Drugs for Anesthesia Flashcards
Stages of anesthesia
stage 1- analgesia stage- dec awareness of pain, may have some anmesia, decreased consciousness
stage 2- disinhibition. loss of consciousness to regular respiration, excitation and delirium may occur, amnesia occurs, vomiting and incontinence may occur
stage 3- surgical stage
regular respiration to respiratory arrest
unconscious, no reflexes. respiration and blood pressure maintained
stage 4- medullary paralysis stage- resp arrest to death. req’s mechanical and pharmacological support
conscious sedation
iv and/or local agents for brief procedures
balanced anesthesia
combination agents for major surgery
inhalable anesthetics
very controllable, readily reversible
disadvantage- not as fast or smooth as fixed agents
depress spontaneous and evoked neuronal activity
may involve actions at various ion channels- voltage gated K+ channels, GABAa receptor Cl- channel resulting in hyperpolarization
agents vary in potency, rate of induction, effect of cv fxn, degree of muscle relaxation produced
nitrous oxide
inhalable anesthetic, gaseous
insufficient potency for surgical anesthesia
analgesic activity
potential toxicity- chronic exposure can cause megaloblastic anemia
volatile inhalable anesthetic
halothane, enflurane, desflurane, isoflurane (most widely used), sevoflurane
pharmacokinetics of inhaled anesthetic
rate at which a given concentration of anesthetic in brain is reached depends on:
1) anesthetic concentration in inspired air- gasses flow from high pressure to low partial pressure–> high pp in lungs results in rapid achievement of anesthetic conc in blood
2) solubility- blood:gas partition coefficient (otswald coefficient)- solubility in blood
lower–> less soluble–> more rapid rise in pp in blood–> faster equilibration with brain
3) brain:blood partition coefficient- solubility in lipid- adequate for all agents, so doesn’t contribute to significant differences between clinically useful anesthetics
4) pulmonary ventilation- better ventilation=rapid onset of anesthetisa
5) pulmonary blood flow- partial pressure rises faster with low blood flow, slower with high blood flow
6) artereovenous concentration gradient- uptake into highly perfused tissue may decrease gas tension in mixed venous blood
7) elimination- reverse of process for uptake- less soluble–> faster elimination (based on blood:gas partition coefficient)
low solubility in blood
less soluble–> more rapid rise in pp in blood–> faster equilibration with brain–> reach anesthetic concentrations in brain more rapidly
elimination dependent on
blood:gas partition coefficient- less soluble–> faster elimination
minimum alveolar concentration (MAC)
concentration of anesthetic in inspired air at equilibrium when there is no response to skin inscision in 50% of pts
high MAC= less potent
nitrous oxide= highest MAC, never anesthetic
inhalable anesthetics that cause vasodilation and tachycardia
desflurane, isoflurane
causes decreased bp
inhalable anesthetic that causes vasodilation
sevoflurane
causes dec bp
inhalable anesthetic that depresses myocardium
nitrous oxide
halothane
enflurane
cause dec BP and dec CO
inhaled anesthetics with rapid rate of induction
nitrous oxide, sevoflurane, desflurane
lowest MAC
halothane
IV or fixed anesthetics
quick, easy, smooth induction
slow elimination
barbiturates
iv or fixed anesthetic
thiopental (redistributes to other tissues, can accumulate in adipose leading to long doa)
methohexital (used for ECT)
short and fast acting barbiturates
no analgesia
decrease in respiration at anesthetic doses
difficult to control level of anesthesia
propofol
iv or fixed anesthetic
actions at GABAa receptor (inc channel open time)
more rapid recovery than barbiturates due to faster hepatic metabolism
maintenance of anesthesia as well as induction
good for out patient because no hangover and those effects
less post op nausea and vomiting
can dec bp and blunts baroreceptor reflex
etomidate
iv
used for induction esp for pts at risk for hypotension
no analgesia
high incidence of nausea and vomiting, pain on injection, myoclonus
ketamine
iv anesthesia
dissociative anesthesia- noncompetitive antagonist at NMDA glutamate receptor ion channel
catatonia, analgesia, amnesia without loss of consciousness
short acting, pain on injection
cardiac stimulation
produces emergence phenomenon- hallucinations and disorientation, can be decreased by benzodiazepines so usually used with scmall children and pts at risk for hypotension or bronchospasm
experimental treatment for depression
midazolam
benzo
shortest acting benzo and least irritating for iv
used for maintenance of anesthesia because induction too slow to induce anesthesia
good amnestic effects
rapid onset and recovery
antagonist flumazenil can accelerate recovery
flumazenil
antagonist for midazolam
fentanyl
opioid
cna achieve anesthesia with sufficient dose or in combo with benzos
-excellent post op analgesia
useful in pts with compromised CV fxn
can cause truncal rigidity and impair ventilation
pre-anesthetic and adjunct medication reasons
inc rate of induction
decrease anxiety
decrease pre and postop pain
decrease side effects of general anesthetics
reduce amt of general anesthesia required
scopolamine
anticholinergics to decrease salivation and gut motility and antiemetic
neuromuscular blocking agents- paralytics
minimize anesthetic use
good for orthopedics
should not be used as a substitute for inadequate anesthesia
competitive neuromuscular blocking agents
at nicotinic ach receptors- antagonists
inhaled anesthetics and certain antibiotics increase potency of agent
isoquinolines-
-d-tubocurarine causes large increase in histamine release- 80 min duration
mivacurium - 10 min duration
rocuronium- steroid derivative: 20 min duration
depolarizing- nicotinic agonist
succinylcholine
stimulates motor end plate leading to persistent partial depolarization so that muscle cannot contract anymore
will cause initial fasciculation leading to muscle soreness
shortest duration of action
d-tubocurarine
competitive antagonist neuromuscular blocking agent
cause histamine release leading to hypotension and bronchospasm
drug interactions of neuromuscular blocking agents
mainly with aminoglycosides and isoflurane increase potency and duration of competitive antagonists
local anesthetics
block sensory transmission from a local area of body to cns
use- infiltration, field block, spinal block, topical application
local anesthetic mechanism
block nerve conduction by blocking voltage gated Na+ channels- preventing depolarization and conduction of cation potential
also blocks K+ channels at higher concentrations
higher frequency of stimualation- higher membrane potential-
higher anesthetic block
clinical effects of local anesthetics
- pain blocked first along pre and post ganglionic sym fibers (Adelta, B and C fibers)
- then cold, warmth, touch, deep pressure (C fibers)
- then muscle tone, proprioception, and motor fxn (Aalpha, Abeta, A y fibers)
(may be different experimentally)
cocaine
esters, local anesthetics-
- vasoconstrictor, medium acting, used topically for nasal and ophthalmic procedures bc penetrates membranes- minimizes bleeding
benzocaine
ester, local anesthetic
surface use only, lipophilic
used for burns, bites, hemorrhoids, catheter and endoscope palcement
lidocaine
amides, local anesthetic
most widely used, medium acting
doa ~2 hrs, when administered with epinephrine (to vasoconstrict to minimize diffusion)
Mepivicaine
medium acting, amide, local anesthetic
vasoconstricts, longer acting than lidocaine
bupivicaine and ropivicaine
longer acting (3-15 hrs) ropivicaine- less cardiotoxic
amides
local anesthetics
used for infiltration, peripheral nerve block, epidural block
potency of local anesthetics affected by
pH
-local anesthetics are weak bases, and the cation interacts with Na+ channel, but unprotonated form is req’d to penetrate membrane to gain access to channel inside cell membrane
potency decreased at low pH
duration of action of local anesthetic proportional to
time the drug is in contact with nerve
use vasoconstrictor (epinephrine) to increase duration and reduce systemic absorption
CNS adverse effects for local anesthetics
low concentrations- sleepiness, light headedness, visual and auditory disturbance, metallic taste
high levels- nystagmus, myoclonus, leading to tonic-clonic seizures (esp esters)
direct neurotoxicity with spinal administration due to pooling in cauda equina
CV adverse effects of local anesthetics
depression of myocardial conduction and peripheral vascular tone
hypotension
cocaine- hypertension, arrhythmias, myocardial failure
allergic reaction of local anesthetics in
esters
due to p-aminobenzoic acid metabolites
cauda equina syndrome
neural injury due to localized toxicity from continuous spinal anesthesia
most likely to occur with lidocaine
transient neurologic symptoms
transient paina fter spinal and epidural anesthesia w/o loss of sensation, motor, or bowel fxn
most common with lidocaine
pharmacokinetics for local anesthetic
readily diffuse for site of injxn and cause systemic effects
metabolism of esters
rapidly hydrolyzed by pseudocholinesterases
metabolism of amides
in liver and or blood followed by urinary excretion
