Pharmacology 9% Flashcards

Question

Vitamin A

Answer 1

- an alcohol, all-trans retinol - Oxidized in the body to retinol and retinoic acid - Both important in the induction and maintenance of normal growth and differentiation of keratinocytes - Only retinol has all the known functions of vitamin A

Answer 2

- Synthesized as a natural metabolite of retinrol - One of the most commonly prescribed retinoids in veterinary medicine - Side effects in dogs: conjunctivitis, hypertriglyceridemia, hypercholesterolemia, increases levels of ALT, AST, ALP. - Side effects in cats: conjunctivitis, diarrhea, anorexia, vomiting - With long-term use, skeletal abnormalities including cortical hyperostosis, periosteal calcification, long-bone demineralization are a concern. - Potent teratogen

Answer 3

One of the most commonly prescribed retinoids | - a synthetic retinoid, no longer available

Answer 4

- Inhibit keratinocyte proliferation, induce terminal differentiation of keratinocytes and decrease immunologic reactivity

Answer 5

NAC is a known mucolytic (breaks down biofilm?) - Proposed to completely inhibit the uptake of amino acids such as cysteine by bacterial cells or to react with bacterial cell proteins with its own sulfhydryl group

Answer 6

Fungistatic

Answer 7

Azole antifungal drugs inhibit sterol 14-alpha demethylase, a cytochrome P450-dependant fungal enzyme involved in synthesis of ergosterol from lanosterol - Ergosterol is a key component of the fungal cell wall - The result is an accumulation of 14-alpha methyl sterols which disrupt the fungal cell membrane - All azole antifungals have the potential to be teratogenic - Some azole antifungals used in humans for treatment of leishmaniasis (ex. fluconazole). * * Azoles inhibit the cytochrome P450 enzyme lanoesterol 14-demethylase; inhibits conversion of lanosterol to ergosterol, causing accumulation of C14 methylated sterolds - also inhibit intracellular triglyceride, phospholipid synthesis, cell wall chitin synthesis and inhibition of oxidative and peroxidative enzymes

Answer 8

Azole antifungals that have either two nitrogen molecules (i.e. an imidazole) or three nitrogen units (i.e. triazole) in their azole ring - Imidazole: ketoconazole, econazole, enilconazole, clotrimazole, miconazole - Triazole: itraconazole, fluconazole. voriconazole, posaconazole, ravuconazole - Triazoles and allylamines are liphophilic and kertainophilic, shorter durations of therapy and pulse therapy are feasible.

Answer 9

- Imidazole antifungal | - large

Answer 10

- Mutations in the gene encoding the demethylase enzyme - Increased production of C-14 alpha demethylase - Increased azole efflux by fungal cell membrane transporters

Answer 11

- Ketoconazole - Itraconazole - Spinosad

Answer 12

- Imidazole antifungal - General inhibitor of P450 enzymes - at higher concentrations KCZ may have a direct physicochemical effect on the fungal cell membrane, leading to fungicidal action. - ALSO blocks 11-hydroxylase; blocks transformation of deoxycorticosterone to corticosterone; also inhibits the transformation of progersterone to pregnenolone - inhibit yeast transforming into mycelial form - Absorption best when given with food, inhibited when given with antacids - Greater toxicity relative to triazole antifungals - Can cause vomiting, diarrhea, lethargy and diarrhea - Mild increases in transaminases can occur - Can cause hepatitis (anorexia, lethargy, increasing ALT, ALP, hyperbilirubinemia) - Pruritus and cutaneous erythema reported in small number of dogs - Lightening of the hair coat associated with loss of guard hairs and cataract formation can occur - Potent inhibitor of mammalian cytochrome P450 enzymes and efflux transporter proteins, such as P-glycoprotein - Inhibits the metabolism of cyclosporine - Inhibits testosterone and cortisol synthesis - give with fats to increase absorption - Metabolized by liver to inactive metabolite - Less effect against aspergillus and sporotrichosis - NOT recommended for feline dermatophytosis - NOT a first choice for animals with fungal infection involving the CNS or ocular disease - Increases concentrations of drugs metabolized by P450 enzymes. - Cats experience alot of side effects (inappetence, weight loss, hepatotoxicity); do not use i cats. - ALT, ALP, bilirubin and bile acids should be monitored before and during therapy (i.e. every 2-4 weeks) - NOT approved for use in cats or dogs in the USA

Answer 13

- Synthetic triazole antifungal - Binds weakly to mammalian P450 enzymes - Concentrated in lipophilic tissues and keratin; secreted in sebum - Persists in skin 2-4 weeks after discontinuation - Does not penetrate well into CNS or ocular tissues - Metabolized by liver into inactive metabolites that are excreted in bile and urine - Given with food, absorption decreased when given with antacids - Compounded versions have very poor absorption, stability etc. - Inhibits metabolism of mammalian P450 enzymes; does not interfere with cortisol synhtesis - Inhibits metabolism of other P450 dependant drugs (cisapride, diazepam, cyclosporin). - Only triazole converted to an active metabolite - Adverse effects: vomiting and transient lethargy - Mild to moderate increase in ALT - Significant hepatotoxicity less likely to occur than ketoconazole - Ulcerative skin lesions occur when especially when doses of 10 mg/kg/day or more are used from cutaneous vasculitis - Does not suppress adrenal and testicular function - Variable efficacy against Pythium - DO NOT administer with ketoconazole, cisapride, or terfenadine - fatal cardiac arrhythmias can occur - Prolongs the effects and increases the toxicity of benzodiazepines, cyclosporine, glucocorticoids, antihistamines, quinidine, digoxin, vincritine, warfarin, sulfonylureas. - Concurrent antacids, H2 blocks and anticholinergics are contraindicated

Answer 14

- A bis-triazole antifungal - higher affinity for fungal enzymes than mammalian enzymes. - Penetrated well into ocular and CNS independant of inflammation - Least active azole antifungal with narrowest spectrum - More water soluble and stable than itraconazole - Diffuses better into body tissues (saliva, urine, synovial fluid, and CSF) - Absorption unaffected by gastric acidity - Primarily excreted via kidneys; reduce dosage in animals with underlying kidney disease and avoid in pregnant animals - Not extensively metabolizes - Side effects uncommon and similar to itra. - Excellent spectrum of activity for yeasts - Potentiates the effects of anticoagulants, thiazide diuretics, rifampin, cyclosporine, glipizide, antihistamines, diphenyldantoin and theophylline - Does not suppress adrenal or sex hormones - Evaluate liver enzymes prior to and during therapy. - The most fungal-enzyme specific azole antifungal - Thought to be less effective than other azole antifungals with treating dermatophytosis

Answer 15

- Second-generation triazole - Derived from fluconazole - Used to treat disseminated mold infections; not affective against Sporothrix or zygomycetes - Good CNS penetration - Of all triazoles, it is the most potent inhibitor of P450 enzymes - Cats extremely sensitive to adverse effects: inappetence, ocular and CNS signs including ataxia, pelvic limb paresis, mydriasis, apparent blindness, decreased PLR's, decreased menace, cardiac arrhythmias and hypokalemia

Answer 16

- Itraconazole analogue - Good efficacy for refractory deep mycoses - Broadest spectrum of all azole antifungals - Spectrum similar to voriconazole - Absorption improve with fatty meal - Gastric acid suppression can reduce bioavailability of posaconazole

Answer 17

- Ketoconazole - Itraconazole - Cyclosporin - Cisapride - Diazepam - Digoxin - vinca alkaloids

Answer 18

Itraconazole

Answer 19

- polyene macrolide antibiotic - Produced by Streptomyces nodosus - Closely related to nystatin - Irreversibly binds sterols (primarily ergosterol; to a lesser degree cholesterol) in fungal cell membranes, forming pores or channels with subsequent leakage of ions - Generally considered fungistatic, can be fungicidal at high doses - Immunomodulatory effects: activated macrophages, and enhances macrophage killing capacity; stimulates lymphocytes, neutrophil function and induces production of TNF-alpha - Active against all important small animal fungal pathogens; also has activity against leishmania - Treatment of choice for visceral leishmaniasis; Thought to bind to ergosterol in the protozoal leishmania membrane and block the ability of Leishmania to bind and enter macrophages; WHO recommends against the use of AMB for treating canine leishmaniasis. - mechanism of resistance is not well understood but believed to be secondary to decreased cell wall ergosterol content - IV infusion in lyophilized form - Nephrotoxicity is the major adverse effect that is dose dependent and transient if detected early; loading sodium before the infusion may decrease severity of nephrotoxicity - Fever, vomiting and inappetence can occur in some dogs - Phlebitis can occur at injection site - Newer lipid formulations are taken up by macrophages and carried to the sites of fungal induced inflammation - Poor penetration into CSF, bones, brain - primarily indicated for the treatment of severe systemic mycotic infections - NOT effective against dermatophytes

Answer 20

- fluorinared pyrimindine related to fluorouracil - Has activity ONLY against cryptococcus and Candida; also used for Aspergillus and some fungi associated with phaeohyphomycosis; NOT affective against dermatophytes or filamentous fungi - Fungal cells only susceptible if they contain the enzyme cytosine permease which allows flucytosine to be taken in by the fungal cell - After taken up, 5-fluorcytosine is then deaminated by cytosine deaminase to 5-fluoro-21-deoxyuridic acid; these substances inhibit thymidylate synthetase and DNA synthesis - These fungi deaminate flucytosine to 5-fluorouracil so toxicity in mammalian cells is limited - resistance occurs during treatment, always pair it with a different antifungal (most commonly AMB) - Resistance to this drug results from modifications in fungal enzymes that required for flucytosine uptake and metabolism - Excellent penetraction into CSF and aqueous humor. - Excreted unchanged in the urine; adverse effects (myelosuppression and and GI upset) increased in animals with kidney disease - Avoid use in dogs; consider in cats with refractory cryptococcosis - contraindicated in animals with renal disease, neonates, pregnancy and preexisting myelosuppression - Dogs develope a severe and reversible drug eruption wihtin 2-3 weeks of starting treatment. - Evaluate CBC and biochemical profile prior to and every 2 weeks during treatment

Answer 21

- oral antifungal derived from Penicillium griseofulvum - Binds to fungal tubulin leading to impaired microtubule function and mitotic arrest; inhibits nucleic acid synthesis and cell mitosis by arresting division at metaphase - also has antiinflammatory properties: known to suppress delayed-type hypersensitivity reactions and irritant reactions in the skin - Rapidly deposited in keratin precursor cells in the skin and hair; disappears from stratum corneum within 48-72 hours; concentrates in newly formed keratinized epithelium and concentrates in the dermis and appendanges - Metabolized by the liver to inactive compounds - Fungistatic with limited spectrum of activity; ONLY ACTIVE AGAINST DERMATOPHYTOSIS - Very effective against dermatophytes but expensive and can cause GI upset and myelosuppression - Used primarily to treat dermatophytosis, also has efficacy against yeasts including Malassezia and Candida; NOT EFFECTIVE AT TREATING MALASSEZIA - Resistance mechanism believed to be due to altered tubulin in some dermatophytes - Potent induce of P450 enzymes; so decreases the efficacy of other drugs that are metabolized to inactive metabolites by P450 enzymes - Teratogenic! Do not use in pregnant animals, or animals with hepatic dysfunction; feline retroviral infections, anemia or leukopenia - Can cause neurotoxicity in overdoses - Interferes with spermatogensis - inappetence, vomiting, diarrhea - cats: myelosuppression; more likely in FIV+ cats - Persians, Siamese, Abyssinians may be predisposed to side effects - Monitor CBC every 2 weeks - Drug carried to stratum corneum by diffusion, sweating, and transepidermal fluid loss

Answer 22

- decrease efficacy of other drugs that are metabolized o inactive metabolites by P450 enzymes - Griseofulvin

Answer 23

- Synthetic allylamine - Inhibits fungal squalene epoxidase; blocks fungal lanoesterol and ergosterol synthesis and leads to accumulation of toxic squalene with resultant fungcal cell lysis - fungistatic and fungicidal - Fungicidal against dermatophytes, aspergillus, sporothrix; less effective against yeast or dimorphic fungi; active against malassezia and candida - Drug delivered to stratum corneum via sebum - Has some effect against pythium (when combined with ITZ) - Reduce dosage with renal or hepatic insufficiency - May be used in pregnancy - Cimetidine increases blood concentration, rifampin decreases blood concentration - Not inhibitory to most P450 enzymes - Most effective for dermatphytes; also useful for Malassezia - Resistance in dermatophytes reported as a result of altered squalene epoxidase - accumulated in hair, skin, claws and fat and persists weeks after medication is discontinued - GI signs (vomiting and increased liver enzymes) occur uncommonly; facial pruritus has been reported in cats - Evaluate liver enzymes prior to and every 2 - 4 weeks through therapy - Adverse effects: vomiting, anorexia, diarrhea, abdominal pain, hepatotoxicity (biliary stasis, increased ALP and ALT), neutropenia, pancytopenia

Answer 24

- An "echinocandin" lipopeptide antifungal - A cyclic hexapeptide that inhibits the formation of beta-1, 3-D-glucans in the fungal cell wall; blocks cell wall synthesis - Inhibits hyphen growth and branching, converts mycelium to small clumps - Fungicidal against Candida spp. and fungistatic against Aspergillus species. - Active against dermatophytes, Sporothrix and some yeasts - Given IV; has been used to treat aspergillosis in humans that do not respond to AMB and azaleas - infusion-related urticaria, pruritus, hepatotoxicity

Answer 25

- A prodrug, metabolized into penciclovir - A guanosine (i.e. nucleoside) analogue; use of nucleoside analogues during viral replication leads to the formation of abnormal nucleic acids or termination of nucleic acid synthesis - Activate by the herpesviral enzyme thymidine kinase (TK) which phosphorylates the drug into a monophosphate form - Host cell enzymes then phosphorylate these drugs further to triphosphate forms, which concentrate in virus-infected cells and interfere with viral DNA replication via inhibition of the viral DNA polymerase enzyme - Drug resistance occurs from reduced viral TK activity, altered viral TK or altered viral DNA polymerase - Potent inhibitor or FHV-1 replication

Answer 26

- Amino acid that interferes with herpes viral replication by poorly understood mechanisms - Antagonism of arginine may somehow be involved because a high lysine to arginine ratio appears to be important

Answer 27

- Cytokines with antiviral properties produced by leukocytes and fibroblasts - IFN-a (alpha) - IFN-b (beta) - IFN-w (omega) - Activate natural killer cells, increase expression of MHC class I molecules and have anti-tumor activity

Answer 28

IFN-y (i.e. gamma); the only type of type II interferon and produced by T lymphocytes and NK cells in response to antigenic stimulation - Plays important role in clearing of intracellular pathogens by macrophages.

Answer 29

- A group of more than 20 molecules that differe slightly - Inhibit vial nucleic acid and protein synthesis - Human recombinant IFN-alpha has been administered to cats for treatment of retroviral infections, feline upper respiratory viral infections and FIP - Inhibits replication of FeLV, FIV, FHV-1 and feline coronavirus in vitro. - Parenteral administration can lead to the development of neutralizing antibodies and apparent loss of activity after 3-7 weeks - Oral administration controversial due to presumed proteolytic degradation by gastric acid; can still benefit if absorbed through mucosa

Answer 30

- Type 1 interferon closely related to IFN-alpha - Secreted by virus-infected leukocytes - Precise mechanism of action is not known - In dogs: increases macrophage and NK cell activity - Antiviral effects against several feline viruses in vitro (FeLV, FHV-1, feline calicivirus, canine and feline parvovirus, feline coronavirus) - Also has anti-tumour activity - Recombinant feline IFN-w produced by silkworms available in Eu and Canada. - Similar effect in both canine and feline cells - Transient lethargy, fever, vomiting, mild diarrhea and anorexia have been documented in some cats - Mild neutropenia, eosinophilia and reversible increases in the activity of serum AST have also been described following treatment

Answer 31

- derived from the heavy metal antimony (i.e. "Sb") - A pentavalent antimondy compound because they contain Sb atoms with give electrons in their outer shell - Recommended as first choice for treatment of leishmanisis - Mechanism of action not completetly clear; suspected that pentavalent antimony goes under reduction to the more toxic trivalent antimony, possibly within macrophage phagolysosomes or within the parasite itself - Trivalent antimony inhibits protozoal enzymes and damages protozoal DNA - - Elimination of the parasite does not always occur - Resistance to antimonials is an increasing problem in humans with leishmaniasis. - Administered subcutaneously - Typically combined with allopurinol for canines - 80% eliminated by kidneys ; can result in lethargy, vomiting, diarrhea, inappetenace and increased serum liver enzyme activity more likley to occur in the presence of kidney disease - Can cause renal tubular necrosis in healthy dogs

Answer 32

- A purine analogue - In parasites, metabolized to derivatives that are incorporated into RNA which leads to impaired RNA synthesis - Resistance can occur from reduced activity of purine transporters and a reduced ability to accumulate purine - Most commonly combined with meglumine or miltefosine. - Rarely causes side effects in dogd - Inhibits mammalian xanthine oxidase, which results in decreased uric acid production from xanthine; long-term use can result in xanthine urolithiasis - Serious adverse effects occur when combined with azathioprine

Answer 33

- Effective alternative to pentavalent antimonials - A phospholipid analogue that activates cellular proteases in Leishmania spp. which result in apoptosis. - First highly active oral drug for treatment of leishmaniasis - Elimination of the parasite does not always occur - Resistance can result from increased P-glycoprotein-mediated drug efflux and decreased drug uptake - WHO recommends decreasing use of this drug to prevent resistance - Does not contribute to renal pathology in dogs.

Answer 34

- allylamine

Answer 35

- synthetic biguanide | -

Answer 36

- Cyclosporine - Certain antihistamines (terfenadine, astemizole) - GI motility agents (cisapride) - Benzodiazepines - Calcium channel blocksers - Anticonvulsants - antimycobacterial agents

Answer 37

- Inorganic halogens - exact anti fungal action unknown; may facilitate phagocyte killing of fungal cells; have no effect against fungal organisms in vitro - Enhance the halide-peroxidase killing system of phagocytic cells - Anti-inflammatory: quench toxic oxygen metabolites and inhibit neutrophil chemotaxis - Used to treat sporothrix, basidiobolus, subcutaneous phycomycosis, rhinosporidiosis - Do not use in animals with thyroid disease, iodide hypersensitivity, renal failure, dehydration, pregnancy - Give orally - Adverse effects: anorexia, hyper salivation, vomiting, muscle twitching, cardiomyopathy, heart failure, death, ocular/nasal discharge, scaling, dry hair coat, hypothyroidism thyroid goiters and/or adenomas - Highly effective in treating sporotrichosis

Answer 38

- a benzoylphenyl urea; an insect growth regulator that acts by inhibiting chitin synthesis, polymerization and deposition - Proposed to interfere with formation of fungal cell wall and insect exoskeleton - Controversial for use for treating fungal infections

Answer 39

- A non selective janus kinase inhibitor (i.e. a "JAKinib") with most potent effects on JAK1 associated with the intracellular portion of type I and type II cytokine receptors - Blocks the transmission of interleukins 2, 4, 6, 13, 31 - Blocking of the cytokine signal prevents gene transcription and protein production mediated by these cytokines.

Answer 40

- A caninized Monoclonal antibody that binds and neutralized IL-31

Answer 41

- Have a beta-lactam ring in their molecular structure - Includes penicillins, cephalosporins, monobactams and carbapenams - Bactericidal - Covalently bind and inhibit pencillin binding proteins (i.e. PBP's); PBP's are needed to catalyze the cross-linking (or transpeptidaiton) or the peptidoglycan layer of bacterial cell walls. - When penicillin binding proteins are inactivated by Beta lactam antibiodics, bacterial enzymes that hydrolyse the peptidoglycan cross-links continue to function and break down the cell wall further - Accumulation of peptidoglycan precursors triggers activation of cell wall hydrolases, which further digest intact peptidoglycan - Results in bacterial rupture

Answer 42

- Results primarily from beta-lactamase production | - Production of altered penicillin binding proteins (such as PBP2a)

Answer 43

time-dependent pharmacodynamics

Answer 44

- An inhibitor of cell wall synthesis - derived from penicillium molds - Categorized as 1) naturally occurring pencillins (i.e. Penicillin g; aka benzyl penicillin); 2) semisynthetic aminopenicillins (ampicillin, amoxicillin), 3) penicillinase-resistant pencillins (methicillin, oxacillin, cloxacillin,), 4) extended-spectrum penicillins (i.e. antipseudomonal penicllins like ticarcillin). - Typically distributed in the extracellular fluid of most tissues - low penetration across the blood-brain barrier and blood-ocular barrier - Rapid renal excretion and concentrated in the urine

Answer 45

- A semisynthetic aminopenicillin - Activity against gram positive aerobic bacteria (cocci and bacilli) and anaerobes, some susceptible gram negative bacteria - Commonly combined with clavulanic acid, a beta-lactamase inhibitor

Answer 46

- An extended spectrum carboxypenicillin - Increased activity against suspectible gram-negative aerobes, including Pseudomonas aeruginosa, Proteus, Klebsiella and anaerobes - Some reduction in gram positive spectrum - Destroyed by beta-lactamases, often combined with a beta lactamase inhibitor such as clavulanate - Typically given parenterally or formulated topically

Answer 47

- A Ureidopencillin - Covers suscpetible gram-positive and gram-negative aerobes including Pseudomonas aeruginosa. Some loss of anaerobic spectrum - Destroyed by beta-lactamases, often combined with tazobactam (a beta-lactamase inhibitor)

Answer 48

- An inhibitor of cell wall synthesis - A group of beta-lactam antibiotics - Originally derived from Acemonium spp. - Broadly grouped into 1st, 2nd, 3rd and 4th generation based on spectrum of activity - As the generation increases, there is more gram negative coverage - Cephalosporings are resistant to staphylococcal beta-lactamases - extended-spectrum third generation cephalosporins are also resistant to many gram-negative beta lactamases - Extended-spectrum beta-lactamase enzymes can hydrlolyze even third-generation cephalosporings and present an important therapeutic challenge. - Using third generation cephalosporins can promote ESBL e.coli - Adverse effects: GI upset and hypersensitivity reactions; cross-sensitivity can occur between penincillins and cephalosporins.

Answer 49

- A group of beta-lactam antibiotics - An inhibitor of cell wall synthesis - Highly resistant to almost all beta-lactamases - Include imipenem, meropenem, ertapenem and doripenem - Penetrate the outer membrane of gram negative bacteria more effectively than any other kind of beta-lactam - Bind to a wide number of penicillin binding proteins, leads to rapid lysis of a broad spectrum of bacteria - In contrast to other beta-lactams, carbapenams have a post antibiotic effect similar to aminoglycosides and flouroquinolones - Reserved for treatment of serious, multiple drug resistant gram-negative infections especially E.coli, Klebsiella pneumoniae and P. aeruginosa that are resistant to other antibioitics - METHICILLIN-RESISTANT BACTERIA ARE RESISTANT TO CARBAPENEMS - Imipenem is metabolized by dehydropeptidase-1, a brush border enzyme in the proximal renal tubules, to an inactive metabolite that is nephrotoxic; imipenem is typically administered with cilastatin which inhibits the dehydropeptidase 1 enzyme

Answer 50

- An inhibitor of cell wall synthesis - A glycopeptide, i.e. a cyclic glycosylated peptide antimicrobial - Bactericidal - inhibit the synthesis of peptidoglycan by binding to amino acids (D-alanyl-D-alanine) in the cell wall, preventing the addition of new units. - Other glycopeptides include teicoplanin, decaplanin - Not absorbed orally, IV infusion required - Useful for treating MDR gram positive bacterial infections such as MR Staph infections, resistant enterococcal infections, encrusting cystitis. - Resistance is extremely rare to this antimicrobial - Resistance occurs from bacterial alteration of the terminal amino acid to which vancomycin binds

Answer 51

- A nucleic acid inhibitor - Bind to DNA gyrase (also known as topoisomerase II) and topoisomerase IV; these are enzymes that cleave DNA during DNA replication - CONCENTRATION DEPENDANT ANTIBIOTICS, best administered as a single high dose. - Poor absorption occurs when given with antacids or supplements containing aluminum, calcium, iron and zinc. - Results in disruption of bacterial DNA and protein synthesis - For the veterinary fluoroquinolones (marbofloxacin, enrofloxacin, orbifloxacin), DNA gyrase is the primary target for gram-negative bacteria; topoisomerase IV is the primary target for gram-positive bacteria - Created by the addition of a fluorine group to nalidixic acid - Newer-generation fluoroquinolone inhibit both DNA gyrase and topoisomerase IV in gram-positive bacteria leading to enhanced activity for treatment of gram-positive bacteria and anaerobic bacterial infections and decreasing selection for resistant strains. - 3rd generation fluoroquinolone: pradofloxacin, moxifloxacin, levofloxacin, gatifloxacin - Most valuable for treating gram-negative infections as well as staphylococci, although Staph tend to have a higher MIC than gram negative bacteria for fluoroquinolone - Enrofloxacin is metabolized to ciprofloxacin - Ciprofloxacin's bioavailability is not the same as humans. - Most concentrated in the urine - Obtain high intracellular concentrations and can be used to treat infections by intracellular pathogens such as Mycoplasma and mycobacterium.

Answer 52

- DNA gyrase mutations - decreased bacterial permeability - Increased drug efflux - Pradofloxacin and ciprofloxacin have higher in vitro efficacy against pseudomonas aeruginosa than other fluorquinolones.

Answer 53

- Cats can go blind with enrofloxacin (>5 mg/kg/day) due to acute retinal degeneration; results from a functional defect in fluoroquinolone transport protein in the cat with accumulation of photo reactive drug in the retina. - Orbifloxacin can also cause retinal degeneration in cats but the dose needed to do so is much higher than what is used therapeutically. - Allegedley no retinal degeneration with marbofloxacin or pradofloxacin unless there is a disease (i.e. renal disease) that impairs clearance. - Because they inhibit proteoglycan synthesis and chelate magnesium, can cause cartilage and joint toxicity in young animals; - avoid fluoroquinolines for longer than 7 days in animals ages 1 month - 7 months; this is a period of rapid growth. - Cats thought to be more resistant to cartilage toxicity - In dogs, >10mg/kg/day or Prado has been associated with myelosuppression. - Fluoroquinolone inhibit some cytochrome P450 enzymes which decrease metabolism of other drugs.

Answer 54

- A "nucleic acid inhibitor" - Rifampin is within the rifamycin antibiotic drug class - Bactericidal; exerts its effect by inhibiting the beta-subunit of DNA-dependent RNA polymerase in bacteria - results in impaired RNA synthesis - Effect against staphylocci, streptococci and a few gram-negative organism. - Also used in antimycobacterial regimens. - Recommended to use in conjunction with other antibiotics to decrease emergency of rifampin resistance - Resistance develops quickly when used alone, however this primarily applies when used for long-term treatment, such as when treating mycobacterial infections - High degree of lipid solubility; provides a degree of intracellular penetrations required for treating infections caused by intracellular bacteria (i.e. mycobacteria, brucella) - Monotherapy has been successful when used to treat MRSP

Answer 55

- Single mutation that leads to an altered RNA polymerase that does not effectively bind rifampin

Answer 56

- vomiting, anorexia - Drug can impart an orange-red color to the urine and a lesser extent the tears, saliva, sclera and mucous membranes - Increased serum liver enzyme activities and hepatopathy - Doses >10mg/kg/day increase risk of liver toxicity in the dog - Rifampin is one of the THE MOST POTENT inducers of hepatic microsomal enzymes and efflux proteins, such as P-glycoproteins - As such, it can increase the clearance of several administered drugs including glucocorticoids, cyclosporin, itraconazole, digoxin

Answer 57

- The combination act synergistically to inhibit folic acid metabolism by bacteria; the combination interferes with purine and therefore DNA synthesis - Trimethoprim: inhibits bacterial dihydrofolate reductase - Sulfonamides: chemical analogs of para-aminobenzoic acid (PABA) and competitively inhibits the incorporation of PABA into dihydropteroic acid by the enzyme dihydropteroate synthetase which leads to decreased folic acid synthesis - When used seperately, trimethoprim and sulfonamide are bacteriostatic; when used together are bactericidal - Preparations used to treat dogs are typicall 1 : 5 trimethoprim to sulfonamide - Folic acid is of dietary origin in animals, only bacterial purine synthesis is affected - Broad-spectrum; can be used to treat many gram-positive and gram-negative infections - Entercocci inherently resistant to TMS - Many anaerobic bacteria are not sucessfully treated with TMS despite in vitro suscept. - TREATMENT OF CHOICE FOR NOCARDIA - Able to penetrate blood-brain barrier and can be used to treat prostatic infections - Actively concentrates in the urine

Answer 58

- Plasmid-mediated production of altered dihydrofolate reductase or hydropteroate synthetase, with reduced binding affinities - Overproduction of dihydrofolate reductase or PABA by bacteria and reduced bacterial permeability to TMS

Answer 59

- Doberman pinschers, Samoyeds, miniature schnauzers at increased risk for adverse effects to TMS - Reaction primarily caused by the sulfonamide component - Some adverse effects may be inability of dogs to acetylate sulfonamide compounds - GI upset - KCS - Polyarthritis - Cutaneous drug eruptions - Fever - ITP - IMHA - hepatitis - Pancreatitis - Meningitis - Interstitial nephritis - Glomerulonephritis - Aplastic anemia - Hypothyroidism - Hepatic necrosis - Sulfonamide cytolithiasis

Answer 60

- A protein synthesis inhibitor - Rapidly bactericidal with a prolonged concentration dependant post-antibiotic effect - Multiple mechanisms of action - Bind electrostatically to the bacterial outer membrane and displace cell wall Mg2+ and Ca2+ which normally link adjacent lipopolysaccharide molecules; initial binding is greater in gram negative organisms than gram positive organisms; results in impaired cell permeability - Subsequently bacterial cell takes up aminoglycosides which become trapped irreversibly within the cytoplasm; this is an oxygen-dependant process - Anaerobes are inherently resistant to aminoglycosides - Once within cell, aminoglycosides bind to the 30s subunit of the bacterial ribosome which results in decreased protein synthesis - Aminoglycosides with that end in "-mycin" derive directly or indirectly from Streptomyces - Those that end in "-micin" are derived from Micromonospora - Used for gram-negative infections and MDR staph infections - Do not penetrate brain, prostate, eyes, or CSF - Do not administer orally - Does not distribute into fat, may need to decrease dose in obese animals

Answer 61

- Enzymatic modification of the drug by bacteria - More than 50 modifying enzymes have been identified - Reduced drug uptake by bacteria may also occur - Enterococci are intrinsically resistant to low levels because of their anaerobic metabolism - Resistance to one aminoglycoside does not confer resistance to numerous aminoglycosides

Answer 62

- Nephrotoxicity (apoptosis and necrosis of renal tubular epithelial cells, direct damage to glomerulus; aminoglycosides accumulate in renal tissue) - Ototoxicity (damage to the cochlear of the vestibular apparatus and more severe in animals with dehydration or renal disease; cochlear toxicity results from damage to the hair cells of the organ of Corti, whereas vestibular toxicity results from damage to hair cells at the tip of the ampullae cristae; auditory toxicity more common in dogs whereas cats tend to develop vestibular toxicity) - Neuromuscular blockade (not been reported in dogs or cats; decreased actylcholine release at neuromuscular junctions)

Answer 63

- Binds to the 50s subunit of the bacterial ribosome and inhibits bacterial protein synthesis - typically described as bacteriostatic, but may be bactericidal - Broad spectrum activity against gram-positive and gram negative bacteria, anaerobes and some rickkettsial pathogens - Diffuses into CNS and eye

Answer 64

- Porin mutations, drug efflux or production of chloramphenicol acetyltransferase enzymes which inactivate the antibiotic - Resistance to one chloramphenicol derivative predicts resistance to others

Answer 65

- irreversible aplastic anemia in humans; ensure owners wear gloves when handling the antibiotic and discourage splitting of tablets - GI upset - High doses for prolonger periods results in reversible bone marrow suppression - Chloramphenicol is a POTENT INHIBITOR OF P450 ENZYMES, so potential drug interactions exist

Answer 66

- Inhibit protein synthesis by binding to the 50s subunit of bacterial ribosomes - Concetrate inside leukocytes - First macrolide discovered was erythromycin, derived from Streptomyces erythreus - Other Macrolides include: azithromycin, clarithromycin, roxithromycin considered to be advanced generation macrolides with extended spectrum against atypical and some gram-negative bacteria, longer duration of activity, greater intracellular concentrations - Azithromycin is considered an azalide because it contains nitrogen - used primarily for gram positive bacterial infections ; generally considered to be bacteriostatic - Clarithromycin has high intracellular concentration and preferred for rapidly growing mycobacterial infections (usually in combination with Rifampin) - Clindamycin used for staphylococcal pyoderma, anaerobic bacterial infections, toxoplasmosis and neosporosis

Answer 67

- Susceptibility to erythromycin predicts susceptibility to other macrolide antimicrobial drugs - Results from decreased bacterial permeability (for gram-negative bacteria), alteration in the target site, increased drug efflux, and enzymatic inactivation of bacterial esterases - Alteration to target site involves production of a ribosomal methylase that adds a methyl group to the 50s subunit RNA preventing macrolides from binding to ribosome - Expression of methylase confers resistance to azithromycin, clarithromycin, clindamycin

Answer 68

- Very safe - Erythromycin causes vomiting, increased GI motility, diarrhea, decreases appetite and nause - Erythromycin and Azithromycin INHIBIT P450 ENZYMES and so can increase drugs metabolized by these enzymes - Oral clindamycin can cause esophagitis in cats

Answer 69

- It is an oxazolidinone - A semi-synthetic antibiotic used for life-threatening infections caused by gram-positive bacteria resistant to other antibiotics; especially methicillin resistant and vancomycin resistant staph. - Binds to 50s ribosome and prevents formation of the initiation complex for protein synthesis - Unique mechanism as other protein synthesis inhibitors interfere with polypeptide extension - It is a type A monoamine oxidase inhibitor that can interact with serotonin reuptake inhibitors

Answer 70

- Resistance to other protein synthesis inhibitors does not correlate with resistance to Linezolid - Resistance can occur due to modification of the drug's target site, but this is extremely rare as this would require several step mutations before resistance occurs - Bacteriostatic

Answer 71

- bacteriostatic, time-dependant antibiotics - Inhibit bacterial protein synthesis by binding to 30S subunit - broad-spectrum activity against gram postivie and gram negative bacteria, some anaerobes, and atypical and intracellular pathogens (spirochestes, Mycoplasma, rickettsia) - examples: tetracycline, oxytetracycline, semisynthetic tetracyline doxycycline - Doxycycline and minocycline have anti-inflammatory and immunomodulatory properties that result in inhibition of nitric oxide synthase and proinflammatory cytokines such as TNF-alpha - All tetracyclines concetrate in bile, sufficient drug excreted in urine to treat UTIs

Answer 72

- Porin mutations that exclude tetracyclines from the bacterial cell and increased drug efflux mediated by the tetK gene - Some bacteria with tetK may still be susceptible to minocycline - Resistance mediated by tetM confers resistance to all tetracyclines

Answer 73

- GI upset (vomiting, diarrhea, decreased appetite, nausea) - Aside from doxycycline hyclate, giving with food can decrease bioavailability - The hyclate salt of doxycycline has been associated with esophagitis and strictures in cats and life threatening esophageal ulcers in dogs - Follow each tablet with a syringe of water - Avoid tetracyclines (aside from doxycycline) in patients with renal failure ; doxycycline excreted in the intestinal tract - Tetracyclines (aside from doxycycline) can interfere with bone growth and cause significant permanent gray-brown or yellow discoloration of the teeth; not recommended for puppies or kittens - Doxycycline does not cause this as does not bind to calcium as readily - All tetracyclines have the ability to cause hepatic failure and renal tubular acidosis

Answer 74

A tricyclic antidepressant with antihistamine properties

Answer 75

- a prodrug that is metabolized into mycophenolic acid - mycophenolic acid specifically and reversibly inhibits the enzyme inosine monophosphate dehydrogenase which is important for de novo guanine (i.e. purine) biosynthesis required for T and B lymphocyte proliferation - Suppresses lymphocyte proliferation and reduces antibody production by B cells

Answer 76

- A fungal metabolite of Tolypocladium inflatum Gams - Blocks T-cell proliferation by suppressing cytokine production including IL-2, IL-6, IL-1 and TNF-alpha - Also suppressed histamine release and epidermal proliferation - Blocks the transcription of many proinflammatory gene in activated cells - Forms a complex with cyclophilin (a cystosolic protein) which inhibits the phosphatase calcineurin, which blocks dephosphorylation of nuclear factor of activated T cells - In activated T cells, the phosphorylated nuclear factor cannot move into the nucleus to induce gene transcription - Main action of cyclosporine is to decrease T-cell activation by inhibiting IL-2 production and release; it also suppresses mRNA production for IL-2, IL-4, IFN-gamma in stimulated PBMCs and inhibits mast cell and eosinophil degranulation and depresses eicosanoid formation

Answer 77

- A PGE1 analog with antiallergic effects - Vomiting and diarrhea can be seen in some dogs - PGE elevates cyclic adenosine monophosphate (i.e. cAMP) which in turn selectively blocks secretion of cytokines by Th1 cells - Inhibits lymphocyte proliferation, granulocyte activation and synthesis of proinflammatory cytokines (IL-1 and TNF-alpha)

Answer 78

- A phosphodiesterase inhibitor - Used in canine atopic dermatitis as an adjunctive -

Answer 79

- JAK1 - JAK2 - JAK3 - TYK2

Answer 80

- a long-chain complex fatty alcoholthat is a water-binding agent - a ceramide precursor

Answer 81

- A novel neonicotinoid - A nicotinic acetylcholine receptor agonist - derived from natural products produced by the actinomycete Saccharopolyspora spinosa

Answer 82

- Semicarbazone insecticide - Block's an insect's voltage-dependant sodium channel along the presynaptic and postsynaptic nerve blocking the influx of sodium required to propagate a nerve impulse - Semicarbazone insecticide that blocks sodium channels in insects, resulting in nerve paralysis. Associated with the development of drug-triggered pemphigus foliaceus and that product was withdrawn from the market. Topical.

Answer 83

- Third-generation neonicotinoid class insecticide - Binds to nicotinic receptors in the nerve synapse causing continuous nerve stimulation and death. This is paralytic. - Contained in Vectra (combined with pyriproxyfen) and Vectra 3D (contains permethrin). Labelled for fleas, ticks, mosquitoes, lice, sand flies and mites. Topicals.

Answer 84

- Flea allergy dermatitis - Cutaneous adverse food reaction - Atopic dermatitis - Dermatophytosis - Cheyletiellosis - Pemphigus foliaceus - Drug reaction - Intestinal parasite hypersensitivity - Pemphigus foliaceus - Feline hypereosinophilic syndrome - Otodectic mange - Trombiculosis - Cat fur mite - Pediculosis - Staphylococcal folliculitis - Dietary imbalances (biotin or fatty acid deficiency)

Answer 85

- Flea allergy dermatitis - Cutaneous adverse food reaction - Atopic dermatitis - Dermatophytosis - Cheyletiellosis - Pemphigus foliaceus - Drug reaction - Intestinal parasite hypersensitivity - Pemphigus foliaceus - Feline hypereosinophilic syndrome - Otodectic mange - Trombiculosis - Cat fur mite - Pediculosis - Staphylococcal folliculitis - Dietary imbalances (biotin or fatty acid deficiency)

Answer 86

- Superficial to deep perivascular to deep perivascular to interstitial dermatitis with numerous eosinophils and mast cells - Infiltrative mural eosinophilic folliculitis may be visible at the sites of flea bites

Answer 87

- Proposed to be a combination of basophil hypersensitivity, type III and type IV hypersensitivity reactions - Resistant animals develop a delayed-type hypersensitivity reaction in addition to a basophil and mononuclear cell infiltration at the tick attachment site - Clinically, hypersensitivity reactions in dogs and cats can be characterized by 1) focal areas of necrosis and ulceration 2) nodules that may be pruritic, erythematous and ulcerated 3) Pruritic pododermatitis - Histo: may reveal leukocytoclastic vasculitis with hemorrhage necrosis and ulceration (type III) or nodule to diffuse dermatitis due to granulomatous-pyogranulomatous inflammation with numerous eosinophils and lymphoid hyperplasia

Answer 88

- Variable pruritic, seasonal type 1 hypersensitivity - Wheals --> papules --> plaques--> nodules-->crusts--> excoriations--> pigmentary changes - Tip and bridge of nose, and on the pinnae, may also be present on the footpads, eyelids, chin, lips - Lesions on nose may involve nasal planum - In severe cases, the paws may become hyperkeratotic - Dark-colored pinnae may be a predisposing factor - Affected cats typically are outdoors or have access to outdoors - Can be year-round in tropical climates, typically more seasonal - Histo: eosinophilic perivascular to diffuse dermatitis , acanthosis, epidermal necrosis and spongiosis, eosinophilic folliculitis, furunculosis, flame figures; can be indistinguishable from herpes viral dermatitis when inclusion bodies not seen. - confinement indoors is the best form of management - Catnip 10 times more effective at repelling mosquitoes than DEET - Extracts from the seeds of the mediterranean plant Vitex agnus castus (monk's pepper) can be used as a spray to repel mostquitoes for roughly 6 hours.

Answer 89

nepetalactone | - Cat nip (Nepeta cateria) shown to repel mosquitoes 10 times more effectively than DEET

Answer 90

A naturally occurring sphingoid base

Answer 91

- Both are forms of sustained-release microvesicle technology used in topicals - Novasome: outer lipid membrane that contains water; as these bind to hair and skin and has long-term moisturizing effect as microvesicles break down - Spherulite: microvesicles have 10-1000 layers that slowly break down and release active ingredients and surfactants that make up each layer; Chitosanide used to make spherulites. Chitosanide is moisturizing and hygroscopic

Answer 92

- Precipitate proteins and do not penetrate deeply - Agents are drying and decrease exudations - Used in acute/subacute/chronic exudative dermatoses - Examples include tannins and witch hazel (hamamelis)

Answer 93

Incorporated into stratum corneum and attract water - Propylene glycol, glycerin, colloidal oatmeal, sodium lactate, cardboxylic acid, lactic acid may be applied between baths

Answer 94

A substance that relieves inflammation, irritation, and leaves a leaves a protective film.

Answer 95

1) Decreasing pruritic load by depleting, removing or inactivating pruritic mediatros. 2) Substituting some other sensation (i.e. heat or cold) for itch. 3) Protecting the skin from external influences (i.e. scratching, biting, trauma, temperature changed, humidity changes, pressure, irritants). 4) Anaesthetizing peripheral nerves 5) Raising the pruritic threshold by cooling or moisturizing and correcting the epidermal barrier function of the skin 6) Using biochemical agents (i.e. topical glucocorticoids and antihistamines)

Answer 96

- Local anaesthetic, chemically different from the other local anaesthetics (i.e. the "-caines") - Low sensitization and irritant potential - No potential to cause methemoglobinemia like the other -caines

Answer 97

Substances that kill or prevent growth of microbes (use especially for preparations applied to living tissue) - a type of germicide

Answer 98

Agents that prevention infection by destruction of microbes (term used especially for substances applied to inanimate objects) - A type of germicide

Answer 99

- Precipitate proteins and dehydrate protoplasm - Can be bactericidal (not sporocidal), astringent, cooling and rubefacient - Irritating to denuded surfaces and contraindicated in acute inflammatory disorders

Answer 100

- Antibacterial, antifungal - 40-50% is best - In dilute solutions, few humectant properties because it is hygroscopic - At 60-75% solution, denatures and solubilizes protein and is keratolytic

Answer 101

- Denature microbial proteins, antipruritic and somewhat antifungal - Used as preservatives at low levels; are irritating, or toxic at higher levels - Few legitimate uses on the skin other than use at low levels - Contraindicated in cats - Ex: hexachlorophene, resorcinol, hexylresorcinol, thymol, picric acid

Answer 102

- Phenol-related biguanide antiseptic and disinfectant - Highly effective against many fungi, viruses, and most bacteria except some Pseudomonas and Serratia strains - 2-4% needed for good Malassezia and anti-staphylococal effects - Non-irritating, rarely sensitizing, not inactivated by organic matter and persistent in action

Answer 103

- Imidazole antifungal - Has antibacterial properties as well including against S. aureus where it has been found to be bactericidal at low concentrations and destabilizes bacterial cell membranes - Synergistic when combined with chlorhexidine - Exerts an effect by blocking lanosterol 14 alpha demethylase preventing the transformation of lanosterol into ergosterol

Answer 104

- A halogenated agent - Elemental iodine is the active ingredient and the mechanism of action is unknown - Rapidly bactericidal, fungicidal, virucidal, sporocidal - Older products (tincture of iodine, lugol iodine solution) are irritating and sensitizing especially in cats - The "tamed" iodines (i.e iodophors) have a lower level of irritation or sensitization. - Povidone-iodine (i.e. Betadine) - iodine with polyvinylpyrrolidone which slowly releases iodine to tissues, has prolonged action (4-6 hours), is non-stinging, nonstaining and not impaired by blood, serum, necrotic debris or pus. - Iodophors can be drying to the skin and staining to patients with light-colored haircoats and the skin of the person applying the product; irritating to scrotal skin and the external ear.

Answer 105

- Effective bactericidal, fungicial, sporicidal and virucidal agents - Effect thought to be due to liberation of hypochlorous acid - Fresh preparations are needed - Sodium hypochlorite diluted 1:10 is generally well-tolerated. - Organic matter greatly reduces the solution's antimicrobial activity - 1:10 - 1:20 used for MRSP - Vetericyn: an oxychlorine compound; this is a sodium salt of hypochlorous acid and has a pH of 7 (dilute bleach has pH of 11); hypochlorous acid is a much stronger antimicrobial agent than sodium hypochlorite and much less toxic; antimicrobial effect against antibiotic-resistant strains of bacteria with the same efficacy as antibiotic-sensitive strains

Answer 106

A 1:10 dilution of bleach in water

Answer 107

- Profound antimicrobial/antifungal properties - Acetic acid: potent antibacterial agent; effective against Staph bacteria (5% kill in 5 minutes), pseudomonas (2.5% solution kills in 1 minute) and malassezia; may be used in the ears (0.25-0.5% solution) as a ceruminolytic, astringent and acidifier - Boric acid (2% with zinc) effective against yeast otitis. - Malic acid (a dicarboxylic acid found in tart fruits) has anecdotally been used as a gentle astringent.

Answer 108

- Potent broad spectrum antibacterial agent - Keratolytic, keratoplastic, antipruritic, degreasing and follicular flushing action - Potent oxidizing agent that reactions with biological materials; resultant benzoyl peroxy radicals interact with hydroxy and sulfoxy groups, double bonds, and other substances resulting in disruption of microbial cell membranses - Metabolized in the skin to benzoic acid and lyses intercellular substance in the stratum corneum to account for keratolytic effect. - 10% irritating in dogs, 25% irritating in cats - Generic or more concentrated formulas are unstable and may be more irritaitng - Drying, irritating - Bleaches hair and clothing, skin tumor-promoting activity in laboratory rodents

Answer 109

- Weak germicide - Acts through liberation of nascent oxygen - Limited usefulness in skin disease - Has been used as an ear flushing agent and cleaning minor skin wounds, useful due to effervescent nature

Answer 110

- Chelating agent - Potent disinfectant, alkalinizing solution and antibiotic potentiating agent - Excellent activity against gram-negative bacteria (especially Pseudomonas) - EDTA-tris effect the permeability of the outer membrane in Gram-negative bacteria by removing Ca2+ and Mg2+ - Have good synergistic effects when combines with enrofloxacin.

Answer 111

- Produce an antiadhesive effect between skin sugars and pathogens; they attach to binding sites on surface glycoproteins and outcompete pathogenic bacteria - Help prevent infection and inflammation

Answer 112

- Antifungal with gram-positive and gram-negative effects - Hyperosmolar and acidic - Generates hydrogen peroxide and phytochemical compounds all leading to bacterial cell death - Resistance unlikely to develop due to multiple mechanisms of action - Can be bactericidal against MRSA, vancomycin resistant enterococcus faecium and MRSP

Answer 113

- An antibiotic derived from the fermentation of Pseudomonas fluorescens - Specifically and reversibly binds to isoleucyl transfer RNA synthetase in bacteria resulting in interrupted bacterial protein synthesis and inhibited bacterial RNA synthesis - Care needs to be used as generic is formulated with polyethylene glycol base and there are concerns for nephrotoxicity

Answer 114

- Concentration of the corticosteroid - Vehicle of the product - Inflammation in the skin - Abraded skin - Under occlusive dressings - Ophthalmic corticosteroids can also suppress adrenocortical responses and produce elevations in hepatic enzyme activity in normal dogs.

Answer 115

- Diester class of glucocorticoids - Lipophilic, ensured enhanced penetration into site skin - Accumulates in the dog's skin, allowing local efficacy at low dosage - Topical dieters have a high therapeutic index; high local activity with reduced systemic secondary effects - Minimal atrophogenic potential in humans because of limited toxicity to epidermal cells and effect on collagen synthesis. - Little impact on hypothalamic-pituitary-adrenal suppression

Answer 116

- Atophy - Scaling - Comedones - Alopecia - Pyoderma - Calcinosis cutis - Atrophy or curling of the pinnae in CATS - Does not have to occur with systemic effects - Side effects a particular issues in the axilla, groin and flanks

Answer 117

Fluorinated steroids are more potent, penetrate better, and are more effective but associated with more side effects. Ex: Triamcinolone, fluocinolone, betamethasone. Maintain a "reservoir" pool in the skin, enough that once daily application suffice to continue the topical effect.

Answer 118

- a 23-member macrolide similar in action to cyclosporine - Calcineurin inhibitor; inhibits antigen-presenting T cells and various cytokine production from T cells as well as keratinocytes and Langerhans cells. - There is a black box warning placed by the FDA regarding the theoretical risk of developing neoplastic

Answer 119

- An ascomycin macrolactam derivative - Acts similarly to tacrolimus - Permeates through skin to a lesser degree than tacrolimus - High anti-inflammatory activity - Used similarly to tacrolimus

Answer 120

- A synthetic imidazoquinoline amine-based immune response modifier with potent antiviral and anti tumor effects in animals and humans - Anti-viral and anti-tumor effects are primarily due to activation of Toll-like receptor 7 - This results in cytokine secretion from monocytes and macrophages - The main cytokines that are released include IFN-alpha, IL-12 and TNF-alpha - This results in a locally generated Th1-dominance and cell-mediated immunity. - Useful for treating viral infections.

Answer 121

- Degreasing agent - Low concentrations: keratoplastic - High concentrations: keratoylytic - Synergistic with salicylic acid for keratoplastic/keratolytic effects - Antifungal and antibacterial: believed to be due to conversion to pentathionic acid and H2S (hydrogen sulfide) - this conversion accomplished by cutaneous bacteria and keratinocytes - More effective than Chlorhexidine, captan, povidone iodine and ketoconazole shampoo in inhibiting Microsporum Canis growth from the infected cat hairs. - Has parasiticidal activity from H2S and polyphonic acid - Adverse effects: excessive drying, irritation of the skin, disagreeable odor, temporary yellow staining of light haricoats and skin, staining of clothing, wood and other materials, tarnishing of jewelry.

Answer 122

- Antiseborrheic properties | - A type I 5-alpha-reductase inhibitor and down regulates sebum production

Answer 123

- Hygroscopic and keratolytic actions - Aids in normalizing the epidermis and quality of the stratum corneum - Softening or moisturizing effects, makes vehicle feel less greasy when used - [2-20%] Humectant - [>20%] Keratolytic as it solubilized keratin and prekeratin and breakage of hydrogen bonds that keep the stratum corneum in tact, dissolves intercellular substance

Answer 124

- lactic, magic, citric, pyretic, glutamic, glycolic and tartaric acid - Modulate keratinization, are keratoplastic, delay terminal differentiation, reduce intercellular cohesion forces of the stratum corneum.

Answer 125

- Similar to benzoyl peroxide, lowers skin's pH. - Hydrolyzed in skin by bacterial lipase to ethanol and lactic acid - Liposoluble, able to penetrate hair follicles and sebaceous glands

Answer 126

- Key molecule in the natural defense mechanism of the skin - a component of ceramics - A sphingoid base naturally present in high levels in the stratum corneum of normal skin - Shown to increase ceramics and improve barrier function

Answer 127

- Solvent and vehicle - Excellent lipid solvent and defats the skin. - Enhances percutaneous penetration of drugs - Potent antibacterial agent, antidermatophyte and anticandidal properties - Superior humectant and can induce keratolysis

Answer 128

- Hygroscopic organic solvent - Freely miscible with lipids, organic solvents and water, excellent vehicle. - When exposed to air, concentrated solutions take in water - DMSO penetrates skin (within 5 minute), mucous membranes and the blood-brain barrier as well as cell, organelle, microbial membranes. - Does not cause membrane damage - Facilitates absorption of many other substances - Cryoprotective, radio protective, antiischemic, anti-inflammatory (free radical scavenger, decreases prostaglandin synthesis, stabilizes lysosomal membranes), analgesic (blocks C fibers). - antibacterial, anti fungal, antiviral properties depending on concentration - Decreased fibroplasia - Garlic-like odor, increased warmth, and/or pruritus, dehydration (too hygroscopic).

Answer 129

- Tee tree oil - Antibacterial (against coat positive Staph) and fungicide (Candida albicans, T. mentag etc.) - Mixture of hydrocarbons and terpenes - Antimicrobial effect primarily related to "terpinen-4-ol" - Toxicosis: hypersalivation, incoordination, weakness, hypothermia, hepatic injury

Answer 130

- Chemical: aminobenzoic acid or benzophenone derivatives act to absorb UV rays; clear lotions/gels - Physical sunscreens: zinc oxide, titanium dioxide, reflect/scatter light by forming opaque barrier

Answer 131

- Application/administration of a photosensitizing agent to the skin and then using light waves to excite or increase the energy of a photosensitive drug that causes a cytotoxic effect on tumors. - Excited molecules transfer energy directly to cellular oxygen, forming highly reactive singlet oxygen that results in cell death; this causes vascular and direct cell damage. - Administered topically or given systemically - Photosensitizers accumulate in tumor cells - Examples: hematoporphyrin derivative porfimer sodium (activated at 630 nm), 5-aminolevulic acid, aluminum phthalocyanine tetrasulphonate, 5-ethylamino-9-diethylaminobenzo[a]phenothiazinium chloride et.

Answer 132

- Fatty acids: long carbon chains with a methyl group at one end - Polyunsaturated fatty acids have multiple double bond - First double bone three carbon molecules away from the methyl group are the Omega-3 series - Omega-6 series of polyunsaturated fatty acids have double bond six carbons away from methyl group - Omega 3 and Omega 6's cannot be synthesized by dogs and cats and therefore needs to be supplemented

Answer 133

- alpha-linolenic acid(18:3N-3; an Omega 3); metabolized into eicosapentaenoic acid (EPA; 20:5N-3) and DHA (docosahexaenoic acid). EPA competes as a substrate for cyclooxygenase and 5- and 15-lipoxygenase. Metabolism of EPA by lipoxygenase enzymes results in the formation of leukotriene B5 and 15-hydroxyeicosapentaenoic acid; both of these are thought to inhibit leukotriene B4 - Linoleic acid (18:2N-6; an Omega 6); metabolized into dihomo-gamma-linolenic acid (DGLA; 20:3N-6). DGLA directly competes with arachidonic acid as a substrate for cyclooxygenase and 15-lipoxygenase. The results of DGLA metabolism is the formation of prostaglandin E1 and 15-hydroxy-8,11,13-eisosatetaenoic acid, both of which thought to have anti-inflammatory effects

Answer 134

- Dihomo-gamma-linolenic acid (DGLA; 20:3N-6), a breakdown product of linoleic acid (18:2N-6), competes with arachidonic acid for cyclooxygenase and lipoxygenase enzymes, modifying leukotriene and prostaglandin synthesis and activity - Competitive inhibition or arachidonic acid and effects of metabolic byproducts proposed to be the mechanism of antiinflammatory action of fatty acid therapy.

Answer 135

- Alteration of vascular permeability - Potentiation of vasoactive substances (histamine, modulation of lymphocyte function, potentiation of pain and pruritus) - Prostaglandins and leukotrienes potentiate one another

Answer 136

- Alteration of vascular permability - Activate neutrophils - Modify lymphocyte function - Potent neutrophil and eosinophil chemotaxis

Answer 137

1) Evening primrose, borage and black current oils 2) Cold water marine fish oils or krill oil 3) Chia seeds and flax seeds (or linseed), breakdown of alpha-linolenic acid 4) Sunflower oil, Safflower oil

Answer 138

A) Omega-3 fatty acid | B) Omega-6 fatty acid

Answer 139

- Pancreatitis; aggravation of pancreatitis has been described, avoid in patients with a history of pancreatitis. - Weight gain and obesity - Diarrhea - Cutaneous xanthomas can be seen in cats fed excessive fat - Platelet abnormalities and bleeding disorders have been theorized but not supported by current research.

Answer 140

- A methylxanthine derivative with a variety of immunomodulatory and rheologic effects - Increased leukocyte deformability and chemotaxis - Decreased platelet aggregation - Decreased leukocyte responsiveness to IL-1 and TNF-alpha - Decreased production of TNF-alpha from macrophages - Decreased production of IL-1, IL-4 and IL-12 - Inhibition of T and B lymphocyte activation - Decreased natural killer cell activity - Inhibit T-cell adherence to keratinocytes - Increased production of collagenase and decreased production of collagen, fibronecting and glycosaminoglycans - 4-10 weeks to see a response

Answer 141

- All chemicals, natural or synthetic, that have vitamin A activity - Expensive and challenging to obtain - Function by entering cells and being transported to the nuclei where they interact with specific gene regulatory receptors - Two main nuclear receptor families: retinoic acid receptors and retinoid X receptors - Nuclear receptor and retinoid complex bind with specific areas of target genes and alter gene transcription - Cells then alter their growth and differentiation by altering the expression of growth factors, keratins and transglutaminases; down regulated nitrites and TNF-alpha - All retinoids have antiproliferative, antiinflammatory and immunomodulatory effects. - Also effect proteases, prostaglandins, humoral and cellular immunity, cellular adhesion and communication - Also enhance wound-healing by stimulating fibroblasts to produce various chemicals (i.e. TGF)

Answer 142

- An alcohol, all-trans retinol - Oxidized in the body to retinal and retinoic acid - Important for induction and maintenance of normal growth and differentiation of keratinocytes - Works at the cellular level by binding first to the cell membrane then transferring through the cellular cytoplasm by specific proteins, cellular retinol binding protein, and cellular retinoic acid-binding protein. Nuclear retinoid receptor molecules transfer the retinoids through the nuclear

Answer 143

- 13-cis-retinoic acid, synthesized as a natural metabolite of retinol - Indicated in diseases that require alteration or normalization of adnexal structures - Adverse effects in dogs: conjunctivitis, hyperactivity, pruritus, pedal and mucocutaneous junction erythema, stiffness, vomiting, diarrhea, KCS; hypertriglyceridemia, hypercholesterolemia and increased levels of ALT, AST and ALP - Adverse effects in cats: conjunctivitis, diarrhea, anorexia, vomiting - With long-term use: skeletal abnormalities (cortical hyperostosis, periosteal calcification, long-bone demineralization) - ALL RETINOIDS ARE POTENT TERATOGENS

Answer 144

- A synthetic retinoid | - No longer available and largely replaced by acitretin

Answer 145

- A carboxylic acid metabolically active metabolite of etretinate - Less toxic due to shorter terminal elimination half-life of 2 days vs. 100 days for etretinate

Answer 146

1) Ketoconazole 2) Fluconazole 3) Itraconazole 4) Erythromycin 5) Doxycycline 6) Methylprednisolone 7) Metoclopramide 8) Allopurinol 9) Furosemide 10) Calcium channel blockers (Diltiazem, verapamil) 11) Flavonoids from grapefruit juice

Answer 147

- a fat-soluble cyclic polypeptide metabolite of the fungus Tolypocladium inflatum gams - Binds to intracellular receptor protein cyclophilin-1; this complex then binds and inhibits calcineurin, preventing dephosphorylaton and activation NF-AT - Blocks IL-2 transcription and T-cell responsiveness to IL-2, leading to impaired T-helper and T-cytotoxic lymphocytes - Inhibits IFN-alpha transcription, diminishing amplification signals for macrophage and monocyte activation - May impair IL-3, IL-4, IL-5, TNF-alpha, IFN-alpha - Inhibits mononuclear cell function, antigen presentation, mast cell and eosinophil production, histamine and prostaglandin release from mast cells, neutrophil adherence, NK cell activity and growth and differentiation of B cells - Directly inhibits histamine release from dog mast cells - You can intradermal test in the face of cyclosporine - Microemulsified form is better absorbed - Food can reduce bioavailability by roughly 20%; fatty meals can enhance absorption in some humans - Side effects in dogs: gingival overgrowth, papillomatosis, vomiting, diarrhea, bacteriuria, bacterial skin infection, anorexia, hirsutism, involuntary shaking, nephropathy, bone marrow suppression, lymphoplasmacytoid dermatosis, plasmacytomas, histiocytomas, systemic infections with deep mycotic organisms - Side effect in cats: GI upset, protozoal and viral infections, fatal toxoplasmosis - In humans: hepatotoxic, nephrotoxic, increases risk of squamous cell carcinomas

Answer 148

A glucocorticoid that was previously satisfactory apparently loses its effectiveness. With variable length of time, reinstating the original corticosteroid can regain its effect.

Answer 149

- Decreased number of glucocorticoid receptors | - Lower affinity of feline glucocorticoid receptors for their ligands than dogs

Answer 150

IFN-α, IFN-β and IFN-ω and IFN-δ, and IFN-τ | - important in antiviral immunity

Answer 151

IFN-γ produced by NK cells, CD4+ helper T cells, and CD8+ cytotoxic cells.

Answer 152

- Hormone synthesized by the pineal gland from L-tryptophan - Involved in neuroendocrine control of photoperiod-dependent molting and/or pelage color in many animals - Can act directly on hair follicles, or within the CNS to alter secetion of melanocyte-stimulating hormone and/or prolactin -

Answer 153

- Hormone synthesized by the pineal gland from L-tryptophan - Involved in neuroendocrine control of photoperiod-dependent molting and/or pelage color in many animals - Can act directly on hair follicles, or within the CNS to alter secretion of melanocyte-stimulating hormone and/or prolactin - Melatonin secretion is tied to photoperiod with greatest productivity during dark hours - Melatonin and prolactin may be involved in the seasonal growth of winter haricots and spring molts in mammalian species - Prolactin and melanocyte-stimulating hormone have an inverse relationship. - Inhibits adrenal 21-hydroxylase and aromatase enzymes, which could result in reduction in estradiol levels

Answer 154

- Hormone synthesized by the pineal gland from L-tryptophan - Involved in neuroendocrine control of photoperiod-dependent molting and/or pelage color in many animals - Can act directly on hair follicles, or within the CNS to alter secretion of melanocyte-stimulating hormone and/or prolactin - Melatonin secretion is tied to photoperiod with greatest productivity during dark hours - Melatonin and prolactin may be involved in the seasonal growth of winter haricots and spring molts in mammalian species - Prolactin and melanocyte-stimulating hormone have an inverse relationship. - Inhibits adrenal 21-hydroxylase and aromatase enzymes, which could result in reduction in estradiol levels

Answer 155

Phytoestrogens (isoflavones, ligdans, genisten) are known to inhibit 3-beta hydroxysteroid dehydrogenase. This combination of melatonin and phytoestrogens may have synergistic effects in cases of elevated estrogen and cortisol levels.

Answer 156

- Rapid freezing - Slow thawing - Three freeze/thaw cycles

Answer 157

When a cell mass is frozen and left to die in situ, membrane lipoprotein complexes, and hence antigen-antibody complexing and receptor sites, are inevitably disrupted or altered. They are probably not totally destroyed. The nucleus may remain relatively intact. Thus, for a short time, antigenicity may be enhanced. Enough antigen is released systemically to produce a strong specific immunologic response that may kill escaped cells of the same tumor species.

Answer 158

Liquid nitrogen can produce -195.8C; -320.5F) and nitrous oxide (-89C; -138F; applied with probes using specific equipment)

Answer 159

Used in cryotherapy, rapid expansion of the gas under pressure provides low freezing temperatures.

Answer 160

Light amplification by the stimulated emission for radiation

Answer 161

- Synthetic modification of 6-mercaptopurine - Antagonizes purine metabolism, interfering with DNA and RNA synthesis - Metabolized to 6-mercaptopurine in the liver and other active metabolites - 6-mercaptourine is then metabolized by three enzyme systems - Xanthine oxidase and thiopurine methyltransferase (TPMT) produce inactive metabolites - Humans and dogs with low or absent TPMT have increased likelihood of becoming myelosuppression, cats have very low levels of TPMT, increasing their risk of toxicity - Primarily affects rapidly proliferating cells with greatest effects on cell-mediated immunity and T lymphocyte-dependant antibody synthesis; primary antibody synthesis is more affected than secondary antibody synthesis - Adverse effects: anemia, leukopenia, thrombocytopenia, vomiting, hypersensitivity reactions (especially of the liver), pancreatitis, hepatotoxicity, elevated serum alkaline phosphatase concentrations, rashes and alopecia, diarrhea (may be hemorrhagic) - Long-term side effects: demodicosis, dermatophytosis, pyoderma - Anemia and lymphopenia most common but oftentimes not to the degree that requires discontinuation of treatment - Monitor CBC and platelet counts every 2 weeks when starting medication; once stable, monitor once every 4 months. - Run chemistry every 8-12 weeks and at least biannually (monitor hepatitis and pancreatitis) - Used in combination with systemic glucocorticoids (proposed treatment of choice for canine PF); lag phase of 3-6 weeks - 50 mg/m^2 or 1.5-2.5 mg/kg every 24 hours until clinical response, then EOD; slow tapering to 1mg/kg every 72 hours may be achieved.

Answer 162

- An alkylating agent derived from nitrogen mustard - Cytotoxic effect is due to cross-linking of DNA - Slow acting and less toxic relative to other alkylating agents - Myelosuppression possible - Adverse effects: anorexia, vomiting, diarrhea (often resolve with every other day dosing) - Monitor with hemograms every 2-4 weeks - Alopecia and delayed hair growth after clipping, particularly in poodles and Kerry blue terriers - Neurotoxicity reported in humans and in one cat - 0.1 - 0.2 mg/kg every 24 - 48 hours

Answer 163

- Old, plant-derived drug; it is an alkaloid - Mechanisms of action: - suppresses neutrophil chemotactic and phagocytes functions via disruption of microtubule assembly and elongation, - increasing cellular cyclic adenosine monophosphate (cAMP) levels and inhibiting lysosomal degranulation - inhibits immunoglobulin secretion, interleukin 1 production, histamine release, human leukocyte antigen (HLA)-DR expression - inhibits cell division during metaphase by interfering with sol-gel formation and the mitotic spindle - Adverse effects: primarily gastrointestinal - Typically administered 0.03 mg/kg every 24 hours - Do not give with NSAIDs due to possible bone marrow suppression; do not use with chlorambucil and azathioprine - Use cautiously with P450 enzyme inhibitors and P-glycoprotein pump inhibitors

Answer 164

- Nitrogen mustard alkylating agent - Metabolized to agents that inhibit mitosis by interfering with DNA replication and RNA transcription and replication - Lymphocytes are especially sensitive - Immunosuppressive to both humoral and cell-mediated immune responses; more effective against B cells than T cells - Suppressed antibody production - Adverse effects: sterile hemorrhagic cystitis, bladder fibrosis, teratogenesis, infertility, alopecia, poor hair growth, nausea, inflammation of the GI tract, increased susceptibility to infections, depression bone marrow and hematopoietic systems - Cats may loose their whiskers

Answer 165

- prodrug of the anti-proliferative agent mycophenolic acid (MPA) - Drug that inhibits de novo purine synthesis and and suppressed both T and B lymphocytes - Specifically and reversible inhibits inosine monophosphate dehydrogenase thereby inhibiting synthesis of guanine nucleotides, blocking synthesis of purine and preventing maturation of T and B lymphocytes - Induced T lymphocyte apoptosis and dendritic cell maturation - Induce human monocyte-macrophage cell line differentiation, decrease the expression of IL-1 and enhance the expression of the IL-1 receptor antagonist - Acts synergistically with cyclosporine in prevention of graft-versus host disease and has steroid sparing effect. - Adverse effects: bone marrow suppression, nausea, vomiting, diarrhea, and increased incidence of infections - Can increase risks of pyoderma, malassezia infection, diarrhea and leukocytosis

Answer 166

- Exact mechanism of action of either drug or the combination for treating inflammatory or immune-mediated disease is unknown - Tetracyclines possess various anti-inflammatory and immunomodulatory properties including: suppression of in vitro lymphocyte blastogenic transformation and antibody production, inhibition of matrix metalloproteinases, downregulation of cytokines, suppression of in vivo leukocyte chemotactic responses, inhibition of activation of complement component 3, inhibition of lipases and collagenases, inhibition of prostaglandin synthesis - Niacinamide/nicotinamide: block antigen IgE-induced histamine release in vivo and in vitro, prevent degranulation of mast cells, act as photoprotectants from inducing immunologic damage, act as a cytoprotectant that blocks inflammatory cell activation and apoptosis, inhibits phosphodiesterase and decreases protease releases - Unknown what the combo does - Can be used in combination, or used for steroid sparing effects; synergistic with Vitamin E, glucocorticoids +/- azathioprine. - Initially given q 8 hours (>10 kg, 500 mg of tetracycline and niacin amide po q 8 hours) - Doxycycline has longer half life, lower dosage and longer interval is reasonable - Side effects: uncommon, vomiting, anorexia, lethargy, diarrhea, increased liver enzyme activity. Thought it might lower seizure threshold for dogs with history of seizures

Answer 167

- AKA diaminodiphenylsulfone, is a sulfone with bacteriostatic and bactericidal activities - Similar actions to other sulfonamides, primarily affecting folic acid synthesis - Has anti-inflammatory properties by decreasing neutrophilc chemotaxis, complement activation, antibody production, and lysosomal enzyme synthesis - Avoid use in cats because of neurotoxicity and hemolytic anemia

Answer 168

- Sulfasalazine is converted by colonic bacteria to sulfapyridine (sulfonamide) and 5-aminosalycilic acid (i.. mesalamine). Mesalamine has anti-inflammatory effect, believed to be mediated by anti-prostaglandin and/or anti-leukotriene activity - Vomiting, anoreia, hypersensitivity reactions, KCS, ataxia, depression, clinical signs consistent with hypothyroidism, hemolytic anemia, leukopenia, cholestatic jaundice, decreased sperm counts, orange-yellow discolouration of the urine or skin