ptp 546 module 9 pharmacology of inflammation & treatment of skeletal muscles jayne hansche...
TRANSCRIPT
Lobert 1
PTP 546 Module 9Pharmacology of Inflammation &
Treatment of Skeletal Muscles
Jayne Hansche Lobert, MS, RN, ACNS-BC, NP
Lobert 2
PharmacologySkeletal Muscle Relaxants
• Treatment of Muscle Spasms– Benzodiazepines• Diazepam (Valium)
– Physical and psychological dependence
– Polysynaptic Inhibitors• Carisoprodol (Soma)• Cyclobenzaprine (Flexeril)• Methocarbamol (Robaxin)
Lobert 3
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
Lobert 4
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
Lobert 5
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)
Lobert 6
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
Lobert 7
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
Lobert 8
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
Lobert 9
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
Lobert 10
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
Lobert 11
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.
Lobert 12
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).
Lobert 13
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
Lobert 14
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
Lobert 15
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
Lobert 16
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)
Lobert 17
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.
Lobert 18
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,
Lobert 19
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
Lobert 20
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.
Lobert 21
PharmacologyManagement of Osteoarthritis
• Treatment of Osteoarthritis (OA)– Analgesics• NSAID’s (ASA, Motrin)• Acetaminophen (Tylenol)
– Viscosupplementation• Hyaluronan (Hyalgan, Synvisc)• Glucosamine and Chondrotin Sulfate
Lobert 22
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
Lobert 23
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