Exam 4 Flashcards

Question

Remdesivir (Veklury)

Answer 1

-Coronavirus -Feline Infectious Peritonitis (FIP) -FDA approved for COVID-19 -Inhibits viral replication by binding to RNA dependent polymerase GS-44124 -Illegal use in USA -FIP

Answer 2

1. Prednisone 2. Prednisolone Backups -Methylprednisolone (oral) -Dexamethasone SP -Dexamethasone -Triamcinolone MOA: bind intracellular receptors, translocate to the nuclei, bind receptor sites on genes. Modulate transcription of CG responsive genes, alter protein synthesis The signal caller -Neutrophils: inhibited apoptosis -Macrophages: inhibited phagocytosis -Lymphocytes: T-cells more affected than B-cells at lower GC levels. Reduced Ig level at high GC doses -Other: Inhibit release of cytokines IL-1, TNF-alpha, prostaglandins, IL-2 -Anti-inflammatory -Immunosuppressive The Three Ds Drug Dose Duration Patient -Comorbidities -Species differences -Cost -Monitoring -Owner's (in) tolerance of side effects -Withdrawal times Potential Side effects -PU/PD -Diabetes mellitus -Polyphagia -Behavioral changes -Opportunistic infections -Adrenal suppression -Delayed wound healing -Catabolic effects on muscle, connective tissue -Gastric ulceration -Panting -Hypertension/CHF -Proteinuria -Calcinosis cutis When to Modify the Plan -When GC aren't being effective -Intolerance of side effects -Illness life-threatening

Answer 3

1. Cyclosporine (Tolycladium inflates soil fungus) -Atopica -Cyclavance -Neoral -Equoral MOA: suppresses IL-2 gene -Decreases production of TNF-alpha, IL-3, IL-4, INF-y -Inhibits IgE -Reduces eosinophil recruitment and lymphocyte activating functions of antigen-presenting cells -More specific for T cell than B cells -Not typically myelosuppressive -Cytochrome P450 enzyme in the liver. Systemic absorption 20-30% **Caution with MDR-1 deficient dogs** -Biliary excretion predominates -Renal excretion is minor **Synergistic with Ketoconazole** Side effects -GI signs +/- maropitant -Gingival hyperplasia -Opportunistic infections, papillomavirus lesions -Elevated liver enzymes +/- glucose -Hirsutism -Rarely: anaphylaxis, Pruritus -Assess peak 2 hours after dosing, trough immediately before next dose -Adjust dosage based on patient's clinical performance -Taper to qod or twice weekly 2. Tacrolimus -aka FK506 -Ointment ONLY, orally terrible side effects -Tx: Atopy, perianal fistula -10-100x cyclosporine

Answer 4

1. Azathioprine -Purine antagonist -Reduces T-cell dependent antibody synthesis -Targets cell-mediated immunity, especially lymphocytes -Inhibition of lymphocyte proliferation, DNA and RNA production -Greater impact on cellular immunity than humoral antibody response -Hepatic metabolism and renal excretion Side effects **TPMT enzyme deficiencies in cats can lead to myelotoxicity** -GI upset -Myelosuppression -Hepatotoxicity -Pancreatitis Drug interactions -ACE inhibitors -Potentiated sulfas -Etc **Monitor frequently, every 2-4 weeks CBC, Chem** 2. Chlorambucil -Nitrogen mustard alkylating agent -2 weeks therapeutic efficacy -Primarily used as a chemotherapeutic agent MOA: Active metabolite in liver, cell-cycle non-specific, cytotoxic. -Cross links DNA -Targets B cells -Highly protein bound -Inactive metabolites excreted in urine **Cytotoxic drug of choice in cats** -Slowly taper dosing frequency Side effects -GI upset -Myelosuppression in the game 7+14 days -Check CBC q 2 weeks 3. Mycophenolate -Purine synthesis inhibitor -Decreased proliferation of T and B cells -Decreases antibody synthesis by B cells -Enterohepatic recirculation: 2 plasma peaks 1-2 hours, 6-12 hours -Heavily protein bound -Urinary excretion **MMF: inhibits de novo synthesis of purine nucleotides** Side effects -GI upset -Myelosuppression -CBC q 2 weeks Interactions -Numerous antibiotics -Glucocorticoids -Cyclosporine -Proton pump inhibitors -Telmisartan 4. Leflunomide **Inhibits DHODH which is critical for de novo synthesis of pyrimidines that are critical for the function of activated and stimulated T and B lymphocytes** -Pyrimidine synthesis inhibitor -Inhibits T cell proliferation -Inhibits antibody production by B cells -Metabolized by GI tract, liver -Excreted in urine, bile **Use when other drugs have failed** Side effects -Decreased appetite, diarrhea, hepatotoxicity -Progressive anorexia, weight loss -Anemia, idiopathic hemorrhage -Death

Answer 5

Oclacitinib Janus kinus (JAK) enzyme inhibitors -JAK1, JAK3 -IL-31 function reduced -May inhibit IL-2, 4, 6, 13. -Rapidly absorbed -Peaks in <1 hr -Half life 3-5 hrs -Metabolized by liver -Excreted in bile and kidneys Adverse effects -Uncommon -Papillomavirus recurrence -UTI -GI upset Clinical Uses -Flea hypersensitivity -Canine atopic dermatitis -Cutaneous adverse food reaction -Contact allergy

Answer 6

Pentoxifylline **Improves tissue perfusion** -Inhibits TNF-alpha, IL-1, 6, 12. -Inhibits activation of T and B cells -Enhances intracellular cAMP -Broad spectrum phosphodiesterase inhibitor -Decreases platelet aggregation -Increases tissue plasminogen activator -Antifibrotic properties **Consider for ischemic/vascular disorders** Side effects -GI upset -Administer with food

Answer 7

Unknown MOA Concern for antibiotic stewardship May take 3-8 weeks to produce effects 1. Doxycycline 2. Niacinamide

Answer 8

-Avoid daycares, dog parks, grooming salons, kennels -Avoid modified-live vaccines -Limit exposure to wooded areas -Avoid raw diets -Curb outdoor hunting behaviors -Screen for feline retroviruses prior to initiating treatment

Answer 9

Canine and Feline Osteoarthritis Omega 3 FA -Evidence for efficacy Chondroitin and glucosamines -(worse than negative control-placebo) DHA/EPA MOA -Specialized pro-resolving mediators (SPMs) -Inflammation: generation of eicosanoids (PGs, leukotrienes) from arachidonic acid (omega-6) in conjunction with cytokines, chemokine, complement -SPMs are enzymatically derived from essential FA to serve as immunoresolvents that limit acute responses and promote the resolution of non-infectious inflammation and tissue injury such as OA pain -SPMs: composed of lipoxins, E-series and D-series resolvins, protecting, and margins (activate regulatory T cells) **RESOLVINS** Glucosamine -Collagen synthesis in cartilage -Contributes to glycosaminoglycans and proteoglycan synthesis Chondroitin -Contributes to extracellular matrix of cartilage -Adds to resistance and elasticity of cartilage -Inhibition of destructive enzymes in joints -Contributes to synthesis of glycosaminoglycans and proteoglycan

Answer 10

Animal Health Products -Not requiring research or safety studies -Can not claim therapeutic benefits DSHEA -"a product (other than tabacco) intended to supplement the diet that bears or contains one or more of the following dietary ingredients: vitamin; mineral, etc." USA -FDA regulated "Good Manufacturing Practices" -Certificate of analysis -NPN: natural product number

Answer 11

Green-Lipped Mussel Extract -New Zealand (Perna Canaliculas) -Chondro-modulatory and anti-inflammatory properties MOA -Contains glycosaminoglycans (chondroitin sulfate) -Amino acid (glutamine) -Omega-3 FA (including DHA, EPA) -Prebiotic activity in the intestines -Proteins and peptides: anti-microbial, anti-inflammatory, anti-oxidant, bio-adhesive and anti-hypertensive properties -Inhibit COX-1, COX-2, Prostaglandisn, Lipogenase, leukotrienes Biota orientalis plant (Epiitalis) -Antioxidant, anti-inflammatory -Hight NMIFA -Reduces: PGE2, COX2, replace AA -Reduces synovial PGEs and GAG -Reduces IL-1 -Inhibition of MAPKs -Increases chondrocyte numbers -Inhibition of osteophytes growth Avocado soybean unsaponifiable -Inhibition of inducible NO synthase and MMP-13 -Tx canine OA -Increases TGF-B1 and 2, chondrocyte production of collagen and proteoglycans UC-II MOA: alleviates inflammatory T cell response and activates T-regulatory cells via its oral tolerance ( immune process to distinguish harmful from non harmful compounds) mechanism, which reduces cartilage damage

Answer 12

Endocannabinoid System -ECS plays key roles in control of various systems -Nervous, metabolic, digestive, reproductive, immune function -Cannabinoid receptor 1 (CB1R) -Cannabinoid receptor 2 (CB2R) -Endogenous cannabinoid ligands (endocannabinoids, eCB) -Anandamide (AEA) -2-AG Metabolizing enzymes -Fatty acid amide hydrolase (FAAH): hydrolyzes AEA -Monoacyglycerol lipase (MGL): hydrolyzes 2-AG Cats with chronic gingivostomatitis: reduces pain, increases healing

Answer 13

-Parallels and interacts with other major endogenous pain systems -Ecosanoid pathways -Vanilloid/transient receptor potential -Endorphin/enkephalin -Endocannabinoidome (eCBome)

Answer 14

**Act as endocannabinoid modulator** -Low affinity for CBR -Inhibits FAAH -Inhibits anandamide reuptake -Inhibits hepatic metabolism of THC -Negative allosteric modulator at CB1R in presence of THC -TRPV1 agonist -GPR55 antagonist -Inhibits TNF-alpha -Activates 5-HT1a receptor -Inhibits voltage gated Ca channels (like Gabapentin) -Inhibits glutamate neurotoxicity -Inhibiting adenosine transporter

Answer 15

-CB1R, CB2R, agonist/partial agonist -Inhibits prostaglandin E2 synthesis -Stimulates lipoxygenase -Inhibition of glutamine release: reduces NMDA response -Serotonergic sytem: increases cerebral serotonin production, decreasing synaptosomal re-uptake, decreases 5-HT release from platelets -Dopaminergic blocking actions -Stimulation of B-endorphin release -Neuroprotective antioxidant

Answer 16

Raw acid forms THCA -Does not cross BBB -Inhibits TRP activity -Inhibits COX1+2 -Reduces levels of TNF-alpha CBDA -Selective COX2 inhibitor -Potent 5-HT -Activates TRPV1 + TRPA1 -Antagonist at TRPM8 -Reduces anticipatory nausea

Answer 17

-Anti-inflammatory and analgesic properties -Weak inhibitor of anandamide reuptake -Potent activity on TRPAV1-4, TRPV8 receptors -No strong activity on CB1+2R **Often coadministered with THC**

Answer 18

-Lacks psychotropic effects -Strong analgesic -Anti-erythema -Lipooxygenase agent -Weak binding to CB1+2 Receptors **Potent GABA re-uptake inhibitor >THC, CBD** **Muscle relaxant** **Inhibits anandamide reuptake** -Reduces PGE2 release in synovial cells -Alpha2 adrenoreceptor activation -5HT1a antagonist

Answer 19

-By product of THC -1/4 potency of THC -Considered for topical application -Stimulates recruitment of mesenchymal stem cell in marrow promoting bone formation

Answer 20

-Anti inflammatory action via inhibiting main inflammatory mediators and enzymes -IL-1B, IL-6, TNF-alpha, NF-kB, iNOS, COX1+2 -Potent CB2R agonist -Synergistic with THC -Reduces immune-inflammatory process -Muscle relaxant effect -TRPV1 activity -Reduces inflammation via PGE2 -Sedative/analgesic effects **Reversible with yohimbine and naloxone**

Answer 21

Boswellia Serrata -Tree native to India -Inhibition of: leukotrine synthesizing 5-lipoxygenase, PGE2, IL-1B, TNF-alpaha -Reduce glycosaminoglycan degradation -Canine inflammatory joint and spinal disease Devils Claw -Harpagophytum procumbens -Native to South East Africa -Extract from plant root -COX-2 inhibition leading to no NO and PGE2 synthesis -Gastroprotective properties