Derm Pharm Flashcards
First and second line oral antifungals for scalp and nail disorders?
scalp:
1st line: griseofulvin
2nd: terbinafine (lamisil)
Nails:
1st line: terbinafine (lamisil)
2nd: itraconazole (sporanox)
Use of griseofulvin: MOA and administration?
- 8 wks for tinea capitis
- MOA: fungistatic, binds to human keratin making it resistant to fungal invasion
- admin:
taken with fatty meal helps to increase absorption, take with food in general to lessen GI upset
Griseofulvin:
Half life, absorption, distribution and metabolism?
- half life: 9-24 hrs (erratic)
- absorption: microsize is variable (25-70% of an oral dose) - enhanced by ingestion of a fatty meal.
GI absorption of ultramicrosize is 1.5x that of microsize - distribution: deposited in keratin layer of skin, hair and nails, concentrates in liver, fat, and skeletal muscles
- metabolism: extensive hepatic
What are the 2 formulations for griseofulvin?
- smaller the particle size the greater the bioavailability
- dosing:
microsize: suspension, grifulvin V tabs: 20-25 mg/kg/day
ultramicrosize: Gris-PEG tabs - 10-15 mg/kg/day
CIs and precautions with admin of griseofulvin?
- liver failure
- porphyria (defect in enzyme for heme synth)
- preg category x
- use with caution if hx of PCN allergy as potential for cross reactivity
- breast feeding not recommended (can use in kids though)
Adverse rxns of griseofulvin?
- skin: photosensitivity, SJS, toxic epidermal necrolysis, erythema multiforme
- liver: jaundice, elevated liver enzymes
- bone marrow: granulocytopenia
- neuro: dizziness, HA, fatigue
- GI: N/V (MC)
- drug induced lupus like syndrome
Drug interactions,monitoring - griseofulvin?
- multiple
- metabolized through CYP1A2, CYP2C9, and CYP3A4
- beware of warfarin, OCPs, alcohol, barbiturates, cyclosporine (just a few)
- monitoring: CBC, renal and liver fxns if long term therapy (beyond 8 wks)
MOA of Terbinafine (lamisil)?
- systemic allylamine antifungal
- MOA: creates ergesterol deficiency w/in the fungal cell wall leading to cell death
Comparison of griseofulvin and terbinafine?
- terbinafine was superior for tx of infections from Trichophton species
- griseofulvin was superior for tx of infections due to Microsporum
- have failure with one drug after tx - switch to the other (don’t know what species you are targeting)
Pharmacokinetics/dynamics of terbinafine?
- half life: 36 hrs
- distribution to sebum and skin
- metabolized hepatically
- inhibition of CYP450 enzymes: mult drug interactions including metoprolol and tramadol
MC terbinafine SEs?
Monitoring tests?
- HA
- diarrhea
- elevated liver enzymes
- monitoring tests:
AST/ALT prior to initiation
repeat if used for greater than 6 wks
CBC
assess for taste and/or smell disturbance
Use of terbinafine for tinea captious? Formulations?
- approved for use in 4 and over
formulations avail: - granules (sprinkle on top of non-acidic foods)
- tablets
Use of terbinafine for onychomycosis?
- greater efficacy and fewer SEs than others
- cure rate is 76%
pts who need tx:
- cosmetic reasons
- diabetes and onychoycosis
- hx of lower extremity cellulitis and ipsilateral onychomycosis
- pain or discomfort secondary to infection
Dosing of terbinafine?
-fingernails:
250 mg daily x 6 wks
- toenails:
250 mg daily x 12 wks
Cure rate for Itraconazole (sporanox) for oncyhomycosis? BBW?
- cure rate 63% for pulse therapy and 59% for continuous therapy
- BBW:
negative inotropic effects have been observed following IV admin. D/C or reassess use if signs or sxs of heart failure occur during tx
CIs for itraconazole?
- ventricular dysfxn
- pregnancy
- CHF
- concomitant use of other drugs that inhibit the CYP450 system
Half life, metabolism of itraconazole?
- half life: 21 hours
- metabolized by liver
- better absorbed with food (capsules) but take the soln on an empty stomach
Drug interactions of itraconazole?
- PPIs, anxiolytics, pain meds, antiplatelet agents, antihypertensives, statins
- drug interaction check is a MUST for this drug and other azole antifungals
(alot of times benefits of tx fungal infections don’t outweigh the risks esp in older pt - use lamisol)
Adverse effects of itraconazole?
- Nausea, diarrhea
- edema
- HA
- rash
- abnormal LFTs
- heart failure
- arrhythmia
- hearing loss
- many others
Monitoring while on itraconazole?
- baseline LFTs
- monthly LFTs if long term therapy
- serum concentrations:
draw 2 wks after starting therapy, draw w/o regard to when last dose was taken
Itraconazole dosing for onychomycosis?
- fixed dosage:
fingernails - 200 mg po qdx 6 wks
toenails - 200 mg po qd x 12 wks
(continue longer if no signs of clearing) - pulse therapy:
fingernails - 200 mg po BID x 1 wk/month x 2 month
toenails - 200 mg po BID x 1 wk/month x 3 months
What is Finasteride (propecia) used for?
- 1st line therapy for tx of androgenic alopecia in men
- 5-alpha reductase inhibitor: ultimately inhibits the conversion of testosterone to dihydrotestosterone
- same as Proscar (but lower dose) - used for tx of BPH