11 - Neuromuscular, Sedative, Anesthetic, & Analgesic Agents

acetylcholinesterase

enzyme that metabolizes ACh

• ends muscle contractions

• can be inhibited with cholinesterase inhibitors

neuromuscular blocking agents

drugs that cause pharmacologic paralysis

• reduce spontaneous breathing

• prevent dislodgment of tubes

• reduce O₂ consumption

• improve patient-ventilator synchrony

non-depolarizing agents

drugs that induce paralysis by preventing motor end-plate from depolarizing

• reversible

• cholinesterase inhibitors

  • neostigmine, pyridostigmine

• examples: pancuronium, rocuronium, rapacuronium

depolarizing agents

drugs that induce paralysis by causing massive depolarization of muscle

• not reversible

  • pseudocholinesterase

• example: succinylcholine

neuromuscular blocking agent (NMBA) selection factors

• liver/renal dysfunction

• vagolytic activity

• any drug interactions!

• does not affect pain/consciousness

succinylcholine (Anectine)

depolarizing agent that induces paralysis

• routes: bolus, infusion, rapid sequence intubation (RSI)

• side effects: malignant hyperthermia

pancuronium

non-depolarizing agent that induces paralysis

• residual neuromuscular blocking effects

• possible pulmonary complications!

rocuronium (Zemuron)

non-depolarizing agent that induces paralysis

• fast onset

• neutral cardiac side effects

atracurium

NMBA that causes histamine release

• don’t use in unstable ICU patients!

cisatracurium (Nimbex)

non-depolarizing agent that treats ARDS

• metabolizes in bloodstream

• decreases likelihood of causing histamine release

vecuronium

non-depolarizing agent similar to rocuronium

• neutral cardiac effects

• no histamine release

• must be reconstituted

• train-of-four (TOF)

skeletal muscle relaxants

• central-acting

• methocarbamol (Robaxin)

• tizanidine (Zanaflex)

• metaxalone (Skelaxin)

• baclofen (Lioresal)

• cyclobenzaprine (Flexiril)

• orphenadrine (Norflex)

• chlorzixazone (Parafen Forte)

• carisoprodol (Soma)

skeletal muscle relaxant

• peripheral-/direct-acting

dantrolene (Dantrium)

sedatives

drugs that reduce CNS arousal

hypnotics

drugs that induce sleep

anxiolytics

drugs that decrease anxiety

benzodiazepines

drugs that have sedative, hypnotic, and anxiolytic effects

examples:

• alprazolam (Xanax)

• chlordiazepoxide (Librium)

• clorazepante (Tranxene)

• clonazepam (Klonopin)

• diazepam (Valium)

• midazolam (Versed)

• lorazepam (Ativan)

• oxazepam (Serax)

dexmedetomidine (Precedex)

α₂-adrenergic agonist, central-acting muscle relaxant

• used for sedation in ICU

• decreased incidence of delirium

• side effects: bradycardia, hypotension

non-benzodiazepines

drugs with decreased daytime residual effects

types:

• z-compounds

  • zolpidem (Ambien)

  • eszopiclone (Lunesta)

  • zaleplon (Sonata)

• melatonin-receptor agonists

  • ramelteon (Rozerem)

  • tasimelteon (Hetlioz)

barbiturates

drugs that decrease levels of CNS arousal

• treats seizures

• causes drowsiness

• overdose effects:

  • respiratory depression → CNS repression → CV collapse → coma → death

conscious sedation

sedation that uses a combination of hypnotics, sedatives, or anxiolytics

• decreases consciousness

• causes retrograde amnesia

• examples:

  • midazolam + fentanyl

  • morphine + lorazepam

steps of general anesthesia administration

1. induction

   • creating appropriate level of __

2. maintenance

   • continuing state

3. termination

   • recovering from __

factors that determine right anesthesia medication

• age

• medical condition

• organ function

• disease

• allergies

• decrement time

stages of anesthesia

• stage 1

stage of anesthesia

• analgesia, conscious sedation

• used for endoscopies, colonoscopies, minor procedures

stages of anesthesia

• stage 2

stage of anesthesia

• unconsciousness with intact reflexes

• can cause coughing, increased salivation, increased CV output, and hypertension

stages of anesthesia

• stage 3

stage of anesthesia

• complete respiratory depression

• loss of blink reflex and eye movement

• used for most surgeries

stages of anesthesia

• stage 4

stage of anesthesia

• complete loss of respiratory drive

• may cause loss of CV tone

• avoid this stage at all costs

inhaled anesthetics

• nitrous oxide (N₂O)

• enflurane (Ethrane)

• isoflurane (Forane)

• sevoflurane (Ultane)

• desflurane (Suprane)

IV anesthetics

barbiturates

• methohexital (Brevital)

benzodiazepines

• midazolam (Versed)

miscellaneous

• propofol (Diprivan)

• etomidate (Amidate)

• ketamine (Ketalar)

local anesthetics

ester

• chloroprocaine (Nesacaine)

• benzocaine (Anbesol)

• tetracaine (Pantocaine)

amide

• lidocaine (Xylocaine)

• bupivacaine (Marcaine)

• ropivacaine (Naropin)

how to reduce risk of post-op nausea and vomiting (PONV)

• use regional anesthesia

• propofol for induction and maintenance of anesthesia

• avoid N₂O and volatile anesthetics

• use supplemental O₂

• maintain hydration

• minimize use of opioids and neostigmine

antiemetic drugs

CLASS	EXAMPLES
dopamine antagonists	droperidol prochlorperazine metoclopramide (Reglan)
serotonin antagonists	ondansetron (Zofran) granisetron (Kytril) dolasetron (Anzemet)
antimuscarinics	promethazine (Phenergan) dimenhydrinate (Dramamine)

analeptics

drugs that induce CNS arousal and ventilatory stimulation

• used to treat sleep apnea, post-anesthesia respiratory depression, acute hypercapnia, weaning from MV, and apnea of immaturity

examples of analeptics

• medroxyprogesterone

  • obesity hypoventilation syndrome

• protriptyline

  • daytime symptoms of OSA

• doxapram

  • post-anesthetic respiratory depression

• caffeine

  • apnea of prematurity

morphine-like drugs

analgesics that target opioid-binding sites

steroidal and non-steroidal anti-inflammatory drugs

analgesics that inhibit formation of pain-producing cytokines

antidepressants

analgesics that increase levels of regulatory neurotransmitters like NE and serotonin

anti-seizure agents

analgesics that slow nerve impulse for pain

drug schedules for opioids

SCHEDULE	DESCRIPTION	EXAMPLES
I	no medical use high addiction potential	heroin marijuana
II	medical use high addiction potential	cocaine opioids amphetamines
III	medical use moderate potential for dependence	codeine hydrocodone
IV	medical use no abuse potential	benzodiazepines

side effects of opioids

BODY SYSTEM	SIDE EFFECTS
general	respiratory depression apnea circulatory depression shock respiratory arrest cardiac arrest
CNS	light-headedness dizziness syncope seizures dysphonia hallucinations
respiratory	depression decreased rate and depth of breathing
CV	reduction in venous and arterial pressures
skin	vasodilation flushing sweating pruritus
GI	nausea constipation

opioid antagonists

drugs that reverse symptoms of opioid overdose

example: naloxone (Narcan, Evzio)

corticosteroids

drugs that prevent leukotrienes and prostaglandins

• stimulates chemical nociceptors → reduced pain sensation

NSAIDs

drugs with antipyretic, anti-inflammatory, and analgesic effects

• usually used for pain caused by tissue destruction

• inhibits cyclooxygenase

• examples:

  • aspirin

  • ibuprofen

  • naproxen

drugs with analgesic synergy

• codeine-acetaminophen

• hydrocodone-acetaminophen (Vicodin, Anexia, Lortab)

• hydrocodone-ibuprofen (Vicoprofen)

common antidepressants

TYPE	EXAMPLES
tricyclic antidepressants (TCAs)	amitriptyline imipramine (Tofranil) doxepin nortriptyline (Pamelor) desipramine (Narpramin) protriptyline (Vivacil)
selective serotonin reuptake inhibitors (SSRIs)	fluoxetine (Prozac) fluvoxamine (Luvox) paroxetine (Paxil) sertraline (Zoloft) vortioxetine (Brintellix) citalopram (Celexa) escitalopram (Lexapro)