CONTENTS

1. Title:Dermatologic%20Pharmacology
1
DermatologicPharmacology
 Munir Gharaibeh,MD, PhD,MHPE
 Facultyof Medicine,The Universityof Jordan
 March, 2014
2
DermatologicPharmacology
 VariablesaffectingPharmacologicResponse
 Regional variationindrugpenetration.
 Concentrationgradient.
 Dosingschedule.
 Vehiclesandocclusion.

3
PercutaneousAbsorption.
4
Skinas a pharmacological target
5
DermatologicFormulations
 Tinctures.
 Wet dressings.
 Lotions.
 Gels.
 Powders.
 Pastes.

2.  Creams.
 Ointments.
6
Adverse Effectsof DermatologicPreparations
 Burningor stingingsensation.
 Dryingand irritation
 Pruritus.
 Erythema.
 Sensitization.
 Staining
 Superficial erosion.
7
Topical Antibacterial Agents
 Bacitracin.
 Gramicidin.
 Gram-positive bacteria.
 PolymyxinB
 Neomycin.
 Gentamicin.
 Gram-negative bacteria.
8
Topical AntibacterialsinAcne
 Clindamycin.
 10 absorbed,so,possibilityof Pseudomembranous
colitis.

3.  Erythromycin.
 Metronidazole.
 Sodiumsulfacetamide.
9
Topical Antifungal Agents
 Azole Derivatives
 Clotrimazole
 Econazole.
 Ketoconazole.
 Miconazole.
 Oxiconazole.
 Sulconazole.
 Activityagainstdermatophytes(epidermophton,
microsporum,andtrichophton) andyeasts,
includingCandidaalbicans andPityrosporum
orbiculare.
10
Topical Antifungal Agents
 Ciclopirox Olamine.
 NaftifineandTerbinafine.
 Tolnaftate.
 NystatinandAmphotericinB
 OnlyforCandidaalbicans.
 Available astopical preparations,oral
suspension,orvaginal tablets

4. 11
Oral Antifungal Agents
 Azole Derivatives
 Fluconazole.
 Itraconazole.
 Ketoconazole.
 Affectthe permeabilityof fungal cell membrane
throughalterationof sterol synthesis.
 Effective insystemicmycosis,mucocutaneous
candidiasis,andothercutaneousinfections.
 Might have systemicside effectshepatitisand
liverenzyme elevations,andinteractions.
12
Oral Antifungal Agents
 Azole Derivatives.
 Griseofulvin
 Effective againstepidermophyton,microsporum,
and trichophton.
 Requiresprolongedtreatment
 4-6 weeksforthe scalp.
 6 monthsforfingernails.
 8-18 monthsfor toenails.
 Has many side effects.
 Terbinafine
 Recommendedforonchomycosis.
 6 weeksforfingernails.
 12 weeksfortoenails.

5. 13
Topical Antiviral Agents
 Acyclovir.
 Valacyclovir.
 Penciclovir.
 Famciclovir.
 Syntheticguanine analogswithinhibitory
activityagainstherpesviruses.
 Ointmentsandcreamsare useful forrecurrent
orolabial herpessimplex infection
14
Immunomodulators
 Imiquimod
 For external genitalandperianal warts.
 Actinickeratosisonthe face and scalp.
 Primarybasal cell carcinoma.
 Stimulatesperipheral mononuclearcellsto
release interferon- ?andto stimulate
macrophagestoproduce interleukins-1,-6,and-8
and tumornecrosisfactor-?.
 Tacrolimus.
 Pimecrolimus.
 Useful foratopicdermatitis.
 InhibitT-lymphocyte activationandprevent
release of inflammatorycytokinesandmastcell
mediators
15
Ectoparasiticides

6.  Permethrin
 Toxicto Pediculushumanus,Pthiruspubis,and
Sarcoptesscabiei
 Pediculosiscreamappliedfor10 minutesand
thenrinsedoff withwarmwater.
 Scabiescreamappliedforthe whole bodyfor
8-14 hours.
 Lindane(Hexachlorocyclohexane)
 10 absorbedandconcentratedinfattytissues.
 Can cause neurotoxicityandhematoxicity
 Crotamiton.
 Sulfur.
 Malathion.
16
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historyof severe pubicitchthatwas worstat
night
Cho S andKimH. N Engl J Med
2009360e11
17
AgentsaffectingPigmentation
 Hydroquinone.
 Monobenzone.
 Mequinol
 Reduce hyperpigmentationof skinbyinhibiting
the enzyme tyrosinase whichwillinterferewith
biosynthesisof melanin.
 Monobenzone maybe toxictomelanocytesresulting
inpermanentdepigmentation.

7. 18
AgentsaffectingPigmentation
 Trioxsalen.
 Methoxsalen.
 Are psoralensusedforthe repigmentationof
depigmentedmaculesof vitiligo.
 Must be photoactivatedbylong-wave-length
ultravioletlight(320-400nm) to produce a
beneficial effect.
 Theyintercalate withDNA.
 Can cause cataract and skincancer.
19
SunscreensandSunshades
 SunscreensabsorbUV light.
 Examplesare para aminobenzoicacid(PABA) and
itsesters.
 Sunshadesare opaque materialsthatreflect
light,like titaniumdioxide.
 Useful inpolymorphouslighteruption,lupus
erythematosus, anddruginducedphotosensitivity.
20
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23
Acne Preparations
 RetinoicAcidandDerivatives

8.  RetinoicAcid( Tretinoin) isthe acidformof
VitaminA.Stabilizeslysosomes,increasesRNA
polymerase activity,increasesPGE2,cAMP,and
cGMP levels,andincreasesthe incorporationof
thymidine intoDNA.
 Decreasescohesionbetweenepidermal cellsand
increasesepidermal cellturnover.Thiswill
resultinexpulsionof opencomedonesandthe
transformationof closedcomedonesintoopen
ones.
 Also,promotesdermal collagensynthesis,new
bloodvessel formation,andthickeningof the
epidermis,whichhelpsdiminishfinelinesand
wrinkles.
 Can cause erythemaanddryness.
 Tumerogenicin animals
24
Acne Preparations
 Isotretinoin( Accutane)
 Restrictedforsevere cysticacne resistantto
standardtreatment.
 Inhibitssebaceousglandsize andfunction.
 Givenorally.
 Toxicdryness,itching,headache,corneal
opacities,pseudotumorcerebri,inflammatory
bowel disease,anorexia,alopecia,andmuscle and
jointpains.Alsolipidabnormalities.
 Teratogenicity
25
Acne Preparations
 Benzoyl Peroxide

9.  Penetratesthe stratumcorneumorfollicular
openingsandconvertedtobenzoicacidwithin the
epidermisanddermis.
 Has antimicrobial activityagainstP.acnesand
peelingandcomedolyticeffects.
 Can be combinedwitherythromycinorclindamycin.
 Potentcontact sensitizer.
 Can cause bleachingof hairor coloredfabrics.
 AzelaicAcid
 Has antimicrobial activityandinhibits
conversionof testosterone todihydrotetosterone.
26
Drugs forPsoriasis
 Acitretin
 Relatedtoisotretinoin.
 Givenorally.
 Hepatotoxicandteratogenic.
 Patientsshouldnotbecome pregnantfor3years
afterstoppingtreatment,andalsoshouldnot
donate blood.
27
Psoriasis
28
Drugs forPsoriasis
 Tazarotene
 Topical.
 Anti-inflammatoryandantiproliferative actions.
 Teratogenic.Also,cancause burning,stinging,
peeling,erythema,andlocalizededemaof skin.

10.  Calcipotiene
 SyntheticvitaminD3derivative
29
Drugs forPsoriasis
 BiologicAgents
 Alefacept
 Immunosuppressive dimerfusionproteinof CD2
linkedtothe Fc portionof humanIgG1.
 Etanercept
 Dimericfusionproteinof TNFreceptorlinkedto
the Fc portionof humanIgG1.
30
Anti-inflammatoryAgents
 Topical Corticosteroids
 Hydrocortisone.
 Prednisolone andMethylprednisolone.
 DexamethasoneandBetamethasone.
 Triamcinolone.
 Fluocinonide.
31
Anti-inflammatoryAgents
 Topical Corticosteroids
 Absorption
 1 of hydrocortisone appliedtothe ventral
forearm.

11.  0.14 timesof hydrocortisone appliedtothe
plantarfoot.
 0.83 timesof hydrocortisone appliedtothe palm.
 3.5 timesof hydrocortisone appliedtothe scalp.
 6 timesof hydrocortisone appliedtothe
forehead.
 9 timesof hydrocortisone appliedtothe vulvar
skin.
32
Anti-inflammatoryAgents
 Topical Corticosteroids
 Absorption
 Absorptionincreasedwithinflammation.
 Increasingthe concentrationdoesnot
proportionallyincrease the absorption.
 Can be givenbyintralesional injection.
33
Anti-inflammatoryAgents
 Topical Cortcosteroids
 Dermatologicdisordersveryresponsiveto
steroids
 Atopicdermatitis.
 Seborrheicdermatitis.
 Lichensimplex chronicus.
 Pruritusani.
 Allergiccontactdermatitis.
 Eczematousdermatitis.

12.  Psoriasis
34
Anti-inflammatoryAgents
 Topical Cortcosteroids
 Adverse Effects
 Suppressionof pituitary-adrenalaxis.
 Systemiceffects.
 Skinatrophy.
 Erythema.
 Pustules.
 Acne.
 Infections.
 Hypopigmentation.
 Allergiccontactdermatitis.
35
Anti-inflammatoryAgents
 Topical Cortcosteroids.
 Tar compounds
 Mainlyfor psoriasis,dermatitis,andlichen
simplex chronicus.
 Can cause irritantfolliculitis,phototoxicity,
and allergiccontactdermatitis.
36
KeratolyticandDestructive Agents
 Salicylicacid

13.  Solubilizescell surface proteinsresultingin
desquamationof keratoticdebris.
 Keratolyticin3-6 concentration,but
destructive inhigherconcentrations.
 Can resultinsalicylismdue tosystemic
absorption.
 Locally,can cause urticaria,anaphylacticand
erythemamultiforme reactions,irritation,
inflammation,andulceration.
37
KeratolyticandDestructive Agents
 Salicylicacid
 Propylene Glycole
 Usuallyusedasa vehicle fororganiccompounds.
 Usedalone as a keratolyticagentin
concentrationsof 40- 70, withplastic
occlusion,oringel with6 salicylicacid.
 Minimallyabsorbed,oxidizedinlivertolactic
acid andpyruvicacid.
 Developsanosmoticgradientthroughthe stratum
corneum,therebyincreasinghydrationof the
outerlayersof skin.
38
KeratolyticandDestructive Agents
 Salicylicacid.
 Propylene Glycole.
 Urea
 Has a humectantactivity,i.e.softeningand
moisturizingeffect onthe stratumcorneum.

14.  Increaseswatercontentasa resultof its
hygroscopiccharacteristics.
 Decreasesthe unpleasantoilyfeel of
dermatologicpreparations.
 Whenabsorbed,itisexcretedinurine.
39
KeratolyticandDestructive Agents
 Salicylicacid.
 Propylene Glycole
 Urea
 PodophyllumResinandPodofilox
 An alcoholicextractof Podophyllumpeltatum(
Mandrake root or May apple).
 Usedin the treatmentof condylomaacuminatumand
otherverrucae.
 Cytotoxicactivitywithspecificaffinityfor the
microtubule proteinof the mitoticspindle.
 Can cause N, V,muscle weakness,neuropathy,
coma, andevendeath.
40
KeratolyticandDestructive Agents
 Salicylicacid.
 Propylene Glycole.
 Urea
 PodophyllumResinandPodofilox.
 Flurouracil

15.  Antimetabolitethatresemblesuracil andinhibits
thymidylate synthetase,thusinterfereswithDNA
and maybe RNA synthesis.
 Usedin multiple actinickeratosis.
41
KeratolyticandDestructive Agents
 Salicylicacid.
 Propylene Glycole.
 Urea
 PodophyllumResinandPodofilox.
 Flurouracil.
 Nonsteroidal Anti-inflammatoryDrugs
 3 gel formulationdiclofenac.

42
KeratolyticandDestructive Agents
 Salicylicacid.
 Propylene Glycole.
 Urea
 PodophyllumResinandPodofilox.
 Flurouracil.
 Nonsteroidal Anti-inflammatoryDrugs.
 AminolevulinicAcid
 Usedin actinickeratosis.
 Aftertopical application(20) andexposure to
light,producesacytotoxicsuperoxide and
hydroxyl radicals.

16. 43
AntipruriticAgents
 Doxepine
 PotentH1 and H2 receptorantagonist.
 Can cause drowsinessandanticholinergiceffects.
 Pramoxine
 Is a topical local anestheticagent.
44
TrichogenicAgents
 Minoxidil (Rogaine)
 Designedasan antihypertensiveagent.
 Effective inreversingthe progressive
miniaturizationof terminal scalp hairs
associatedwithandrogenicalopecia.
 Vertex baldingismore responsive thanfrontal
balding.
45
TrichogenicAgents
 Minoxidil.
 Finasteride (Propecia)
 5?-reductase inhibitorwhichblocksthe
conversionof testosterone todihydrotestosterne.
 Oral tablets.
 Can cause decreasedlibido,ejaculation
disorders,anderectiledysfunction.
46
AntitrichogenicAgent

17.  Eflornithine
 Is an irreversible inhibitorof ornithine
decarboxylase,therefore,inhibitspolyamine
synthesis.Polyaminesare important incell
divisionandhairgrowth.
 Effective inreducingfacial hairgrowthin30
of womenwhenusedfor6 months.
47
Drugs forLeishmania
 Causedbythree Leishmaniaspecies
 L.tropicacausesCutaneousleishmaniasisor
oriental sore.
 L. brazeliensis causesMucocutaneous
leishmaniasis.
 L. Donovani causesVisceral leishmaniasis
48
SodiumStibogluconate
 Pentavalentantimonial
 Bindsto SH groupson proteins.
 Typical preparationscontain30 to 34
pentavalentantimony(??????) byweightaswell as
m-chlorocresol addedasapreservative.
 Also,inhibitsphosphofructokinase
 Local,IM or slowIV,irritant.
 Givenfor20-28 days.
 Drug of choice forall formsof leishmaniasis.
 Resistance isincreasing,especiallyinIndia.
 Cough,V,D, myalgia,arthralgia,ECGchanges,
Rash,Pruritus.

18. 49
AmphotericinB
 Antifungal agent,difficulttouse,andtoxic.
 Alternativetherapyforvisceral leishmaniasis,
especiallyinareaswithhighresistance.
50
Miltefosine
 For visceral leishmaniasis.
 Givenorally,for28 days.
 CausesV D, hepatotoxicity,nephrotoxicity,and
it isteratogenic.
51
Pentamidine
 InhibitsDNA replication.
 Also,DHF reductase inhibitor
 GivenIMor IV injectionandInhalation
 Bindsavidlytotissues,notthe CNS.
52
Pentamidine
 Leishmaniasis
 AlternativetoNastibogluconate
 Pneumocystisjiroveci
 Treatmentandprophylaxisof patientswho
cannot tolerate orfail otherdrugs.
 Trypanosomiasis
 For earlyhemolymphaticstage.

19. 53
Pentamidine
 Adverse Effects
 RapidInfusionHypotension,tachycardia,
dizziness.
 Painat the injectionsite.
 OthersPancreatic,Renal,andHepatictoxicity.

54
AntilepromatousDrugs
 Dapsone andSulphones
 Relatedtosulphonamides.
 Inhibitfolate synthesis.
 Resistance develops.
 CombinedwithRifampinandClofazimine.
 AlsousedforPn.Jeroveci inAIDSpatients.
 Well absorbedanddistributed.
 Retainedinthe skin,muscle,liverandkidney.
55
AntilepromatousDrugs
 Dapsone andSulphones
 Hemolysis,particularlyinG-6-PDdeficiency.
 GIT intolerance
 Fever,Pruritus,Rashes.
 ErythemaNodosumLeprosum

20.  suppressedbysteroidsorthalidomide.
56
AntilepromatousDrugs
 Rifampin
 Discussedwithantituberculousdrugs.
 Clofazimine
 Bindsto DNA.
 StoredwidelyinRESandskin.
 Releasedslowlyfromstorage sites,t1/22
months.
 Givenforsulphone- resistantorintolerant
cases.
 Causesskindiscoloration(red-browntoblack)
and
 GIT intolerance
ermatopharmacology
 Prof WernerSinclair
 Departmentof Dermatology
 University of the Free State
2
OutcomesforthisLecture
 Afterthislecture the studentshouldbe able to

 Name the most importantcharacteristicsanduses
of the followingantifungals

21.  Griseofulvin
 Terbinafine
 Ketoconazole
 Fluconazole
 Itraconazole
 Topical imidazole creams
 Discussthe characteristicsandusesof the
differentstrengthsandformulationsof topical
steroids
 Name the indicationsforandmostimportant
side-effectsof chloroquine
 Discussthe indicationsanduse of topical
retinoids
 Discussthe origin,characteristicsof and
indicationsformupirocin
 Discussthe use of tetracyclinesindermatology
 Name the usesof the differenttypesof
antihistamines(sedatingvsnon-sedating) in
dermatology
 Name the indicationsforandside-effectsof
anti-androgensandimiquimod
3
Drugs To Be Discussed1
 AntifungalsGriseofulvin
 Terbinafin
 Fluconazole
 Itraconazole
 Ketoconazole

22.  CorticosteroidsTopical
 Systemic
 Chloroquine
4
Drugs To Be Discussed2
 RetinoidsTopical
 Systemic
 Benzoyl peroxide
 Shampoos
 Barriers
 AntibioticsTopical
 Systemic
 AntiviralsAcyclovir
 Podophyllin
 AntiscabiesBenzoyl benzoate
5
Drugs To Be Discussed3
 Antihistamines
 Anti-androgens
 Imiquimod
6
Antifungals
 Griseofulvin
 Terbinafin
 Fluconazole

23.  Itraconazole
 Ketoconazole
7
Griseofulvin
 Onlyactive againstdermatophytes(keratolytic
fungi)
 Fungistatic
 Absorbedwithfattyfood(milk)
 Verysafe inchildren
 10 20 mg per kg perday
8
Terbinafin
 Onlyactive againstdermatophytes
 Fungicidal
 Tabletsandcream
 Some severe immunological side-effects
9
Fluconazole
 Broad spectrum
 Fungistatic
 Convenientonce perweekdosage
 Can be usedinneonates
 Usedfor Candida
 Cryptococcus

24. 10
Itraconazole
 Verybroadspectrum
 Fungistatic
 To be takenwithmeals
 Capsulesandsuspensionavailable
 Usedfor Anyfungal infection
 Notbetterthan terbinafinfor

dermatophytes
11
Ketoconazole
 Broad spectrum
 Fungistatic
 To be takenwithmeals
 Tablets,creamand shampooavailable
 Usedfor Seborrheicdermatitis
 Pityriasisversicolor
 Candidiasis
 Side-effectsLivertoxicity
 P450 inducer
12
Imidazole Creams
 Varietyavailable
 Similarspectra

25.  Little tochoose
 Price decidingfactor
 E.g.. Ketoconazole,econazole,clotrimazole
13
Corticosteroids
 Topical
 Systemic
14
Topical Corticosteroids
 3 Strengths
 FluorinatedvsNon-fluorinated
 Ointments,Creams,Lotions,Shampoos

15
Topical Corticosteroids
 OintmentsMore potent
 Penetratesdeeper
 More atrophy
 Usedfor Dry lesions
 Thicklesions
 Thickskin
16
Topical Corticosteroids
 CreamsLesspotent
 Penetratesless

26.  Lessatrophy
 Usedfor Acute,thinlesions
 Moist lesions
 Thinskin(Face,skinfolds)

17
Topical Corticosteroids
 LotionsLeastpotent,leastatrophy
 Usedfor Hairy areas(scalp)
 Wet lesions(Waterysolutions)
18
Topical Corticosteroids
 Shampoos
 Clobetasol Usedforpsoriasisof the scalp
19
SystemicCorticosteroids
 Prednisone /Prednisolone
 Potent,fastactinganti-inflammatory
 Cheap
 Side-effectsShorttermAlmostnone
 Long termSevere
 Usedonce daily,inthe morning
20
Chloroquine
 IndicationsCutaneouslupuserythematosus

27.  Porphyriacutaneatarda
 Side-effectsCorneal deposits(Temporary)
 Maculopathy(Permanent)
 Other
21
Retinoids
 Topical Tretinoin
 Adapalene
 Tazarotene
 Comedolytic,anti-inflammatory
 IndicationsAcne (All forms)
 Anti-aging
 Other
22
Retinoids
 SystemicIsotretinoin
 Acitretin
 IndicationsAcne
 Psoriasis
 Lymphomas
 Many others
 Side-effects,etcSee acne lecture
23
Benzoyl peroxide
 Comedolytic,antiseptic

28.  Gel / Cream
 Superficial,inflammatoryacne vulgaris
24
Shampoos
 Ketoconazole Seborrheicdermatitis
 Pityriasisversicolor
 (Notfor tinea
capitis)
 Coal tar (LPC) Psoriasis
 Povidone iodine (Betadine)
 Seleniumsulfide (Selsun)
 Zincpyrithione
25
Barriers
 Zinc/Castoroil BPNappyrash
26
Antibiotics
 Topical Mupirocin
 Fucidicacid
 Gentamycin
 Erythromycin
 Clindamycin
 SystemicTetracyclines(oxytetracycline,
doxycycline,minocycline,lymecycline)
 Penicillins(amoxycillin,
cloxacillin,amoxycillin-clavulanicacid

29.  Erythromycin
27
Mupirocin
 ManufacturedbyPseudomonasbacteria
 Broad spectrum
 Esp effectiveagainstStaphylococci
 Ointmentandcream
 No systemicuse
 Reservedforshorttermuse
28
Tetracyclines
 Bacteriostaticantibiotics,potentanti-

inflammatoryeffects
 Usedwidelyinacne,rosacea,bullousdiseases
 Oxytetracycline Rosacea
 Lymecycline Drugof choice foracne
 Minocycline Acne inwhite patients
(pigmentation)
 Doxycycline Acne inblackpatients
(phototoxicity)
29
Penicillins
 Cloxacillin,Flucloxacillin,Amoxycillin-Clavulani
c acidStaph infections
 Amoxycillin,erythromycinStrepinfections

30. 30
Antivirals
 AcyclovirCream,tabletsandIV
 Usedfor Herpessimplex 1and2
 Herpeszoster
 (Creamuselessonskin)
 Side-effectsPracticallynone
 Podophyllin25in TBCo Usedfor condylomata
acuminataand verrucae
31
Antiscabies
 Benzoyl benzoate
 Onlyeffective treatmentforscabies
 Methodof use See lecture onskininfections
32
Antihistamines
 SedatingPromethazine
 Chlorpheniramine
 Hydroxyzine (Aterax)
33
Antihistamines
 SedatingPromethasine
 Chlorpheniramine
 Hydroxyzine (Aterax)
 Usedfor Atopicdermatitis

31.  Acute urticaria
 Otherformsof night-time
pruritus

34
Antihistamines
 SedatingPromethasine
 Chlorpheniramine
 Hydroxyzine (Aterax)
 Usedfor Atopicdermatitis
 Acute urticaria
 Otherformsof night-time
pruritus
 Side-effectsSedation(NBDriving)
 Photo-allergy(not
hydroxyzine)
 Dry mouth
35
Antihistamines
 Non-sedatingLoratidine
 Cetirizine
 Desloratidine
 Levocetirizine
 Usedfor Acute and chronicurticaria
 Allergicrhinitis
 Side-effectsAlmostnone

32. 36
Anti-androgens
 Cyproterone acetate
 Progestogen,blocks5a-reductase
 2mg in Diane-35
 10mg inAndrocur
 Usedmostlyfor acne
 Side-effectsDepression,weightgain
 Drosperinone
 Ingredientof Yasmin
37
Imiquimod(Aldara)
 Topical immunostimulant
 Usedfor condylomataacuminata
 Superficial spreadingbasal
cell CA
 Side-effectsSevere local inflammation