b10ph01 - dermatologic pharmacology
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Block X | Pharmacology | Lesson 1Dermatologic PharmacologyMyrna L. Abello, MD, Ed.D.SGD 4CSeptember 18, 2015
DERMATOLOGIC PHARMACOLOGY
Drugs used in the treatment of the skin can be:1. Delivered Systemically
o Gets into the system2. Applied Topically
o Apply to site where the drug is wanted to act
3. Injected Directly to the Dermis4. Phototherapy-Ultraviolet Radiation
PHARMACOLOGICAL RESPONSE DETERMINED BY:
1. Regional variation in drug penetration Areas in the body are more permeable and may
require less drug for equivalent effect Examples: scrotum, face, axilla and scalp >
forearm (in terms of permeability)
2. Concentration Gradient An increase in concentration gradient increases
the mass of the drug transferred per unit time Example: Resistance to corticosteroids can
sometimes be overcome by use of higher concentrations of drug
3. Dosing schedule “Local Half-life” may be long enough to permit
once daily application with short systemic half-lives
Example: steroids (given once a day) is as effective as multiple applications in many conditions
4. Vehicles & Occlusion An appropriate vehicle maximizes the ability of
the drug to penetrate the outer layers of the skino Vehicles may themselves have important
therapeutic effects Occlusion (plastic wrap to hold drug and vehicle
to skin)
SGD 4C| GANZON, JUMAWAN, PINEDA, UDDIN Page 1 of 10
SUMMARY/OUTLINEI. Dermatologic PharmacologyII. Pharmacological ResponseIII. AbsorptionIV. Choice of a VehicleV. Topical ApplicationVI. Glucocorticoids
a. Anti-Inflammatory Effects b. 7 Classesc. Principles in the use of Steroidsd. Adverse Effects
VII. Systemic GlucocorticoidsA. Adverse Effects
VIII. Tar CompoundsIX. Topical Antibacterial Agents
A. BACITRACINB. GRAMICIDINC. MUPIROCIND.RETAPAMULINE. POLYMYXIN B SULFATEF. NEOMYCING. GENTAMICIN
X. Topical Antibiotic in AcneA. CLINDAMYCINB. ERYTHROMYCINC. METRONIDAZOLED. TETRACYCLINE. SODIUM SULFACETAMIDE
XI. Acne PreparationsA. RETENOIC ACIDB. ISOTRETINOINC. ETRITINATE
XII. Anti-Pruritic AgentsA. DOXEPINB. PRAMOXINE
XIII. Anti-histaminesA. OLDER H1 RECEPTOR ANTAGONISTSB. NEWER H1 RECEPTOR ANTAGONISTSC. H2 RECEPTOR BLOCKERS
XIV. Agents Affecting PigmentationA. HYDROQUINONE & MONOBENZONEB. HYDROQUINONE C. MONOBENZONE D. GLUTATHIONEE. POLYPHENOLIC-GLUTATHION (GSH)
XV. SunscreensXVI. Keratolytic Agents
Block X |PHARMACOLOGY | Lesson 1Dermatologic Pharmacology
o Extremely effective in maximizing efficacy
5. State of the stratum corneum Topical absorption increased in dermatologic
disorders due to the presence of breaks/lesions in the skin
6. Presence of “Penetration Enhancers” Examples: Organic solvents such as dimethyl
sulfoxide (DMSO), urea, salicylic acido Added to the drug for better penetration
ABSORPTION CONTROLLED BY:
1. Concentration of drug in the vehicle Rate of diffusion is proportional to concentration The higher the concentration, the more effective
it is
2. The partition coefficient of drug between the stratum corneum and the vehicle Partition coefficient is the Drug’s ability to escape
from the vehicle Application of topical preparation is incorporated
into a vehicle and will take time for the drug to get out of vehicle and exert its effect
Increased lipid-solubility favors penetration through the skin in the relatively lipophilic stratum corneum
3. Diffusion coefficient of the drug in the stratum corneum Refers to the extent to which the matrix of the
barrier restricts the mobility of the drug An Increase in the molecular size of the drug will
decrease the diffusion coefficient. Drugs with greater molecular size, would cross
the membrane with difficulty while drugs with smaller molecular size will cross the membrane with ease
CHOICE OF A VEHICLE
A vehicle is any of various media acting usually as solvents, carriers, or binders for active ingredients.
A. Acute inflammation with oozing, vesiculation & crusting
Best treated with drying preparations (e.g. Tinctures, Wet dressings, lotions)
Lotions & Solutions are ideal for hairy & intertriginous areas
Choice of vehicle will depend on the type of lesion
B. Chronic Inflammation with xerosis, scaling & lichenification
Best treated with more lubricating preparations (e.g. Creams or Ointments)
Creamo Most acceptable and common
preparationo Safer to use if in doubt if lesion is wet or
dry o Emulsion of oil and water
Ointmento Most effective hydrating agentso Greasy & often undesirable (oleaginous
base e.g. petrolatum, mineral oil)
HOW MUCH TO APPLY?
“Fingertip Unit” (FTU)o Amount of ointment when squeezed out of a
tube to the palmar aspect of the index finger from the distal skin crease to the end of the finger
o Sort of an estimateo Approximate Value
- Males: 0.47g
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TRIVIA: 282 sq. cm. when spread on skin
approximately area covered by 2 hands2 FTU 4 hand areas
FACE & NECK 2.5 FTU (1.3g)
FRONT OF TRUNK 7 FTU (3.5g)
ONE ARM 3 FTU (1.5g)
ONE HAND (FRONT AND BACK)
1 FTU (0.5g)
ONE LEG 6 FTU (3.0g)
Block X |PHARMACOLOGY | Lesson 1Dermatologic Pharmacology
- Females: 0.42g- Generally rounded off to 0.50g or 1/2 g
TOPICAL GLUCOCORTICOIDS
Known as steroids in laymen’s term Therapeutic effectiveness based primarily on their
anti-inflammatory activity Antimitotic activity on human epidermis may account
for additional mechanism of action in psoriasisMechanism of Action:All natural and synthetic glucocorticoids act by:
ANTI-INFLAMMATORY EFFECTS OF GLUCOCORTICOIDS/STEROIDS
Decreased production of prostaglandins, cytokines & interleukins
o Inhibit synthesis of these substances which are called autacoids
Decreased proliferation & migration of lymphocytes & macrophageso By the inhibition of accumulation of neutrophils
and monocytes at the site of inflammation
7 CLASSES OF TOPICAL GLUCOCORTICOIDS
1. Betamethasone 0.05% Diproprionate (Diprolene®) in optimized vehicle (ointment, cream etc)
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Block X |PHARMACOLOGY | Lesson 1Dermatologic Pharmacology
Clobetasol Propionate (Temovate®) 0.05%- Highest efficacy, most potent
2. Amcinonide ointment 0.1% (Cyclocort®)Betamethasone Dipropionate ointment 0.05% (Diprosone®)
- High efficacy
3. Betamethasone Dipropionate Cream 0.05%Betamethasone Valerate Ointment 0.1% (Valisone®)
- Intermediate efficacy
4. Fluocinolone Acetonide Cream 0.025% (Synalar®) Triamcinolone Acetonide Ointment 0.9% (Kenalog®)
- Low efficacy
5. Betamethasone Dipropionate Lotion 0.05% (Diprosone®)
6. Aclomethasone Dipropionate Cream, Ointment 0.05% (Aclovate®)
- Low efficacy
7. Dexamethasone Sodium Phosphate Cream 0.1% (Decadron®)Hydrocortisone Cream, Ointment, Lotion 0.5% 1%, 2.5% (Hytone, Nutracort, Penicort)
- Lowest efficacy- Least potent
Class 1 – Most Potent Class 7 – Least Potent Important since there are instances when we
need a high or low efficacy drugs
PRINCIPLES IN THE USE OF STEROIDS
Steroid to be used chosen on basis of potency, site of involvement &severity
o Face is easy to penetrate so we use dose with lesser efficacy
Often a more potent steroid is used initially- Class 1 Twice-a-day application is sufficient; more frequent
application does not improve responseo There is such a thing as half-life and it will stay
there for a certain period of time
ADVERSE EFFECTS Usually, the adverse effects may be found topically but
our problem with adverse effects is those that are absorbed into the system. As much as possible, we would not want them to be absorbed in the system
All absorbable topical corticosteroids possess the potential to suppress the pituitary-adrenal axis
o “See-saw effect”o From local application, they can be absorbed
into the system
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Block X |PHARMACOLOGY | Lesson 1Dermatologic Pharmacology
Applying potent corticosteroid to extensive areas of the body for prolonged periods increases the likelihood of systemic effects
Children more susceptible & growth retardation is a concern
o Results to early closure of long boneso Be more careful when dealing with children
and steroids Adverse local effects:
o Usually occurs when applying topical steroids
o Atrophy- Present as depressed, shiny, often
wrinkled “Cigarette Paper”- appearing skin with prominent
telangiectasia- Occurs in the site of application
A tendency to develop purpura & ecchymosis (aka Steroid Rosacea)
o Persistent erythema, telangiectatic vessels, pustules, & papules in central facial distribution; Perioral dermatitis, steroid acne
Alterations of cutaneous infections, hypopigmentation, hypertrichosis, increased intraocular pressure, & allergic contact dermatitis
Intralesional glucocorticoids can cause cutaneous atrophy & hypopigmentation
o They are not very safe drugs
SYSTEMIC GLUCOCORTICOIDS Systemic: absorbed in the system
Reserve for acute treatment of transient illnesses or life-threatening dermatoses
Fewer side effects with every other day dosing & prednisone tapered to every other day ASAP
o e.g. Daily dose of 3x a day then reduce to 2x a day, then to once a day, to every other day
o Reason: reduced gradually for less adverse effects for withdrawal, and to prevent ADRENAL CRISIS
ADVERSE EFFECTS: SYSTEMIC GLUCOCORTICOIDS Short Term Oral
o Psychiatric problems, cataracts, myopathy, avascular necrosis, hypertension
Pulsed IVo Intravenous administration of steroidso Hypo or hypertension, hypo or hyperkalemia,
anaphylactic reaction, acute psychosis, seizures,& sudden death
“If we can avoid them, we avoid them.”
TAR COMPOUNDS Used mainly for the treatment of psoriasis, dermatitis
& lichen simplex chronicus Has Antipruritic properties (due to phenolic
constituents) Acute dermatitis may be irritated by even a weak
preparation (Contraindicated) Useful in sub-acute and chronic dermatitis and
psoriasisADVERSE EFFECTS: irritant folliculitis, photoirritation,
allergic contact dermatitis
TOPICAL ANTIBACTERIAL AGENTS Not recommended because of possibility of
sensitization Not given systemically due to many side effects Sensitization - main cause of the discontinuation of
certain drug practiceso e.g. use of sulaminamide, applying penicillin to
open wounds, discontinue of usage of antihistaminic drugs
BACITRACIN & GRAMICIDIN Gram (+) organisms, streptococcus, pneumococcus &
staphylococcus Not used systemically because they are toxic MOA: inhibits cell wall synthesis Sensitization low in therapeutic concentrations
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Block X |PHARMACOLOGY | Lesson 1Dermatologic Pharmacology
Most anaerobic cocci, Neisseriae, Tetanus bacilli, Diphtheria bacteria are sensitive
A. BACITRACIN Compounded in ointment base alone or with
neomycin, polymyxin B or both (aka BNP ointment) Microbial resistance may develop after prolonged use Side Effects: Contact urticaria, anaphylaxis, systemic
toxicity (rare), contact dermatitis (frequent) was isolated from a girl named Tracy very harmful antibiotics in a sense that they have side-
effects that’s why they’re only given locally and not systemically..
B.GRAMICIDIN Combined with neomycin, polymyxin, bacitracin,
nystatin Available only for topical use Neomycin is an aminoglycoside
o Side Effects: Nephrotoxic, Ototoxic, Neuromuscular defects
o Sensitization is low in therapeutic concentration
o Also used as antiseptic in surgery because aminoglycosides are not absorbed in GI tract and stay in GI canal to disinfect area
C.MUPIROCIN (Bactroban®) Relatively new drug Effective against most Gram (+) aerobic bacteria
including MRSA Effective in impetigo caused by S. Aureus & Group A
Beta Hemolytic Strepo Used to treat Impetigo contagiosa specificallyo Mercury was the former treatment but is now
known to be toxic and bannedo E.g. mercurechrome and merthiolate
Not appreciably absorbed systemically on intact skin Not absorbed systemically is preferred for topical
drugs
D. RETAPAMULIN New synthetic drug, newer than mupirocin Semisynthetic drug derived from pleuromutilin Effective in treatment of uncomplicated superficial
skin infection caused by Grp. A beta-hemolytic strep and S. aureus excluding MRSA for adult and pediatric patients 9 months and older
E. POLYMYXIN B SULFATE Mixed with drugs mentioned earlier Peptide antibody effective against Gram (-) organism
including P. Aeruginosa, E. Coli, Enterobacter & Klebsiella
Also effective with Proteus, Serratia, Gm (+) resistant species (Katzung: they are resistant)
MOA: Act on cell membrane. Toxic because the normal cell membrane will be affected
Not to exceed 200mg when applied to denuded skin o Causes neurotoxicity and nephrotoxicity
Hypersensitivity is uncommon because it is not usually used
F. NEOMYCIN Aminoglycoside Gm (-) including E. Coli, Proteus, Klebsiella &
Enterobacter MOA: inhibits CHON synthesis Available in topical formulation Rarely detectable in serum concentrations In presence of renal failure, it accumulates and results
in neurotoxicity, nephrotoxicity and ototoxicity, neuromuscular blockage
o Adverse effects of aminoglycosides in general Sensitization in eczematoid dermatitis Cross sensitivity to streptomycin, kanamycin,
paromomycin and gentamicin (other aminoglycosides)o Cross-sensitivity means that even if an individual
has not been exposed to these drugs, he may still develop allergies to other related drugs (same family and structure)
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Block X |PHARMACOLOGY | Lesson 1Dermatologic Pharmacology
o If the patient is allergic to one aminoglycoside, avoid administering other aminoglycosides
G. GENTAMICIN Aminoglycoside, narrow spectrum antibiotic for Gram
Negative Greater activity against pseudomonas More active against Staph & Group A Beta Hemolytic
Streptococci Used systemically, not topically Widespread topical use should be avoided
o Produces gentamicin resistant strain Serum concentration of 1-8 µg Accumulation in renal failure
o Results to Neurotoxicity, nephrotoxiciy and ototoxicity, neuromuscular blockage
Discouraged use for topical use to limit/prevent resistance since it is a potent broad-spectrum antibacterial drug
Avoid topical use as much as possible unlike in neomycin which can be used topically
TOPICAL ANTIBIOTIC IN ACNE Effectiveness of topical formulation is less than
systemic. For mild to moderate cases only. Systemic antibiotics to be used for severe cases Blast from the past: A plant called “earrings” (plant
with violet flowers) was said to be effective against acne. Not studied yet.
A. CLINDAMYCIN Very effective drug Approximately 10% absorbed. May cause rare cases
of bloody diarrhea & pseudomembranous colitis when absorbed systemically
Known commercially as (Dalacin C®) which is mixed in products such as Eskinol
Increased chance of systemic absorption and associated side effects with the use of Eskinol daily
Water based gel vehicle well-tolerated
“Not a good practice to use it left and right.”
B. ERYTHROMYCIN Used systemically; broad-spectrum antibiotic Avoid topical use as much as possible Inhibitory effect on P. Acnes Complication: Development of Resistant strains of
Stapho Correlated with the use of the topical formo If this occurs, topical form should be
discontinued and systemic therapy started Side Effects: Burning, drying, irritation Prescribed in patients allergic to penicillin. Reserved
for special cases
C. METRONIDAZOLE Topical Gel effective in acne rosacea Drug of choice (DOC) for Amoebiasis MOA: UNKNOWN but may relate to the inhibitory
effects on Demodex brevis (face mite) Oral form is carcinogenic in rats
o Main reason why we avoid giving topical use in pregnant women
Side Effect :Drying, Burning, Stinging Caution when applying near eye Not allowed for pregnant women
D. TETRACYCLINE Tetracyline HCl in a hydroalcoholic base containing N-
Decyl Methyl Sulfoxide Meclocycline sulfosalicylate in a cream base No demonstrable absorption when applied twice daily Inhibitory action on P. Acnes Side effect: Staining of teeth and bones No longer recommended today, just mentioned in the
discussion for history’s sake Used to be a popular drug for acne According to Katzung, it is no longer mentioned for
treating acne but other books say otherwise. Dr. Abello also states that it is still effective
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Block X |PHARMACOLOGY | Lesson 1Dermatologic Pharmacology
E. SODIUM SULFACETAMIDE Available as a 10% lotion (Klaron) & as 10% wash
(Ovace) combined with sulfur in the treatment of acne vulgaris & acne rosacea
MOA: Inhibition of P. Acnes by competitive inhibition of PABA utilization
Approximately 4% is absorbed percutaneously Contraindicated in patients sensitive to sulfonamides
ACNE PREPARATIONS Very popular nowadays
A. RETINOIC ACID Topically applied Remains in the epidermis with less than 10% systemic
absorption Action in acne is attributed to decreased cohesion
between epidermal cells and increased epidermal cell turnover
Results in expulsion of open comedones Efficacious
B. ISOTRETINOIN For severe cystic acne Recalcitrant to standard therapy MOA: inhibit sebaceous gland size & function Adverse effects: Similar to hypervitaminosis A
o Highly teratogenico Should not administer in pregnant womeno Stopped 6 months before pregnancy
C. ETRETINATE Still a Vitamin A/retinoid Treatment of psoriasis especially pustular forms Given orally 1-5mg/kg/day starting with 0.5mg Adverse effects: Similar to hypervitaminosis A
o Should not be taken by women of childbearing age
o More teratogenic than other vitamin A preparations
ANTIPRURITIC AGENTSFor itchiness, we administer anesthetics or
antihistaminicsAvoid antihistaminics locally because we expose the
individual to development of sensitization
A. DOXEPIN MOA: H1 & H2 antagonists property percutaneous
absorption Can cause drowsiness like other antihistamines Contraindications: Narrow angle glaucoma Tend to cause urinary retention because of
anticholinergic effects Drug must be discontinued 2 weeks prior to use
when patient uses Monoamine oxidase inhibitor (MAOi)o Doxepin enhances action of MAOi
B. PRAMOXINE Topical anesthetic available as 1% Cream, Lotion, Gel Applied 2-4x a day Adverse effect: transient burning and stinging
ANTIHISTAMINESA. OLDER H1 RECEPTOR ANTAGONISTS 1st generation antihistaminics Have some Anticholinergic activity Are sedating because they can cross the blood-brain
barrier. Advise patients taking antihistamines to avoid driving
or operating machineries as these drugs could cause sedation and drowsiness.
B. NEWER H1 RECEPTOR ANTAGONISTS Have lesser side-effects because they do not cross
the blood brain barrier Generally do not cause drowsiness/sedation Examples:
a.Terfenadineb.Astemizolec. Loratadine
C. H2 RECEPTOR BLOCKERSPage 8 of 10
“THEY SAY THAT BEAUTY IS IN THE EYE OF THE BEHOLDER & I SAY THAT THE
MOST LIBERATING THING ABOUT IT IS REALIZING YOU ARE THE BEHOLDER. THIS
EMPOWERS YOU TO FIND BEAUTY IN PLACES WHERE OTHERS HAVE NOT
DARED TO LOOK, INCLUDING INSIDE OURSELVES.”
MYRNA L. ABELLO, M.D., ED.D.
Block X |PHARMACOLOGY | Lesson 1Dermatologic Pharmacology
Better used for patients with peptic ulcero Decreases gastric acid secretiono Examples
i. Cimetidine- enzyme inhibitor- Problem: inhibits cytochrome P450
which inhibits drug metabolizing enzyme causing increased effect sensitive to these enzymes
ii. Ranitidineiii. Famotidineiv. Nizatidine
AGENTS AFFECTING PIGMENTATIONA. HYDROQUINONE & MONOBENZONE
Appears to involve inhibition of the enzyme tyrosinase thus interfering with the synthesis of melanino E.g. Michael Jackson (MJ) who had irreversible
depigmentation leading to VITILIGO Do patch test prior to administration
o For local irritation/ allergic sensitizationHYDROQUINONE Causes temporary lightening Found in lightening agents
MONOBENZONE (Most likely what MJ used) Causes irreversible depigmentation TRIOXSALEN & METHOXSALEN
o Psoralens used for repigmentation of depigmented molecules of vitiligo
o Intercalate with DNA – inhibit DNA synthesiso Major Risks:
- Cataracts- Skin Cancer
B. GLUTATHIONE not among the whitening agents listed in
pharmacologic books, just included because of its increasing popularity
Principal intracellular non-protein thiol
Plays major role in maintenance of intracellular redox state
very important and useful
C. POLYPHENOLIC-GLUTATHIONE (GSH) Reduced glutathione Conjugates and their metabolites retain the
electrophilic and redox properties of the parent polyphenol
The reactivity of thioether metabolites exceed that of the parent polyphenol
Contribute to the Nephrotoxicity, Nephrocarcinogenicity& Neurotoxicity of a variety of polyphenols
Side effects:o
Allergic
reactionso Zinc deficiency after long periods of useo Skin whitening observed when taken in high
doses- Made possible as antioxidant that aids in
cell regeneration & counteracts free radicals
SUNSCREENS Topical agents useful in protecting against sunlight
A. PABA (Para-AminoBenzoic Acid) & its esters (Benzophenones, Dibenzoyl Methanes)
Absorb UV light in UV B wavelength 280 – 320 nm (range for erythema & tan)
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Take note: When drugs are applied topically, the person has more tendency
to develop hypersensitivity.
Hypersensitivity is more likely to develop with use of topical drugs.
Block X |PHARMACOLOGY | Lesson 1Dermatologic Pharmacology
B. SPF (Sun Protection Factor) For light skin: SPF 15 or more For dark skin: SPF 10-15
KERATOLYTIC AGENTS
A. SALICYCLIC ACID Solubilize cell-surface proteins that keep the
stratum corneum intact, resulting in desquamation of keratotic disorders
Keratolytic in concentrations of 3-6% Used in the treatment of warts Care should be practiced when used in patients
with diabetes “mantica de papel”
o Indication: warts removalo MOA: Contains salicylic acid which burns
warts
REFERENCES:
Katzung, BG, Masters, SB and AJ Trevor. 2012. Basic and Clinical Pharmacology. 12th Edition. USA:McGraw-Hill, Chapter 61, p 1061-1079.Excelsior. 2014. Dermatologic Pharmacology Handouts.Abello, ML. 2015. Dermatologic Pharmacology Lecture. September 18, 2015.
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