Exam 1 Flashcards
study of how drugs alter the transmission of information in the nervous system, by altering neurotransmission drugs can treat disease and change behavior, information transmission is BOTH electrical and chemical
neuropharmacology
transmission WITHIN a neuron is _________ (electrical/chemical)
electrical (action potential)
transmission BETWEEN neurons is ________ (electrical/chemical)
chemical (synaptic transmission)
almost every neuron has what 3 parts?
axon, cell body, dendrites
part of a neuron that receives input from other neurons (excitatory and inhibitory inputs and the balance between the types of inputs)
dendrites
what is the principle excitatory neurotransmitter?
glutamate
what is the principle inhibitory neurotransmitter?
GABA
part of a neuron that has the myelin sheath, myelin helps information travel
axon
part of a neuron right between cell body and axon
axon hillock
part of a neuron where neurotransmitters are released
presynaptic terminals (axon buttons)
embedded in cell membranes, provide passageway from out to in
ion channels
type of ion channel that opens when a ligand (neurotransmitter or drug for example)
ligand-gated
type of ion channel that opens when there is a change in membrane potential
voltage-gated
type of ion channel that opens when a high energy phosphate is added to the channel, phosphate disturbs interactions between amino acids allowing the protein/channel to be in open conformation
phosphorylation-gated
this involves the disturbance of the resting potential to a threshold that initiates propagation of the disturbance along the length of the axon
electrical transmission
K+ channels are always _________ (open/closed) at the resting membrane potential
open to allow K+ to move freely both in and out equally
what happens when a Na+ channel opens (movement of Na+) and what happens to charge of the neuron?
Na+ goes into the cell because more found on the outside, makes neuron more positive
what happens when a Ca2+ channel opens and what happens to charge of the neuron?
Ca2+ goes into the cell because more found outside the cell, makes the neuron more positive
what happens when K+ channels are open and what happens to charge of the neuron?
K+ leaves the cell because more K+ inside the cell, makes the neuron more negative
what happens when Cl- channels are open and what happens to charge of the neuron?
Cl- goes into the cell because more found on the outside of the cell, makes the neuron more negative
what channel corrects for any “leakiness” in Na+ channels?
Na+/K+ symporter
small, transient changes in membrane potential produced by some stimulus
local potentials
term used when a stimulus makes the membrane potential more positive, positive charge going into the neuron, results from opening of Na+ channels and influx of Na+
depolarization
depolarization produced by a neurotransmitter at a synapse
excitatory postsynaptic potential (EPSP), depolarization = excitation because getting closer to threshold of action potential
term used when a stimulus makes the membrane potential more negative, K+ going out or Cl- going in, results from opening of Cl- channels and influx of Cl- OR opening of gated K+ channels and efflux of K+
hyperpolarization
hyperpolarization produced by a neurotransmitter at a synapse
inhibitory postsynaptic potential (IPSP), hyperpolarization = inhibition because going farther from threshold of action potential
summation of inputs from the SAME presynaptic terminal, summed over TIME
temporal summation
summation of inputs from DISTINCT presynaptic terminals, inputs are summed over SPACE
spatial summation
if summation of local potentials at the axon hillock reaches the ___________ of -50 mV (for most neurons) an action potential is generated
threshold
rapid change in membrane potential that is propagated down the length of the axon
action potential
at -50 mV, large numbers of voltage-gated/fast Na+ channels open causing the membrane potential to quickly rise to +40 mV, this is what phase of the action potential?
rising phase
this period of the action potential happens after the neuron reaches +40 mV and the Na+ channels close and cannot reopen for a period of time (can’t be stimulated anymore)
absolute refractory period
the change in potential that occurs in the rising phase opens voltage-gated K+ channels resulting in the return of the membrane potential to a level slightly more negative than the resting potential of -70 mV, not impossible to fire again but harder because goes beyond -70 mV rest, what is this period called?
relative refractory period
what happens at the end of an action potential?
all voltage-gated channels close and the neuron returns to resting potential
greater stimulus _______ (does/doesn’t) mean greater size of action potential
doesn’t –> means greater FREQUENCY of action potentials
action potentials open _______-gated Ca2+ channels and Ca2+ goes ________ (into/out of) axon terminal
voltage, into
neurotransmitter release is exocytosis that is ______ dependent (what ion?)
Ca2+
presynaptic G-protein coupled receptors _______ (promote/inhibit) further neurotransmitter release after the initial Ca2+ dependent neurotransmitter release, these are drug targets
inhibit
this structure transports neurotransmitter out of the synapse back into the presynaptic terminal and what is this process called (drug target)?
neurotransmitter transporter, reuptake
there are ________ in some synapses that metabolize neurotransmitters into unusable parts
enzymes
receptors that are ion channels and are extracellular (embedded in the cell), ligand-gated
ionotropic receptors
receptors that are biochemically coupled to effectors and second messengers, have enzymatic activity and are extracellular (embedded in cell)
metabotropic receptors
effector molecule, second messenger, altered activity of Gs proteins (alpha subunit)
adenylyl cyclase (stimulated), cAMP (increased), increased PKA (protein kinase A) activity
effector molecule, second messenger, altered activity of Gi proteins (alpha subunit)
adenylyl cyclase (inhibited), cAMP (decreased), decreased PKA (protein kinase A) activity
effector molecule, second messenger, altered activity of Gq proteins (alpha subunit)
phospholipase C (stimulated), diacylglycerol (DAG) for increased PKC (protein kinase C) activity, inositol trisphosphate (IP3) for Ca2+ release from endoplasmic reticulum
drugs that prevent skeletal muscle function (produce paralysis of muscle), prevent patients from moving around during a surgical procedure, useful in setting and aligning fractures, endotracheal intubation, laryngoscopy, bronchoscopy, esophagoscopy, useful because general anesthetics don’t paralyze patient muscles enough alone
neuromuscular blocking agents/paralytics/neuromuscular junction blockers (NMJ blockers)
site of action for neuromuscular blocking agents/paralytics, similar to synapse (motor neuron axon terminals –> muscle), acetylcholine is the neurotransmitter and nicotinic receptors expressed by skeletal muscle
neuromuscular junction
ligand-gated ion channel that is opened by acetylcholine, Na+ flows through it
nicotinic receptor
minimum and maximum number of ACh molecules that can bind to nicotinic receptors
2 and 5
a nicotinic receptor has ____ subunits with alpha/beta/gamma/delta subtypes that dictate what type of nicotinic receptor it is, different tissues have different subunits and subtypes in their nicotinic receptors
5
activity in a motor neuron causes contraction of the muscle is called what?
excitation-contraction coupling
what are the 2 sodium channels that allow Na+ influx in excitation-contraction coupling of muscle
nicotinic receptor that is gated by ACh, fast voltage-gated Na+ channels along the T tubule
what type of ion channels reset muscle (repolarization) for the next muscle contraction?
K+
somatic motor neuron releases ACh at NMJ because of what?
action potential
net entry of what ion through ACh receptor-channel initiates a muscle action potential IF threshold is reached and because there is an influx of this ion into muscle there’s an action potential that fires along the T-tubule
Na+
what ion has to come out of the sarcoplasmic reticulum to initiate muscle contraction which happens due to action potential that changes DHP conformation to open allowing RyR to open allowing this ion’s release
Ca2+
ACh is broken down very quickly by ________ so ACh isn’t present very long (lots of control over contractions)
acetylcholine esterase (AChE)
these NMJ blockers are competitive antagonists of the nicotinic receptor, competes with the other agonists (ACh) for the binding site, when these agents bind to the nicotinic receptor it doesn’t open so no contraction
non-depolarizing agents
tubocurarine, atracurium, doxacurium are examples of what type of non-depolarizing NMJ blockers?
benzylisoquinolines
benzylisoquinolines metabolism is _________ (dependent/independent) of the liver and kidneys
independent, happens in the blood so a better choice for liver/kidney dysfunction patients
pancuronium, vecuronium, pipecuronium, rocuronium are examples of what type of non-depolarizing NMJ blockers?
aminosteroids
aminosteroids metabolism is _________ (dependent/independent) of the liver and kidneys
dependent
how can the actions of non-depolarizing NMJ blocking agents be overcome/reversed?
increasing the ACh with cholinesterase inhibitor like neostigmine (prevents metabolism of ACh so ACh starts binding to nicotinic receptor therefore “winning” the competition with the non-depolarizing agent
what breaks down the benzylisoquinolines in the plasma?
esterases in the plasma (butyrylcholinesterase, pseudocholinesterase, plasma esterase)
histamine release (doesn’t usually happen), ganglionic block (blocking communication between pre and postganglionic neurons in autonomic nervous system causing decreased BP due to decreased SNS), vagolytic effects (less parasympathetic activity due to potential binding at muscarinic receptors, increased HR due to loss of vagal input to the heart)
non-depolarizers adverse effects
bind to and stimulate nicotinic receptors at the NMJ similar to ACh, unlike ACh this agent is RESISTANT to AChE so nicotinic receptors stay open with no rest, longer lasting depolarization leading to flaccid paralysis (uncontrolled muscle paralysis, no muscle tone)
depolarizing agents (succinylcholine)
only depolarizing agent use clinically, onset of action is rapid (30-60 sec), duration of action is ultra short acting (5-10 min), hydrolyzed by succinic acid and choline by plasma butyrylcholinesterase, used for brief procedures, may be used in long procedures for fast onset but followed by a longer acting agent (non-depolarizing agent), no way to reverse paralysis induced by this, prolonged use causes hyperkalemia, malignant hyperthermia
succinylcholine
________ are highly polar with 1 or 2 quaternary amines (positively charged at physiological pH), not orally active, very water soluble, don’t penetrate the BBB, administered parenterally (usually IV), drug interactions with inhaled anesthetics, aminoglycosides/tetracyclines (less dose of agent)
NMJ blockers
used to decrease muscle spasticity, hyperhidrosis, cosmetics, migraines (newer indication),
botulinum toxin (BOTOX)
muscle relaxant that is an agonist of alpha 2 to decrease glutamate leading to a decrease in muscle spasm and contraction
tizanidine
muscle relaxant that can inhibit motor neurons through agonist activity at GABAB, can also inhibit release of glutamate to cause muscle relaxing
baclofen
etiology of anxiety model, autonomic nervous system is overreactive to stimuli, stimuli increases NE activity in CNS, NE subsequently stimulates glutamate release, increased excitatory neurotransmitter activity may promote anxiety
noradrenergic model
etiology of anxiety model, GABAA receptor system is impaired and/or downregulated, makes GABA have less inhibitory effect in CNS, decreased CNS inhibition secondary to decreased GABA activity may result in uncontrolled anxiety
GABA receptor model
etiology of anxiety model, 5-HT system is downregulated so 5-HT activity in CNS is abnormal, abnormal 5-HT activity may directly promote anxiety or may indirectly through dysregulation of NE neurotransmission
serotonin (5-HT) model
an inhibitory neurotransmitter primarily biosynthesized from glutamate by glutamic acid decarboxylase (GAD), stored in vesicles in presynaptic neurons, released into synaptic cleft when presynaptic neuron depolarizes, binds with postsynaptic receptors, may be transported back into presynaptic neuron by reuptake channels, inactivated by an aminotransferase to succinate OR it is stored in vesicles
GABA
channel formed from protein subunits (so lots of different binding sites), ligand-gated (channel only opens when GABA binds), ionotropic (allows chloride to pass through when open), medications may bind to and allosterically (change shape) modulate this receptor at various sites with most CLASSES of medications having a DISTINCT binding site from each other and from GABA, some medications enhance the influx of Cl- that occurs when GABA ALSO binds to this receptor (called GABAergic effect)
GABAA
these drugs share a common ring system (pharmacophore), structure is responsible for the GABAergic activity of the drugs, modifications of substituents on the ring may change duration of action and PK properties for better or worse
benzodiazepines
these drugs are positive allosteric modulators of GABAA, bind at a different site from GABA, when GABA also bound these drugs induce an allosteric change in GABAA that enhances Cl- influx through GABAA, this change increases affinity of GABA for binding to GABAA and increases FREQUENCY of Cl- channel opening (hyperpolarization, harder to reach action potential)
benzodiazepines
risk of dependence and addiction (all are C-IV drugs), excess drowsiness/sedation, amnesia, pregnancy considerations (all are category D or X), contraindications (myasthenia gravis, severe hepatic impairment, severe respiratory insufficiency, sleep apnea), overdose (rarely fatal if NOT combined with other CNS depressants)
adverse effects of benzodiazepines
these benzodiazepines do not undergo CYP450 metabolism and are directly glucuronidated so some clinicians prefer these for patients with liver insufficiency
lorazepam, oxazepam, temazepam (LOT)
this drug is structurally like benzodiazepines, functions as a competitive antagonist at benzodiazepine receptors within GABAA (competes with the benzodiazepine NOT GABA), indicated for benzodiazepine reversal during procedural sedation or general anesthesia, management of benzodiazepine overdose, administered IV
flumazenil
old class of anxiolytics and sedatives derived from barbituric acid, various chemical substitution on the barbituric acid pharmacophore has generated large family of drugs, similar to benzodiazepines but bind at a distinct site at GABAA, increase the DURATION that GABAA chloride channel is open, often fatal upon overdose even when administered without other CNS depressants because of channel opening duration and they can act as a direct GABA agonist in place of GABA at high doses
barbiturates
why does flumazenil NOT work at reversing barbiturate overdose?
flumazenil binds to benzodiazepine site NOT barbiturate site on GABAA
these drugs have positive allosteric enhancement of GABAA receptor, enhances GABAA currents in a synergistic manner with diazepam since a different binding site, have a steroid structure, used for postpartum depression, risk of excessive sedation and motor impairment
neuroactive steroid GABAA modulators, brexanolone, zuranolone
which neurosteroid is administered as an IV continuous infusion over 60 hours and is metabolized by non CYP routes (UGT, SULT, ketoreductase)?
brexanolone
which neurosteroid is administered PO daily for 14 days with fat containing foods in the evening to enhance absorption and metabolized by CYP3A4 primarily?
zuranolone
azapirone similar in structure to some antipsychotic medications, 5-HT1A receptor partial agonist (not full effect of serotonin) that modulates 5-HT activity, similar antianxiety effect as benzodiazepines, does not have the sedative, anticonvulsant, dependency properties of benzos, may align with the 5-HT dysregulation model of anxiety, indicated ONLY for GAD, may make panic disorder worse, oral agent only, not helpful for acute anxiety because may take several weeks for noticeable effect, contraindicated with medications that have MAOI properties due to risk of hypertensive crisis, mostly eliminated by CYP3A4
buspirone
stage of sleep between wakefulness and sleep, some eye movement, tonic muscle activity, brief duration
stage 1
stage of sleep with little to no eye movement, less tonic muscle activity, brief duration
stage 2
stage of sleep known as delta sleep, high amplitude slow activity delta waves on EEG, low tonic muscle activity, deepest stage of sleep
stage 3
part of sleep where brain becomes electrically and metabolically active, increased cerebral blood flow, muscle atonia, dreaming, increased internal temperature
REM sleep
the “perfect” _______ drug would allow sleep to occur without disrupting normal sleep architecture instead of pharmacologically altering sleep pattern, not cause side effects the next day such as sedation or rebound anxiety, not interact with other medications, be safe to use chronically without risk of dependance
hypnotic
these drugs decrease sleep latency (time it takes to fall asleep), increase sleep maintenance (overall time spent asleep), decrease number of awakenings/time spent in stage 0, increased arousal threshold from sleep (more difficult to wake up), decrease time spent in delta sleep and REM sleep but number of REM cycles increases
benzodiazepines
active metabolites of benzodiazepines _________ (increase/decrease) the combined duration of parent drug + active metabolites
increase
a _____ (short/long) half life may cause daytime sedation (hangover effect) due to excessive GABAergic activity, may accumulate and cause toxicity (increased fall risk in elderly patients)
long
clorazepate, midazolam, oxazepam, triazolam eszopiclone, zaleplon, zolpidem are all _______-acting
short
alprazolam, lorazepam, estazolam, temazepam are all ______-acting
intermediate
clonazepam, diazepam, flurazepam, quazepam are all _____-acting
long
function as agonists at the benzodiazepine binding site on GABAA, do NOT produce a GABAergic effect in the absence of GABA, bind SELECTIVELY bind to GABAA receptors containing alpha-1 subunit (they don’t bind to other alpha subunits), activation of alpha-1 GABAA causes sedative, hypnotic, amnesic, motor impairing effects, activation of alpha-1 GABAA does NOT cause an anxiolytic, muscle relaxant, or alcohol-potentiating effect
Z drugs
which Z drug has the shortest duration?
zaleplon
adverse effects include complex sleep behaviors, tolerance and dependence, dizziness, drowsiness, headache, drug interactions include CNS depressants (enhances depressant effect, avoid use with alcohol), CYP3A4 inhibitors may cause enhanced response to these drugs, alternative therapies (St, John’s Wort induces CYP3A4)
Z drugs
hormone that regulates our sleep-wake cycle, biosynthesized from 5-HT (serotonin), released from the pineal gland, interacts with receptors in the suprachiasmatic nucleus (SCN) which is associated with circadian rhythm, an increase in this concentration in the SCN correlates with drowsiness and sleep, darkness promotes the biosynthesis of this leading to increased activation of receptors in the SCN promoting sleep/rest, light inhibits biosynthesis of this signaling to body via SCN that it is time to wake
melatonin
G protein coupled receptors, two subtypes (MT1 and MT2) that both share a high degree of sequence homology and bind to their hormone with high affinity, widely expressed throughout CNS, activation of melatonin receptors inhibits neuronal firing with SCN, mediates the phase shifting effect of the hormone on light/dark cycle
melatonin receptors
share structural similarity with melatonin, agonists at MT1 and MT2 receptors, shortens sleep latency, generally well tolerated, low incidence of residual adverse effects, extensively metabolized by CYP (3A4, 1A2, 2C), low oral bioavailability due to metabolism
melatonin agonists (ramelteon, tasimelteon)
which melatonin agonist is indicated for treatment of sleep onset insomnia?
ramelteon
which melatonin agonist is indicated for non-24-hour sleep-wake disorder (individuals who are blind)?
tasimelteon
excitatory neuropeptides involved in CNS signaling, ligands at two receptors (OX1R and OX2R), reduced signaling of this is associated with somnolence (sleepiness) in mammals
orexin
reducing orexin signaling with drug therapy leads to ______ (induction/inhibition) of somnolence (sleepiness)
induction
these drugs inhibit orexin activity at both orexin receptors, reduce sleep latency, decrease orexin-mediated arousal (may help with sleep maintenance), turn off wake signaling, indicated for treatment of insomnia characterized by difficulties with sleep onset/sleep maintenance, administered orally, high oral bioavailability, take on empty stomach for rapid onset of action, metabolized mostly by CYP3A, well-tolerated overall, fatigue/headache are adverse effects, avoid with alcohol, STRONG CYP3A4/5 inhibitors/inducers may impact therpay
orexin antagonists, suvorexant (Belsomra), daridorexant (Quviviq), lemborexant (Dayvigo)
this is dependent on half-life of the benzo and the half-life of any active metabolites that the body creates from the benzo, chemical changes that decrease metabolism of benzodiazepines to active metabolites results in a shorter this
duration of action
this ring is required for binding to benzodiazepine receptor, planar structure enables pi bonding interactions (pi-pi stacking) between benzodiazepine and aromatic amino acid residues of the receptor, pi bonding helps spatially anchor benzo in active site, 6-membered ring
Ring A
an electron withdrawing substituent at position _____ on ring A is required for GABAergic activity and activity increases with electron withdrawing strength (increases binding affinity)
7
substitution at positions ____, _____ and _____ on ring A DECREASE GABAergic activity
6, 8, 9
sterically small alkyl chain substitution at position 1 of this ring MAINTAINS activity, proton accepting group at position 2 is REQUIRED for binding to GABAA, alkyl substitution at position 3 DECREASES activity, hydroxyl substitution at position 3 MAINTAINS activity (important for duration of action issues), saturated bond between positions 4 and 5 DECREASES ACTIVITY (so need a double bond there), this is the 7 membered ring
ring B
ring that is not necessary for binding to GABAA but is REQUIRED for activity, electron withdrawing substituents at the ortho position INCREASES binding affinity to GABAA receptor
ring C
imidazole and triazole benzos have _______ (less/greater) binding affinity for GABAA and are ______ (less/more) potent, they are also shorter acting because the possibility of metabolism to a long-acting active metabolite is removed
greater, more
benzos with alkyl substituents at position 1 (ring B) have a ______ (short/long) half life, gradually undergoing CYP450 N-dealkylation, the generates ________ (additional/less) active metabolites
one the solution is to synthesize a drug with a 3-hydroxy group that has a shorter duration of action because this creates a spot for glucuronidation for faster metabolism
long, additional
3-hydroxy benzos (LOT) are directly glucuronidated, bypassing what type of metabolism and generation of active metabolites? (glucuronide metabolites are inactive and quickly excreted into the urine since the metabolites are more polar)
CYP450
synthesizing an aromatic ring at position _____ on ring B removes the possibility of active, long-acting metabolites due to CYP450 N-dealkylation, these imidazole and triazole benzos have active metabolites but they are shorter acting, shorter onset of action, more potent, imidazole/triazole benzos are metabolized in two step process (CYP3A4, then glucuronidation)
1
polar chemistry of this drug allows for rapid dissolution from solid dosage form, activation by acid hydrolysis happens quickly in the stomach leading to a faster acting oral benzo with a similar elimination profile as older benzos like diazepam
clorazepate
benzos have a relatively _______ (high/low) logP value meaning they are more lipophilic and good for crossing BBB, they are also weak ______ (acids/bases) at N-4 position and older benzos have a relatively low pKa meaning they are mostly unionized at physiological pH
high, bases
condition of reversible unconsciousness in which normally painful stimulus produces neither an outward response nor a memory
anesthesia
ether, nitrous oxide, halothane, etc. are examples of what type of general anesthetic (used in major surgery)?
inhaled
barbiturates, benzos, opioids are examples of what type of general anesthetics (used in outpatient procedures and induction)?
intravenous
stage of anesthesia where patient is conscious but drowsy, analgesia, amnesia, euphoria
stage I
stage of anesthesia where patient has a loss of consciousness but can see vomiting, delirium, combative behavior, excitement, want to move through this stage quickly to avoid these effects
stage II
stage of anesthesia where patient is fully unconscious, regular respiration, decreasing eye movement, surgical anesthesia
stage III
stage of anesthesia where patient is in respiratory arrest, cardiac depression and arrest, no eye movement, death quickly follows this stage, medullary depression
stage IV
the more lipophilic an anesthetic is, the ________ (smaller/greater) the potency
greater
what receptor is a glutamate ionotropic receptor that opens and allows positive ions to go in?
NMDA
anesthetics could work by enhancing inhibitory effects or interfering with excitatory effects?
both
with administration of an anesthetic, the Cl- current shifts to the ______ (left/right) showing an increase in potency and increase in efficacy (increased max) of GABA’s ability to inhibit a neuron’s firing
left
with administration of anesthetic, the amount of ACh compared to membrane current graph shifts to the _____ (left/right) and the max is _______ (increased/decreased) showing that anesthetics are noncompetitive antagonists of glutamate receptors
right, decreased
depth of anesthesia varies with the concentration in the brain, anesthetic must go from _______ to _______ to _______ and travels down is PARTIAL PRESSURE gradient (not concentration gradient)
alveoli, blood, brain
important factors to consider in administration of inhaled anesthetics include concentration of inspired gas, pulmonary ventilation (faster you breathe the faster the induction occurs but NO EFFECT ON DEPTH of anesthesia), solubility in blood so the ________ (more/less) soluble in blood means slower onset because anesthetic that is dissolved in blood does NOT exert a partial pressure so blood is a reservoir that must be SATURATED before distribution to the brain, well perfused tissues (brain) reach equilibrium faster than less well perfused tissues (fat)
more
induction time of an inhaled anesthetic depends on what?
blood solubility (more soluble in blood slower onset)
recovery time from an inhaled anesthetic depends on what?
solubility in brain, more soluble in brain slower the recovery
what is the primary mechanism of elimination of inhaled anesthetics?
ventilation/exhalation
describes the ability of the anesthetic to dissolve in blood, ratio of concentrations when partial pressures are equal between alveoli and blood, MAIN DETERMINANT OF INDUCTION TIME
blood:gas partition coefficient
concentration of gas at which 50% of patients don’t move in response to noxious stimulation like incisions, patients may require 0.5-1.5 of this to reach anesthesia, this of different anesthetics is are additive so can avoid adverse effects by using 2 agents at lower concentrations
minimum alveolar concentration (MAC)
describes anesthetics ability to dissolve in brain, ratio of concentrations when partial pressures are equal between blood and brain, MAIN DETERMINANT OF RECOVERY
brain:blood partition coefficient
inhaled anesthetic that is potent, has good margin of safety but flammable, explosive, unpleasant induction, produces secretions due to irritation, cause nausea/vomiting during recovery, slow induction time
ethyl ether
inhaled anesthetic that is potent, relaxes skeletal muscle, non-flammable, non-irritating, narrow safety margin, liver/kidney toxicity, causes cardiac arrest and arrhythmias (due to lots of chloride atoms in molecule)
chloroform
this type of anesthetics all depress respiration to some degree, produce skeletal muscle relaxation but not enough alone so paralytic still needed, all have onset of action 5-10 minutes, differ in terms of CV effects and adverse events
inhaled anesthetics
this inhaled anesthetic has slow induction (high blood/gas) and recovery, can cause decrease in BP, HR, force of contraction, inhibits baroreflex, sensitizes to arrhythmogenic effects of epinephrine, hepatitis, trifluoroacetic acid metabolite damages liver, malignant hyperthermia, hepatic metabolism
halothane
this inhaled anesthetic has a faster induction than halothane, can cause an initial decrease in BP and CO but then recovery, mild sensitization to arrhythmogenic effects of epinephrine, seizure like EEG under deep anesthesia so caution in patients with history of seizures, renal toxicity
enflurane
this inhaled anesthetic has a faster induction and recovery than halothane, used for maintenance rather than induction because of pungent odor, can cause decreased BP and CO, decreased risk of sensitization to arrhythmogenic effects of epi, depth of anesthesia can be adjusted rapidly because not very soluble in blood or brain, no renal/hepatic toxicity
isoflurane
this inhaled anesthetic has a substitution of single Cl with F which decreases blood and tissue solubility and slightly decreases potency, very low blood:gas coefficient, low brain:blood coefficient so quick onset and quick recovery, CV effects of decreased BP and CO, decreased risk of sensitization to arrhythmogenic effects of epi
desflurane
this inhaled anesthetic is similar to desflurane in onset/recovery and potency, sweet taste, small amounts are metabolized but are not toxic, newest inhalation anesthetic
sevoflurane
this inhaled anesthetic very low blood:gas coefficient so fast induction, not very potent so better for analgesia, valuable as adjuvant because MACs are additive
nitrous oxide
this type of anesthetic can be used as sole agent for short procedures or for induction prior to inhalation anesthetic, provide deep sedation while patient breathes spontaneously, responds to verbal commands, recovers rapidly, MOA includes enhancement of GABA actions, blocking of glutamate actions, or stimulating opioid receptors
IV anesthetics
very lipophilic barbiturate (potentiates effect of GABA at GABAA receptors), fast onset and short duration due to redistribution not metabolism, used for induction prior to inhalation anesthetic, decreases BP and respiration and has little analgesic activity
thiopental
most popular IV anesthetic that potentiates effect of GABA at GABAA receptors, onset and duration similar to thiopental, decreases BP and respiration similar to thiopental but less N/V, abuse potential and PIS
propofol
this can be caused by a specific IV anesthetic, involves metabolic acidosis, hyperlipidemia, rhabdomyolysis, enlarged liver in young or head-injured patients
propofol infusion syndrome (PIS)
potentiates the effect of GABA and GABAA receptors, similar to thiopental in onset and duration, only IV anesthetic that doesn’t affect BP or CO, good for patients with coronary artery disease, used for single injection not recommended for continuous infusion (serious N/V)
etomidate
PCP analog, dissociative anesthetic (person may seem awake on this but is in an analgesic and amnesic state, potential for abuse), antagonist of the glutamate NMDA receptor, produces analgesia, amnesia, paralysis without loss of consciousness, hallucinations, delirium, irrational behavior during recovery that is not seen in children, increases BP and bronchodilation
ketamine
morphine like drug that produces very good analgesia but profound respiratory depression
fentanyl
