pharm chapter 18

neuromuscular blocking agents

paralytics/muscle relaxant given IV causing SKELETAL muscle weakness/paralysis.

fxn of NMBAs

1. intubations

2. surgery (do not extubatne if they’re still paralyzed after surgery!)

3. enhance vent synchrony

4. reduce ICPs

5. reduce O2 consumption (ex. shivering)

6. terminate status epileptics (cont. seizure), tetanus or asthmaticus

7. facilitate procedures and studies

8. keep pt. immobile

clinical concerns of NMBAs

1. prolonged ICU acquired weakness (disengaging muscle to contract causes muscle atrophy)

2. prolonged vent (diaphragm paralyzed)

3. risk of pt. awareness during paralysis

4. increased risk for DVT

5. corneal abrasions

6. anaphylaxis (shock due to allergies from NMBA)

What does the CNS and PNS make up?

CNS = brain + spinal cord

PNS = somatic motor nervous system (skeletal) for voluntary control and the autonomic nervous system for involuntary control

physiology of the NM junction

neuron is made up of a cell body, axons and dendrites and neurotransmitters’s nerve conduction in skeletal muscles is mediated by Ach

2 ways to block muscle contraction

1. competitive inhibition through nondepolarizing agents to block Ach

2. prolonged occupation + persistent binding through depolarizing agents that makes post-synaptic endings unexcitable

Nondepolarizing agents

Competitive by blocking Ash receptors W/O ACTIVATiNG them. This affects postsynaptic cholinergic receptors at NMJ and is reversible w/ acetylcholinesterase inhibitors (neostigmine)

pharmacokinetics of non depolarizing agents

DOES NOT CROSS THE BBB as it is poorly lipophilic and is poorly absorbed in GI tract (must be given IV!). Onset + duration is based on dose, age and hepatic/renal failure, but have a longer duration than depolarizing agents.

metabolism of non depolarizing agents? how do you choose which drug to use?

Even when the effect wears off, 75% of receptors can still be occupied by blocker as additional boluses may appear more potent.

ALWAYS choose drug based off of organ status!

how does the non depolarizing agent d-Tubocurarine + doxacurium metabolize?

Minimally metabolize w/ 60% excreted in kidneys + rest in bile

how does the non depolarizing agent pancuronium + vecuronium metabolized? what is unique about pancuronium?

Hepatic system

Pancuronium has the greatest potential to cause CVS side effects

how does the non depolarizing agent atracurium + cisatracurium metabolize

optimal choices for pt w/ hepatic or renal failure with cis. being MC due to it being gentle + long-lasting.

how does the non depolarizing agent mivacurium metabolize?

by plasma cholinesterase, being one of the shortest acting one (10-20min)

adverse effects + hazards of non depolarizing agents. What do you always need when paralyzing a pt?

1. CVS effects (causes vagolyic effect: increased HR, BP, MAP, which if continued, means pt. is not sedated).

2. histamine release (causes HR increases bc BP decreases, bronchospasm)

3. inadequate ventilation (paralysis of muscles, as you ALWAYS need a vent when paralyzing)

What end tail of a word means paralysis?

-curium/-curonium

-ine

Reversal of non depolarizing blockade w/ indirect-acting agent? Example of agents (3)

ND-NMBAs produced by AChE inhibitors. These inhibit cholinesterase which breaks down Ach allowing more @junction to displace the blocker (aka., get rid of AChE→build up Ach→entity cram through blockade). not a rapid reversal as effects can last BEYOND OR despite monitoring + reversing!

1. neostigmine

2. edrophonium

3. pyridostigmine (used for myasthenia gravis)

Sugammadex

Newer selective relaxant reversal ND-NMBA that reverses Rocuronium + Vecuronium, but makes them DROOL like crazy! yankauer!

Depolarizing agents and its only agent?

Shorter acting than ND ones and has no reversal agents. Paralysis happens in 60-90s but lasts 10-15min, being ideal for intubating patients.

Only agent is SUCCINYLCHOLINE!

Mode of action for depolarizing agents

Depolarizes muscle membrane like Ach and causes fascinations (body is shaky then limp once muscle relaxes). Phase 1 block is prolonged depolarization/flaccid paralysis; whereas, p2 block resembles ND block and limits use in repeat doses

metabolism + reversal for depolarizing agents

metabolized by rapid hydrolysis by plasma cholinesterase, but there is NO REVERSAL AGENT. Only way to remove it is by redistribution + metabolism.

Hazards for depolarizing agents

1. sympathomimetic + vagal response w/ repeat boluses

   1. do NOT BAG, will increase pressure + barf

2. muscle pain/soreness

3. histamine release

4. increased IC, intraoptic, intragastric pressure, temperature + potassium levels

Why do you NOT give depolarizing agent to trauma patients?

causes hyperkalemia which endangers burns, closed head injuries and nerve/spinal cord injuries

Who will not metabolize succ effectively?

pt w/ abnormal or deficient pseudocholinesterase, being the plasma cholinesterase that metabolizes succ

Key points about succ

1. quick onset, off quick

2. facilitates ventilation/intubation

3. NO bagging + NO trauma pt

when to use succ

Improves ventilation, oxygenation + reduces pressure

1. ARDS, status asthmatics + epilepticus

2. HFOV + inverse ratio ventilation

3. NM toxins

4. tetanus

precautions + risks of NMBAs and vent

1. proper eye care

2. sxn

3. proper sedation + analgesia

4. prolonged skeletal muscle weakness

5. aspiration/nosocomial pneumonia

6. decubitus ulcers

7. DVT

use of sedation + analgesia NMBA for mech vent

ABSOLUTELY ESSENTIAL FOR SEDATION + ANALGESIA! MUST monitor tachycardia, hypertension, diaphoresis + lacrimation as those are all signs the patient is awake!

Examples of analgesics and amnestic sedatives

1. analgesics

   1. fentanyl (MC)

   2. morphine

2. amnestic sedatives

   1. propofol (MC)

   2. lorazepam

   3. midazolam (MC)

What reduces rate of drug elimination for NMBAs?

age + hypothermia

electrolyte disturbances affect elimination of what for NMBAs?

1. hypokalemia, MORE paralyzed (augments blockade, limits reversal agents)

2. hypermagnesium, LONGER paralyzed (prolongs blockade)

3. hypercalcemia, LESSER paralyzed (reduces sensitivity + duration

pH disturbances w/ NMBAs

resp + met ACIDOSIS enhances blockade + reversal agents work slower.

interaction w/ NMBAs

1. prolonged NMBA (inhaled anesthetics and ahminoglycosides do this)

2. agents antagonizing NMBA (phenytoin, azathioprine, theophylline)

What factors do you choose agents based on?

1. duration of procedure (quick intubation, IR stuff, etc.)

2. adverse effects

3. route of eliminations

4. drug interactions

5. cost

monitoring NM blockade. What use be ruled out first for cause of agitation?

VENT MALFXN must be ruled out first as cause of agitation before initiating NMBA. Paralysis can mask clinical signs/symptoms, so key to monitor first.

Issues with order of loss of muscle activitiy

Starts from HEAD to TOE:

1. eyelids

2. face

3. neck

4. extremities

5. abdomen

6. intercostals

7. diaphragm

issue with this is that the airway goes AWAY first and the diaphragm comes BACK first! because of this, do NOT extubatne right away, as airway will still not be working even though the diaphragm is. You can confirm this by asking pt to lift head off the bed.

Monitoring of NMBAs

1. twitch monitoring

2. Train of four (ToF)evaluations (2Hz over 2 seconds)

   1. 0 twitches = 100% blocked, 1 twitch = 95%, 2 twitch = 90%, 3 = 80%, 4 = <75%)

Rocuronium duration, elimination and adverse effects

20-70minutes

15% eliminated by liver, 85% kidneys

tachycardia, hypotension, flushing

current trends in intubation induction drugs paired w/ paralytics

Laryngoscopy + intubation MUST have a short-acting IV drug w/ sedative or combined sedative/analgesic properties. Potential drugs:

1. etomidate (hypnotic, preferred!)

2. fentanyl (analgesic + sedative properties, but @higher doses can cause chest wall rigidity)

3. ketamine (dissociative anesthetic w/ cardiostimulatory properties + can cause hallucinations or bizarre behavior on awakening)

Etomidate onset, advantages + disadvantages/cautions

3-5min

does not alter hemodynamics, ICPs, histamine, apnea. useful for trauma patients.

painful, causes adrenal suppression, does not suppress sympathetic response to laryngoscopy, nausea, vomitting, + DOES NOT PROVIDE ANALGESIA.

Tensilon test

uses Tensilon/edrophonium to diagnose myasthenia graves by preventing breakdown of chemical Ach. Positive test = if muscles get STRONGER after being injected w/ drug, as MG pt reacts to Ach differently as their muscles tire when antibodies attack their Ach receptors.

What treats MG?

neostigmine, being a cholinesterase inhibitor that slowly breaks down Ach when released from nerve endings, causing more Ach available to attach to muscle receptors, improving strength of their muscles.