Pharmacology Flashcards
benefits of using topical drug admin?
for local effect and to treat underlying tissue etc.
benefits of using transdermal/subcutaenous deposit admin?
good for prolonged systemic effects
name a few epithelial routes of drug admin other than topical or transdermal/subcutaenous
- airways
- bladder
- conjunctival sac
- nasal mucosa
- rectum
- vagina
all good for local effects that minimise systemic absorption
name the most important layer in skin for skin defence?
stratum corneum
what is the stratum corneum?
- consists of layers of hard dead keratinocytes
- forms 10-30 sheets of tissue that consistently shed
describe the brick and mortar model reference in the stratnum corneum
- Bricks = corneocytes
- Mortar = intercellular lipids in lamellar structures
what are corneocytes?
hardened dead keratinocytes
where is the stratnum corneum located in the epidermis?
outermost layer of the epidermis
where are the keratin filaments of the corneocytes embedded into?
embedded in filarggrin matris surrounded by a conrified cell envelope
what holds the corneocytes together?
corneo-desmosomes
what is the mortar in the stratnum conreum?
- liquid layer
- has multiple bilayers of lamellar intracellular lipids
- can act as a resovoir for drugs
- incredibly hydrophobic
- liquid itself contains ceramides, cholesterol, free fatty acids etc.
what do drugs need for both local and systemic effects to work effectively?
be able to move through the stratnum corneum
how do most drugs move through the stratnum corneum?
- via intercellular route
- rely on molecules being small and hydrophobic
what law calculates how easily a drug is absorbed?
FIck’s law
Give the drug absorption equation
J (for john peters) = permability coefficient (K) X concetration of drug in medicine
what is the permeability coeffcient (K)?
basically involves what the drug is like and what the barrier contains
what is J in the drug absorption equation?
rate of absorption
give the rate of absorption equation
- J = rate of absoprtion
- Km = partition coefficient
- D = diffusion coefficient
- L = length of diffusion pathway
- Cv = concentration of drug in the vehicle
what is the best combination of frug solubility for absorption?
- hydrophobic (lipophilic) drug in a hydrophilic base
- best for absorption as it moves preferntially in to the skin
what is the distribution of a hydrophobic (lipophilic) drug in a lipophilic base?
- drug can move through the skin but will equal out between the skin and the blood vessels
what occurs when you have a hydrophilic drug in a hydrophobic (lipophilic) base?
the two dont dissolve into eachother
- so the drug partions only into the stratum corneum (weakly)
- as the drug has limited solubility in both the vehicle AND the skin
why is a lipophilic (hydrophobic) drug in a hydrophilic base beneficial?
drug is more soluble in the skin and preferentially partitions into it
describe the solubility of a lipophilic (hydrophobic) drug in a lipophilic (hydrophobic) base?
drug is soluble in both vehicle (blood vessels) and skin so partitions between the two
describe what happens to a hyrophilic drug in a hydrophilic base on the skin?
- soluble in vehicle but not skin so remains on the surface of it
why does a hydrophobic drug work so well in a hydrophilic base?
because a hydrophobic drug can make its way through the hyrophobic stratum corneum but wont bind to the base itself
why are excipients added to drugs?
so the drug correctly dissolves into the liquid vehicle to make it through the skin
give examples of vehicles for drugs?
- lotions
- creams
- ointments
- gels
- pastes
- powders
what is the function of an excipient?
- enhance the solubility of the drug in the vehicle
- therefore enhance absorption
- the excipients are compounds that will sit in patches and convert undissolved into soluble drug to move across skin
- allow a constant drug flow to occur
give an exmple of an excipient
propylene glycol
what is the partiton coefficient?
- concept for drugs to move in well they need to partition into the stratum conreum and enter the deeper layers of the skin
- physical and chemical barriers of the skin help with this
what is one factor that increases the partition coefficient?
Hydrated skin
- allows hydrophilic base to settle into the skin better
- can be done through addition of a good hydrating vehicle e.g. ointment
- cling film will also help as it prevents water loss through exaporation
how can increased partition be achieved by the skin itself?
reduction in the barrier function of the stratum corneum
does location of application affect drug potency?
yes
- e.g. steroid on sctorum will be far more potent than on the nail bed
list some factors that may affect absorption of topically applied drugs?
- hydration of skin
- integrity of epidermis (moist/weeping vs. normal)
- hair vs dry vs damages moist skin etc.
- drug salt matters (some are more powerful than others)
- some drugs more soluble in ointment than a cream (drug vehicle matters)
what can long term use of high potency steroids result in?
- steroid rebound
- skin atrophy
- systemic effects
- spread of infection
- steroid roasacea
- production of stretch marks
- superficial blood vessels
what is transdermal drug delivery?
- drugs penetrate through stratum corneum, epideris and dermis into systemic circulation
- then delivered throughout the body to the site of action
name the 4 features of a suitable drug for transdermal drug delivery?
- low molecular weight
- lipophilic/hydrophobic
- potent
- relatively brief half life
give advantages of transdermal drug delivery
- steady state of drug delivery
- decreased dosing frequency
- avoidance of first-pass metabolism
- rapid termination of action
disadvantages of transdermal drug delivery (TDD)?
- relatively few drugs are suitable for this administration route
give examples of TDD drugs?
- nicotine
- GTN
- fnetanyl
- oestradiol
what can be incorporated into the TDD’s?
- strain of chemicals that can be used to make the stratum conreum more permeable
- makes it cheaper to administer some drugs
- can be incorporated into TDD’s
- can also be toxic for the skin and not effectuve for some soluble drugs
why is the skin good for drug administration?
- simple to apply
- steady state plasma conc.
- avoids first-pass metabolism
- can be terminated rapidly because you can just wipe it off
why is first-pass metabolism avoidance a good thing?
first-pass metabolism means that only a proportion of the drug reaches circulation due to it passing through portal vein into liver
