General Anesthetics, Neuromuscular Junction drugs, Local Anesthetics

what is the goal for balanced anesthesia?

- control surgical and procedural pain via CNS depression

causing less neuronal firing in the brain/spinal cord

what are the characteristics of ideal anesthetics?

- smooth, rapid loss of consciousness

- fast recovery

- wide margin of safety (dont want it too close to a dose that can cause harm)

- no adverse effects

what are the requirements for general anesthetics?

- loss of conciousness

- Analgesia

- Amnesia

- inhibition of autonomic reflexes including sensory and cardiovascular reflexes

- skeletal muscle relaxation (important for ventilator)

- safe, transient and predictable

what are the stages of anesthesia?

- Induction: entering LOC

- Maintenance: maintaining LOC (can range from quick procedure to 12+ hours)

- Emergence: coming out of anesthesia

what goes into a balanced anesthesia?

- a drug cocktail to approximate ideal GA

- combination of inhaled and IV anesthetics

- used commonly for procedures

what are the mechanisms of general anesthesia?

- increase of inhibitory synapse (releases GABA that makes decreased chance for 2nd neuron to fire)

- decrease excitatory synapse (excitatory synapse release glutamate or ACh that makes 2nd neuron more likely to fire)

Overall: decrease activity in the diff areas of the brain

what are the 3 types of IV general anesthetics?

- propofol

- benzodiazepines

- ketamine

what is the use of propofol?

induction of anesthesia and sometimes maintenance

what are the effects of propofol?

hypnotic (causing sleepiness) but not analgesic

what is the mechanism action for propofol?

considered to be via a GABA receptor causing more of an inhibitory effect and potentiating Cl - current

what is a positive of use for propofol as a GA?

it causes less of a hangover effect than others due to quick clearance

what are the cautions of propofol use?

can cause more CV depression (especially in elders) than other drugs and depresses respiratory drive

not good for patients with CV or respiratory disease

what is the use of benzodiazepines (midazolam and lorazepam)?

a premedication used with other anesthetic for anxiolytic, amnesia, and sedative

whats important to note with the synergistic effect of benzodiazepines?

if benzodiazepines are taken with opioids and propofol they will have a synergistic effect on CV and respiratory function

(DECREASING their function aka not good)

what is a caution with benzodiazepines?

causes CV and respiratory depression with worse effects in elderly

what is the use of ketamine?

anesthetic and analgesic

why is ketamine not often used for GA?

because of the side effects but its possible for short procedures or high-risk patients due to decrease in CV and respiratory depression

what are the effects of ketamine?

- CV and respiratory effects are minimal

- does produce dissociative anesthesia with psychomimetic side effects like vivid dreams, illusions, post-operative disorientation

what are the cautions with ketamine use?

those with increased intracranial pressure (like those with TBI) dont do well with this drug, and it can be misused

what are the types of inhaled anesthetics?

- volatile liquids

- gases

what are the volatile liquids used for GA?

desflurane and sevoflurane

what are the gases used for GA?

really just nitrous oxide

are volatile liquids or gases more often used?

volatile liquids, NOS is really only used in short procedures or for labor pain

what are the uses of inhaled anesthetics?

- pediatric anesthesia

- maintaining anesthesia with the goal of systemic action to decrease CNS activity

how do you administer inhaled anesthetics?

via mask or endotracheal tube

what are the pharmacokinetics of inhaled anesthetics?

Uptake: by gas exchange in lung

Distribution: blood

Target tissue: brain

what are the general pharmacokinetics of IV/inhaled GA?

Distribution: widely and uniformly

Solubility: lipid

Elimination: inhaled is primarily through lungs, IV is either lungs or liver

why is lipid solubility important in pharmacokinetics of IV and inhaled GA?

because there can be post-operative washout and redistribution can take a long time especially if patient has more adipose tissue

these GAs can get reservoir effects and patients can experience confusion, lethargy, and disorientation for a HOT min

what is the historical origin of neuromuscular blockers?

curare

these are the poison darts made my Indians

what are the current uses for neuromuscular blockers?

muscle paralysis for ventilator use or surgeries

what is the site of a action for neuromuscular blockers?

neuromuscular junction

what is the administration for neuromuscular blockers?

NOT ORAL

if it was oral it would go polar and inactivate

what is the site and mechanism of action for neuromuscular blockers?

Site: Nicotinic ACh Receptors at the motor endplate

General Mechanism: stop neurotransmission at the neuromuscular end-plate causing lack of muscle contraction

succinylcholine is what type of neuromuscular blocker?

depolarizing

how do depolarizing neuromuscular blockers like succinylcholine work?

so succinylcholine is a nicotinic ACh receptor agonist, so it works by blocking the open channel by it opening normally then the depolarizing blocker attaches to the open channel and doesn't allow for sodium to pass through

what are the 2 phases of action for succinylcholine (depolarizing neuromuscular blocker)

phase 1: extended depolarized period where muscle cell is unresponsive to further stimulation

phase 2: repolarized muscle cell but resistant to stimulation

what is the impact on muscle for depolarizing neuromuscular blockers?

- initial tremor followed by flaccid paralysis

what is a caution with succinylcholine?

it can cause extended paralysis for days/weeks

Cistaracurium is what type of neuromuscular blocker?

non-depolarizing neuromuscular blocker

what is the mechanism of action for nondepolarizing neuromuscular blockers?

nicotinic receptor antagonist (so blocks ACh from binding). it competes with ACh for binding to the nicotinic receptor

what is sugammadex?

a reversal drug for neuromuscular blocks

what is the site or mechanism of action for sugammedex? (neuromuscular blocker reverser)

it binds to the common nondepolarizing neuromuscular blocker (binds to blocker itself) and causes it to diffuse out from the neuromuscular junction so they can no longer do their action

what is an acetylcholinesterase (AChE) inhibitor?

a nondepolarizing neuromuscular blocker reversal that inhibits acetylcholinesterase from breaking down ACh into 2 parts

what are some drug examples for AChE inhibitors?

- neostigmine and pyridostigmine

what is the use of neostigmine and pyridostigmine?

reversal of nondepolarizing neuromuscular blockage or treatment for myasthenia gravis

what is the mechanism of action for neostigmine and pyridostigmine?

to inhibit acetylcholinesterase so there is more circulating ACh around the cell

what are the adverse effects of AChE inhibitors?

- autonomic related like diarrhea, increased salivation, bradycardia

what is the goal of local anesthetics?

to cause loss of sensation in a specific body part or region

what is the purpose of a local anesthetic?

to prevent or relieve pain without loss of consciousness or systemic effects

what are the typical uses of local anesthetics?

- relatively minor procedures, non surgical anesthesia, or analgesia

what is a pro/con of local anesthetic use?

Pro: can offer fast recovery without the huge side effects of GA

Con: may take awhile to get an effect and may not get enough of an effect

what do local anesthetics usually end in?

Caine

like lidocaine and procaine (novocaine)

what are the routes of administration for local anesthetics?

- topical for minor surface injuries or pretreatment

- transdermal for deeper tissue target via patch, iontophoresis, or phonophoresis

- infiltration anesthesia: injected directly into selected tissue

- IV regional anesthesia: injected into peripheral vein

Sympathetic blockade: selective for sympathetic function

what is an example of infiltration anesthesia?

- peripheral nerve blocks!

you inject close to the nerve trunk during or after procedure to block peripheral nerve transmission

- central neural blockade (many types)

what is the mechanism of local anesthetics?

block sensory neuron action potential propagation by blocking voltage gated sodium channels and preventing sodium from entering the neuron to cause an action potential

SO painful stimuli is still there but the signal cant reach so the patient doesn't interpret any pain

what is the goal of a local anesthetic?

to stay at the site of administration (no systemic action)

how is systemic absorption possible for local anesthetics?

- depends on vascularization! look at if the area administering has many blood vessels

- may need to be coupled with vasoconstrictor to avoid systemic absorption

what are the adverse effects possible for systemic absorption?

- neurotoxicity (too much CNS activity like seizures)

- cardiovascular toxicity (why we can use cocaine as vasoconstrictor) causing decrease in CV activity

- allergies to some LA

what is a central neural blockade?

an injection within the spaces surrounding the spinal cord for regional anesthesia

what is an epidural block?

this is the least invasive block involving needle to epidural space outside of the dura

used for labor pain, LE surgeries, spinal surgeries, C-sections

what is a caudal block?

specialized epidural where needle goes through caudal space

what is a spinal block?

a needle going into the dura to the subarachnoid space and into the CNS

how does fiber size play a role in nerve blocks?

the smaller the diameter the fibers is the more sensitivity it will have to local anesthetics. so your pain fibers are small type C dorsal root motor neurons and they have a higher sensitivity to a block than the alpha Type A motor fibers due to their large size.

recovery of a block would be in reverse order, so larger diameter motor will recover before sensation

why does the reversal of nerve block matter?

basically your patient may be able to move their leg but cant provide any protective sensation causing an increased risk for injury

what are the anesthetic adjunct drugs?

- neuromuscular blockers

- local anesthetics

- opioids

- anti-emetics

what is an opioid analgesic in regard to adjunct drugs?

they anent used as an anesthetic or sedative but useful in intra and postoperative pain control

usually fentanyl

what are the special concerns for rehab patients with GA?

- a patient may have not fully recovered from GA or adjust meds when PT arrives

so you can see confusion, delirium, muscle weakness, or bronchial secretion accumulation (often seen in elderly who cant clear GA as well)

there is also the possibility of long-term cognitive decline after GA especially for elderly

what are the special concerns for rehab patients for nerve blocks?

- PT may be involved in topical or transdermal application for pain or inflammation

- avoid disturbing transdermal patches

- do not apply heat on or near transdermal patches as it will accelerate drug release due to increase blood flow to area

- nerve blocks can decrease motor control causing knee buckling or lack of protective sensation