Pharmacology

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lafor1be
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78114
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Pharmacology
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2011-04-07 14:56:45
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Large Animal Pharmacology
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spring large animal pharmacology
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  1. AVMA Guidlines for drug use
    • “Drugs restricted by federal law to use by or on the order of a licensed veterinarian” prescription drugs
    • NOT - for vet use only, sold to vets only
    • MUST HAVE A VALID DOCTOR-CLIENT PATIENT RELATIONSHIP!!!
  2. Prescription Drugs
    • May be dispensed by non-vet staff AFTER they have received instructions from a vet
    • Prescription drugs should be kept separately from OTC drugs and not accessible by the public
    • Records must be kept of all prescriptions and updated quarterly or more often
    • Prescriptions cannot be changed except by prescribing vet with a signature
  3. Prescription Drug Labels
    • Doctor, clinic name, address, license number
    • Date
    • Patient name, owner name
    • Drug name , strength and amount
    • Explicit instructions
    • Refills
    • Withdrawal times
  4. Economics of Drug use
    • Many drugs are not routinely used in large animals because the amounts needed are cost prohibitive and food animals have a set value (price of meat)
    • Baytril (enrofloxacin) - 2.5 mg/kg BID
    • Average bovine - 1300 pounds
    • > 3 grams BID; 68mg tabs are $3 each > 44 tabs BID > $264 per day
    • Penicillin - $7 per day
  5. Legend Drugs
    • Prescription drugs and drugs in which there is some potential for abuse, misuse, side effects or the instructions are not easy for the lay person to understand
    • Off label use
    • Controlled drugs - CI - CV
  6. Controlled Drugs
    • CI - research use only, special license required (LSD, heroin)
    • CII - high abuse potential (morphine, carfentanil, pentobarbital)
    • CIII - some abuse potential (telazol, ketamine, phenobarb, pentothal
    • CIV - low abuse potential (butorphanol, diazepam)
    • CV - state or local control – codeine

    Meticulous records need to be kept for every drop C1-C4
  7. Technicians Role
    • Vet techs can dispense legend drugs under the supervision of a vet only
    • You need to use your training to make sure the drug and dose makes sense
    • Knowledge of proper injection sites, amount per site, techniques of administration, withdrawal times, etc
    • If there is any doubt, ASK! Vets do screw up!
  8. Drug Residues
    • A big problem in the food animal industry (this does include some horses!)
    • Any drug residues found in meat or milk are cause for a producer to lose his profits, his animals and/or his livelihood
    • Different species metabolize drugs at different rates, differences between individuals within a species, physical condition of the individual, age of individual, concurrent drug use
  9. Drug Metabolism
    • Liver is the key organ for drug metabolism
    • Oxidized, reduced or hydrolyzed
    • Cats - hard time with aspirin, dogs - hard time with sulfonamides
    • Ruminants - hard time with sedatives/paralytics
    • Concurrent drug use, age effects
    • Half life
  10. Inflammation
    • Mediated by several classes of chemicals that activate an “inflammatory cascade” that can be difficult to stop once started
    • Histamine - vasodilation, bronchoconstriction, gastric secretion, sensitized nerve endings (pain)
    • Kininogens - vasodilation, pain
    • Prostaglandins - pain, vasodilation, gastric secretions
    • All inflammatory responses begin with vasodilation, 5-10 minutes later blood vessels become leaky and mediators which are released from blood cells can enter the area
    • 4 cardinal signs of inflammation
  11. Anti-inflammitory drugs
    • Adrenocortical hormones
    • Corticosteroids
    • Anabolic steroids
    • Non-steroidal anti-inflammatories (NSAIDS)
  12. Adrenocortical hormones
    • Produced in the adrenal gland (ACTH)
    • Mineralocorticoids - aldosterone - facilitates sodium and water retention by the kidneys (anti-diuretic)
    • Glucocorticoids - cortisol - increases carbohydrate, protein, and fat metabolism - fight or flight
    • Sex hormones – minor source of estrogen, progesterone and testosterone (FSH, LH not stimulated by ACTH)
    • Epinephrine
  13. Corticosteriods
    • Uses - anti-inflammatory, anti-pruritic, immune suppression, vasoconstriction, anti-pyretic
    • Problems - decreased immune function, PU/PD (inhibits ADH), muscle catabolism, laminitis in horses, ulcers, slows wound healing
    • Water soluble - fast and short acting;
    • water insoluble - slow and long acting
  14. Corticosteriod activity
    • Cortisol/cortisone - base standard
    • Prednisone, prednisolone - 4X cortisol, 12-36 hr onset
    • Methylprednisolone (Depo Medrol) - 5X cortisol, 12-36 hours onset
    • Trimacinolone (Vetalog) - 5X cortisol, 12 -36 hour onset
    • Betamethasone (Celestone) - 30X cortisol, 36-72 hour onset
    • Dexamethasone (Azium, Voren) - 30X cortisol, 36-72 hour onset
  15. Anabolic Steroids
    • CIII
    • Stimulates appetite, bone marrow and muscle anabolism
    • Stanozolol (Winstrol),
    • Boldenone (Equipoise)
    • Hard on liver, kidneys and physes
  16. Non-Steroidal-Ani-Inflammatory-Drugs (NSAIDs)
    • Uses - anti-inflammatory, anti-pyretic, analgesic, anti-endotoxic
    • Contraindications - GI ulcers or diarrhea, kidney disease, dehydration, anemia, liver disease
    • Mechanism of action - inhibits migration of inflammatory cells from the blood vessels, blocks prostaglandin production, inhibits phagocytocis
  17. Aspirin
    • Acetylsalicylic acid
    • Short half life in horses so not used much
    • Large boluses used frequently in food animals
    • Has some anticoagulant effects with long term use
    • Acetominophen (Tylenol) - too expensive
  18. Flunixin
    • Banamine
    • Excellent visceral analgesic - #1 choice for colic
    • Anti-endotoxic at low doses (1/4 of anti-inflammatory dose, but TID vs BID)
  19. Phenylbutazone
    • Bute
    • Excellent analgesic for musculoskeletal pain, less so for visceral pain
    • Can be used for long periods of time at a reasonable dose
    • NSAID most likely to cause toxicity (ulcers, colitis, major kidney damage)
  20. Prostiglandin and Hormones
    • Prostaglandin
    • Progesterone
    • HCG
    • Oxytocin
    • Deslorelin
    • Used almost exclusively to manipulate the estrous cycle to facilitate breeding
  21. Prostaglandins- PGF2a
    • Lutalyse
    • Use to lyse a CL, brings mare back into heat within 5 days IF CL is responsive (>5 days post ovulation)
    • Used for abortion
    • Causes signs of colic, sweating and severe cramping within 10-15 minutes - effects will pass
  22. Progesterone
    • Regumate
    • Maintains the uterus during pregnancy, prevents mares from coming into estrus, may reduce objectionable behavior in stallions
    • DO NOT GET REGUMATE ON YOUR SKIN - IF YOU ARE PREGNANT, DON’T EVEN GET NEAR IT!!!!
  23. Human Chorionic Gonadotropin
    • HCG
    • Causes a mature follicle (>35mm in size) to ovulate within 36-48 hours
    • Used to time ovulation with semen availability
    • Only works once in any given breeding
    • season - they develop antibodies!
  24. Deslorelin
    • Ovuplant - subcutaneous implant
    • GNRH analogue - causes increase in LH levels
    • Causes ovulation of a follicle >32 mm in size within 36 hours
    • Can be used multiple times in a season
    • $$$$
  25. Oxytocin
    • Stimulates smooth muscle contraction
    • Milk letdown
    • Retained placenta
    • Induction of labor
  26. Anthelmintics
    • Many different classes that treat different types of parasites
    • Cestodes, nematodes, trematodes
    • Coccidia
  27. Coccidiostats
    • Amprolium - mimics vitamin B1 and binds to vB receptors on the schizonts, thereby retarding the schizonts development
    • Sulfonamides - inhibits folic acid synthesis
    • These are both coccidiostats - they do not kill the coccidia, just stop its development
  28. Organophosphates
    • Dichlorvos, Trichlorfon
    • Blocks nervous conduction in the parasite - if the dose is too high, it will block conduction in the host as well!
    • DO NOT use in pregnant animals or young animals
    • Very toxic - causes diarrhea, cramping and colic
    • Used to kill bot larvae
  29. Avermectins
    • Ivermectin (Eqvalan, Zimectrin), moxidectin (Quest), “Heartgard”
    • Dosed orally, IM or pour-on
    • Blocks the neurotransmitter GABA in the worm’s nervous system, thereby paralyzing it so it can be passed
    • Used for nematodes and bots - no effect on trematodes and cestodes, they have no GABA
    • NOT FOR use in animals intended for food or lactating dairy cattle
  30. Benzimidazoles
    • Very large group - all drups end in ‘-azole’
    • Very safe drugs (80 times recc dose)
    • Affects the microtubules (strength and movement) and glucose levels (decreases) of the parasites, thereby killing nematodes and trematodes
    • Thiabendazole - TBZ
    • Fenbendazole - ‘Panacur’, ‘Safeguard’ - 8 day withdrawl, not for breeding dairy cows - also kills cestodes at double dose
    • Mebendazole - ‘Telmintic’
    • Oxyfenbendazole - ‘Anthelcide’
    • Levamisole- ‘Levasole’, not for horses
  31. Phenothiazines
    • Affects the nervous system of nematodes
    • Very harsh on the host
    • Not used much in large animals
    • Also used as a tranquilizer (acepromazine)
  32. Piperazine
    • Affects nervous system of nematodes, causing paralysis
    • Affects adults only, retreat in 2-4 weeks to get newly molted larvae
    • Can cause diarrhea and neuro signs
    • Not used much in large animal but is used in pigs
  33. Pyrantel - "Strongid"
    • Paralyzes adult nematodes at recc dose, paralyzes tapeworms at double dose (springtime)
    • Safe up to 20X recc dose
    • Can be fed daily - ‘Strongid C’
  34. Praziquantel
    • “Droncit”
    • Just recently approved for use in horses
    • Effective against cestodes and some trematodes
    • Causes paralysis of parasite and results in digestion
    • Used in combination with an avermectin as an “all in one” dewormer
  35. Combination of Anthelmintics
    • Many anthelmintics combine classes and are sold under a new name
    • Be sure all of the ingredients are safe in the animal you are treating
  36. Beta-Lactam Antibiotics
    • All drugs in this group are based on a b-lactam ring
    • Penicillins and cephalosporins
    • Mechanism of action - binds to bacterial cell wall proteins to cause holes in the cell walls, resulting in cell death
    • Bacteria can become resistant by developing “b-lactamases” that destroy the b-lactam ring
  37. Penicillins
    • Discovered in 1928
    • Bacteriocidal to Gram (+)bacteria, aerobic and anaerobic
    • Dosed in international units (IU) - amount of activity in 0.6mg of pure crystalline penicillin
    • Rapidly absorbed IM; not given orally in large animals (diarrhea and GI upset)
    • Excreted by the kidney
  38. Penicillin - types
    • Pen G benzathine - IM only, longer acting (q 48 hour dosing)
    • Pen G procaine - IM only, contains anesthetic due to large doses used, slows absorption
    • Label dose is WRONG! 10,000 IU/lb = 3cc per 100lb body weight
    • Sodium pen, potassium pen, ampicillin - IV only, good for resistant bacteria
  39. Penicillin - toxicity
    • Toxicity - not routinely seen
    • Hypersensitivity reactions - can be immediate - anaphylaxis, seizuring, collapse, hypersalivation, temporary blindness
    • Contraindications - known allergy to B-lactam antibiotics (including cephalosporins); concurrent use of bacteriostatic antibiotics (tetracycline)
  40. Clavulanic Acid
    • Added to some penicillins to prevent destruction of the drug by penicillinases (Clavamox)
    • ‘Potentiated’ penicillin
  41. Cephalosporins
    • First isolated in 1945 from sewage
    • Modified penicillins - same mechanism of action
    • 1st, 2nd and 3rd generations
    • Broader spectrum than pens, more Gram (+) and some Gram (-), 3rd generation less effective against Staph
    • More expensive
  42. Cephalosporins - types
    • Cephalexin (Keflex) - 1st generation, oral
    • Cefazolin - 1st generation, oral
    • Ceftiofur (Naxcel) - 3rd generation, IM or IV
    • Exceed new long acting Ceftiofur
    • Excreted by the kidney
  43. Cephalosporins - toxicity
    • Ceftiofur is the only cephalosporin used in large animals - orally causes diarrhea and GI upset
    • Toxicity - high doses can cause pain at injection sites, diarrhea and ataxia
    • If allergic to penicillins, then considered allergic to cephalosporins
    • Contraindications - known allergies
  44. Aminoglycosides
    • Bacteriocidal to Gram (-) bacteria, aerobic only
    • Inhibits bacterial protein synthesis by binding to the ribosome and rendering it useless
    • Gentamycin (Gentocin), amikacin ($$), tobramycin ($$$)
    • Given IV, IM or ophthalmic
    • Resistance - on the increase due to ribosomal mutation
    • Use VERY carefully in dehydrated animals - may be best to delay administration until dehydration is corrected
  45. Aminoglycosides - toxicity
    • Toxicity - ototoxicity, nephrotoxicity, neuromuscular blockade (respiratory paralysis)
    • SID dosing decreases negative effects
    • Contraindications - concurrent diuretic and anesthetic use, dehydration, severe renal disease
  46. Tetracyclines
    • Bacteriostatic
    • Gram (-) and (+), aerobic and anaerobic and rickettsia, but considerable resistance exists
    • Inhibits bacterial protein synthesis by ribosomal binding
    • Resistance is widespread
    • Given IV (SLOWLY) and orally, IM can be used, but is irritating
    • If given orally, do not combine with milk, antacids or Maalox (binds to the calcium)
    • Excreted by the kidney
  47. Tetracyclines - toxicity
    • Toxicity - generally safe, can cause GI upset
    • May cause diarrhea, yellow teeth (chelates calcium) - use very cautiously in young animals! New born foals for contracted tendons
    • Doxycycline
    • Contraindications - concurrent penicillin use, methoxyflurane use
  48. Chloramphenicol
    • Was the 1st broad spectrum antibiotic
    • Bacteriostatic against Gram (+) and (-), aerobes, anaerobes and rickettsia
    • Inhibits protein synthesis by binding to ribosome - this is reversible and can infection can recur if drug is withdrawn too soon
    • Given orally or IV, can cross the placenta, excreted by the kidney
  49. Chloramphenicol - toxicity
    • BANNED IN ALL FOOD ANIMALS!!!!!
    • Public health issues - blood dyscrasias (aplastic anemia) - handle the drug carefully (preferably wearing gloves)
    • Toxicity - short term therapy (<10 days) rarely causes side effects; GI upset if given orally
    • Contraindications - concurrent bacteriocidal drug use, phenobarbital
  50. Sulfonamides
    • #1 cause of drug residue violations, esp in swine, veal and poultry
    • 1st discovered in 1936
    • Bacteriostatic - Gram (-) and (+), coccidia
    • Bacteriocidal if combined with trimethoprim
    • Inhibits bacterial production of folic acid - bacteria must produce their own, mammalian cells must acquire it elsewhere
    • IV, IM and oral forms available (oral most common)
    • Resistance has developed
    • Excreted by liver and kidney
  51. Sulfonamides - toxicity
    • Toxicity - skin rashes, thrombocytopenia, arthritis, urinary disease
    • Contraindications - known allergy, folate deficiency, late term pregnancy, renal or liver diease
  52. Macrolides
    • Erythromycin, Streptomycin
    • Bacteriostatic (cidal at high doses) against Gram (+)
    • Inhibits bacterial protein synthesis by binding to the ribosome
    • May cause life threatening diarrhea in adult horses (can be used carefully in foals), rabbits and guinea pigs
  53. Macrolides - uses and toxicity
    • Given orally only on an empty stomach
    • IV or IM use is painful
    • Can cross the placenta
    • Excreted by the liver in bile
    • Toxicity - generally safe in ruminants
    • Contraindications - can interact with methylprednisolone (Depo-Medrol) and warfarin
  54. Fluroquinolones
    • Ciprofloxacin, Enrofloxacin (Baytril)
    • Bacteriocidal to Gram (+) and (-) aerobics; NO ANAEROBICS
    • Inhibits bacterial DNA from coiling into its double helix
    • Very useful in skin, respiratory and urinary tract infections
    • BANNED IN LACTATING DAIRY CATTLE
  55. Fluroquinolones - toxicity
    • Toxicity - GI upset
    • Damaging to developing cartilage - do not use in growing animals!
    • Contraindications - concurrent use of chloramphenicol or other fluroquinolones, magnesium containing antacids
  56. Drugs Banned in Food animals
    • Chloramphenicol, Clenbuterol
    • Diethylstilbestrol, Dimetridazole
    • Furazolidone, Glycopeptide
    • Ipronidazole, Nitrofurazone
    • Nitrofurans, Nitroimidazoles
    • Fluoroquinolones
    • Phenylbutazone (female dairy cattle >20 months of age)
    • Sulfonamides (lactating dairy cattle, except sulfadimethoxine)

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