are the 4 classifications of penicillins?

1) Narrow spectrum, B-lactamase-SENSITIVE

2) Narrow spectrum, B-lactamase- RESISTANCE

3) Extended spec. AMINOpenicillins

4) Extended spec. ANTI-PSEUDOMONAL penicillins

15

What are some limitations of penicillin G?

Narrow spectrum
Short duration of acid
Poor penetration into CNS

Unstable in stomach acid
Useless against B-lactamase
Allergy for some

16

What are some COMMON adverse effects of Penicillin G?

Diarrhea
Seizures (esp. in epileptic patients)

17

What are some RARE adverse effects of Penicillin G?

Low toxicity > allergy

Acute interstitial nephritis

Decreased coagulation

Cation toxicity

18

How can antistaphlyococcal penicillin resist B-lactamase?

BULKY SIDE GROUPS can block B-lactamases that hydrolyzes the B-lactam ring

Resist acid degradation

19

Name some antistaphlyococcal penicillin (B-lactamase-resistant penicillins)? which one is highly nephrotoxic?

methicillin (highly nephrotoxic)
Cloaxacillin
flucoxacillin
oxacillin

-xacillin

20

When is antistaphlyococcal penicillin used and what is one disdavantgae?

Used to B-lactamase resistant STAPHYLOCOCCAL infections

Harder to penetrate cell membrane due to bulky side chain> less effective

21

Extended spectrum aminopenicillins are effective against which bacteria?

Gram +ve and Gram –ve cocci, Gram –ve
bacill

Not effective against Pseudomonas spp.

22

When is Extended spectrum aminopenicillins used?

 Excellent oral agent for bacterial sinusitis, bronchitis

23

What are the advantages and disadv. of Extended spectrum aminopenicillins ?

Advantages: Acid stable, good oral bioavailability (amoxicillin > ampicillin)


Disadvantage: Do not resist B-lactamases

24

Name 2 Extended spectrum aminopenicillins?

Ampicilin
Amoxicillin

25

Name 2 classes and 3 examples of extended spectrum antipseudomonal penicillins?

 Carboxypenicillins (e.g. carbenicillin, ticarcillin)

 Ureidopenicillins (e.g. piperacillin )

26

What are some advantages and disadvantages of extended spectrum antipseudomonal penicillins?

Good: effective against many gram -ve bacilli and very effective against Pseudomonas aeruginosa (unlike aminopenicillins)

Bad: sensitive to B-lactamses, acid labile

27

What are B-lactamase inhibitors

Name 3

= potent irreversible inhibitor of many β-lactamases producing bacteria, esp. in respiratory tract


E.g.:
1. Clavulanate (clavulanic acid)
2. Sulbactam
3. Tazobactam

28

What drugs is usually given with B-lactamase inhibitors and why?

normally formulated / combined
with a broad spectrum penicillin derivative

>> to protect them from enzymatic inactivation by β-lactamases

29

Name the 4 combo preparations of B-lactamase inhibitors?

Combo broad spectrum penicillin and B-lactamase inhibitor

 Augmentin (amoxicillin + clavulanic acid = co-amoxiclav

 Unasyn (ampicillin + sulbactam = sultamicillin)

 Timentin (ticarcillin (= carboxypenicillin) + clavulanic acid)

 Tazocin (piperacillin (= ureidopenicillins) + tazobactam)

30

Cephalosporin is effective against which bacteria? Bacteriocidal or static?

Broad spectrum (vs. Gram +ve, Gram –ve, some vs. anaerobes)
** improved activity against gram -ve bacteria **

Bactericidal

31

Name some first, second, third, fourth, fifth gen cephalosporins?

First: cefadroxil
2nd: Cedaclor
3rd: Ceftriaxone
4th: Cefepime
5th: Ceftaroline

32

What is 1st gen cephalosporin best used against?

gram +ve
community acquired enterobacter

33

What is 2nd gen cephalosporin best used against?

both grams

34

What is 3rd gen cephalosporin best used against?

Mainly against gram -ve

35

What is 4th adn 5th gen cephalosporin best used against?

4th: wide spectrum + B-lactamase resistant
5th: wide spectrum + MRSA active

36

Which cepahlosporins can be given orally unlike others that are given IV or IM dur to poor oral absorption?

cefalexin
cefuroxime
ceftibuten

37

Which gen cephalosporin has good CSF penetration?

All gens are shit except 3rd gen

38

What is the half-life and path of excretion for cephalosporins?

long half-life (e.g. 6-8hr)

Renal secretion (except ceftriaxone > bile excretion)

39

Adverse effects of cephalosporin? aside from being very expensive

Oral admin> GI irritation

Allergic

Infrequent nephrotoxicity

40

Compare the spectrum between tetracyclines and macrolides?

Tetra = broad

Macrolides = Moderate

41

Difference between erthyromycin vs clarinthromycin and azithromycin?

Erythromycin (= prototype)
clarithromycin and azithromycin are new analogues >> improved pharmacokinetic properties, broader antibacterial
spectrum

42

What is the MoA of macrolides?

Bind irreversibly to a site on 50S subunit
of the bacterial ribosome

>> inhibit translocation of the polypeptide chain from A-site to P-site catalyzed by peptidyltransferase


>> block movement of peptidyl tRNA from acceptor to donor site

>> incoming tRNA cannot bind to the still occupied acceptor site >> inhibit bacterial
protein synthesis

43

When is erythromycin used?

Active vs. Gram +ve organisms (same as
penicillin G)
>> narrow spectrum

For patients allergic to penicillins

44

When is Clarithromycin used?

 Slightly greater activity than erythromycin

 Higher activity vs. intracellular pathogens, e.g. Chlamydia, Legionella, Moraxella

 Also has activity vs. Mycobacterium
leprae, Toxoplasma gondii, H.pylori

45

When is Azithromycin used?

 Slightly less active than erythromycin
vs. Gram +ve
 But enhanced activity vs. some Gram –ve organisms, e.g.Haemophilus
influenzae

46

Rank the three macrolides antibiotics in terms of activity against gram +ve bacteria?

Clarithromycin > erythromycin > azithromycin

47

When is Telithromycin used?>

Different site of action >>
effective vs. macrolide-resistant strains

48

What is the difference in absorption between erythromycin and newer macrolides?

Newer macrolides are more acid stable (instead of labile in gastric acid) and better obsorbed

49

Are all macrolides orally absorbed?

Yes

50

Are all macrolides converted to an active metabolite?

All except Erthyromycin

51

Which of the 4 macrolides are extensively metabolised in body?

Erthyromycin and telithromycin

52

Which of the 4 macrolides are exreted in bile in an active form (undergo enterohepatic circulation)?

Erthyromycin and azithromycin

53

Which macrolide is metabolized to active 14-hydroxy metabolite and eliminated in urine?

Clarithromycin

54

What is the toxicity and therapeutic index of macrolifdes?

High therapeutic index, relatively non-toxic

55

What are some adverse effects of macrolides?

GI disturbances (due to stimulation of motilin receptors

High dose of ethromycin can cause deafness

Risk of arrhythmia

Drug interactions (except azithromycin)

56

What respiratory tract infections are treated by macrolides?

Upper and Lower, including pharyngitis and tonsilitis

57

Macrolides is the drug of choice for which type of pneumonia?

Atypical

Caused by Mcoplasma and Legionella

58

Macrolides is used to replace which drug in case of allergy?

Penicillin substitute

for infections caused by staph. Strep. or pneumococci

59

Macrolides is used as an empirical therapy for which diseases?

Early outpatient pneumonia or bronchitis

60

Macrolides cannot be used for which patients?

Those with Liver disease

61

What are the 3 bacteria mechanisms against macrolides?

Effluc pump/ reduce permeability of cell membrane

Modify 50s subunit (methylases encoded by erm)

Release endogenous esterases to hydrolyse macrolides

62

Name 2 teracyclines? Which one it most popular?

Doxycycline *popular*

Glycylcycline

63

Tetracycline spectrum and bacteriocidal or static?

Broad spectrum

Bacteriostatic > inhibit protein synthesis

64

MoA of tetracyclines?

Bind to 30s ribosome > prevent access of tRNA to -site on mRNA- ribosome complex

> block addition of amino acid to growing peptide

> peptide not transferred to amino acid receptor

65

What type of infections if tetracyclines used against and why?

Not against common infections (reduce resistance)

Treat uncommon infections (like Chlamydia, Mycosplasma, spirochetes infections)

66

Why can Doxycycline be used in renal impaired patients? *think absorption and excretion*

Absorbed orally

Exreted in bile and not accumulate in kidney

67

What is Glycylcyclines effective against and not?

Effective: multi-resistant Gram +ve pathogens, some gram -ve, anaerobic organisms

Ineffective: Protus and pseudomonas spp.

68

When is glycylcyclines used?

Treat complicated skin and soft tissue infections

complicated intra-abdominal infections

69

Excretion of Glycylcycline?

Biliary excretion

70

Why is IM injection avoided for tetracyclines?

Cause local tissue irritation

71

What are some adverse effects of tetracyclines?

Permanent teeth
discoloration in children

Photosensitization
(abnormal sunburn)\


GI irritation

Hepatotoxicity (jaundice,
fatty liver esp in pregnant
women)

Vestibular problems (e.g.
dizziness)

72

3 mechanisms in bacteria against tetracyclines?

Efflux pump/ impaired influx (porin)

Synthesis of blocking molecule to interfere binding to 30s ribosome

Production of tetracycline inactivating enzyme

73

Name the prototype quinolone and fluoroquinolone?

Quin = Nalidixic acid

Fluoro = Ciprofloxacin

74

What is the difference between 1st gen and 2nd, 3rd gen quinolones/ fluoroquinolones?

2nd gen = expanded activity:
against gram -ve
some gram +ve
atypical organisms

75

What is the general improvement of generations of quinolones?

Improve coverage against more gram -ve, +ve, atypical, anaerobic coverage

76

Name one 1st, 2nd, 3rd, 4th gen quinolone/ fluoroquinolone?

1= nalidixic acid (urinary
antiseptics)
2 = ciprofloxacin
3 = levofloxacin
4 = gemifloxacin

77

Spectrum and bactericidal or static for quinolones/fluoro--?

Bactericidal

Broad spectrum

78

When is quinolone/ fluoro -- used? Which patients should not take it?

Treating lower respiratory tract infections


Contraindicated in children,
nursing mothers, pregnancy
(arthropathy >> potential: problem in joints)

79

What is the MoA for quinolones/ fluoro--?

Dual action: inhibit DNA gyrase and topoisomerase IV

DNA gyrase:
form quinolone-DNA- gyrase
complex >> induce cleavage of DNA

80

Penetration, excretion of quinolones/ fluoro--?

 High tissue penetration
 Mainly excreted into the
urine

81

3 mechanisms for resistance in bacteria against quinolones/ fluoro--?

Overexpress efflux pump

Reduce membrane permeability (less porin in gram -ve)

bacterial chromosomal mutations for genes that encode for bacterial DNA
gyrase, topoisomerase IV

82

Adverse effects of quinolones/ fluoro--?

GI disturbance

CNS problems (e.g. confusion, dizziness)

Photosensitivity

Ruptured tendons in elderly

83

What drugs interact with quinolones/ fluoro--?

with cations (divalent and
trivalent)

antacids,

theophylline,

warfarin, etc.

84

What is the outpatient therapy for pneumonia?

1) Macrolides, doxycycline or oral, anti-pneumococcal B-lactam

e.g. Augmentin

2) Oral fluoroquinolone active against S. pneumonia for allergic patients or highly resistant infection

85

What is the inpatient therapy for pneumonia?

1) Parenteral B-lactam* + macrolide
*e.g. ceftriaxone, ampicillin-sulbactam, cefotaxime

2) Fluoroquinolone in some patients

86

S. pneumonia is highly resistant to which antibiotics?

erthromycin, tetracycline, co-trimoxazole

87

3 things recommended by CDC against pneumonia?

Only prescribe antibiotics when its beneficial

Use specific agent to target pathogen

Use appropriate dose and duration

88

Adv. and Disadv. of amoxicillin.

Adv. = high dose kills 60-96% s, pneumonia

Disadv. = cannot kill atypical or B-lactamase bacteria

89

Adv. and Disadv. of Augmentin (amoxicillin - clavulanate)?

Adv. = kill B-lactamase bacteria

Disadv. = cannot kill atypical agents

90

Adv. and Disadv. of Cephalosporins?

Adv = active against all H. influenzae and 75-85% S. pneumoniae

Disadv. = cannot kill atypical agents

91

Adv. and Disadv. of Macrolides.

Adv. = kill most common + atypical pthogens

Disadv. = drug resistance problem

92

Adv. and Disadv. of F- quinolone?

Adv = kill H. influenzae + atypical pathogens

Disadv. = less effective against S. pneumoniae, risk of increasing resisitance

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