Id Therapeutics Exam 2 Set 1

Front 1

1. 0.25 - 1 mg/kg IV (0.7 mg/kg)

2. Side Effects (Infusion related): Phlebitis
Chills, rigors, anaphylaxis; Long term side effects--Electrolyte abnormalities
(K+, Mg++, BUN, Scr, LFT’s)

3. Prehydration to decrease nephrotoxicity (Normal saline 500 ml)

4. Premedication to lessen infusion reactions
Tylenol, Ibuprofen, Hydrocortisone, Meperidine, Benadryl
5. Test dose not necessary
6. Infuse over 4-6 hours
7. Protect from light?

Back 1

Amphoteracin B Deoxycholate

Front 2

amphoteracin B lipid based products (4)

Back 2

1. Abelcet (Amphotericin B Lipid Complex, ABLC)
2. AmBisome (liposomal, unilamellar lipid vesicles)
3. Amphocil (Amphotericn B Colloidal Dispersion, ABCD)
4. Amphotec (Amphotericn B cholesteryl sulfate complex

Front 3

1. 5 mg/kg IV daily
2. 2.5 mg/kg/hr
3. Infusion time > 2 hours mix contents of bag by shaking
4. Admixture: use 5 micron filter for each vial
5. Dilute with D5W
6. Final concentration 1-2 mg/ml

Back 3

abelcet

Front 4

1. Liposomal Amphotericin B
2. 3-5 mg/kg/d
3. given over 1-2 hours

Back 4

ambisome

Front 5

1. Ampho B cholesteryl sulfate complex
2. 3-4 mg/kg/d IV
3. given as 1 mg/kg/hr
4. Admixture: reconstitute powder with sterile water then dilute with D5.
5. Do not use filter for preparation or administration.

Back 5

amphotec

Front 6

PO and IV good bioavailability most renally cleared, least drug interactions. Covers most Candida Spp but not C.krusei. Does cover Coccioides and Cryptococcus

200-400 mg BID (400-800 mg/day) IV/PO

nearly 100% bioavailable

Back 6

fluconazole

Front 7

covers Histoplasmosis, and Coccioides. Poorly bioavailable (soln. highest F). Drug interactions. No longer available IV.

Dosage forms
1. Capsules – take with food, avoid grapefruit juice
2. Solution – take on an empty stomach
3. Intravenous injection – removed from market

Back 7

itraconazole

Front 8

covers Aspergillosis, Candida, some variability in bioavailability, available IV/PO IV vehicle accum. in RF

1. Available IV/PO
2. 6 mg/kg x2 doses then 4 mg/kg or 400 mg BID x2 then 200 mg BID
3. IV not recommended in pts with Clcr < 50 (accumulation of vehicle).
4. Visual disturbances (most resolve after D/C), do not drive at night.
5. Administer at least 1 hr before or after a meal.
6. Drug interactions.

Back 8

voriconazole (Vfend)

Front 9

covers Aspergillosis, zygomycosis, poorly bioavailable. Available PO only but IV in development

1. Available PO only
2. Approved for prophylaxis of disseminated candidiasis and aspergillosis, clinical studies indicate it has activity against zygomycosis.
3. Prophylaxis 200 mg PO TID
4. Treatment 800 mg/day in 2 or 4 divided doses
5. Refrigerate suspension (do not freeze), take with a full meal or nutritional supplement, shake well, use supplied dosing spoon (rinse after each use)

Back 9

posaconazole

Front 10

St John’s Wort. H2 blockers, antacids, sucralfate, proton pump inhibitors, didanosine, carbamazepine, rifampin, isoniazid

what doe these do to levels for antifungals?

Back 10

decrease level of antifungal (inducer)

Front 11

Amitriptyline, calcium channel blocker, cyclosporine, phenytoin, statins, methadone, warfarin, hypoglycemics, pimozide, protease inhibitors, sirolimus, tacrolimus, theophylline, trazodone, zidovudine

what do these do to antifungal levels?

Back 11

increase antifungal levels (inhibitors)

Front 12

what is the interaction between capsofungin and tacrolimus?

Back 12

capso decrease tac concentration by 20%

Front 13

what is the interaction between cyclosporine and capsofungin?

Back 13

cyclosporine increases capso by 30%

Front 14

1. interferes with ergosterol biosynthesis by inhibiting squalene epoxidase in the fungal cell membrane.
2. 250 mg PO QD ($4)
3. Generally well tolerated, but liver toxicity can occur.
4. Not recommended for pts with chronic or active liver disease, baseline LFTs recomm.
5. Used for nail infections
6. Also available as a cream for tinea

Back 14

allylamine--terbinafine

Front 15

1. absorption enhanced with fatty meal
2. Ultramicronize = best absorption
3. Avoid sunlight
4. SE: Headache - may go away with continued treatment
5. Not used much anymore, more effective therapies (nail infections)

Back 15

griseofulvin (fulvicin)

Front 16

1. yeasts
2. produce by budding

(2)

Back 16

1. candida
2. cryptococcus

Front 17

1. moulds
2. produce by branching

(1)

Back 17

hyphae

Front 18

1. Active in vitro against Candida spp. and Aspergillus spp. (Not active against Cryptococcus spp.)
2. Available for intravenous administration only (oral formulations in dev’t)
3. Act by inhibiting 1,3 b-D- glucan synthase complex. This enzyme is responsible for incorporation of glucose into glucan fibrils that compose the cell walls of most fungi. Depletion of glucan in the fungal cell wall leads to osmotic instability and cell death.

Back 18

echinocandin (capsofungin, micafungin, andiulafungin)

Front 19

what is used to identify candida? (2)

Back 19

1. KOH
2. gram stain positive

Front 20

where is candida normally found? (4)

Back 20

1. GI tract including oropharynx
2. Female genital tract
5. Skin
4. May be colonizer or contaminant – if in blood it should be treated.

Front 21

Risk Factors for candida Infection (5)

Back 21

1. Broad spectrum antibiotics
2. Indwelling intravenous catheters
3. Immunosuppression (chemo, transplant, HIV, etc)
4. Parenteral nutrition (high glucose?)
5. Colonization

Front 22

How would you treat thrush/oral candidiasis

(white plaques on tongue and buccal surfaces)

(4)

Back 22

Topical
1. Nystatin Susp.
2. Clotrimazole troches
3. Amphotericin B oral suspension 100 mg QID

Systemic
4. Fluconazole 100 mg QD

Front 23

How would you treat esophagitis resulting fungal infection

(pain and difficulty swallowing; dx via scope)

(2)

Back 23

systemic treatment necessary

1. fluconazole PO/IV 200 mg QD
2. chinocandin (capsofungin, micafungin, anidulafungin)

Front 24

Predisposing factors for vaginitis (5)

Back 24

1. oral contraceptives
2. obesity
3. diabetes
4. steroids
5. hot/humid conditions

Front 25

how would you treat vaginitis resulting from a fungal infection?

(thick, curd-like vaginal discharge, pruritis)

(7)

Back 25

TOPICAL
1. Miconazole (Monistat)--1 applicator of 2% cream (100 mg) or 100 mg vag. supp. for 7 days
200 mg vag. supp. for 3 days
2. Clotrimazole (Gyne-lotirmin, Mycelex)--1% vag. cream 1 applicator for 7 days; 100 mg vag. tablets 1 nightly for 7 days; 500 mg vag. tablets one time
3. Butoconazole nitrate (Femstat-1)--2% vag. cream 1 applicatorful QHS single dosen
Do not use during 1st trimester of pregnancy
4. Tioconazole (Vagistat -1) --6.5% ointment 1 applicatorful single dose; Petroleum base - latex condoms, diaphragms (3 days following tx)
5. Terconazole (Terazol) --0.4, 0.8% cream; 80 mg vag. supp. for 7 days
6. Nystatin (Mycostatin, Nilstat)--100,000 units/vag. tab Qhs for 2 weeks

SYSTEMIC
7. Fluconazole 150 mg po single dose ($4)

Front 26

risk factors for candida urinary tract infection (2)

Back 26

1. foley catheter
2. diabetes mellitus

Front 27

How would you treat candida urinary tract infection?

(2)

Back 27

1. catheter removal
2. bladder irrigation (NS vs. Ampho B 50 mg/500ml; Fluconazole 200 mg PO/IV; Amphotericin B single IV dose; Amphotericin B 0.3-1mg/kg/day IV)

Front 28

_______does not reach the urine at active drug and does not reach effective levels in the urine and should not be used for C. glabrata urine infections.

Back 28

voriconazole

Front 29

How would you treat disseminated candidiasis

(4)

Back 29

1. Amphotericin B 0.7 mg/kg IV
2. Fluconazole 400 - 800 mg/d (12mg/kg load, followed by 6 mg/kg)
3. Lipid based Amphotericin B product
4. Echinocandin (Caspofungin 70 mg X1, 50 mg/d; Anidulafungin 200 x 1, 100 mg/d; Micafungin 100 mg/d)

Front 30

Clinical manifestations of what?

Ear and Sinus
Allergic bronchopulmonary
-Severe asthma
-Fever
-Malaise
-Chest pain
-Sputum: blood streaked
Pulmonary
-Fungus balls in pre-existing cavities
-Chest pain
-Dyspena
-Sputum production
-Hemoptysis

Back 30

aspergillosis

Front 31

how would you treat aspergillosis

(5)

Back 31

1. Voriconazole 400 mg Q12 x2 doses, 200 mg Q12 or 6 mg/kg Q12 x2 then 4 mg/kg Q12 for IV.
2. Amphotericin B 1-1.5 mg/kg/d;
3. Liposomal Amphotericin B
4. Echinocandin (capsofungin, micafungin, anidulafungin)
5. Surgery (contraindicated in capillary lesion)
Duration may be prolonged, guided by clinical response

Front 32

For aspergillosis what do you want your trough/peak to be for:

1. voriconazole
2. posaconazole

Back 32

1. voriconazole: Trough concentrations should be at least 0.5 micrograms/ml and a peak should be at least 2 micrograms/ml

2. posaconazole: Long half life so random level is okay; Random concentrations of at least 0.5 micrograms/ml may be adequate.

Front 33

1. Dimorphic fungi--grows as mould in soil, spores released in alveoli spores germinate releasing yeast which multiplies by binary fision
2. Similar to tuberculosis
3. Granulomatous inflammatory response
4. Viable organisms may remain latent in healed granuloma
5. Recrudescent disease may occur if host’s cell mediated immunity is imparied

Back 33

histoplasmosis

Front 34

How would you treat acute pulmonary histoplasmosis

1. mild- moderate
2. moderate severe-severe

Back 34

1. mild- moderate: Itraconazole 200 mg TID x 3 d then 200mg BID or QD x 3 months

2. moderate severe-severe: Lipid Amphotericin B 3-5 mg/kg x 1-2 wks followed by Itraconazole 200 mg TID x 3 days then 200 mg daily for a total of 12 weeks

Front 35

How would you treat chronic cavitary pulmonary histoplasmosis

Back 35

Itraconazole 200 mg TID x 3 days then BID or QD for at least a year (some recommend 18-24 months)

Monitor blood levels after 2 weeks to ensure absorption.
A level of at least 1 microgram/ml is recommended, concentrations of >10 are probably unnecessary.
If both itra and the active hydroxy metabolite are reported then the sum is considered

Front 36

How would you treat progressive disseminated histoplasmosis

Back 36

Liposomal Amphotericin B 3-5 mg/kg daily x 1-2 weeks followed by Intraconazole 200 mg TID x 3 days followed by 200 mg BID for a total of 12 months.

Especially in immune compromised patients
Wt. loss, chills, night sweats, splenomegaly, hepatomegaly, lymphadenopathy, anemia
Pulmonary symptoms in 30% of cases

Front 37

How would you treat coccidioidomycosis

(3)

Back 37

1. fluconazole 200-400 mg/day
2. amphoteracin B for pregnant patients
3. surgery (if necessary)

Front 38

diagnosis of what?

KOH: large multinucleated yeast with single broad based buds.

Back 38

blastomycosis

Front 39

How would you treat blastomycosis

(1)

Back 39

Amphotericin B 1 mg/kg/day or lipid formulation of 3-5 mg/kg/day for 1-2 weeks followed by
Itraconazole 200 mg TID x 3 days followed by 200 mg BID for a total of 6-12 months.

Front 40

Pathogenic dermatophytes (3)

Back 40

1. Trichophyton
2. Microsporum
3. Epidermophyton

Front 41

What dermatophytes cause athletes foot (tinea pedis)

(2)

Back 41

1. Trichophyton rubrum (Sole of foot; erythematous; Dry scales)
2. T. mentgrophytes (interdigitale)--Itching, Bullae


Treated topically

Front 42

What dermatophytes cause jock itch (tinea cruris)

(2)

Back 42

1. T. rubrum
2. E. foccsum


Scaling/irritation
Follicular papules or pustules
Treated topically

Front 43

What dermatophyte cause ring worm (tinea corporis)

(1)

Back 43

T. rubrum


Prominant edge with pustules or papules
Center scaly and inflamed
Generally treated topically

Front 44

How long is tinea capitis treated for?

Back 44

requires systemic therapy for 6-12 weeks

Front 45

How long is onychomycosis (fungal nail infection) treated for?

Back 45

requires systemic therapy for prolonged time (6 months)