Prescriptions and pharmacokinetics

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XQWCat
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238014
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Prescriptions and pharmacokinetics
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2013-10-06 01:31:53
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Pharm Tox
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Prescriptions, pharmacokinetics, Pharm & Tox
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  1. Dispensing drug label (12)
    • 1. hospital name, address, phone #
    • 2. DVM name
    • 3. Client name
    • 4. animal name, species, ID #
    • 5. date
    • 6. Drug name (trade and generic)
    • 7. dosage strength
    • 8. number of units dispensed
    • 9. directions for use
    • 10. manufacturer's expiration
    • 11. precautions
    • 12. prescription expiration date
  2. Prescription
    • an order for a medication, therapy or therapeutic device given by an authorized person.  
    • Legal document, order to a pharmacist.
  3. Prescription must contain (10)
    • 1. DVM name, address, phone #
    • 2. client name and address
    • 3. animal name and species
    • 4. date
    • 5. name of drug
    • 6. dosage strength
    • 7. directions to pharmacist
    • 8. directions to client
    • 9. # refills permitted
    • 10. precautions
  4. Pharmacokinetics
    • Route of administration
    • Absorption
    • distribution
    • metabolism
    • excretion
  5. Route of administration
    How the drug is introduced into the body.
  6. Enteral administration
    via some part of alimentary canal (oral, buccal/transmucosal, rectal)
  7. factors that influence route of admin (5)
    • available form
    • is it irritating, etc.  
    • rate of onset of action
    • behavior of patient
    • nature of condition
  8. factors that influence GI absorption (6)
    • pH (must closely match where absorbed)
    • fat/water solubility
    • size and shape of molecule
    • presence or absence of food
    • degree of GI motility
    • presence and nature of disease
  9. Oral administration
    • PO
    • cheap, convenient
    • distasteful, patient must be conscious, capable of swallowing, not vomiting, cats are hard to pill
    • dry swallowing may cause esophagitis and stricture formation (Doxy)
  10. Parental Administration
    • Any route other than via alimentary canal
    • Usually by injection
  11. Routes of parental administration
    IV, IM, SQ, ID, IP, intraarterial (IA), Intraarticular, IC, intramedullary (IO), epidural, subdural
  12. injectable administration + and -
    • +: total absorption, rapid absorption, rapid effect
    • -: shortest duration, painful, can't be used at home, requires restraint, sterile equipment and skill.
  13. IV considerations
    • Intravenous
    • inject slow, so you can stop.  Some cause death if too fast
    • irritating agents IV only
    • oil-based drugs, suspensions and milky-looking drugs not given IV
  14. IM injections given at __________ angle
    90 degrees
  15. IM injection
    • goes into interstitial fluid, absorbed into capillaries.  
    • Aqueous agents, rapid absorption, rapid effect.
    • Can use repository/depot preparations
  16. depot/repository preparations
    formulated to release a sustained dose of drug that is absorbed into bloodstream over an extended time period
  17. SQ administration given at ___________ angle
    45 degrees
  18. SQ administration
    slower to act, longer duration.  Never use irritating substances if possible.  Avoid hyperosmotic (won't absorb)
  19. intradermal administration
    injection into skin, allergy skin testing mostly
  20. intraperitoneal
    into abdominal cavity.  Rarely used in clinical medicine due to possible infection, puncture of organs, adhesion on abdominal organs.
  21. Intraarterial
    • rare clinically, plunger will pull back on its own.
    • In horses, can shoot into carotid, go right into brain.  Fatal drug dose in brain.
  22. Intraarticular
    • into joint.  Rare in clinical medicine.  Joint taps for diagnosis or local block in equine for lameness.  
    • STERILE
  23. Intracardiac
    only life-threatening due to possibility of lung puncture, pericardial adhesion, pericarditis.  Also, in cardiac arrest in heart doesn't help, want in circulation.
  24. Intramedullary, Intraosseous
    • proximal humerus, proximal tibia, trochanteric fossa of femur, wing of ilium (ilial crest).  
    • Tiny patients, when you can't get a catheter.  STERILE
  25. Epidural injection
    between L7 and SI vertebrae, epidural space between ligamentum flavum and dura mater.
  26. Intrathecal injection
    subdural.  past epidural into subarachnoid space.
  27. Inhalation
    • absorbed through mucus membranes of respiratory tract and alveolar membranes.  
    • Potential to move into pulmonary capillaries.
  28. Intratracheal administration (IT) (NAVEL)
    • absorbed through mucous membranes of respiratory tract and alveolar membranes.  Double dose, + 3-5 ml sterile water, catheter in intratracheal tube, put in to carina, follow with two breaths.  
    • Drugs that can go this way are NAVEL (Naloxone, Atropine, Vasopressin, Epinephrine, Lidocane.
  29. topical administration
    application on skin, mucous membranes, eyes, ears.  Local effect.
  30. Transdermal administration
    • application on skin for systemic circulation.  
    • Vehicle must penetrate epidermis.  
    • Disadvantages (risk of local inflammation, ingestion during grooming, owner must avoid, absorption variable)
  31. drug absorption
    • the movement of drug from its site of administration into the blood circulation
    • depends on route, usually faster the greater the blood supply.
  32. Routes that end up with 100% absorption
    • Intraveinous, Intracardiac, Intraarterial, Introosseus
    • slow--intramuscular, subcutaneous (via interstitial fluid)
  33. Three ways for drug to get into capillaries through passive transport.  
    Active transport?
    • 1. lipid-soluble substances diffuse across endothelial cells
    • 2. small, water-soluble substances pass through pores
    • 3. pinocytosis (vesicles break off from membrane).  
    • Active--electrolytes.  Use the pores but uphill, so uses energy.
  34. Method of absorption depends on
    • water or lipid soluble (partition coefficient)
    • size and shape of molecule
    • degree of ionization of molecule (can depend on pH.  Same diffuses readily, opposite becomes trapped
  35. factors influencing absorption
    • lipid-solubility of drug in body fluid (higher partition coefficient=higher solubility=faster absorption)
    • total surface area for absorption (largest space is small intestine)
    • contact time at site of absorption (GI motility)
    • blood flow to absorption site (higher=higher)
  36. Bioavailability
    • fraction of unchanged drug reaching systemic circulation following its administration.
    • 100% (IM, SQ, IV, etc.)
  37. factors influencing bioavailability
    • cell membrane/lipid solubility
    • first pass biotransformation
    • chemical stability
    • nature of drug formation/vehicle
    • degree of GI motility/stomach emptying time
    • inflammation of mucosa/damage to villi
    • amount of composition of food
    • altered microorganisms
  38. first-pass biotransformation
    • when liver metabolizes drug, leaves metabolites.  
    • Baytril very little, morphine, lidocaine, buprenorphine, a LOT.  Some go through not at all.
  39. Bioequivalence
    Two drugs show same plasma concentration at same dose.  FDA only requires that.
  40. Drug distribution
    process by which drug leaves sytemic circulation and reaches its site of action in ISF or ICF (interstitial or intracellular)
  41. major factors determining drug distribution
    blood flow to tissues, concentration gradient, capillary permeability/lipid-solubility of drug, plasma-protein binding, barriers, disease processes
  42. how pH effects absorption/distribution
    a base in acidic medium will ionize, picks up an H+, then can't absorb.  When it gets into intestines which have basic pH, loses the H+, absorbs.
  43. Blood-brain barrier
    • endothelial cells of capillary wall with tight junctions, no pores, a thick membrane.  Has astocytes with astocytic end feet that provide biochemical support of barrier.  
    • small lipids can diffuse, specific proteins carry special molecules like glucose.  
    • P-glycoproteins also eject unwanted metabolites
  44. Astrocytes
    Cells around capillaries in blood-brain barrier.  Astrocytic end feet provide biochemical support of barrier.
  45. p-glycoprotein
    specific transporter found in brain capillary endothelial cells needed to pump many drugs and toxins out of brain tissue
  46. distribution into CNS
    • lipid-solubility important.  Some water-soluble might penetrate CNS.  
    • Specific uptake transporters that normally transport nutrients and endogenous compounds into brain and cerebrospinal fluid
  47. MDR1 gene mutation
    3 out of 4 collies have mutant multi-drug resistance gene, which makes p-glycoprotein.  Can't pump some drugs out of brain.  (washington state found)
  48. Drugs that cause a problem with MDR1
    Ivermectin, milbemycin, acepromazine, loperamide (immodium) and others.
  49. Plasma-protein binding
    • some drugs reversibly bind to plasma proteins, drug exists in both bound and free forms, extent variable
    • when bound, drug is pharmacologically inactive (too big to leave capillaries, can't even do job in capillaries).
  50. Tissue redistribution
    • After leaving site of action some drugs accumulate in tissues (don't continue to work inside tissues)
    • Then slowly released into circulation, plasma levels of drug are too low to produce a pharmacological effect
    • Usually in fat, muscle, bone and kidneys
    • Thiopental redistributes to fat
  51. Drug biotransformation
    • process by which chemical reactions carried out by the body convert a drug into a compound that is different from the originally administered drug (metabolite)
    • Usually to make lipid-soluble substances more water-soluble so they can be more easily eliminated.
  52. Sources of biotransformation
    • liver (almost always)
    • GI tract mucosa
    • lungs
    • skin
    • nasal mucosa
    • kidneys
  53. Reactions of phase I of biotransformation
    • Oxidation (loss of electrons), Reduction (gain of electrons), Hydrolysis (splitting of parent compound molecule with water molecules), alcohol dehydrogenation
    • catalyzed by enzymes called microsomal oxidases or cytochrome P450 enzymes in hepatocytes.  
    • can increase, decrease or not change pharacological activity
  54. biotransformations, phase II
    • Conjugation reactions, drug joined to body molecule
    • makes water-soluble
    • may be BEFORE OR AFTER phase I
  55. Glucuronidation
    • drug + glucuronic acid (glucuronyl transferase) --> "drug" glucuronide
    • Cats are bad at this, why they die from Tylenol
  56. factors influencing biotransformation
    • age (very young or old)
    • species (glucuronidation in cats)
    • malnutrition
    • liver disease
  57. excretion
    • process by which drugs or their metabolites are removed from the body to the outside environment
    • Routes include renal (urine), hepatic (biliary, defecation), lungs, mammary glands (milk), sweat, saliva
  58. Lipid soluble drugs are excreted
    by hepatic/biliary, goes into feces
  59. water-soluble drugs are excreted
    through the renal system into urine
  60. 2 ways kidney excretes drugs
    • 1. passively through glomerulus, may get reabsorbed
    • 2. active transport into lumen at proximal tubule
  61. Elimination half-life
    amount of time it takes for the plasma concentration of drug in the body to be reduced by half

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