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PTP 546 Module 9Pharmacology of Inflammation &

Treatment of Skeletal Muscles

Jayne Hansche Lobert, MS, RN, ACNS-BC, NP

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PharmacologySkeletal Muscle Relaxants

• Treatment of Muscle Spasms– Benzodiazepines• Diazepam (Valium)

– Physical and psychological dependence

– Polysynaptic Inhibitors• Carisoprodol (Soma)• Cyclobenzaprine (Flexeril)• Methocarbamol (Robaxin)

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PharmacologySkeletal Muscle Relaxants

• Benzodiazepines– Ex: Diazepam (Valium)– Action: potentiates the inhibitory effects of GABA– Therapeutic Effect: short term treatment of acute

muscle spasms– Side Effects: sedation, psychomotor impairment,

abrupt withdrawal rebound symptoms anxiety, seizures, death

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PharmacologySkeletal Muscle Relaxants

• Polysynaptic Inhibitors– Ex: Carisoprodol (Soma); Cyclobenzaprine (Flexeril); Methocarbamol (Robaxin); Chlorzoxazone(Paraflex)

– Action: decrease reflex activity in the spinal cord & generalized reduction in CNS excitability

– Therapeutic Effect: skeletal muscle relaxant – Side Effects: drowsiness, dizziness, ataxia, vertigo,

potential for tolerance and physical dependence, should not drive

– Note: typically used in combination with rest, physical therapy & NSAID’s-anti-imflaminatory

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PharmacologySkeletal Muscle Relaxants

• Treatment of Spasticity– Traditional Agents• Diazepam (Valium)• Baclofen (Lioresal)• Dantrolene (Dantrium)

– Newer Agents• Gabapentin (Neurotin)- also for diabetic neuropathy,

seizures. • Tizanidine (Zanaflex)

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PharmacologySkeletal Muscle Relaxants

• Traditional Agent: Diazepam (Valium)– Action: potentiates the inhibitory effects of GABA– Therapeutic Effect: short term treatment of acute

muscle spasms and spasticity from cord lesions – Side Effects: significant sedation, psychomotor

impairment, abrupt withdrawal rebound symptoms anxiety, seizures, death; physical and psychological dependence

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PharmacologySkeletal Muscle Relaxants

• Traditional Agent: Baclofen (Lioresal)– Action: acts as a GABA agonist inhibits transmission within

the spinal cord; reduction of firing of the alpha motor neuron relaxation of skeletal muscles

– Therapeutic Effect: treatment of spasticity secondary to spinal cord injury and demyelination associated with multiple sclerosis

– Side Effects: transient sedation; avoid sudden withdrawal seizures, hallucinations

– Note: intrathecal Baclofen is used for severe spasticity, rigidity and pain

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PharmacologySkeletal Muscle Relaxants

• Traditional Agent: Dantrolene (Dantrium)– Action: inhibits calcium release in the muscle cell

inhibition of contractions & muscle relaxation– Therapeutic Effect: muscular relaxation; treatment

of severe spasticity – Side Effects: generalized skeletal muscle weakness;

hepatoxoicity

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PharmacologySkeletal Muscle Relaxants

• Newer Agent: Gabapentin (Neurontin)– Action: GABA like inhibition in the spinal cord

reduces alpha motor neuron excitation muscle relaxation

– Therapeutic Effect: treatment of spasticity associated with MS and spinal cord injuries

– Side Effects: sedation, fatigue, dizziness

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PharmacologySkeletal Muscle Relaxants

• Newer Agent: Tizanidine (Zanaflex)– Action: alpha 2 adrenergic agonist: binds alpha

receptors in the spinal cord and brain pre and post synaptic inhibition

– Therapeutic Effect: treatment of spasticity– Side Effects: sedation, dizziness, dry mouth

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PharmacologySkeletal Muscle Relaxants

• Newer Agent: Botulinum Toxin(BoTox)– Action: reduces presynaptic acetycholine release

muscle paralysis– Therapeutic Effect: three month inhibition of local

dystonias, (prevent Ach release to minimize muscle contractions very locally)

– Side Effects: additive effects paralysis• Need an educated injector.

– Note: dose limitations needed to avoid individual antibody production• Does not work as well with repeated use.

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PharmacologyNonsteroidal Anti-Inflammatory Drugs (NSAIDs)

• Prototype “gold standard” NSAID: Acetylsalicylic Acid(Aspirin)– Action: inhibits cyclooxygenase (COX 1 & 2) enzymes inhibition of the

prostaglandin production associated with pain, inflammation, thrombus formation & fever

– Therapeutic Effect: antipyretic; anti-inflammatory; antiplatelet– Side Effects: gi effects dyspepsia, gi bleed, ulcers; hearing effects

tinnitus, hearing difficulties; hypersensitivity– Note: avoid use in children with influenza to avoid Reyes

Syndrome(Reye's Syndrome is a two-phase illness because it is almost always associated with a previous viral infection such as influenza (flu), cold, or chicken pox.)

– Note: preventative usefulness have been suggested in colorectal cancers, cv disease, ms, etc. (small amount in reduction of cancers (81mg-antiplatet, to decrease MI and CVA).

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PharmacologyNonsteroidal Anti-Inflammatory Drugs (NSAIDs)

• Acetylsalicylic Acid (Aspirin)

• Diclofenac (Voltaren)• Etodolac (Lodine)• Indomethacin (Indocin)• Flubiprofen (Anasaid)• Ibuprofen (Motrin)• Ketorolac (Toradol)

• Naproxen (Naprosyn)• Piroxicam (Feldene)• Ketoprofen (Orudis)• Nabumetone (Relafen)• Sulindac (Clinoril)• Tolmetin (Tolectin)

• See table 15-2; page 207

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PharmacologyNonsteroidal Anti-Inflammatory Drugs (NSAIDs)

• Ibuprofen (Motrin) & Naproxen (Aleve)– Action: Inhibition of COX 1 and COX 2– Therapeutic Effect: analgesic and anti-inflammatroy:

treatment of pain and inflammation– Side Effect: fewer gi side effects than aspirin but still

occurs in 15% of patients; long term use may contribute to renal impairment, Motrin is “hard on the gut”.

– Note: monitor dosage, length of administration• Can contribute to renal impairment

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PharmacologyNonsteroidal Anti-Inflammatory Drugs (NSAIDs)

• COX-2 Selective Drugs– Ex: Celecoxib (Celebrex)– Action: inhibition of COX 2– Therapeutic Effect: suppression of inflammatory

response– Side Effects: lack of inhibition of COX1 no gi side

effects– Note: FDA removal of other COX 2 agents in 2004

secondary to MI and stroke risks

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PharmacologyManagement of Rheumatoid Arthritis (RA)• Treatment of RA– Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)

• Ex: Aspirin (need large dose, and watch for GI bleeds); Dicofenac (Voltaren); Ibuprofen (Motrin)

– Corticosteroids• Ex: Hydrocortisone (Cortef); Methylprednisolone (Medrol)

– Disease Modifying Antirheumatic Drugs (D-MARD)• Antimalarials Ex: Hydroxychloroquine (Plaquenil)• Gold Compounds Ex: Auranofin (Ridaura)• Classic Immunosuppressants Ex: Azathioprine (Imuran)• Tumor Necrosis Factor Inhibitors Ex: Adalimumab (Humira) • Antimetabolite Ex: Methotrexate (Rheumatrex)

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PharmacologyManagement of Rheumatoid Arthritis

• Nonsteroidal Anti-Inflammatory Drugs (NSAIDs)– Ex: Aspirin; Dicofenac (Voltaren); Ibuprofen

(Motrin)

– Key Points:• Side effects of aspirin (more gi bleeding, tinitus) versus

Motrin• Around the clock administration is important.

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PharmacologyManagement of Rheumatoid Arthritis

• Corticosteroids– Ex: Hydrocortisone (Cortef); Methylprednisolone

(Medrol)• Acute: need a high dose, for anti-inflmmatory

– Key Points:• Side Effects: short term versus long term

• Tapering of Doses: to allow the adrenal to “kick-back-in” if not Addison’s disease,

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PharmacologyManagement of Rheumatoid Arthritis

• Disease Modifying Antirheumatic Drugs– Classic Immunosuppressants Ex: Azathioprine

(Imuran)• Key Points: infection risk

– Tumor Necrosis Factor Inhibitors Ex: Adalimumab (Humira)• Key Points: SQ/IV meds that may retard the progression

of joint inflammation; infection risk

– Antimetabolite Ex: Methotrexate (Rheumatrex)• Key Points: side effects are major limiters

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PharmacologyManagement of Rheumatoid Arthritis

• Disease Modifying Antirheumatic Drugs– Antimalarials Ex: Hydroxychloroquine (Plaquenil)

• Action: decrease T cell stimulation• Therapeutic Effect: treatment of RA (and malaria)• Side Effects: retinal toxicity

– Gold Compounds Ex: Auranofin (Ridaura)• Action: inhibits T cells and phagocytes• Therapeutic Effects: treatment of RA• Side Effects: high incidence of se’s; diarrhea, indigestion,

proteinuria, thombocytopenia -bleed out, leukopenia-bleed out and be infected.

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PharmacologyManagement of Osteoarthritis

• Treatment of Osteoarthritis (OA)– Analgesics• NSAID’s (ASA, Motrin)• Acetaminophen (Tylenol)

– Viscosupplementation• Hyaluronan (Hyalgan, Synvisc)• Glucosamine and Chondrotin Sulfate

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PharmacologyManagement of Osteoarthritis

• Viscosupplementation– Hyaluronan (Synvisc, Hyalgan)• Action: restore normal viscosity of synovial fluid• Therapeutic Effect: reduces joint stress, limits

progression of articular destruction; reduces pain• Side Effects: pain with injection, localized inflammation• Note: intrarticular injections 2-10 weeks of weekly

injections; pain relief possible for 3-12 months

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PharmacologyManagement of Osteoarthritis

• Viscosupplementation– Glucosamine and Chondroitin Sulfate• Action: replacement or articular cartilage and synovial

fluid components• Therapeutic Effect: may slow the progression of joint

degeneration• Side Effects: rare gi intolerance• Note: typically no effect for weeks to months; xrays

have shown stabilization of joint spaces