201 skin Flashcards

1
Q

what drugs can penetrate the skin

A

-intermediate partition coefficient (not too polar or non-polar)
-if weak acid or weak base, it should be unionized
-low molecular weight (<500)
-log p (1-3.5)
-high potency
- aqueous solubility (>100μg/ml)
-non-irritant to skin
-high permeability coefficient

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2
Q

what are different dosage forms in topical drug delivery

A

-creams (o/w or w/o)
-ointments (greasy, viscous)
-gels (aqueous)
-pastes (very viscous, contain undissolved solid)
-sprays
-dusting powders
-patches

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3
Q

how can we provide occlusivity

A
  • hydrophobic polymer (plaster, patch)
    -ointment (white soft paraffin)
    -w/o cream
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4
Q

what is microdialysis

A
  • use it to evaluate topical drug delivery
    -involves insertion of a dialysis tubing into skin
    -perfusate pump through tubing
    -drug molecules enter perfusate
    -analyisis
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5
Q

what are other methods of evaluating topical drug delivery

A

-tape stripping :layers of skin are removes using a tape
drug on tape removed with solvent and quantified
-physiological response: relies upon the drug having some form of physiological effect (vasodilation- laser droppler velocimetry used to monitor blood flow)
-franz-type diffusion cells (in vitro)- different skin membrane option (human, animal, synthetic)- samples removed and quantified (receptor fluid is aqueous and buffered at specific pH, co-solvents used, maintain at constant temperature 37C)

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6
Q

why is the transdermal route desirable

A

-avoids first pass metabolism
-controlled rate of drug delivery
-avoids GI problems
-can be administered by the patient
-favored by patients
-reduces dosage frequency

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7
Q

what are the challenges of topical drug delivery

A

-only potent drugs suitable
-drugs metabolized by skin
-unsuitable for irritant drugs
-more expensive to manufacture
-small volume of distribution required/ lag-time
-tolerance induced by plasma levels

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8
Q

how do we calculate the Kp (permeability coefficient)

A

log Kp= 0.71logP- 0.0061MW- 2.74
J=Kp*C (μg cm s)

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9
Q

how can we increase the number of drugs deliverable transdermaly

A

-formulation manipulation (switching to occlusive formulation or employing a cosolvent
-skin modification: penetration enhancers (increase rate of dissrupsion of permeant through the skin
disrupt the highly ordered multiple lamellar lipid arrangement
interact with intercellular properties
increase partitioning into the skin

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10
Q

what are the ideal propertied of enhancers

A

-non-toxic
-no pharmacological activity
-act rapidly reversibly
-compatible with drug and excipients
-cosmetically acceptable to patients

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11
Q

what are the ideal properties of adhesives

A

-non-irritant
-keep patch in place for the duration of treatment
-compatible with drug and excipients
-allow bathing but also removable

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12
Q

what are the ideal propertied of backing layer

A

-needs to be strong but permit multidirectional strech
-can be opaque or clear
-may be occlusive for shorter duration use but permeable for longer
-should not interact with drug or other excipients

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13
Q

what are the ideal properties of a liner

A

-should be easily removed by the patient
-polymeric or aluminum foil
-compatible with formulation
-usually occlusive to prevent loss of volatile adhesive components

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14
Q

what are the types of patches

A

-drug-in-adhesive patch
-drug-in-matrix patch (controlled release)
-rate-limiting membrane patch

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15
Q

what are the physical enhancement methods

A
  • electrocorporation (high voltage electrical current is applied to skin to create pores
    -sonophoresis (skin temperature increases, cavities and bubbles are created at corneocyte-lipid interface and this dirsupts the SC- ultrasound
    -micorneedles (create channels through the SC)
    -iontophoresis (involves use of low electric current to drive drugs across the SC), can work for neutral drugs by electroosmosis
    works best for cationic drugs because skin has negative charge
    -reverse iontophoresis: extract drugs/molecules from skin (both charges and uncharged molecules)- glucose monitoring
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16
Q

what are the functions of the skin

A

-protect against hear, injury, UV and infections
-regulation of body temperature
-retention/excretion of water
-sensory detection
-synthesis of essential molecules

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17
Q

what is the processes of keratinization

A

-s. basale : mitosis
-S.spinosum: cells become specialised
-s.granulosum: increased keratin and lipid production (organelle breakdown)
-s.lucidum: dead cells containing keratin filaments
-S.corneum: many layers of squamous cells containing keratin (waterproof)

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18
Q

what are the resident and the transient residents of the skin

A

-Resident: constantly found in microbiota, stable, not associated with infections
-transient: temporary, removed by washes, associated with opportunistic infections

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19
Q

why is skin a barrier for infections

A

-low pH
-low moisture content
-nutrient poor
-production of a range of antimicrobial molecules (antimicrobial peptides, lysozymes- phagocytose bacteria)
-constant exfoliation of cells
-microbiota residents prevent colonization
eg propionibacterium. acnes : release fatty acid (low pH)
staph.apidermis: inhibit s.aureus, induce keratinocytes to produce antimicrobial peptides

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20
Q

what can cause skin infections

A

-cuts
-alteration of normal microbiota (metabolic changes, antibiotic)
-co-infections

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21
Q

what are the virulence factors of S.aureus and strept. pyogenes? (both gram+)

A

-invade tissues (hyaluronidase: breaks down proteogycian)
-evade host defences (produce coagulase, neutralise AMPs)
-cause host damage (exfoliatins-skin separarion, toxic shock syndrome, enterotocins)
can cause impetigo
-strep.pyogenes: invade tissues (hyaluronidase)
evade host defences (M protein- evades phagocytosis)
exotoxins (streptolysis O and S- lyse RBC and neutrophils)
can cause non-bullous impetigo

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22
Q

what is bullous and non-bullous impetigo
what are the complication of impetigo

A

non-bullous: thin-walled vesicles that rupture quickly, leaking pus and becoming brownish crust
-bullous: larger fluid-filled blisters, their rupture leaves a thin flat yellow crust
-complications: scalded skin syndrome (exotoxins spread)
toxic shock syndrome (fever, hypotension, organ failure)

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23
Q

what is folliculitis

A

-bacterial infection of hair follicles
-deep foliculitis: infection spreads to dermis and hypodermis
furuncles: redness, swelling, tenderness, neutrophils are drawn to the infection site releasing pus. accumulation of pus is walled off the stop the spread
carbuncles: furuncle is not walled off, larger and harder areas of inflammation with fever

24
Q

what are streptococcal skin infections

A

-erysipelas: infection localised in epidermis and upper dermis
shiny light-red, inflamed swollen patches on defined area
fever and nausea
-cellulitis: deep dermis and subcutaneous adipose tissue
skin is dark-red/purple, warm, tense, oedematous, can spread along tendons and muscles
-necrotizing faciitis: bacteria damage the tissue and penetrate into subcutaneous tissue, destroy the tissue
release pyrogenic exotoxins (toxic shock syndrome)

25
Q

what is the treatment of bacterial skin infections

A

-topical hydrogen peroxide cream (impetigo): generate free radicals that destroy cell components
-topical antibiotics (fusidic acid or mupirocin) : inhibition of protein synthesis
-oral flucloxacilin: non-bullous, bullous impetigo, cellulitis, erysipelas
-intravenous cefuroxime or oral co-amoxiclav or oral clindamycin (severe complicated infections)

26
Q

what is the treatment of MRSA

A

-intravenous vancomycin or teicoplanin (non- beta lactam)
-linezolid

27
Q

what is cutaneous warts

A

-non-cancerous keratinocyte cell growth in basal layer of epidermis
-transmitted by contact or sexually
cutaneous wart formation:
HPV enter skin through cuts, infect basal cells of epidermis, encode proteins that act as oncogenes and stimulate cell division, keratinocytes cannot mature

28
Q

what is the treatment of warts

A

-topical salicylic acid: lyses epidermis and reduces thickness of warts
-cryotherapy using liquid nitrogen (nectoric destruction of keratinocyte infected keratinocyte
-topical podophyllotoxin cream (blocks cell division)
-topical imiquimod cream (immune stimulator)

29
Q

what is the treatment of herpesvirus infection

A

-topical acyclovir cream for recurrent infection (against viral DNA polymerase)
-systemic treatment required for buccal, vaginal herpes infection and shingles in neonital or immunosuppressed patients

30
Q

what are fungal skin infections and how do you treat them

A

-ringworm
-athlete’s foot
-treatment: imidazole cream (clotrimazole, miconazole) block the ergosterol synthesis
terbinafine cream: block ergosterol synthesis
griseofulvin cream: microtubule inhibitor

31
Q

what are the pharmacological actions of corticosteroids

A

-anti-inflammatory
-immunosuppressive
-antiproliferative
-vasoconstrictive

32
Q

what is the mechanism of action of TCS

A

Anti-inflammatory: inhibit phospholipase A so less arachidonic acid so less prostaglandin and leukotrienes
-inhibit COX so less production of prostaglandin
-increase expression of anti-inflammatory genes and indirectly inhibit inflammatory transcription factor such as NFkB
Anti-proliferative: increase lipocortin 1 so reduces keratinocytes proliferation and collagen synthesis in the epidermis and dermis
immunosuppressive: inhibits humoral factor involved in the inflammatory response as well as suppression of the maturation, differentiation and proliferation of immune cells
Vasoconstrictive: inhibit vasodilators, histamine, bradykinins and prostaglandin

33
Q

what are side effects of TCS

A

-atrophy
-striae
-rosacea
-telangiectasias
-purpura
systemic: hypertension
hyperglycemia
glaucoma
crushing syndrome

34
Q

what are the symptoms of topical steroid withdrawal syndrome

A

-intense redness
-stinging
-burning

35
Q

what is the pathophysiology of acne vulgaris

A

-over-production of 5α-reductase enzyme that converts testosterone to dihydrotestosterone
-DHT binds to receptors in sebaceous glands with higher affinity leading to hyperproliferation of follicular epidermis
-increased sebum production
-keratin and sebum clog inside the hair follicles and form comedomes
-open comedomes: black (oxidized by air)
-close comedomes: white (not oxidized)
-the blocked follicle ruptures and releases into dermis (inflammation)
-increased sebum production stimulates overgrowth of p.acne
-P.acne digest digest sebum and release fatty acids which exacerbates inflammation (cyst)
-

36
Q

what can trigger acne

A

-high glycaemic food
-a premenstrual flare up
-cosmetics and facial massage
-anxiety

37
Q

what is the treatment of acne

A
  • benzoyl peroxide (antibacterial, anti-inflammatory)
    -retinoids (anti-inflammatory, reduce sebum production, unclog blocked pores) eg. isotretinoin
    -antibiotics: topical-clindamycin or erythromycin
    oral: doxycycline +combined with retinoids and benzoyl peroxide
    -azelaic acid: inhibit 5α-reductase enzyme
38
Q

what is the pathophysiology of psoriasis

A

-many factors stimulate migration of T cells into dermis
-T cells release large amounts of inflammatory cytokines

39
Q

what is the treatment of psoriasis

A

-topical emollient (moisturize, relieve itching)
-topical salicylic acid
-topical vitamin D
-topical coal tar
-topical dithranol (reduce hyperproliferation)
-methotrexate (folic acid inhibitor, anti-inflammatory, immunosuppressive)
-ciclosporin (calcineurin inhibitor)

40
Q

what are the types of injuries

A

-superficial (epidermis)
-partial thickness (epidermis, dermis)
-full thickness (epidermis, dermis, fat, bone)

41
Q

what is the physiology of wound healing

A

-haemostasias (blood vessel vasoconstriction, formation of platelet plug, activation of coagulation cascade to form thrombus
-inflammation (hydrogen peroxide-antimicrobial activity, chemokines-recruit neutrophils-phagocytosis-enzymes, macrophages-growth factors, engulf dying neutrophils, activate fibroblasts, deposit extracellular matrix)
-proliferation (granulation: fibroblasts synthesize new ecm, angiogenesis: delivery of nutrients and maintenance of oxygen)
-remodeling: replacing collagen of granulation tissue with the synthesis of stronger collagen, macrophages break down excessive ECM and engulf ECM debris and apoptotic cells

42
Q

what factors affect healing

A

-blood flow
-infection
-age, gender
-stress
-sex hormones
-obesity

43
Q

what can cause chronic wounds

A

-diabetic ulcers
-pressure injuries
-venous stasis ulcer

44
Q

what is a biofilm

A

-community of microbial cells
-delay healing and cause chronic wounds
-potential to develop systemic infections
-drainage and removal of necrotic tissue to eradicate biofilms

45
Q

how do we manage wounds

A

-cleaning of the wounds
-removal of necrotic tissue
-infection prophylaxis
-wound dressing
-wound drainage
-skin grafts
-wound closure

46
Q

what are the ideal properties of wound dressings

A

-remove excessive exudate and maintain moisture
-allow gaseous exchange
-thermally insulating
-impermeable to microorganisms
-free from toxic substances/non-allergic
-avoid damaging the granulating tissue
-provide debridement action and enhance leucocyte migration
-maintain moist environment

47
Q

what are the types of wound dressing

A

-gauze (for infected wounds that require frequent dressing changes)
-transparent films (good for partial thickness wounds)
-foam (highly absorbent, use on draining)
-alginates (form a gel like material when they come in contact with exudate, highly absorbent)
-hydrocolloids (waterproof, swells with exudate)
-hydrogel (provide soothing, pain relieve, soften dry necrotic eschar
-antimicrobial dressing (lower pH, anti-inflammatory activity, stimulation of granulation, odour management and pain reduction)

48
Q

what is UV

A

-form of non-ionizing radiation
-UVA: longest wavelength, can pass through ozone and clouds,
penetrates deeper(dermis), responsible for aging, wrinkles and skin cancer
-UVB: intermediate wavelength, filtered by atmospheric conditions, can cause sunburn, redness, skin cancer and vitamin D synthesis
-UVC: shortest wavelength, doesn’t reach earth

49
Q

describe vitamin D synthesis

A

-UVB photons are absorbed by 7-dehydrocholesterol which is converted into pre–vitamin D3
-pre-vitamin D3 undergoes thermal isomerization to form vitamin D3 which reaches plasmatic peak
-vitamin D3 is converted by enzymes into 1α,25-dihyxyvitamin by two hydroxylation reactions
-keratinocytes can convert vitamin D3 into its active form calcitriol
-calcitriol acts as a hormone that regulates calcium intake in intestine, bones and kidney

50
Q

what skin conditions can vitamin D deficiency cause?

A

-skin cancer
-psoriasis
-skin dermatitis

51
Q

what is treatment of psoriasis

A

-phototherapy (narrowband UVB, psoralen with UVA)
mechanism: reduce cytokine production, immunosuppression effect, induction of apoptosis in keratinocytes, antipruritic effect

52
Q

what is skin cancer?

A

-uncontrolled cell division of cancerous cells, lose of cell differentiation
-risk factors: genetics, light skin, types of moles, long term sun exposure, history of childhood sunburns, frequent artificial tanning, levels of melatonin (can block UV photons and induce a more efficient DNA repair)
-Types: actinic keratosis (pre-cancerous), squamous cell carcinoma, basal cell carcinoma, melanoma (asymmetry, size, color, shape, bleeding)

53
Q

what is skin cancer initiation

A

-UVB: incorrect base pairing between non-complementary bases (mutations can distort DNA’s structure, introducing bends or breaks, impending transcription of crucial gene)
-UVA: DNA oxidation inducing base modifications and strand breaks

54
Q

what are the types of wounds

A

-pink (final stage of healing- epithelial cells, delicate)
-Red (bumpy tissue- new vasculature formed, granulation consists of collagen and elastin)
-yellow (dead cells that are sticking to the wound exudate)
-black (deal tissue caused by lack of blood supply, bacterial growth, needs removal)
-wounds with signs of infection (heat, erythema, swelling, fever, pus discharge, delayed healing)

55
Q

what are the types of wound dressings

A

-low adherence: used for low exudate epitheliasing or granulating wounds, prevent secondary dressing from direct contact with wound, eg. Jelonet (tule gras)- cotton with paraffin to help prevent adherence to the wound
-vapour permeable: allow water vapour and oxygen to permeate, often used as secondary dressing over absorbent dressings eg. opsite film dressing
-soft polymer: use for low or moderate exudate, subcategory used for hypertrophic or keloid scarring eg. cica-care
-hydrocolloid: hydrophilic colloidal particles on vapor permeable films, have adhesive border eg. duoderm
-foam: polyurethane foam with or without adhesive, require moisture to promote healing eg. biatain ibu is impregnated with ibuprofen eg. allevyn
-alginate: made of calcium alginate, used for heavy exudate, release calcium ions with facilate heamostasis, form gel when in contact with wound eg. sorbsan
-dressing for infected wounds: used for local wound infections,
honey, iodine, silver, polyhexanide eg. activon tulle