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-liver
2-kidney
3-fat
4-brain
5-fetus
6-teeth, gingiva & saliva
7-volume distribution
1-large BF, drug metabolism, portal-hepatic first pass
2-high BG, site of excretion
3-low BF, slow accum of lipid soluble drugs, site of loss
4-BB barrier, small lipid soluble can cross
5-placental barrier isnt stong
6-applied topically or injected, pH can affect
7-not true volume—volume which drug would have to be dissolved to acct for all drug at conc in plasma
= amt of drug in body/concentration in plasma
1-drug metabolism
2-microsomal oxidation of drugs (phase 1)
3-non-microsomal
4-reductions
5-hydrolyses
6-conjugation reactions (phase 2)
1-active drug (non-polar) then metabolized into inactive drug (polar)
2-“pinched off”—pieces of smooth ER
highest conc in liver
contain mixed function oxidases & cyto P450
induction & inhibition of microsomal drug metabolizing
3-some oxidative enzymes arent associated
in hepatic & extrahepatic
4-microsomal & non-microsomal
5-mostly non-microsomal
6-coupling of drugs or metabolites to small polar molecules
-microsomal & non-microsomal
1-kinetics
2-factors affecting metabolism
renal excretion
3-filtration
4-tubular secretion
5-reabsoprtion
6-biliary & fecal excretion
1-determined by conc of drug in relation to the saturation of the metabolic enzymes
2-age, disease, nutrition, genetic factors & duration of tx
3-low MW drugs are readily filtered
- drug bound to plasma protein isnt excreted
- alterations in GFR can affect drug excretion
4-active process
- system for organic acids & base
- competition of drugs for transport systems
5-passive
- lipophilic are reabsorbed—hydrophilic remain in tubules
- pH effects on acids/bases—acidic urine favors excretion of basic drugs, basic urine favors excretion of acidic drugs
6-secretion of conjugates in bile
enterohepatic cycling
1-clearance
2-kinetics of drug elimination
3-plateau principle
1-rate of elimination/ concentration
-elimination of the drug from the blood by all routes
2-elimination of most drugs= 1st order kinetics some are 0 order kinetics
1st order elimination= depends on conc of drug that is present, exponential, fixed half life
0 order elimination= rate of metabolism doesnt depend on conc of drug, linear, no fixed half life
3-time course of drug action w/ multiple dosing regimens
- double the dose—inc conc but will take a while to reach the plateau
- *loading dose**- give a relatively high dose of drug to achieve blood level
- *maintenance dose**- once high level, cut back to lower dose to maintain blood level
1-agonist
2-competitive antagonism
3-affinity
4-intrinsic activity
5-potency
6-efficacy
1-drug interacts w/ receptors to activate mechanisms/transduction
—affinity & intrinsic activity
2-binds to the same site but has different reation
prevents agonist from binding to the receptor
—affinity & no intrinsic activity
3-propensity of drug to bind to a given receptor
4-describes ability of a drug to initiate response—activates receptor or initiates specific signaling
5-refers to amt of drug needed to produce a given effect
6-refers to ability of a drug to produce an effect w/o regard to conc
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)
1-graded dose response relationship
2-threshold dose
3-potency
4-maximal effect (efficacy)
5-slope
6-bio variation
7-quantal dose response relationship
1-shows intensity of a drug effect in a subject
2-dose below which no effect is seen
3-position of curve on X axis—pharmacokinetics of drug & ability of drug to bind to receptor & produce an effect
4-determined by both pharmacokinetics of drug & ability to produce an effect
5-varying the dose will affect response
very steep slope= slight inc in drug dose= large inc in response
shallow slope= small inc in dose= less effect on intensity
6-give same dose to diff subjects= may have diff intensities
-diff doses of a drug may be needed to produce same intensity in diff people
7-% of subjects in a pop that exhibit a response of a given intensity as a function of drug dose
- compare effects of diff drugs in a population
- comparing doses of a single drug that will produce different effects in a pop
1-intravenous GAs
2-propofol
3-etomidate
4-ketamine
1-fast acting drugs—surgical anesthesia
- highly lipophilic
- goes to CNS & spinal cord
2-MJ death
- heavy sedation—only used if heart is healthy & isnt high TAG level
- not H20 soluble
- very fatty
- enhanced GABA
- dec in BP, vasodilation & contractility
- *-dec ventilation**
- *-anti-emetic**—*widely used bc of this
3-intravenous GA
-same action of propofol except it is emetic
4-water soluble—comes concentrated
analgesia —doesn’t need an opoid
battlefield use
-competitive antagonist & inhibition of Na channels
-no pain on injection
-hallucinations= drug of abuse “special k”
-modest dec in ventilation rate= bronchodilator
-inc BP, inc CO, inc HR…good for pts w/ hypotension
-frequent peeing
