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288 Cards in this Set
- Front
- Back
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Local anesthetics are divided into chemical classes, which can be ___ or ____.
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esters and amides
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How are esters metabolized?
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hydrolyzed by cholinesterase --> short duration of action, readily metab. at site of injection
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How are amides metabolized?
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in liver by CYP450 enzymes --> longer duration of action
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Which class of LAs has a higher allergy potential? Is cross allergy likely?
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esters
can have a cross-allergy within a class but not between classes |
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Which class do the following LAs belong to:
cocaine, procaine (novocaine), chloroprocaine (nesacaine), tetracaine (pontocaine), benzocaine (topical) |
esters
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Which chemical class do the following LAs belong to:
lidocaine (xylocaine), prilocaine (citanest), ropivacaine (naropin), bupivicaine (marcaine, sensorcaine), articaine (septocaine), mepivacaine (carbocaine) |
amides
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What are the miscellaneous category LAs?
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EMLA cream, hyaluronidase (wydase, vitrase), oraverse
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Can you give an amide to a pt with an ester allergy?
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yes!
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The epinephrine that might be mixed with LAs may cause these adverse effects:
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palpitations, sweating
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All LAs have the same _____, but their ___ and ____ varies.
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same efficacy,
onset/duration varies |
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What are the 3 components of a local anesthetic's structure?
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1. lipid soluble portion (aromatic benzene ring)
2. water soluble portion (Amine) 3. intermediate chain (ester or amide linkage) ester: O=C-O amide: NH-C=0 |
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The longest acting ester is
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tetracaine
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_____ are longer acting because they are more lipophilic, protein bound, and require transport to liver for metabolism by CYP1A2 and CYP3A4
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amides
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Mepivacaine, bupivacaine, and ropivacaine are chiral drugs because....
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the molecules possess an assymetric carbon atom
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This type of nerve fiber is heavily myelinated with intermediate or late anesthetic block onset, and includes alpha, beta, gamma and delta fibers. Functions include proprioception, pressure, muscle tone, and pain/cold temp.
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Type A
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This type of nerve fiber is lightly myelinated with early block onset, and functions as preganglionic autonomic vasomotor.
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Type B
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This type of nerve fiber is not myelinated, has early block onset, includes both sypathetic and dorsal root fibers, and functions include postganglionic vasomotor and pain/temperature sensation.
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Type C
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Quaternary amine LA molecules are ______ and tertiary amines LA molecules are ____.
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ionized, nonionized
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LAs are strongly influenced by the ____ and ___ of the environment into which they are injected.
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pH and pKa
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LAs can be ionized or nonionized depending upon the ___ of the solution that you put them in.
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pH
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How does the structure of LAs play into their mechanism of action?
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lipid soluble (nonionized) portion penetrates neuron cell membrane --> inside axoplasm, ionized portion attaches to anesthetic receptor inside sodium channel --> blocks sodium channel so that it can't depolarize and no action potentials are generated --> no neurotransmission
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When LA is injected, there is a ___ spread from the injection point.
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360 degree
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Once LA is injected, some is wasted in nonspecific _______ and some takes effect to create a ______.
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tissue binding, nerve blockade
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After bloodstream uptake and removal of LA from the injection site, there is systemic _______ and ______ metabolism, followed by renal excretion.
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systemic tissue distribution, hepatic or plasma hydrolysis
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What does it mean that LAs have "Backwards pharmacokinetics?"
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absorption away from injection site is what makes LAs wear off, opposite of onset of other drugs that require systemic absorption for onset, offset occurs when LAs are systemically absorbed
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LAs are ____ Drugs due to their nitrogen content.
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basic
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____ influences the duration of action of LAs. The higher the number, the longer the duration due to greater receptor affinity. However, this does not play a large role with ____ LAs due to fast metabolism.
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protein binding, ester
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LA pKa ranges from ___ to ___, and relates to the drug _____.
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7.6 to 8.9, onset
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The ____ the pKa is to body pH, the _____ the onset.
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closer/lower, faster onset
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The fastest LA onset is _____ and the slowest LA onset is _____.
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fast: mepivacaine, etidocaine
slow: procaine |
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Chloroprocaine has a high pKa (8.7) but fastest onset because...
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used in such high concentrations that it can overcome higher pKa and work faster (dose-dependent)
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When the pH and pKa have a difference of < 0.5...
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50% ionized/50% nonionized
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The more lipid soluble (nonionized) a LA is, the more available it is to ....
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enter the nerve and produce a block (close pH and pKa)
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The higher the pKa of an LA, the more ionized it becomes, so it cannot...
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easily penetrate the nerve and take action
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What are the reasons for adding epi to a LA injection?
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incr hemostasis, incr duration of action, decr toxicity (by preventing incr in blood and brain levels, not as systemically absorbed), speeds onset (except spinals), used as a marker (if accidently intravascular you will see immediate result on monitor)
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Adding epi to a spinal LA ____ onset.
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prolongs
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Increasing dose will _____ onset time of LAs.
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decrease
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Adding epi to an LA that isn't spinal will _____ onset.
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decrease
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Increased dose and addition of epi has what effects on pharmacokinetics outside of onset?
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- incr motor blockade
- incr sensory blockade - incr duration of blockade - incr area of blockade - incr peak plasma concentration (except if epi added) |
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What denomination of epi is used to add to LA injections?
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1:200,000 (5 mcg/mL)
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A more pronounced prolongation of LA duration of action is seen in...
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short acting LAs
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The toxicity of LA depends on ....
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vascularity of the area being injected (intercostals > foot)
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Since epi slows absorption of LAs, you can give ____ doses.
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higher
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What is the max dose of procaine
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14
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What is the max dose of chloroprocaine
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14
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What is the max dose of tetracaine?
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1mg/kg (most toxic)
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What is the max dose of cocaine?
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3 mg/kg (200 mg total)
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What is the max dose of lidocaine 1% and 2%?
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7 mg/kg
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What is the max dose of mepivacaine?
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7 mg/kg
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What is the max dose of prilocaine?
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8.5 mg/kg
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What is the max dose of bupivacaine?
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3 mg/kg
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What is the max dose of ropivacaine?
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3 mg/kg
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Since LA injections vary on so many levels, dosing must be adjusted according to..
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injection site, type of LA, pt weight, etc
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____ occurs when LA cannot leave the brain due to increase ionization.
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ion trapping
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LAST
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local anesthetic systemic toxicity
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In the event of LA overdose, respiratory depression may occur resulting in ____ and ____.
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hypoxia and acidosis
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The acidosis resulting from hypoxia during LA overdose may increase the ____ fraction of the drug within _____ circulation.
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ionized, cerebral -- decr ability to pass BBB and leave brain to reenter systemic circulation
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Ion trapping enhances ____ toxicity of LAs.
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CNS
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To prevent ion trapping after giving LA...
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avoid hypoventilation or ineffective circulation of drug around body (prolonged toxicity)
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How are LAs trapped in fetal circulation?
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fetal pH more acidotic that maternal --> more ionized LA --> LA gets trapped in fetal circulation
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LAs injected into ______ tissue are ineffective due to loss of lipid solubility.
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infected/acidotic
(pH of 5 in pus) loss of lipid solubility prevents absorption into nerve preventing access to site of action-- must use GA or use block proximal to infection site |
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_____ of LAs speeds onset and intensity of action of neural blockade. ______ readily diffuses into nerves lowering pH within the nerve.
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carbonation, CO2
unavailable in US, higher concentration at site of action at Na channel |
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LAs are prepared in slightly ____ formulation to improve stability of the drug by incr concentration of ionized water-sol. form. Addition of _____ increases the concentration of nonionized lipid soluble form of the drug, giving more rapid onset, as it can enter neurons more readily
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acidic, Na-HCO3
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The inherent fetal acidotic pH in utero compared to maternal pH leads to fetal ______. The more acidotic the fetus becomes, the more LA will be trapped in fetal circulation, and _____.
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ion trapping, accumulation
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How does lipid solubility affect LA administration?
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correlates w potency, greater lipid solubility enhances diffusion through neural coverings and cell membrane, allowing a lower dosage
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How does dissociation constant affect LA administration?
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correlates w time of onset, determines portion of an administered dose that exists in the lipid-soluble, tertiary molecular state at a given pH -- agents w lower pKa have greater proportion in tertiary, diffusable state, hastening onset
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How does chemical linkage affect LA administration?
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correlates w metabolism, esters are principally hydrolyzed in plasma by cholinesterases; amides biotrans. in liver
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How does protein binding affect LA administration?
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correlates w duration, affinity for plasma proteins also corresponds to affinity for protein at receptor site within Na channels, prolonging presences of anesthetic at site of action
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Progression of s/s during LA toxicity (LAST)
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lightheadedness, tinnitus, mouth/tongue numbness --> visual disturbance --> muscle twitching --> convulsions --> unconsciousness --> coma --> resp arrest --> CV arrest
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LAs depress the _____. Patients experience convulsions from LAs due to _____.
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CNS, disinhibition
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Describe how a beer block works?
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inflate "BP" cuff, give IV lido --> diffuses out of veins into nerves --> creates block below cuff --> IV regional block --> lasts about 2 hrs (length of cuff inflation time)
standard dose of IV lido 40 mL of 0.5% |
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Why is only 0.25-0.5% bupivacaine used for regional anesthesia (Beer blocks)?
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difficult, if at all possible, to resuscitate -- bupivacaine preferentially binds to myocardial protein, leading to arrest --> hrs of resus. to get a response -- unique toxicity
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This is the bupivacaine isomer without cardiac toxicity, also long acting.
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ropivacaine
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How is cardiotoxicity from bupivacaine treated?
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IV lipid rescue- "lipid sink" - gives bupivicaine a place to bind other othan heart and brain, so it can be excreted in the urine
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When LAs are accidently injected into a vessel and a patient begins fasciculating, it is important to give...
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versed
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What is the duration of LAST after an LA overdose?
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occurs quickly, immediately after injection, and subsides within approx 10 min after it has been redistributed into the tissues, LAST is self-limiting, be vigilant w ABCs until this passes!
alpha phase- first 10 min beta phase- 11 min-120 min |
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What systems is LAST most likely to present in?
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CNS or CNS&CV (45% each),
CV only is 11% |
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Most common CNS sign of LAST
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seizure (68%)
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Most common CV sign of LAST
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bradycardia/asystole (27%)
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Because LAST occurs so quickly, 50% of the time during injection, and less than 1 minute after, it is important to...
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have supplies ready to treat LAST just in case
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In order to prevent LAST, is important to use the ____ dose of LA (dose = product of volume x concentration)
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lowest effective
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What is the technique of LA injection desirable to avoid LAST?
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- incremental injection 3-5 mL at a time, pause 15-30 sec between pushes
- aspirate needle before each injection (2% false neg), if in vessel, will see abrupt tachycardia - use intravasc. marker if giving potentially toxic doses (Epi) - use of ultrasound guided injection to prevent intravasc. injection |
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What is the effect on BP and HR of inadvertent injection of 10-15 mcg/mL intravascularly?
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> 10 bpm incr in HR
> 15 mmHg incr in SBP (in absence of beta blockade, active labor, old age, gen/neurax. anesthesia) |
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During LAST, CV changes start as ______ and then becomes _____.
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stimulation (HTN, tachycardia, dysrhythmia), depression (bradycardia, conduction block, asystole, decr contractility)
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If LAST onset is prolonged 1-5 min after injection, this suggests...
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partial /intermittent intravasc. injection, delayed circulation time or delayed tissue absorption
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It may take as long as ___ minutes for LAST to develop, so patients should be closely monitored for at least this long after potentially toxic LA doses are given.
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30 min!
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LAST is more common in what population?
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unhealthy people! (underlying cardiac, neuro, pulmonary, renal, hepatic or metabolic disease), old age
heart failure, ischemic heart disease, conduction abnormalities, metabolic (mitochondrial) disease, liver disease, low plasma protein concentration, metabolic/resp acidosis, meds that inhibit Na channels, low EF |
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The most important initial LAST management is...
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ABCs!
prompt and effective airway mgmt to prevent hypoxia/acidosis which potentiate LAST (give versed, mask and ventillate) |
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If LAST causes seizure, the most appropriate action is
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benzo administration
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If you need to take over the airway during seizures from LAST, your most appropriate action is
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use small dose of propofol or succinylcholine to stop seizure and take over airway, but seizure is self-limiting
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Although propofol can stop seizures, why is it not the best drug to use during LAST?
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large doses further depress CV function- avoid if CV compromise noted
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What are the ACLS prefered techniques for LAST induced cardiac arrest?
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- small initial doses of epi (10-100 mcg bolus)
- avoid vasopressin - avoid ca channel blockers and beta blockers (depress heart) - if ventricular arrhythmias, amiodarone preferred, avoid locals (lidocaine, procainamide) |
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After airway management during LAST, the next appropriate step is
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lipid emulsion therapy
- 1.5 mL/kg of 20% lipid emulsion bolus, then start gtt 0.25 mL/kg/min - if circulatory stability not obtained, give additional bolus, and incr gtt to 0.5 mL/kg/min (max dose 10 mL/kg/30 min) |
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Can propofol be used as a substitute for lipid emulsion?
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nope!
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What do you do if vasopressor therapy and lipid emulsion do not produce LAST relief?
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institute cardiopulmonary bypass
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LA toxicity arises from associated _____, not the LA itself.
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hypoxia
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Possible CNS signs of LAST
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excitation (agitation, confusion, muscle twitching, seizure)
depression (drowsiness, obtundation, coma, apnea) nonspecific (metallic taste, circumoral numbness, diplopia, tinnitus, dizziness) |
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Although sedative hypnotic drugs lower seizure risk in pts receiving LAs, it may abolish the patients ability to...
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recognize or report symptoms of rising LA concentrations
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Mechanism of action of LAs
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block voltage-gated Na channels and interrupt initiation and propagation of impulses in axons
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The low potency and lack of specificity of LAs available is due to
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weak structural constraints at binding site on Na channel
(features derive from ability to be highly soluble and diffusable in both aqueous and lipid environments) |
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______ of the tertiary amine group tends to make LAs less charged at more basic pH and more charged at neutral/acidic pH.
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Reversible protonation
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The neutral base form of LA is more soluble in _____environments, and the charged acidic form is more soluble in _____ environments.
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lipid, aqueous
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Hypoxemia and acidosis exacerbate LA toxicity because they further cause _____.
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ion trapping
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Injection of LA into a constrained tissue space increases risk for
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local toxicity
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_____, as opposed to racemic mixture, has reduced incidence of systemic toxicity and improved sensory selectivity.
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Single-stereoisomer formulations
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A growing use of LAs outside of procedures in the OR is the management of...
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chronic pain (post op infusions, local and systemic)
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Pregnancy _____ the effect of LAs.
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enhances
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Appropriate administration of epidural anesthesia (does/does not) adversely affect uterine tone or uterine to umbilical flow.
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does NOT
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Repeated epidural injections of lidocaine may result in greater accumulation of drug in women with ____ rather than in health pregnant women.
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preeclampsia
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_____ has greater cardiotoxicity than lidocaine because of its greater electrophysiologic effects,which predisposes to ventricular arrhythmias.
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bupivacaine
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____ isomer formations of amide LAs (ropivacaine and levobupivacaine) have lower potential for cardiotoxicity than racemic bupivacaine.
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single/levorotary
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Are LAs teratogenic?
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not if used clinically
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The elimination half-life of amide local anesthetics is longer in newborns than adutls because
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newborns have greater volume of distribution
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Alkalinization of LA solution shortens the ___ of neural blockade but increases risk for ____ during epidural.
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onset time, hypotension
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Neuraxial opioid admin produces analgesia without
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loss of sensation or proprioception
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Combo of neuraxial anesthesia w opioid increases block ____ and allows for admin of ____ dose of LA --> lower incidence of side effects.
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density, lower dose
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Spinal bioavailability is greater with ____ Drugs.
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greater w hydrophilic drugs (morphine, dilaudid) than hydrophobic (fentanyl)
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Most common side effects of neuraxial opioid admin are
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pruritus, N/V
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Most serious complications of neuraxial opioid admin is
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fetal bradycardia and maternal resp depression
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Why do some practitioners mix a fast and slow LA?
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for more ideal duration (drugs that work fast also wear off quickly, and vice versa)
fast- chloroprocaine and lidocaine slow- bupivacaine and tetracaine |
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When mixing LAs to improve duration (a fast and a slow LA), _____ should also be presumed to be additive
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toxicities (when mixing 2 LAs, use half of each's max dose to prevent toxicity)
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Spread and depth of epidural and spinal anesthesia is greater in ____ Women.
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pregnant (epidural speed greatest in first trimester)
due to: dilated epidural veins, hormones (progesterone) |
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What is tumescent anesthesia and when/why is it used?
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using way too much (large doses, very diluted) - started in liposuction cases, used in plastic surgeries
decreases blood loss when mixed w epi, toxic dose but when placed in fat w epi (Very low systemic vascular absorption) -- sucked right back out w liposuction |
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Topical anesthesia in the form of creams and patches are available in which LAs?
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lidocaine, dibucaine, tetracaine, benzocaine,
takes 1 hr to work, effective, short duration w application to mucous membrane or abraded skin |
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TAC (Tetracaine/epi/cocaine mixture) is ____ through intact skin but in contrast can be absorbed rapidly and become ____ in mucosal surfaces. Potential adverse reaction may include...
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ineffective in intact skin, toxic in mucosal surfaces,
seizures, cardiac arrest |
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Both EMLA and topical cetacaine spray can cause this nasty little side effect
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methemoglobinemia
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What are the max doses of EMLA according to weight between <5 kg to > 20 kg?
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<5 kg 1 g
>5 kg 2 g <10 kg 1-6 yrs 10 g >20 kg 7-12 yrs 20 g |
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What drug is used to reverse oral local anesthesia after a dentist visit (helps with prolonged face numbing and drooling, biting tongue)?
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oraverse
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How does oraverse work?
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alpha receptor antagonist--> vasodilation --> better blood flow absorbs it away from site of injection --> wears off faster
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____ anesthetics have 2 "I"s in the name
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amide
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____ was the first LA used in humans, is naturally occuring, blocks reuptake of epi/norepi/dopamine, and is a sympathetomimetic vasoconstrictor from catecholamine release.It is used during ENT procedures to numb the area, decr bleeding, and provide pain releif/sedation.
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cocaine
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Sympathomimetic drugs can be divided into these 2 categories:
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adrenergic amines, nonadrenergics
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What are the 2 types of adrenergic amines and give examples:
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1. catecholamines: epi, norepi, dopamine, dobutamine
2. noncatecholamines: ephedrine, phenylephrine, clonidine |
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Give examples of nonadrenergic sympathomimetics
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aminophylline, glucagon, digitalis, narcan, amrinone
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What are the 2 branches of the ANS?
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sympathetic and parasympathetic
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What is the process of an amino acid being manufactured into catecholamines?
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tyrosine--> dopa --> dopamine --> NE --> epi
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What is the rate limiting step in catecholamine synthesis?
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tyrosine hydroxylase (Enzyme inside sympatheic nerve terminal/adrenal medulla)
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Why is NE stored in a vesicle?
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MAO enzyme that breaks it down is stored next to it so it must be protected
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What are the 2 enzymes involved in metabolism of catecholamines?
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MAO (monamine oxidase, in nerve mitochondria) and COMT (synaptic enzyme)
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What is the job of the presynaptic autoreceptor?
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neurotransmitters released (NE, ACh) act back on the nerve that released it, creating negative feedback which causes less catecholamines to be secreted, end result is sympatholytic
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Why aren't drugs designed to have parasympathomimetic effects?
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little clinical effectiveness so drugs do not manipulate to produce this response -- causes vagal actions like bradycardia, salivation, diarrhea, and bronchoconstriction
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Give examples of parasympatholytic drugs
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glycopyrrolate, atropine
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Describe the response of the cholinergic system to interference with the systhesis of Neurotransmitters
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agents: choline acetyltransferase inhibitors (alpha methal tyrosine)
effects: minimal depletion of ACh overall action: sympatholytic |
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Describe the response of the adrenergic system to interference with the synthesis of neurotransmitters
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agents: inhibition of tyrosine hydroxylase
effects: depletion fo NE action: sympatholytic |
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Describe the adrenergic response to metabolic transformation by the same pathway as the precursor of the neurotransmitter
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agent: methyldopa
effects: displacement of NE by alpha-methyl NE, which is an alpha 2 agonist, similar to clonidine, that reduces sympathetic outflow from CNS action: sympatholytic |
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Describe the cholinergic response to blockade of transport system at nerve terminal membrane
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agent: hemicholinium
effect: block of choline uptake with consequent depletion of ACh action: sympathomimetic |
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Describe the adrenergic response to blockade of transport system at nerve terminal membrane
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agents: cocaine, imipramine
effect: accumulation of NE at receptors action: sympathomimetic |
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Describe the cholinergic response to blockade of transport system of storage vesicles
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agent: vesamicol
effect: block ACh storage action: sympatholytic |
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Describe the adrenergic response to blockade of transport system of storage vesicle
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agent: reserpine
effect: destruction of NE by mitochondrial MAO, and depletion from adrenergic terminals action: sympatholytic |
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Describe the cholinergic response to promotion of exocytosis or displacement of transmitter from axonal terminal
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agent: latrotoxins
effect: cholinomimetic followed by anticholinergic action: sympathomimetic |
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Describe the adrenergic reponse to promotino of exocytosis or displacement of transmitter from axonal terminal
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agent: amphetamine, tyramine
effect: adrenomimetic action: sympathomimetic |
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Describe the cholinergic response to prevention of release of neurotransmitter
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agent: botulinum toxin
effect: anticholinergic action: sympatholytic |
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Describe the adrenergic response to prevention of release of neurotransmitter
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bretylium, guanadrel
effect: antiadrenergic action: sympatholytic |
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Describe the muscarinic cholinergic response to mimicry of NT at postjunctional sites
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agent: methacholine, bethanachol
effect: cholinomimetic action: sympathomimetic |
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Describe the nicotinic cholinergic response to mimicry of NT at postjunctional sites
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agent: nicotine, epibatidine
effect: cholinomimetic action: sympathomimetic |
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Describe the alpha 1 adrenergic response to mimicry of NT at postjunctional sites
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agent: phenylephrine
effect: selective alpha 1 adrenomimetic action: sympathomimetic |
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Describe the alpha 2 adrenergic response to mimicry of NT at postjunctional sites
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agent: clonidine
effect: adrenomimetic (periphery) action: sympathoLYTIC agent: precedex effect: reduced sympathetic outflow (CNS) action: sympathoMIMETIC |
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What is the alpha1/alpha2 adrenergic response seen with agent oxymetazoline to mimicry of NT at postjunctional sites?
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effect: nonselective alpha adrenomimetic
action: sympathomimetic |
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What is the beta 1 adrenergic response to mimicry of NT at postjunctional sites
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agent: dobutamine
effect: selective cardiac stimulation action: sympathomimetic |
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What is the beta 2 adrenergic response to mimicry of NT at postjunctional sites?
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agent: terbutaline,albuterol, metaproterenol
effect: selective beta 2 receptor agonist (selective inhibition of smooth muscle contraction) action: sympathomimetic |
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What is the beta1/beta2 adrenergic response as with agent isoproterenol to mimicry of NT at postjunctional sites?
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effect: nonselective beta adrenomimetic
action: sympathomimetic |
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What is the cholinergic muscarinic response to blockade of postsynaptic receptor?
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agent: atropine
effect: muscarinic blockade action: sympatholytic |
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What is the nicotinic cholinergic response to blockade of postsynaptic receptor?
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agent: d-tubucurarine, atracurium, trimethaphan
effect: neuromuscular blockade, ganglionic blockade action: sympatholytic |
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What is the alpha1/alpha2 adrenergic response to blockade of postsynaptic receptor, as seen with phenoxybenzamine?
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effect: nonselective alpha receptor blockade (irreversible)
action: sympatholytic |
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What is the alpha1/alpha2 adrenergic response to blockade of postsynaptic receptor, as seen with phentolamine?
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effect: nonselective alpha receptor blockade (Reversible)
action: Sympatholytic |
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What is the alpha 1 adrenergic response to blockade of postsynaptic receptor as seen with prazosin, terazosin, doxazosin?
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effect: selective alpha 1 receptor blockade (Reversible)
action: sympatholytic |
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What is the alpha 2 adrenergic response to blockade of postsynaptic receptor as seen with yohimbine?
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effect: selective alpha 2 receptor blockade
action: sympatholytic |
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What is the beta1/beta2 adrenergic response to blockade of postsynaptic receptor as with propranolol?
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effect: nonselective beta receptor blockade
action: sympatholytic |
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What is the beta 1 adrenergic response to blockade of postsynaptic receptor as with metoprolol and atenolol?
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effect: selective beta 1 receptor blockade (Cardiac)
action: sympatholytic |
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What is the cholinergic response to inhibition of enzymatic breakdown of transmitter?
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agent: AChE inhibitors (edrophonium, neostigmine)
effect: cholinomimetic (muscarinic sites), depolarization blockade (nicotinic sites) action: sympathomimetic |
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What is the adrenergic response to inhibition of enzymatic breakdown of transmitter?
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agent: nonselective MAOI (paragyline, nialamide), selective MAOB inhibitor (Selegeline), peripheral COMT inhibitor (entacapone), peripheral and central COMT inhibitor (tolcapone)
effect: little direct effect on NE or sympathetic response; potentiation of tyramine; adjunct to parkinsons action: sympathomimetic |
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What is the adrenergic response to interference with second messenger system?
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agent: PDE3 inhibitors, milrinone
effect: inotrope action: sympathomimetic |
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Mech 1: interference w synthesis of catecholamines
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ex: tyrosine hydroxylase inhibitor
sympatholytic depletes catecholamines |
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Mech 2: false transmitter
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ex: alpha methyl NE
fool the nerve into synthesizing the wrong NT by giving it the wrong starting product sympatholytic |
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Mech 3: block NE reuptake
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ex: cocaine, TCAs
if NE can't be reuptaken into the nerve, incr NE in synapse, sympathomimetic blocks active transport at nerve membrane and NE cannot go back into nerve |
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Mech 4: inhibition of vescular storage of NE
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ex: reserpine
if you prevent storage of NE in its protective package, NE will be broken down by MAO, no catecholamines stored in nerve, sympatholytic |
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Mech 5: indirectly acting agents
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drugs that cause catecholamine release from neuron into synapse, sympathomimetic, do not act directly on receptor, but incr amt of NE in synapse to act
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Mech 6: blockade of NE release
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ex: clonidine, precedex
cannot release NE from the nerve, sympatholytic, drugs that stimulate alpha 2 autoreceptors - negative feedback to prevent NE release |
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Mech 7:directly acting agents
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ex: levophed, phenylephrine, isoproterenol
drugs that go directly to postsynaptic receptor and stimulate it, sympathomimetic, classic drug agonists (alpha, beta, dopamine) |
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Mech 8: receptor blockade
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ex: propranolol, regitine
drugs that go directly to postsynaptic alpha, beta or dopamine receptor and block it, sympatholytic, NE cannot act on receptor |
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Mech 9: inhibition of enzymatic breakdown of transmitter
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ex: AChE inhibitors, relaxants
interference w breakdown/metab of catecholamines, can inhibit MAO or COMT, sympathomimetic, neostigmine interferes w breakdown of ACh in parasympathetic synapse |
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Mech 10: interference w second messenger system inside cell
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stimulating cell membrane receptor causes G protein to stim release of enzyme adenyl cyclase--> converts ATP into cAMP--> release 2 high energy phosphate bonds,
cAMP is second messenger for sympathetic nerves cAMP incr is sympathomimetic PDE (phosphodiesterase) breaks down cAMP -- PDE inhibitors prolong cAMP --> sympathomimetic (Ex. milrinone, inotrope), viagra and cialis inhibit PDE 5 --> vasodilation |
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What is the only tyrosine hydroxylase inhibitor, and what does it cause?
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metyrosine (Demser),
decr in circulating catecholamine levels (antihypertesive) |
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This type of drug helps to prevent fluctuations in dopamine levels in brain between doses in Parkinsons patients.
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tolcapone (tasmar)
selective/reversible inhibitor of COMT, enhances action of L-Dopa and produces less fluctuation in drug response (Decr dose of isoproterenol, dobutamine and methyldopa in these pts due to interaction) decreases diastolic filling, EF, CVP, Ventric EDV, PA pressure |
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What do PDE inhibitors do?
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inactivate cAMP or cGMP, 7 families, sympathomimetic
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What do atropine eye gtts do?
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antimuscarinic/anticholinergic, cause pupil dilation (mydriasis) because will block sphincter muscle in eye, also interferes w accomodation (cycloplegia)
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What do neosynephrine eye gtts do?
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mydriasis (dilation) but no cycloplegia
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What are the effects of beta 1 agonists and where do they take effect?
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in heart - sympathomimetic
incr HR, BP pos inotropic/chronotropic/ dromotropic |
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What is the effect of vagal stimulation on the heart?
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heart block, decr HR, acts on muscarinic receptors
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How do anticholinergic drugs affect the heart?
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incr HR
pos. inotropic/chronotropic/ dromotropic used to treat heart block |
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Except for the blood supply to the salivary glands, what part of the nervous system controls vascular tone?
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sympathetic
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______ constrict, ______ dilate in vessels
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alpha constrict
beta dilate |
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During the stress response, the patient becomes pale because
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body wants to shunt blood to vital organs and skeletal muscles
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If you are vasoconstricting in alpha vascular beds, then you are ______ in beta vascular beds.
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vasodilating
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How does atropine (a parasympatholytic) cause tachycardia?
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by blocking muscarinic receptors
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What happens if you give neostigmine without the coadministration of robinul?
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bronchoconstriction because only parasympathomimetic effects
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Neostigmine causes what GI side effect
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N/V
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During traumas, patients undergoing the stress response should be considered full stomach for induction because...
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"scared shitless"
release of catecholamines causes GI shut down and decr gastric emptying |
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What effect to beta blockers have on the RAAS system?
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renin secretion is regulated by beta 1 receptors
beta blockers inhibit release of renin from kidney, and RAAS activation |
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What is a tocolytic drug used for?
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prevent/prolong delivery, uterine relaxation
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Why is hyperglycemia common in traumas?
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stress response causes incr release of glucose
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What are the sympathetic effects on the eyes?
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alpha 1: mydriasis (dilation) in radial muscle of iris
beta 2: relaxation for far vision in ciliary muscle |
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What are the parasympathetic effects on the eye?
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miosis (constriction) of sphincter muscle in iris,
contraction for near vision accomodation of ciliary muscle |
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What are the sympathetic effects on the heart?
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beta 1: incr SA HR, incr atrial contractility and conduction velocity, incr AV HR, incr His-Purkinje automaticity and conduction velocity, incr ventricular contractility, conduction velocity, and automaticity
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What are the parasympathetic effects on the heart?
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decr HR, decr contractility, decr conduction velocity, AV block
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What are the only 3 places outside the heart where you can find beta 1 receptors?
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kidney vessels, parts of GI wall, adipocytes
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What are the sympathetic effects on blood vessels?
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alpha 1 and 2 constrict, beta 2 dilates
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What is the only parasympathetic influence on blood vessels?
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dilation and incr secretions in salivary glands
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What are the sympathetic effects on the tracheal and bronchial smooth muscles?
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beta 2: relaxation, bronchodilation
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What are the parasympathetic effects on tracheal and bronchial smooth muscle?
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contraction, bronchoconstriction
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What are the sympathetic effects on the GI tract?
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inhibitory
decr motility and tone, sphincter contraction, secretion inhibition, gallbladder and duct relaxation alpha 1/2, beta 1/2 |
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What are the parasympathetic effects on the GI tract?
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stimulate gut
incr motility and tone, relax sphincters, stimulate secretions, contraction of gallbladder and ducts |
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All cholinergic receptors are called _____.
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muscarinic
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What are the sympathetic effects on the kidney and bladder?
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incr renin secretion (Beta 1)
detrusor relaxation (Beta 2) trigone and sphincter contraction (alpha 1) |
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What are the parasympathetic effects on the bladder?
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detrusor contraction, trigone and sphincter relaxation
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What are the sympathetic effects on the uterus?
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contraction- pregnant (alpha 1)
relaxation- pregnant and nonpregnant (beta 2) |
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What are the sympathetic effects on the liver?
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alpha 1/beta 2- glycogenolysis and gluconeogenesis, incr glucose
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What are the sympathetic effects on the pancreas?
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depends on glucose levels
alpha 2- decr insulin secretion in beta cells in islets beta 2- incr insulin secretion from beta cells |
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What are the sympathetic effects on adipocytes?
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alpha 1, beta 1/2/3- lipolysis (burning fat for energy)
some weight loss drugs stimulate catecholamines to cause lipolysis w unhealthy side effects |
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What pts should you exercise caution or even contraindication for beta blocker administration?
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- reactive airway disease
- asthmatics (Causes bronchoconstriction) - intermittent claudication/PVD (Causes further vasoconstriction in already poor circulation to legs/feet and exacerbate) - diabetics (can decr glucose) |
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List the effects of alpha agonists?
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mydriasis, reflex bradycardia, vasoconstriction, decr GI motility and secretion, uterine ctx., incr glucose production in liver
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Lists the effects of alpha antagonists?
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miosis, reflex tachycardia, incr contractility, vasodilation
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List the effects of beta agonists
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positive ino/chrono/dromotropic,
vasodilation, bronchodilation, decr GI motility/secretion, uterine relaxation, incr glucose production in liver |
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List the effects of beta antagonists
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decr IOP (Glaucoma pts), negative ino/chrono/dromotropic, vasoconstriction, bronchoconstriction, hypoglycemia
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List the effects of cholinergic agonists
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miosis, decr IOP, negative ino/chrono/dromotropic, bronchoconstriction, incr GI motility and secretion
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List the effects of anticholinergics
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mydriasis, cycloplegia, incr IOP, positive ino/chrono/dromotropic, bronchodilation, decr GI motility/secretion
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How does dopamine dose influence its effects in the body?
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low dose- stimulates dopamine receptors
med/high dose- stimulates alpha/beta/dopa |
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Diastolic BP correlates w ____
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SVR
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What are the effects of phenylephrine on BP, HR and SVR, and what receptor does it act on?
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big incr BP and SVR, reflex brady,
pure ALPHA |
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What are the effects of norepinephrine on BP, HR and SVR, and what receptor does it act on?
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big incr BP and SVR, incr HR
mostly alpha, some beta |
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What are the effects of epinephrine on BP, HR and SVR, and what receptor does it act on?
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incr SBP but decr SVR and DBP, big incr HR
mostly beta, some alpha |
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What are the effects of dopamine on BP, HR and SVR, and what receptor does it act on?
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incr SBP but decr DBP and SVR, incr HR
acts on dopamine, alpha and beta depending on dose |
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What are the effects of dobutamine on BP, HR and SVR, and what receptor does it act on?
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incr SBP, big decr DBP, tachy, decr SVR
acts on pure BETA positive ino/chrono/dromotropic |
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What are the effects of presynaptic vs postsynaptic stimulation of alpha 2 receptors?
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pre- decr NE release and symp outflow due to negative feedback autoreceptors
post- vasoconstriction |
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Dopamine receptors are mainly found in the ____, but outside the CNS they can be seen in _____ and _____.
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brain, renal arteries and mesentery
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Which type of drug is ideal for shock states?
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beta agonists w alpha agonists combo- improve tissue perfusion, positive inotropic without incr HR and BP is your goal
(dopamine and dobutamine, norepi and dopamine/nipride)-- enhances inotropy without too much stress on theheart |
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Describe the dose dependent effects of dopamine
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2-5 mcg/kg/min: incr renal and mesenteric blood flow, dopamine only
5-10: beta 1 agonist and dopamine, vasodilation >10-15: ALPHA 1, beta 1 and dopamine agonist, vasoconstriction, no more improved RBF |
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If a pt has a BP 60/20 and HR 130, which pressor is best to use?
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phenylephrine bc incr BP with reflex brady
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If pt has a BP 60/20 and HR 70, which pressor is best to use?
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ephedrine to incr BP and avoid reflex brady, will incr HR
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What is the mechanism of action for ephedrine?
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direct alpha and beta stimulant, also indirect (causes catecholamine release), has both central and peripheral action (Crosses BBB)
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Which is more likely to make a pt tachycardic and bradycardic? phenylephrine and ephedrine
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tachy- ephedrine
brady- neosynephrine |
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Which sympathomimetic drugs are direct acting vs indirect?
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direct: epi, norepi, dopamine, phenylephrine
indirect: amphetamines both: ephedrine |
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Epinephrine dose
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bolus: 2-8 ug
gtt: 1-20 ug/min |
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norepi dose
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gtt: 4-416 ug/kg/min
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dopamine dose
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gtt: 2-20 ug/kg/min
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dobutamine dose
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gtt: 1-2 ug/kg/min
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ephedrine dose
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bolus: 5-25 mg
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phenylephrine dose
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bolus: 0.5-10 mg
gtt: 20-200 mcg/min |
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What are the clinical uses of beta blockers?
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tx of essential HTN, mgmt of angina, tx of ACS, periop beta blockade, tx for intraop cardiac ischemia, supression of dysrhythmia, mgmt of CHF, prevention of excessive SNS activity, preop for hyperthyroid, tx of migraine
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Which anesthesia drugs increase tone of lower esophageal sphincter to decr regurg and aspiration risk
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reglan, prochlorperazine, edrophonium, neostigmine, histamine, succ, pancuronium, metoprolol, adrenergic agonists, antacids
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Which anesthesia drugs decr tone of lower esophageal sphincter to incr regurg and aspiration risk
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atropine, glycopyrrolate, dopamine, Na nitroprusside, ganglion blockers, thiopental, TCAs, beta agonists, halothane, enflurane, opiates, N20
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Why is cricoid pressure possibly dangerous for incr aspiration risk during RSI?
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reflexively enhances sphincter relaxation
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Where are muscarinic receptors located?
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CNS, heart, glands, GI tract
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What are the important parasympathetic clinical effects of M1-M5 muscarinic receptors?
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incr cognition and memory, gastric acid production, bradycardia, smooth muscle contraction, salivary secretions, bladder contraction, promotes dopamine release, dilation of cerebral arteries
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Which can pass the BBB and the placenta: atropine or glycopyrrolate?
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atropine!
glycopyrrolate is not lipid soluble and 100% ionized. it has no PO absorption, no CNS effects, and no fetal effects |
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Which is better to use during pregnancy: atropine or glycopyrrolate?
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glycopyrrolate, cant pass placental barrier
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What pronounced effects does scopalamine have?
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sedation, drying secretions, mydriasis/cycloplegia, preventing N/V (motion)
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Which anticholinergic is great to use with ketamine and why?
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scopalamine and glycopyrrolate bc they dry secretions and ketamine will cause incr secretion
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Effects of anticholinergic drugs
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sedation, drying secretions, incr HR, relax smooth muscle, mydriasis/cycloplegia, prevent N/V (motion), decr h+ gastric secretion
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Which anticholinergic has the greatest incr in HR seen?
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atropine
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What are the effects of a 0.5 mg atropine dose?
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slight cardiac slowing, dry mouth, anhydrosis (no sweat)
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What are the effects of a 1 mg dose of atropine?
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CPR dose
dry mouth, thirst, incr HR, mydriasis |
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What are the effects of a 2 mg dose of atropine?
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rapid heart rate, palpitations, drymouth, mydriasis, blurred vision
completely blocks vagal/parasymp. nerve stim--> maximal effect of dose response curve |
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Which dose of atropine causes "atropine flush"?
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5 mg
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What are the effects of a 10 mg dose of atropine?
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rapid/weak pulse, iris obliterated, blurred vision, skin flushed hot and dry, ataxia, restlessness, excitement, hallucinations, delirium, coma (Accidental OD)
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What is the mnemonic device for atropine poisoning?
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red as a beet, blind as a bat, dry as a bone, mad as a hatter, hot as a hare
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neuroleptic
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blocks or depresses brain
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analeptic
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CNS stimulation: incr wakefulness, alertness, decr fatige, elevated mood, incr initiative, self confidence, incr concentration, elation, euphoria, anorexia, incr motor/speech activity
amphetamines and cocaine cause this!-- negative side effects elsewhere in the body! |
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Effects of alpha 1 postsynapic receptors
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vasoconstriction, mydriasis, GI relaxation, sphincters tight
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List the effects of beta agonists
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positive ino/chrono/dromotropic,
vasodilation, bronchodilation, decr GI motility/secretion, uterine relaxation, incr glucose production in liver |
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List the effects of beta antagonists
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decr IOP (Glaucoma pts), negative ino/chrono/dromotropic, vasoconstriction, bronchoconstriction, hypoglycemia
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List the effects of cholinergic agonists
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miosis, decr IOP, negative ino/chrono/dromotropic, bronchoconstriction, incr GI motility and secretion
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List the effects of anticholinergics
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mydriasis, cycloplegia, incr IOP, positive ino/chrono/dromotropic, bronchodilation, decr GI motility/secretion
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Effects of alpha 2 presynaptic receptors (clonidine, precedex)
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inhibition of NE release, sedation, decr BP
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Effects of alpha 2 postsynaptic receptors
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platelet aggregation, CNS stim (hyperpolarization)
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Effects of beta 1 postsynaptic receptors
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in the heart!
positive dromo/chrono/inotropic |
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Effects of beta 2 postsynaptic receptors
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vasodilation, bronchodilation, GI/uterine/bladder relaxation, incr glucose,lipolysis
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Effects of dopamine 1 postsynaptic recptors
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vasodilation in renal arteries
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Effects of dopamine 2 presynaptic receptors (autoreceptors)
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inhibition of NE release
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Beta 2 agonists incr _____ secretion.
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insulin - watching for decr blood sugar
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Which receptor relieves congestion?
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alpha 1 (phenylephrine)
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Which receptor causes urine retention and constipation?
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alpha 1 (phenylephrine)
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Which receptor aids in mast cell stabilization (good in anaphylaxis)?
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beta 2 - epinephrine
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Which type of drug is useful for old men with HTN and BPH?
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alpha antagonists (promotes micturition and decr BP)
watch out for postural hypotension! |
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Which type of drug has negative ino/chrono/dromotropic effects?
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beta antagonists
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Which drug is useful for cardiac deceleration?
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beta 1 antagonists
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Which type of drug decr blood pressur by inhibiting renin release?
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beta 1 antagonists
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What happens if you antagonize beta 2 receptors?
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bronchoconstriction! yikes!
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