Pharmacology and the Anesthetic Care Plan (Lecture 1)

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Pharmacology and the Anesthetic Care Plan (Lecture 1)
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2013-05-25 09:49:02
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Flashcards over the First Lecture in Pharm
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  1. THE ANESTHETIC CARE PLAN IS ________ SPECIFIC. 

    A. PATIENT
    B. PROCEDURE
    PATIENT!!
  2. What are the two main categories of pharmacological issues in respect to the anesthetic care plan?
    • 1. Chronic Medications-what to continue day of surgery, if the diagnosis is 'controlled' with the medication
    • 2. Choice of Anesthetic-type of anesthetic directed at patient, surgeon, and anesthetist choices/preferences, specific choice of anesthetic must remain goal directed
  3. Identify variables that affect the anesthetic care plan.
    • 1.Chronic Medications
    • a. Which meds to continue day of surgery
    • b. Need for pre-operative fine tuning (if pt. comes to preoperative assessment with high blood pressure, and needs anti-HTN adjusted- refer to PCP)

    • 2. Choice of Anesthetic
    • a. Type of Anesthesia- goal directed
    • 1) Patient- wants comfort throughout; have a sense of what they want
    • 2) Surgeon-have a sense for what they want; what they’re comfortable with
    • 3) Anesthetist- careful to make decision based on science, not preference
    • b. Specific Choice of Agent- opioid,
    • NMB, induction agent, local for spinal, Inhaled

    Want to consider Patients history, Duration of the Agent v. Duration of Surgery, Side effects of the agent/technique, Contraindications to the agent/technique, Availability of the Agent
  4. What factors can lead to surgical stress?
    • -psychological.most common is loss of control, fear of mutilation, pain, and death
    • -Tissue Injury-incision
    • -Intravascular volume changes
    • -Anesthetic agents-cause vasodilation and fluid status changes
    • -Pain**
    • -Organ Manipulation**

    **Pain and Organ manipulation can lead to stimulation of the autonomic nervous system  (think vagal stimulation)
  5. Surgical Stress Results in the STRESS RESPONSE.

    The stress response is the activation of: 

    Which causes the increase of: (3 Things)
    The stress response is the activation of the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system

    • Stimulation of the stress response results in the increase of: 
    • 1. cortisol
    • 2. catecholamines
    • 3. cytokines
  6. Increased cortisol, catecholamines, and cytokines result in what types of physiologic manifestations?
    Tachycardia, hypertension, increased metabolism, hypercoagulability, decreased immune function

    Morbidities associated with the stress response: perioperative ischemia/infarction, arrythmias, thrombosis, infection, and delayed wound healing
  7. What is anesthesia? (per Eger)
    Anesthesia is the REVERSIBLE state mediated by the CNS that produces IMMOBILITY and AMNESIA. (along with unconsciousness, analgesia, suppression of autonomic reflexes, and relaxation of muscle)
  8. What is the difference between anterograde amnesia and retrograde amnesia?
    Anterograde: amensia from the time you give the drug on

    Retrograde: amensia preceeding the stimulus (we can't control this)- typical result in head injuries
  9. What characteristics make up the ideal anesthetic?
    • Induce anesthesia smoothly and rapidly
    • Permit rapid recovery
    • Wide margin of safety
    • No adverse effects
    • Low cost
    • Patient is "street ready"- go home safely/quickly with no PONV
  10. What are the two types of synapses?
    • 1. CHEMICAL
    • 2. ELECTRICAL
  11. Compare and contrast the two types of synapses.
    • Chemical: 
    • -most CNS synapses are chemical
    • -dependent on the release of NT from 1 neuron that then affects the next
    • -presynaptic neuron secretes NT (like Epi, Ach, Norepi)
    • -NT acts on receptor proteins on membrane of post synaptic neuron
    • -May be excitatory or inhibitory- depends on how it effects the postsynpatic membrane

    • Electrical:
    • -NOT the same as voltage gated channels
    • -Gap junctions permit free moments of ions from one cell into another
    • -Found mostly in cardiac and smooth muscles
  12. Which synapse composes the majority of chemical synapses?
    Chemical
  13. True or False:
    Electrical synapses are the same thing as voltage gated channels.
    FALSE!!
  14. Walk me through the stages of synaptic transmission.
    • 1. Action potential spreads over the presynaptic terminal/knob
    • 2. Membrane depolarizes
    • 3. Depolarization causes vesicles to empty into the synaptic cleft
    • 4. NT is released from the vesicles
    • 5. The release of NT causes a change in permeability of the postsynaptic terminal
    • 6. The change in permeability leads to either excitation or inhibition depending on the characteristics of the channel

  15. THE AMOUNT OF NEUROTRANSMITTER RELEASED INTO THE SYNAPSE IS DIRECTLY RELATED TO THE NUMBER OF ________ IONS THAT ENTER THE PRESYNPATIC TERMINAL. 

    A. Calcium
    B. Sodium
    C. Acetylcholine
    D. Potassium

    Explain your answer.
    A. the amount of neurotransmitter released into the synapse is directly related to the number of CALCIUM ions that enter the presynaptic terminal. 

    This is true because: the presynaptic terminal contains a large amount of voltage gated calcium channels, when an action potential depolarizes it causes the calcium channels to open- so that the calcium will flow into the terminal and the neurotransmitter will flow out.
    (this multiple choice question has been scrambled)
  16. What does the mitochondria do?
    • Cell powerhouse!
    • -generates new ATP to make new neurotransmitters
  17. What are the two types of ion channels?
    • 1. Cationic
    • 2. Anionic
  18. Compare and contrast the two types of ion channels.
    • Cationic
    • -only allows positive ions to move through 
    • -mostly conduct sodium and calcium, but can conduct some K+ too. 
    • -lined with anions so that it will draw the + charges through them 
    • -any NT that opens channels and allows cations to move in is EXCITATORY

    • Anionic
    • -only allows negative ions to move through
    • -any NT that allows anions (like chloride) to move in is considered INHIBITORY due to its effect on the action potential
  19. Where is the main anesthetic site of action?
    • TRICK QUESTION!
    • -There isn't one- anesthetic action is a culmination of many different things

    We think the synapse itself is the most likely target of anesthetic action because anesthetics can disrupt synaptic transmission at various locations within the synapse.
  20. What affect does anesthetic have on the CNS?
    Specifically, the Spinal Cord, Reticular Activating System, and Cerebral Cortex?
    • 1. Spinal Cord
    • -MAJOR focus of our anesthetics is the spinal cord (where the idea of MAC comes from)
    • -immobility
    • -action here underlies determination of MAC
    • -specific location may be the motor neuron

    • 2. Reticular Activating System
    • -involved in arousal behavior
    • -inhibit information transfer through the brain stem

    • 3. Cerebral Cortex
    • -site for storage, integration, and retrieval of information
    • -memory and awareness interference
    • -alteration of corticol electrical activity: BIS MONITOR (monitors changes in the surface EEG)
  21. How does anesthetic effect the presynaptic actions in synaptic transmission?
    • Alters NT release
    • Alters NT reuptake following release
  22. How does anesthetic effect the postsynaptic actions in synaptic transmission?
    Alters binding of NT to receptor sites
  23. What are the two types of transport proteins?
    • 1. Channel Proteins
    • 2. Carrier Proteins
  24. Compare and contrast the two types of transport proteins.
    • 1. Channel Protein: 
    • -act by simple diffusion
    • -transports water soluble, small molecules
    • -ex. Sodium

    • 2. Carrier Protein:
    • -act by facilitated diffusion or active transport
    • -provides a means for substances to bind and get moved into the cell

  25. True or False: 
    Only channel proteins are selective to what they allow in and out of the cell.
    • FALSE. 
    • Both channel and carrier protein channels are highly selective to what they allow to cross the membrane (ions/molecules)
  26. If a potassium channel protein is accustomed to allowing the large potassium ion through (mass of 39, anatomic # of 19) would it then, therefore, allow sodium ions to pass as well? (mass of 22, anatomic # of 11)
    NO! 

    Channel proteins are HIGHLY selective! It is not just the size of the ion or molecule that dictates passage... Potassium channels are potassium specific. They allow dehydrated potassium to pass because the filter is lined with carbonyls (C=O) which will pull off the H2O molecule and allow the potassium ion to pass- because sodium is smaller it will not come into contact with the carbonyls (C=O) and therefore will not pass.
  27. What is the difference between voltage gated and ligand gated channels? (give examples)
    • Voltage-gated channels: 
    • -opening/closing occurs due to the electrical gradient 
    • -ex. Na channel

    • Ligand-gated channels:
    • -chemical or NT binds with channel protein 
    • -ex. Ach channel
  28. An aquaporin is a clinical example of what type of Protein?
    A. Channel
    B. Carrier
    A. CHANNEL!

    • Aquaporins depend on ADH secretion. They allow more H2O to pass through the very narrow opening, water molecules must pass single file
    • -Number of aquaporins depend on physiologic requirements and are directly related to the secretion of ADH by the hypothalamus released by the posterior pituitary
  29. How will molecules/particles move in regard to the concentration gradient?
    Molecules/Particles will move from high concentration to less concentrated portions
  30. How will molecules/particles move in regard to the electrical potential gradient?
    Overarching charge on inside/outside of cell will cause movement of the oppositely charged ion. 

    For instance, if the inside of the cell is move positive, negative ions from the ECF will move intracellularly, regardless of the concentration gradient (Typically the Nernst potential will provide a balance between the two gradients)
  31. The Nernst potential is also known as:
    The Goldmann Equation
  32. Which gradient is fundamental to all action potentials? 
    A. electrical gradient
    B. concentration gradient
    C. Both A & B
    C. Both electrical and concentration gradients contribute to the action potential
    (this multiple choice question has been scrambled)
  33. At what membrane potential (mV) will Potassium stop diffusing  (even if a gradient still exists)?
    -94 mV- diffusion will stop even if a concentration gradient still exisits
  34. At what membrane potential (mV) will Sodium stop diffusing (even if a gradient still exists)?
    +61 mV
  35. What is the diffusion potential?
    The diffusion potential is the electrical potential difference between the inside and the outside of the cell that opposes net diffusion (that would ordinarily occur because of the concentration gradient)
  36. What 3 Factors is the Resting Membrane Potential Dependent On?
    • 1. Polarity of the electrical charge of each ion
    • 2. Permeability of the membrane to each ion
    • 3. Concentration Gradient of each Ion across the membrane
  37. What happens when the cell is depolarized?
    Before depolarization, the resting membrane potential is -90 mV and the activation gate on the voltage gated sodium channel is closed

    A stimulus occurs that causes the -90 mV to move closer to 0, for example to -50 mV. 

    Following the move to -50 mV the activation gate will flip open and subsequently there is a rapid influx of sodium ions into the cell

    Membrane potential may overshoot (to +20 for example) and shortly after the inactivation gate will close slowly so that no more sodium can get into cell

    Potassium voltage gated channels open and potassium moves out of cell to help repolarize the cell (and bring the membrane potential back to resting)
  38. What is the resting membrane potential?
    When the cell is "polarized"

    Typical value is -70 to -90 mV (inside of cell relative to outside of the cell)
  39. What maintains the resting membrane potential?
    KNaATPase Pump and Potassium leak Channels
  40. ATPase PUMP MOVES ___ SODIUM IONS OUT OF CELL FOR EVERY ___ POTASSIUM IONS MOVED INTO CELL.
    ATPase pump moves 3 sodium ions out of the cell for every 2 potassium ions moved into the cell.
  41. When does depolarization occur?
    • Happens when membrane becomes suddenly permeable to sodium ions- making the cell more positively charged
    •  
    • Occurs following the membrane potential- when the threshold reaches -50mV
  42. When does repolarization occur?
    Occurs after cell membrane becomes increasingly permeable to potassium

    K moves outside of cell returning the negative charge inside cell
  43. Is it possible that the first excitatory stimulus could cause transient depolarization and not reach threshold?
    Yes... but by increasing the stimulus strength, will increase the depolarization and reaches threshold to stimulate the action potential
  44. What effect does inhibition have on the action potential?
    Inhibition causes hyperpolarization of the resting membrane (making the mV -110 instead of -90)- so a stimulus that would've otherwise reached threshold won't anymore... THIS IS HOW ANESTHETICS WORK!
  45. By what two mechanisms do anesthetics work in regard to the action potential?
    • 1. Depressing excitatory potential
    • 2. Enhancing inhibitory potential 

    Thereby inhibiting action potentials in the CNS
  46. By what mechanism does excitatory neurotransmitters typically work? Give an example.
    typically increase permeability 

    ex. Acetylcholine attaches to its receptor and causes increased permeability of the membrane to sodium (Sodium will move intracellullarly)
  47. By what mechanism does inhibitory neurotransmitters typically work?
    Usually reflect selective increase to permeability to potassium and chloride ions. 

    Will have the same effect of making inside of the cell more negative because taking + charges out of the cell and moving - charges into the cell.
  48. What is the major excitatory NT in the CNS?
    Glutamate
  49. What is the major inhibitory NT in the CNS?
    GABA
  50. What are examples of NT in the CNS?
    Ach, Norepi, Epi, Endorphins, Glycine, Serotonin, GABA, Glutamate
  51. What are three types of transmembrane proteins involved in cell communication?
    • 1. Voltage Gated Ion Channels
    • 2. Ligand Gated Ion Channels
    • 3. Transmembrane Modulators
  52. What are some examples of Voltage Gated Ion
  53. What are some examples of Voltage Gated Ion Channels?
    • -can be for both cations and anions
    • Sodium
    • Potassium
    • Calcium
    • Chloride
  54. What are some examples of Ligand Gated Ion Channels?
    • Nicotinic Cholinergic Receptors- found in NMJ and ganglia
    • Amino Acid Receptors
    • GABA
    • NMDA (N-methyl-D-aspartate)- MOA Ketamine
  55. What are some examples of transmembrane modulators?
    • Adrenergic Receptors (alpha/beta)
    • Muscarinic Cholinergic (end organ)
    • Opioid
    • Serotonin
    • Dopamine
  56. What does GABA stand for? What does the structure look like?
    • Gamma amino butyric acid
  57. What is the major inhibitory ion in the CNS?
    GABA
  58. Where are GABA receptors located?
    Throughout the CNS: cortex, cerebellum, spinal cord, and basal ganglia
  59. True/False:
    It is estimated that 1/3 of the synapses in the brain are gabenergic?
    TRUE
  60. When GABA binds to the receptor, what ion does it allow to flow into the cell?
    Chloride- makes cell hyperpolarized
  61. What receptors are the prime anesthetic targets (except for Ketamine)?
    GABA receptors

    Almost all inhaled and IV drugs rely on chloride shift from GABA
  62. Can life be sustained without GABA transmission?
    NO. GABA transmission helps to counteract excitatory NTs
  63. Can GABA cross the blood brain barrier?
    No, because it's polarized
  64. What does the Meyer-Overton Theory state?
    POTENCY OF INHALED ANESTHETIC IS DIRECTLY CORRELATED TO LIPID SOLUBILITY

    Proposes that all inhaled gases share component at a molecular level that causes the anesthetic effect
  65. Name 4 Limitations of the Meyer-Overton Theory?
    • 1. Only applies to gases and volatile liquids- because olive oil:gas partition CoE can't be determined for liquids (IV drugs)
    • 2. Olive Oil is a poorly characterized mixture of oils
    • 3. Not all lipid soluble compounds are anesthetics**
    • 4. Some lipid soluble compounds are convulsants**

    **think non-immobilizers as example
  66. What is lipid solubility measured with?
    Oil-Gas Partition CoE
  67. The Meyer-Overton Theory suggest that anesthetics act by:
    Proposes anesthetics act by disrupting the structure or dynamic properties of the lipid portion of nerve membranes
  68. What is the agent specific theory state?
    inhalation agents don't have a predominant structure-function relationship
  69. What is another name for the Meyer-Overton Theory?
    Unitary Hypothesis
  70. What does the Critical Volume Hypothesis propose?
    agents expand lipid bilayer beyond the critical volume
  71. What does the disruption of membrane form theory suggest? What are some other names for this theory?
    disrupt ion channels

    Fluidization theory, Lateral Phase Separation Theory
  72. What is the 5 Angstrom Theory and who proposed it?
    Eger proposed that anesthetics produce anesthesia by an action on 2 sites separated by a distance of 5 angstroms

    -maximum potency is achieved with a molecule that is 4 carbons long have 2 active sites attached at each end
  73. Describe the ASA physical status classifications.
    • 1. Healthy, no meds, no comorbidities
    • 2. Smoker, HTN but well controlled
    • 3. Uncontrolled HTN, ischemic heart disease, fragile DM
    • 4. Unstable patient
    • 5. Die with or without surgery
    • 6. Organ Donor

    Adding an E- emergency case

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