Anesthesia Pharm Lecture 3

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Anesthesia Pharm Lecture 3
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2013-06-01 10:27:13
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BC CRNA Anesthesia Pharm Lecture
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Pharmacokinetics and Pharmacodynamics
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  1. Basic definition of absorption
    transfer of a drug from site of administration to the blood
  2. What is bioavailability?
    • the fraction of drug that reaches the systemic circulation
    • 100% for IV drugs
  3. Basics of Distribution
    • blood ↔  ECF and/or cells: depends on blood flow, capillary permeability, protein binding, hydrophobicity (lipophilicity) of drug
    • Volume of Distribution:  hypothetical volume into which a drug is distributed
    • Protein binding: inactive reservoir
  4. Metabolism is basically what two things?
    biotransformation & excretion
  5. Drug delivery to target organ means must cross cell membrane. What two ways does this happen?
    • Passive diffusion: 
    • -Most drugs
    • -Concentration gradient
    • - Fick’s Law
    • -(can be water soluble depending on size)
    • Active transport
    • -Absorption from GI tract
    • -Energy dependent
  6. ________have an uneven distribution of electrons within the molecule but no net charge
    polar molecules
  7. ____are molecules with a net electrical charge
    Ions
  8. Rule of solubility is that “like dissolves like." What does this mean?
    • things with a charge will dissolve in other things with a charge or uneven electron distribution
    • -Salt NaCl & water (hydrophilic/lipophobic)
    • -Things without a charge are lipophilic because they dissolve in lipids which also have no charge
  9. What is the equation for Bioavailability?
  10. What are some determinants of tissue uptake of drugs?
    • blood flow
    • concentration gradient
    • blood brain barrier
    • physicochemical properties of a drug
    • --ionization
    • --lipid solubility
    • --protein binding
  11. What are some determinants of capacity of tissue to store a drug?
    • Solubility
    • Tissue Mass
    • Binding to macromolecules
    • pH
  12. Why do we see the "hangover" or duration effect of some drugs
    Because they were taken up by the tissues and when the concentration gradient in the blood falls, the drug moves  from the tissues back into the blood where it gets redistributed or excreted
  13. What happens if we keep giving boluses of a drug (like Fentanyl)?
    At some point we saturate the tissue stores. In that case, the tissue stores get saturated, and we kept giving repeat doses, the drug is no longer going to those tissues, the clinical action of drug (duration) is not dependent on distribution but on metabolism.(metabolism instead of redistrubution is the problem). So once the tissue stores (in the case of fentanyl fat) are saturated the duration of action is longer
  14. The capacity of the tissue to store the drug is dependent on_____________________
    the solubility and mass of the tissue
  15. What is the protonated form of an acid? Is it ionized?
    HA (non-ionized)
  16. What is the protonated form of a base. Is it ionized?
    BH(ionized)
  17. Is the non-protonated form of an acid ionized?
    yes
  18. Is the non-protonated form of a base ionized?
    No
  19. What is pKa
    the pH (environmental) at which the drug is 50% ionized and 50% nonionized
  20. Does the pka (ionization constant) have a relationship to the pH of the drug preparation?
    NO!
  21. Does the pKa (ionization constant) have a relationship with the acid/base nature of the drug?
    NO!
  22. Why is the ionization constant (pKa) important?
    Important factor in determining drug onset because only the nonionized fraction will readily cross the lipid bilayer
  23. TRUE or FALSE.
    Ionization constant = onset of action
    TRUE
  24. Describe ion trapping
    Only the non-ionized fraction readily crosses the lipid membrane

    Once on the other side, the drug may ionize depending on the pH of that new environment
  25. What is a classic case of ion trapping?
    Assume the membrane is the placenta & that there is fetal acidosis.  Opioids (basic drug) will cross the placenta and become trapped because free hydrogen ions (from the acid environment) attach to the nonionized drug (B) resulting in ionized opioid (BH+).  There will still be a concentration gradient for the nonionized fraction (B) so B continues to cross the membrane, becomes ionized, and is  trapped.
  26. TRUE or FALSE. If the pH is less than pKa than
    the non-protonated form predominates
    FALSE. The protonated form predominates (there are a lot of hydrogen ions around to protonate everything---HA and BH+)
  27. True or False If the pH is more than pKa the non-protonated form predominates.
    • TRUE! (Not a lot of hydrogen to go around protonating everyhing---A- & B)
  28. Tell me about the non-ionized form of drugs
    • Pharmacologically ACTIVE
    • Lipid soluble (able to cross lipid membranes like the GI tract, BBB & placenta)
    • NOT renally excreted
    • Hepatically metabolized
  29. Tell me about the ionized form of drugs
    • Pharmacologically INACTIVE
    • Water soluble (so it can't cross lipid membranes like the GI tract, BBB, & placenta)
    • Renally excreted
    • NOT hepatically metabolized
  30. Name some acid drugs used in anesthesia
    • Thiopental
    • Other barbiturates
    • Propofol

    • * Weak acids unite with cations like Na+
    • * Cation of salt of the acid often named first…. i.e. “Sodium pentothal”
  31. Name some basic drugs used in anesthesia
    • Local anesthetics
    • Ketamine
    • Benzodiazepines
    • Etomidate
    • Opioids

    • *Weak bases unite with anions like Cl-, sulfate
    • *Anion named second…i.e. Lidocaine hydrochloride  or Morphine sulfate
    • Any drug that is an amine is a base
  32. What are the three compartments? What % of total body weight are they? in L of 70kg?
    1.Plasma: 6% (8%) of body weight = 4 L in 70 kg patient

    2.ECF: 20% (23%) of body weight = 14 L in 70 kg patient

    3.Total body water: 60% (64%) of body weight = 42 L in 70 kg patient
  33. ECF is made of what two things
    interstitial fluid and plasma
  34. Distribution of drugs in central compartment (plasma) changes in extremes of age. Give me an example
    old people have relative decrease in skeletal muscle mass (more fat relative to muscle)  and so could have smaller afferent volume of distribution of drugs depending on the drug and what compartments it tends to distribute too. Also older people tend to be hypovolemic in central compartment. So if we give drug to elderly, higher concentration in plasma (same drug to smaller tank)
  35. What are some physiological conditions that could change the volume of distribution?
    • abnormal accumulation of fluid (Acites or pleural effusion)--depending on where the drug goes.
    • There are extreme situations, acidosis,
    • hypovolemic, etc. that alter volume of distribution.
  36. Name the three Physicochemical characteristics influencing Vd:
    • Lipid solubility
    • Protein binding
    • Molecular size
  37. Describe distribution by compartment
    • Plasma: large MW, high protein binding, hydrophilic
    • ECF: low MW, hydrophilic (goes through slit junctions so capillary → ECF)
    • Total body water: low MW, lipophilic (hydrophobic)
  38. Would a drug that is highly protein bound and hydrophillic have a small, medium, or high Vd? Would the plasma concentration be low, medium, or high?
    • Small
    • High
  39. Describe the capillary permeability of the BBB
    • Tight junctions only
    • Drugs must pass through (be lipophilic) –or- be actively transported
  40. Describe the structure of endothelial cells in the liver (capillary membrane)
    They have slit junctions that allow drug exchange freely between the blood and the interstitium of the liver

  41. describe this picture
    • A: single compartment, no elimination
    • B: single compartment,  but elimination
    • C:Common situation, (like us, has more than 1 compartment) administration into
    • circulation and goes to ECF (for example), initial rapid drop in plasma concentration and then it will level off, only drops to certain amount until it equilibrates with ECF, not really being eliminated just moving compartments.
    • D: both distribution and elimination. Rapid drop d/t distribution and then gradual
    • d/t biotransformation and elimination.
  42. What is the equation for determination of Vd?
    • Vd= D
    •        C
    •  
    • C = plasma concentration of drug
    • D = total amount of drug in body (what was given)
  43. Any factor that increases Vd,increases half-life and extends duration. Why?
    • Drug elimination depends on drug delivered to liver or kidney per unit time
    • Delivery to these organs depends on blood flow & fraction of drug in plasma
    • If Vd is large, most of drug is extraplasmic & unavailable to excretory organs
  44. Tell me about protein binding
    Reversiblebinding to plasma proteins sequesters drugs in non-diffusible form so bound drugs stay in the vascular (plasma) compartment concentration of free drug decreases from metabolism or excretion, bound drug then dissociates from the protein.
  45. Most drugs bind to _____(esp. acid drugs) & __________ may act as a reservoir.
    albumin. plasma albumin
  46. Most basic drugs bind to _______________
    alpha acid glycoprotein
  47. Protein binding is an important factor in determining _____________ & only
    unbound drug is available for metabolism/clearance
    duration of action
  48. One drug can displace another from albumin increasing the concentration of displaced drug which can cause ______
    toxicity
  49. What is 1st order kinetics
    • Most drugs
    • Linear kinetics
    • Constant fraction (%) of available drug metabolized per unit time
  50. What is zero order kinetics
    Constant amount of drug metabolized per unit time

    When plasma concentration of drug exceedscapacity of enzymes
  51. What is the role of metabolism?
    to convert pharmacologically active lipids soluble drugs to water soluble and sometimes pharmacologically inactive metabolites. (some are active metabolites)
  52. how is the rate of metabolism determined?
    by theconcentration of drug at site of metabolism and the rate of the metabolic process itself, liver blood flow is important, if not getting to liver then not getting to site of metabolism
  53. What is a common drug that is metabolized by zero order kinetics?
    • alcohol
    • ASA
    • Phenytoin
  54. Where does most metabolism take place?
    • hepatic enzymes found mostly in endoplasmic reticulum in the liver.
    • Are also present in kidney, GI tract, and even the adrenal cortex.
    • Liver is main site but there are other locations.
  55. What is the goal of Phase I metabolism and how is this accomplished?
    Goal is to convert lipophilic molecules into more polar molecules by introducing or unmasking a polar functional group

    May increase, decrease, or leave unaltered the drug’s pharmacologic activity

    • Oxidation
    • Reduction
    • Hydrolysis
  56. There are other mechanisms for metabolism, one way some of our drugs are metabolized
    is by esterases in the plasma. Esterases are responsible for hydrolysis of drugs that have ester bonds. Name some of these drugs
    succinylcholine, esmolol, remifentanyl, and also the ester local anesthetics
  57. Phase II metabolism is what?
    Conjugation
  58. Do all drugs go through Phase I and Phase II metabolism?
    NO. Some drugs can get eliminated by kidneys after Phase I. Some drugs are still to lipid soluble after Phase I. So go to Phase II  (conjugation) and become more polar and usually more water soluble compound. Most often these are therapeutically inactive. 

    Some drugs go through Phase I and Phase II in reverse order. Goal is to make it water soluble so it can get eliminated.
  59. What are the FIVE consequences of drug metabolism?
    • Accelerated renal drug excretion
    • --Most important role
    • --If lipid drug isn’t converted to water-soluble (polar) drug, it will just be reabsorbed back into the circulation
    • Drug inactivation
    • ↑therapeutic action
    • --i.e. conversion of codeine to morphine
    • Activation of prodrug
    • ---Inactive prodrug to active form occurs within the body
    • ↑ or ↓ toxicity
    • --i.e. metabolism of acetaminophen into hepatotoxic metabolite
    • --Not all metabolites are inactive
  60. _______ have limited drug metabolizing ability.
    Infants. During 1st year of life, particularly atrisk for toxicity
  61. What does steady state mean?
    • Plasma concentration is constant
    • Elimination balances input
    • Input of drug = clearance of the drug.
  62. What are two factors influencing steady state concentration?
    • Rate of drug infusion
    • --Css is directly proportional to infusion rate (if we double the infusion rate, the  concentration once we get to steady state
    • (elimination balancing input), is also doubled)
    • --Css is inversely proportional to drug clearance (anything that would decrease clearance (renal or liver disease) that will increase the steady state concentration)

    • Time to reach steady state
    • --Independent of rate of infusion
  63. TRUE or FALSE. Time to get to steady state is always achieved the same, only difference is what the concentration is once it gets to steady state
    TRUE
    • A: drug given by infusion
    • B: drug given 2x/day
    • C: drug given 1x/day
    • The plasma concentration will essentially oscillate about a mean, as we use smaller intervals (looking at B instead of C) don’t’ have the same peaks and valleys (smaller amplitude) but the concentration of steady state and the rate at which we achieve it are independent of the frequency of dosing.
  64. Tell me about the plasma concentration curves.
    • (Re)Distribution = α
    • Drug moves from central compartment (circulation) to periphery
    • Begins immediately after injection

    • Elimination= β
    • Drug is eliminated from circulation by liver & kidneys
    • More gradual decline in plasma concentration
  65. Tell me about the 3 compartment phase model
    • Rapid (distribution) α
    • -Drug from plasma to rapidly equilibrating tissues (VRG, MG)
    • Intermediate β
    • -Reversed flow between plasma & rapidly equilibrating tank 2° ↓ plasma levels
    • Slow γ (gamma)
    • - Elimination phase
    • - Terminal phase
    • - Drug returns from periphery to plasma
    • - Rate of elimination is slower than earlier phases due to ↓ plasma concentration
    • (first order kinetics)
  66. Why is the timing of IV drug administration important?
    • for titration of drugs to effect. Want to give Versed in pre-op area, want to wait until it sees it’s full effect, if not, see an apnic
    • patient….because you gave another dose to the anxious patient too early.
  67. What is the Onset of clinical effect?
    time needed for the drug to be delivered to the site of action (brain)
  68. TRUE or FALSE. Dosing intervals are also influenced by redistribution to inactive tissue sites
    TRUE
  69. Which has a more rapid equilibration with the effect site (producing a quicker onset of action) Fentanyl or Alfentanyl
    • Alfentanil
    • Part of story is the pKa, with fentanyl 92% is in ionized form and Al fentanyl 89% in non-ionized form
    • *Sufentanil takes the longest
  70. Tell me about elimination for the different compartment models
    for a 1-compartment model, t ½  describes the time required for ½ of the drug to be eliminated from the compartment (body).  In multi-compartment pharmacokinetics this is more complex as time to ↓ concentration by ½ isn’t equal to complete elimination from the body
  71. In clinical practice, how do we use context sensitive 1/2 time?
    The time until loss of analgesia depends on the opioid dose, neuronal, & receptor kinetic processes, the transport of the opioids from the brain to the plasma, & the context sensitive 1/2 time.
  72. For fentanyl, the context sensitive 1/2 time _______ with the duration of the infusion, while for remifentanil the 1/2 time is independent of the duration of the infusion because of it's _______ ________.
    • increases; rapid clearance
    • Remifentanil has a 50% drop in plasma concentration in 2 minutes and 75% drop in 8 minutes.
    • (Propofol also has a 1/2 time that is independent of the duration of the infusion.
  73. What does context sensitive 1/2 time refer to?
    • Time to decrease plasma drug concentration by 50% (from a steady-state plasma concentration, aka, infusion) after the infusion has stopped.
    • Depends on the duration of the infusion, which is the context to which the term applies. 
    • No constant relationship with elimination ½ time
  74. TRUE or FALSE. 1/2 time only applies in zero order kinetics.
    FALSE! ½ time only in 1st order kinetics!!!
  75. Drug X is eliminated by 1st order kinetics. If 4 gms of drug x are administered to your
    patient and 5 hrs later 2 gm have been metabolized. After 15 hours how much of the total drug will be metabolized?
    • 4gm--> 2gm (1st 1/2 life = 5hr)
    • 2gm--> 1gm (2nd 1/2 life = 10hr)
    • 1gm--> 0.5gm (3rd 1/2 life = 15hr)
    • Total drug metabolized in 15 hr = 4-0.5gm so 3.5 gm


  76. Goal is to have pt just asleep enough, but we’d like to be in ideal therapeutic range, we don’t want to take too much time for patient to wake up
  77. TRUE or FALSE. Clearance is multifactorial
    TRUE

    CLtotal = CLhepatic+ CLrenal+ CLpulmonary+ CLother
  78. 2 major sites for clearance are the
    • liver and kidney
    • Liver= biotransformation, phases 1 & 2
    • Kidney= clearance of unchanged drug in the urine
  79. What is the equation for clearance
    • CL = Rate of elimination of drug
    •          Plasma drug concentration

    *units = volume/unit time
  80. Clearance, half-life, and volume of
    distribution can be related in one equation. What is it?
    • t1/2 = 0.693 X Vd
    •                        Cl

    • Any factor that ↑’s Vd →↑’s half-life
    • Any factor that ↓’s clearance → ↑’s half-life
  81. What is the definition of pharmacodynamics
    the study of the biochemical and physiological effects of drugs & their mechanisms of action.
  82. What is the definition of mechanism of drug action?
    most drugs cause their effect by interacting with a macromolecular component (receptor) altering function & initiating a biochemical or physiologic change
  83. A drug receptor could be a  cell membrane embedded enzyme. How does this work?
    • Drug binds on surface of the cell
    • Receptor spans the membrane
    • Binding causes enzyme activation
    • Insulin acts in this way
  84. Nicotinic Ach receptor is one of the best characterized of all the cell surface receptors. Explain how it works
    When Ach, binds to the alpha subunits on that receptor, that causes internal aqueous channel or pore to open transiently, and when that happens Na will go in from ECF into cell. It’s a rapid signaling mechanism. GABA also acts through this mechanism. Since we’re talking about Ach receptor, the function of many of these agents is to act as an agonist, Succinylcholine. The antagonist at the nicotinic Ach receptor is the non-depolarizing muscle relaxants.
  85. A drug receptor could be a ligand gated ion channel. How does this work?
    • Drug binds on surface of cell
    • Regulate flow of ions in and out of cell according to concentration gradient
    • Specific for individual ion
    • Receptor spans the membrane
    • Acetylcholine & GABA act through this mechanism
  86. What are the 4 types of Drug Receptor families?
    • Ligand Gated Ion channel
    • Cell membrane embedded enzymes
    • G protein-coupled receptor system
    • Transcription factors
  87. A drug receptor could be a  G protein-coupled receptor system. How does this work?
    • 3 components to this system
    • 1. Receptor
    • 2. G protein (binds GTP)
    • 3. Effector (ion channel or enzyme)

    Drug activates receptor → then activates G- protein → then activates effector

    Norepinephrine,histamine, peptide hormones use this system
  88. A drug receptor could be a transcription factor. Explain how this works
    • Found within the cell not on the surface on DNA of nucleus
    • Stimulates transcription of mRNA molecules & regulate protein synthesis
    • Response to activation is delayed (hours to days)
    • Thyroid hormone, steroid hormones act through transcription factors
  89. What is the Lock-and-key analogy regarding selectivity of action of a drug?
    that only the drug with proper size, shape, and properties will stimulate a given receptor
  90. TRUE or FALSE. Stimulation of a receptor by a drug yield usually 1 physiologic response
    FALSE! Stimulation of receptor by a drug rarely yields just 1 physiologic response

    • Opioids cause analgesia, respiratory depression, constipation, etc.
    • Isomers vs racemic mixtures
  91. What does high affinity mean in the dose response curve?
    • POTENCY
    • the amount of drug required to produce a particular effect.  Can bind to receptor even when present in low concentration
  92. What does intrinsic activity mean in the dose response curve?
    • EFFICACY. 
    • the maximum effect that can be produced by a drug. This is independent of dose
  93. What are the three types of drug receptor interactions?
    • Agonists: bind to & activate receptor causing effect
    • Antagonists: bind to receptor preventing binding by agonist
    • Partial agonists: bind to receptor but don’t evoke as strong a response (not as efficacous)
  94. What terminates the effect of a drug?
    Dissociation from receptor terminates effect

    Effect may be prolonged after dissociation if coupling molecule is still present & activated

    • Drugs covalently bonded to receptor may require synthesis of new receptor for termination of action (Ex: benoxybenzes
    • (alpha blocker) and the alpha receptor for Epi. Effect will only be after new alpha receptors are synthesized (alpha blockers are good for pheochromocytoma)
  95. What are the three types of drug antagonist
    • Competitive antagonist: Interacts
    • with receptors at same site as agonist
    • -Shifts curve to the right so drug appears less potent
    • -seen with beta blockers
    • Non-competitive antagonist:
    • Prevents binding of agonist or activation of receptor
    • -Decreases maximal response of the drug
    • (appears less effective)

    • Partial agonist:
    • -Blocks binding site but ↓ response than full agonist
  96. Describe sensitization
    • Continuous activation or inhibition of receptors can cause physiologic changes
    • Exposure of receptor to agonist drug can
    • cause desensitization from “down-regulation” or destruction of receptors
    • ---Body becomes refractory to additional
    • drug (can happen w/Epi or Succs)

    • Exposure of receptor to antagonist drug
    • can cause hypersensitivity (to agonist ligand) from “up-regulation” or synthesis of new receptors (can happen w/Beta blockers)
  97. Describe up-regulation
    an increase in the number (density) of receptors as a result of drug induced receptor antagonism

    Example: beta adrenergic receptor blockade

    Abrupt withdrawal of the antagonist results in exaggerated response to receptor agonist
  98. Describe down regulation
    a decrease in the number or density of  receptors in response to excess circulating ligand (neurotransmitter)

    Example : beta adrenergic agonists, pheochromocytoma
  99. What are pharmacokinetic drug/drug interactions?
    Altered absorption, distribution, biotransformation, renal excretion
  100. What are pharmacodynamic drug/drug interactions?
    2 drugs acting at same receptor (usually inhibitory)

    • 2 drugs acting at different sites (potentiative or
    • inhibitory) i.e. 2 CNS depressants (propofol or Benzos & opioids)

    Combined toxicity (not used together)
  101. What is the therapeutic index?
    • Margin of safety
    • Difference between the dose of the drug producing the desired effect & the dose  producing the undesirable (toxic) effect

    • LD 50
    • ED 50
  102. Tell me about anaphylaxis
    • Form of distributive shock caused by an acute immunologic response the result of an
    • immediate type 1 hypersensitivity reaction

    • Mediated by IgE (usually but rarely IgG)
    • Severe reaction
    • Sudden onset
    • Mortality rate 3.5-10%
    • Classification types I, II, III, IV
    • *Vasodilation, decreased CO even w/normal blood volume (larger tank)
  103. What is anaphylactoid
    • Clinical presentation like anaphylaxis
    • Non-immunologic, chemically mediated
    • Can occur abruptly
    • severe reaction
  104. What are the two phases of anaphylaxis?
    • Sensitization phase: (maybe 1st time they get drug)
    • Antigen triggers B-cell production of IgE
    • Antibodies bind to receptors on the surface of effector cells (mast cells & basophils)

    • Elicitation phase:Reintroduction of antigen causes activation of effector cells and histamine release
    • Clinical presentation is immediate
    • hypersensitivity
  105. What are some risk factors for anaphylaxis
    • History of drug allergy
    • --Always question & document specific reaction
    • Gender (women more likely than men to have allergic rxn)
    • Age (peak incidence in 4th-5th decade of life)
    • Atopy: May be a risk factor for histamine release in the presence of histamine releasing drugs because basophils of atopic individuals more readily release histamine
  106. Who is at risk for a latex allergy?
    • Children with spina bifida (multiple surgeries & prolonged catheterization)
    • Healthcare workers
    • Allergy to avocado, Kiwi, banana, fig, chestnut, hazelnut, sweet pepper, melon, pineapple, & papaya
    • Eczema, asthma, other atopy
  107. What are some histamine releasing drugs?
    • morphine
    • cisatracurium
    • succinylcholine
    • thiopental
    • may see a bit of a flush, histamine release but not full blown anaphylaxis
  108. What are some pharmacologic agents that causative factors for anaphylaxis
    • NDMR – most common
    •   ☔ Cross-sensitivity common
    •   ☔ Quaternary ammonium ion is the antigen (common in drugs, cosmetics, household products)
    • Latex
    • Antibiotics
    • Hypnotics (thiopental, propofol)
    • Colloids (dextrans, hetastarch)
    • Opioids (rare)
    • Local anesthetics (esters)
  109. What kind of reaction can vancomycin cause?
    anaphylactoid rxn (red man syndrome) not true allergy, d/t rapid administration of vanco
  110. What sign of anaphylaxis won't we see in our patients?
    The neurological signs: disorientation, LOC, dizziness, lightheadedness, malaise
  111. How do you treat a patient in anaphylactic shock?
    • DC drug administration
    • Administer 100%
    • Epi (0.01-0.5mg IV or IM)*start low & ↑
    • Consider intubation or Tracheostomy
    • IVF (1-2L of LR) *up to 2-4L
    • Diphenhydramine (50-75 mg IV)
    • Hydrocortisone (up to 200mg IV) or methylprednisolone (1-2mg/kg)
    • (Last two are really secondary)
  112. Propofol has higher Vd than thiopental. (Propofol is 4.6L/kg and thiopental is 2.4 L/kg) You would expect propofol to have a longer duration in terms of distribution so why isn't it?
    that’s because it’s clearance is higher. Propofol clearance is 25ml/min/kg vs thiopental 3.4ml/min/kg. So thiopental has a longer duration.
  113. Propofol has a pKa of 11. So what form is it in (in terms of protonation and ionization)
    pH < pKa so it's protonated and non-ionized (propofol is an acidic drug)
  114. Etomidate has a pKa of  4.2. Which form is it in (in terms of protonation and ionization)
    • Basic drug. pH >pKa
    • So it is in the non-protonated non ionized
  115. If a drug is excreted by 1st order kinetics, how long will it take for the plasma concentration to fall to 50mg if it’s ½ life is 20hrs and 200mg was administered.
    • 200mg → 100mg = 20hrs (1st ½ life)
    • 100mg → 50mg = 40 hrs (2nd ½ life)

    Two ½ lives (40hrs)
  116. What is the equation to figure out the % ionized
    •        100        
    • 1 + 10(pH –pKa)

    • if pH and pKa are the same then 
    • 100      =    100   = 100   = 50% ionized
    • 1+100           1+1           2
  117. What is the ionized % of Fentanyl (pKa of 8.4) in a pH of 7.4?
    •  100           =    100      = 100  = 91% 
    • 1 + 107.4-8.4   1 + 0.1       1.1

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