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Antimicrobials Flashcards

1
Q

Beta-Lactam Antibiotics:

Penicillins

A

contain a beta-lactam ring as part of their structure

bactericidal against susceptible MO by blocking bacterial transpeptidase, an enzyme that cross-links polymers of bacterial cell wall

typically used to treat susceptible strep and staph infections

bacteria have developed beta-lactamase enzymes, leading to the development of combo meds containing a beta-lactamase inhibitor

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2
Q

Penicillins: ADME

A

A: variable absorption; sometimes food affects absorption

D: wide distribution, inc. CSF

M: minimal liver metabolism (except nafcillin/oxacillin, which have hepatic metabolism)

E: rapid and extensive renal elimination

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3
Q

Penicillins: Patient Education

A

Women on BCP should use alternative method until next period, or at least for one week after abx course complete

GI side effects common, esp. diarrhea

Ideally taken on an empty stomach

Finish entire course of abx

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4
Q

Beta-Lactam Antibiotics:

Cephalosporins

A

Similar mechanism of action to PCNs, but more stable to many beta-lactamases, and therefore are broader spectrum

General rule of thumb: later generations have better gram negative coverage

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5
Q

Cephalosporins: ADME

A

A: variable absorption; rate but not total extent affected by food, so may be taken with or without

D: wide, inc. to CSF

M: minimal metabolism, except cefpodoxime is de-esterified in GI tract to active form

E: high percentage excreted in urine

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6
Q

Cephalosporins: Patient Education

A

Most common side effects are GI

Cross-sensitivity with PCN allergy ranges from 2-12% in studies (give if mild allergy to PCN like rash without urticaria; avoid if severe allergy to PCN)

Ceftriaxone should not be used in premature neonates (can compete with bilirubin for binding sites and result in kernicterus)

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7
Q

Types of Beta-Lactam Antibiotics

A

Penicillins, Cephalosporins, and Carbapenems (used in acute care setting only, broad spectrum, typically not first-line agents)

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8
Q

Examples of First Generation Cephalosporins & Common Uses

A

Cephalexin (Keflex), Cefadroxil (Duricef), IV Cefazolin (Ancef)

Often used for simple skin & soft tissue infections

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9
Q

Examples of Second Generation Cephalosporins & Common Uses

A

Cefuroxime (Ceftin), Cefaclor (Ceclor), Cefprozil (Cefzil)

Often used as an alternate choice for URI

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10
Q

Examples of Third Generation Cephalosporins & Common Uses

A

Cefpodoxime (Vantin), Cefixime (Suprax), IV Ceftriaxone (Rocephin), IV Ceftazidime (Fortaz or Tazicef), IV Cefotaxime (Claforan or Cefotan)

Part of most protocols for CAP

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11
Q

Examples of Fourth Generation Cephalosporins & Common Uses

A

IV Cefepime

Clinical role similar to that of third generation cacapabilities

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12
Q

Vancomycin

A

bactericidal for susceptible gram positive bacteria by inhibiting bacterial cell wall synthesis

po form used to treat C Diff if metronidazole is ineffective

very poor oral absorption, results in no detectable serum level

IV dosing requires monitoring levels and adjustment for patient size and renal function

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13
Q

Examples of Tetracyclines

A

Vibramycin, Tetracycline, Doxycycline, Minocycline, Demeclocycline

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14
Q

Tetracyclines

A

four ring chemical structure

bacteriostatic by entering MO (in part by active transport and in part by passive diffusion) and binding to 30s subunit of bacterial ribosome, interfering with protein synthesis

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15
Q

Tetracyclines: ADME

A

A: divalent cations (calcium, magnesium, iron) bind to drug and inhibit absorption

D: highly protein bound; widely distributed, EXCEPT for CSF

M: concentrated by liver in bile and feces

E: all (except doxycycline) extensively renally excreted as unchanged drug

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16
Q

Tetracyclines: Patient Education

A

Potential for increased photosensitivity

GI side effects common- take with food

Should not be given to children 8yr or younger (binds to calcium deposits in bone/teeth, causing deformity of bone, tooth enamel dysplasia); avoid in pregnancy for same reason

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17
Q

Examples of Macrolides and Common Uses

A

Erythromycin, Clarithromycin (Biaxin), Azithromycin (Zithromax)

Firstline in many CAP protocols (generally have good coverage versus atypical bacteria; staph/strep coverage based on local susceptibility patterns)

Treatment of STIs (chlamydia)

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18
Q

Macrolides

A

macrocyclic lactone ring

bacteriostatic at low concentrations, but bactericidal at higher concentrations

inhibit protein synthesis via binding to 50s ribosomal subunit

*caution in patients with baseline prolonged QT or on other meds that prolong QT (erythromycin and clarithromycin worse than azithromycin)

azithromycin has long half-life (48-96hrs) allowing for shorter abx course (stays in system) due to extensive tissue penetration (exceeds serum concentration; slowly releases from tissues)

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19
Q

Macrolides: ADME

A

A: clarithromycin and azithromycin more readily absorbed than erythromycin

D: wide, EXCEPT for CSF

M: CYP450 inhibitors; extensive hepatic metabolism

E: < 10% excreted unchanged

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20
Q

Telithromycin (Ketolide class)

A

structurally related to macrolides

binds to ribosomal subunit 50s to inhibit protein synthesis

second or third line against CAP

hepatoxicity, loss of consciousness, and visual disturbances are serious side effects

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21
Q

Examples of Fluoroquinolones and Common Uses

A

ciprofloxacin (Cipro), moxifloxacin (Avelox), levofloxacin (Levaquin)

CAP (levofloxacin & moxifloxacin)
UTIs (NOT moxifloxacin; use cipro or leva)
Skin/soft tissue infections
Osteomyelitis (cipro- better bone penetration)

22
Q

Fluoroquinolones

A

bactericidal by blocking bacterial topoisomerases which prevents relaxation of coiled DNA that is required for normal bacterial transcription

newer quinolones have better gram positive coverage=respiratory FQs (levaquin, avelox)

older quinolones were developed for gram negative activity (cipro)

mechanism of quinolone resistance developed- point mutations in quinolone binding region, also change in permeability of organism

  • may cause significant QT prolongation (avelox more than levaquin)
  • may cause altered glycemic control
23
Q

Fluoroquinolones: ADME

A

A: excellent po absorption (80-95%); divalent cations (Mag, Ca+, iron) inhibit absorption

D: wide

M: minimal hepatic metabolism except moxifloxacin, which has extensive hepatic metabolism

E: other than moxifloxacin, extensive renal excretion (must dose adjust for CrCl <50)

24
Q

Fluoroquinolones: Patient Education

A

Caution for CNS ADRs such as dizziness, confusion, somnolence

Potential for phototoxicity

Not used in pediatric patients, other than in those with cystic fibrosis (due to arthralgias/joint swelling risk)

25
Examples of Aminoglycosides and Common Uses
Garamycin, Gentamicin, Neomycin, Tobramycin mostly used in acute care setting
26
Aminoglycosides
dosing and therapeutic drug monitoring necessary; adjust for patient size/renal function nephrotoxicity- highest risk with prolonged use/concomitant nephrotoxin administration ototoxicity (8th cranial nerve)
27
Types of Sulfonamides and Common Uses
Zonisamide (Zonegran), Sulfamethoxazole/Trimethoprim (Bactrim or Septra or TMP) UTI, otitis media, traveler's diarrhea, sinusitis
28
Sulfonamides
bacteriostatic mimics PABA which is required in order to form dihydrofolic acid; prevents nucleic acid formation
29
Sulfonamides: ADME
A: agent specific D: wide, inc. CSF M: all have some element of hepatic metabolism E: parent drug and inactive metabolites excreted (reduce dose in renal dysfunction or *choose a different agent*)
30
Sulfonamides: Patient Education
photosensitivity GI side effects; ideally taken on an empty stomach, but okay to take with food for GI upset adquate hydration to prevent crystaluria severe but rare: blood dyscrasias (contraindicated in patients with G6PD deficiency- may present with jaundice, purpura, or sore throat)
31
Linezolid (Oxalodinone class)
treatment of MRSA/VRE binds to 23s ribosomal RNA of the 50s subunit and interferes with protein synthesis
32
Linezolid: ADME
A: complete po absorption D: approx 30% protein bound, distributes into well-perfused tissues M: liver oxidation E: 30% unchanged in urine
33
Linezolid: Patient Education
ADRs include: GI side effects, headache Serious ADRs include: myelosuppression, neuropathy (with long courses may give vitamin B6/pyridoxine supplement to help prevent) this drug is an MAO inhibitor, and may react with SSRIs and other agents that depend on MAO for metabolism (consider DC other MAOIs or SSRIs during treatment) avoid foods high in tyramine (cheese, wine, beer)
34
Clindamycin
binds to 50s ribosomal subunit of susceptible organisms inhibiting protein synthesis (similar to macrolides) highly protein bound with wide Vd, but does not penetrate CSF well enough to use to treat CNS infections
35
Clindamycin: Common Uses
used for strong anaerobic coverage, but covers mixed infections as well used in aspiration PNA protocols penetrates well into abcesses (staph)
36
Clindamycin: Patient Education
common GI side effects may cause antibiotic-associated colitis
37
Metronidazole
mechanism of action not well understood, but interferes with bacterial DNA synthesis adjust in severe hepatic disease good tissue penetration
38
Metronidazole: Patient Education
Disulfuram reaction (vs ETOH)- avoid all alcohol, even from cold medications may cause darkening of urine (no concern unless volume of urine decreases)
39
Metronidazole: Common Uses
used for anaerobic coverage covers certain gram negative and gram positive organisms used for bacterial vaginosis, trichomonal vaginitis (treat both partners), C Diff infecctions, and other GI infections
40
Nitrofurantoin
used exclusively for UTIs, as therapeutic concentrations achieved ONLY in urine inactivates bacterial ribosomal proteins excreted through kidneys and not recommended for CrCl < 50-60 (drug loses effectiveness- less gets to site- and toxic effects are increased- lower excretion rate)
41
Examples of Azole Antifungals and Common Uses
ketoconazole, itraconazole, fluconazole, voriconazole, posaconazole vaginal or cutaneous candidiasis, tinea infections, onychomycosis, systemic fungal infections (step-down from heavy IV antifungal therapy- use ID specialist)
42
Azole Antifungals
increased use has led to more resistant strains, esp in people with heavy usage of azole antifungals work by reducing ergosterol synthesis by inhibiting fungal CYP450 enzymes (also cause human CYP450 interactions)
43
Azole Antifungals: Patient Education
look up drug interactions! LFTs must be assessed prior to, starting, and throughout course (unless short course in otherwise healthy person) avoid in pregnant women and nursing mothers elderly patients more susceptible to hepatic effects, and may require lower doses for renal function as well
44
Examples of Adamantanes and Common Uses
Amantadine & Rimantidine specifically inhibit replication of influenza A viruses, but not B; currently not being used for flu treatment due to recent CDC recommendation on resistant virus strains now used for Parkinsons/movement disorders
45
Antivirals: Adamantanes
interfere with influenza A virus M2 protein, leading to virus uncoating and therefore inhibition of viral replication and decreased viral shedding work for movement disorders due to CNS effects
46
Adamantanes: Patient Education
GI and CNS (anticholinergic) effects caution in elderly, consider dose adjusting teratogenic psychological- can cause worsening of mental illness
47
Antivirals: Neuraminidase Inhibitors
block the active site of influenza viral enzyme neuraminidase, which reduces number of viruses released from infected cell works on influenza types A and B
48
Examples of Neuraminidase Inhibitors & Common Uses
Zanamivir (Relenza)- inhaled powdered drug approved for age 7 and older for flu treatment and age 5 and older for flu prophylaxis Oseltamivir (Tamiflu)- capsule or oral suspension for treatment or prophylaxis of flu in ages one and up
49
Neuraminidase Inhibitors: Patient Education
Be careful with Tamiflu in children- post marketing research shows increased incidence of self-injury and delirium in children; teach parents to watch for unusual behavior must use within 48 hours of symptom onset decreases s/sx by one day, but more importantly decreases viral shedding, so less risk of spreading ADRs include GI effects, and in zanamivir, bronchospasm precipitation NOT a substitute for vaccination
50
Herpes Antivirals
Acyclovir, Valacyclovir (prodrug of acyclovir), famciclovir (prodrug of penciclovir) suppressive, not curative phosphorylated by viral thymidine kinase (resistant strains often lack) and inhibit DNA polymerase and thus formation of viral DNA

Pharmacology (11 decks)

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