Topicals Flashcards
Describe the three absorption pathways of intact and diseased skin?
1) through appendages - down the hair follicle- shunt route
2) Through intracellular lipid domains
3) Transcellular route (through corneocytes of stratum corneum)
- hydrates keratin in corneocytes allows hydrophilic drugs to pass
- What is rate limiting step of percutaneous absorption (PCA)?
- What are the factors?
- passage through stratum corneum
1) [] of drug in the vehicle
2) partitioning of drug from vehicle into stratum corneum (partition coefficient)
3) molecular aspects of drug allowing diffusion across skin layers (drug diffusion coefficient)
4) thickness of stratum corneum
What kind of process is conventional trandermal drug delivery?
passive process
what is name of equation to calculate rate of absorption or flux of substance across barrier
Fick’s Law
Drug variables for PCA?
1) concentration-directly related to PCA
2) lipophilicity-must be at least a little fat sol
3) Molecular size-most effective if <600daltons
Innate skin variables for PCA?
1) stratum corneum thickness - rate-limiting - inversely related
2) cutaneous vasculature-inc vaculature=inc local and systemic drug effects
3) area of absorptive surface-inc surface area=inc PCA (But concentration is still the more important variable)
4) mucosal surfaces-not much of a barrier compared to S. corneum-systemic effects with any mucosal barrier
What are vehicle factors?
1) how occlusive (hydrating) it is - the more=the greater hydration & absorption
2) how drug released from vehicle
Best occlusive vehicle for topical?
ointment
Best vehicle to use for transfering drug to stratum corneum lipids?
-Ointment
Dont use ointments where?
where skin rubs against skin - integrous areas
Which vehicle is best to prevent evaporation of topical?
ointment
Alergic reactions most often from what vehicle?
emulsifying agents
most penetration vs least penetration areas?
1) BEST ABSORPTION=MOST SYSTEMIC EXPOSURE = mucous membranes
2) scrotum
3) eyelids
4) face
5) chest and back
6) upper arms and legs
7) lower arms and legs
8) Dorsa of hands and feet
9) palmar and plantar skin
10) WORST = Nails
Psoriasis pathophysiology
- describe disease?
- what areas?
- most common type?
- autoimmune=inflammation and keratinocyte hyperproliferation
- scalp, groin/genetalia, lower back, elbows & knees, nails
Acne
- describe the disease?
- steps?
- hyperproliferation of epidermis + sebum secretion –> increased sensitivity to androgens
- gram + bacteria –> perifollicular inflammation
1) Microcomedone
2) Comedone
3) inflammatory pustule
4) nodue - deeper inflammation
atopic dermatitis (eczema)
- what is it?
- secondary problems?
- chronic inflammatory skin (unk mech but food, allergy, irritation related) disorder associated with intense pruritus and dried flaking skin
- secondary S. Aureus infection
mechanism of itch (pruritus)
- histamine released from dermal mast cells causes itch related to utricaria (hives) and insect dites
- g-proteins on somatosensory nerves activated
- Ca entry TRPV1 ligand activated
- Substance P induced histamine release
types of pruritus
1) dermatologic (primary skin disorder)
- xerosis, atopic dermatitis, psoriasis..
2) systeic (affect other organ systems)
- CRF, liver disease, hematologic or lymphoproliferative, malignancy
3) neruologic (PNS or CNS issues like MS)
4) Psychogenic (psych disorders)
- depression, anxiety…
5) mixed - more than one cause
Benzoyl peroxide
- type?
- MOA?
- used for?
- topical antibiotic for non-inflammatory and inflammatory acne
- broad cidal
- non-specific oxydizing activity (no development of resistance)
Clindamycin?
- type?
- used for?
-topical antibiotic -broad cidal
-for acne
(Binds 50S subunit)
Erythromycin
- type
- used for?
-topical antibiotic -gram positive - cidal
-for acne
(Bind 50S subunit)
Metronidazole
- type?
- used for?
-topical antibiotic- gram + and - anaerobic coverage - static
-for acne
(disruption of DNA and inh of nucleic acid synth)
azelaic acid
- type?
- used for?
-topical antibiotic -against P Acnes –> cidal & static
-for acne
(disruption of mitochondiral respiration and DNA synth)
sodium sulfacetamide
- type?
- used for?
-topical antibiotic -against P acnes
-for acne
(inh dihydropteroate synthetase)
- use of whcih topical antibiotic DOES NOT lead to resistance over time?
- MOA?
- benzoyl peroxide
- non specific oxydizing agent
Retinoids
- what are they?
- what do they do generally?
- chemicals with activity like Vit A - binds retinoic acid receptors (RARs) and retoinoid X receptors (RXRs)
- different isomer metabolites bind differentially to RARs and RXRs
- direclty bind DNA and alter DNA transcription