2© Paradigm Publishing, Inc. Chapter 10 The Muscular System and Drug Therapy

Chapter 10 Topics Anatomy and Physiology of the Muscular System Muscle Spasm and Relaxation Other Muscle Disorders Herbal and Alternative Therapies 3© Paradigm Publishing, Inc.

Anatomy and Physiology of the Muscular System Muscular System and Skeletal Muscles Muscular system  Is responsible for movement, posture, and body heat  Divided into three types: skeletal, cardiac, and smooth Skeletal muscles  Are connected to bones and joints by tendons  Provide voluntary movement, such as walking, clapping, and chewing  Developed and enhanced through bodybuilding and performance training 4© Paradigm Publishing, Inc.

Anatomy and Physiology of the Muscular System Cardiac and Smooth Muscles Cardiac muscle  Is found only in the heart  Provides pump and squeeze action for heartbeat Smooth muscle  Is found in the intestines and blood vessel walls  Provides peristalsis  Movement that pushes material through tubes, such as food through the intestines or blood flow  Are involuntarily controlled by the autonomic nervous system 5© Paradigm Publishing, Inc.

Anatomy and Physiology of the Muscular System © Paradigm Publishing, Inc.6 Types of Muscle Tissue Under the microscope, cardiac and skeletal muscles appear to have stripes called striations

Anatomy and Physiology of the Muscular System The Process of Muscle Contraction Nerve cells interface with muscle cells to initiate muscle contraction in the neuromuscular junction Nerve cells release Ach and this neurotransmitter moves across the synaptic cleft to stimulate muscle cell receptors  Membrane depolarization occurs (positive and negative electrical charges along membranes surface change)  Sodium influx occurs causing the release of intracellular calcium, stimulating muscle fibers to contract  Muscle fibers then shortens and pulls on the attached bones and joints, creating movement 7© Paradigm Publishing, Inc.

Anatomy and Physiology of the Muscular System © Paradigm Publishing, Inc.8 Neuromuscular Junction and Contraction Muscle contraction stops when ACh is deactivated in the synaptic cleft by acetylcholinesterase, an enzyme

Anatomy and Physiology of the Muscular System Drug Therapy and Muscles Muscle injury  Is the most common reason for using drug therapy  Common in the lower back (latissimus dorsi); head and neck (trapezius); and legs (hamstring group, quadriceps, and soleus) IM drug administration  Administered to adults in the deltoid of upper arm and the gluteus medius in buttocks  Administered to children in the vastus lateralis (muscle group in the quadriceps group of the legs) 9© Paradigm Publishing, Inc.

Anatomy and Physiology of the Muscular System © Paradigm Publishing, Inc.10 Anatomy of the Muscular System

Anatomy and Physiology of the Muscular System © Paradigm Publishing, Inc.11 Anatomy of the Muscular System

Muscle Spasm and Relaxation Muscle Spasm and Spasticity Diseases and disorders of muscles relatively uncommon, but injuries occur often at all ages Spasm  Is an involuntary contraction of muscle fibers  Occurs after muscle is inflamed from cell damage  Can be painful Spasticity  Is a condition where the muscles become rigid and difficult to control for coordinated movement  Caused by brain damage, spinal cord injury, multiple sclerosis, cerebral palsy, or malignant hyperthermia 12© Paradigm Publishing, Inc.

Muscle Spasm and Relaxation Drugs for Muscle Relaxation Mechanisms of Action  Block signals from the brain and spinal cord that control muscle contraction  Inhibit ACh at the neuromuscular junction  Prevent intracellular calcium release Are CNS depressant drugs Indications: all generally sedating which slows reflexes and relaxes muscle spasms; some are used as anticonvulsants and antianxiety agents 13© Paradigm Publishing, Inc.

Anatomy and Physiology of the Muscular System © Paradigm Publishing, Inc.14 Muscle Control and Relaxation Three ways to block muscle contraction

Muscle Spasm and Relaxation Centrally Acting Muscle Relaxants Indication: muscle spasms related to acute injury Usage: usually given for a defined amount of time (days to weeks) until relief and healing occur Indications (baclofen and tizanidine): muscle spasticity Indications (other): give along with OTC and prescription- strength anti-inflammatory drugs like ibuprofen to control pain and swelling associated with injuries Routes: all are oral; methocarbamol (Robaxin) and orphenadrine citrate (Norflex) are also IM and IV; baclofen (Lioresal) is also IT 15© Paradigm Publishing, Inc.

Muscle Spasm and Relaxation Centrally Acting Muscle Relaxants (continued) Side Effects (common): sedation, drowsiness, dizziness, fatigue, confusion, impaired judgment, and altered coordination Side Effects (other): headache, nausea/vomiting, dry mouth, blurred vision, and constipation Side Effects (rare): can cause serious changes in heart function and blood pressure 16© Paradigm Publishing, Inc.

Muscle Spasm and Relaxation Centrally Acting Muscle Relaxants: Cautions Do not take with alcohol Should not use with drugs that also cause CNS depression  Antihistamines, opioids/ narcotic pain drugs, or other controlled substances Monitor closely if taking antidepressants or antipsychotics Do not take with MAOIs Monitor closely or do not take if have heart conditions, high blood pressure, or clotting disorders If skin rash or yellowing of the eyes develop, could be an allergic reaction or liver dysfunction 17© Paradigm Publishing, Inc.

Muscle Spasm and Relaxation Centrally Acting Muscle Relaxants: Cautions (continued) Tolerance and dependence can occur if taken long term Do not stop taking abruptly due to withdrawal symptoms Methocarbamol  Can turn urine brown, black, or green  Patients should be warned of this effect Orphenadrine  Should be swallowed whole, not chewed  Apply a warning label 18© Paradigm Publishing, Inc.

Muscle Spasm and Relaxation Centrally Acting Muscle Relaxants: Cautions (continued) Carisoprodol (Soma)  Requires heightened monitoring for abuse and addiction  Is metabolized by the liver to meprobamate  Meprobamate » Is an antianxiety medication and a controlled substance with high risk for abuse  Technicians should alert the pharmacist if patient receives multiple refills at once or requests early refills 19© Paradigm Publishing, Inc.

Your Turn Question 1: A technician notices that a patient often asks for early refills of carisoprodol (Soma). What should the technician do? Why? Answer: The technician should alert the pharmacist because the patient may be abusing or has an addiction to carisoprodol. This drug is metabolized to meprobamate, an antianxiety medication with high risk for abuse. Question 2: How is muscle spasticity different than muscle spasm? Answer: In spasticity, the muscles become rigid and difficult to control for coordinated movement. A spasm is an involuntary contraction of muscle fibers. 20© Paradigm Publishing, Inc.

Muscle Spasm and Relaxation Locally Acting Muscle Relaxants: Botulinum Toxin (Botox) Mechanism of Action: blocks release of ACh in the neuromuscular junction Indications: migraine headache, spasticity, and hyperhidrosis (excess sweating) Indications (most common): reduce facial lines and wrinkles  Administration: subdermal injection  Localized muscle paralysis occurs, so lines and wrinkles are less apparent  Effects lasts weeks to months  Rarely covered by insurance 21© Paradigm Publishing, Inc.

Muscle Spasm and Relaxation Locally Acting Muscle Relaxants: Botulinum Toxin (Botox) (continued) Side Effects (rare): dry mouth, headache, neck or back pain, pain/itching at injection site, upper respiratory tract infection, fever, and flulike symptoms Side Effects (severe): allergic reaction, chest pain, difficulty swallowing or breathing, heart attack, arrhythmias, and muscle weakness or paralysis in a larger area than where administered  More likely at high doses (low doses used for cosmetic) Cautions: use carefully if have muscle dysfunction and avoid deodorant for 24 hours if patient has hyperhidrosis 22© Paradigm Publishing, Inc.

Muscle Spasm and Relaxation Direct Acting Muscle Relaxants: Dantrolene (Dantrium) Mechanism of Action: blocks the intracellular release of calcium and weakens muscle contractility Indications: muscle spasticity due to spinal cord injury or cerebral palsy Indication (drug of choice): malignant hyperthermia, an emergency situation  Injectable dantrolene often in emergency drug kits in areas where anesthesia is administered  Technicians stock and monitor these kits 23© Paradigm Publishing, Inc.

Muscle Spasm and Relaxation Direct Acting Muscle Relaxants: Dantrolene (Dantrium) (continued) Routes: IV injection and oral (capsule) Dosage: 1–10 mg/kg Side Effects (common): drowsiness, dizziness, fatigue, confusion, impaired judgment, altered coordination, diarrhea, and photosensitivity Side Effect (long-term use): can be toxic to the liver Cautions: used with great caution in patients with liver disease and can turn urine orange or red 24© Paradigm Publishing, Inc.

Muscle Spasm and Relaxation Neuromuscular Blocking Agents Cause temporary paralysis Indications (with anesthesia): short-term muscle relaxation  Used during endotracheal intubation, mechanical respiration, and surgical procedures Are not prescribed in the outpatient setting for anyone not on a ventilator  Technicians in inpatient setting handle these agents Mechanism of Action: block ACh receptors or inhibit breakdown of Ach allowing muscle to continuously contract until fatigue and paralysis occur 25© Paradigm Publishing, Inc.

Muscle Spasm and Relaxation Neuromuscular Blocking Agents (continued) Choice of agent depends on the length of the procedure or the desired amount of time for ventilation Routes: all are IV; succinylcholine is also IM Side Effect: Low blood pressure and respiratory depression should be closely monitored Cautions: cardiac arrest and changes in cardiac function, especially in children; drugs are dosed individually Technicians should apply warning label to indicate the drugs should be given for intubation or to ventilated patients only 26© Paradigm Publishing, Inc.

Other Muscle Disorders Rhabdomyolysis Is a rare syndrome where muscle breakdown occurs and toxic cell contents are released into the bloodstream Occurs as a serious side effect of the cholesterol-lowering class of drugs called statins Symptoms may be silent but can include muscle aches and pain, red- to brown-colored urine, and muscle weakness Laboratory tests are used to detect muscle enzymes (CK) in the blood Acute renal failure is common; patients closely monitored Unexplained muscle pain or weakness should be reported 27© Paradigm Publishing, Inc.

Other Muscle Disorders Fibromyalgia Is a chronic muscle pain condition that is not fully understood Symptoms include musculoskeletal pain in the neck, back, shoulders, chest, arms, and legs; fatigue; tingling/numbness; dizziness; and mood disturbances Drug therapy includes duloxetine, pregabalin, and milnacipran (Savella)  Milnacipran (Savella)  Mechanism of Action: blocks reuptake of norepinephrine and serotonin  Side effects and cautions similar to SSRIs and SNRIs 28© Paradigm Publishing, Inc.

Other Muscle Disorders Myasthenia Gravis Is an autoimmune process that attacks and destroys ACh receptors on muscle cells in the neuromuscular junction Is a progressive disease that begins with muscle weakness in face and neck and eventually impairs movement in all limbs Drug therapy includes neostigmine (Prostigmin) and pyridostigmine (Mestinon) to enhance muscle strength; and azathioprine (Imuran) and cyclophosphamide (Cytoxan) to slow the disease progression  Neostigmine and pyridostigmine also used to reverse the action of muscle relaxants in cases of overdose 29© Paradigm Publishing, Inc.

Other Muscle Disorders Poliomyelitis (Polio) Is a rare infection of nerves that control the muscular system Is nearly eradicated in U.S. and most developed countries due to vaccine Remains a health threat in Africa, Asia, and South America Muscular Dystrophy Is a group of genetically acquired conditions causing muscle atrophy (shrinking) and wasting Can be severely debilitating and fatal Few drugs used to treat this condition 30© Paradigm Publishing, Inc.

Your Turn Question 1: What is the primary purpose for administration of botulinum toxin (Botox)? Answer: The most widespread use of this drug is to reduce facial lines and wrinkles. Question 2: A patient is complaining of severe, unusual muscle pain and weakness. The patient is taking atorvastin (Lipitor), a statin used to lower cholesterol. What is the probable diagnosis of this situation? What will the physician do? Answer: The physician thinks the patient may have rhabdomyolysis and will order laboratory tests to measure muscle enzymes CK in the blood. 31© Paradigm Publishing, Inc.

Herbal and Alternative Therapies Few herbal and natural products are used for muscular conditions Several herbal therapies taken for other problems can interact with prescription muscle relaxants  Includes St. John’s wort, valerian, and kava  Technicians take note if patients purchase such products along with their prescription muscle relaxants Spinal realignment  Performed by a chiropractor  Used to relieve muscular pain 32© Paradigm Publishing, Inc.

Summary Muscle injury is the most common reason for using drug therapy Centrally acting muscle relaxants are used for muscle injury Direct acting muscle relaxants are used primarily for muscle spasticity due to select conditions Botulinum toxin is an expensive cosmetic agent Neuromuscular blocking agents temporarily relax and paralyze muscles during intubation and ventilation 33© Paradigm Publishing, Inc.