Exam 1 Flashcards
Local Anesthetics (LA)
1-structures
2-pH levels for LA
3-neuron sensitivity ot LA block
1-
- lipophilic domain—entry of LA into axon
- intermediate chain—amides=metabolize in liver (long acting) &&& esters=metabolize in blood (short acting)
- hydrophilic N terminal= inhibitory Na Channels
2-more acidic= more charged LAs are
but the LA must be uncharged for it to enter into neurons
once in the neruon it becomes charged again, causing Na channel block
***channels more active= greater inhibition of LAs
3-sensitivity isn’t equal
small= first to be blocked (sensory—convey pain)
large= last to be blcoked (motor)
high frequency (sensory)= preferential to low frequency (motor)
*fast first, slow last &&& small first, big last
*size matters
*if both axons are same size the myelinated ones are blocked first (bc there is less resistance)
1-surface anesthesia
2-infiltration/field block anesthesia
3-nerve block anesthesia
4-intravenous regional anesthesia
5-epidural block
6-spinal block
1-topical—very little anesthesia
2-subcutaneous injection—numbs distal to injection
3-peripheral nerves or plexus—less LA needed (group)
4-injection of LA into vein w/ tight flow
5-space w/in vertebral canal but superficial to dural sac
- *-not limited to injection site of L2**
- less risk for puncture headache
- catheter for long term pain reduction
6-CSF in subarachnoid space
- limited to injection site below term of spinal cord L2
- less time/discomfort
- less LA needed—bc no metablosim in CSF
- intense nerve blocks
1-absorption
2-distribution
3-metablosim
4-excretion
1-dependent upon: site of injection, coadmin w/ vasoconstrictors (epi & levonordefrin)
—vasoconstrictors are given so drugs stay where its supposed too—if given w/in BV bundle it will leave the body quickly
2-given to all tissues—passes BB barrier= CNS side effects
- esters metabloized in plama= too fast to be redis at low doses
- amides taken up by everything but muscle & gut
- amides highly bound to plasma proteins—affected by cancer & etc
3-amides metabolized in liver (CYP 3A4) & esters by plasma esterases
-CSF doesnt have esterase—so less LA needed for spinal block —so give esters
4-water soluble metabolizes taken away in urine
acidification of urine promote excretion
1-epinephrine
2-side effects
3-CNS
1-helps LA stay longer so less LA needed
- dec rate of absorption & prolonged anesthesia via vasocontriction at site
- reduces amt of LA needed to reach effect
- can vasodilate skeletal muscle=inc toxicity
- shouldnt be given at peripheral sites= hemostasis= bleeding
2-adverse effects bc of accidental intravascular injection of LA
3-seizures then depression
- *low conc**- sleepiness, dizziness, restlessnes, euphoria
- *high conc**- shivering—CNS depression= resp failure->death
- restlessness & tremor—tonic convulsions
- barbiturates treat convulsions
1-cardio system
2-peripheral nervous system
3-blood
4-allergic reactions
5-pregnancy
1-minimal changes in electrical excitability, conduction rate & force of contraction
- @ high levels= depression of cardiac excitability to collapse
- all LA are vasodilators except cocaine
- Bupivacaine= cardiotoxic= hypotension & arrhythmias
2-prolonged sensory & motor deficits (prilocaine)
3-high doses of prilocaine or benzocaine=
conversion of hemoglobin to methemoglobin= O2 not carried causing anemia
4-allergic reactions—mainly ester LA
allergic dermatitis & asthma attacks
5-LA can cross placental barrier…so CNS, peripheral & cardiac can be affected
Amides
1-lidocaine
2-bupivacaine
3-mepivacaine
4-prilocaine
5-articaine
1-most widely used LA
- for all types of local anesthesia
- good diffusion & penetration
2-longest duration of action of all LA (good for long term procedures)
- more sensory than motor block so its useful in analgesia during labor
- not needed for intravenous anesthesia bc of cardiotoxic potential (blocks Cardiac Ca channels)
3-similar to lidocaine in potency & toxicity
- not topical
- if sulfite allergies—3% mepivacaine solution w/o epi in it
4-less toxic & effective than lidocaine
- if sulfite allergies—4% prilocaine solution w/o epi in it
- infiltration anesthesia—not topical
- if intravascular= anemia by methemoglobin
5-metabolized in 2 places
-rapid metabolized in plasma & the rest in the liver
Esters
1-benzocaine
2-cocaine hydrochloride
1-topical for surface anesthesia—skin & mucous
- toxicity bc of methemoglobin, but toxicity low
- poor H20 solubility, not well absorbed
2-topical only
- drug well absorbed via mucous membranes
- high abuse potential
- only LA that is vasoconstrictive
- low toxicity= nervousness/convulsions/cardiac failure
- if w/ epi= inc cardiac toxicity
Anesthetic state
1-amnesia
2-immobility in response to noxious stimulation
3-attenuation of autonomic response to noxious
3a-balance anesthesia
4-preop surgery
5-induction & maintenance of anesthesia
6-post op recovery
1-depressing neuronal activity in hippocampus
2-inhibiting conscious brain acitivity or reflexes
—absolute relaxation
3-sensing of pain the autonomic system will inc HR & BP
- combo drug therapy to reduce neuronal activity
- sensory neurons sense pain, causing reflex of BP inc
3a-multiple classes of drugs to get certain anesthesia
-relaxers, opoids, N2O, inhaled IV etc
4-serotonin receptor antagonist & histamine antagonist to prevent vomiting & acid reflux—reduce regurgitation (bc of lower esophageal sphincter)
5-intravenous GAs are faster acting than inhaled
-some inhaled = unpleasant orders but inhaled are used for maintenance
“balanced anesthesia”
6-hypertensive
- emergence excitement—restless, crying, moaning
- hypothermia—give NSAIDS
1-inhaled GAs
2-pharmacokinetics
a-high water solubility
b-low water solubility
c-blood/gas partition coefficient
3-N2O speed of induction vs Halothane
4-potency
1-N2O is a gas—others are voltaile
2-effect of gas is proportional to conc of CNS
- rate of GA diffusion= rate of aesthetic induction/recovery
- inhaled GA rate of recovery= imp—faster effects of inhaled GA wear off post-surgery, faster the patient can recover & spend less time in recovery
2a-slow induction—long time for GA to fully dissolve in blood before entering CNS
2b-rapid induction—GA not soluble in blood and goes from blood to CNS
2c-measure of water solubility—GA in blood/ GA in lung
3-N2O= poorly sobule in blood---rapid inudction(low#) Halothane= very soluble in blood= slow induction(high#)
4-Minimum alveolar concentration—conc of inhaled GA in 50% of patients to not respond to pain (pin prick)
- proportional to lipid solubility
- inc speed of induction= dec H20 solubility
- N20= doesnt take long to saturate blood to brain
- Halothane= takes long to saturate bc more soluble
1-Nitrous Oxide (N2O)
1a-acture exposure
1b-chronic exposure
2-isoflurane
3-sevoflurane
1-weak anesthetic—rapid inudction & recovery
20% inhaled air= analgesia
30-80% inhaled air= sedation
-analgesic can be abolished with opoid antagonist—so uses opoid receptors
-colorless & odorless
-used to relieve anxiety
1a-depresses ventilary response to hypoxia
- air pockets expand
- change BP
- doesnt trigger malig hyperthermia
1b- infertility & abortion
- blood dyscrasias
- neuro deficits
- dec vit B12—reduced myelin & nucleic acids
2-inhaled GA
- eliminated unchanged via the lungs (not really metabolized)
- dec in BP, vasodilation only
- tachycardia
- dec ventilary= hypoxia
3-reacts w/ dried out soda lime to produce CO—airway burns possible fire
- non-irritating to airways & induce anesthesia
- eliminated unchanged via lungs (not really metabolized)
- dec in BP, vasodilation
- short term renal damage
1-pharmacodynamics
2-pharmacokinetics
3-pharmacotherapeutics
4-pharmaceutics
5-toxicology
1-branch of pharm that deals w/ biochemical & physiological effects of drugs & mechansms underlying effects
2-deals w/ quantitative description of the time course for absorption, distribution, metabolism & excretion of drugs
3-deals w/ use of drugs in tx of specific disease
4-chemistry, compounding, formulation & dosage
5-adverse effects of drugs & other agents
1- actions of body
2-actions of the drug on the body
3-ADME overview
4-narrow therapeutic
5-wide therapeutic
1-ADME—absorption, distribution, metabolism, & excretion
2-therapeutic effects, side effects, & toxic effects
3-oral tablet taken, drug is dissolved, absorbed into GI, goes into plasma, bound to drug or free drug (only unbound)
drug can be metabolized & have some sort of effect
4-chemo agents & general anesthetics IV
5-polyethylene glycol (miralax)
1-bioavailability
2-factors that determine blood levels of a drug
3-enteral
4-parenteral (injection)
5-topical
6-inhalation
1-fraction or percentage of drug dose that reaches systemic circulation—determined from area under the time vs plasma conc curve
2-amt given, route of admin, rate & extent of absorption (epi & levon reduce these in anesthetic), distribution to tissues, & rate/extent of excretion
3-drug intro at some part of the GI tract (SI)
oral ingestion
4-intravenous—no absorption, very rapid of high BP
- *intraarterial**—not very common, invasive
- *intramuscular**—drugs w/ slow/erratic absorption from GI
- *subcutaneous**—<2 mL vol given
- *intrathecal**—direct injection into subaracnoid
5-skin, more keratinized than mucous membranes—less systemic—keratinized skin= less likely it’ll absorb
-mucous membranes= systemic
6-general anesthetics—asthma medications
1-absorption of drugs
2-passive, paracellular transport
3-passive diffusion
4-active, facilitated diffusion
5-active, drug transport
1-for drug to be absorbed must pass through intracellular gaps or cell membrane
2-limited to small sized molecules
3-most common drug transport & greatly affected by pH
- —materials move down conc
- –small quicker than large
- –lipid solubility
- –pH effects- only non-ionized forms can cross membranes
4-no input of energy, requires conc gradient—glucose w/ GLUT4 transporters in muscles cells
5-5-fluorouracil chemo agent
1-acidic drugs
2-basic drugs
3-pKa
4- influencing drug absorption
1-aspirin—non-ionized (absorbed) at low pH & ionized (not absorbed) at high pH
2-codeine—non-ionized (absorbed) at high pH & ionized (not absorbed) at low pH
3-pKa is the pH at which half the drug is in ionized form.
pKa= pH + log (protonated drug)/(non-protonated drug)
4-H20 solubility, area of absorbing
Blood flow to area—epi & levono = vasoconstrictors & dec BF
rate of gastric emptying & transity
presence of food, lipids or drugs
1-oral/nasal mucosa absorption
2-stomach abosrption
3-small intestines absorptions
4-formulations
5-BB barrier
6-placental barrier
7-binding to plasma proteins
8-sites of loss
1-neutral drugs/weak bases are absorbed
-first pass metabolism by the liver
2-acidic environment—favors ionization of most drugs
-bc of small surface area & low pH, few drugs absorbed from stomach
3-large pH gradient—acidic & basic—portal hepatic circulation delivers drugs to liver (main metabolism)
-some drugs can be metabolized on first pass (first pass effect)
4-eneteric coating & sustained release
5-prevents passage of large or ionized molecules—less of a barrier in kids as in adults
6-similar to BB barrier but less selective
7-albumin is the most imp. one—bound drug cant distribute to tissues
8-fat & GI & others
1-Drug A= more potent than Drug B (Drug A bc takes less nM to do the same amt Drug B—less needed to have a given response)
Drug A & B= similar efficacies
Drug A= more potent & more efficacious than Drug C (drug A taller)
