Dermatopharmacology Flashcards
What 5 things does the skin protect the body from?
- temperature fluctuations
- allergens
- pollutants
- toxic chemicals
- bacteria, fungi, parasites, viruses
Where is skin the thickest? Thinner? Thinnest?
THICKEST: over head; dorsum of the neck, back, and sacrum; plantar and palmar surfaces of the feet
THINNER: ventral abdomen; medial surface of the limbs; inner pinnae
THINNEST: over the scrotum
What are the 2 primary cell types in the epidermis? What are the 5 layers?
keratinocyte origin and nonkeratinocyte origin
- stratum corneum - primary barrier to percutaneous drug absorption
- stratum lucidum
- stratum granulosum
- stratum spinosum
- stratum basale - constantly dividing
What happens when drugs are able to pass through the stratum corneum?
subjected to drug-metabolizing enzymes similar to those in the liver
- oxidation
- reduction
- hydrolysis
- conjugation
What part of the epidermis acts as the primary barrier to prevent loss of water, electrolytes, and macromolecules and excludes external agents? Why?
stratum corneum
- abundance of keratin
- configuration and content of intercellular lipids
What are the 3 routes of absorption of topically applied drugs to the skin? How do they move through the stratum corneum?
- stratum corneum - between cells, not through
- hair follicles
- sweat or sebaceous glands (that open into hair follicles)
passive diffusion
What is the structure of the stratum corneum like?
“brick and mortar”
brick = stratum corneocytes
mortar = intercellular lipids where drugs penetrate
What kind of drugs move best through intact skin? More of the drug is able to pass through the skin of what kind of animal?
lipophilic > polar
heavily haired - larger number of hair follicles
What 2 things must occur before a drug can be delivered to the epidermis under the stratum corneum?
- drug must move out of the vehicle and onto the surface of the stratum corneum
- drug must be able to penetrate the stratum corneum
What is a vehicle? What affects its movement through the skin?
substance in which a medicinally active agent is topically administered, usually inactive (but can be therapeutic)
physical and chemical properties
Which pH of drugs allows them to move best across the stratum corneum?
nonionized moiety of a weak acid or base - pH/pKa from 4.2 to 7.3
What are the optimal vehicles?
those in which the drug is soluble enough to enter into solution, but it not too soluble that it will persist in the vehicle and slow down the release of the drug into the skin
What 4 other factors affect percutaneous absorption?
- MW of the chemical
- temperature of the air
- blood flow
- skin age
What are 2 types of antiseborrheics?
- KERATOLYTICS: hydrate and soften stratum corneum to promote mechanical removal
- KERATOPLASTICS: normalize keratinization by slowing basal cell proliferation
How are salicylic acid and sulfur used as antiseborrheics?
SALICYLIC ACID: keratinolytic and keratoplastic with mild antibacterial, antifungal, and antipruritic actions
SULFUR: keratinolytic and keratoplastic with mild follicular flushing action and antibacterial/antipruritic effects
How are coal tar and benzoyl peroxide used as antiseborrheics?
COAL TAR: keratinolytic and keratinoplastic with degreasing action and commonly used with salicylic acid and sulfur
BENZYOL PEROXIDE: keratinolytic with bactericidal, degreasing, and follicular flushing activity, and is a strong oxidizer that generates free radicals
In what patients is coal tar avoided in?
feline - frequent irritant, commercial shampoos can be used
When is it indicated to use benzoyl peroxide?
treatment of keratosis and pyoderma
How are resorcinol and selenium sulfide used as antiseborrheics?
RESORCINOL: keratinolytic with bactericidal and fungicidal properties that promotes hydration of keratin (typically combines with other keratinolytics, sulfur, salicylic acid)
SELENIUM: keratinolytic and keratoplastic that slows down cell proliferation and sebum formation
- muscous membrane irritation may result in accidental contact
What do antipruritics do? What are the 4 mechanisms?
provide temporary relief from itching
- substitutes itching sensation
- protects the skin
- anesthetizes peripheral sensory nerves
- biochemical agents given topically
How do antipruritics substitute itching sensations? How can they protect the skin?
substitute with another sensation, like heat or cold: menthol, camphor, warm soaks/baths, ice packs
protect from external factors, like scratching, burning, irritants, and changes in humidity/temperature: bandages, impermeable agents
What antipruritics are used to anesthetize peripheral sensory nerves? What biochemical agents are given topically to treat pruritis?
local anesthetics: benzocaine, lidocaine, pramoxine (Dermacool) - can cause allergic sensitization
glucocorticoids
What type of glucocorticoids provides greater efficacy? How do they cause systemic effects? When does this happen more commonly?
ointment (still not as potent as oral or injectables)
absorbed through the skin - potent fluorinated agents (betamethasone, dexamethasone, triamcinolone, flumesthasone, fluocinolone)
Which glucocorticoid has been formulated to the applied to the entire body?
Triamcinolone (0.015% Genesis spray) - good for spot treatment of pruritis
When should highly potent preparations of glucocorticoids not be used?
on abraded skin
What 3 products are used to inflame or irritate the skin?
- rubefacients - hyperemia
- irritants - inflammation
- vesicants - cutaneous blisters
What are caustics? What are 9 examples?
corrosive agents that destroy tissue after one or more applications
camphor, COAL TAR, creosote, menthol, methyl salicylate, iodine, mercuric iodine, alcohols, pine tar
What is the most widely used caustic in veterinary medicine? What does it do?
coal tar - byproduct of bituminous coal distillation that decreases the epidermal synthesis of DNA
What are escharotics? What are 6 examples?
corrosives that precipitate proteins to form a crust and eventually scar
glacial acetic acid, aluminum chloride, gentian violet, phenol, salicylic acid, silver nitrate
What are the 2 proposed modes of action for irritant products?
- mask moderate to severe pain by milder pain caused by application
- induce healing action on chronic wounds
What 2 products are sometimes used to treat acral lick dermatitis in dogs?
- menthol-containing products
- Capsaicin (arthritis pain in humans, too)
What 3 antimicrobials can be effective in treating infectious skin diseases?
- alcohol
- iodine
- chlorhexidine
What 5 antibiotics are available in topical ointments? What are they often combined with?
- neomycin
- bacitracin
- polymyxin B
- gramicidin
- nitrofurazone
each other or steroids
Why isn’t topical therapy of dermatophytosis in dogs and cats commonly effective?
thick hair coat —> unable to reach the site of infection in adequate concentrations
What is Amphotericin B? Chlorhexidine?
AMPHOTERICIN B - Fungizone available as a cream, lotion, or ointment for Candida infections
CHLORHEXIDINE - mild antifungal and antibacterial available as a rinse/shampoo (not effective by itself for dermatophytosis treatment)
What is commonly used to treat Malassezia dermatitis?
combinations of chlorhexidine with miconazole (Malaseb rinse) or ketoconazole (Ketochlor)
What is Clotrimazole? Miconazole?
CLOTRIMAZOLE - 1% Lotrimin, Veltrim effective against dermatophytes, Candida and Malassezia
MICONAZOLE - cream (Conofite), lotion (Resizole), shampoo (Dermazole) to treat Candida and Malassezia dermatitis
What is nystatin effective in treating? What can it not treat?
some yeast and dermatophytes
Malassezia
How is sulfur used as an antimicrobial? Why should it be carefully used in cats?
effective against dermatophytes and can be used for localized or generalized dermatophytosis (LymDyp)
- lime sulfur dip is cost-effective and an antiparasitic and antipruritic, but it has a stong odor
may become ill if they groom after treatment —> E collar until the product is dry
What is Thiabendazole? What is it commonly combined with to treat local lesions?
treats dermatophytes and some yeast, including Malassezia
neomycin and dexamethasone (Tresaderm)
- be cautious combining antifungals and corticosteroids
In what 6 ways are antiparasitics delivered?
- SPRAY - residual effect depending on active compound and concentration
- POWDER - SAFEST, but must be frequently applies
- SHAMPOO - little residual effect and must stay on skin for at least 10 mins
- FOAMS
- SPOT-ONS - broad-spectrum and ease make it most preferred
- DIPS
What are the active ingredients in antiparasitic shampoo formulations? Are they systemically absorbed? What species are susceptible to toxicity?
pyrethrin, pyrethroids, carbaryl
NO - any factor that increases their absorption can result in toxicity
cats - ingestion (grooming), percutaneous absorption
- salivation, tremors, seizures
- symptomatic treatment + bath
How do spot-on products act? Where are they applied? What are 5 common examples?
- adulticides, and some are effective against juvenile stages
- infrascapular area from where they diffuse over the body
- Imidacloprid (Advantage)
- Fipronil (Frontline)
- Selamectin (Revolution)
- Metaflumazone (ProMeris)
- Dinotefuran (Vectra 3D)
What are the active ingredients in flea collars? What is an effective antidote for acute toxicity upon ingestion?
carbaryl, pyrethrin, organophosphates
Yohimbine
How do collars containing methoprene (Ovitrol) and amitraz (Preventic) compare?
METHOPRENE = sterilizes fleas, does not kill adults
AMITRAZ = effective against ticks but not fleas
How do pyrethrins and pyrethroids work?
PYRETHRINS: disrupt neurological function by prolonging Na+ in nerve membrane to kill fleas, lice, cheyletiella, otodectes, and mosquitoes (from chrysanthemums)
PYRETHROIDS: same MOA, synthetic analog with slower knockdown
What is toxicity of carbamates (like carbaryl) associated with? How is it treated?
overstimulation of the parasympathetic system
atropin and 2-pyridine aldoxime methylcholride
What are the most toxic insecticides in veterinary medicine? In what animals are they not used usually in?
organophosphates
cats
What organophosphate is able to be used in cats? What are 3 other common ones used?
Malathion
- Chlorpyrifos (Dursban, Duratol) - flea sprays and dips
- Diazinon - environmental flea and tick control
- Phosmet (Paramite Dip) - flea control, scabies
What is Fipronil? How does it work? What version of it is mixed with another active ingredient?
Frontline, synthetic phenylpyrazole that is a flea adulticide with tick efficacy, scabies prevention, and mite infection protection
GABA receptor antagonist that regulates chloride influx into nerve cell
Frontline Plus = fipbronil + methoprene for ovicidal properties
What is Imidacloprid? How does it work?
Advantage, spot-on agent that kills adult fleas
prevents postsynaptic binding of ACh, leading to respiratory paralysis (applied every 30 days)
What are the 2 types of mixtures of Imidacloprid?
- K9 Advantix = imidacloprid + permethrin for dogs to treat ticks and mosquitoes
- Advantage Multi = imidacloprid + moxidectin for dogs and cats to treat fleas, heartworm, intestinal worms, and ear mites
What is Selamectine? What is it used to treat in dogs and cats?
Revolution, spot-on
DOGS: fleas, hearworm, Dermacentor ticks, sarcoptes (scabies), octodectes (ear mites) in those 6 weeks old
CATS: fleas, heartworm, octodectes, roundworms, and hookworks in those 8 weeks old
What is Amitraz? What is it licensed to treat? What is it used off-label for?
Mitaban, monoamine oxidase inhibitor
generalized demodicosis
scabies and ticks
Why should Amitraz be mixed fresh and be entirely used? What is the large animal form of amitraz?
rapidly oxidized upon light and air exposure and the resulting product is more toxic than the parent compound
Taktic - DON’T use in small animals
What is ProMeris? How is it used in cats?
spot-on formulation for dogs containing amitraz and metaflumazone approved to treat localized and generalized demodecosis in those older than 8 weeks and is effective against fleas and ticks
does not contain amitraz and is only used for fleas
What 3 compounds are found in Vectra 3D? How is it used? How does the feline formulation compare?
dinotefuran, permethrin, pyripoxyfen
spot-on product for dogs older than 7 weeks that is effective against fleas and ticks, and kills mosquitoes
does not contain permethrin and is given once they;re older than 8 weeks
What allows transdermal absorption of drug products to produce systemic effects? What are 3 benefits to transdermal drug delivery?
high plasma concentrations after it is applied to the skin and absorbed
- easier to administer
- drug delivery can be sustained
- fewer factors that complicate transdermal absorption (avoids first pass metabolism)
What 4 products used in veterinary medicine are not intended for transdermal absorption, but can result in systemic absorption in the person treating the animal?
- DMSO
- anticancer drugs
- nitroglycerin ointment
- all antiparasites (dips and shampoos)
(use nonpermeable gloves!)
What 3 drugs are typically given transdermally?
- nitroglycerin ointment - relaxes smooth muscle and used in dogs and cats to treat cardiogenic edema; applied to glabrous areas
- fentanyl - narcotic analgesic is an effective and safe alternative for dogs and cats
- selamectin - systemic insecticides
(scopolamine, nitroglycerin, and clonidine transdermal patches are used in humans for motion sickness, angina, and hypertension)
