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195 Cards in this Set
- Front
- Back
Bioavailability
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The physiological availability of a given amount of a drug, as distinct from its chemical potency; the amount of drug that is actually absorbed from a given dose
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First Pass effect
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The metabolism of orally administered drugs by gastrointestinal and hepatic enzymes, resulting in a significant reduction of the amount of unmetabolized drug reaching the systemic circulation
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What drug undergoes some first pass effect in the lungs?
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Fentanyl
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Beta elimination half-life tells us:
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How long the drug remains in the body (explains hang-over effect of some anesthetic agents)
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Alpha redistribution phase tells us:
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How long the drug remains in the biophase or at the effect site (how long the drug works); this is especially important for lipid soluble drugs
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The Vessel rich group consists of
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The heart, brain, kidneys, and liver
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The muscle group makes up ________% of the average size patient, but receives ________% of Cardiac output
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50% of body mass, 19% of Cardiac output
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The Vessel rich group makes up ________% of the average size patient, but receives ________% of Cardiac output
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10% of body mass, 75% of Cardiac output
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The fat group makes up ________% of the average size patient, but receives ________% of Cardiac output
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20% of body mass, but only receives 6% of CO
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The vessel poor group (bone, etc) makes up ________% of the average size patient, but receives ________% of Cardiac output
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20% of body mass, receives <1% of CO
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Plasma drug level (does or does not) explain how long or how much of a physiologic effect a drug will have
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Does not directly relate to drug effect or duration; rather we are more concerned with the drug concentration in the peripheral (effect) compartment versus the plasma
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Elimination half life ________ predict how long the drug will be active or have a physiologic effect
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Does not predict
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KE0-
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Rate of movement of drug into the biophase or effect site where the drug is going to do its job
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Generally, drugs that are less potent have a _______ onset time
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faster
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Less potent drugs require a larger number of molecules, and may therefore have more _________
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Side effects
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A1 gylycoprotein binds _______ drugs
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Basic
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Albumin binds _______ drugs
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Acidic
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Lipid solubility of anesthetic drugs leads to _________
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More rapid onset and greater effectiveness because the brain is the effect site and it is made of lipids
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_________ limits volume of distribution
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Protein binding
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___________ binds drugs like pentothal
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Albumin
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___________ binds drugs such as local anesthetics
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Alpha 1 glycoprotein
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Does the concept of altered drug effects resulting from administration of two drugs that are both highly protein bound have much clinical significance?
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No, this does not have much clinical application
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Renal failure alters the _________ of albumin
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Functional binding
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What groups of patients may have decreased albumin, resulting in variable effects of drugs that are highly protein bound?
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Renal failure, pregnancy, elderly, neonates
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Volume of distribution
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A theoretical value that describes the movement of the drug out of the vascular compartment; a volume of plasma needed to dilute a given amount of drug to an observed plasma concentration
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If you give 4 mg of drugs, and then measure a plasma concentration of 1 mcg/ml, what is the volume of distribution?
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4,000 mcg x n = 1 mcg/ml
n= 4 L Volume of distribution here is 4L |
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The mathematical equation for volume of distribution
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VD = total amount of drug in the body/observed plasma concentration
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How do you calculate a loading dose (mathematical equation)
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Loading dose = (desired plasma concentration x volume of distribution)/ (bioavailability)
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If you have a highly lipid soluble drug, you will have a _______ volume of distribution
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High; the drug easily leaves the plasma and enters the peripheral compartments
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Why is a loading dose given?
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To rapidly acheive a therapeutic level (desired plasma concentration)
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Maintenance dosing:
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Dosage should equal ongoing metabolism/clearance
Maintenance dose = (clearance x plasma concentration)/ (bioavailability) |
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Elimination half-time:
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Time for plasma concentration to reach 50%
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How many half-times does it take for a drug infusion to reach equilibrium if a loading dose is not given?
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5 half times
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Will increasing the rate of a drug infusion decrease the amount of time it takes to reach a steady state/equilibrium?
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No, but it will increase the plasma concentration at the steady state
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Context sensitive half time is affected by:
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Distribution, effect of compartment partitioning, metabolism, duration of IV infusion
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Context sensitive half time is:
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The time that it takes for the plasma concentration of a drug to decrease 50% after discontinuation of an infusion of a particular duration
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After about ______ hours, Fentanyl concentration really starts to build up unless you decrease your infusion rate
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2 hours and then context sensitive half time increases dramatically and patient takes forever to wake up
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Sufentanil context sensitive half time is about _______ minutes in infusions up to about 8 hours
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30 minutes
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Name 4 reasons why anesthetic infusions are better than intermittent dosing
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1. Avoid under and overshoot in dosage
2. Avoid latency in reaching effect site 3. Reduce intraoperative workload 4. Reduce total drug usage by 25-50% |
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Liver extraction ratio:
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drug broken down by liver/drug delivered to the liver
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Capacity dependent elimination:
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When liver extraction ratio is low, the amount of drug overpowers the enzymes available to break it down- in liver failure, the capacity to break down these drugs decreases even further
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Flow dependent elimination:
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When extraction ratio is high, the amount of drug broken down is dependent on blood flow to the liver (how much drug the liver actually sees)
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What are two factors that might decrease the flow dependent elimination of drugs
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Sepsis
Volatiles |
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Lidocaine is a _______ extraction ratio drug;
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High; if you give it for cardiac arrest/shock, it is going to build up and hang around a lot because flow to the liver is decreased and therefore metabolism is decreased
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IV drugs that have a low extraction ratio are _______ to changes in liver enzymes. What is one example of this?
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Very sensitive; alfentanil is extremely sensitive to P450 induction or inhibiton
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IV drugs that have a high extraction ratio are _______ to changes in liver enzymes. What is an example of this?
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Not very sensitive to changes; Fentanyl and Morphine are not affected much by liver induction or inhibition
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PO drugs have_________ effect as IV drugs regarding the extraction ratio response to enzyme induction or inhibition in the liver
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Opposite; PO drugs that have a high extraction ratio will still be greatly effected by changes in liver enzymes because they undergo first-pass effect
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What are 4 possible results of metabolism/biotransformation?
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1. Inactivate drug
2. Change to a more or less potent metabolite 3. Activate an inactive precursor drug 4. Change an active drug into a toxic metabolite |
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What is an example of a drug that is made more active or potent by metabolism?
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Codeine is metabolized into Morphine; Morphine is metabolized into Morphine-6 glucorondide which is much more potent than Morphine
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What is an example of a drug that is metabolized into a toxic metabolite?
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Meperidine is metabolized into normeperidine; Atracurium is metabolized into laudenosine
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In general, metabolism of lipid soluble drugs changes them ______
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Into water soluble metabolites that can then be excreted by the kidneys
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Phase 1 reactions change the drug by:
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Changing a functional group to make the compound more ionized and therefore more water soluble
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Phase 2 reactions change drugs by:
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Conjugation- the drug is hooked onto something else to make the whole complex more water soluble
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T/F: all drugs undergo both phase 1 and phase 2 reactions
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False; drugs can be eliminated as Phase I metabolites, Phase II conjugates, or can be excreted unchanged
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The three types of chemical reactions that make up Phase I reactions are:
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Hydrolysis
Oxidation Reduction |
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Mnemonic for remembering oxidation- reduction reactions
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Oil Rig: Oxidation is loss (of an electron), Reduction is gain (of an electron)
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Oxidation and reduction reactions change:
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The charge of the compound by loss or gain of electrons
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P450 enzymatic metabolism is a Phase ______ reaction
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Phase I
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Cytochrome P450 enzymes are also known as
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Mixed function oxidases- can perform both oxidation and reduction
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Anesthetic drugs are often metabolized by ______
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p450 system
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The electron donors and acceptors in the p450 system
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Nicotanamide adenine dinucleotine (NAD) and O2 donate electrons; O2 is split and one O atom donates its charge to the drug while the other is incorporated in H20
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The CYP1A enzymes are inducible by:
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Cigarette smoke, charbroiled foods, cruciferous vegetables, omeprazole
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CYP2A metabolizes
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Coumarin into coumadin ((rat poison) and sweet clover disease are examples); also metabolizes halothane, valproic acid, and nicotine
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CYP2B metabolizes _______ and is induced by _______
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Benzos, verapamil, lidocaine, propofol, ketamine, tamoxifen
Induced by barbiturates |
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Receptor, agonist, antagonist, and effector of the neuromuscular junction
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Receptor: Nicotinic cholinergic receptor
Agonist: Acetylcholine Antagonist: Rocuronium Effector: Calcium |
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What enzymes are responsible for the hepatic and renal toxicity of volatile anesthetics?
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CYP2E1
These enzymes metabolize halogenated or volatile compounds |
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What effect do anti-convulsants have on the p450 system?
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Induce them
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What drugs are frequent culprits in inducing the p450 system?
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Anti convulsants very common
ETOH |
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Induction of the p450 system has what effect?
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Makes patients metabolize other drugs faster and therefore makes them resistant to the effects of these other meds (such as anesthetic agents)
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What is the most clinically significant group of p450 enzymes?
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CYP3A
30-60% of all p450 enzymes; metabolizes a large number of commonly used drugs (including opioids, benzos, local anesthetics, zofran) |
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What effect does drinking grapefruit juice have on drug metabolism?
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Grapefruit juice inhibits the CYP3A4 system which can cause accumulation of many drugs including coumadin, Calcium channel blockers, and anti-arrhythmics
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Are carboxylestereases inducible? What do they do?
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Not inducible like P450 system; they hydrolize non-specific amide bonds and make them more water soluble, converting them to alcohols, amines, and acids
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What is the physiologic role of plasmacholineserase (i.e. why do we have it)?
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Unknown physiologic purpose
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What are the byproducts of succinylcholine metabolism?
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Broken down into succinylmonocholine and then succinic acid
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What are the types of cholinestereases and what do they each do?
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Acetylcholinesterease- breaks down acetylcholine;
Plasmacholinesterase: breaks down succinylcholine, mivacurium, ester (one i) local anesthetics |
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What percent of succinlycholine is metabolized in the first minute?
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90%
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Normal pseudocholinesterase is inhibited by _________.
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Dibucaine, a local anesthetic; abnormal pseudocholinesterase is not inhibited by dibucaine
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A normal dibucaine number is ______. What does this mean?
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>80; more than 80% of plasmacholinesterase is inhibited by dibucaine (20% is NOT inhibited)
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A patient with heterozygous plasmacholinesterase would have a dibucaine number of ________, and succinylcholine will last ________.
Homozygous? |
Heterozygous- dibucaine number 40-60 (meaning only 40-60% is inhobited) and sux will last 1-2 hours
Homozygous will have dibucaine number <20 (meaning that less than 20% is inhibited) and sux will last 4-8 hours (i.e. >80 % of your pseudocholinesterase is abnormal, as indicated by the fact that it is not inhibited by dibucaine) |
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RBC and non-specific esterases metabolize ________ and _______.
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Esmolol and Remifentanil
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Will abnormal pseudocholinesterase impact the non-specific RBC esterases?
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No
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Considering the type of metabolism that esmolol and remifentanil undergo, should you be concerned administering these drugs to a patient with abnormal pseudocholinesterase?
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No
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What conditions are known to decrease your acetylcholinesterase and plasmacholinesterase?
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Liver failure, pregnancy, renal failure, cardiopulmonary bypass
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In what type of reaction do endogenous substrates bind with drugs or metabolites to produce a water soluble conjugate?
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Phase II reactions
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How do the transfereases metabolize drugs?
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Conjugate lipophilic drugs in Phase II reactions by covalent bonding to glucoronic acid
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The transfereases are examples of what phase reactions?
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Phase II
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Genetic polymorphism can cause alterations in what compound, leading to fast or slow acetylation. What is the significance of this?
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N- acetyltransferase; slow acetylators will have decreased metabolism of procainamide and hydralazine (leading to increased therapeutic response and potentially leading to hepatotoxicity); Fast acetylators will metabolize some drugs much more quickly and have decreased therapeutic response (to drugs such as isoniazid)
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________ helps elimination of acetaminophen and morphine in neonates
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Sulfation (addition of a sulfate group; phase II reaction, occurs in mitochondria)
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Conjugation of Sevoflurane by __________ leads to production of __________.
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Conjugation of sevo by Glucothionine-S-transferase leads to Compound A production
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Enterhepatic recirculation can cause _________ excretion of some drugs, such as ______.
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Delayed excretion, chloramphenicol (antibiotic)
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Describe the process of enterohepatic recirculation
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Glucuronides are hydrolyzed by b-glucuronidase in the intestines back to the parent compound, which is reabsorbed and transported back to the liver, where it is re-conjugated and then re-excreted
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Where else are most hepatic enzymes found? What does this contribute to?
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Intestine (especially proximal intestine); intestine participates in metabolism and contributes to first-pass effect of PO drugs
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Where does extrahepatic metabolism take place?
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Proximal intestine, decreasing distally
Kidney- most extrahepatic glucoronidation takes place here (oxidation and conjugation) Lungs: some metabolism of Fentanyl and local anesthetics Blood- non-specific esterases break down esmolol and remifentanil |
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Name some causes of interindividual drug effects
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Age, race, sex, enzyme polymorphisms, Environment (smoking, alcohol use, diet), concurrent drug use (enzyme induction or inhibition, physiologic antagonism), disease
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Kinetic consequences of enzyme inhibition or induction depend on _______ and _______.
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Route of administration and extraction ratio
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First order kinetics:
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Amount of clearance is determined by amount of drug present (like a concentration gradient); A set fraction of whatever is present (50%, 25%, etc) is metabolized over a given period of time (concentration dependent)
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Zero Order kinetics
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A fixed amount of drug is metabolized over a given period of time
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A patient has overdosed on a drug, and there is an overabundance of drug present. What order kinetics will likely be responsible for clearance?
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Zero order kinetics, because the amount of drug present is so high, that the liver will be clearing drug at maximal capacity and will clear a fixed amount during each pass through the liver
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With each pass through the liver, enzymes clear 25% of the drug present. This is an example of ______ order kinetics.
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First order
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A half-time is an example of ______ order kinetics
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First order kinetics- half-time is the amount time necessary for 1/2 of the drug to be cleared from the plasma; first order kinetics say that a fixed percentage (in this case, 50%) of drug will be cleared during a given amount of time
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What is the most important route of excretion for unchanged drug or active metabolites?
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Kidneys (i.e. don't give drugs that are excreted unchanged or excreted as active metabolites to patients in renal failure because they can't excrete them and they will accumulate to toxic levels)
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_________ neuromuscular blocking drugs are largely excreted by the kidneys
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Aminosteroids;
Neostigmine and edrophonium are also very dependent on the kidneys for excretion |
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Glomerular filtration is responsible for excretion of _______ and rate of filtration/excretion is largely reliant on _________.
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Small, non-ionic drugs pass most easily through fenestrations in the Bowman's Capsule by diffusion; flow is largely dependent on blood pressure
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Tubular secretion occurs by _______ through specific carriers and transporters. Are size and charge important during this type of transport?
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Active transport through specific transporters at the efferent arteriole. Size and charge are less important for this type of transport.
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During tubular reabsorption, _________ molecules move by ________ from the nephron tubule back into the blood stream
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Small, non-ionic molecules move by diffusion (drugs that are metabolized into a more ionic form are less likely to be reabsorbed)
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Excretion of drugs can be increased by altering tubular reabsorption by way of changing urine ______
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Changing urine pH (ex. with NaHCO3)
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Which gives us a better idea of how long a drug will work- alpha distribution phase or beta-elimination phase (half-life)
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alpha distribution phase (ex. pentothal has a beta-elimination half life of 10 hours, but patient is only anesthetized for 10 minutes)
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The quantitative study of the absorption, distribution, metabolism, excretion of drugs and their metabolites
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Pharmacokinetics
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Pharmacodynamics
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The study of the intrinsic sensitivity or responsiveness of receptors to a drug
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Efficacy
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Maximal effect that a drug can cause regardless of dose; for example tylenol and NSAIDs have well defined efficacy or maximal acheivable effect
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Physiologic antagonism: what is it, and give an example
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A drug of a different class binding to one site or type of receptor is antagonized by a drug working by a different means or at a different site or type of receptor; for example, beta blockers will decrease HR hy blocking beta receptors (in the adrenergic system), but concurrently given atropine will antagonize this effect by modulating parasympathetic system (increasing firing of the SA node and conduction through the AV node)- key here is antagonism by DIFFERENT MECHANISMS
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Examples of physiologic antagonism:
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Beta Blocker and Atropine
Beta Blocker overdose treated with glucagon (which increases cAMP), Glucagon and opiods at sphincter of Odie, Reglan and Atropine at the LES |
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Non-competitive antagonism: what is it and give an example
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A receptor is activated at one site that causes an effect somewhere else (ex. 2,3 DPG and the affinity of hemoglobin for oxygen in the oxyhemoglobin dissociation curve)
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Partial agonist
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Binds to the same receptor and brings about some, but not complete effect (ex. nubain, stadol)
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Example of efficacy
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Rocuronium ( can't make more paralyzed than fully paralyzed), NSAIDs, Neostigmine
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Name 4 ways that drugs can bring about effects, give examples of each
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1. Modulate, activate, or inactivate cellular proteins (most common mechanism)
2. Inhibit nucleic acids (ex. chemo drugs) 3. Bind to and inactivate other substances (ex. Shigamadex binding Rocuronuim, Protamine binds to and inactivates Heparin, Kayexalate) 4. Altering fluid movement (mannitol) 4. |
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Covalent bond
Give an example of a drug that works using this bond |
Strong, stable, lasting double bond made by the sharing of electrons between two molecules
Neostigmine forms a covalent bond with acetylcholinesterase, deactivating it and causing increased concentrations of acetylcholine at the NMJ |
|
Ionic/electrostatic bond
What is it and what law does it demonstrate? Give an example of a drug that works this way |
Bond created by transfer of electrons from one molecule to another; weaker bond than covalent, demonstrates Coulomb's Law (describes the electrostatic "opposites attract" reaction between two molecules)
Edrophonium forms a weaker ionic bond with acetylcholinesterase than the strong covalent bond formed by neostigmine) |
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Hydrogen bond
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Relatively weak bond formed by attraction of Hydrogen to Oxygen; responsible for observed surface tension of water
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Van der Waals forces (London dispersion forces): what are they and what effect are they responsible for?
|
Very weak, transient attractions caused by temporary polarity due to random movement of electrons; increased under pressure
Joule Thompson Effect- as oxygen is released from a pressurized cylinder, these bonds are broken and carry energy away as they exit the pressurized cylinder, resulting in cooling effect on cylinder stem |
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G-protein coupled receptors
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Receptors on the outside of the cell membrane are activated by a drug which then activates Guanine Nucleotide Peptides inside the cell membrane, which causes changes on the inside of the cell membrane by way ion concentration changes, enzyme activation, etc, usually causes second messenger activation
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Order types of bonds from strongest to weakest
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Covalent
Ionic/electrostatic Hydrogen Van der Waals |
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G-protein coupled receptors usually result in ________ activation
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Second messenger activation
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Ligand gated ion channels: definition and example
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Lock and key- the ligand is the key that fits in the lock and causes the ion channels to open; acetylcholine (Na/K channels), GABA (chloride channels)
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Voltage gated ion channels
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Open in response to change in voltage (action potential propagation/ conduction down neuron)
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Signal transduction caused by cytoplasmic changes: what is this and give an example
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Molecule actually goes into the cell and causes changes on the inside; example is milrinone (goes into cell annd inhibits phosphodiesterase, which normally breaks down cAMP; this causes increased cAMP within the cell and results in increased myocardial contractility); steroids are another example (enter cell and cause changes in DNA transcription, etc)
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Bupivicaine toxicity and milrinone is an example of
|
Physiologic antagonism (bupivicaine blocks Na channels resulting in cardiac arrest when too much is given; milrinone acts by a different mechanism to increase cardiac contractility)
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Name 3 common second messengers
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cAMP, cGMP, Calcium
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Name 3 common second messengers
|
cAMP, cGMP, Calcium
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What happens when a receptor is stimulated by epinephrine?
|
Receptor activates g-protein inside cell, which leads to phosphorylation of GDP which activates adenlyl cyclase and causes increased cAMP which acts as a second messenger causes a kind of cascade and causes intracellular calcium release and activates Protein Kinase A and leads to vasoconstriction in addition to other effects
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cGMP causes
|
Vasodilation
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The most common ligand gated channel that we deal with in anesthesia
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Acetylcholine at the neuromuscular junction
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Metabotropic
|
G-protein;
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Ionotropic; what does it do and give an example of a common ionotropic receptor
|
Causes ions to flow; acetylcholine at the nictotinic acetylcholine receptor is an ionotropic receptor which allows Na and K to flow across the cell membrane
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Growth hormone is an example of what type of receptor
|
Tyrosine-kinase receptor
|
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Action potential propagation is an example of what type of signaling?
|
Voltage gated ion channels; ligand is not needed for this type of signaling
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Excitatory neurotransmitters usually work by
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Allowing increased permeability to ions
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Inhibitory neurotransmitters often work by:
|
Hyperpolarizing the cell membrane, often by causing increased permeability to chloride ions
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GABA is a ________ neurotransmitter that works by causing increased permeability to __________
|
Inhibitory neurotransmitter, increased permeability to chloride
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An GABA agonist causes:
|
Increased GABA which leads to increased inhibitory function
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Propofol and benzodiazepines work by:
|
Causing increased release of GABA, which is inhibitory in the CNS
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Why do benzos and propofol have a ceiling effect (i.e.cannot put a patient fully comatose or into burst suppression with these drugs alone)?
|
Because they act indirectly to cause increased inhibition (have a well defined efficacy)
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What are GABA antagonists? What are potential side effects of these drugs?
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Flumazenil, romazicon; can cause seizures
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Does GABA cross the BBB?
|
No; GHB (date rape drug) is a common offshoot that is effective orally and crosses the BBB
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Antagonism of GABA causes
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Excitation (Flumazenil can cause seizure activity)
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Glycine is __________ in the ________
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Inhibitory in the spinal cord; works in much the same way as GABA
|
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What is the role of glycine in TURP syndrome?
|
Excess glycine causes inhibition of CNS leading to confusion, altered LOC, and can cause transient blindness by inhibiting neural transmission at the retina
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Dopamine is a _________ neurotransmitter in the CNS. that has a major role in the __________ of the brain. Dopamine levels are disrupted in __________ disease.
|
Inhibitory in the CNS, major role in the reward center of the brain (partially responsible for addiction "need" ); decreased levels are found in patients with Parkinsons Disease
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5-Hydroxytriptamine is commonly known as ________. This neurotransmitter is _____tropic and _________, and plays a large role in modulating mood and behavior.
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Serotonin; Metabotropic (activate G-protein), inhibitory
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The 5-HT3 receptor is a type of ______ receptor responsible for _______. What drugs work at the serotonin receptors?
|
Serotonin receptor responsible for nausea and vomiting (PONV). "Tron" drugs work as antagonists here (ondansetron, etc);
|
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Tricyclic antidepressants work at ______ receptors, by causing reuptake of _______
|
serotonin but also increase uptake of catecholamines leading to anticholinergic effects
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|
Ketamine and LSD work at what type of receptors
|
Serotonin receptor agonists
|
|
What drugs are agonists at the acetycholine receptors?
|
Succinylcholine, nicotine, butanechol (for urinary retention), pylocarpine (for glaucoma)
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Ach is inhibitory in
|
the parasympathetic nervous system
|
|
Ach antagonists:
|
NDMB, Atrovent (iatrproprium), atropine, scopalamine, glycopyrolate, botulism (decreases release)
|
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Ach is excitatory in
|
The sympathetic nervous system and the adrenal gland
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Glutamate is a _______ neurotransmitter that is produced _______ in response to _______. What does it do?
|
Excitatory neurotransmitter produced in local glial cells in response to injury. Responsible for pain signaling and causes inflammatory cytokine release.
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NorEpi and Epi are inhibitory neurotransmitters in ______
|
RAS (and hypothalamus)
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Glutamate effects are terminated by:
|
Reuptake
|
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Is glutamate ionotropic or metabotropic? Does it cross the BBB?
|
Both ionotropic and metabotropic; but effects we are most concerned with in regards to pain signaling are ionotropic; produced in the brain and does not cross BBB
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NMDA and AMPA are ______ receptors; what are agonists and antagonists at the NMDA receptors?
|
pain; glutamate is agonist, ketamine, dextromethorphan, NO, and glycine are antagonists here
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|
Where is substance P found?
|
Substantia gelatinosa
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What is the major neurotransmitter for pain in the central and peripheral nervous system
|
Glutamate
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Substance P is a _______ neurotransmitter released by pain fibers. What receptors are found nearby? What drugs will block the effects of Substance P?
|
Excitatory; Mu receptors found nearby; opiods work here to block pain signal transduction
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|
Constitutional isomers:
|
Same atoms present but arranged differently
|
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Stereoisomers:
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Atoms in same lineup, but different spatial orientation
|
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Isomers
|
Molecules with the same chemical formula but different arrangement, and therefore can have very different effects and side effects
|
|
Enantiomers/ chiral molecules
|
Stereoisomers which are mirror images of each other but do not superimpose
|
|
Optical isomers
|
Pair of entantiomers that are differentiated by the direction that they rotate light
|
|
Racemic mixtures
|
50/50 mixture of two enantiomers
|
|
What enzymes are responsible for morphine metabolism?
|
CYP3A4
|
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Dose response curve is a function of:
|
Drug potency, efficacy, and individual response
|
|
ED50
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Effective dose (dose necessary to induce a particular response) in 50% of people; analagous to MAC of volatile anesthetics
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Hyper-responsiveness to a drug means:
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Over-exaggerated response to a drug; a low dose produces a normal response
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Tolerance is a type of _______ caused by _________
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Hyporeactivity; caused by long term exposure to a drug or drug of the same class
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Cross-tolerance is _________ to a drug _____________
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hyporeactivity to a drug caused by long-term exposure to a different class of drug (ex. alcohol and benzos)
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Hypo-reactivity
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A larger than typical dose is needed to produce a response
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Immunity to a drug means
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Antibodies have been built up to a drug or receptor (ex. myasthenia gravis and succinylcholine)
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Tachyphylaxis
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Rapid tolerance that builds up to a drug in a short period of time- catecholamines (especially ephedrine) are prone to this
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Tachyphylaxis is one of the first signs of
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Phase II block with succinylcholine
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If you add bicarb to epinephrine, what happens?
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It deactivates the epi
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Pentothal and Rocuronium are ______
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Incompatible in admixture- clouding occurs
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Drugs that are stored in light resistant bottles are trying to prevent what type of reaction?
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Auto oxidation
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What are 5 types of pharmaceutical ractions/interactions (take place before a drug even reaches the body)?
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1.Oxidation/reduction
2. Hydrolysis 3. Salt formation 4. Acid-base reactions 5. Auto oxidation |
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Name 5 types of pharmacokinetic alterations that affect absorption and give an example of each
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1. Alter the pH of the stomach (aspirin not absorbed as well if taken with antacids)
2. Alter GI motility (opiods decrease GI motility and can slow absorption of drugs that are absorbed in the small intestine) 3. Alterations in regional blood flow (Epi added to local anesthetics to decrease their absorption) 4. Inhibition/stimulation of first-pass metabolism (rectal tylenol either undergoes first pass metabolism or bypasses it depending on how far suppository is inserted) 5. Changes in metabolism (grapefruit juice and p450 enzyme induction) |
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What types of drugs (other than reversal agents) antagonize NDMRs?
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Drugs that cause p450 enzyme induction (anticonvulsants, glucocorticoids)
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If a patient is taking a high-extraction ratio drug, and then given a volatile anesthetics, what might happen?
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High extraction ratio drugs are flow dependent; volatile anesthetics (or beta blockers, others that decrease liver blood flow) decrease liver blood flow, and could therefore decrease the metabolism of high extraction ratio drugs (like lidocaine)
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__________ and __________ inhibit plasmacholinesterase and could therefore cause _________
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Echothiophate and phenelzine inhibit plasmacholinesterase and would therfore have a prolonged reaction to succinylcholine
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Volatile anesthetics _________ muscle relaxants
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Potentiate
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Additive drug response is analagous to ________ Law
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Dalton's Law; the result is the sum of the parts
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Synergistic drug effects mean:
When does this typically happen? Give an example of two drugs that work this wa |
The drug response is greater than the combined effect of two drugs; This usually happens when two drugs are from two classes or do the same thing by two different mechanisms;
for example Cisatracurium and Rocuronium have a synergistic effect because they are two different classes |
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Potentiation: what is this?
Give an example |
A drug that has no effect increases the activity of the target drug;
Calcium channel blockers (which in themselves have no effect on muscle relaxation) can cause increased sensitivity to non-depolarizers and exaggerate the effect of NDMB; Ephedrine increases the onset of rocuronium |
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Antagonism: what is it and give examples of drugs that work this way
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A drug that normally has no reaction on its own inhibits the action of another drug; for example, narcan does not cause pain, but it inhibits the effect of opioids; neostigmine and NMDB, Flumazenil and benzos, protamine and heparin
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What does G6PD do in a normal patient? If a patient has a G6PD deficiency, what drugs might trigger a reaction and what would this present as?
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Glucose-6-phosphate dehydrogenase is responsible for some carbohydrate metabolism and has protective effect on RBCs. When patients have a G6PD deficiency, they respond to triggering oxidative drugs with hemolytic anemia; drugs include tylenol, penicillin, chloraquine, and sulfonamides
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1:100,000 nomenclature means
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1 gram in 100,000 ml
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