Term
| iontophoresis (electrophoresis) |
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Definition
| implies the delivery of ionic (charged) drugs in the body by the use of electric current (single digit volts) |
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Term
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Definition
| no its painless from minutes to hous |
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Term
| what are examples of iontophoresis |
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Definition
| local dermal anesthesia (lidocaine) icorticosteroids (products) and Glucowatch |
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Term
| what is iontophoresis useful for? |
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Definition
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Term
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Definition
| charge breaks down lipid barriers and permits passive transport of ordinarily impermeable molecules. |
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Term
| Which barrier does electroportation affect? |
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Definition
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Term
| What is the type of voltage and how long for electroportation? |
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Definition
| use of high voltage and short time treatment (hundreds of volts for microseconds) |
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Term
| How does electroporation change the phenotype of electroporation? |
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Definition
| creates new aqueous pores across the stratum corneum |
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Term
| examples of electroporation? |
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Definition
| few model compounds such as heparin, calcein, and vaccines |
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Term
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Definition
| lipid bilayer disordering and convection, this eliminates lag time |
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Term
| therapeutic frequency of ultrasound? |
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Definition
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Term
| what does sonophoresis do to lag time? |
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Definition
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Term
| mech involving ultrasound? |
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Definition
- thermally enhanced diffusion
-structural changes by mechanical oscillations and cavitation (=1/ultrasound frequency)
-cavitation (formation of vapor bubbles of a flowing liquid in a region where the pressure of the liquid falls below its vapor pressure)
-convective transport through hair follicles |
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Term
| Is the pro-drug approach therapeutically active? |
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Definition
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Term
| Pro-drug: explain lipophilicity compared to parent drug |
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Definition
| This drug is more lipophillic than the parent drug (increase in permeability and partitioning through the skin) |
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Term
| How does the pro-drug produce therapeutically active drug in biological environment |
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Definition
| Bioconversion by hydrolysis or enzymatic degradation. |
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Term
| What is the most important epidermis barrier to chemical penetration? |
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Definition
| Stratum corneum (layer of dead, flattened keratinocytes) |
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Term
| The three types of penetration pathways |
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Definition
| intracellular, intercellular, follicular |
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Term
| What are the two main types of dermal delivery? |
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Definition
| Topical delivery (ointments and creams) and systemic delivery |
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Term
| What are the two main types of topical delivery? and what are they used to treat? |
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Definition
| surface epithelium and appendages (dry skin, surface infections) , lower epidermis/dermis (infections and inflammation) |
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Term
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Definition
Thermoregulation (termperature control)
Barrier to pathogens and foreign chemicals (sloughing)
Protection against massive loss of water (50M)
Protection against physical abrasion and UV radiation. |
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Term
| What are the five layers of the epidermis? |
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Definition
stratum corneum layer (keratin layer, glycine/alanine and disulfide bonds)
stratum lucidum
Stratum granulosum
stratum spinosum
stratum germinativum |
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Term
| Is the epidermis vascular or avascular? |
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Definition
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Term
what is the turnover of epidermis?
where is the highest turnover? the lowest? |
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Definition
21-28 days
highest turnover is the scalp, the lowest turnover is at the toes |
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Term
| What is the average thickness of the epidermis? |
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Definition
|
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Term
| what is the percent that is needed of moisture for the epidermis? |
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Definition
| 10% to remain soft and supple |
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Term
| what is the average thickness of the stratum corneum? |
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Definition
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Term
| where are blocks of keratin embedded in the stratum corneum? |
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Definition
| in the extracellular lipids |
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Term
| are the cells in the stratum corneum alive? |
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Definition
| they are flattened, dead cells with no nucleus |
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Term
| Which layer is the major barrier towards permeation of water and other molecules? |
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Definition
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Term
| explain the layout of exracellular lipids of the stratum corneum |
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Definition
| arranged in bilayers that form sheets |
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Term
| Explain the vascular and nerve supply in the dermis |
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Definition
| contains a rich blood supply, lymphatic vessels, and nerve endings |
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Term
| explain the speed of diffusion of drugs through the dermis |
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Definition
| drugs quickly diffuse through this area |
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Term
| Explain elastin fiber layouts in the dermis |
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Definition
| elastin fibers are loosely arranged in all directions and give elasticity to the skin |
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Term
| What types of cells and tissues/nerves are involved in the dermis? |
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Definition
the dermis containes nerves, sweat glands, and origin of hair follicles
cell types: mast cells, fibroblasts (synthesis of collagen and elastin), Langerhan cell (allergic response), schwann cells |
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Term
What are types of skin appendages?
how much % do they occupy of the total skin? |
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Definition
arectir pili muscle
hair follicle
sebaceous glands
sweat glands
skin appendages occupy only 0.1% of the total skin surface |
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Term
| what is a sebaceous glands associated with? |
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Definition
| associated with a hair follicle |
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Term
| which hormone is the sebaceous gland dependent on? |
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Definition
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Term
| When is there an enormous increase in sebaceous gland |
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Definition
| increases activity in puberty |
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Term
| what is the function of the sebaceous gland. where do they discharge sebum? |
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Definition
Discharge sebum into the hair follicle
essentially an oil:
protect against the penetration of foreign chemicals
antibacterial and fungicidal: fatty acid esters (ph5)
Barrier against loss of water (role duplication by commercial dry skin products)
Lubricant, providing slip |
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Term
What are eccrine glands?
Where are eccrine glands? |
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Definition
| These are sweat glands. they are distributed over all of the body (palms and soles) |
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Term
| Eccrine glands- what do they have? |
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Definition
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Term
| What kind of stimulation do eccrine cells respond to? |
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Definition
| thermal and CNS stimulation |
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Term
| What are apocrine glands and when do they develop? |
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Definition
| They are hormonal glands. They are associated with sexual development and do not appear until puberty |
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Term
| what kind of substance is secreted from apocrine glands? |
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Definition
| milky, fatty secretion. This is the development of body odor (by bacteria decomponsition of the contents of sweat (acid and dead cell debris) |
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Term
| Where are apocrine glands located? |
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Definition
| found in relatively small numbers in the underarm area, on the abdomen, and the genito-anal region |
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Term
| Where the melanocytes located? |
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Definition
| they are every 4th cell in epidermal-dermal interface (basale layer) |
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Term
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Definition
| They synthesize and distribute melainin (a dark polymer capable of absorbing UV radiation) |
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Term
| What do langerhan cells do? |
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Definition
| uptake and processing of antigenic material |
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|
Term
thickness of the:
stratum corneum
dermis
erythrocyte membrane
Leukocyte membrane |
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Definition
stratum corneum: 4X10^-3
dermis: 2X10^-2
erythrocyte membrane: 5X10^-7
Leukocyte membrane: 1X10^-6 |
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|
Term
Diffusivites of:
stratum corneum
dermis
erythrocyte membrane
Leukocyte membrane |
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Definition
stratum corneum:4.2X10-10
dermis: 2X10^-6
erythrocyte membrane: 6.5X10^-9
Leukocyte membrane: 2.8X10^-9 |
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Term
| What are the pathways of drug permeation through skin? |
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Definition
Transcellular (accross the cell membrane)
Paracellular (between cells or intercellular junctions)
Transappendageal(hair follicles and glands) |
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Term
| Mechanism of drug absorption through the skin. What is fick's first law of diffusion? |
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Definition
dM/dt= (DKAdelta C)/h
dM/dt= steady state flux across stratum corneum
D- diffusion coefficient or diffusivity of drug molecules
K- partition coefficient of drug between the skin and formulation
delta C- drug concentration gradient across the stratum corneum
h= thickness of the stratum corneum |
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Term
| How do you find the flux of the solute? |
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Definition
Js= (Dm*Km delta c)/h
Js= flux of a solute
Km= partition coefficient between vehicle and skin
Dm- diffusion coefficient of drug in skin
h- membrane thickness |
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Term
| How do you find the permeability coefficient of drug in skin? |
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Definition
Pm=(Dm*Km)/h
Pm= permeability coefficient of drug in the skin
Dm= diffusion coefficient of drug in skin
Km= partition coefficient between vehicle and skin |
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Term
| Absorption of the drug is affected by: |
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Definition
Cs- concentration of drug in vehicle
h- thickness of barrier
D- mobility of drug molecule in the barrier
k- relative solubility of the drug
A- contact surface area of vehicle |
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Term
| General rules for diffusion through the skin |
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Definition
-small hydrophilic, polar molecules are rate-controlled by the stratum corneum
-small hydrophobic molecules are controlled by their partitioning from the stratum corneum into the lower epidermal layers
-diffusion decreases with increasing molecular size(limit about 1000 daltons)
- occluding the skin results in an increase in hydration of the stratum corneum and increase permeability
-damage destroys the barrier properties of the stratum corneum |
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Term
| What are physiological factors affecting transdermal F? |
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Definition
-stratum corneum
-anatomic site
-skin metabolism (cytochrome p450)
-skin hydration
-age: premature neonates (<30 weeks)
-desquamation (shedding) |
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Term
| What are formulations factors affecting trasdermal F? |
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Definition
-o/w partition coefficient of drug
-size and charge of drug
-contact time
-drug concentration
-active surface area of the transdermal delivery system
-penetration enhancers (surfactants) |
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Term
| Where is the highest site of drug permeation? Lowest? |
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Definition
highest- post auricular, then the back
the lowest is the thigh |
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Term
| what are methods to modify SC? |
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Definition
| hydration, chemical enhancers, thermal passive |
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Term
| What are passive (diffusions) method? |
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Definition
| Methods to modify SC (hydration, chemical enhancers, thermal passive) |
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Term
| What are sc poration methods |
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Definition
| mechanical or electrically-driven methods |
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Term
| What are electrically-driven methods? |
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Definition
| sonophoresis, thermal poration, radio frequency poration, ionophoresis, electroporation |
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Term
| what are mechanical methods? |
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Definition
| Microstructure array, SC removal, high velocity particles/liquids |
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Term
| What is the generally impermeable principle barrier of the skin? |
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Definition
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Term
| What part of a drug does the permeability of transdermal systems correlate to? |
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Definition
-water solubility
-Mw (size)
-oil/water partition coefficient |
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Term
| Transdermal systems are useful for which kinds of drugs? |
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Definition
-low dose requirement
-high skin permeability |
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Term
| Why do we use transdermal systems for systemic drug administration? |
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Definition
-bypass first-pass effect (eg estradiol)
-reduce side effects by more controlled release
-reduced inter-and intra-patient variability
-increased patient compliance with fewer dosing events- self-administration
-easy to apply and remove |
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Term
| What are marketed transdermal products? |
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Definition
scopolamine- antinausea
nitroglycerine-angina
clonidine- hypertension
fentanyl- analgesic
testosterone- cancer
nicotine- smoking cessation
estradiol- post-menapausal conditions
ethinyl estradiol/norelgestromin- contraception. |
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Term
| physiochemical and PK properties of transdermally administered drugs |
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Definition
1-octanol-water partition coefficients
2- total clearance
3-biological half-life
4- base form of the drug |
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Term
|
Definition
-lipophilic (moderately) drugs with low MW only
-potent drugs only (<10mg/day)
-drugs with short half-lives only
-atopic dermatitis @ the site of application is possible (by the drug or adhesive)
-Lag time to reach steady state (2-6 hours in some cases)
-skin damage due to adhesion (elderly)
-expensive
-excess drug content in patches (proper disposal) |
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Term
|
Definition
adhesive patches (SC regulates drug absorption)
reservoir (membrane) controlled system
matrix controlled system |
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