SYSTEMIC PHARM Flashcards
1
Q
oral antifungal drugs
A
⦁ Griseofulvin
⦁ Terbinafine (Lamisil) = allylamine class
⦁ Itraconazole (Sporanox) = triazole class
2
Q
terbinafine (Lamisil) is which antifungal class
A
allylamine = fungicidal
3
Q
1st line therapy for fungal scalp infection
2nd line therapy for fungal scalp infection
A
1st = griseofulvin
2nd = terbinafine (Lamisil)
4
Q
1st line therapy for nail scalp infection
2nd line therapy for nail scalp infection
A
1st = terbinafine (Lamisil)
2nd = itraconazole (sporanox)
5
Q
duration of treatment for tinea capitis
A
griseofulvin x 8 weeks
6
Q
MOA OF GRISEOFULVIN
A
FUNGISTATIC - inhibits fungal cell division
griseofulvin binds to keratin and makes keratin resistant to fungal invasion
7
Q
GRISEOFULVIN IS FUNGI___________
A
STATIC
8
Q
how to take griseofulvin
A
take with food to lessen GI upset
taking with a fatty meal can help increase absorption
9
Q
Griseofulvin is deposited in the keratin layer of skin, hair and nails, and concentrates in the
A
liver, fat & skeletal muscle
metabolized in the liver
10
Q
do you have to check LFTs while on griseofulvin
A
if being used > 8 weeks, check LFTs
monitor CBC
renal & hepatic function if on griseofulvin for long term
11
Q
microsize vs ultramicrosize griseofulvin
A
2 formulations of Griseofulvin
- the smaller the particle size, the greater the bioavailability.
- So the ultramicrosize is less of a dose than microsize, but has a greater bioavailability, so need less of a dose of ultramicrosize
⦁ Microsize = 20-25 mg/kg/day
⦁ Ultramicrosize = 10-15 mg/kg/day
12
Q
Griseofulvin Contraindications
A
- liver failure
- porphyria
- pregnancy (CATEGORY X)
- breastfeeding (not recommended)
- use with caution if hx of PCN allergy
13
Q
use griseofulvin with caution in pts with
A
hx of pcn allergy; potential for cross reactivity
14
Q
drugs that can induce lupus
A
procainamide hydralazine isoniazid methyldopa griseofulvin
15
Q
ADVERSE REACTIONS OF GRISEOFULVIN
A
o Skin
⦁ photosensitivity
⦁ Erythema multiforme / SJS / TEN
o Liver
⦁ jaundice
⦁ elevated LFTs
o Bone Marrow
⦁ granulocytopenia
o Neuro
⦁ dizziness
⦁ headache
⦁ fatigue
o GI
⦁ nausea
⦁ vomiting
o Drug induced lupus like syndrome
16
Q
griseofulvin drug interactions
which drugs in particular
A
warfarin, OCPs, barbiturates, alcohol, cyclosporine
- griseofulvin has multiple drug interactions
- metabolized through CYP1A2, CYP2C9, and CYP3A4
- beware in particular of Warfarin, OCPs, Alcohol, Barbiturates, Cyclosporine
17
Q
griseofulvin monitoring
A
CBC
- renal & liver function if on long term therapy
18
Q
terbinafine MOA
A
fungicidal
creates an ergotamine deficiency within fungal cell wall, leading to fungal cell death
19
Q
Trials comparing griseofulvin to terbinafine
_____________ was superior for the treatment of infections from Trichophyton species
____________ was superior for the treatment of infections due to Microsporum
A
terbinafine
griseofulvin
20
Q
griseofulvin distributes to the
A
hair, skin and nails
21
Q
terbinafine distributes to the
A
skin & sebum
22
Q
Multiple drug interactions with terbinafine including
A
metoprolol & tramadol
**THINK BETA BLOCKERS
23
Q
drug interactions with beta blockers, such as tramadol & metoprolol
A
terbinafine (Lamisil)
24
Q
obtain AST/ALTs prior to starting therapy on
A
terbinafine (Lamisil)
repeat if using for > 6 weeks
25
side effects of Lamisil
headache
diarrhea
elevated LFTs
altered sense of smell / taste
26
Lamisil monitoring
CBC
AST/ALTs prior to starting Lamisil, repeat if using for > 6 weeks
assess for changes to smell and/or taste
27
terbinafine for tinea capitis
| 2nd line for tinea capitis after griseofulvin
- approved for use in ≥ 4 years of age
- available in granules or tablets (ex: if can't take griseofulvin and can't swallow pills = give terbinafine granules and sprinkle onto non-acidic foods)
28
terbinafine for onychomycosis
- cure rate
- which patients would you give terbinafine to for onychomycosis
- greater efficacy & fewer SE than others
- 76% cure rate
- Patients who need Lamisil treatment
⦁ for cosmetic reasons (don't like the way it looks)
⦁ have DM & onychomycosis
⦁ have a hx of lower extremity cellulitis & ipsilateral onychomycosis***
⦁ have pain or discomfort secondary to fungal infection
29
terbinafine dosing for fingernails vs toenails
- fingernails = 250mg x 6 wks
| - toenails = 250mg x 12 wks
30
ITRACONAZOLE (SPORANOX) BBW
NEGATIVE INOTROPIC EFFECTS
Negative inotropic effects have been observed following intravenous administration. Discontinue or reassess use if signs or symptoms of heart failure (HF) occur during treatment.
31
itraconazole has a higher cure rate for ____________ therapy vs _________ therapy
higher cure rate with pulse therapy vs with continuous therapy
itraconazole (sporanox) = 2nd line therapy for onychomycosis
32
can cause altered sense of smell / taste
terbinafine (Lamisil)
33
contraindications to itraconazole
ventricular dysfunction
CHF
pregnancy
Concomitant use of other drugs that inhibit the CYP450 system
34
use with caution if hx of PCN allergy
griseofulvin
35
how to take itraconazole (sporanox) capsules vs solution
take capsules with food = better absorbed
take solution on an empty stomach
36
LOTS OF DRUG INTERACTIONS for itraconazole and other azole antifungals
- drug interactions such as with
PPIs, anxiolytics, pain meds, antiplatelets (Plavix / aspirin), antihypertensives, statins, etc.
37
adverse effects of itraconazole (sporanox)
```
⦁ Nausea
⦁ diarrhea
⦁ edema
⦁ headache
⦁ rash
⦁ abnormal LFTs
⦁ heart failure
⦁ arrhythmia
⦁ hearing loss
⦁ many more!
```
38
monitoring for itraconazole (sporanox)
⦁ baseline LFTs, then monthly if long term therapy
⦁ serum itraconazole concentrations - draw 2 weeks after starting therapy, regardless of when last dose was taken
39
so baseline LFTs are obtained for which drugs
terbinafine & itraconazole
check again for terbinafine if on > 6 weeks
check monthly for itraconazole if on long-term
40
itraconazole dosing: continuous vs pulse therapy
o Continuous or Fixed
⦁ fingernails = 200mg qd x 6 wks
⦁ toenails = 200mg qd x 12 wks
o Pulse therapy
⦁ fingernails = 200mg BID x 1 wk/month x 2 months
⦁ toenails = 200mg BID x 1wk/month x 3 months
41
First line therapy for the treatment of androgenic alopecia in men
Finasteride (Propecia)
42
Finasteride (Propecia) MOA
5-alpha-reductase inhibitor
Ultimately inhibits the conversion of testosterone to dihydrotestosterone
Same as Proscar (used for BPH), but a lower dose
43
Finasteride & PSA levels
5-alpha-reductase inhibitors decrease the PSA by about 50%, so in patients taking finasteride for ≥6 months, remember to double the PSA when comparing to normal (untreated) values
44
Finasteride monitoring
obtain baseline PSA levels
re-check in 6 months
if PSA increases while on this med, refer to urology
if PSA doesn't decrease by about 50% after 6 months of therapy, may indicate an increased risk for prostate cancer
45
efficacy of finasteride (propecia)
- after 2 years of therapy, hair counts may increase by about 25%
- mostly used to maintain the hair they have left, because it only increases hair count slightly
46
side effects of finasteride
```
⦁ sexual dysfunction (decreased libido, ejaculatory dysfunction, ED)
⦁ gynecomastia
⦁ testicular pain
⦁ depression
⦁ orthostatic hypotension
⦁ dizziness
⦁ weakness
```
47
women of childbearing age should avoid contact with crushed or broken tablets of finasteride, because it is
TERATOGENIC!!!
48
most common SE of finasteride
sexual dysfunction
orthostatic hypotension
dizziness
weakness
49
finasteride metabolism
- hepatic metabolism
- caution for drug interactions
- DON'T USE IN LIVER FAILURE
50
finasteride dosage
1mg daily. Continuous dosing for a minimum of 1 year before assessment for efficacy.
Maximal results at 2 years
- a much lower dose is used for alopecia (1mg qd) vs for BPH (5 mg qd)
51
wait until _______ of therapy of finasteride before assessing efficacy
maximal results are seen at _________
1 year
max results at 2 years
52
oral antibiotics used in derm
```
⦁ Cephalexin (Keflex)
⦁ Mupirocin (Bactroban)
⦁ Doxycycline
⦁ Minocycline (Minocin)
⦁ Clindamycin
```
53
cephalexin (Keflex) distribution
- 1st gen cephalosporin (beta-lactam antibiotic)
- for skin / skin structure infections
- Distribution = widely distributed to all body tissues, except does NOT penetrate the CSF well
54
cephalexin (Keflex) is widely distributed to all body tissues, except
does NOT penetrate the CSF well
55
dosage of keflex
⦁ skin / skin structure infections = 500mg Q6hrs
| ⦁ furunculosis & skin abscess = 250mg Q6hrs
56
what bugs does Keflex cover
⦁ staph
| ⦁ strep
57
Keflex pregnancy category
B (safe-ish!)
58
MOA of keflex
inhibits bacterial cell wall synthesis
inhibits bacterial cell wall synthesis by binding to one or more of the Penicillin-binding proteins (PBPs) which in turn inhibits the final transpeptidation step of peptidoglycan synthesis in bacterial cell walls --> inhibits cell wall biosynthesis
59
Keflex & renal dysfunction
Decrease keflex dose for severe renal impairment (CrCl < 10mL/min)
can still take Keflex with renal impairment, just have to lower the dose
60
indications for mupirocin (Bactroban)
⦁ Impetigo (due to staph & strep) = ointment TID x 3-5 days
⦁ Treat secondarily infected skin lesions due to staph or strep = cream TID x 10 days
⦁ Intranasal to eradicate MRSA = BID x 5 days (use intranasal formula)
impetigo = ointment
2ndary infections = cream
intranasal MRSA = intranasal formula
61
inhibits protein synthesis by binding to isoleucyl transfer-RNA synthetase
inhibits bacterial protein & RNA synthesis
mupirocin (Bactroban)
inhibiting isoleucyl-transfer RNA, thereby inhibiting bacterial protein and RNA synthesis.
62
absorption of mupirocin
topical ointment & cream penetrates the outer layers of skin with some minimal systemic absorption
- Intranasal - about 3% of what is applied is systemically absorbed in adults, but can be significant in neonates
63
MOA OF TETRACYCLINES
Inhibition of protein synthesis by binding with the 30S ribosomal subunit (and possibly the 50S) of susceptible bacteria, may also cause alterations in the cytoplasmic membrane
64
SE OF TETRACYCLINES
photosensitivity
65
SE of doxycycline
nausea if taken on an empty stomach
can cause esophagitis if not taken with fluids
photosensitivity
66
Absorption of Doxy may be delayed with
achlorydia (high pH)
67
indications for doxy
⦁ Tick-borne rickettsial infections
⦁ Acne
⦁ Rosacea
⦁ off label when 1st line therapy is unavailable = animal & human bites, cellulitis secondary to MRSA, skin & soft tissue infections
68
indications for minocycline
⦁ acne
| ⦁ off-label = MRSA cellulitis
69
SE of minocycline
⦁ vertigo (especially at higher doses)
⦁ esophagitis if not taken with water (just like doxy)
⦁ GI upset if taken on an empty stomach (just like doxy)
70
which acne antibiotic is associated with the most resistance
ERYTHROMYCIN
71
reducing antibiotic resistance when treating acne
- most resistance is associated with Erythromycin
- to reduce abx resistance, start Benzoyl Peroxide 5 days prior to abx therapy, and continue during abx therapy
- If BP not an option, note increased efficacy if using a topical retinoid + oral abx therapy
- try to limit abx to 12-18 weeks
- don't change therapy too quickly (evaluate after 6-8 weeks, don't give up after just a few weeks)
- don't give the same antibiotic in topical & oral form (ex: clindamycin)
72
derm indications for clindamycin
⦁ Acne
| ⦁ Rosacea
73
Avoid oral clindamycin for treatment of acne due to risk of
C. dif
74
- for treatment of severe, recalcitrant, nodular acne
- Acne with many inflammatory nodules (greater than 5 mm) that is unresponsive to conventional therapy, including systemic antibiotics
Accutane (isotretinoin)
75
Accutane MOA
⦁ shrinks sebaceous glands
⦁ decreases sebum production
⦁ decreases the number of sebum dependent bacteria Propionibacterium acnes
76
The only acne medication that can permanently alter the natural course of the disorder
accutane
77
duration of accutane
duration of therapy = 15-20 weeks
can discontinue sooner if the cyst count is decreased by > 70%
if a second course of therapy is necessary, it is of a shorter duration
78
requirements with Accutane due to high risk of birth defects
EXTREMELY HIGH RISK OF BIRTH DEFECTS...
- 2 forms of birth control required - have to have started at least 1 month prior to rx
- 2 negative pregnancy tests prior to initial prescription
- pregnancy test & counseling once a month
- need to be a registered prescribed in IPledge program and document expertise in prescribing isotretinoin per FDA regulations
79
ACCUTANE SIDE EFFECTS
⦁ cheilitis
⦁ dry skin & mucous membranes
⦁ epistaxis
⦁ desquamation
⦁ photosensitivity
⦁ pruritus
⦁ ocular symptoms related to dysfunction of meibomian glands within conjunctiva --> can lead to corneal abrasion
⦁ more prone to cutaneous staph infections (paronychia, pyogenic granulomas)
⦁ temporary diffuse alopecia or nail brittleness
⦁ depression
⦁ hypertriglyceridemia (up to 45% of pts, Alcohol may potentiate this rxn)
⦁ elevated total & LDL cholesterol (up to 30%)
- these SE usually resolve after discontinuation of the drug
80
baseline Accutane labs
```
⦁ CBC with diff
⦁ ESR
⦁ fasting glucose
⦁ CPK
⦁ Pregnancy test x 2 (2nd test done 19 days after 1st test, and within 7 days of starting rx and within first 5 days of menstrual cycle)
⦁ LFTs
⦁ Lipid panel
```
81
Accutane monitoring
- monthly pregnancy test - until 1 month after d/c therapy
- monthly CBC & glucose
- weekly or biweekly Fasting LP & LFTs x first 4 weeks, then monthly
82
DISCONTINUE ACCUTANE IF...
⦁ TG > 800
| ⦁ LFTx 3x the upper limit of normal
83
retinoid acid derivative
accutane
84
topical calcineurin inhibitors
Tacrolimus (Protopic)
| Pimecrolimus (Elidel)
85
indications for topical calcineurin inhibitors
⦁ atopic dermatitis
⦁ lichen planus
⦁ vitiligo
⦁ psoriasis
86
BLACK BOX WARNING FOR topical calcineurin inhibitors
- associated with rare cases of malignancy (skin cancer & lymphoma) - so should be limited to short-term and intermittent treatment using the minimum amount necessary for control of symptoms and only in involved areas
87
BLACK BOX WARNING FOR topical calcineurin inhibitors = associated with rare cases of malignancy = __________ & _____________
skin cancer & lymphoma
88
DO NOT USE TOPICAL CALCINEURIN INHIBITORS WHEN....
1) patient is < 2
2) patient is on systemic immunosuppressant (cyclosporine)
3) patient is immunocompromised
89
MOA of topical calcineurin inhibitors
suppresses cellular immunity - by inhibiting T-lymphocyte activation; binds to an intracellular protein to inhibit calcineruin phosphatase activity
90
Concomitant __________ with topical calcineurin inhibitors can cause redness & flushing
alcohol ingestion
so avoid TCIs with alcohol
also, sun protection recommended
91
do NOT use topical calcineurin inhibitors under an
occlusive dressing!
it is a topical medication, but has enough systemic absorption to cause malignancy and interact with alcohol, so don't occlude
92
SE OF TACROLIMUS (PROTOPIC)
- headache (20%)
- skin burning at application site (58%)
- pruritus (46%)
- erythema (28%)
93
ELIDEL (PIMECROLIMUS)
- less burning reaction than with protopic
- cream
- 1 strength = 1%
94
which topical calcineurin inhibitor has less burning SE
elidel
95
drug induced lupus symptoms
- arthralgia
- myalgia
- fever
- malaise
- rash
- serositis
usually are on the drug for 1 month or more
multiple drugs can be responsible for drug-induced lupus
96
mainstay of therapy for drug induced lupus
d/c drug
NSAIDS for symptom relief
Usually spontaneous resolution of clinical manifestations of the disease within several weeks to months after discontinuing the causative drug
97
If drug-induced lupus symptoms don't resolve within 4-8 weeks = give
HYDROXYCHLOROQUINE
98
if drug-induced lupus symptoms are SEVERE or if quick relief is needed (like pleurisy or pericarditis) = give
systemic corticosteroids
