Dermatologic Pharmacology

Question 1

___ drugs have higher distribution to the site of action, but ____ drugs have prolonged concentrations/remain longer

Answer 1

Hydrophilic; lipophilic

Question 2

MoA of transdermal drugs

Answer 2

absorbed through skin, reach blood supply (reach therapeutic concentration in the plasma = goal) and then reach the site of infection -> meant to treat infection in NON-dermal regions of the body!

e.g., mirtazapine

Question 3

Benefits of transdermal drug delivery

Answer 3

improved efficacy for time-dependent drugs; reduced toxicity (similar to CRI admin); prolonged Tmax (time to reach maximum concentration); bypasses first-pass metabolism; avoid GI effects

Question 4

Ideal characteristics of transdermal drug?

Answer 4

• low dose required (due to prolonged Tmax)
• low MW
• lipophilic (moderately)

Question 5

Rules for mirtazapine administration

Answer 5

1. clear ear with DRY cloth
2. wear gloves
3. keep apart from other pets for 2 hours
4. alternate ears (avoid irritation)

Question 6

What transdermal drug is used for analgesia in beef cattle?

Answer 6

Flunixin

ID treated cattle; medication is red

Question 7

What transdermal drug is used for hyperthyroidism in cats?

Answer 7

Methimazole (as a compounded formulation)

Question 8

What type of skin infections can be treated with topical antimicrobials?

Answer 8

SF local or generalized conditions (SF pyoderma, otitis externa)
- ideally in glabrous skin (derm devoid of hair)

requires frequent admin (contact time)

Shampoos, ointments, otic preparations

Question 9

topical

Chlorohexidine

Answer 9

• broad organism spectrum (bacteria, fungi, protozoa)
• cell wall destabilizer bactericidal

Question 10

topical

Benzoyl Peroxide

Answer 10

• broad organism spectrum (bacteria, fungi)
• bactericidal (releases free oxygen radicals)
• reduces skin oils/opens pores; reduces follicular hyperkeratosis

Question 11

topical & systemic

Nitrofurans

Answer 11

• horses
• (gram + and -) & is bactericidal (topical)
• UTIs (systemic)
• prohibited use in food animals b/c of toxicity in people!

Question 12

topical

Mupirocin

Answer 12

• protein synthesis inhibitor
• FDA-approved for topical use in dogs
• Anti-stapylococcal acation (MRSA, MRSP use)

Question 13

topical

Silver Sulfadiazine

Answer 13

• antifungal properties

Question 14

topical

Baytil Otic

Answer 14

enrofloxacin + silver sulfadiazine
- syngergistic comboination (+, -, fungi)
- FDA-approved

enro = fluoroquinolone; inhibits DNA gyrase

choose ruputred ear drum +/- suspect pseudomonas

Question 15

topical

Mometamax

Answer 15

abx + steroid + antifungal
- aminoglycosides can cause oto-toxicity! (especially if ruptured ear drum!!

amingoglycosides = gram(-)

Question 16

topical

CLARO

Answer 16

• florfenicol + terbinafine +mometasone
• Does not treat pseudomonas; treats staphylococci

Choose over mometomax if ruptured ear drum; suspect no psuedomonas

Question 17

What derm conidtions to use systemic antimicrobials

Answer 17

widespread conditions: deep pyoderma, otitis media/interna

Question 18

What drug classes are first-tier systemic antimicrobials?

Answer 18

• Beta-lactams abx (1st gen cephalosporins; amoxicillin-clavulanate)
• lincosamides (clindamycin)

Question 19

What drug classes are case-by-case systemic antimicrobials?

Answer 19

3rd generation cephalosporins (cefpodoxime, cefovecin)

Question 20

Systemic antifungals Terbinafine and Itraconazole: precautions & how to avoid:

Answer 20

drug detectable in the hair/skin weeks after the last administration -> pulse dosing for skin/hair fungal infections

Question 21

autoimmune/inflammatory

Major adverse dermatologic and soft tissue effects of corticosteroid therapy:

Answer 21

Cushingoid appearance
Skin thinning
Alopecia
Hirsutism (horses)
Hypertrichosis

Hirsutism is the presence of an abnormally long, sometimes. abnormally structured or dense hair coat

Question 22

Allergic/inflammatory

Cyclosporine
- MoA
- uses

Answer 22

• immunomodulator: blocks IL-2 production, inhibits calcineurin (T-cell activator)
• systemic use: atopic dermatits in dogs/cats (Atopica)

Capsule for dogs, solution for cats: bioavailability GREATLY affected by formulation! and feeding.

Interleukin-2 is made by a type of T lymphocyte. It increases the growth and activity of other T lymphocytes in the immune response/activation

Question 23

What is cyclosporine metabolized by?

Answer 23

EXTENSIVLEY metabolized by liver // CYP450; p-glycoprotein efflux pump substrate

CYP450 = enzyme that metabolizes drug, predominately expressed in the liver

P-glycoprotein efflux pumps = drug clearance from cells

Question 24

Describe the cyclosporine + ketaconazole synergism

Answer 24

Most likely does not have much long-term effects, issue b/c these treatments are usually long-term

Question 25

Precautions with Cyclosporine

Answer 25

- *GI issues* - potential renal toxicity - gingival hyperplasia - decreases insulin secretion/increases insulin resistance - **may take several weeks for effect**

Question 26

**Oclacitnib** - MoA - common drug - PK and PD

Answer 26

- **kinase inhibitor** (Janus-kinase = JAK-1 and -3) -> blocks signal transduction of cytokines (IL-31, IL-2, IL-4) - **Apoquel** in dogs - PK: well absorbed, distrbuted; **HIGH hepatic metabolism** -*no CYP450 :)* - PD: controls itch within 4 hours; SID dosing ## Footnote IL-31 = cytokine that triggers the process of sending itch signals to the brain

Question 27

Monoclonal Antibodies (-vetmabs) - MoA - Use - PK & PD

Answer 27

- **Blocks IL-31** (**monoclonal antibody** against it) -> **monoclonal antibodies are VERY species-specific!!** - **Cytopoint** (dogs) = lokivetmab - **Solensia** (cats) = frunevetmab - IV, IM, SC -> **distribute within lymphatic system!** -> has to hitch a ride on target cell in order to enter the tissues ## Footnote IL-31 = cytokine that triggers the process of sending itch signals to the brain

Question 28

Possible sequela of long-term use of monoclonal antibodies

Answer 28

Formation of antidrug antibodies -> drug stops being effective

Question 29

Antihistamines - precautions with first-generations

Answer 29

Cause BBB => drowsiness - diphenhydramine - benadryl

Question 30

Adverse effects of antihistamines

Answer 30

Relatively safe - mild GI signs - antimuscarinic (inhibits parasymp) - severe overdose => CNS excitation / convulsions

Question 31

Which formulation of Claritin (second-generation "antihistamine") to use

Answer 31

Claritin (24-hour) - indoor and outdoor alleries (**formulation without decongestant!!**) ## Footnote Decongestant = Claritin-D (behavioral changes, panting, tachycardia, hypertension)