Myasthenia Gravis A lack of nerve impulses and muscle responses at the myoneural junction causes fatigue and muscular

r weakness of the respiratory system, facial muscles and extremities.

Multiple Sclerosis Attacks the myelin sheath of nerve fibers, causing lesions known as plaques.

Muscle Spasms y Have various causes, including injury or motor neuron disorders that lead to conditions such as cerebral palsy, MS, Spinal cord injuries (paraplegia), cerebral vascular accident (stroke), or hemiplegia.

Myasthenia Gravis A chronic autoimmune neuromuscular disease that affects approximately 14 in 100,000 persons. It occurs at any age; however occurs more commonly in women younger than 30 years and men older than 50. Pathophysiology Myasthenia Gravis results from lack of acetylcholine (ACh) receptor sites. This autoimmune disorder involves an antibody response against an alpha subunit of the acetylcholine receptor (AChR) site at the neuromuscular junction. Antibodies attack AChR sites, obstructing the binding of ACh and eventually destroying receptor sites. When AChR are reduced, ACh molecules are prevented from binding to receptors and stimulating normal neuromuscular transmission. The result is ineffective muscle contraction and muscle weakness. About 90 % of clients with MG have anti- acetylcholine antibodies that can be detected through serum testing. When muscular weakness of the client with MG becomes generalized, myasthenic crisis may occur. This complication is a severe generalized muscle weakness and may involve the muscles of respiration, such as the diaphragm and intercostals muscles. Overdosing with AChE inhibitors may cause another complication of MG called cholinergic crisis, which is an acute exacerbation of symptoms. It occurs within 30 to 60 minutes after taking anticholinergic medications. This complication is due to continuous depolarization of postsynaptic membranes that create neuromuscular blockade. The client with cholinergic crisis often has severe muscle weakness that can lead to respiratory paralysis and arrest.

Acetylcholinesterase Inhibitors / Cholinesterase Inhibitors -group of drugs used to contol MG, which inhibits the action of the enzyme, which activates the cholinergic receptors and promote muscle contraction. Ambenomium (Mytelase) for myasthenia gravis. A long acting AChE inhibitor. It is 6 times more potent than neostagmine. Frequently used when client cannot take neostagmine or pyridostigmine because of the bromide component. Edrophium Cl (Tensilon) for diagnosing myasthenia gravis. Very short acting drug. Ptosis should be absent in 1- 5 minutes. Neostigmine Bromide (Prostigmin) for controlling myasthenia gravis. Must be given on time to prevent myasthenia crisis. Parenteral route is used if chewing , swallowing and breathing are affected. Because of its short half life (0.5 to 1 hour), dose is usually given in 3 to 6 divided doses. Pyridostigmine Bromide (Mestinon) has an intermediate action and is given every 3 to 6 hours. Side Effects and Adverse Reactions y y Others y y y y Miosis Blurred vision Bradycardia Hypotension GI disturbances (N and V, diarrhea, abdominal cramps) Increased salivation and tearing

Multiple Sclerosis An autoimmune disorder that attacks the myelin sheath of nerve fibers in the brain and spinal cord, causing lesions that are called plaques. MS affects approximately 300,000 persons (ages 20 to 40), mostly white women. Onset of MS is usually slow. It is a condition in which there are remissions and exacerbations of multiple symptoms (sensory and cerebral) such as diplopia, weakness in extremities, or spacity. Available laboratory tests that may suggest MS include elevated immunoglobulin G in the cerebrospinal fluid, increased IgG/albumin ratio and multiple lesions observable through MRI. Treatment Strategies for the Three Phases of Multiple Sclerosis

Phases of Multiple Sclerosis y Acute attack

Characteristics

Treatment Strategies

Fatigue; motor weakness; optic neurtitis

y y y

Remission Exacerbation

Recurrence of clinical MS symptoms; spacity

y y Chronic Progressive Progressive MS symptoms y

Tapering course of glucocorticoids (prednisone) Adrenocorticotropic hormone stimulates the adrenal cortex to secrete cortisol 6- alpha methylprednisolone sodium succinate Biologic Immune response modifiers (Betaseron) Reduces spacity and improves muscle movement. Interferon beta 1-a includes (Rebif and Anovex), used in relapsing forms of MS Immunosuppressant cyclophosphamide (Cytoxan)

Skeletal Muscle relaxants relieve muscular spasms and pain associated with traumatic injuries and spacity from chronic debilitating disorders. Spacity results from increased muscle tone from the cerebral neurons or lack of inhibition in the spinal cord or at the skeletal muscles. It is a muscular hyperactivity that causes contraction of the muscles, resulting pain and limited mobility. The centrally acting muscle relaxants depress neuron activity in the spinal cord or brain and act directly on the skeletal muscles. They are used in cases of spacity to suppress hyperactive reflex and for muscle spams that do not respond to anti-inflammatory agents, physical therapy or other forms of therapy. Muscle Relaxants Anxiolytics Diazepam (Valium) used to relieve muscle spasms associated with paraplegia and cerebral palsy Meprobamate (Miltown) has a muscle relaxant effect. Muscle Relaxants Spacity (Centrally Acting) Baclofen (Lioresal) for muscle spasms caused by MS and spinal cord injury. Tizanidine (Zanaflex) used to manage spacity, especially for spinal cord injury and multiple sclerosis.

Spacity ( Direct Acting) Dantrolene sodium (Dantrium) for chronic neurologic disorders causing spasms: spinal cord injuries, stroke, MS. Centrally Acting Muscle relaxants Carisoprodol (Soma) Chlorzoxazone (Parafon forte) for acute or severe muscle spasms. Cyclobenzaprine HCl (Flexeril, Cycoflex) for short term treatment of muscle spasms. Methocarbamol ( Robaxin, Marbaxin) for acute muscle spasms; drug used for treatment of tetanus. Metaxalone (Skelaxin) for acute painful muscle spacity. Orphenadrine citrate (Norflex, Flexon) for acute muscle spasm. Can be toxic with mild overdose. Depolarizing Muscle Relaxants( Adjunct to Anesthesia) Pancuronium Bromide (Pavulon) used in surgery for relaxation of skeletal muscles. Succinylcholine Cl (Anectine Cl, Quelicin, Sucostrin) - used in surgery with anaesthesia for skeletal muscle relaxation. Vecuronium Bromide (Norcuron) use is similar as anectine Cl; Can be used in clients with asthma, renal disease, or limited cardiac reserve. Tubocurarine Cl Adjunct to general anaesthesia. To induce muscle relaxation. Side effects and Adverse Effects y y y y y y Drowsiness Dizziness Light headedness Headache Occasional GI sensitivity Anticholinergic effects.

Antiinflammatory Drugs

Inflammation A response to tissue injury and infection. The process of inflammation is a protective mechanism in which the body attempts to neutralize and destroy harmful agents at the site of injury and to establish conditions for tissue repair. Infection is caused by microorganisms and results in inflammation , but not all inflammations are caused by infections.

Pathophysiology Five characteristics of inflammation ( Cardinal signs of inflammation) y y y y y Redness Swelling (edema) Heat Pain Loss of function

2 phases of inflammation  Vascular Phase y occurs 10 - 15 minutes after injury. y Associated with vasodilation and increased capillary permeability, during which blood substances and fluid leave the plasma and go to the injured site.  Delayed Phase y Occurs when leukocytes infiltrate the inflamed tissue. Various chemical mediators released during inflammation process  Prostaglandins have many effects: vasodilation, relaxation of smooth muscle, increased capillary permeability and sensitization of nerve cells to pain.  Cyclooxygenase enzyme responsible for converting arachidonic acid into prostaglandins and their products. There are 2 enzyme forms of cyclooxygenase: COX-1 protects the stomach lining and regulate blood platelets, COX -2 triggers inflammation and pain.

Anti-inflammatory Agents Inhibit the biosynthesis of prostaglandin which affect the inflammatory process. It also relieve pain, reduce elevated body temperature and inhibit platelet aggregation. Nonsteroidal Antiinflammatory Drugs Aspirin or aspirin- like drugs that inhibit the enzyme COX, which is needed for the biosynthesis of prostaglandins. These drugs may be called prostaglandin inhibitors with varying degrees of analgesic and antipyretic effects, but they are used primarily as anti-inflammatory agents to relieve inflammation and pain. NSAID s are more appropriate for reducing swelling, pain and stiffness in joints. Seven Groups of NSAID s 1. 2. 3. 4. 5. 6. 7. Salicylates Para- Chlorobenzoic acid derivatives, or indoles Phenylacetic acids Propionic acid derivatives Fenamates Oxicams Selective COX-2 inhibitors

The first six NSAID groups are known as first generation NSAID s, and the COX-2 inhibitors are called second- generation NSAID s. Salicylates Aspirin (Acetylsalicylic Acid) developed in 1899 by Adolph Bayer. It is a prostaglandin inhibitor that decreases the inflammatory process. It is also considered an antiplatelet drug for clients with cardiac or cerbrovascular disorders; aspirin decreases platelet aggregation, thus blood clotting is decreased. Aspirin and other NSAID s relieve pain by inhibiting the enzyme COX, which is needed for the biosynthesis of prostaglandins. Hypersensitivity to Salicylate Products Symptoms of aspirin overdose or hypersensitivity to aspirin y y y Tinnitus Vertigo Bronchospasm

Diflusinal (Dolobid) Acts by inhibiting prostaglandin synthesis. Relief of mild to moderate pain; used to treat osteoparthritis and rheumatoid arthritis. Avoid if hypersensitive to aspirin.

Salicylate Derivatives Olsalazine Sodium (Dipentum) treat inflammatory bowel disease, especially ulcerative colitis. Sulfasalazine (Azfulfidine) treatment of ulcerative colitis and rheumatoid arthritis.

Para Chlorobenzoic Acid (Indoles) Indomethacin (Indocin) for moderate to severe arthritic conditions (rheumatoid arthritis, gouty arthritis and osteoarthritis). It is highly protein bound and displaces other protein- bound drugs, resulting potential toxicity. It has moderate half life of 4 to 11 hours. It is very irritating to the stomach and should be taken with food. Sulindac (Clinoril) for acute and chronic arthritis, bursitis and tendinitis. Not as potent as indomethacin. Should be taken with food. Tolmetin ( Tolectin) For acute and chronic arthritis, including juvenile rheumatoid arthritis. Less potent than indomethacin; more effective than aspirin. Should be taken with food. Phenylacetic Acid Diclofenac Sodium (Voltaren) It is indicated for rheumatoid arthritis, osteoarthritis and spondylitis. Has a plasma half life of 8 to 12 hours. Its analgesic and anti-inflammatory effects are similar to those of aspirin. Etodolac ( Lodine) used for acute pain, rheumatoid arthritis and osteoarthritis. Take with food or antacid to avoid GI distress. Ketorolac tromethamine (Toradol) first injectable NSAID. For short term pain management of 5 days. Like other NSAID s, it inhibits prostaglandin synthesis and has greater analgesic properties than other anti-inflammatory agents. Poprionic Acid Fenoprofen Calcium (Nalfon) treatment for mild to moderate pain. Also for arthritic conditions. Flurbiprofen Sodium ( Ansais, Ocufen) treatment foracute and chronic arthritis. Ibuprofen (Motrin, Advil, Nuprin, Medipren) Ketopren (Orudis, Actron) - relief of pain and acute and chronic arthritis. Naproxen (Naprosym) relief of mild to moderate pain. Also for arthritic, gout, bursitis conditions and dysmenorrhea.

Oxaprozin (Daypro) treatment for acute and chronic arthriris. Arthranilic Acids (Fenamates) Meclofenamamate (Meclomen) for acute and chronic arthritis. GI can be severe. Mefenamic Acid (Ponstel) - for acute and chronic arthritis. Oxicams Piroxicam(Felderne) - For arthritic conditions. Long half life; effective at 2 weeks. Meloxicam (Mobic) For treatment of osteoarthritis. Naphthylalkanones Nabumetone (Relafen) treat chronic inflammation and pain, especiall for arthritic conditions such as rheumatoid arthritis. COX 2 Inhibitors (Second Generation NSAIDs) Celecoxib (Celebrex) treat arthritic typr of pain. Relieves inflammation and pain without causing GI distress.

Corticosteroids this group of drugs controls inflammation by suppressing or preventing many of the components of the inflammatory process at the injured site. They are frequently used to contol arthritic flare-ups. It has a long half life (greater than 24 hours). Disease Modifying Antirheumatic Drugs     Gold drug therapy Immunosuppressive agents Immunomodulators Antimalarials

Gold drug therapy (chrysotherapy) is used to arrest progression of rheumatoid arthritis and prevent deformities caused by disease. It depresses migration of leukocytes and suppresses prostaglandin activity. It inhibits destructive lysosomal enzymes contained in leukocytes which are released in the joints. Gold Preparations y y Aurofarin (Ridaura) orally administered Aurothioglucose (Solganal) and Sodium thiomalate (Myochrysine) parenteral administered

Side effects and Adverse Reactions y y y y y y y y y y y Dermatitis Urticaria Erythema Alopecia Stomatitis Pharyngitis Gastritis Colitis Hepatitis Severe blood dyscrasias Anaphylactic shock

Contraindications y y y y y Eczema Urticaria Colitis Hemorrhagic conditions Systemic lupus erythematosus

Immunosuppressive Agents Used to treat refractory rheumatic arthritis ( arthritis that does not respond to anti-inflammatory drugs). Drugs such as azathioprine (Imuran), Cyclophosphamide (Cytoxan) and Methotrexate (Mexate), used to suppress cancer growth and proliferation, might be used suppress inflammatory process of rheumatoid arthritis when other treatments fail. Immunomodulators Treat moderate to severe rheumatoid arthritis by disrupting the inflammatory process and delaying the disease progression. 2 Groups of drugs classified as immunomodulators y Interleukin( 1L-1) is a proinflammatory cytokine that contributes to synovialinflammation and joint destruction. Example is Anakinra (Kineret) Tumor necrosis factor (TNF) blockers TNF blockers bind to TNF and block it from attaching to TNF receptors on the synovial cell surfaces. B yneutralizing TNF, a contributor to synovitis, inflammatory disease process is delayed. Example is Etanercept (Enbrel)

Antimalarials Used to treat rheumatoid arthritis when other methods of treatment fail. The mechanism of action of antimalarials are unclear. The effect may take 4 to 12 weeks to be apparent. Antigout Drugs Gout an inflammatory condition that attacks joints, tendons and other tissues. The most common site of acute gouty inflammation is the joint of the big toe. It is characterized by uric acid metabolism disorder and defect in purine (products of certain proteins) metabolism, resulting in an increase in uric acid salts and accumulation of uric acid in the kidneys. Example is Colchicine which inhibits the migration of leukocytes to the inflamed site. Uric Acid Inhibitor Allopurinol (Zyloprim) it inhibits the final steps of uric acid biosynthesis and therefore lowers serum uric acid levels, preventing precipitation of attack. This is used as a prophylactic to prevent gout. Uricosurics Increase rate of uric acid excretion by inhibiting its reabsorption. Effective in alleviating chronic gout. Probenecid (Benemid) is a uricosuric that blocks the reabsrption of uric acid and promotes its excretion. Another uricosuric is sulfinpyrazone ( Anturane) it is a metabolite of phenylbutazone and is more potent than probenecid. Side effects and Adverse Reactions y Flushed skin y Sore gums y Headache Others y y y Kidney stones Blood dyscrasias Uric acid retention