anti-inflammatory agents H1-receptor antagonists and antimicrobial therapy

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  1. acute inflammation
    • normal protective response to tissue injury caused by physical trauma, noxious chemicals or microorganisms
    • body's attempt to destroy or inactivate invading pathogens
    • back to normal when healing is complete
  2. inflammation
    • protective response to tissue injury
    • 2 objectives: counteract injury by removal or wall off damaged area and repair or replace damaged tissue
    • 3 stages, 4 cardinal signs
  3. "recent" treatment for chronic pain
    • frontal lobotomy
    • Dr. Walter Freeman and his travelling van
  4. mechanism of inflammation (3)
    • 1. changes in caliber of vessels. Dilation increase blood flow, oxygen and necessary cells and proteins
    • 2. increased vascular permeability.  Contraction of endothelial cells allows cells (WBC) and fluid to damaged site, becoming exudite and causing swelling and edema
    • 3. chemotaxis from WBC, now in tissue. Neutrophils on site first, cytokines bring macrophages etc. to start clean up and phagocytosis.
  5. 4 cardinal signs of inflammation
    • erythema: redness due to vasodilation from increased blood flow
    • edema: swelling due to exudation of plasma into ISF (site of trauma)
    • heat: vasodilation from increased blood flow
    • pain: stimulation of nocioceptors, from cytokines and from where swelling presses on nerve endings
  6. chronic inflammation
    • disease state causing progressive tissue injury and pain
    • cycle of neuroendocrine changes, plasticity of nocioception pathway from chronic stimulus. The longer the pain lingers, the harder it is to treat.
    • Caused by innoculus exogenous substance (allergy/hypersensitivity) or endogenous body substance (autoimmune)
  7. chemical mediators of inflammation
    • inflammation is triggered by chemical mediators released by injured tissues and migrating WBCs.  
    • Cause things like vasodilation, increased vascular permeability and bronchoconstriction
    • specifics mediators may vary
    • prostaglandins (PGs): fats, lipid compound. Causes cardinal signs
    • Leukotrienes (LTs): allergies
    • Histamine: vasodilation, bronchoconstriction, acid production
    • serotonin (5-HT): vasoconstrictor, smooth muscle contraction, inhibits gastric secretions
    • Bradykinin: vasodilator, increased permeability of capillaries, smooth muscle contraction
  8. Platelet activating factor
    • made from arachadonic acid.
    • Increases blood clotting and platelet adherence
  9. Eicosinoid
    family of endogenous fatty acids from cell-membrane phospholipids.  Involved in every body function.
  10. lipoxygenase
    • turns arachadonic acid into leukotrienes
    • allergic inflammation, vasodilation, vascular permeability
  11. How arachadonic acid becomes available
    • damaged cell membrane releases phospholipids.  Phospholipase A2 breaks them down, releasing arachadonic acid.  
    • Oxidized by enzymes, becoming platelet activating factor, leukotrienes or prostaglandins.
  12. COX-1
    • constituitive enzyme, "good" functions. 
    • Present in all cells in healthy animal.
    • maintain adequate gastric and intestinal mucus production
    • decrease HCl and gastrin production
    • maintain adequate renal and hepatic blood flow
    • platelet aggregation
  13. COX-2
    • inducible prostaglandins, low in healthy but high in activated macrophage and inflammation.  "Bad" functions
    • Produces inflammatory prostaglandins
    • maintains physiological homeostasis, CNS processing, renal tubular function and gastric mucosal repair. 
    • PGE and PGA, vasodilation
  14. Glucocorticoids in inflammation
    inhibit cyclooxygenases and phospholipases, preventing prostaglandin formation and some platelet activating factor and leukotrienes
  15. Transitional cell carcinomas
    Sometimes COX2 is up-regulated in these tumors, so block with COX-2 selective NSAIDs to decrease inflammatory prostaglandins
  16. Inflammatory effects of prostaglandins
    • vasodilation - increased blood flow (PGA and PGE)
    • increased permeability of capillaries and post-capillary venules allows exudation of plasma into ISF
    • Chemotactic for WBC
    • increased sensitivity of nocioceptors to histamine, bradykinin, serotonin
    • endogenous pyrogens (fever)
  17. inflammatory effects of Leukotrienes
    • increased permeability of capillariesand post-capillary venules allowing exudation of plasma into ISF
    • highly chemotactic for phagocytic WBC, esp neutrophils
  18. chemotaxin
    • substance that causes WBC to migrate towards it
    • recruits histamine-release from mast cell
  19. Therapeutic effects of NSAIDs
    • All act to decrease prostaglandin synthesis.  
    • decrease inflammation: block vasodilation, permeability, chemotaxis
    • decrease pain: block increased sensitivity of nocioceptors to histamine, bradykinin and serotonin
    • decrease fever: block exogenous pyogens
  20. History of first NSAID
    • Aspirin.  
    • 4000 years ago used willow bark (salicylic acid
    • Bayer started in 1876.
  21. acetylsalicylic acid
    • aspirin, nonselective COX inhibitor
    • irriversibly blocks by occupying active site.
    • Most extensively used drug of all time.  1 million tabs per hour.
    • Therapeutic effects: decreases inflammation, fever, pain, platelet aggregation (anti-thrombotic)
  22. side effects of acetylsalicylic acid
    • #1 is hemorrhage
    • #2 is GI
    • Causes ulcers in the stomach of every dog that takes it chronically
    • approved in extremely low doses in cats for saddle thrombus (1/4 of 80 mg tab every 3 days)
  23. 2 ways aspirin causes GI disturbance
    • ion trapping: alkaline pH. directly damages mucosal cells.  Better with food, water and enteric coatings
    • decreases PG synthesis: decreases mucus production, decreases HCl and gastrin production
    • Leads to GI ulceration and hemorrhaging, can't heal without COX2.
  24. Toxicities of aspirin
    • hemorrhage
    • GI ulceration
    • decreases renal blood flow, can cause kidney damage
  25. Toxic doses fo aspirin (dogs, cats and signs of toxicity)
    • dogs: >50mg/kg TID
    • cats: > 25 mg/kg/day
    • emesis (esp bloody), fever, hyperventilation, GI ulceration and bleeding, depression, seizures, coma (COX 2 in CNS), abdominal pain, VDA with blood
  26. NSAIDS (non-aspirin)
    • reversibly inhibit COX, compete for active site
    • antiinflammatories, anagesic and antipyritic
    • almost all inhibit platelet aggregation
    • most not in cats, the ones that are extreme caution
  27. Phenylbutazone
    • nonselective COX inhibitor
    • most common NSAID in horses
    • used in musculoskeletal disorders in dogs and horses, relief of colic in horses
    • PO or IV
    • high toxicity with chronic usage, including GI, rare irreversible bone marrow suppression.
    • Ponies more sensitive than horses, but don't have to increase dose much to increase toxicity
  28. COX-2 selective NSAIDS
    • developed based on idea that COX2 was just inflammation
    • fewer GI toxicities than other NSAIDS (still have GI and renal toxicity)
    • Not totally COX-2 selective
  29. Coxibs
    • developed after COX-2 selective.  TRULY COX 2 selective.  
    • Ferocoxib (prevacox)
    • Deracoxib (Deramaxx)
  30. Carprofen
    • Rimadyl
    • SQ or PO
    • COX-2 selective
    • dogs only to treat osteoarthritis and post-op pain. May inhibit platelets
    • major adverse: GI, with idiosyncratic hepatopathy (usually reversible)
  31. Deracoxib
    • Deramaxx. PO
    • COX-2 selective
    • post-op pain and osteoarthritis, dogs.
    • Severe ulceration of proximal duodenum.  Surgical, fatal
  32. Meloxicam
    • metacam. SQ and PO
    • COX-2 selective
    • Dogs and cats and rabbits.  Cats 1mg dose post-op.  
    • Acute renal failure if repeated.
  33. Robenacoxib
    • Onsior. PO or IV
    • application limited in cats, good for dogs.  Recent.  COX-2 selective.  
    • Less GI, no kidney.
    • Goes away fast in serum, lingers at site of inflammation.  Short half life, localized. 
    • Pain at injection site, some GI.  
    • Cats: for acute musculoskeletal pain, 1 tab SID every three days.  
    • dogs in osteoarthritis
  34. Ketoprofen
    • ketofen, anafen, orudis
    • Not approved in US (Europe and Canada)
    • LOX and non-selective COX inhibition
    • dogs, PO or IV.
    • Anti allergy/inflammation, anti-thrombo
    • acute renal failure/hemorrhage follow surgery
    • GI ulcers
  35. Tepoxalin
    • Zubrin. COX and LOX inhibitor
    • inhibits oxygenase metabolites, inhibit COX1: COX2 (30:1)
    • no studies outside FDA requirements.
  36. Signs of NSAID-caused gastroduodenal ulceration
    • emesis/hematemesis
    • melena
    • cranial abdominal pain, can include hunchback or praying position
    • anorexia
    • weakness, lethargy
    • pallor
  37. acetaminophen
    • Tylenol, non-opiod analgesic
    • analgesic and antipyretic effects
    • synergistic with opioids.
    • good for breakthrough pain (play too hard on managed chronic pain, need extra boost)
  38. acetominophen toxicity
    • broken down with glucuronidation (liver), cats are bad at it
    • hepatic necrosis, anorexia, methemoglobinemia and cyanosis (brown serum and urine, drooling)
  39. Acetominophen toxicity therapy
    • N-acetylcysteine (Mucomyst): supplies cysteine, makes glutathione which can conjugate acetominophen to get rid of it.
    • vitamin C: antioxidant to help with damage
    • cimetidine (Tagamet): decreases metabolism in liver but can make methemoglobin WORSE
  40. Glucocorticoids
    • treatment for all, cure for none. Antiinflammatory and immuno-suppressive, dose-dependant.
    • secreted by adrenal cortex in response to ACTH
    • Cortisol comes from zona fasciculata
    • androgens come from zona reticularis
    • aldosterone comes from zona glomerulus
  41. Metabolic effects of glucocorticoids
    • increase plasma glucose levels by increasing protein catabolism and lipolysis (increase in gluconeogenesis) (hyperglycemia)
    • Breadown of skeletal muscle causes decreased muscle mass and weakness, pendulous abdomen, dorsal spinous processes
    • breakdown of connective tissue and skin causes fragility, ruptured ACL or hyperextension due to weak connective tissue
    • slows healing, decreases hair growth because of lack of protein, immunosuppressive (know because hair won't grow back post-surgery
    • Lipolysis causes redistribution of fat, causing pear-shape(Cushings)
    • inhibit ADH secretion PUPD
    • Hyperglycemia stimulates insulin release, chronic release causes resistance, Iatrogenic type II diabetes mellitus
    • GI ulceration
  42. anti-inflammatory effects of glucocorticoids
    • COX inhibition, decrease of PGs
    • blocks phospholipase from releasing arachadonic acid.
    • inhibits WBC phagocytosis
    • helps stabilize lysosomal membranes
    • decreases histamine formation
  43. immunosuppressive effects of glucocorticoids
    • decreases circulating lymphocytes and eosinophils
    • decrease antibody formation
    • decreases cytokine release from WBC
    • increased risk of infection, used with caution, can mask signs or exacerbate infection
  44. list of synthetic glucocorticoids
    • prednisone (biotransformed to prednisolone, intermediate, 12 hour)
    • prednisolone (becomes methypred, intermediate, 12-hour) animals tolerate better
    • methylprednisolone (Medrol) (12-hour)
    • dexamethasone (Azium) long-acting
    • triamcinolone (Vetalog) intermediate acting. 24-36 h
    • fluticazone inhalant steroid for asthmatics
    • fast-acting IV agents Dexmethasone sodium phosphate (more rapid onset, IV, SQ) prednisolone sodium succinate (Solu-medrol) (IV only, back trauma)
  45. Repeated or long term use of glucocorticoids
    • iatrogenic diabetes mellitus
    • iatrogenic hyperadrenocorticism
    • administration must be tapered off gradually, abrupt causes Addison's.
  46. Histamine
    • primarily stored in mast cells in lungs and skin (where they may see pathogens), enterochromaffin-like cells in gastric mucosa, basophils in blood
    • Triggers for release allergens, noxious chemicals, bacterial toxins, venoms
    • physical trauma to cell membranes (removing mast cell tumor can cause)
  47. Mast cell degranulation
    • allergen cross-links on sensitized B cell, differentiates into plasma cell or memory cell.  Allergy specific IgE, binds to FC receptor creating "sensitized" mast cell.  
    • Original allergen binds to sensitized mast cell, causes degranulation
    • Effects smooth muscle, smooth blood vessles (increases vasodilation and permeability), mucous gland (production), blood platelets (increases aggregation, releases platelet aggregating factor), sensory nerve endings (itchy/sensitized), histamine is chemotaxic for eosinophils
  48. Effects of histamine on H1 receptors
    • brochoconstriction at bronchial smooth muscle
    • spasmodic contraction (v/d) at GI smooth muscle, as in post-vaccine allergy
    • vasodilation and increased permeability at vascular endothelium (swelling and red)
    • pain and itching at sensory nerve endings in skin
    • motion sicknes from emetic center and CTZ
  49. H1 receptor antagonists
    • diphenhydramine (Benadryl), chlorpheiramine (Chlor-Trimeton)
    • hydroxyzine, meclizine (Dramamine non-drowsy)
  50. Therapeutic uses of H1 receptor agonists
    • antihistamines
    • control symptoms of allergy, esp in skin
    • before manipulation of mast cell tumors
    • antiemetic (car sickness) (meclizine)
    • More effective if given early and consistently throughout.
  51. H1 blockers effect
    sedation, CNS excitement, GI disturbance, local anesthetic, allergenic, teratogenic (birth defects if pregnant), parasympatholytic action (atropine-like effects, dry mouth, mydriasis, tachycardia, blurred near vision)
  52. H1 blockers adverse effects
    • sedation (second generation are nonsedating, no antimuscarinic effects--P-glycoprotein pump gets rid of better. fexofenadine, loratadine, ceritizine)
    • high doses case irritability, convulsions, hyperpyrexia, death
    • prolonged administration causes VDA, constipation, nausea
  53. fexofenadine
    • second generation H1 blocker
    • allegra
  54. loratadine
    • second generation H1 blocker
    • claritin
  55. cetirizine
    • second generation H1 blocker
    • zyrtec
  56. diphendydramine
    • H1 receptor antagonist
    • Benadryl
  57. chlorpheniramine
    • H1 receptor antagonist
    • Chlor-Trimeton
    • good in cats
  58. hydroxyzine
    • H1 receptor antagonist
    • good in dogs
  59. meclizine
    • H1 receptor antagonist
    • dramamine non-drowsy
    • anti-emetic
  60. H2 receptor
    • increases gastric acid production
    • Histamine from enterochromaffin-like cell binds to parietal cell which makes acid.
    • Cimetidine
    • rinididine
    • famotidine
  61. Cimetidine
    • H2 blocker
    • tagamet
  62. Rinididine
    • H2 blocker
    • Zantac
  63. Famotidine
    • H2 blocker
    • Pepsid
  64. Prednisone
    • oldest synthetic glucocorticoid
    • biotransformed to prednisolone
    • intermediate-acting, 12-hour
    • usually PO, can be IV
  65. prednisolone
    • synthetic glucocorticoid
    • biotransformed to methylprednisolone
    • intermediate-acting, 12-hour
    • usually PO, can be IV
  66. methylprednisolone
    • Medrol, metabolized prednisolone.  Better-tolerated. 
    • synthetic glucocorticoid
    • intermediate-acting, 12-hour
    • usually PO, can be IV
  67. dexamethasone
    Azium, long-acting synthetic glucocorticoid, > 48h, IV or PO
  68. Triamcinolone
    Vetalog, intermediate-acting synthetic glucocorticoid, 24-36h, IV or PO
  69. dexmethasone sodium phosphate
    Dex SP, more rapid onset than dex.  IV, SQ
  70. Prednisolone sodium succinate
    • Solu-medrol
    • Faster, IV only
    • back trauma (disc)
  71. Fluticazone
    inhalant synthetic glucocorticoid for asthma
  72. antimicrobial agent
    • an agent that kills or suppresses the growth of microorganisms
    • ANY.  Fungal, bacterial, etc
  73. antibacterial agent
    • an agent that kills bacteria or inhibits bacterial growth and/or replication
    • JUST bacteria
  74. antibiotic agent
    technically, a chemical substance produced by microorganisms which, in high dilution, kills or suppresses the growth of other microrganisms
  75. bactericidal agents
    • kill bacteria at serum levels that are safe for patient
    • always best choice if right one is available
  76. bacteriostatic agents
    • arrest or inhibit growth and replication of bacteria at serum levels that are safe for the patient. 
    • P must be immunocompetent, immune system must kill bacteria
    • if doses are skipped or dosage is too low, or if administration is stopped too soon, resistant bacteria may emerge and enough viable organisms may remain to re-start infection
  77. broad-spectrum antimicrobial agent
    agent that is effective against a wide variety of microbial species (gram+, gram-, anaerobes, facilitative anaerobes. "4 quadrants")
  78. narrow-spectrum antimicrobial agent
    agent that is effective against a single or very limited number of microbial species
  79. selection of antimicrobial agent
    • get a sample and submit for culture and sensitivity.  
    • pick agent that is most selectively active and least potentially toxic to P
  80. Selection of antimicrobial in emergencies
    start with broad-spectrum, get C&S, switch to narrow when results are available
  81. drug resistance
    • when growth of organism is not halted by maximum level of drug tha tis tolerated by P (safe)
    • bacteria may be naturally resistant or may acquire resistance through overuse and misuse of antibiotics.
  82. MRSA
    methacillin resistanct staphylococcus aureus (human)
  83. MRSP
    • methacillin resistant staphylococcus pseudointermedius
    • What dogs get.  
    • Penicillin Binding Protein mutation.
  84. B-lactam antibiotics
    • include penicillins and cephalosporins
    • all bactericidal
    • all inhibit synthesis of bacterial cell wall, especially gram + bacteria. 
    • B-lactamase leaves B-lactam ring, inactivates penicillin
  85. bactericidal actions of B-lactam antibiotics
    • stop cross-linking of peptidoglycan chains in cell wall
    • bind to penicillin binding protein, causing cell wall to relase autolytic enzymes, which destroy existing wall.  
    • Cell has to be growing/wall being formed to work
  86. Penicillin was discovered
    in 1920s when Alexander Fleming accidentally contaminated culture, wouldn't grow
  87. history of cephalosporins
    raw sewage in 1940s
  88. Penicillin G
    • narrow-spectrum, only active against Gram+ bacteria and anaerobes
    • used in tetanus
  89. Penicillin G benzathine
    • Flo-Cillin, Pro Pen G
    • 1st antibiotic in medicine measured in units
    • repository preparatin, IM administration
    • poorly absorbed, subtherapeutic
    • often given with fluoroquinalone or aminoglycoside to give gram- coverage
    • inactivated by penicillinases (B-lactamases
  90. B lactimases
    • penicillinases
    • enzymes secreted by some bacteria that cleave B lactam ring, inactivating penicillin
    • Bacteria can acquire ability to synthesize B-lactamases
  91. Pen Gen
    Penicillin and genomyocin
  92. extended-spectrum penicillins
    • better activity against gram - than regular Pen G, also includes anaerobes and some spirochetes.  (lyme, lepto, Pasteurella, Listeria, Actinomycin)
    • still susceptible to inactivation by B-lactimases.
    • Includes amoxicillin(PO) and ampicillin(IV)
  93. Amoxicillin
    • PO extended-spectrum penicillin
    • Susceptible to B-lactimases
    • gram +, okay gram - (pasteurella, Listeria, Actinomycen)
    • anaerobes, spirochetes (lyme, lepto)
  94. Ampicillin
    • IV extended-spectrum penicillin
    • Susceptible to B-lactimases
    • Gram +, okay gram - (pasteurella, listeria, actinomycin)
    • anaerobes and spirochetes (lyme, lepto)
  95. Clavulanic acid
    • Inhibits B-lactimases, so combined with B-lactam antibiotics to expand spectrum.  
    • Clavamox (augmentin in people)
    • Absorption poor in large animal.
  96. Clavamox
    • amoxicillin and clavulanic acid
    • expands spectrum (not inactivated by B-lactamase).
    • Oral, absorption is poor in large animals.
    • augmentin in people
  97. Sulbatam-ampicillin
    • IV clavamox.  Sulbatam works like clavulanic acid (inhibits B lactamase) to expand spectrum of ampicillin.  
    • Okay in large animals.
  98. Rabbits and penicillin
    causes clostridial overgrowth in cecum (clostridial enteritis)
  99. Clostridial enteritis
    side effect of penicillin in rabbits.
  100. Side effects of penicillin
    • hypersensitivity
    • Inject slowly or neurotoxicity, seizures, vomiting due to GABA inhibition.
    • Injecting too fast causes hemolysis in horses and cats
    • Rabbits can get clostridial enteritis
  101. MIC
    • minimum inhibitory concentration
    • minimum amount of drung that has to accumulate to be effective
  102. Cephalosporins
    • Bactericidal--inhibit cell wall synthesis
    • Side effects like penicillin (neuro, seizures, vomiting), GI in cats, hemolysis in cats, horses
    • Resistance problem.
    • #1 for pyoderma, surgery
    • four generations.
  103. First generation cephalosporins
    • Like extended-spectrum penicillins
    • effective against gram+ and some gram- bacteria (better at - than PenG, worse at anaerobes)
    • less sensitive to some B-lactamases
    • cefazolin (IV), cephalexin (PO), cephadroxil (PO)
  104. cefazolin
    • IV first generation cephalosporin (bactericidal, inhibit wall synth, gram +/-)
    • Best at gram-, some bone penetration
  105. cephalexin
    • PO first generation cephalosporin (bactericidal, inhibit wall synth, gram +/-)
    • Can be BID (staph) or TID (gram-), more often in horses, less often in cats
  106. fourth generation cephalosporin
    • bactericidal, inhibit synthesis of cell wall
    • broad-spectrum coverage in emergencies
    • gram - in enteric pseudomonas
  107. Convenia
    • 3rd generation cephalosporin (IV), 14 days of broad spectrum tx with 1 injection
    • skin infections in dogs (staph intermedius and strep canis) and skin wounds in cats (Pasteurella multocida)
    • use in 28 days
  108. ceftiofur
    • 3rd generation cephalosporin, bactericidal, inhibit cell wall synthesis
    • broad-spectrum, includes gram-
    • Used in large animal
  109. Cefpodoxime
    • Simplicef.  SID 3rd generation cephalosporin
    • Most gram - of oral cephalosporins
    • Pyoderma and off-label (UTI, dental)
    • horses okay, BID
  110. B-lactam hypersensitivity (rules)
    • allergic to one penicillin = all penicillins
    • one cephalosporin = all cephalosporins
    • pencillin allergy = +/- allergy to cephalosporins
    • cephalosporin allergy = +/- allergy to penicillins
  111. Protein synthesis inhibitors, list (static or cidal)
    • aminoglycosides (bactericidal, only one)
    • tetracyclines (bacteriostatic)
    • macrolides (bacteriostatic)
    • lincosamines (bacteriostatic)
    • chloramphenicol (bacteriostatic)
  112. protein sythesis inhibitors, mechanism
    • interefere with ribosomes in bacteria to inhibit proteins
    • Dif than ribosome in mammalian cells but can be similar to mammalian mitochondria (toxicity).
  113. Aminoglycoside side effects/toxicities
    • Ototoxicity (accumulates in ear, exc neomycin)
    • nephrotoxicity
    • apnea if IV too fast
    • Deafness if eardrum is not intact
    • anaphylaxis if put in eye of cats (neomycin)
  114. Aminoglycosides
    • only bactericidal protein syntesis inhibitor, most IV
    • #1 against gram -, no anaerobes, synergistic with B-lactams, but causes toxicity
    • excreted unchanged in urine
    • gentamicin, amikacin, neomycin, streptomycin, tobramycin
  115. aminoglycosides mechanism (3+)
    • diffuse through aqueous porin channels in outer membrane into periplasmic space. O2-requiring transport into cell itself to interact with ribosomes. 
    • 1. blocks initiation of protein synthesis
    • 2. causes premature termination of protein synthesis
    • 3. causes incorporation of incorrect amino acids
  116. Gentamicin
    • IV aminoglycoside (protein synthesis bactericide)
    • used in nebulization
    • Good for respiratory
  117. amikacin
    IV aminoglycoside (protein synthesis bactericide)
  118. neomycin
    • topical aminoglycoside (protein synthesis bactericide)
    • used in eye/ear, NEVER for systemic absorption
    • does not accumulate in ear
    • anaphylaxis in eye of cats
  119. streptomycin
    IV aminoglycoside (protein synthesis bactericide)
  120. tobramycin
    • topical aminoglycoside (protein synthesis bactericide)
    • used in eye.
  121. tetracyclines, mechanism
    • bacteriostatic protein synthesis inhibitor
    • prevent 1st step in elongation (tRNA to mRNA at 30s(heel), binds Ca, Mg and Al (so no food or antacids). Don't give with B-lactam
    • Broad-spectrum, good for tick-borne and rickettsial diseases, and lepto.
    • tetracycline, doxycycline
  122. Tetracyclines active against
    • gram +, gram -, anaerobes, spirochetes (DOC in Lyme/Borrelia), Rickettsia (DOC for Rocky Mountain Spotted Fever and Ehrlichiosis), Mycoplasma haemofelis, Chlamydia (psittacosis), lepto, some protozoa
    • Resistance in staph, pseudomonas, and enterobacteria like e coli and salmonella
  123. doxycycline
    • tetracycline, bacteriostatic protein synth inhibitor. 
    • VERY SLOW IV or hypotension, collapse, sudden death in horses
    • Biliary secretion in dog
    • Don't give with B-lactam
    • intracellular, good for rickettsial, spirochetes, anaerobes, gram +/-, mycoplasma haemofelis, chlamydia, protozoa
    • binds Ca, Mg, Al (no food/dairy/antacid)
  124. Tetracycline and B-lactam
    Don't give together.  bacteriostatic (tetras) stop cell wall growth.  B-lactams only work on growing cell wall.
  125. Tetracyclines contraindications and side effects
    • V/D
    • no pregnant or growing, binds Ca so slows bone growth and discolors teeth
    • fever, depression and anorexia in cats
    • strictures and esophagitis with pill in cats
    • hypotension and collapse if too fast IV (Ca and heart)
    • sudden death in horses
  126. Psittacosis and treatment
    • chlamydia in birds
    • zoonotic
    • treat with tetracyclines
  127. Mycoplasma haemofelis and treatment
    • most common cause of infectious hemolytic anemia
    • treat with tetracyclines
  128. Chloramphenicol
    • bacteriostatic protein inhibitor
    • broad spectrum, good for gram +/-, anaerobes, rickettsiae, chlamydia, some protozoa
    • from streptomyces in 1940s
    • some toxicity (not selective enough), no cats
    • used rarely so good for resistant drugs
    • metabolized rapidly by liver, glucuronidation (give often)
    • CNS effective, good for respiratory (kennel cough), goes into eye, doesn't cause GI in horses
  129. chloramphenicol mechanism of action
    • bacteriostatic, protein synthesis inhibitor
    • Binds at 50s, stops enzyme that links amino acid to mRNA
  130. chloramphenicol side effects/toxicity
    • not selective enough, inhibits mammal protein synth as well.  Causes mitochondrial and bone marrow suppression, especially in cats (also cleared with glucuronidation).  Anorexia and depression in cats, also aplastic anemia (rare)
    • ALWAYS ANEMIA, dose-related, reversible.  Aplastic rarely in humans, O wear gloves.
    • Not in food or milk-producing animals
    • can't use with macrolide or lincosamines
  131. Erysipelothrix
    • "diamond skin disease" in pigs
    • use Tylosin to treat (macrolide)
  132. Macrolide antimicrobial agents
    • bacteriostatic protein synthesis inhibitor, binds at 50s near chloramphenicol, between tRNA and mRNA so amino acid doesn't get transferred
    • Causes GI (V/D)
    • gram + mostly, NOT pasteurella, some anaerobes
    • erythromycin, tylosin, azithromycin, clarithromycin
    • don't use with chloramphenicol or lincosamines
  133. Tylosin
    • macrolide bacteriostatic protein synth inhibitor
    • chronic colitis in small animals, not proven
    • use in erysipelothrix in pigs
    • GI upset
  134. Erythromycin
    • macrolide bacteriostatic protein synth inhibitor
    • 1st discovered, best with alkaline so no absesses
    • GI upset
  135. Azithromycin
    • macrolide bacteriostatic protein synth inhibitor
    • Z-pack
    • respiratory infections
  136. Clarithromycin
    • macrolide bacteriostatic protein synth inhibitor
    • resistant e coli, UTI
    • bad for GI
  137. Lincosamines mech and use
    • bacteriostatic protein synth inhibitor
    • binds at 50s near chloramphenicol and macrolide, stops aa from transferring from tRNA to mRNA
    • narrow spectrum (gram + and anaerobes)
    • rarely used so good for MRSA, toxoplasma, osteolitis, periodontal disease
    • Clindamycin, lincomycin
  138. Lincosamines side effects
    • don't use to macrolide or chloramphenicols (same spot, physical interference)
    • V/D
    • hepatotoxicity
    • clostridial overgrowth in rabbits, horses, ruminants
  139. Clindamycin
    • Lincosamine, bacteriostatic protein synth inhibitor
    • narrow spectrum, gram+ and anaerobes
    • most complete absorption of lincos.  
    • Good for MRSA, toxoplasma, osteolytis, periodontal disease
  140. Sulfonamides
    • Folic acid synthesis inhibitors, only work on folic acid-users. Binds to PABA so Pteridine never activated (Sulfaadimethoxine) or blocks phosphorylation of dihydrofolic acid to activated form, tetrahydrofolic acid
    • Broad-spectrum (gram +/-, protozoa), kidney elim, concentrated in urine (UTI), respiratory, soft tissue, pasteurella
  141. Side effects of Sulfonamides
    • Precipitate into crystals in urine (hydrate!)
    • salivation in cats (PO)
    • KCS (secreted in tears and milk) in dogs
    • allergies, liver failure
  142. Pasteurella can be killed by
    • extended-spectrum penicillins (amoxicillin, ampicillin)
    • folic acid synthesis inhibitors
    • Pradofloxacin (fluroniated quinolones?)
    • NOT macrolides
  143. Sulfonamide list
    • folic acid synthesis
    • Sulfadimethoxine (Albon), bacteriostatic for coccidia
    • trimethoprim, bacteriostatic
    • trimethoprim-sulfa, bactericidal, good for rabbits.
  144. fluorinated quinolones
    • "-floxacin"s. 
    • Interferes with bacterial DNA Gyrase, un-helixes
    • Bactericidal (inhibit replication of bacterial DNA), 100% oral bioavailability
    • Gram-, safer than aminoglycosides.  Doesn't need rapid growth or division
    • Binds Ca, Mg, Al, don't give with antacids
    • enrofloxacin, orbifloxacin, marbofloxacin, ciprofloxacin
  145. ciprofloxacin
    fluroinated quinolone, used in humans for traveler's diarrhea, pseudomonas
  146. marbofloxacin
    Fluroinated quinolone, SID for pseudomonas
  147. enrofloxacin
    • vet approved fluroinated quinolone
    • "Baytril"
    • oral, parenteral and otic
    • good for exotics
    • neurotox (GABA inhibition) if not diluted IV
    • Blindness (retinal damage) in cats above 5mg/kg/day
    • no puppies or kittens, cartilage toxicity
  148. Pradofloxacin
    • 3rd gen fluorinated quinolone, newest.  
    • Gram +, -, anaerobes.  Inhibits DNA gyrase and topolsomerase IV. PO
    • CATS ONLY, bone marrow suppression in dogs
    • skin conditions (Pasteurella, strep canis and staph)
    • no food, careful with hypoproteinemia (30% plasma protein bound)
    • GI, reversible leukocyte suppression in young kittens
  149. Nitroimidazoles
    • anaerobic bacteria and protozoa (giardia)
    • metronidazole
    • bactericidal
    • DNA breaks into strands, loses helix
  150. DNA gyrase
    allows DNA to untwist (for replication).  Inhibition causes DNA to permanently untwist, break into strands.
  151. PABA
    • para-amino benzoic acid.
    • Binds to Pteridine, series of reactions, becomes tetrahydrofolic acid (active folic acid)
    • Pathway inhibited by sulfonamides.  PABA binds to sulfadimethoxine instead or trimethoprim stops phosphorylation of dihydrofolic acid into tetrahydrofolic acid
  152. Metronidazole and side effects
    • nitroimidazole, bactericidal (DNA loses shape, inhibits GABA)
    • Bitter, metallic taste (cats salivate and shake head)
    • lethargy, VDA
    • neurotoxicity from GABA, ataxia, lethargy, nystagmus, rigidity, seizures (recover)
    • Dose at 22mg/kg/day, 60=seizures
    • Caution in pregnant/nursing, banned in food animals
  153. Mycoses
    • infectious diseases caused by fungi.
    • systemic: blastomycosis, histoplasmosis, aspergillosis
    • superficial invade skine, fur, claws, nails (ringworm)
    • hard to treat, fungi are eukaryotic like mammal cells, so toxicity
  154. antifungals (list)
    • amphotericin B
    • Imidazoles including Miconazole, ketoconazole, itraconazole, fluconazole
    • Griseofulvin
  155. Amphotericin B
    • antifungal, punches hole in fungal cell membrane.  Binds to ergosterol in plasma membrane to make permeable.  Leaks electrolytes, dies.
    • Systemic mycoses only (IV, diluted in D5W).
  156. Amphoterin B side effects
    • antifungal. 
    • Chills, fever, nausea, vomiting, anorexia
    • cardiac arrhythmias, seizures, anemia
    • nephrotoxic (decreases GFR, renal epithelium).  ALL dogs will show renal toxicity, usually reversible.
    • NOT VERY SAFE.  use of imidazoles more common
  157. Common yeast in the body
    • Malassezia
    • Candida
  158. Imidazoles
    • anti-fungals
    • inhibit cell membrane formation and impair function by binding to P450 and using up ergosterol.
    • Includes miconazole, ketoconazole, itraconazole, fluconazole
  159. Miconazole
    • imidazole antifungal
    • topical admin in superficial mycoses
  160. ketoconazole
    • imidazole antifungal
    • systemic administration in systemic and superficial. 
    • dose-related anorexia, nausea, vomiting, depression (give with food to help)
    • interferes with synth of testosterone and cortisol in dogs (p450), low hepatotoxicity (more in cats)
  161. Itraconazole
    • imidazole antifungal
    • safer and more expensive, treatment of dermatophytosis (ringworm)
    • No hormones, less intersted in mammalian P450
  162. Dermatophytosis
    • ringworm
    • killed by itraconazole
  163. Fluconazole
    • imidazole antifungal
    • birds with aspergillosis
  164. Griseofulvin
    • inhibits mitosis in fungal cells.  Cheap, often used as a shelter medication
    • superficial mycoses only (dermatophytosis). PO
    • Bone marrow suppression, esp in cats (check CBC q2w)
    • Not in pregnant or bleeding animals(terratogenic)
  165. Flucytosine
    • Fungicide for systemic mycoses, not used much
    • interrupt protein synth in RNA or turned into something that inhibits DNA synth
    • Less toxic than ketaconozole
    • Bone marrow suppression, give uracil.  5-FU is product with both. 
    • Synergistic with amphotericin B (A-B punches holes in membrane, lets Fluc in), but increases nephrotoxicity of A-B caused it.
  166. 5-FU
    • Flucytosine and uracil
    • antifungal (causes bone marrow suppression) and RNA building-block to balance.
  167. Terbafine
    • fungicidal
    • disrupts cell membrane on active systemic mycoses, yeast, dermatophytes.
    • Lipophylic (goes to skin, hair, nails), where you need it.
    • no P450, does not bother hormones
    • mild increase in liver enzymes, resolve post-drug
    • cats get facial pruritus.
Card Set:
anti-inflammatory agents H1-receptor antagonists and antimicrobial therapy
2013-12-13 03:51:56
pharm tox
anti-inflammatory agents, H1-receptor antagonists and antimicrobial therapy in veterinary pharmacology and toxicology
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