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147 Cards in this Set
- Front
- Back
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How are most drugs metabolized? give 2 names
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First order Kinetics
Linear Kinetics |
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Name 3 drugs eliminated by zero order kinetics
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Alcohol, Aspirin, Dilantin
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What is the goal of drug metabolism?
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Convert lipophilic molecules into more polar molecules by introducing or unmasking a plar functional group
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What takes place in Phase I of metabolism?
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oxidation
reduction Hydrolysis |
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What are the 3 phases in a 3 compartment model
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Alpha phase: rapid (Re)Distribution
Beta: Intermediate Equilibrating Gamma: Slow Elimination phase |
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what does an increase in clearance do to half-time?
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half-time will decrease
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What does context-sensitive half time refer to?
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context refers to duration of infusion
time to decrease plasma concentration by 1/2 |
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What does time to recovery depend on?
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depends on how far the plasma concentration has to decrease to get to point where patient will be able to wake up
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What is the equation for clearance 1/2 life and volume of distribution?
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t1/2 = 0.693 X Vd/Cl
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What are the Determinant of tissue uptake of drug?
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Blood flow to the tissue
Concentration gradient Blood-Brain barrier Physicochemical properties of the drug (ionization, lipid solubility, protein binding) |
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What are the determinant of capacity of tissue to store a drug?
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Solubility of drug in a particuliar tissue
tissue mass binding to macromolecules pH |
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What is a racemic mixture?
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a mixture that has two enantiomers present in equal proportions (50:50)
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What does chiral mean?
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term used to designate a molecule that has a center of 3-dimensional asymmetry
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What is competitive antagonism?
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when increasing concentrations of the antagonist progressively inhibit the response to unchanging concentration of agonist
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What is noncompetitive antagonism?
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present when high concentrations of agonist cannot overcome the antagonist
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What kind of receptor does insulin use?
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cell membrane embedded receptors
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What kind of receptors do Ach andGABA use?
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Ligan-Gated ion channels
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What drugs use the G protien-coupled receptro system?
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Norepinephrine, histamine, peptide hormones
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Whare are the transcription factor receptors found?
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within the cell (on DNA of nucleus)
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What drugs use transcription factor receptors?
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thyroid hormone, steroid hormones
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What is potency (high affinity)?
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amount of drug required to produce a particuliar effect
Can bind to receptor even when present in low concentration |
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What is efficacy (intrinsic activity)?
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the maximum effect that can be produced by a drug regardless of amount of drug given
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Give an example of 2 drugs with similiar efficacy, but different potency
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Demerol morphine
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What neurotransmitter acts on Nicotinic receptor?
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Ach-- binds to receptor and Na channel opens to let Na into cell causing depolarization
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Name 2 excitatory amino acids that act through ligand gated channel receptors
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Glutamate and Glycine
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What does a competitive antagonist do to the dose-response curve?
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shifts it to the right, so that the drug appears less potent
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Does a non-competitive antagonist affect efficacy or potency?
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Decreases efficacy by preventing binding of the agonist
Decreases maximal response of drug |
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What is therapeutic index?
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Margin of safety
Difference b/t the dose of the drug pproducing the desired effect and the dose producing the undesirable (toxic) effect LD50/ ED50 |
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What is anaphylactoid?
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clinical presentation like anaphylaxis, but is non-immunologic (chemically mediated)
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What are 2 phases of anaphylaxis?
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Sensitization
Elicitation |
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What drives distribution of inhaled anesthetics?
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Pressure Gradient
Pi-PA-Pa-Pbr |
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What determines inspired gas concentration (Fi) of inhaled anesthetics?
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FGF rate (gas flow)
Breathing circuit volume Circuit absorption |
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What determines the alveolar gas concentration (FA) ?
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Uptake
Ventilation Concentration and second Gas Effect |
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What determines the relationship b/t partial pressure of gas in the tissue and volume % that is delivered by the anesthesia machine
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Solubility of the gas
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List the Determinant of Alveolar Partial Pressure
FA/ Fi |
Inhaled partial pressure
Alveolar ventilation Spontaneous vs mechanical ventilation Cardiac Output Alv. to Venous partial pressure difference Concentration Effect Second gas effect Solubility |
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How does the inhaled partial pressure increase/decrease the alveolar partial pressure?
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Increased inspired concentration helps to off-set uptake which speeds the rise in alveolar partial pressure
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What is overpressurization?
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increasing the amount of inspired concentration (Fi) anesthetic being delivered, so providing more to be taken up by the artery
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How will spontaneous vs mechanical ventilation affect alveolar partial pressure?
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mechanical ventilation allow to make sure getting Tidal Volume needed for uptake of inhaled anesthetic
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How will an increase in cardiac output affect alveolar partial pressure?
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it will decrease the rate of rise of alveolar partial pressure and slow induction
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What are the 3 factors that determine the fraction of anesthetic removed from the blood as it passes through the tissues
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solubility of anesthetic
blood flow partial pressure difference (in the tissue group) |
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How many time constants does it take for the VRG to become saturated (equilibrate with arterial partial pressure)?
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3 (5-15 minutes)
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Time Constant = ?
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an estimate of the time of anestheitc to reach equilibrate with tissues
= amount of inhaled anesthtic that can be dissolved in the tissue divided by tissue blood flow Capacity/ Flow |
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What % is 1 time constant?
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63%
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What % is 2 time constants?
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86%
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What % is 3 time constants?
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95%
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What % is 4 time constants?
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98%
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What does it mean if a drugs time constant is 4 minutes?
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In 4 minutes 63% of drug will be equilibrated
in 8 minutes, 86% of drug will be equilibrated |
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If you give 2% Iso and the time constant is 4 minutes, after 1 time constant, 63% of it will be equilibrated. How much of the original 2% given is this?
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2 x .63 = 1.26%
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What is involved in pharmacokinetics of inhaled drugs?
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1. absorption (uptake)
2. distribution (transport of durg to sites of action) 3. Metabolism: LIMITED with inhaled anesthetics 4. Elimination: principally via the lungs |
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what determines the Fresh Gas Flow (FGF)?
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vaporizer and the flow meter settings
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What is the route of inhaled anesthetics?
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1. Anesthesia Machine (FGF)
2. Breathing Circuit 3. Inspired Concentration (Fi) 4. Alv. Gas Concentration (FA) 5. Arterial Gas concentration (Fa) |
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What are the 2 components of the Concentration Effect?
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1. Concentrating Effect
2. Augmentation of Tracheal Flow |
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What is the alveolar conc. (FA) if the concentration of gas inspired is 80% (utilizing the concentrating effect)
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80 parts in 100
after 50% taken up it is 40 parts in 60 40/60 = .67 = 67% |
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what is the second gas effect?
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Concnentration effect of one gas on another
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What gas is second gas effect most significant with and why?
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Nitrous
It has more significant effect b/c can be given in much higher concentrations High Nitrous concentration will augment its own uptake and also that of the volatile gas |
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What does the augmentation of tracheal flow do?
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Creates a negative pressure that pulls in more inspired gas b/c the uptake of gas from the alveoli must be replaced by an equal volume of gas to prevent alveoli collapse
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Desflurane
MAC Solubility Oil:Gas Coefficient |
6
0.42 18.7 |
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Isoflurane
MAC Solubility oil:Gas coefficient |
1.2
1.46 98 |
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Sevo
MAC Solubility Oi:Gas coefficient |
2
.69 55 |
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Halothane
MAC Solubility OIl:Gas coefficient |
0.75
2.54 224 |
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Things that will increase MAC
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Hyperthermia
young age chronic alcohol abuse Hypernatremia |
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Things that will decrease MAC
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Hypothermia
elderly age Acute intoxication Anemia (HCT < 10%) Hypoxia (PaO2 < 40) Hypercarbia (PaCO2 > 95) Hypotension (Map < 40) Hypercalcemia Hyponatremia Pregnancy |
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Drugs that decrease MAC
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Local anesthetics
Opioids Ketamine Barbiturates Benzos Verapmil Lithium Sympatholytics (inhibit Symp. Nervous System): -Methyldopa -Reserpine -Clonidine -Dexmedetomidine Sympathomimetics: acute amphetamine use |
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Drugs that increase MAC
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Sympathomimetics:
-Chronic Amphetamine use -Cocaine -Ephedrine |
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What Factors Do not affect MAC?
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Duration of anesthesia
MAP > 50 Gender Size |
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What inhaled anesthetic increases CBF and ICP more than any others?
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Halothane
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What drug decrease HR and does not alter Systemic vasc. resistance?
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Halothane
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What drug does not alter HR?
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sevoflurane
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What is normal CBF amount?
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750 ml/min
15% of resting CO |
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At what level MAC does cerebral metabolic rate begin to decrease?
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0.4
All inhaled agents produce dose-dependent decreases in cerebral metabolic O2 requirements |
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What can you do to off-set the increase in ICP secondary to increased CBF?
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Hyperventilation
Decrease CO2 to prevent vasodilation |
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What drug is linked to coronary steal syndrome?
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Isoflurane
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How can you minimize the production of compound A with sevoflurane
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maintain gas flow at least 2 L/min
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Which drug is a respiratory irritant?
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Desflurane
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Which inhaled anesthetic does not maintain Cardiac Output by increasing HR?
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Halothane
hypotension is related to this fact (not a decrease in systemic vascualr resistance like the other drugs) |
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Which drug sensitizes Heart to Epinephrine more than others?
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Halothane
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At what MAC level is tidal volume no longer reaching alveolar level?
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1 MAC
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What do inhaled anesthetics do to the pattern of breathing?
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RR is increased
TV and Minute volume is decreased Response to CO2 and Hypoxemia are decreased |
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What drugs can cause Fluoride induced nephrotoxicity?
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Methoxy and Enflurane
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What is Vinyl Halide nephrotoxicity?
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Compound A (vinyl halide) is formed when Sevo reacts with CO2 absorbers
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Which inhaled anesthetic does not produce muscle relaxation?
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Nitrous
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What are the effects of Nitrous on the organ systems?
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Stimulates SNS
Depresses myocardial contractility BP,CO, HR slightly increased or unchanged (good to use to off set the decrease with volatiles) |
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What anesthesia drugs are the most potent triggers of malignant hyperthermia?
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Halothane and Succs
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When would you not use any volatile agents on a patient?
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when they are genetically susceptible to malignant hyperthermia
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Can pregnant patients get Nitrous
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No Teratogenic effects
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What can happen in prolonged exposure to Nitrous Oxide?
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Bone Marrow Depression
Neuropathies Pernicious anemia |
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What are contraindications of Halothane use?
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Pheochromocytoma (endogenous catecholamine re. and halothane sensitizes heart to these)
Epinephrine use Liver dsiease Myocardial depression (beta blockers and calcium channel blockers) Dysrythmias with concurrent aminophylline |
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What 2 inhaled anesthetics are isomers?
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isoflurane and Enflurane
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What chemical does Iso have that Desflurane does not have in chemical structure
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Chloride
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What is MACawake?
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the average concentration permitting voluntary response to a command
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MAC awake for:
Iso Des Sevo |
1/3 of MAC
Iso: 0.4% Des: 2% Sevo: .67% |
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MACawake for Halothane?
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1/2 of MAC
0.375% |
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MACawake for Nitrous?
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60% of MAC
63% |
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What is MAC BAR
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Block autonomic responses
MAC level that prevents response to sugical stimulation Considerably higher than MAC |
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What does adding nitrous to carrier gas do to MAC of volatile?
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Decreases the MAC
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Which volatile agent increases the HR the most?
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Desflurane
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What are the sites of action of inhaled anesthetics?
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CNS
Spinal courd Reticular activating system Cerebral cortex Synaptic transmission |
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What is the normal resting potential across the cell membrane?
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-70 to -90
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What is the Meyer Overton Theory of Anesthetic Action?
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Unitary Hypothesis
Potency of inhaled anesthetics is directly correlated to lipid solubility |
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What do anesthetics do to synaptic transmission?
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Alter neurotransmitter release
Alter uptake of neurotransmitter following release alter binding of NT to receptor sites |
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What does the cerbral cortex control
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memory and awareness
also integration, storage, and retrieval of info. |
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What is the "ideal anesthetic"?
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Induce anestheia smoothly and rapidly
permit rapid recovery Wide margin of safety no adverse effects (no CV changes, allergic people) |
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At what threshold is action potential triggered?
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-50 mV
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Variables that impact care plan
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pharmacology issues
chronic medications perioperative fine tuning Choice of anesthesia-- Goal directed (3 different goals: surgeon, us, patient) Choice of agent (patient history, duration of agent, durationof surgery, side effects, contraindications, availability, cost) RATIONALE |
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Etiology of surgical stress
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Psychological (fear)
tissue Injury Intravascular changes Anesthetic agents Pain Organ Manipulation |
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What is the stress response?
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Activation of hypothalamic-pituitary-adrenal axis and sympathetic nervous system
increased cortisol, catecholamines, cytokines |
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What is result of stress response?
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tachycardia
hypertension increased metabolism hypercoagulability decreased immune function r/o stroke, emboli, infection, MI |
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What does anesthesia do at spinal cord?
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immobility
actions here underlie the determination of MAC |
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What does BIS monitor show?
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Alteration of cerebral cortex electrical activity
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Give an example of post synaptic action of inhaled anesthetics
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They enhance neuromuscular blockade by decreasing hte affectiveness of Ach at receptor sites (NM junction)
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What does action potential do to the presynaptic membrane
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depolarizes it
this causes vesicles containing NT to empty into the cleft (junction) |
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major excitatory neurotransmitter in CNS
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Glutamate
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Does Ketamine work by GABA?
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no
all inhaled and some IV anesthetics work by GABA |
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What is the 5-Angstrom theory?
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Eger's theory
Anethetics produce effects by an action on 2 sites separated by a distance of 5 angstroms |
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What is the problem with meyer-overton theory?
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olive oil is a poorly characterized mixture of oils
Immobilizers are lipid soluble and are not anesthetics (convulsants) |
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How does GABA act?
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GABA binds to the receptor, casuing the chloride channel to open allowing chloride ions to flow into the neuron causing it to become hyperpolarized (more negative)
same stimulius will not cause an action potential |
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Which drug is more potent, Desflurane or Isoflurane and why?
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Iso is more potent b/c it has a chloride and Desflurane has Flouride in that place
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What are the pharmacokinetic variables?
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Absorption
Bioavailability Distribution Volume of Sistribution Protien binding Drug metabolism |
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What determine the amount of drug present in the nonionized form?
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pH of the environment
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pH=?
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pH = -log [H+] or log(1/H+)
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What is pKa?
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the pH at which a drug is 505 ionized and 50% nonionized
onset of action of drug |
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What is the Henderson Hasselbach equation?
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pH = pKa + log [A-]/ [HA]
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When pH is less than pKa (ie the environment is acidic) is the drug more ionized or more nonionized
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Acid Drug = nonionized form
Basic drug = ionized form |
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When the pH is > pKa (ie the environment is alkalotic) is the drug more ionized or nonionized?
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Acid Drug = ionized form
Basic Drug = nonionized form |
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when an acidic drug is ionized, is the the protonated form?
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No
the protonated form of acids is the nonionized form (HA) |
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What kind of ions do weak acids unite with?
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Cation (Na+)
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What kind of ions do weak bases unite with?
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Anions (Cl-) and sulfate
Lidocain Hydrochloride Morphine Sulfate |
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Give examples of Acid drugs
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Thiopental
Barbiturates Propofol |
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Give examples of Basic drugs
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Benzos, Etomidate,
Ketamine local anesthetics Opioids |
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Vessel Rich Group
Body Mass Cardiac Output |
9%
75% |
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Muscle Group
Body mass Cardiac Output |
50%
18% |
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Fat Group
body Mass Cardiac Output |
19%
7% |
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Vessel Poor Group
body mass Cardiac Output |
22%
0 |
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Factors related to Bioavailability
(What fluid compatment the molecules can get into) |
lipid solubility
protien binding molecular size |
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What kind of molecules go into the Plasma
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large MW, highly protein binding, hydrophilic
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What kind of molecules go into the ECF (plasma and interstitium)?
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Low molecular, Hydrophilic (but small enough to fit through slit junctions)
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How can drugs pass through the blood brain barrier?
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Must be lipophilic or actively transported
b/c no slit junctions |
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Vd = ?
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Vd = dose given / plasma concnetration
D/C |
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How is Vd determined?
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by the distribution of drugs into different compartments and the elimination of drugs
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Volumes % and Liters:
Plasma, ECF, Total body Water |
Plasma: 6-8 % and 4 L
ECF: 20-23% and 14 L TBW: 60-64% and 42 L |
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What does protein binding relate to?
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duration of action of a drug b/c only unbound portion of drug is available for metabolism/elimination
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What is happening to the drug during the alpha phase of the plasma concentration curve (3 compartment model)?
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Drug is going from plasma to rapidly equilibrating tissues (VRG, MG)
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What is happening to the drug druing the beta phase of the plasma concentration curve?
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there is reversed flow b/t the plasma and rapidly equilibrating tank secondary to decreased plasma levels
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What are the factors to achieving steady state of plasma concentration?
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Rate of drug infusion
Steady state is directly porportional to infusion rate and inversely proportional to clearance |
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what is the principle degradation product of Sevo?
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Compound A
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How do solubility and speed of induction relate?
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the drugs that are less soluble in the blood (Desflurane, sevo, Nitrous) have faster rise in FA/Fi ratio and faster induction
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on the rare of induction curve for the inhaled anesthtics, what is the flattening of the curve indicative of?
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equilibration with the vessel rich groups
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