First Aid Micro -- Antimicrobials

Front 1

M. tuberculosis prophylaxis?

Back 1

Isoniazid

Front 2

M. avium-intracellulare prophylaxis?

Back 2

Azithromycin

Front 3

M. leprae prophylaxis?

Back 3

N/A

Front 4

M. tuberculosis treatment?

Back 4

"RIPE for treatment"

R - Rifampin
I - Isoniazid
P - Pyrazinamide
E - Ethambutol

Front 5

M. avium-intracellulare treatment?

Back 5

- rifampin
- ethambutol
- azithromycin
- streptomycin

Front 6

M. leprae treatment?

Back 6

- rifampin
- dapsone
- clofazimine

Front 7

Anti-TB drugs?

Back 7

"INH-SPIRE (inspire)"

INH - Isonizid (prophylaxis)

S - Streptomycin
P - Pyrazinamide
I - Isoniazid
R - Rifampin
E - Ethambutol

Front 8

Anti-TB drugs 2nd line of therapy?

Back 8

Cycloserine

Front 9

Important ethambutol side effect?

Back 9

- optic neuropathy (red-green colorblindness)

Front 10

Important side effect of other anti-TB drugs?

Back 10

Hepatotoxicity

Front 11

Isoniazid (INH) mechanism?

Back 11

- decreases synthesis of mycolic acids

- different INH half-lives in fast vs. slow acetylators

Front 12

Clinical uses of isoniazid (INH)?

Back 12

- Mycobacterium tuberculosis

- the only agent used as solo prophylaxis against TB

Front 13

Isoniazid (INH) toxicity?

Back 13

"INH = Injures Neurons and Hepatocytes"

- neurotoxicity
- hepatotoxicity

- Pyridoxine (vitamin B6) can prevent neurotoxicity

Front 14

What can prevent neurotoxicity in Isoniazid (INH)?

Back 14

- pyridoxine (vitamin B6)

Front 15

Rifampin mechanism?

Back 15

- inhibits DNA-dependent RNA polymerase

Front 16

Clinical uses of rifampin?

Back 16

- Mycobacterium tuverculosis
- delays resistance to dapsone when usedused for leprosy

- meningococcal prophylaxis

- chemoprophylaxis in contacs of kids with Haemophilus influenzae type B

Front 17

Rifampin toxicity?

Back 17

- minor hepatotoxicity
- minor drug interactions (increase P-450)

- orange body fluids (non-hazardous side effect)

Front 18

Which drug causes orange body fluids as a side effect?

Back 18

- Rifampin

- nonhazardous side effect

Front 19

Rifampin's 4 R's?

Back 19

- RNA pol inhibitos
- Revs up microsomal P-450
- Red/orange body fluids
- Rapid resistance if used alone

Front 20

Resistance mechanism for penicillins/cephalosporins?

Back 20

- beta-lactamase cleavage of beta-lactam ring

or

- altered PBP in cases or MRSA penicillin-resistant S pneumoniae

Front 21

Resistance mechanism for aminoglycosides?

Back 21

- modification of drug via acetylation, adenylation, or phosphorylation

Front 22

Resistance mechanism for vancomycin?

Back 22

- terminal D-ala of cell wall component is replaced with D-lac causing decreased affinity

Front 23

Resistance mechanism for chloramphenicol?

Back 23

- modification of drug via acetylation

Front 24

Resistance mechanism for macrolides?

Back 24

- methylation of rRNA near erythromycin's ribosome-binding site

Front 25

Resistance mechanism for tetracycline?

Back 25

- decreased uptake

or

- increased transport out of cell

Front 26

Resistance mechanism for sulfonamides?

Back 26

- altered enzyme (bacterial dihydropteroate synthetase)
- decreased uptake
- increased PABA synthesis

Front 27

Resistance mechanism for quinolones?

Back 27

- altered gyrase

or

- reduced uptake

Front 28

Nonsurgical antimicrobial prophylaxis:

Meningococcal infection

Back 28

- rifampin (DOC)
- minocycline

Front 29

Nonsurgical antimicrobial prophylaxis:

Gonorrhea

Back 29

Ceftriaxone

Front 30

Nonsurgical antimicrobial prophylaxis:

Syphilis

Back 30

Benzathine penicillin G

Front 31

Nonsurgical antimicrobial prophylaxis:

history of recurrent UTIs

Back 31

TMP-SMX

Front 32

Nonsurgical antimicrobial prophylaxis:

Pneumocystis jiroveci pneumonia

Back 32

- TMP-SMX (DOC)
- aerosolized pentamidine

Front 33

Nonsurgical antimicrobial prophylaxis:

Endocarditis with surgical or dental procedures

Back 33

Penicillins

Front 34

Treatment of highly resistant bacteria:

MRSA

Back 34

Vancomycin

Front 35

Treatment of highly resistant bacteria:

VRE

Back 35

Vancomycin-Resistant Enterococci

- linezolid
- strptogramins (quinopristin/dalfopristin)

Front 36

Which anti-fungals form artificial pores, disrupting fungal membranes?
(2)

Back 36

- amphotericin
- nystatin

Front 37

Which anti-fungal disrupts microtubules?

Back 37

Griseofulvin

Front 38

Which anti-fungal blocks pyrimidine precursors?

Back 38

Flucytosine

Front 39

Which anti-fungal blocks squalene --> lanosterol in ergosterol synthesis?

Back 39

Terbinafine

Front 40

Which anti-fungal blocks lanosterol --> ergosterol in ergosterol synthesis?

Back 40

Azoles

Front 41

Amphotericin B mechanism?

Back 41

"amphoTERicin TEARS holes in the fungal membrane by forming pores"

- binds ergosterol (unique to fungi) and forms membrane pores that allow leakage of electrolytes

Front 42

Clinical uses of amphotericin B?

Back 42

- wide spectrum of systemic mycoses

- Cryptococcus
- Blastomyces
- Coccidioides
- Aspergillus
- Histoplasma
- Candida
- Mucor (systemic mycoses)

- intrathecally for fungal meningitis

- does not cross BBB

Front 43

Amphotericin B toxicity?

Back 43

"amphoterrible"

- fever/chills ("shake and bake")
- HYPOtension
- nephrotoxicity
- arrhythmias
- anemia
- IV phlebitis

Front 44

What reduces the nephrotoxicity of amphotericin B?

Back 44

Hydration

Front 45

Complexing amphotericin B to what reduces its toxicity?

Back 45

Lipids --> liposomal amphotericin

Front 46

Nystatin mechanism?

Back 46

- binds to ergosterol, disrupting fungal membranes

- too toxic for systemic use

Front 47

Clinical uses of nystatin?

Back 47

- "Swish and swallow" for oral candidiasis (thrush)
- topical for diaper rash or vaginal candidiasis

Front 48

Why isn't nystatin used systemically?

Back 48

- too toxic

Front 49

Azoles?
(6)

Back 49

- fluconazole
- ketoconazole
- clotrimazole
- miconazole
- itraconazole
- voriconazole

Front 50

Azole mechanism?

Back 50

- inhibit fungal sterol (ergosterol) synthesis

Front 51

Clinical uses of azoles?

Back 51

- systemic mycoses

Front 52

Clinical uses of fluconazole?

Back 52

- cryptococcal meningitis in AIDS pts (because it can cross BBB)
- candidal infections of all types (ie. yeast infections)

Front 53

Clinical uses of ketoconazole?

Back 53

- Blastomyces
- Coccidioides
- Histoplasma
- Candida albicans

- hypercortisolism

Front 54

Clinical uses of clotrimazole and miconazole?

Back 54

- topical fungal infections

Front 55

Azole toxicity?

Back 55

- hormone sunthesis inhibition (gynecomastia)
- liver dysfunction (inhibits cytochrome P-450)
- fever
- chills

Front 56

Flucytosine mechanism?

Back 56

- inhibits DNA synthesis by conversion to 5-FU

Front 57

Clinical uses of flucytosine?

Back 57

- systemic fungal infections (ie. Candida and Cryptococcus) in combo with amphotericin B

Front 58

Flucytosine toxicity?

Back 58

- nausea
- vomiting
- diarrhea
- bone marrow suppression

Front 59

Caspofungin mechanism?

Back 59

- inhibits cell wall synthesis by inhibiting synthesis of beta-glucan

Front 60

Clinical uses of caspofungin?

Back 60

Invasive aspergillosis

Front 61

Caspofungin toxicity?

Back 61

- GI upset
- flushing

Front 62

Terbinafine mechanism?

Back 62

- inhibits the fungal enzyme squalene epoxidase

Front 63

Clinical uses of terbinafine?

Back 63

- used to treat dermatophytoses (especially onychomycosis)

Front 64

Griseofulvin mechanism?

Back 64

- interferes with microtubule function --> disrupts mitosis

- deposits in keratin-containing tissues (ie. nails)

Front 65

Clinical uses of griseofulvin?

Back 65

- oral treatment of superficial infections
- inhibits growth of dermatophytes (tinea, ringworm)

Front 66

Griseofulvin toxicity?

Back 66

- teratogenic
- carcinogenic
- confusion
- headaches
- increased P-450 and warfarin metabolism

Front 67

Which anti-viral drugs block viral adsorption?

Back 67

- gamma-globulins (non-specific)

Front 68

Which anti-viral drugs block viral uncoating?

Back 68

- amantadine (influenza A only)

Front 69

Which anti-viral drugs block viral nucleic acid synthesis?

Back 69

- purine and pyrimidine analogs
- reverse transcriptase inhibitors

Front 70

Which anti-viral drugs block viral packaging and assembly?

Back 70

- Rifampin (vaccinia)

Front 71

Which anti-viral drugs block viral release?

Back 71

- neuraminidase inhibitors (influenza)

Front 72

Amantadine mechanism?

Back 72

"A man to dine" takes off his COAT

- blocks viral penetration/unCOATING (M2 protein)
- may buffer pH of endosome
- also causes the release of dopamine from intact nerve terminals

Front 73

Clinical uses of amantadine?

Back 73

"Amaintadines blocks influenza A and rubellA and causes problems with the cerebellA"

- prophylaxis and treatment for influenza A
- Parkinson's disease

Front 74

Amantadine toxicity?

Back 74

"Amaintadines blocks influenza A and rubellA and causes problems with the cerebellA"

- ataxia
- dizziness
- slurred speech

- Rimantidine is a derivative with fewer CNS side effects --> does not cross the BBB

Front 75

Amantadine resistance mechanism?

Back 75

- mutated M2 protein

- 90% of all influenza A strains are resistant to amantadine, so not used

Front 76

Zanamivir and Oseltamivir mechanism?

Back 76

- inhibit influenza neuraminidase --> decreasing the release of progeny virus

Front 77

Clinical uses of Zanamivir and Oseltamivir?

Back 77

- both influenza A and B

Front 78

Ribavirin mechanism?

Back 78

- inhibits synthesis of guanine nucleotides by competitively inhibiting IMP dehydrogenase

Front 79

Clinical uses of ribavirin?

Back 79

- RSV
- chronic hepatits C

Front 80

Ribavirin toxicity?

Back 80

- hemolytic anemia
- severe teratogen

Front 81

Acyclovir mechanism?

Back 81

- monophosphorylated by HSV/VZV thymidine kinase
- guanosine analog
- triphosphate formed by cellular enzymes
- preferentially inhibits viral DNA polymerase by chain termination

Front 82

Clinical uses of acyclovir?

Back 82

- HSV, VZV, EBV

- used for HSV-induced mucocutaneous and genital lesions as well as for encephalitis
- prophylaxis in immunocompromised patients
- for herpes, zoster, use a related agent, famciclovir
- no effect on latent forms of HSV and VZV

Front 83

What drug do you use for herpes zoster?

Back 83

- famciclovir --> related to acyclovir

Front 84

Acyclovir toxicity?

Back 84

generally well tolerated

Front 85

Acyclovir mechanism of resistance?

Back 85

- lack of thymidine kinase

Front 86

Ganciclovir mechanism?

Back 86

- 5'-monophosphate formed by a CMV viral kinase or HSV/VZV thymidine kinase
- guanosine analog
- triphosphate formed by cellular kinases
- preferentially inhibits viral DNA polymerase

Front 87

Clinical uses of ganciclovir?

Back 87

- CMV --> especially in immunocompromised patients

Front 88

Ganciclovir toxicity?

Back 88

- leukopenia
- neutropenia
- thrombocytopenia
- renal toxicity

- more toxic to host enzymes than acyclovir

Front 89

Ganciclovir mechanism of resistance?

Back 89

- mutated CMV DNA pol
- lack of viral kinase

Front 90

Foscarnet mechanism?

Back 90

"FOScarnet = pyroFOSphate analog"

- viral DNA pol inhibitor that binds to the pyrophosphate-binding site of the enzyme
- does NOT require activation by viral kinase

Front 91

Does foscarnet require activation by viral kinase?

Back 91

No

Front 92

Clinical uses of foscarnet?

Back 92

- CMV retinits in immunocompromised patients when ganciclovir fails
- acyclovir-resistant HSV

Front 93

Foscarnet toxicity?

Back 93

- nephrotoxicity

Front 94

Foscarnet mechanism of resistance?

Back 94

- mutated DNA pol

Front 95

HIV Therapy:

Protease Inhibitors
(5)

Back 95

"NAVIR (never) TEASE a proTEASE"

- all protease inhibitors end in -navir

- saquiNAVIR
- ritoNAVIR
- indiNAVIR
- nelfiNAVIR
- ampreNAVIR

Front 96

HIV Therapy:

Protease Inhibitors
Mechanism

Back 96

- inhibit maturation of new virus by blocking protease in progeny virus

Front 97

HIV Therapy:

Protease Inhibitors
Toxicity

Back 97

- GI intolerance (nausea, diarrhea)
- hyperglycemia
- lipodystrophy
- thrombocytopenia (indinavir)