Derm Pharm Flashcards
1
Q
Absorption is enhanced when
A
Stratum corners is thinner (scrotum, face, axilla)
Skin integrity is compromised
Temperature increased
Increased hydration
Increased concentration
2
Q
The more ____ the vehicle, the more hydrated the skin is
A
Occlusive
More hydrated skin = more absorption of drug
3
Q
Rank the vehicles from best absorption to worst
A
Ointment –> cream —> lotion –> gels (worst)
4
Q
Creams
A
Semisolid emulsions of oil
Easily washed off with water
Middle ground potentcy
5
Q
Ointments
A
Water suspended in oil, excellent lubricant
Decreases water loss, enhances absorption
MOST potent due to occlusive effect
Patient acceptance is low (greasy) and not good in hair areas
6
Q
Lotions
A
Powder in water so you must shake before use
Cooling and drying but least potent
Useful in large hair areas
7
Q
MOA of topical corticosteroids
A
Act against inflammation at cellular level
Inhibition of formation, release, and activity of mediators of inflammation –> decreases inflammation
Inhibits the migration of macrophages and leukocytes (reverses vascular dilation and permability)
Antimitotic effect on epidermal cells
8
Q
When topical agents are applied to skin (Big Macs)
A
Inhibit migration of macrophages and leukocytes to reverse vascular dilation and permeability
Decreases edema, pruritis, edema
9
Q
Absorption of topical corticosteroids increases with:
A
Increased hydration
Breaks in skin
10
Q
Metabolism of topical corticosteroids
A
Primarily in the liver
Some in the skin
Elimination is primarily in the kidney
11
Q
Potency of topical corticosteroids is dependent upon
A
- Characteristics of the drug (fluorinated to make more potent)
- Concentration of the drug
- Vehicle for delivery
12
Q
General approach to topical corticosteroids
A
Start with lower potency, less occlusive vehicles (creams) then titrate up
Thin film of preparation
Only low-mid potency for children and short duration
13
Q
What corticosteroids should be used on the face?
A
Non fluorinated/low potency areas
Used in all areas with thin stratum corneum
High potency can be used for BREIF periods
14
Q
Lowest efficacy corticosteroid (concentration)
A
Hydrocortisone (0.25-2.5%)
15
Q
Low efficacy corticosteroid (concentration)
A
Triamcinolone actinide/Aristocort Kenalog (0.025%)
16
Q
Intermediate efficacy corticosteroid (concentration)
4
A
Hydrocortisone valerate/Westcort (0.1%)
Flurandrenolide/Cordran (0.025%)
Desonide/Desowen (0.05%)
Triamcinolone acetonide/kenalog (0.1%)
17
Q
High efficacy corticosteroid (concentration)
3
A
Fluocinonide/Lidex (0.05%)
Triamcinolone acetonide/Kenalog (0.5)
Desoximetasone/Topicort (0.25%)
18
Q
Highest efficacy corticosteroid (concentration)
A
Clobetasole propionate/Temovate (0.05%)
19
Q
Intralesional corticosteroids
A
Preparations that are insoluble upon injection and solubility gradually
Ex. Triamcinolone acetonide/Kenalog-10
20
Q
Triamcinolone acetonide
A
Intradermal
Limited to 1.0mg per injection site
Multiple sites can be injected
Greater volume of corticosteroid injected results in greater likelihood of systemic absorption/effects
21
Q
Adverse reactions to topical corticosteroids
A
- HPA suppression
- Excessive absorption = Cushing’s disease, hyperglycemia, and hypokalemia
Under most conditions systemic absorption is very minimal and therefore these ADRs are minimal
22
Q
When do we worry about systemic involvement of topical corticosteroids
A
- High potency agents in occlusive preparations
- Large amounts of topical over large area of the body
- Topical corticosteroids over breaks in the skin
- Topical corticosteroids in pediatric patients
23
Q
Most significant ADR Topical corticosteroids
A
Skin thinning/atrophy
Secondary infection due to immunosuppression
Tolerance (reversible if used cyclically)
24
Q
Pathogens from most dermatological concerts are
A
Group A b-hemolytic streptococcus
Staphylococcus aureus
We try to cover these but also take into account regional patterns of resistance (Antibiogram)
25
Topical antibiotics
1. Bacitracin
2. Gramicidin
3. Polymixin B sulfate
4. Aminoglycosides (Gentamicin)
5. Mupirocin
6. Metronidazole
26
bacitracin and gramicidin
Peptide antibiotics
Activity against pretty much everything (anaerobes and gram positives)
Minimally absorbed thru skin but have significant toxicity if given oral/systemically
27
Bacitracin MOA
Inhibits bacterial cell wall synthesis
Prevents transfer of mucopeptides into the growing cell wall
28
Gramicidin
Interferes with bacterial protein synthesis by binding to 30s ribosomal subunits
29
Polymixin B sulfate
Peptide antibiotic
Detergent (attaches and disrupts cellular bacterial membranes)
Gram -
No activity against gram +, proteus or serration
Often used in combo
30
Neomycin
Aminoglycosides
Interferes with bacterial protein synthesis (30S ribosomal subunit)
Gram negatives
Minimally absorbed from skin, can cause sensitization
** NUMBER 2 LEADING CAUSE OF CONTACT DERMATITIS
31
Gentamicin
Aminoglycosides
Increased activity against P. Aeruginosa compared with neomycin
Increased activity against staph and group A strep when compared to Neomycin
Interferes with bacterial protein synthesis (30s ribosomal subunit)
32
Gentamicin ADME
Can serum levels
Esp. When applied to large areas of denuded (burn lesions)
Possible to see accumulation in patients with renal impariment = toxicity
33
Mupirocin
Bactroban
Inhibits protein synthesis
Active against Gram + and Gram - aerobic bacteria
MRSA
Used intranasally for prophylaxis post op infections
34
ADME, ADR, Use
Mupirocin
Minimally absorbed through the skin
Can cause adverse drug reactions
For nasal colonization: 1/2 tube in ea. Nares (bid x 5d)
35
Metronidazole
Treatment of rosacea
Demodex brevis inhibition
Acts as an anti-inflammatory agent
36
Approach to treating mild-moderate acne (and agents)
Agents that correct defect in keratinization by producing exfoliation
1. Salicylic acid
2. Benzoyl peroxide
3. Topical retinoids
4. Topical antibiotics
37
Salicylic acid
Keratolytic (softens layer)
Reduced cohesion of corneocytes
Shedding of epidermal cells
Breakdown of keratin
Can cause burning, reddening, local skin peeling
38
Benzoyl peroxide
Pro-Active
Bactericidal agent
Stratum corneum and concentrates in pilosebaceous unit
Slowly releases oxygen acts against gram-positive and gram-negative anaerobic bacteria, yeast, and fungi
Decreases sebum production and consequently free fatty acids which decrease inflammation
Wash or apply ONCE daily and begins to work 8-12 weeks after starting
39
ADRs of Benzoyl peroxide
Dry skin -- marked peeling and erythema
Benzoyl peroxide will bleach clothing
40
Normal epithelial differentiation is dependent upon which vitamin?
Vitamin A
Therefore most powerful peeling agents are vitamin-A related
41
Retinoid
Topical agents
Oral:
Retinoid Retin-A
Adapalene/Differin
Tazarotene/Tazorac
ALSO oral: Isotretinoin (Claravis, amnesteem)
42
Retinoids MOA
Act to reduce obstruction within the follicle
Useful in comedian and inflammatory acne
Normalize abnormal keratinocyte desquamation
43
Indications for oral Retinoid
Severe recalcitrant nodular acne
Acne vulgaris
44
Retinoid topical use
Apply in concentration that causes slight erythema with mild peeling
Apply once in evening at bedtime
Thin
45
1/3 rule
1/3 of patients have success with Retinoid
1/3 of patients will have to do combo Benzoyl and Retinoid
1/3 ill have to go right back on
46
IPledge program
Isoretinoin is teratogen (causes spontaneous abortion and life threatening congenital malformations )
THEREFORE it can only be prescribed by a iPLEDGE provider and dispensed by and iPLEDGE pharmacy and given to an iPLEDGE patient
Must be on 2 forms of contraceptive
47
Clindamycin
Cleocin T/Evoclin
MOA: binds to 50s ribosomal subunit, interferes with protein synthesis
Less irritating if water based gel
48
Clindamycin ADR
Cases of drug being systemically absorbed to levels that cause bloody diarrhea and pseudomembranous colitis (RARE for other topical agents)
49
Erythromycin
Binds to P site of 500s ribosomal subunit
50
Which medications should not be used as mono therapy for acne?
Clindamycin and e-mycin
Due to risk of increasing resistance
51
Sulfacetamide
Topical
Inhibition of P. Canes via PABA utilization
Warning: hypersensitive to sulfa
52
Oral antibiotics used for acne
Tetracycline
Doxycycline
Minocycline
These three are very affective but can't give to pregnant ladies or children
Erythromycin
Hormonal agents
53
Tetracyclines
Bacteriostatic
Inhibits protein synthesis (30 and 50s subunits)
Minocycline > Doxycycline > Tetracycline
Can cause vertigo, photosentivity
54
Erythromycin
Limited to those who cant use tetracycline (i.e. Pregnant women or children under 8)
55
Hormonal agents
Used to treat acne
Oral contraceptives (some have FDA approval specifically for acne, but all of them have same effects)
Appear to control inflammatory component of acne (control the androgen levels)
56
Topical Antifungal agents
azole derivatives
Ciclopirox/Loprox
Naftin/Lamisil
Tolnaftate/tinactin
57
Topical azole derivatives
Alters cell membrane permeability
58
Ciclopirox
Topical antifungal
Loprox
Broad spectrum
Activity against dermatophytes, candida species and P. orbiculare
Available as a nail polish for onychomycosis (low cure rate)
59
Naftin
Aka lamisil
Topical antifungal
Activity against dermatophytes and P. Orbiculare but NOT candida
60
Oral antifungal agents
Useful in treatment of systemic mycosis
Treatment may take up to a year for oral antifungal treatment
Take with acidic beverage then run to sweat it out
61
Herpes simplex type 1 and 2
Spread by intimate contact, shedding to succeptible host
Viral replication continues local inflammation and cell lysis lead to distinct vesicles
62
Varicella zoster
Direct contact, droplets and airborne transmission
Infects via respiratory tract
Disseminated vascular rash after 10-14 days
Stress can play a role in deactivation (also age and immunosuppresion)
63
Oral antivirals
Acyclovir
Valacyclovir
Famciclovir
64
Acyclovir
HSV 1, HSV 2, varicella
Decrease duration of acute infection for HSV 2
Decreased number of lesions in varicella
65
Valacylovir
Useful for recurrent HSV outbreaks
Activity against varicella and herpes zoster
66
Famciclovir
Recurrent HSV outbreaks, herpes zoster
67
Topical antivirals
Zovirax
Denavir
Abreva
68
Zovirax
Acyclovir
Topical antiviral
Management of inital herpes episodes
69
Denavir
Penciclovir
Treatment of recurrent herpes labialis (HSV) on lips and face
"Cold sore"
70
Abreva
OTC treatment of cold sores
71
Immunomodulators
imiquimod
Tacrolimus/Protopic
Pimelcrolimus/Elidel
72
Imiquimod MOA
Aldabra/Zyclara
TLR-7 agonist that induces cytokines and chemokines with antiviral and immunomodulating effects (attacks the cells in question)
73
Imiquimod indications
Condylomata acuminata
Molluscum contagiosum
DNA viral infections
WARTS
ACTINIC keratosis
Superficial basal cell carcinoma (also includes skin around the tumor)
74
Protopic and Elidel MOA
Suppresses cellular immunity by inhibiting T cell activation
Therefore prevents release of inflammatory cytokines and mediators
75
Psoriasis treament overview
Limited disease = topical therapy
More than 20% of body = complex and/or systemic therapy
76
Emollients
Psoriasis topical treatment
Used during therapy free periods to minimize dryness
Hydrate stratum corneum and minimize evaporation of water
Decrease binding forces of horny layer and enhance desquamation and eliminate scaling
Mild vasoconstrictor
77
Keratolytics
Remove scale, smooth skin and decrease hyperkeratosis
Salicylic acid is MC used (2-10%)
78
Keratolytics MOA
Decrease corneocyte to corneocyte cohesion producing exfoliating action
79
Salicylic acid/Keratolytics ADRs
Local irritation
Application to large areas can result in salicylism (n/v/tinnitus/hyperventilation)
80
Corticosteroid
Psoriasis efficacy
Clears psoriasis in 25% of patients within 3-4 weeks
50% of patients experience 75% clearing (mostly gone)
81
High potency corticosteroids for psoriasis
Used for finite periods of time when local therapy is possible
Esp. For thick, chronic psoriatic plaques
Clobetasol proprionate (0.05%)
82
Intermediate potency corticosteroid for psoriasis
CAN be used on face if needed for limited amount of time
83
Low potency corticosteroid for psoriasis
Safest for long term use, face and thin skin areas, young children and infants
Hydrocortisone 1%
84
corticosteroid for psoriasis
Advantage
Prompt relief
Convenient and acceptable
Disadvantage is that it cant be used on face
85
corticosteroid for psoriasis
Useage
Daily or twice daily
More effective the more often it is used but continuous application for more than a month is discouraged
When lesions flatten then use intermittently
86
Calcipotrience
MOA
Dovonex
Topical vitamin D3 analog
- Suppress keratinocyte proliferation
- Anti-inflammatory effects
- Decrease IL-2 production
87
Dovonex
Efficacy
Calcipotriene
Most patients see improvement b it not clearing of lesions
Similar results to corticosteroids but it takes longer to work
88
Calcipotriene ADRs
Systemic absorption is small but can still effect body so urine calcium excretion must be monitored
89
Tazarotene
Normalized abnormal keratinocyte dififerntiation
Reduces hyperproliferation
Decreased inflammation
Psoriasis
90
Tazarotene
Advantage
Anti-psoriatic effects last for longer amount of time when compared to corticosteroid
91
Tazarotene ADR
Teratogenic (topical are not shown to cause this but must tell patient)
92
Topical, 1st line agents in psoriasis (4)
1. Keratolytics
2. Corticosteroids
3. Calcipotriene
4. Tazarotene
93
Topical second line agents for psoriasis (3)
1. Coal tar
2. Anthralin
3. immunomodulators
94
Coal tar
Mixture of hydrocarbons formed from distillation of bituminous coal
Not popular bc it takes a lot of time and has cosmetic disadvantages (messy, stains skin and close has odor)
Typically used at bed time (shampoo or cream) can be used with UVB
95
Anthralin
Reduction of mitotic rate and proliferation of epidermal cell by inhibiting synthesis of nuclear protein from inhibits of DNA synthesis to affected areas
Concurrent application of petrolatum ointment around the lesion minimizes irritation
96
Anthralin
Advantage
Effective for widespread plaques
Produces long remission
97
Anthralin disadvantage
Staining of skin, clothes
Irritation to normal skin and flex urges
Can precipitate generalized psoriasis
98
T or F
Immunomodulators are FDA approved for psoriasis
FALSE
They are only approved for atopic dermatitis
Can cause lymphoma and skin cancer
99
1st Line psoriasis systemic therapy agents
Acitretin/Soriatane
Methotrexate
Remicaid
100
Acitretin
Soriatane
Used in severe, recalcitrant psoriasis
Unknown MOA
101
Acitretin
Pharmacokinetics
Absorption is optimal if given with food
Mostly all of it is bound to albumin in the blood
Achieves steady state plasma concentration in 3 weeks
102
Acitretin
ADRs
Hyperlipidemia
Liver enzyme elevation and hepatitis
Known teratogen (must not be pregnant/intend on getting pregnant in 3 years bc of accumulation in adipose)
103
Acitretin Drug interactions
Interferes with contraceptive effects in single progesterone agents
Must not be used in concurrent ingestion of alcohol = longer half life (harming liver more and more)
104
Methotrexate
Rhumatrex/Trexall
Immunosuppressive
Produces anti-psoriatic effects (lower dose than chemo patients)
105
Methotrexate MOA in psoriasis
Inhibits dihydrofolate reductase (needed for AA, pyrimidines and purine synthesis)
Inhibits epidermal cell proliferation
Inhibits replication and function of T and B cells and suppresses cytokines secretion
Causes prolonged remission and Many patients have improvement
106
Methotrexate ADR
Hepatotoxic *can cause fibrosis and cirrhosis)
Bone marrow depletion
Nausea
Diarrhea
107
Methotrexate
Relative CIs
Decreased renal function
Pregnancy or breast feeding
Must delay conception for one full ovulatory cycle or 3 months in men
NSAID and aminoglycoside use can reduce clearance of MTX and cause toxic levels
108
Remicade
Infliximab
Chimeric monoclonal Ab that binds to soluble and transmembrane forms of TNF-alpha and inhibits it binding with receptors
IV infusion only
Modulates expression of adhesion mollyecuels responsible for leukocyte migration and cytokines serum levels
THEREFORE IT BLOCKS INFLAMMATORY AND IMMUNE RESPONSES
109
Entercept
Enbrel
Reduces signs and symptoms and inhibits progression of structural damage of active arthritis in patients with psoriatic arthritis
Can be used in combo with MTX
110
Enbrel MOA
Binds to TNF and blocks interaction with cell surface receptors
Blocks inflammatory and immune responses
SQ injection, half life of 102 hours and peaks at 69 hrs
111
Alefacept
Amevive
Interferes with lymphocyte activate and proliferation
May increase risk of malignancies and increased risk of infection
112
Efalizumab
Indication, MOA
Plaque psoriasis
Blocks T cell activation
AKA raptiva
113
Adalimumab
AKA Humira
Immunomodulator used for mod-severe plaque psoriasis
Blocks TNF-alpha
114
Psoriasis immunomodulatory drugs (5)
Etanercept/Enbrel
Alefacept/Amevive
Infliximab/Remicade
Efalizumab/Raptiva
Adalimumab/Humira
115
Scabies 1st line treatment
Permethrin 5% topical cream
Elimite
116
Elimite
MOA
Scabies
Acts on nerve cell membrane of mite to disrupt sodium channel that regulates membrane polarization
Causes paralysis and death of the parasite
117
Alternative treatments
Scabies
Lindane 1% lotion/shampoo
Ivermectin/stromectol
Crotamiton 10% /Eurax
Malathion 0.5%/Oviedo
118
Lindane 1%
Scabies alternative treatment
Lotion or shampoo
Directly absorbed by parasites and ova thru exoskeleton
Simulates nervous system resulting in seizure and death of parasite arthropod
Wet or warm skin increase risk of systemic absorption (therefore neurotoxicity of patient)
119
Ivermectin
Stromectol
Binds CHLORIDE ion channel in nerve and muscle cells
Causes hyperpolarization and death of parasite
2nd line agent for scabies
120
Eurax
Crotamiton 10%
Scabies 2nd line if Permtehrin failed
121
Ovide
Malathion 0.5%
Excessive stimulation of cholinergic receptors in CNS and PNS causing cell death
122
1st line Pedicuolosis capitis
Permethrin 1% topical
Acts on sodium channel nerve cell membrane to result in paralysis and death
Apply to scalp and behind ears, nape of neck
Must reapply if lice are seen 7 days after initial treatment
123
2nd line agent of Lice
Natroba/Spinosad
Topical Ivermectin
Benzoyl Alcohol
124
Natroba
derived from fermentation of Bactria in soil (Saccharopolyspora Spinosa) causing neuronal excitation that causes paralysis and death
125
Topical Ivermectin
| MOA
Binds to chloride ion channel in nerve and muscle cells
Causes hyperpolarization of nerve or muscle cell
Death of parasite
Used in lice (2nd line)
126
Benzyl Alcohol
LICE MOA
Asphyxiation of lice
