Drugs Used For Treating Acne, Rosacea, And Hsv/vzv

Front 1

Four primary factors are identified as being involved in the formation of acne lesions

Back 1

1. Increased sebum production
2. Abnormal keratinization within the pilosebaceous canal (hypercornification)
3. Bacterial colonization by P. acnes
4. Immune-mediated inflammation

Front 2

A. Benzoyl peroxide
1. Mechanism of action
a. Antibacterial effects

Back 2

i. The drug is lipophilic and penetrates to the site of P. acnes growth;
releases oxygen free radicals that damage bacterial cell walls.
ii. Resistance cannot develop to this bactericidal mechanism thus it is
often paired with oral antibiotics to prevent the development of
antibiotic resistance to the oral drug

Front 3

A. Benzoyl peroxide
1. Mechanism of action
b. Comedolytic

Back 3

i. Increases the rate of sloughing of epithelial cells
ii. Loosens follicular plugs

Front 4

A. Benzoyl peroxide
1. Mechanism of action
c. Hastens resolution of inflammatory lesions

Back 4

The irritant effects of benzoyl peroxide cause vasodilation which
increases blood flow

Front 5

Benzoyl Peroxide--Adverse Effects

Back 5

a. Sunburn
Patients should use sunscreen while using benzoyl peroxide because the skin is more prone to burn
b. Benzoyl peroxide can bleach or discolor towels, pillowcases, rugs, or
other fabrics on which it is wiped or spilled.

Front 6

Benzoyl Peroxide --Clinical Uses

Back 6

a. Improves both inflammatory and noninflammatory lesions
b. Benzoyl peroxide is available over the counter and by prescription in a variety of dosage forms (cleansers, lotions, creams, and gels) and concentrations (2.5%–10%).
c. It is usually applied to the affected area once or twice daily.

Front 7

B. Salicylic acid
1. Mechanism of action

Back 7

Concentration-dependent keratolytic

Front 8

Salicylic Acid--Adverse Effects

Back 8

Salicylate toxicity due to percutaneous absorption is used over large body surfaces

Front 9

Salicylic Acid-- Clinical Uses

Back 9

a. Less effective than topical benzoyl peroxide or tretinoin.
b. Useful in patients with mild acne who cannot tolerate other comedolytics
c. Augments effectiveness of other agents when used in combination
d. It is available in nonprescription creams, lotions, and gels in strengths ranging from 0.5% to 2%

Front 10

Antibiotics
1. Mechanism of action

Back 10

a. Antibacterial activity
Antibiotics prevent future lesions by decreasing P. acnes colonization;
they have no effect on existing lesions
b. Antibiotics also can exert anti-inflammatory effects independent of their
antibacterial activity.
i. Antibiotics can reduce neutrophil chemotaxis and inhibit cytokines,
even at subminimal inhibitory concentrations
ii. Antibiotic courses do not necessarily eradicate P. acnes
c. Antibiotic courses used in acne are 2–3 months long, unlike the short
courses used in most infectious diseases. This may be due to the fact
that P. acnes colonies encase themselves within a polysaccharide
biofilm that shields them from antibiotics.

Front 11

Antibiotics--Adverse Effects

Back 11

a. Systemic side effects are rare
b. Topical side effects include stinging and tingling
c. Bacterial resistance

Front 12

Antibiotics--Clinical Uses--name the 3 types

Back 12

a. Clindamycin, erythromycin and metronidazole
b. Available in a number of dosage forms (e.g., gel, lotion, ointment)
c. Available as combination products (e.g., Erythromycin or clindamycin combined with benzoyl peroxide; clindamycin combined with tretinoin)

Front 13

Tretinoin
1. Mechanism of action--Retinoids

Back 13

Retinoids exhibit vitamin A activity and have many important functions throughout the body, including roles in vision, regulation of cell proliferation and differentiation and bone growth, immune defense, and
tumor suppression.

Front 14

Tretinoin
1. Mechanism of action--Retinoic Acid

Back 14

Retinoic acid (RA) exerts its effects on gene expression by activating two families of receptors—retinoic acid receptors (RARs) and the retinoid X receptors (RXRs). Human skin contains mainly RARα and RARβ. Retinoids (ligands) bind transcription factors (nuclear receptors), and the ligand-receptor complex then binds to the promoter regions of target genes to regulate their expression. The gene products formed contribute to the desirable pharmacological effects and their side effects.

Front 15

Tretinoin
1. Mechanism of action--The skin

Back 15

In the skin, the retinoids may act in the keratinocyte nucleus to correct
abnormal cell differentiation.

Front 16

Tretinoin
1. Mechanism of action--Topical Vit A analogue

Back 16

i. Reduces hyperkeratinization that leads to microcomedone formation
ii. Decreases cohesiveness of follicular cells, leading to extrusion of existing comedones and inhibition of the formation of new comedones
iii. Reduce inflammation by inhibiting production of inflammatory mediators

Front 17

Tretinoin--Adverse Effects

Back 17

a. Skin irritation, peeling, erythema, and dryness; patients should use sunscreen because the newly exfoliated skin is prone to burn
b. A “flare” of acne may appear suddenly after initiation of treatment (followed by clinical clearing in about 8–12 weeks)
c. Teratogenic
i. Less teratogenic than other retinoids because the drug is rapidly metabolized in the skin
ii. Use for pregnancy only when benefit to mother outweighs risk to fetus

Front 18

Tretinoin--Clinical Uses

Back 18

a. Topical retinoids are the most potent comedolytic agents
b. Mild acne cases with mostly noninflammatory lesions.
c. They may also be used in combination with antibiotics and/or other therapies to manage moderate to severe acne
d. Usually applied once daily at bedtime
e. Topical preparations contain from 0.01% to 0.1% tretinoin in cream, gel, and solution formulations

Front 19

Doxycycline--Adverse Effects

Back 19

Systemic Antibiotic--
i. Resistant bacteria
ii. Folliculitis
iii. Candidiasis
iv. GI effects (e.g., nausea and vomiting, diarrhea)
v. Phototoxicity (e.g., photoonycholysis [separation of the nail from the distal nailbed in conjunction with sun exposure])
vi. Impairment of bone growth and discoloration of forming teeth (tetracyclines should not be used in children or pregnant women [due to similar effects on the fetus])

Front 20

Erythromycin--Adverse Effects

Back 20

Systemic Antibiotic
i. Resistant bacteria (higher rates compared to doxycycline)
ii. GI effects (e.g., abdominal pain, nausea and vomiting, diarrhea)

Front 21

Trimethoprim/Sulfamethoxazole--Adverse Effects

Back 21

Systemic Antibiotic
i. GI effects (e.g., nausea and vomiting, anorexia)
ii. Skin reactions (e.g., rash, urticaria, Stevens-Johnson syndrome)

Front 22

Systemic Antibiotics--Clinical Uses

Back 22

a. Oral antibiotics (usually in combinations with topical retinoids and/or benzoyl peroxide) are used in patients with moderate to severe acne
b. Oral antibiotics can also replace topical antibiotics when other topical combination regimens fail
c. Oral antibiotics are initiated with twice daily dosing for 6 to 8 weeks; if a good clinical response is noted, dose frequency may be reduced to once daily for maintenance. To minimize the emergence of bacterial resistance, the patient should attempt to discontinue antibiotic therapy after achieving treatment success for a few months.

Front 23

Systemic Antibiotics--Drugs

Back 23

i. Doxycycline is commonly used
ii. Erythromycin can be used for patients who cannot tolerate tetracyclines, or who acquire bacterial strains resistant to tetracyclines
iii. TMP/SMX (trimethoprim-sulfamethoxazole) may be used for treating patients who do not tolerate tetracyclines and erythromycin or in
cases of resistance to these antibiotics

Front 24

Isotretinoin
1. Mechanism of action

Back 24

Systemic isotretinoin exhibits all four of the mechanisms of action outlined above, making it uniquely effective monotherapy.
a. Induces atrophy of the sebaceous gland with decreased sebum production and change in sebum composition
b. Inhibits P. acnes growth within follicles
c. Inhibits inflammation
d. Alters patterns of keratinization within follicles (decreased size and
increased differentiation)

Front 25

Isotretinoin--Adverse Effects

Back 25

a. Dose-dependent adverse effects on the skin and mucous membranes are observed most commonly including cheilitis, mucous membrane dryness, epistaxis, dry eyes, blepharoconjunctivitis, erythematous eruptions, and xerosis
b. Hyperlipidemia (increased triglyceride levels)
c. Myalgia and arthralgia
d. Teratogenicity is a major problem
i. Occurs if the drug is given within the first 3 weeks of gestation
ii. Teratogenic effects include CNS, cardiac, thymus, craniofacial abnormalities
iii. Spontaneous abortion can occur
iv. Pregnancy is an absolute contraindication to the use of isotretinoin

Front 26

Isotretinoin--Clinical Uses (not in females)

Back 26

a. Isotretinoin is prescribed for severe, recalcitrant nodular acne, moderate acne unresponsive to oral antibiotics, and acne that produces scarring
b. Essentially all patients will respond to systemic isotretinoin; in most cases, one or two 5-month-long courses of therapy induce a remission lasting for several months or years after the drug is stopped

Front 27

Isotretinoin--Clinical Uses in Females

Back 27

i. Females of childbearing potential should initiate therapy at the beginning of a normal menstrual period and obtaining two negative pregnancy tests.
ii. Two forms of birth control must be practiced during therapy and for 1 month both before beginning therapy and after completion of therapy
iii. Pregnancy tests should be repeated monthly
iv. All isotretinoin patients, male and female, must refrain from donating blood during or for a month after therapy to ensure no isotretinoin-contaminated blood products are unknowingly administered to a pregnant woman.

Front 28

Pathophys of Rosacea

Back 28

A. Common, chronic inflammatory facial eruption of unknown cause is characterized by erythema, telangiectasia and recurrent, progressive crops of acneiform papules and pustules, usually on the central part of the face.
B. Some patients develop cystic nodules, granulomas and tissue hypertrophy, sometimes leading to rhinophyma (a bulbous nose).
C. Blepharitis and conjunctivitis are common.
D. Rosacea is more prevalent in women, but rhinophyma occurs more frequently in men

Front 29

Azelaic acid, Metronidazole, Sulfacetamide ± sulfur--Mechanism of action

Back 29

Topical Treatment of Rosacea--Antimicrobial and antiinflammatory effects

Front 30

Azelaic acid, Metronidazole, Sulfacetamide ± sulfur--Adverse Effects

Back 30

Burning, stinging, pruritus

Front 31

Azelaic acid, Metronidazole, Sulfacetamide ± sulfur--Clinical Uses

Back 31

-Effective in the treatment of inflammatory lesions and erythema
-Neither medication improves telangiectatic blood vessels

Front 32

Isotretinoin--Rosacea

Back 32

Systemic Treatment--same mech as with acne

Front 33

Isotretinoin--Rosacea Clinical Uses

Back 33

1. Patients with severely inflamed rosacea, or those whose disease has a marked nodulocystic component
2. Treated with isotretinoin for 6-8 months
3. As with acne, careful monitoring is necessary in women of childbearing age
4. Significant reductions in erythema, papules and telangiectasia occur after about 2 months of treatment; the only pharmacologic treatment that can reduce telangiectasia

Front 34

HSV/VZV Pathophys

Back 34

Better check the handout, it's extensice

Front 35

Acyclovir
A. Mechanisms of action

Back 35

1. Acyclovir is a prodrug. It is converted
to the monophosphate (MP) derivative
by viral thymidine kinase.
2. Acyclovir-MP is then phosphorylated to
acyclovir-DP and acyclovir-TP by cellular enzymes. Uninfected cells convert very little or no drug to the phosphorylated derivatives. Thus, acyclovir is selectively activated in cells infected with viruses encoding the appropriate thymidine kinases.
3. Incorporation of acyclovir-MP from acyclovir-TP into the primer strandduring viral DNA replication leads to chain termination and formation of an
inactive complex with the viral DNA polymerase irreversibly inactivating the
enzyme.

Front 36

Acyclovir Resistance

Back 36

Acyclovir resistance in HSV/VZV
a. Absence or partial production of viral thymidine kinase
b. Altered thymidine kinase substrate specificity (e.g., phosphorylation of thymidine but not acyclovir)

Front 37

Acyclovir Administration

Back 37

Orally, IV, or topically

Front 38

Acyclovir--Adverse Effects

Back 38

1. GI disturbances (for oral administration; e.g., nausea, vomiting, diarrhea)
2. Renal dysfunction
IV acyclovir can also cause reversible renal dysfunction due to crystalline nephropathy
3. CNS effects
a. Headache
b. IV and, rarely, oral, acyclovir have been associated with encephalopathy, including tremors, hallucinations, seizures and coma
4. Burning, stinging, pruritus with topical administration

Front 39

Acyclovir --IV Clinical use

Back 39

IV acyclovir is the drug of choice for treatment of HSV infections that are visceral, disseminated or involve the central nervous system (CNS) and for
serious or disseminated VZV infections.

Front 40

Acyclovir--Oral Clinical Use

Back 40

--Oral acyclovir is effective for primary orolabial, genital and anorectal HSV infection as well as for recurrent orolabial and genital HSV infections. Long-term oral suppression with acyclovir decreases the frequency of symptomatic genital HSV recurrences and asymptomatic viral shedding.
--Oral acyclovir begun within 24 hours after the onset of rash decreases the severity of primary varicella infection and can also be used to treat localized zoster.

Front 41

Acyclovir--Topical Uses

Back 41

Topical acyclovir cream reduces the duration of herpes labialis (cold sores) by about half a day.