1 Therapeutic Agents for the Musculoskeletal System Chapter 17 1 Anatomy and Physiology of the Skeletal System Provides structural support for the body Consists of muscles, tendons, ligaments, and bones Bone marrow: Blood cells are produced here Storage banks for minerals (calcium, phosphorus) important in bodily functions Two types of bone: Compact and spongy 2 Compact bone, also known as cortical bone, is very dense and located near the surface of the bones, where there is the greatest need for strength. Spongy bone, on the other hand, is typically located on the inner part of bones and is composed of a network of thin strands of bone known as trabeculae. Spongy bone is sometimes called cancellous bone. The skeletal system provides structural support for the body, provides protection for many of the organs within the body, and facilitates movement. Bones also serve as storage banks for minerals such as calcium and phosphorus. The skeletal system provides structural support for the body and provides protection for many of the organs within the body. Bones also serve to facilitate movement. 2 Anatomy and Physiology of Skeletal Muscle 3 Each muscle is composed of fibers that are grouped into bundles called fascicles. Bones serve as storage banks for minerals such as calcium and phosphorus. Three types of muscle: Skeletal Cardiac Smooth Attach to bones and aid in movement Each muscle contains muscle fibers 3
Anatomy and Physiology of Skeletal Muscle (Cont.) 4 The point where a motor neuron meets and signals the skeletal muscle is known as the neuromuscular junction. Groups of fascicles: Myofibrils, actin and myosin filaments Signals cause muscles to contract Motor nerves carry signals from central nervous system (CNS) to skeletal muscles Neuromuscular junction 4 Osteoarthritis Common form of joint disease Loss of normal cushioning Usually affects knees, hips, spine, hands, feet There is no cure for osteoarthritis (OA), but slowing the disease is possible 5 Medications are used to maintain quality of life and to control pain. Risk factors for osteoarthritis include increasing age, obesity, repetitive joint overuse, and joint trauma. Osteoarthritis, commonly abbreviated OA, is a disease associated with aging that affects articular cartilage, which is cartilage that lines the joints. OA is the most common form of joint disease. Unlike rheumatoid arthritis, no systemic illness is generally associated with osteoarthritis. 5 Treatment for Osteoarthritis Occupational and physical therapy, regular exercise, weight loss Acetaminophen (APAP) (analgesic and antipyretic) Nonsteroidal antiinflammatory drugs (NSAIDs) (antiinflammatory) Steroid injections 6 6 Although acetaminophen, NSAIDs, and opioid analgesics can be used for a variety of pain conditions, they are discussed in detail here largely in the context of the treatment of OA. An antipyretic drug is used to prevent or reduce fever. Although acetaminophen affects cyclooxygenase enzymes in an inhibitory way to relieve pain and fever, it works in the CNS and does not alleviate inflammation in the periphery. Respiratory depression is the most severe side effect of opioid medications. Acetaminophen (Tylenol) is not an anti-inflammatory agent. Although it affects cyclooxygenase enzymes in an inhibitory way, thereby relieving pain and fever, it works in the central nervous system (CNS) and does not alleviate inflammation in the periphery. An important difference between acetaminophen and aspirin is that acetaminophen does not have peripheral antiinflammatory properties or inhibitory effects on platelet function, which makes it safer to use with warfarin. Misuse of acetaminophen is the most common cause of acute liver failure in the United States and therefore is not considered risk free. First-generation NSAIDs inhibit COX-1 and COX-2 enzymes, which results in a decrease in inflammation, pain, and fever. Unfortunately, inhibiting COX-1 enzymes has serious side effects such as gastric ulceration, bleeding, and renal damage. Celecoxib (Celebrex) is currently the only COX-2 inhibitor approved for use in the United States. The COX-2 inhibitor Vioxx was withdrawn from the market because of safety concerns, including the potential for an increased risk of cardiovascular events, such as heart attack and stroke. Mobic and
Acetaminophen Both an analgesic and an antipyretic Does not have peripheral antiinflammatory or inhibitory effects on platelet function Misuse of this is most common cause of liver failure Most cases are unintentional 7 Acetaminophen is widely considered the analgesic of choice for osteoarthritis, largely because when compared with NSAIDs, acetaminophen has fewer hematologic, gastrointestinal (ulcer), and renal effects. Maximum dose of acetaminophen (N-acetyl-p-aminophenol [APAP]) is 4 grams per day. 7 Aspirin Discovered from bark of willow tree Marketed by Bayer in 1899 Treats pain, fever, inflammation Shouldn't be given to children Reye s syndrome associated with its use 8 Maximum dose for adults is 4 g per day. A common side effect is upset stomach. Reye syndrome is a life-threatening metabolic disorder in young children of uncertain causes but is sometimes precipitated by the use of aspirin (acetylsalicylic acid). 8 Nonsteroidal Antiinflammatory Drugs (NSAIDs) Close structure to aspirin Suppress inflammation by inhibiting the cyclooxygenase (COX) enzyme COX-1: Promotes platelet aggregation, metabolic function COX-2: At site of tissue injury 9 NSAIDs suppress inflammation and also can be used for mild to moderate pain. They also have an antipyretic function (fever reducing). Celecoxib (Celebrex) is currently the only selective COX-2 inhibitor approved for use in the United States. Tylenol (acetaminophen) inhibits COX-1 and COX-2 enzymes within the CNS. Vicodin is a combination of hydrocodone and acetaminophen. 9
Common NSAIDs 10 Vioxx and Bextra, both of which are COX-2 inhibitors, were withdrawn from the market due to safety concerns. Advil and Motrin are both brands of ibuprofen, whereas the generic naproxen is marketed as Naprosyn. Naproxen, meloxicam, ibuprofen Should be taken with food to avoid stomach irritation 10 Cyclooxygenase-2 Inhibitors Two forms: COX-1 COX-2 Side effects of inhibiting COX-1: Gastric ulceration, bleeding, renal damage COX-2 inhibition does not reduce NSAID side effects 11 The theory behind COX-2 selective inhibitors is that they could treat pain and inflammation without the risk of nonselective agents that also inhibit COX-1. COX-2 inhibitors are now usually reserved for patients who are intolerant of traditional NSAID agents. 11 Opioid Analgesics Mechanism of action: Act on opioid receptors in brain Changes perception of pain at CNS and spinal cord level Morphine is prototypical opioid agent Schedule II (controlled substances) Causes sedation and respiratory depression 12 12 The three main types of opioid receptors in the brain are mu, kappa, and delta opioid receptors. Activation of mu-receptors produces analgesia, miosis (pupillary constriction), respiratory depression, euphoria, decreased gastrointestinal motility, and physical dependence. Overdose is potentially life threatening. Analgesia with opioids is mediated through changes in the perception of pain at the level of the spinal cord and CNS. Opioid medications are controlled substances, with the schedule depending on the agent and formulation. Tylenol with codeine is designated a C-III medication. Ultram is not a scheduled medication, and both Percocet and Duragesic are designated as C- II medications because of their high abuse potential. Opioid analgesics may cause dizziness or drowsiness, and alcohol will intensify these effects. All opioid analgesics are scheduled medications and therefore require the auxiliary label that reads, Caution: Federal law prohibits. Opioid antagonists, such as naloxone (Narcan) and naltrexone (Vivitrol), can be used to reverse the effects of opioid agonists by competing for opioidreceptor sites. Percocet is the combination of oxycodone and acetaminophen.
Osteoporosis Systemic skeletal disease Low bone mass and deterioration Danger is bone fracture Affects postmenopausal women 13 Osteoporosis is a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, which leads to bone fragility. Osteoporosis occurs when bone resorption outpaces the laying down of new bone. Fosamax, Boniva, and Actonel are all bisphosphonates. Evista is an estrogen modulator. Boniva may be administered 3 mg IV bolus every 3 months, as well as orally. Actonel and Fosamax are only available orally. Some prescription agents, such as the bisphosphonates and raloxifene (Evista), are indicated for both the prevention and the treatment of osteoporosis. Others, such as calcitonin, are used only for treatment. Adequate intake of vitamin D and calcium are critical co-therapies. Bisphosphonates (Fosamax and Actonel) and raloxifene (Evista) are indicated for both the prevention and the treatment of osteoporosis. 13 Osteoporosis Management and Treatment 14 According to the National Osteoporosis Foundation, approximately 10 million people have osteoporosis, and 34 million are estimated to have low bone mass, which can lead to osteoporosis. Loss of calcium from the bones resulting in bones that become brittle and fracture or break easily Prevention of osteoporosis: Must be started early in life Lifestyle changes, exercise, diet, smoking cessation Exercise, calcium, vitamin D: Increase bone density 14 Osteoporosis Management and Treatment 15 An adequate intake of vitamin D and calcium are critical co-therapies. New studies: 15 minutes of direct sunlight twice weekly supplies enough vitamin D for body Multivitamins act as replacement for sun Long-term use of corticosteroids, medroxyprogesterone, excessive thyroid hormones promote osteoporosis 15
Gout Arthritis that occurs when uric acid builds in blood Uric acid crystals in joints lead to inflammation and pain Acute attack: Usually affects a single joint Treatment: Weight loss; abstaining from alcohol; diets low in beef, lamb, pork Drug treatments: Therapies include colchicine, NSAIDs, and corticosteroids 16 Ninety percent of patients with gout have trouble excreting uric acid, and 10% are overproducers. The prognosis for gout can be good if contributing factors can be identified and resolved to prevent recurrent gout attacks. Gout is a form of arthritis that occurs when uric acid builds up in the blood, leading to the development of uric acid crystals in the joint and resulting in inflammation and pain. A variety of nonpharmacologic interventions can be made to decrease the risk of gout attacks. Weight loss, abstaining from alcohol, and adopting a low purine diet (i.e., avoiding meats such as beef, lamb, and pork) can be particularly beneficial. Therapies include colchicine, NSAIDs, and corticosteroids, as well as maintaining low uric acid levels by using uricosuric drugs or xanthine oxidase inhibitors. 16 Skeletal Muscle Relaxants Used in injuries to musculoskeletal system Severe or chronic pain may require more care Drug therapies: Analgesics, muscle relaxers, physical therapy 17 For severe injuries, surgery may be an option if medications and physical therapy prove ineffective for treating the condition and maintaining quality of life and functionality. Skeletal muscle relaxants may cause dizziness and drowsiness, and alcohol can intensify these effects. Baclofen (Lioresal) is a skeletal muscle relaxant. 17 Neuromuscular Blockers Used with anesthetics in surgery Relax skeletal muscles to induce paralysis Two categories: Depolarizing and nondepolarizing Depolarizing: Succinylcholine (mimics acetylcholine) Nondepolarizing: Block receptor activation, preventing transmission of impulses 18 They are used to help place the patient on a ventilator and to suppress the patient s spontaneous breathing once a ventilator is in place. The type of neuromuscular blocker used depends on the duration of anesthesia required. Depolarizing agents, such as succinylcholine, mimic the effects of the neurotransmitter acetylcholine. Nondepolarizing agents block receptor activation by acetylcholine and thus prevent the transmission of impulses leading to muscle relaxation. 18