Pharmacology for Skin Conditions 1 PDF 2024

PHARMACOLOGY FOR SKIN CONDITIONS JENNIFER L DAVIS 231-2192 [email protected] Outline Routes of administration ◦ Topical ◦ Systemic ◦ Transdermal Not really used to treat skin disorders Drugs for treatment of infectious diseases of the skin/ear Drugs for treatment of inflammatory or auto-immune diseases...

PHARMACOLOGY FOR SKIN CONDITIONS JENNIFER L DAVIS 231-2192 [email protected] Outline Routes of administration ◦ Topical ◦ Systemic ◦ Transdermal Not really used to treat skin disorders Drugs for treatment of infectious diseases of the skin/ear Drugs for treatment of inflammatory or auto-immune diseases of the skin (lecture 2) Principles of therapy Topical For very superficial, localized diseases ◦ Drug is applied locally to the site of action so that is stays at the site of action to exert its effect ◦ Typically the skin, ear, local areas (ie joints) ◦ Low concentrations in plasma, if any Approved for use in horses (NSAID) will penetrate locally into the joint its over Principles of therapy Systemic administration ◦Drug administered parenterally, enterally, etc. ◦Absorbed and distributes to the site of action ◦ Dermis, SC space for dermatology ◦Therapeutic concentrations in plasma required! Treats an infection/ disease somewhere in the body Cephalexin in horses 23% PPB Principles of therapy Systemic drugs and the skin ◦ Site of action is ECF/ISF interstitial fluid ~ ◦ Protein binding limits drug movement ◦ Hydrophilic drugs reach site of action &◦ Lipophilic drugs reach site of action Take a little longer to have an affect ◦ Lower but prolonged concentrations ◦ Diffusion into and out of cells 65% PPB Top TD Sy s 3 - > (pannisius Principles of therapy Transdermal - drug reaches plasma ◦ Drug applied locally at a site ◦ Not the site of action ◦ Absorbed systemically to have effect at the site of action ◦ Therapeutic concentrations in plasma Hopefully… Transdermal drug delivery ◦Why? ◦ Improved patient compliance ◦ Decreased dosing frequency/ cost ◦ Avoid painful injections/ injection site reactions ◦ Hard to pill animals…Cats! Depending on the drug Transdermal Drug Delivery More steady plasma concentrations Improved efficacy for time dependent drugs Reduced toxicity with lower peaks (low and slow) Prolonged Tmax (need LD?) time for drug to reach maximum concentration Bypass first pass metabolism avoid liver processing (get higher concentrations) Oral > - - ◦ Cutaneous metabolism? Avoid GI side effects Hope: Lower but more consistent absorption of the drug across the skin. Reality… Transdermal Drug Delivery Ideal drug characteristics ◦Low dose required ◦Low molecular weight ( - ◦ Animal control calls Flea and tick products Absorption is different for the different species Transdermal drugs in vet med Opioids LIM/IV Often given oral transmucosally. ◦ Zorbium® - transdermal buprenorphine for cats ◦ Apply 1-2 hours before surgery ◦ Wear gloves, glasses and lab coat ◦ Don’t clip Part the hair instead ◦ Dries within 30 minutes ◦ Lasts 4 days ◦ Little potential for abuse human ◦ Better than fentanyl patches > - Clip the hair for patches and put on immediately after shaving to avoid putting on irritated skin. Takes at least 12 hours for the patch to work. Reservoir patch Multiple layers. Adhesive Cannot cut the patches to change the dose Membrane Has adhesive that gets stuck to the animal’s skin Drug Outer Liner Covers a reservoir of drug Can get toxicity if you cut b/c it’ll all come out of the patch Can’t cut the patches!!! people may chew excess fentanyl not absorbed initially Transdermal delivery Compounded formulations ◦Maintain a healthy skepticism… ◦Not appropriate for treating a systemic infection ◦Make sure there is research available to support its use Don’t use antibiotics transdermally. Need to reach therapeutic concentrations to avoid resistance development. Vet Derm 14: 83-89, 2003. Transdermal delivery Compounded products with potential for use in cats ◦ Methimazole – hyperthyroidism, slower onset, fewer GI ADRs ◦ Phenobarbital – seizures, 3x oral dose, need more drug monitoring due to variability in absorption ◦ Levetiracetam – seizures, q8h application (60 mg/kg), no efficacy data Calcium channel blocker ◦ Amlodipine – hypertension, induce remission with oral first ◦ Fluoxetine – behavioral issues, 10x oral dose, no efficacy data (Prozac) ◦ Maropitant – vomiting, 6/8 cats improved?, no diagnosis, no PK ↳ Cerenia 4 drug class meds of Antiarrythmics/ blood pressure 1A: procainamide Quinanidine 1B: lidocaine Mexlietine Phenytoin Tocainide 1C- not often used in vet med 2: beta blockers (lol) i.e. tenolol, propranolol, carvedilol 3: sotilol (the only exception, not a B-blocker) amiodarone 4: amlodipine, diltiazem Transdermal delivery NEVER appropriate for antibiotics for the treatment of systemic infections!!! Know the principles of transdermal drug delivery INFECTIOUS DISEASES OF THE SKIN BACTERIAL/FUNGAL Topical antimicrobials Superficial local or generalized conditions ◦Superficial pyoderma, otitis externa Require frequent administration ◦Contact time lif shampor) May require clipping of the hair coat May become ORAL Need to sud up the dog and wait Don’t want anything toxic in case the animal licks it Topical antimicrobials Site ◦ Glabrous vs non-glabrous Gfree from hair ↳ covered in hair Armpit, groin, short-haired dogs, thin skin dogs can be treated topically Topical antimicrobials Use controversial in wounds/incisions ◦Some formulations may actually delay wound healing Topical antimicrobials than weof stronger High concentrations directly at the site Think ◦ Culture and susceptibility results underestimate activity!!! may be ◦ Intermediate sensitivity drugs may work ◦ Avoid those listed as resistant Includes ◦ Shampoos ◦ Ointments ◦ Otic preparations Topical antimicrobials Common formulations ◦ Chlorhexidine ◦ Benzoyl peroxide ◦ Nitrofurans ◦ Mupirocin more potent ◦ Silver sulfadiazine ◦ Otic > - · use sparingly. ◦ Antibiotic + antifungal + anti-inflammatory ◦ Otitis externa Topical antimicrobials Chlorhexidine-antiseptic & Found more in shampoos & ◦ Broad spectrum – bacteria, fungi, protozoa ◦ Ointment, shampoos, sprays, wipes ◦ May be combined with other antifungal or anti-inflammatory drugs Benzoyl peroxide > - greasy looking dogs ◦ Broad spectrum – bacteria, fungi ◦ Anti-inflammatory/ degreaser, shampoos Topical ointment more likely to stay in the area after use of Benzoyl Topical antimicrobials Illegal to use in food animals Nitrofurazone ◦ Gram positive and negative ◦ Staph, E. coli Gets aerobic bacteria ◦ Possible mutagen/carcinogen in lab animals ◦ Prohibited from use in food animals ◦ Topical and systemic can cause systemic exposure if applied to invision site Topical antimicrobials Little resistance to it Mupirocin ◦ Unique mechanism precludes cross-resistance with other antibacterials ◦ Active against aerobic Gram-positive organisms, some gramnegative ◦ Anti-staphylococcal (including some MRSA, MRSP) ◦ FDA approved for topical use in dogs do not put topicals Topical antimicrobials Silver sulfadiazine Combination product ◦ Silver component interferes with the cell wall ◦ Has antifungal properties ◦ Sulfadiazine – folic acid pathway leads to synthesis of required precursors for cellular function amino acids , nucleotides Human topical products ◦ Burns Soothing. Used on wounds , othevolecules in the eye Topical antimicrobials - otic Fluorquinolone antibiotic ↳ Enrofloxacin + silver sulfadiazine -fungus Synergistic combination ◦ Gram-positive and ram-negative bacteria ◦ includes Pseudomonas ◦ Fungus FDA approved canine product ◦ Baytril Otic Fluoroquinolone – inhibits DNA gyrase Posatex = fluorquinolone mometamax Topical antimicrobials - otic (gentamycin) claro-amphenicol Orbifloxacin + mometasone + posaconazole ③ - ◦ Fluoroquinolone ◦ Steroid ◦ Triazole antifungal antibiotic : (floxacin) aminoglycoside (florfenicol) Topical antimicrobials - otic Gentamicin + mometasone + clotrimazole - ◦ Aminoglycoside ◦ Gram–negative aerobes, staphylococci ◦ Steroid ◦ Azole antifungal ◦ Malessezia -yeast Otic gentamicin increases risk for ototoxicity ◦ Especially if ear drum is ruptured!!! Make sure the ear drug isn’t ruptured before putting this in it Amphenicol (broad spectrum- not pseudomonas) antibiotic T Topical antimicrobials - otic Allylamine antifungal Steroid Florfenicol + terbinafine + mometasone ◦ Amphenicol ◦ Similar to chloramphenicol ◦ No aplastic anemia ◦ Broad spectrum ◦ Staphylococci, not pseudomonas ◦ Allylamine antifungal ◦ Steroid Long-acting otic formulation good for 30 days Topical antimicrobials - otic Florfenicol + terbinafine + mometasone ◦ One dose lasts one month! ◦ Neurogenic KCS only see if dung goes where its not allowed. > - ◦ Within 1 day of administration ◦ Reversible (median 86 days) ◦ Pilocarpine didn’t alter course ◦ Likely ruptured ear drum… J Am Vet Med Assoc. 2022 Nov 8;261(1):97-103. Systemic antimicrobials Deep conditions Widespread conditions ◦Deep pyoderma, otitis media/interna Can be combined with topical Systemic antimicrobials Canine bacterial folliculitis ◦ Target MSSP until proven otherwise! First tier treatments ◦ β-lactam antibiotics ◦ Cephalexin ◦ First generation cephalosporins ◦ Amoxicillin-clavulanate ◦ β-lactam plus β-lactamase inhibitor claramox ◦ Lincosamides ◦ Clindamycin ◦ Potentiated sulfonamides ◦ Trimethoprim-sulfa ◦ Concerns over toxicity Systemic antimicrobials First or 2nd tier treatments ◦Case-by-case basis ◦ 3rd generation cephalosporins ◦ Cefpodoxime – once daily simplicet ◦NOT Cefovecin – onceNEED weekly – cats? ALL CATS CEFOVECIN!!! 2nd or 3rd tier ◦ Culture based! injectivene A single dose is usually not enough Acetyl CoA Systemic antimicrobials Fungal therapies Squalene Epoxidase ◦ Combination topical and systemic treatment a conc in body ◦ Commonly used systemic drugs ◦ Accumulate in skin and hair 14-a-demethylase ◦ Griseofulvin – ringworm ◦ Terbinafine Pulse dosing regiments for tx of fungal skin diseases 7 ◦ Itraconazole Squalene X Terbinafine. Squalene-2,3 oxide Lanosterol X Itraconazole Ergosterol Systemic antimicrobials Terbinafine ◦ Administration of 30-40 mg/kg PO q24h for 14 days results in detectable drug in the hair for an additional 8 weeks! Itraconazole ◦ Concentrations in sebaceous glands 5-10 x plasma concentrations ◦ Detected in surface skin 3-4 weeks after discontinuing therapy Don’t pulse dose fungal pneumonia (need to treat everyday) Systemic antimicrobials Unique PK is the basis for pulse dosing regimens Examples: ITZ (Itraconazole) ◦ Dogs: Malassezia: 5 mg/kg/day for 2 days x 3 weeks ◦ Cats: dermatophytosis: 10 mg/ kg/day once a day for 28 days then alternate week therapy √ √ √ √ √ √ Fungal therapies - Topical Drug Class Drug Formulation Imidazole Miconazole Conofite Cream Clotrimazole Lotrimin topical Mometamax and Otomax (with other agents) Polyene Nystatin Mycostatin Allylamine Terbinafine Osurnia and Claro (with other agents) For your information only. Not on test. Questions?