DƯỢC LÍ Goodman & Gilman's The Pharmacological Basis of Therapeutics 12th, 2010

HEXACHLOROCYCLOHEXANE
Lindane has been used as a commercial insecticide as well
as a topical medication. Due to several cases of neurotoxicity in
humans, the FDA has labeled lindane as a second-line drug in treating
pediculosis and scabies and has highlighted the potential for neurotoxicity
in children and adults weighing <110 pounds and in
patients with underlying skin disorders such as atopic dermatitis and
psoriasis (U.S. Food and Drug Administration, 2003). Lindane is
contraindicated in premature infants and patients with seizure disorders.
The FDA advises that lindane prescriptions should be limited
to amounts for a single application.
Malathion (OVIDE) is an organophosphate that
binds acetylcholinesterase in lice, causing paralysis and
death. Its structure is:
O
O
S
P S
O
O
It is approved for treatment of head lice in children ≥6 years
of age. The currently available formulation contains alcohol and is
flammable.
Benzyl alcohol (ULESFIA) 5% lotion has recently
received FDA approval for the treatment of lice.
Benzyl alcohol inhibits lice from closing their respiratory
spiracles, which allows the vehicle to obstruct the
spiracles and causes the lice to asphyxiate. This mechanism
may be less likely to cause resistance than traditional
pesticides.
Ivermectin (STROMECTOL) is an oral anthelmintic
drug (see Chapter 51) approved to treat onchocerciasis
and strongyloidiasis, but it also is effective in the offlabel
treatment of scabies and lice.
O
Because ivermectin does not cross the blood-brain barrier of
humans, there is no major CNS toxicity. Nevertheless, minor CNS
side effects include dizziness, somnolence, vertigo, and tremor. For
both scabies and lice, ivermectin typically is given at a dose of
200 μg/kg, which may be repeated in 1 week. It should not be used
in children weighing <15 kg.
Other, less effective topical treatments for scabies
and lice include 10% crotamiton cream and lotion
(EURAX) and extemporaneously compounded 5% precipitated
sulfur in petrolatum. The later preparation is
sometimes used during pregnancy or during nursing (on
infected mothers). Crotamiton and sulfur may be considered
for use in patients in whom lindane or permethrin
may be contraindicated.
ANTIMALARIAL AGENTS
Antimalarials used in dermatology include chloroquine
(ARALEN, others), hydroxychloroquine (PLAQUE-
NIL, others), and quinacrine (ATABRINE) (see Chapter 49).
Common dermatoses treated with antimalarials
include cutaneous lupus erythematosus, cutaneous
dermatomyositis, polymorphous light eruption, porphyria
cutanea tarda, and sarcoidosis. Other than lupus
erythematosus, all dermatological uses of antimalarials
are off label. The detailed use of these drugs in
those conditions is discussed elsewhere (LaDuca and
Gaspari, 2008).
The mechanism by which antimalarial agents
exert their anti-inflammatory therapeutic effects is
unknown. Proposed mechanisms of action include stabilization
of lysosomes, inhibition of antigen presentation,
inhibition of prostaglandin synthesis, inhibition of
pro-inflammatory cytokine synthesis, photoprotection,
inhibition of immune complex formation, and antithrombotic
effects. In patients with porphyria cutanea
tarda, chloroquine and hydroxychloroquine bind to porphyrins
and/or iron to facilitate their hepatic clearance.
The usual dosages of antimalarials are 200 mg twice a day
(maximum of 6.5 mg/kg/day) of hydroxychloroquine, 250-500
mg/day (maximum of 3 mg/kg/day) of chloroquine, and 100-200
mg/day of quinacrine. Clinical improvement may be delayed for several
months. Hydroxychloroquine is the most common antimalarial
used in dermatology. There is strong evidence that smoking may
decrease the effectiveness of antimalarials used for lupus erythematosus.
If no improvement in the dermatosis is noted in 3 months,
quinacrine is added. Alternatively, chloroquine is used as a single
agent. Patients with porphyria cutanea tarda require lower doses of
antimalarials (100 mg of hydroxychloroquine or 125 mg of chloroquine
two to three times weekly) to avoid severe hepatotoxicity.
The toxic effects of antimalarial agents are described in
Chapter 49.
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CHAPTER 65
DERMATOLOGICAL PHARMACOLOGY