anesthetics

Question 1

measurement of anesthetic potency

Answer 1

potency=concentration of anesthetic that prevents movement in response to pain

for inhaled anesthetics, minimal alveolar concentration (MAC)- prevents movement in response to pain of 50% of subjects

Question 2

mechanism of anesthesia

Answer 2

multicomponent common effects by all anesthetics include membrane hyperpolarization, and effects on synaptic function–> inhibitory neurotransmission is increased and excitatory neurotransmission is reduced

likely molecular target: GABAa receptors, GABA- regulated chloride channel, function is enhanced by most but not all anesthetics, anesthetics produce allosteric interactions; not a direct effect on GABA binding

NMDA receptors, Glutamate- regulated cation channel

Question 3

stages of anesthesia

Answer 3

premedication, induction (needs to be non frightening, usually IV anesthetic is used, emergency inhaled)

Question 4

parenterally administered anesthetics

Answer 4

generalities: used to facilitate rapid induction of anesthesia and have replaced inhalation as the preferred method of anesthesia induction

all are hydrophobic and a single IV bolus results in high concentration in brain and sp cd within a single circulation time–> rapid induction of anesthesia

subsequently, blood levels drop and the anesthetic redistributes back into the blood from the brain–> in other tissues where its slowly released and metabolized (t.5 of the anesthetic in the body and the duration of action are not the same)

Barbituates and sodium thiopental (10-30 seconds) duration of action= 10 minutes

Question 5

sodium thiopental

Answer 5

used to induce anesthesia, produces uncosciousness in seconds, duration of action is 10 minutes

has a long half life (12 hours) so hung over after anesthesia has worn off. Dose should be reduced if premedicated with other CNS depressants including opiates, benzodiazepines and alpha 2 agonists

Intra arterial injection can produce sever inflammation and can even be necrotic so this is not done, can be administered to peds rectally

Question 6

sodium thiopental side effects

Answer 6

CNS- reduces cerebral oxygen utilization and as a consequence reduces cerebral blood flow and intracranial pressure

CV- produces vasodilation (mainly venous side), can produce hypotension, with impaired ability to compensate venodilation, not CI in patients with coronary artery disease bc demand is reduced, no arrythmogenic effects

respiratory depression

Question 7

propofol

Answer 7

onset and duration of anesthesia are the same as barbituates, maintains and induces anesthesia, is used to maintain and induce anesthesia

antimimetic: advanatge to avoid nauseated following surgery

shorter half life than thiopental: used when you dont want hangover, rapidly metabolized in liver and in lungs to inactive metabolite excreted in urine

Question 8

SE of propofol

Answer 8

pain upon injection, can be given with lidocaine or administered into larger veins

prodrug for popofol, fospropofol (watersoluble and less paiful on injection)

can produce excitation during induction

CNS: same as barbituates
CV: more severe decrease in BP than thiopental, produces both vasodilation and depression of myocardial contractility, age related, blunts baroreceptors (use with caution in patients with intolerace of decreased BP_

more respiratory dpression than thiopental

propofol has demonstrated abuse liability

Question 9

etomidate

Answer 9

induces anesthesia in pts at risk for hypotension
high incidence of pain on injection and myclonus (quick jerk)
Pain is dealt with using lidocain and myoclonus is reduced premedication with benzodiazepines or opiates

Question 10

etomidate SE

Answer 10

CNS: like thiopental
CV: less than thiopental and propofol which is the major advantage of etomidate
produces a small increase in HR with little to no decrease in BP
less respiratory depression than thiopental

Drawbacks: significantly more nausea and vomiting than thiopental

increased post-surgical mortality due to suppression of the adrenocortical stress response, primarily when the anasthetic has been given for a prolonged period of time. therefore only used to induce anesthesia in patients prone to hemodynamic problems

Question 11

ketamine

Answer 11

produces dissociative anesthesia

Characterized by: progound analgesia, unresponsiveness to commands even though eyes can be open, amnesia (incomplete unless used with benzodiazepines) spontaneous respiration, typically administed iv but can also be used via intramuscular, oral and rectal routes

Advantages: profound analgesia, very little respiratory depression, bronchodialation

Question 12

ketamine SE

Answer 12

produces nystagmus, salivation lacrimation spontaneuous limb movements and increased muscle tone

increased intracranial pressure

emergence delerium hallucinations, vivd dreams, illusions, not really used, can be used in combo with benzodiazepines to reduce symptoms

increased BP due to indirect sympathomimetic activity

usefulness: reserved for pts with bronchospasm, children undergoing short painful procedures

Question 13

midazolam

Answer 13

short acting benzodiazepine used for conscious sedation, anxiolysis and amnesia during minor surgical procedures

used as an induction agent, used as an adjuct during regional anesthesia, anti anxiety effects make it useful preop

slower induction time and longer duration than thiopental and propofol

metabolized by hyrdroxylation to an active metabolite

Question 14

SE of midazolam

Answer 14

has been associated with respiratory depression and respiratory arrest especially when used IV to produce conscious sedation

should be used in caution in pts with NMJ diseases, parkinsons bipolar

CV: like thiopental

effects reversed with FLUMAZENIL

Question 15

inhalation anesthetics general consideration

Answer 15

very low therapeutic indicies LD50 2-4

pharmacokinetics are unique and important

all the compounds are easily vaporized liquids or gases at room temp thus they can be administered by inhalation

rather than a concentration gradient across a barrier, the partial pressure of anesthetics determines transmembrane movement

equilibrium is reached when partial pressures are the same in adjacent compartments (not necessarily equivalent to equal concentration bc solubility can differ)

Question 16

3 partition coefficients to consider in inhaled anesthetics

Answer 16

blood:gas partition coefficient (determines absorption in lung; inhaled anesthetics are taken into body through gas exchange at the alveoli): measure of the anesthetic in an aqueous versus gaseous environment, low blood:gas coefficient–> rapid equilibration in blood bc there is low solubility in blood, since the concentration in brain cannot rise unless the concentration in blood concentration rises rate of induction of anesthesia is inversely related to the blood gas coefficient

Brain:blood (determines distribution to the brain, which is the site of action)

Fat:blood (determines redistribution and recovery from anestheic effect)

Question 17

factors that affect induction

Answer 17

anesthetic partial pressure (Fi) in the inspired air (affects the max partial pressure of the gas at the alveoli Fa), ultimately affects the partial pressure in the blood, the rate of transfer will increase as the concentration is increased therefore rapid induction can be achieved with higher concentrations the faster Fa/Fi approaches 1 the faster anesthesia will occur

Alveolar ventilation: directly controls Fa/Fi: increased ventilation increases the rate of rise of Fa/Fi. Magnitude of effect of ventilation is dependent on blood gas partitiion coefficient moderately blood soluble anesthetics are affected more than low soluble agents

Pulmonary blood flow (determined by cardiac output)- increased blood flow slows the rate of rise in Fa/Fi–> decreases the rate of induction of anesthesia, effect is most dramatic for moderately soluble anesthetics

Question 18

factors that affect tissue distribution

Answer 18

Blood: tissue partition coefficient

tissue blood perfusion; organs with highest perfusion include brain, heart liver, kidneys spanchnic beds

brain-high partition coefficient and high perfusion compared to fat with high partition coefficient but low perfusion

Question 19

factors that affect anesthetic elimination (rate of recovery from anesthesia)

Answer 19

reverse of induction- blood:gas partition coefficient is the most important determinant- low solubility anesthetics are eliminated fastest

duration of exposure: bc of tissue accumulation–longer the exposure the longer it takes to eliminate the anesthetic

ventilation

metabolism- hepatic metabolism can contribute to recovery from some older anesthetic not a desirable property

Question 20

malignant hyperthermia

Answer 20

serious adverse effect of gaseous anesthetic exposure, rare but potentially fatal

heritable, pockets of individuals

skeletal muscle disorder, triggered by anesthetic

Consists of muscle rigidit hyperthermia, tachycardia, hyoercapnia, hyperkalemia metabolic acidosis

Question 21

isoflurane

Answer 21

moderate blood:gas PC, moderate rates of induction and recovery, excreted unchanded in expired air

inhaled anesthetic in us and worldwide

can be used to induce and maintain anesthesia, but is mostly used for maintanence

often used with NO to reduce amount needed

Question 22

isoflurane SE

Answer 22

airway irritant, coughing, decreases tidal volume, increases respiratory rate, all anesthetics depress respiration in the CNS center and increase PaCO2

Myocardial depression, results in decrease in BP, arrythmias, cerebral vessel vasodilation can result in increased intracranial pressure

Question 23

desflurane

Answer 23

Volatile liquid at room temp, very low solubility in blood:gas partition coefficient) therefore induction and recovery are rapid

excreted unchanged in expired air

used for outpatient surgeries/maintenance not used to induce because of respiratory irritation

skeletal muscle relaxation
SE: relative to isoflurane, Cv same, Resp: worse as an irritant can produce bronchospasm

Question 24

sevoflurane

Answer 24

Very low blood:gas partition C
5% administered dose is metabolized to fluoride ion in the liver, there is some concern that can cause renal damgage

degraded to compund A by absobants in the anesthesia administration administration apparatus

Uses: very popular in and out patient, can be used to induce and maintain, children and adults, NOT a respiratory irritant

SE: similar to isoflurane not as much as respiratory depression

Question 25

nitrous oxide

Answer 25

a gas not volatile, very insoluble in blood, rapidly equilibrates, uptake from the air results in increased concentration of other anesthetics, so its useful as an agent to enhance induction with isoflurane

during emergence can dilute O2 so pts can breathe 100% O2, 99% excretion via lungs

Clinical uses weak anesthetics, cannot get enough into the air to produce MAC, good sedation and analgesia at 50% concentration,

CX in pneumo, negative inotrope and sympathomimetic so CO is preserved

REspiratory effects are minimal except oxygen dilution, abuse liability,

–> megablastic anemia

Question 26

local anesthetics

Answer 26

bind reversible to a site within the pore of voltage gated Na channel, blocking sodium entry when the channel is opened, all are weak bases bind in the BH+ form but need to be in unionized form to cross nerve cell membrane (amides are metabolized by the liver, esters metabolized by plasma cholinesterases)

Na channel-> AP initiation and generation, local anesthetics, reversibly block nerve conduction, cause sensory loss and motor paralysis

applied to skin mucous membranes or ulcerated surfaces, ophthalmic - produces anesthesia of cornea and conjunctiva

local infiltration- injecting sites (no consideration for nerve course

nerve block- injection around individual nerves or plexi (including sensory nerves from the operative site)

Question 27

local anesthetic effect are frequency and voltage dependent

Answer 27

drugs gain access to the channel binding site more easily when the channel is open (BH+ can slip in), have higher affinity for the inactive channel than unopened channel, resting nerves are less sensitive to local anesthetic block, resting nerves are less sensitive to local anesthetic block, nerves with positive membrane potential more sensative to block

efficacy decreased when tissue pH is decreased such as during infection or inflammation, too little drug can get to site of action (too little is in B form)

co administered with vasoconstrictors (decreases the rate of absorption into the circulation) increases depth and duration of anesthesia, less potential for systemic toxicity, epineohrine and phenylephrine

autonomic fibers and small non-myelinated C fibers are blocked fitst

Question 28

order of block of nerve conduction

Answer 28

pain-cold-warmth-touch-deep pressure-motor

recovery of function occurs in reverse order

Question 29

toxicity and adverse effects of local anesthetic

Answer 29

interfere with the function of all organs in which conduction or transmission of impulses occurs (CNS ganglia, NMJ, muscle)

systemic toxic reactions are related to high concentration of local anesthetic in the circulation, intraneuronal injection can produce irreversible damage

S enantiomer is less toxic than R enantiomers

Question 30

CNS toxicity local effects

Answer 30

CNS stimulation is seen first (due to depression of cortical inhibitory neurons restlessness, tremors, convulsions)

CNS depression at higher doses (drowsiness, general depression, respiratory depression, and potentially respiratory arrest

Death associated with sever toxicity usually caused by respiratory depression

Question 31

CV toxicity local anesthetics

Answer 31

general depression of the CV system usually seen after CNS affects develop–decreases myocardial contractility which lowers BP, decreases rate of conduction- decreases HR, AV block, arrythmias, arteriorlar vasodilation, can develop hypotension and arrythmias leading to cardiac arrest

Question 32

hypersensitivity

Answer 32

hypersensitivity- rare individuals exhibit hypersensitivity (allergic dermatitis or anaphylactic-type reaction) must distinguish from effect of co administered vasoconstricotors more frequent with ester local anesthetics, sometime associated with preservatives

Question 33

metabolism of local anesthetics

Answer 33

toxicity depends on the balance between the rate of absorption into the systemic circulation and elimination

ester local anesthetics inactivated by plasma esterases

Amide local anesthetics metabolized in the liver, used in caution in pts with sever livdr disease

Question 34

cocaine

Answer 34

an ester local anesthetic, but also blocks uptake of norepinephrine into presynaptic adrenergic nerves. Potent vasoconstrictor, used for topical anesthesia of the upper respiratory tract

Question 35

procaine

Answer 35

ester, short acting, first synthetic local anesthetic

still used for infiltration

low potentcy slow onset short duration of action

Question 36

tetracaine

Answer 36

ester, long acting ester local anesthetic
more potent and longer duration of action that procain

widely used in spinal anesthesia and in topical and ophthalmic preps not for peripheral nerve block

Question 37

benzocaine

Answer 37

anesthetic with low water solubility, therefore too slowly absorbed when applied topically to be toxic

applied to wounds and ulcerated surfaces

Question 38

lidocaine

Answer 38

amide, intermediate duration of action, produces faster more intense, longer lasting, extensive

used with vasoconstrictorys to decrease toxicity

Question 39

bupivicaine

Answer 39

long acting amide, capable of producing prolonged anesthesia, provides more sensory than motor block

more cardiotoxic than lidocain

levobupivicaine that is less toxic

Question 40

ropivicaine

Answer 40

long acting amide local anesthetic (S enantiomer), anesthetic similar to bupivicaine with less cardiotoxicity, suitable for epidural and regional anesthesia

even more motor-sparing than bupivicaine