ID: Quinolones, Urinary Antiseptics, and Anti-mycobacterial agents Flashcards
1
Q
*Ending for fluoroquinolines
A
-floxacin or -oxacin
2
Q
*first gen quinolone? And its spectrum
A
- nalidixic acid
- narrow spectrum for gram-
3
Q
*what was the quinolone class modified to? Spectrum? Resistance? Kinetics?
A
- fluoroquinolones
- larger spectrum vs quinolones
- more effective against resistance vs quinolones
- improved kinetics vs quinolones
4
Q
*Pros to Floroquinolones (4)
A
- highly effective
- broad spectrum
- high PO bioavailability
- large volume of distribution
5
Q
*cons to floroquinolones (3)
A
- widespread use had lead to resistance
- serious adv eff can occu
- multiple drug-drug interactions
6
Q
*generally when do we use fluoroquinolones?
A
-when benefits outweight the risk
7
Q
- list the second gen Fluoros + routes
* spectrum
A
- Ciprofloxacin—PO, IV, ophthalmic, otic
- Ofloxacin—PO, ophthalmic, otic
Spectrum:
- increased acitivty
- aerobic gram- bacteria **
- *cipro has weak coverage aganst strep pneumoniae
Ofloxacin: enhanced coverage of staph and strep
8
Q
- List the third gen fluoros + routes
- spectrums
A
-levofloxacin—PO, IV
Spectrum:
-same as second gen
+
better gram+ coverage and atypical organisms
9
Q
*list the fourth gen Fluoros + routes
A
- Gatifloxacin—ophthalmic
- Delafloxacin—PO, IV
- Moxifloxacin—PO, IV, ophthalmic
10
Q
*two enzymes that fluoros target?
A
- DNA gyrase: found in gram-
- Topoisomerase IV inhibition: in gram+
11
Q
*action of fluoros on bacteria— bacteriostatic or cidal
A
-cidal bcause it causes cell death
12
Q
*MOA fluoros
A
-targets two enzymes: DNA Gyrase and Topoisomerase IV inhibition
DNA gyrase—removes excess positive supercoiling in the DNA helix (gram-)
T. IV Inhib—affects separation of interlinked daughter DNA molecules (gram+)
13
Q
*Spectrum for fluoros:
A
- aeriobic gram +
- aerobic gram-
- atypical: chlamydia, Legionelle, Mycoplasma
- anaerobes
14
Q
*should fluoros be used for tx of uncomplicated infecetions? Why?
A
- NO
- due to adverse effects—also when alternative agents with lower toxicity profiles are available
- in 2016 FDA recommended this
15
Q
*ex of uncomplicated infections that should not be tx with fluoros
A
- acute rhinositis
- uncomplicated cystitis
- acute bronchitis
16
Q
which is the best fluoro for aerobic, gram-, pseudomonas
- UTI
- Pyelonephritis
- gastroenteritis
- otitis
- eye infections
A
Ciprofloxacin
17
Q
Spectrum for Ciprofloxacin
A
aerobic gram-
Pseudomonas
*not much gram+ coverage
18
Q
indications for Cirpofloxacin
A
UTI Pyelonephritis gastroenteritis Otitis--drops eye infections
***much better for gram- vs gram+
19
Q
which has better gram + coverage:
-Ciprofloxacin or Levo/Moxifloxacin
A
Levo and moxi
20
Q
spectrum and indications for Levofloxacin
A
spectrum:
* *more gram + coverage vs cipro
* gram-
* gram+
* anaerobes
* mycobacterium
* respiratory infections: strep, hamepholius, and moraxella
- 2nd DOC for mycobacterium TB
- UTI
- Pyelonephritis
- pneumoina
21
Q
which fluroquinoloine is best for anaerobes, esp gram+
A
Moxifloxacin
22
Q
Kinetics for Fluoros
- abs?
- wht reduces absoprtion
- where are [ ] high
- dose adjustments?
- drug-drug interactions
A
Absorption: good after PO— bioavail of <90%
- zinc *iron *sucralfate *Ca can reduce absoprtion
- [ ] are high in bone, CNS, urine, prostate tissue, lungs, kidney
- most excreted renally–needs dose adjustment EXCEPT FOR MOXIFLOXACIN
Ciprofloxacin is a CYP450 INHIBITOR
23
Q
SE fluoros (8)
A
- generally well tolerated*
but. .. when cmpared to other ABX: - GI upset more common
- CNS: HA, dizziness, sleep issues are more common
- Incidence of C. Diff is more common
- small risk of photoxicity
- hypersensitivity
- dysglycemia: hyper or hypo
- periph neuropathy
BBW: Tendinopathy*****
24
Q
Contra for fluoros (4)
A
hx of Aortic aneurysm
pregnancy/BF
<18
avoid in Myasthenia gravis
25
which fluoroquinolone is CYP450 inhibitor
Ciprofloxacin
*if given with those other drugs, will increase their serium [ ]
EX: warfarin, theophylline, caffiene,
26
Sulfonamines
- new/old drug?
- moa
- spectrum
- how does resistance occur
- contras (3)
old drug
MOA: folate antagonists
- compete with PABA to prevent production of dihydrofolic acid
* *bacteriostatic
spectrum:
+ and -
resistance:
- when bacteria are able to obtain folate from the environment, plasmid transfer or random mutations
contra:
* pregnant PT bc of kernicterus
* newborns <2 MO
* pt on methenamine
27
Kinetics for Sulfas
- abs
- penetrates?
- excretion
*well absopred EXCEPT FOR SULFASALAZINE
* penetrates CNS, and placenta
* excretion: urine, breastmilk, have to renally dose
28
ADV rxn to sulfas (5)
1. hypersensitivity
2. Crystalluria
3. Hemolytic anemia
4. Kernicterus
5. Inhibition of CYP P2C9
29
Trimethoprim
- MOA
- spectrum
- potency
- indications
- se (2)
MOA:
* alone or combo with Sulfamethoxazole (MC used in combo)
* potent inhibitor of dihydrofolate reductase--blocks folic acid production--abnoral cell function in bacteria
Spectrum:
*same as sulfonamide BUT 20-50X more potent
INd:
- UTI
- prostatitis
SE:
- hyperK
- FOlic acid deficiency
30
pharmkinetics of Trimethoprim
-rapidly absorbed after oral admin
- good penetration in acidic fluids-- like vagina and prostate
- good CNS penetration
31
Cotrimoxazole
- route
- dosing
- adv rxn
IV, PO
spectrum: better antimicrobial activity together versus alonE AKA synergistic******
* renal dosing needed
Adv Rxn:
- n/v
- skin rash
- hematologic toxicity
- hyperK
32
Silver Sulfadiazine (Silvadene)
- spectrum
- indications
INDS: **topical**
* superficial skin infections
* burns
***silver natural superficial abx
Gram +/- bacteria
33
Sulfacetamide
| -indications (2)
```
topical
-bactericidal
-gram+/-
Indications:
-blepharitis
-ocular infections
```
34
Methenamine
- MOA
- only effective when?
- indications
- contra 2
- adv rxn
MOA
* hydrolyzed to ammonia + formaldehyde-->denatures protein and nucleic acid-->cell death
* **bacteriocidal
* *only effective if urinary ph is acidic
INDS:
*chronic suppression of frequent UTIs
adv rxn: gi upset
contra
* sulfonamide tx
* hepatic dysfunction
35
Nitrofurantoin
- moa
- indications
- adv rxn (3)
- contras (3)
MOA: inhibits DNA and RNA synthesis
*bactericidal
Indications: UTI caused by:
- e. coli
- enterococcus
- Klebsseila
- staph
adv rxn:
- N/v/d
- rare: drug induced liver injury, periph. neuropathy
contra:
- renal dz
- last 30 days of pregnancy
- elderly
36
Mycobacteria
- explain cell wall
- creates?
highly lipid cell wall---- so does not retain the normal gram stain...
**acid fast staining necessary
Acid-fast bacilli
creates granulomatous dz and serious infections (TB)
37
Mycobacterium avium and intracellulare
- cause?
- which population
mainly affects the immunocomp--HIV
Pulmonary dzs
38
Mycobacterium Tuberculosis
- growth rate
- treatment length?
- tx? Acute
slow growing... so long duration of treatment
RIPE or RIPS
x2MO: all four drugs
x4 more MO: rifampin and Isoniazid
x6MO total drug tx
Rifampin
Isoniazid
Pyrazinamide
Ethambutol (or streptomycin)
39
Rifamycins
- list the drugs
- MOA
- why is it not given alone?
Rifampin
Rifabutin
Rifapentine
MOA:
*blocks RNA transcription--bacteriCIDAL
*not given alone bc of resistance
Indications:
- TB
- mycobacterium avian complex
- Mycobacterium Leprae (leprosy)
40
Pharmkinetics of Rifampin
- abs
- distribution
- metabolism
- interactions
- adv rxn
* adequately absorbed
* well distributed in all body fluids and organs--poorly in CNS
* enterophepatic recycling
* CYP 450 Inducer--decreases [ ] of other drugs
Adv Rxn:
- metabolites can turn urine, tears, sweat organge/red
- flu like s/s
contra:
- caution with heptatic dz PT
- concomitant hepatotoxins
41
Rifabutin
| -indications
better to give to PT's for tx of TB who are also undergoing HIV treatment
**because it is a less potent inducer of CYP 450
42
Rifapentine
- indications
- T 1/2?
Latent TB
| VERY long half life
43
Isoniazid
- MOA
- abs
- penetrates?
- indication
- SE
* prodrug
* when activated MOA: inhibs mycolic acid-->disrupts cell wall
* ****only works specifically for M. tuberculosis
IND:
*TB only
abs: readily via PO on empty stomach
penetration:
* good tissue pen
* good CNS
SE:
* potentially fatal hepatitis
* periphereal neuropathy/parethesia caused by peroxidase deficiency------ to prevent this give B6********
* Seizures=common
44
cannot have fattys meals when administering wht medication?
Isoniazid
45
Pyrazinamide
- MOA
- inds
- SE 3
MOA: unclear
Distribution:
- CNS
- tissues
INDS:
-acute TB... only for the first two MO.. then discontinued
SE:
- hepatitis and Hyperuricemia (avoid in PT with gout)
- photosensitive dermatologic rash
- arthralgias
46
Ethambutol
- MOA
- spectrum
- distribution
Cell wall inhibitor of Mycobacteria
**bacteriostatic
Narrow spectrum
CNS penetration is variable
but generally good distribution
SE:
-optic neuritis--esp in PT with renal dz
-caution in gout bc it can elevate uric acid
47
what to do before putting patient on ethambutol tx?
test visual acuity and color
48
Dapsone
- structure
- uses
- SE
- abs
structurally sim to sulfonamides
-MOA inhibits folate synthesis, has anti-inflamm., anti-protozoal, antimicrboial effects
*bacteriostatic
abs:
* good levels in skin
* well abs
INDS:
* mycobacterium leprae
* Pneumocyctis Jirovecci Pneumonia (PCP)
* dermatitis herpetiformis
* malaria
SE:
* severe hemolytic anemia *esp in pt with G6PD
* peripheral neuropathy
49
Clofazimine
- moa
- penetration
MOA:
- binds to DNA
- Bactericidal against: M. leprae, Mycobacterium TB, and non TB mycobacterium
penetrates tissues but NOT CNS
SE:
* photoxicity
* brownish/black skin discoloration during tx
* QT>>>>
* GI upset
50
what is the triple tx for leprosy and how long
Dapsone
Clofazimine
Rifampine
for 12 MOnths
