Reading...
Play button
Play button
Use LEFT and RIGHT arrow keys to navigate between flashcards;
Use UP and DOWN arrow keys to flip the card;
H to show hint;
A reads text to speech;
98 Cards in this Set
- Front
- Back
|
Which type of nerve fibers are the most sensitive to anesthetics?
|
-high frequency nerve fibers
-the channels become open more often and the drug has an affinity for the open channels -higher surface area:volume ratio = more rapid diffusion -no myelination -a small amount may enter externally |
|
|
uses of anesthetics
|
nerve, ganglion, spinal block
cardiac dysrhythmias (heart has Na channels) |
|
|
What are three ester-linked local anesthetics?
|
cocaine
procaine tetracaine |
|
|
What are the three molecular parts of an anesthetic?
|
aromatic ring (lipophlic)
ester or amide linkage tertiary amine (hydrophilic) |
|
|
What are two amide linked local anesthetics?
|
lidocaine
mepivacaine |
|
|
How are ester-linked local anesthetics metabolized?
|
Plasma Colinesterase
|
|
|
How are amide-linked local anesthetics metabolized?
|
Liver
|
|
|
In terms of the molecular structure of the local anesthetics what does the tertiary amine contribute to?
|
-hydrophilic
-Determines the ability to move through the axoplasm |
|
|
In terms of the molecular structure of the local anesthetics what does the aromatic ring contribute to?
|
-It is the lipophilic portion of the drug.
-Determines two things: 1) Na channel receptor affinity 2) Ease in crossing axonal membrane |
|
|
Receptor affinity for a local anesthetic is directly proportional to.....?
|
lipophilicity
|
|
|
Local anesthetic's axoplasmic movement across the membrane is directly propotional to.....?
|
hydrophilicity
|
|
|
If a drug is net hydrophilic than what are its onsets and how potent is it?
|
less potent, but faster onset and shorter acting
|
|
|
If a drug is net lipophilic than what are its onsets and potentcies?
|
highly potent, but slower onset and longer acting
|
|
|
How what happens when an anesthetic binds to a sodium channel?
|
It raises the threshold for depolarization therefore limiting the electric signal along the axon of a nerve.
|
|
|
How does the anesthetic reach the Na channel receptor?
|
-A small portion goes to an uncharged form.
-The uncharged form crosses the membrane driven by a concentration gradient -The uncharged form becomes ionized and binds with the Na channel receptor |
|
|
How do the pKa of the drug and the pH play a role in anesthetizing?
|
-pKa determines the proton association
-the higher the pKa the more drug you will need -association is influenced by the pH -the lower the pH the more drug you will need |
|
|
How does infected tissue play a role in local anesthesia?
|
-infected tissue has a low pH
-vasoconstrinction increases so the drug will be taken away -need more drug, toxicity increases |
|
|
What is a special feature of the ester-linked procaine and tetracaine that has to be considered before administration?
|
They compete with the antibiotic, sulfanilamide, used in treating UTI's.
|
|
|
What is it about the excretion of local anesthetics that has to be considered? How would you deal with this?
|
-local anesthetics are weak bases
-drugs that have been excreted can be reabsorbed back into the plasma by the collecting tubule -acidifying the urine (w/ ammonium chloride) will ionize the drug and prevent reabsroption |
|
|
What 5 factors must you consider in regards to how toxic a drug may be?
|
1) type of drug and how it is excreted
2) amount administered 3) vascularity of injection site 4) vasoconstrictors - prolongs therapeutic effect (epinephrine on procaine, lidocaine and mepivacaine) 5) rate of injection - greater pressure = larger field |
|
|
What are the symptoms of CNS toxicity from local anesthetics?
|
-tinnitus (ringing in the ears)
-euphoria -confusion -numbness -stimulation followed by depression, affects the cerebral cortex and the medulla |
|
|
What are the symptoms of cardiovascular toxicity from local anesthetics?
|
-hypertension (initially)
-then myocardial depression because Ca channels may be blocked--> -hypotension |
|
|
What are the toxicities from cocaine?
|
-problem in highly trained athletes
-hypertension -arrhythmias -coronary artery spasm |
|
|
What are some good ways to prevent the toxic effects of local anesthetics?
|
-premedicate
-smallest dose -use vasoconstrictor (epinephrine) -get a history |
|
|
How would you use local anesthetics for surface anesthesia?
|
-tetracaine,lidocaine and cocaine (for respiratory)
|
|
|
How would you use local anesthetics for under the skin anesthesia?
|
lidocaine, procaine, and bupivacaine w/ epinephrine
|
|
|
Where would you place anesthetic for a spinal block?
What does anesthetize? |
-L3/L4
-everything inferior to the waist |
|
|
Where would you place anesthetic for a pudendal nerve block?
What does it anesthetize? |
-near the ischial spine by Alcock's canal
-anesthtizes S2-S4 and lower 1/4th of vagina |
|
|
Where would you place anesthetic for a epidural block?
What does it anesthetize? |
-through the sacral hiatus to the epidural space
-anesthetizes S2-S4 nerve fibers, pain fibers from cervix, upper vagina and afferent fibers from the pudendal nerve. -WILL STILL FEEL CONTRACTIONS! |
|
|
Salicylates
|
Aspirin
|
|
|
nociceptive pain
|
-result of stimulating free nerve ending and peripheral pain receptors
-can be suppressed or enhanced |
|
|
Two types of nociceptive pain
|
neospinothalmic tract: sharp, well defined, A-delta fibers, treated with cyclo-oxygenase inhibitors (COX)
paleospinothalmic tract: dull, persistent, less well defined, burning, carried by C-fibers, treated with opioids |
|
|
neuropathic pain
|
nervous system dysfunction
-burning or tingling -tumors, shingles, phantom limb, diabetes -defect in NMDA receptor function from a glutamate pathway dysfunction |
|
|
What are the treatments for neuropathic pain?
|
Antisiezure drugs:
gabapentin carbamazepine SNRI's (selective norepinephrine inhibitors) |
|
|
What are the therapeutic uses of salicylates?
|
Analgesia,
anti-inflammatory anti-rheumatoid (arthritis) antipyretic (fever) anticoagulant |
|
|
How do salicylates treat pain?
|
-they prevent the formation of prostaglandins, which are responsible for maintaining the sensitivity free nerve endings
-block both COX-1 and COX-2 -these produce the prostaglandins from arachidonic acid |
|
|
COX-2
|
-induced by inflammatory cells
from the brain and kidney -maintains kidney circulation -it would be best just to treat this one |
|
|
COX-1
|
-in most tissues
-involved in homeostasis -platelet aggreagation |
|
|
How do salicylates have an antirheumatoid effect?
(4 things) |
-reduces edema by maintaining capillary wall integrity
-inhibits the release of neutrophils -stabilizes lysozomes to prevent the release of proteases -inhibits the formation of free radicals |
|
|
What are the mechanisms for the salicylates' antipyretic effects?
|
-COX inhibition in the CNS
-inhibition of interleukin-1 (released from macrophages) |
|
|
Absorption of salicylates
|
-low pH in stomach keeps it at a unionized form so it can be absorbed
-mostly in the small intestine where there is a high surface area |
|
|
What are the mechanisms for the salicylates' anticoagulant effect?s
|
-decrease in platelet adhesive
-decrease in prothrombin levels |
|
|
excretion of salicylates
|
-the acid form will keep it from being reabsorbed in the kidneys
-increasing urine volume prevents reabsorption -tubular secretion by active transport out of blood to urine |
|
|
What are the toxicity problems of salicylates?
|
-GI problems, ulcers, gastritis
-this is from COX-1 inhibition -also disruption of acid base balance |
|
|
Phase-1: low level overdose of salicylates
|
-Uncoupling of OX PHOS
-increased respiration from uncoupling and medulla mechanism -increased respiration blows off the CO2 -decreases [H2CO3] -respiratory alkalosis |
|
|
What are the effects of salicylate overdose?
|
-increases temp from uncoupling
-metabolic acidosis from lactic acid build up -renal failure -cardiovascular: vasodilation |
|
|
Phase-2: high level overdose of salicylates
|
-respiratory rate decreases by mechanism on medulla
-CO2 levels are maintainted -[H2CO3] increases -respiratory and metabolic acidosis |
|
|
How would you treat an salicylate overdose?
|
-charcoal to reduce GI absorption
-give bicarbonate as a buffer -lower body temp -fluids for excretion |
|
|
What are the interaction precautions to worry about with salicylates?
|
-displaces thyroid hormone and corticosteroids from plasma proteins (heart problems)
-Reye's syndrome in children-> encephalopathy and hepatic injury |
|
|
Pharmacologic effects of acetaminophen (tylenol)
|
-Analgesia and antipyresis
-not antiinflammatory or antirheumatic -only inhibits COX at inflammation sites in the brain |
|
|
What are the added benefits of acetaminophen compared to salicylates?
|
-no gastric erosion
-no anticoagulant effect -no change in acid base -does not interfere with gout treating agents -no problem with Reye's syndrome |
|
|
Side effects or toxicities of acetaminophen
|
-formation of a toxic intermediate (NAPQI) which can cause cell death
-alcoholics are at risk bc CYP450 is induced (is this true, not inhibited?) -overdose has problems bc glutathione cannot remove toxic intermediate -blood problems (cyanosis) |
|
|
4 reasons to use opioids
|
pain relief (dull visceral)
antitussive effects diarrhea acute pulmonary edema |
|
|
What are the origins of opioids?
|
Phenanthrenes
Benzylisoquinolines |
|
|
What are the mechanisms of action from opioids?
|
-receptors in the brain and SC
-bind to sites where endogenous ligands bind |
|
|
What is it about the morphine that doesn't allow it to be as effective as heroine?
|
-heroine gets into the brain 2.5 times betters because of its structure.
|
|
|
What are the two endogenous ligands that bind to the opioid receptors?
|
-leu- and met-enkephalin
-five amino acid sequence found in beta-endorphin, dynorphin and other things |
|
|
What type of receptor are the opioid receptors?
|
7-transmembrane g-protein
|
|
|
What it is mechanism of the opioids?
|
-cAMP induced ---->
-presynaptically preventing pain NTs' -hyperpolarizes membrane -blocks calcium transport |
|
|
chronic effects of opiods
|
-no long-term pathology
-high pain tolerance, need more for the same amount of pain -metabolic tolerance, GI becomes better at digesting |
|
|
Effects of opioids on CNS
|
-elevates pain threshold
-codeine has a ceiling effect -euphoria (less so for acute pain) -miosis (constriction of pupil) -need laxative -respiratory depression (deadly) -lowering of the seizure threshold, especially head injuries -nausea -hypothermia -antitussive -endocrine - inreases water retension and decreases other things |
|
|
Effects of opioids on CV
|
-hypotension
-dilates capillary bed from histamine release -increases cerebral circulation from vasodilation -useful in patients with an MI or pulmonary edema (left ventricle failure), lowers workload of heart |
|
|
Effects of opioids on GI
|
-spastic paralysis leading to a decrease in peristalsis
-leads to constipation (treat with laxative) |
|
|
Effects of opiods on GU
|
-spasm of ureter
-reduce urine production (ADH) -depressed sexual activity -passed to neonates |
|
|
How do you stop the withdrawal effects?
|
give them more of the drug
|
|
|
cross tolerance of opioids
|
if you are tolerant to one opioid you are tolerant to all of them
|
|
|
Mechanism for opioid tolerance
|
-dysfunction in G-protein receptor
-change in the NMDA receptor action (pre- and post-synaptic events) |
|
|
Effects of opioid on immune system?
|
-immune supressive
-mu effect |
|
|
Absorption of opioids
|
-codeine is absorbed much faster than morphine, therefore more addictive
-heroin crosses the blood brain barrier 2.5 times as easily than morphine |
|
|
metabolism of opioids
|
-the first metabolite of morphine is active
-activation is in the liver |
|
|
Side effects of opiodis
|
-dizziness, nausea, vomiting
-constipation -biliary colic -allergic rxns -hypotension (give with antihistimine) -respiratory problems |
|
|
What other drugs do opioids interact with?
|
-tricyclic antidepresents
-phenothiazines -barbiturates that enhance respiratory depression |
|
|
Tramadol (ULTRAM)
|
-codeine analog
-mild or moderate pain -binds to mu-opioid receptors -inhibits amine reuptake -less nausea and constipation -thought to have less abuse potential, but not really true |
|
|
Methadone (DOLOPHINE)
|
-orally, longer acting
-this avoids dependence -heroin detoxification (LAAM) -long-acting methadone analog -well absorbed by all routes |
|
|
Propoxyphene (DARVON)
|
-half as analgestic as codeine
-well absorbed -different euphoria -abuse potential is lower |
|
|
meperidine
|
-consists of a few analogs
-shorter duration of action, similar to morphine -antimuscarinic effects causing tachycardia -less constipation |
|
|
Absorption and excretion of meperidine
|
-rapid by all routes
-metabolism by liver -is excreted by urine |
|
|
Toxic effects of meperidine
|
-seizures caused by normeperidine accumulation
-this is seen more in patients with kidney problems -otherwise similar side effects to morphine -interacts with the tricyclic antidepressancts, phenothiazines and barbituates -CNS excitation with MAO inhibitors |
|
|
Fentanyl
|
-type of meperidine
-used short term or chronically ill -patches, lozenges or lollipops |
|
|
Opiod Antagonists
|
-pretreatment prevents the action of the agonist (addicitive opioid)
-will precipitate withdrawal in a chronic user |
|
|
What are two antagonists used to treat heroin addicts?
|
naloxone and naltrexone
|
|
|
Alvimopan (ENTEREG)
|
-opioid antagonist that relieves bowel obstruction following bowel resection
-doesn't cross blood brain barrier |
|
|
What is methylnaltrexone (RELISTOR) used for?
|
-It is an antagonist to opioid
-form of the antagonist naltrexone -doesn't cross blood brain barrier -reduces constipation |
|
|
Partial Agonists
|
-agaonist properties when given alone
-antagonist properties when gievn with an opioid |
|
|
Nalophine
|
-k-opioid effects
-blocks mu receptors so it can precipitate withdrawal -used to diagnose physical dependence |
|
|
Butorphanol (STADOL)
|
-similar to pentazocine (inc HR + BP)
-moderate to severe pain -low abuse/dependence -better for acute |
|
|
Pentazocine (TALWIN)
|
-oral low level analgestic
-used for those that are addicted -can't substitute to sustain addiction -may precipitate withdrawal in chronic users -may increase HR and BP |
|
|
Nalbuphine (NUBAINE)
|
-some analgestic but no cardiovascular or hypotension problems
|
|
|
Buprenorphine (BUPRENEX)
|
-mu-agaonist activity
-antagonist if given with morphine -good substitute for heroin maintenance -REDUCES CRAVING |
|
|
Antitussive agents
|
codeine
dextromethorphan benzonatate (related to procaine) |
|
|
*What would you use to treat biliary/renal colic?*
|
meperidine
|
|
|
*For moderate pain what drug would you choose?*
|
-codeine
-sometimes combined with aspirin or acetaminophen |
|
|
*What types of drugs would you use for diagnostic procedures?*
|
short acting
|
|
|
*Which drug is widely used as a substitue for heoin detoxification?*
|
methadone
|
|
|
*How do you reverse respiratory depression in opioid overdose?*
|
naloxone/nalemefene IV
|
|
|
*what opioid can you use to treat dyspnea from left ventricular failure?*
|
morphine
|
|
|
What is it about a nerve fiber that makes it more susceptible to an anesthetic?
|
1) Diameter: smaller diameter is more susceptible, large surface area:volume ratio
2) Frequency of Discharge: on open channel is more susceptible 3) Myelination: less myelination makes it more susceptible |
|
|
Which surface anesthetics limit antibiotics?
|
The ester linked anesthetics (PTC) are metabolized to a metabolite that interacts with the antibiotic sulfonamide
|
