Module 2 Section 4 (Neuromuscular Blocking Drugs and Anesthetics) Flashcards
What is the peripheral nervous system composed of?
The peripheral nervous system is composed of the autonomic nervous system and the somatic nervous system.
What do the autonomic and somatic nervous systems innervate?
The autonomic nervous system innervates smooth and cardiac muscle
The somatic nervous system innervates skeletal muscle, which is under voluntary control and consists primarily of the muscles of posture and movement.
How many neurons are required for the somatic nervous system to reach the target skeletal muscle?
Unlike the autonomic nervous system, which consists of two neurons to reach the target organ, the somatic nervous system requires just one neuron to reach the target skeletal muscle.
True or false: in the somatic nervous system, the voluntary motor nerves extend from the CNS all the way to the skeletal muscle.
True
Describe the structure of the neurons in the somatic nervous sustem and what they release.
Some neurons in the somatic nervous system can be very long.
At the skeletal muscle, the neuron releases acetylcholine, which binds to nicotinic receptors on skeletal muscle.
- Receptor activation on the skeletal muscle causes contraction of the muscle
What is the neuromuscular junction?
The synapse between a motor neuron and skeletal muscle.
What occurs when the NN receptors on the skeletal muscle are activated?
When the NM receptors on the skeletal muscle are activated, they cause the muscle to contract.
In order for a muscle to contract, multiple NM (N= nicotinic; M = muscle) receptors on the muscle fibre have to be activated at once, causing depolarization of the skeletal muscle membrane followed by muscle fibre contraction.
Full muscle contraction is achieved when many NM receptors on many muscle fibers are activated simultaneously.
Drugs that target skeletal muscle act by interfering with neurotransmission within the neuromuscular junction. These drugs are called neuromuscular blocking drugs. What are the 2 types of neuromuscular blocking drugs?
Non-depolarizing neuromuscular blockers: these drugs act like competitive antagonists, blocking the NM receptors, thereby inhibiting the binding of acetylcholine to the receptors.
- Since less NM receptors are available for acetylcholine to bind to, the muscle is unable to depolarize and muscle contraction is inhibited.
Depolarizing neuromuscular blockers: these drugs function like agonists, activating the NM receptors, thereby initially causing muscle contraction.
- However, these drugs are resistant to acetylcholinesterase breakdown and therefore cause continual activation of the NM receptors without allowing time for the muscle to repolarize, leading to muscle paralysis.
What is the different between non-depolarizing and depolarizing neuromuscular blockers?
Ex: compare stopping a car by using the brakes to not being able to start a car because of a flooded engine.
A non-depolarizing neuromuscular blocker is similar to using the breaks to stop your car. It inhibits the acetylcholine (i.e. gas) from activating the receptors (i.e. engine), thereby stopping muscle contraction (i.e. the car).
A depolarizing neuromuscular blocker is similar to flooding the engine, since too much acetylcholine is in the neuromuscular junction activating the receptors (i.e. too much gas is in the engine), which results in a desensitization of the receptors (i.e. engine will not start), and therefore the muscle becomes paralyzed (i.e. the car cannot run).
Provide an example of non-depolarizing neuromuscular blockers.
The majority of clinically relevant neuromuscular blockers are non-depolarizing blocking agents.
The prototypical example drug in this class is tubocurarine.
- Onset of action of tubocurarine = four minutes
- Pharmacological effect = 45-60 minutes.
Clinically, tubocurarine is no longer commonly used, as it has been predominantly replaced by related drugs that have better safety profiles.
- However, the agents currently used clinically act in the same manner as tubocurarine.
How can the effect of non-depolarizing blocking agents be overcome?
The effect of non-depolarizing blocking agents can be overcome by using acetylcholinesterase inhibitor drugs (e.g. physostigmine). By inhibiting acetylcholinesterase, the buildup of acetylcholine is able to out compete the non-depolarizing blocking drug, resulting in muscle contraction.
How do depolarizing blocking agents work?
Depolarizing blocking agents activate the NM receptors similar to acetylcholine, depolarizing the plasma membrane of the muscle fiber. However, the drugs are more resistant to the enzyme acetylcholinesterase.
Therefore, the drug is not broken down in the synapse and the muscle fibers are persistently depolarized. The result is paralysis of muscle fiber
What depolarizing blocking agents are used clinically?
The only depolarizing blocking agent used clinically is succinylcholine.
- It has rapid onset (30 seconds) and a short duration of action (5-10 minutes).
- The short duration of action is due to the fact that succinylcholine is metabolised by cholinesterase in the plasma of the blood, which is why the duration of action is short compared to non-depolarizing blocking agents.
Two phases exist to the depolarizing block. What are they?
1) Depolarizing phase: the muscle fibers depolarize in a disorganized manner, resulting in muscular fasciculation (i.e. twitching).
- Once the muscle fibers depolarize, they are unable to repolarize due to the continual presence of the drug activating the receptors, resulting in paralysis.
2) Desensitizing phase: this occurs after prolonged exposure to the depolarizing blocking agent.
- The muscle membrane eventually repolarizes, but it is now desensitized. Therefore, the muscle is no longer responsive to acetylcholine and full neuromuscular block has been achieved.
- The result is flaccid paralysis, a condition where your muscles are unable to contract.
What occurs during the desensitization phase?
During the desensitization phase, once the NM receptors become desensitized to the depolarizing blocker, the NM receptors act as if an antagonist is binding instead of an agonist.
Consequently, binding of acetylcholine to the NM receptors also no longer activates them.
Because of this desensitization, the effect of depolarizing blocking agents is prolonged by the use of acetylcholinesterase inhibitor drugs, since neither acetylcholine nor the depolarizing blocking drug can activate the NM receptors.
What are some adverse effects of depolarizing neuromuscular blockers?
Hyperkalemia: normal activation of NM receptors opens the receptor’s intrinsic Na K channel, causing Na to rush into the cell and K to trickle out of the cell.
- Usually, the channel is more permeable to Na than to K, however, during sustained depolarization, K can rush out of the cell and into the blood.
- Elevated levels of K in the blood can lead to cardiac arrest.
- Patients with burns, nerve damage, or neuromuscular disease are susceptible to this adverse effect, as NM receptors are often upregulated in these conditions.
Muscle pain: use of depolarizing blockers such as succinylcholine are associated with postop pain.
- This is more common for heavily muscled patients.
Malignant hyperthermia: this is an uncommon, genetically linked condition that can occur after exposure to succinylcholine and manifests as a rise in body temperature, tachycardia, and muscle rigidity.
- Symptoms usually develop within an hour of exposure.
What are some clinical indications of neuromuscular blockers?
Not many drugs target skeletal muscle.
However, a few therapeutic indications for targeting skeletal muscle exist, such as during surgical procedures (e.g. to produce muscle paralysis as adjuncts to anesthetics) or to reduce spasticity (e.g. muscle relaxants for chronic back pain or fibromyalgia).
Surgery: the most common use of neuromuscular blockers is during surgical procedures.
- By using drugs to target skeletal muscle, it is possible to achieve adequate muscle relaxation for all types of surgical procedures, especially during intra-abdominal and intra-thoracic procedures, without the cardiorespiratory depressant effects of deep anesthesia.
Endotracheal intubation: relaxation of the tracheal and pharyngeal muscles, facilitating the insertion of the endotracheal tube, which maintains airways during surgery. - Succinylcholine is often used, as short-term paralysis is needed for endotracheal intubation.
Control of ventilation: for critically ill patients who have respiratory failure.
- By administering a neuromuscular blocker, chest wall resistance and ineffective spontaneous ventilation is eliminated, allowing the ventilator to maintain respiration.
What are the neurotransmitters used in the parasympathetic, sympathetic, and somatic nervous system?
The parasympathetic nervous system releases acetylcholine from the presynaptic neurons and the postsynaptic neurons.
The sympathetic nervous system releases acetylcholine from the presynaptic neurons and norepinephrine from the postsynaptic neurons.
The somatic nervous system, a one-neuron system, releases acetylcholine from the motor neurons.
What is anesthesia? What is the purpose?
Anesthesia is defined as a state of loss of sensation.
The purpose of anesthesia is to protect the patient from the pain of surgery, and secondarily to provide a still surgical field.
What are the 5 physiological characteristics of general anesthesia?
- hypnosis (loss of consciousness)
- amnesia (loss of memory)
- analgesia (loss of response to pain)
- areflexia (loss of autonomic response)
- relaxation (skeletal muscle relaxati
True or false: general anesthetics are often used in combination.
True
As you can probably guess, no single anesthetic agent is capable of achieving all of these desirable effects. Therefore, general anesthetics are often used in combination.
How do anesthetics work?
In general, anesthetics work by globally depressing the CNS.
Specifically, anesthetics depress the reticular activating system (a bundle of nerve fibres near the brainstem that filters unnecessary information from reaching the brain, such as a crowd of talking people) in the brain.
What are the potential theories by which neural depression occurs?
1) Facilitation of GABA-mediated inhibition at GABAA receptor chloride channel: strengthens the inhibitory function of GABA, increasing CNS depression.
2) Antagonism of glutamic acid excitation of NMDA channel receptor: decreases excitation in the CNS, enhancing CNS depression.
What are the 2 categories that general anesthetics can be divided into?
1) Inhaled anesthetics
2) Intravenous anesthetics
