Pharmacology Ch. 3

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Pharmacology Ch. 3
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2011-02-13 14:20:53
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Pharmacology
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Pharmacokinetics and Pharmacodynamics: The principle of how drugs work
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  1. Pharmacokinetics
    study of how drug moves into, through, and out of the body
  2. Pharmacodynamics
    study of how the drug produces its effect on the body
  3. Therapeutic range, or therapeutic window
    ideal range of drug concentrations within the body
  4. Max effective concentration
    top end of the therapeutic range and represents the border between those concentrations that are beneficial and those at which signs of toxicology develop
  5. Min. effective concentration
    bottom end of the normal therapeutic range
  6. subtherapeutic
    below therapeutic range, insufficient drug, will not achieve benefical effect
  7. loading dose
    larger than the drug's maintenance dose and is designed to raise the drug concentration to the therapeutic range in a short time
  8. Maintenance dose
    smaller amount of drug given more frequently; used to maintain the therapeutic concentrations established by the loading dose
  9. Dosage interval
    the time between administration of separate drug doses
  10. Total daily dose
    the combined amount of drug administered in a given day
  11. Dosage regimen
    dosage interval of 24 hours
  12. IV
    Intravenous; drug injected into vein, drug is carried from the tissues toward the heart where it is diluted by the venous blood returning to the heart from the body
  13. Intravenous bolus
    single injection, large volume at one time
  14. intravenous infusion
    slowly injected or "dripped" into a vein over a period of several seconds, minutes, or hrs
  15. Steady state
    when drug concentration plateaus and remain there until infusion is stopped
  16. Extra-vascular injection or perivascular injection
    accidental injection of an IV administered drug outside the blood vessel; some can cause extreme tissue inflammation and tissue necrosis (tissue death)
  17. Intraarterial injection
    places the drug directly into the blood vessel; injected into artery and thus carries the injected drug away from the heart and toward a specific tissue or organ; produces local toxicosis
  18. Intramuscular administration
    within the muscle
  19. Subcutaneous injections
    beneath the skin
  20. Intradermal injections
    administered within the skin with very small needles, reserved for skin testing
  21. Intraperitoneal injections
    administered into the abdominal body cavity and frequency used when IV or IM are not practical or when volumes of solution must be administered for rapid absorption
  22. Per os
    PO, by mouth
  23. Topically administered drugs
    drugs applied to the surface of the skin such as lotions and liniments
  24. Aersol administration
    meaning "air or gas solution", indicates that the drug is administered in an inhaled mist or gas and absorbed at different speed and efficiency
  25. Passive Diffusion
    majority of drug movement through tissue fluid or membrane barriers; random movement of drug molecules from high to low concentration
  26. Concentration gradient
    movement of drug molecules from area of high concentration to an area of low concentration or vice versa
  27. Facilitated diffusion
    passive transport mechanism across cell membrane that involves a special "carrier molecule" located in the cell membrane
  28. Active transport
    involves a specialize carrier molecule and energy expended to either move the drug across the membrane or to "reset" the carrier molecule after transport so that it can transport again
  29. Pinocytosis
    meaning cell drinking; involves a small invagination forming in the cell membrane that surrounds the drug molecule and brings it into the cell; require energy
  30. Phagocytosis
    meaning cell eating, a process in which most or the entire cell surrounds the drug molecule; require energy
  31. Saturated transport system
    when more drug molecules are available for transport than available carrier molecules; all carrier molecules are continuously occupied with drug molecules
  32. Transportation max
    rate at which drug molecules move across the membrane, cannot be increased
  33. Lipophilic
    fat loving, nature of the molecule- reflecting the molecule's ability to dissolve in phospholipids of the cell membrane
  34. Hydrophilic
    water loving; molecules that do not readily dissolve in fat or oil
  35. Aqueous
    liquid medium
  36. 4 Steps of pharmacokinetics
    • 1. Absorption
    • 2. Distribution
    • 3. Metabolism
    • 4. Excretion
  37. Absorption
    of a drug is defined as the movement of drug molecules from the site of administration to the system circulation
  38. Bioavailability
    the degree to which an administered drug is absorbed
  39. Plasma (serum) concentrations
    blood concentrations of drug because mostly occupy only fluid or water component of blood and not within the blood cells
  40. Acid drug
    drug whose chemical structure causes it to release a hydrogen ion or proton into the liquid as the drug is placed in increasingly alkaline environments; becomes more hydrophilic as it is placed in a more basic environment
  41. Basic drug
    becomes more hydrophilic when placed in an increasing acidic environment and more lipophilic when placed in a more alkaline environment
  42. Different compartments of the body have different pH environments:

    -Stomach
    -Duodenum
    -Cells and body fluid
    • -pH 1-3
    • -pH 6-7
    • -pH 7.4
  43. Ion trapping
    when lipophilic drug passes through a cell membrane and enters a body compartment whose pH results in a significant shift to hydrophilic form which leads to the drug molecule not being able to exit the compartment
  44. Dissolution
    dissolving of the drug, critical step in absorption for PO drugs
  45. Gastric Motility
    refers to stomach contractions that mix mix stomach contents and move the contents from the stomach to the small intestine
  46. Intestinal Motility
    defined as the mixing and propulsive contractions of the intestine
  47. Hepatic portal system
    conducts the blood from the intestine to the liver, where the materials from the intestine can be acted on
  48. Xenobiotics
    foreign substances
  49. First pass effect
    the phenomenon by which the liver removes so much of the drug that little reaches the systemic circulation; those with extensive FPE are not recommended PO administration
  50. Perfusion
    the extent to which a tissue is supplied with blood
  51. Vasodilation
    dilation of blood vessels; enhances perfusion of tissues and therefore increases drug absorption in SC tissue and muscle
  52. Vasocontriction
    can be caused by the sympathetic nervous system, contrict blood vessels, decreases perfusion of tissue and drug absorption
  53. Distribution
    movement of a drug from the systemic circulation into the tissues
  54. Fenestrations
    small gaps, "windows," parts of the body capillary walls between adjacent cells; allows water and small drug molecules to pass through; not in brain
  55. Blood-brain barrier
    made up from astrocytes and glial cells around the capillaries to provide for additional barrier
  56. Equilibrium
    when concentrations between the blood and perfused tissues (brain) are equal
  57. Redistribution
    movement of drug from the blood, to the tissue (brain), back to the blood, and then to a second tissue (fat), continues until equilibrium is reached
  58. Free form of the drug molecules
    small enough to distribute through the capillary fenestrations; in equilibrium with protein-bound molecules
  59. Protein-Bound Pool
    acts as a storage pool and component of the drug dose that is largely inactive
  60. Volume distribution, Vd
    pharmacokinetic value that provides an approximation of the extent to which a drug is distributed throughout the body; larger Vd= more tissues the drug appears to be able to penetrate = lower drug concentration in the blood
  61. Receptor
    specifically shaped protein located on the cell's surface or within the cell that drug molecules combine with for cells to respond
  62. Agonists
    bind to receptor to exert a certain effect
  63. Antagonists
    block effect of other drugs, ex. antidotes
  64. Competitive antagonism/ reversible/ surmountable
    when 2 drugs have an equal opportunity to exert their own effect on the cell; determined by which drug is present in greater quantity
  65. Noncompetitive antagonism/ irreversible/ insurmountable
    a drug has a greater affinity for the receptor than another or it may alter the shape so that the other drug will not fit into receptor
  66. Partial Agonist
    two drugs attaching to a receptor may have different levels of intrinsic activity
  67. Partial antagonist
    one drug is more powerful than another but produces same effect
  68. Intrinsic activity
    when drug combines with its receptor to produce a specific effect on the cell
  69. Non-receptor mediated reactions
    some drugs produce an effect without combining to receptors; mannitol: osmotic diuretic
  70. Chelators
    types of compounds used as drugs that physically combine with ions or other specific compounds in the environment to produce thier effects
  71. Biotransformation/ Metabolism
    process by which many drugs are altered by the enzymes and chemical reactions in the body before they are eliminated
  72. Metabolite
    altered drug molecule
  73. Conjugation
    enzymatic process where the metabolite is combined with another molecule
  74. Mixed function oxidase
    most common biotransformation enzyme system in the liver
  75. Metabolic Induction
    the effect of repeated exposure to a drug resulting in an increase rate of biotransformation for the drugs
  76. Routes of Elimination
    kidney (urine) and liver (bile to feces)
  77. Renal elimination
    circulating drugs are cleared from the blood through filtration and active secretion
  78. Filtration
    passive process that occurs as the blood flows from renal arteriole through the glomerulus
  79. Glomerulus
    specialized tuft of capillaries in the kidney
  80. Bowman's Capsule
    first part of renal nephron; its wall structure prevents blood cells and larger protein molecules from leaving the blood
  81. Protein bound drugs
    not filtered through unless in free form
  82. Proximal Convoluted tubule
    active segment of the nephron that contains many active transport mechanisms for moving electrolytes, glucose and drug molecules back and forth among the urine, renal tubular cells, and the surrounding capillaries
  83. Active secretion
    process where some drug molecules are actively transported from the peritubular capillaries into the urine; not dependent on concentration gradient
  84. Loop of Henle
    where some of the drug molecules may move from the filtrate back into circulation, which is called reabsorption (passive diffusion; reabsorbed molecules must be in lipophilic form)
  85. Drug is considered to have been eliminated or excreted from the body by the time the urine filtrate moves through the _____,________, and into the ______ and _________
    • - distal convoluted tubule
    • - collecting ducts
    • - renal pelvis
    • - ureter
  86. Biliary excretion or Hepatic excretion
    elimination of drugs by the liver
  87. Enterohepatic circulation
    movement of drug from the liver to the intestinal tract and back to the liver
  88. Drug's Clearance
    measure of how fast a volume of blood is cleared of the drug and is typically expressed as a volume of blood cleared over time
  89. Drug's half life of elimination
    time value that describes how long the drug concentration takes to decrease by 50%
  90. Withdrawal time
    time (usually in days) after drug administration during which the animal cannot be sent to market for slaugher and the eggs or milk must be discarded
  91. alkaline pH
    pH greater than 7
  92. acidic pH
    pH less than 7
  93. excretion
    removal from body
  94. Sig
    SIGNA: to write or label
  95. Therapeutic effect
    desired effect wanting to achieve
  96. Toxic effect
    when administering drugs long-term and they may pass therapeutic effect
  97. ED50=effective dose 50
    dose of drug that is effective for 50 % of the population
  98. Indiosyncratic reactions
    individual reactions to a particular drug from an individual animal (not expected, rare)
  99. Toxin
    biological source
  100. emesis
    vomiting; may be induced to help during toxicity of certain substances; not for corrosive substances or when patient is semiconscious or unconscious; certain species do not vomit (ruminants)
  101. Gastric lavage
    flush out stomach contents with pump
  102. Acetominophen
    lethal in cats, dogs tolerate it, toxicity signs: depression, weakness, ICTERUS (jaundice), hepatic failure; antidote: acetylcysteine
  103. Ibuprofen/ Aspirin
    fatal for cats, may cause liver disease; usually given to dogs for arthritic pain but if given over a period of days may cause gastric ulcers (sign may vomit)
  104. 5FU
    anti cancer cream, interferes with DNA/RNA transcription; dogs love it; sloughs off lining of intestinal tract; lead to gastric and intestinal lavage
  105. Chocolate
    in high concentration can kill a dog, active ingredient is thiobromine, causes nervous system stimulation, heart rate increases, seizures; induce emesis and give activated charcoal
  106. Drug absorption is governed by
    • 1. solubility
    • 2. route of administration
    • 3. chemical properties
  107. Dose response relationship (DR)
    determines how much of a dose to be given; if they have the same mechanism of actions you are able to determine the potency by looking at the curve
  108. Potency
    administer less concentration to produce effect; Effective dose
  109. Time response curve
    to determine at which interval to give drug
  110. Lethal Dose, LD50
    dose that will kill 50% of the population
  111. (TI)Therapeutic index
    LD50/ED50 : gives estimate of relative safety of drug
  112. Toxicology
    the study of harmful effects of chemical compounds on biologic systems, including their properties, actions, and effects
  113. toxic agent
    toxicant or poison
  114. toxicosis, posioning, and intoxication
    the disease produced by a toxicant
  115. toxicity
    amount of a toxicant necessary to produce a detrimental effect
  116. hazard
    describes the likelihood of poisoning under conditions of use
  117. Emetic agents
    • -hydrogen peroxide 3%
    • -apomorphine (dogs): can be given subconjuctively
    • -dexdomitor (dogs)
    • -xylazine (cats)
    • -syrup of ipecac- only if directed
  118. Xylitol
    artifical sweetener, highly toxic to dogs, behaves as glucose in the body and increases insulin causing severe hypoglycemia leading to coma, respiratory depression, or death

    • treat with IV dextrose
    • in some gum
  119. Rodenticides
    Rat baits; Vitamin K can be an antidote for one type
  120. Toxic plants
    lilies, onions and garlic, grapes and raisins, not pointsettas
  121. Household Hazards
    • Acids- burn mucosa or intestinal lining (usually dogs)
    • Alkalines- worse burns
    • Detergents
    • Ant baits- dogs will usually just vomit
    • Silica gel- low toxicity
    • Toilet bowl tablets- if dilute not has harmful as if they chew the tablet
    • Glow necklaces
    • Liquid potpourri- very toxic
    • batteries- acids will cause ulcers
    • nicotine- highly toxic, stimulant
    • pennies- 99.7% zinc, starts to dissolve quickly- highly toxic, cause liver failure
    • mothballs- all are toxic
    • moldy foods- common, fungi release cause tremors and neurologic disorder, worse case: seizures
  122. Ethylene glycol
    antifreeze is the active ingredient, worse toxicans seen routinely ingested, cause renal failure, crystal clogs renal tubules, death within 18-24 hours; paladin (antidote, enzyme competitor, must be given before crystals form or before 12 hours pass)

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