Chapter 12 Neuromuscular Blockade, Muscle Spasms PDF

7/4/2023 CHAPTER 12 Neuromuscular Blockade and Muscle Spasms 2 Treatment of Neuromuscular Blockade and Muscle Spasms (1 of 2) 1. Learn the terminology associated with neuromuscular blockade and muscle spasms. 2. Discuss the process of neuromuscular transmission. 3. List medical co...

7/4/2023 CHAPTER 12 Neuromuscular Blockade and Muscle Spasms 2 Treatment of Neuromuscular Blockade and Muscle Spasms (1 of 2) 1. Learn the terminology associated with neuromuscular blockade and muscle spasms. 2. Discuss the process of neuromuscular transmission. 3. List medical conditions that cause spasticity. 4. List and classify neuromuscular blocking drugs and drugs used to treat muscle spasms. 5. Describe the mechanism of action for peripheral and central-acting skeletal muscle relaxants. 1  7/4/2023 3 Treatment of Neuromuscular Blockade and Muscle Spasms (2 of 2) 6. List uses for neuromuscular blocking drugs. 7. Describe the mechanism for reversal of neuromuscular blockade. 8. List strategies for safe management of neuromuscular blocking drugs in the pharmacy. 9. Identify significant drug look-alike/sound-alike issues. 10. Identify warning labels and precautionary messages associated with neuromuscular blockers and medications used to treat spasticity. 4 Key Terms Acetylcholinesterase Amyotrophic lateral sclerosis (ALS) Anaphylactic shock Cerebral palsy Botulinum toxin Multiple sclerosis Central-acting muscle relaxants Tetanus Clonus Depolarizing neuromuscular blockers Endotracheal intubation End plate Neuromuscular junction Nondepolarizing competitive blockers Peripheral-acting muscle relaxants Sarcomere Sole plate Spasticity 2  7/4/2023 5 Overview (1 of 2) Skeletal muscle contraction occurs as a response to communication between peripheral nerves and muscles. Acetylcholine (ACh) transmits messages between nerve cells and muscle cells. ACh-filled vesicles are located in the motor neuron endplate. Calcium increases release of Ach Drugs that decrease the release of Ach or deplete Ach also cause skeletal muscle relaxation 6 Nerve and Muscle Interaction https://thebrain.mcgill.ca/flash/d/d_06/d_06_m/d_06_m_mou/d_06_m_mou.html 3  7/4/2023 7 Overview (2 of 2) ACh binds to nicotinic receptor sites located in the muscle soleplate. ACh binding causes an influx of sodium (Na+), calcium (Ca++), and potassium (K+) ions, increasing the endplate potential. Once endplate potential exceeds 15 mV, an action potential is produced, resulting in muscle contraction. 8 Acetylcholine in Synaptic Gap https://thebrain.mcgill.ca/flash/d/d_06/d_06_m/d_06_m_mou/d_06_m_mou.html 4  7/4/2023 9 Neuromuscular Blocking Agents Found in Nature Botulinum toxin, Magnesium Decreases release of acetylcholine Black widow spider venom Causes massive release of acetylcholine Results in contractions, cramping Ethanol (high doses) 10 Skeletal Muscle Relaxants Skeletal muscle relaxants are categorized by: Site of action Mechanism of action Two primary MOAs are: Central nervous system depression (central-acting muscle relaxants) Bind and block calcium channels Blockade of nerve transmission between the motor endplate and skeletal muscle receptors (peripheral-acting muscle relaxants) 5  7/4/2023 11 Peripheral-Acting Skeletal Muscle Relaxants Classifications: Nondepolarizing competitive blocking agents “-curonium” and “-curium” are common endings Blocks Ach receptors (antagonist) Atracurium Cisatracurium Pancuronium† Rocuronium Vercuonium‡ Depolarizing blocking agents: Binds to Ach receptors produce sustained depolarization, causing receptors to convert to their inactive state Inactivated by cholinesterases Succinylcholine Rapid onset of action and short duration of action In hospital setting *** Caution *** improper use may lead to death ‡ not available in Canada † available under emergency authorization https://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2020/72911a-eng.php 12 Peripheral-Acting Skeletal Muscle Relaxants Uses Surgery To relax muscles for ease of surgery General anesthesia Intubation 6  7/4/2023 13 Botulinum Toxin Type A Uses Temporarily remove wrinkles Excessive sweating Uncontrollable blinking Spasticity associated with cerebral palsy (not FDA approved) Treat migraines 14 Neuromuscular Blocking Agents: Adverse Reactions Allergic reactions: Itching or burning at the Rash/redness on face and injection site neck Hypotension Bronchospasm Flushing (vasodilation) Laryngospasm Tachycardia or bradycardia Anaphylactic shock Pulmonary edema Muscle pain Hyperkalemia Respiratory depression (depolarizing agents) Cardiac arrest 7  7/4/2023 15 Botulinum Toxin Type A: Adverse Reactions Droopy eyelid muscles (blepharoptosis) Headache Nausea Flulike syndrome Redness 16 Reversal of Neuromuscular Blockade Anticholinesterase drugs inhibit the action of ACh esterase at the neuromuscular junction. Neostigmine Pyridostigmine (Mestinon®) – tablets only in Canada Results in increased acetylcholine Adverse reactions include: Salivation Muscle twitching Muscle weakness Abdominal cramping Nausea Increased bronchial secretions Difficulty breathing 8  7/4/2023 17 Strategies for Safe Use of Neuromuscular Blocking Agents Neuromuscular blocking drugs are given USP classification of high alert because improper use can cause: Permanent injury Respiratory arrest Death Problems may result from: Improper product selection, storage conditions, or labeling Inappropriate dosing Inadequate patient monitoring 18 Recommendations for Pharmacy Practice with NMBAs There are recommendations for: Product selection Product storage Limiting access Auxiliary labels and warning labels *** PARALYZING AGENT *** Ordering practices and dispensing 9  7/4/2023 19 Overview (1 of 2) Spasticity: Debilitating motor disorder Affects 12 million people worldwide Interferes with activities of daily living Inhibits effective walking Causes fatigue and stiffness Disturbs sleep 20 Overview (2 of 2) Positive symptoms: Increased muscle tone Exaggerated tendon jerks Hyperexcitable stretch reflex Negative symptoms: Muscle weakness Decreased endurance Reduction in the capacity to make voluntary muscle movements ie. decreased coordinated movement 10  7/4/2023 21 Pathophysiology of Spasticity Four phases: Decreased muscle contractility Excessive muscle tone and increased reflex activity lasting from days to years Decreased reflex excitability Stiff, contracted muscles 22 Conditions That Produce Spasticity (1 of 2) Spinal cord injury Stroke Cerebral palsy Amyotrophic lateral sclerosis (Lou Gehrig’s disease) Multiple sclerosis Muscle strain 11  7/4/2023 23 Conditions That Produce Spasticity (2 of 2) Stroke or cerebral palsy: Formation of lesions in the brain or spinal cord Multiple sclerosis: Damage to myelinated nerves in the central nervous system Muscle injury or strain: Spasms are typically related to local injury or irritation of a specific muscle group 24 Spinal Cord Injury (1 of 2) Initial paralysis Loss of tendon reflexes below level of injury After shock period ends, increased muscle tone, exaggerated tendon jerks, and involuntary muscle spasms occur. Neurons branch out; muscles and tissues grow new synapses Stronger reflex connection and a greater response to stretching of the muscle 12  7/4/2023 25 Spinal Cord Injury (2 of 2) Normal inhibitory control of sustained neuron firing lost Unopposed motor neuron excitability Receptor sites more sensitive to neurotransmitters Muscle fibers atrophy; number of sarcomeres decreases 26 Amyotrophic Lateral Sclerosis (ALS) Lou Gehrig’s Disease Damage to upper motor neurons results in release of acetylcholine Release of acetylcholine causes desensitization of motor nerves, muscle weakness and cell death Stephen Hawking - physicist 13  7/4/2023 27 Neurotransmitters Involved in Spasticity (1 of 2) Acetylcholine ɣ-Aminobutyric Acid (GABA) Glycine Glutamate 28 Neurotransmitters Involved in Spasticity (2 of 2) Role of acetylcholine: Transmits messages between nerve and muscle cells Binds to nicotinic receptors to open sodium, calcium, and potassium channels Increases endplate potential Produces muscle contraction 14  7/4/2023 29 Role of ɣ-Aminobutyric Acid Major inhibitory neurotransmitter GABAA receptor binding causes chloride ion channels to open Hyperpolarization inhibits formation of action potentials GABAB receptor binding inhibits release of excitatory neurotransmitters and substance P Neuronal excitability reduced and nerve impulse transmission decreased 30 Role of Glycine Inhibitory neurotransmitter Defective receptors are associated with hyperekplexia Produces hypertonia 15  7/4/2023 31 Role of Glutamate Amino acid responsible for flow of calcium into motor neurons Voltage-dependent calcium channels may be involved in spasticity 32 Drugs Used to Treat Spasticity Peripheral-acting drugs: Act directly on contractile mechanisms in muscle Botulinum toxins Dantrolene 16  7/4/2023 33 Peripheral-Acting Drugs (1 of 2) Botulinum toxins A and B: Inhibit presynaptic release of ACh at neuromuscular junction to cause paralysis in muscles that received injections Paralysis reversed when motor neurons sprout new terminals that release ACh Onset of effect within 3 to 7 days of injection, lasting 3 to 6 months 34 Peripheral-Acting Drugs ( 2 of 2) Dantrolene: Weakens hyperexcited muscles Acts directly on contractile mechanism Inhibits release of calcium from sarcoplasmic reticulum, which inhibits calcium-dependent excitation Used to treat malignant hyperthermia Condition triggered by use of succinylcholine or anesthetic inhalation gases 17  7/4/2023 35 Drugs Used to Treat Spasticity (1 of 2) Central-acting drugs: Bind to receptor sites that control motor movement in brain and spinal cord Categorized according to mechanism of action GABAergic: baclofen (Lioresal®), diazepam Alpha2-adrenergic drugs: tizanidine 36 Drugs Used to Treat Spasticity (2 of 2) Adverse reactions: Sedation or dizziness (tizanidine, baclofen, dantrolene) Hypotension (tizanidine, baclofen) Headache (baclofen) Nausea (baclofen) Confusion (baclofen) Weakness or fatigue (baclofen, dantrolene) Diarrhea (dantrolene) Hepatotoxicity (dantrolene) 18  7/4/2023 37 MOA: Central-Acting Drugs (1 of 2) GABAergic drugs: Bind directly to GABA receptors or enhance GABA binding Baclofen: acts as agonist at GABAB receptor sites, where it decreases release of neurotransmitters that cause muscle contractions and inhibits release of substance P Does not cross BBB readily  effectiveness increased by giving drug intrathecally (directly into cerebrospinal fluid) Diazepam: increases binding of GABA to GABA receptors, decreasing excitability of nerve terminals and hyperpolarizing the nerve Improves range of motion Decreases anxiety and insomnia 38 MOA: Central-Acting Drugs ( 2 of 2) Alpha2-adrenergic drugs: - tizanidine Act like naturally occurring neurotransmitters Prevent release of excitatory neurotransmitters in spinal cord and increases actions of inhibitory neurotransmitter glycine Cause hyperpolarization of motor neurons and interfere with release of substance P 19  7/4/2023 39 Drugs Used to Treat Muscle Strain Skeletal muscle relaxants treat muscle stiffness, pain, and spasms associated with muscle tension, strain, sprains, or injury Drugs in this category are central acting Cyclobenzaprine (Flexeril®) Methocarbamol Orphenadrine (Norflex®) Chlorzoxazone+acetaminophen+codeine (Acetazone Forte®) ‡ The mechanism of action is unknown; may be related to sedative effects on the CNS ‡ discontinued in Canada 40 Tech Alert: Look-Alike/Sound-Alike Drugs Baclofen and Bactroban® Lioresal®, Lotensin®, and lisinopril Diazepam and Ditropan® Tizanidine and nizatidine Cyproheptadine, cyclobenzaprine 20  7/4/2023 41 Drugs Used to Treat Muscle Strain Adverse reactions: Dizziness or drowsiness Blurred vision Discoloration of urine—chlorzoxazone (orange to reddish purple) and methocarbamol (black, brown, or green) Warning Labels May cause dizziness or drowsiness. May impair ability to drive. Avoid alcohol Take with food May be habit forming 42 21