Chapter 13

Muscle Relaxants,
Nonnarcotic Analgesics,
and Anti-Inflammatories
 Chapter 13 Topics

• Muscle Relaxants
• Nonnarcotic Analgesics
• Forms of Arthritis
• NSAIDs
• Gouty Arthritis
 Learning Objectives
• Define muscle relaxants
• Identify muscle relaxants and their various
mechanisms of action
• Identify the nonnarcotic analgesics and
describe their uses and mechanisms
 Learning Objectives
• Define rheumatoid arthritis and gouty
arthritis or gout
• Identify agents used to treat arthritis,
rheumatoid arthritis, and gout, and discuss
their usage and side effects
 Skeletal Muscle Contractions
• Voluntarily controlled
• ACh is released
• Binds with ACh receptors
• Sodium ions are released which releases
calcium and causes a contraction
 Skeletal Muscle Contractions
• Voluntarily controlled
• ACh is released, binds with ACh receptors,
sodium ions are released which releases
calcium and causes a contraction
• Relaxation occurs when ACh is broken
down by acetylcholinesterase
 Muscle Relaxants
• Block normal muscle function by:
– Blocking release of ACh
– Preventing destruction of ACh (paralysis by
fatigue)
– Preventing ACh from reaching receptors
 Muscle Relaxants’ Side Effects
• Sedation
• Reduced mental alertness
• Reduced motor abilities
• GI upset

• **Avoid alcohol**
 Drug List
Muscle Relaxants

• baclofen (Lioresal)
• carisoprodol (Soma)
• chlorzoxazone (Paraflex, Parafon Forte
DSC)
• cyclobenzaprine (Flexeril)
 Drug List
Muscle Relaxants

• dantrolene (Dantrium)
• diazepam (Valium)
• metaxalone (Skelaxin)
• methocarbamol (Robaxin)
• orphenadrine (Norflex)
 diazepam (Valium)
• Benzodiazepine that is thought by some to
be the best muscle relaxant
• Has abuse potential
• Do not discontinue abruptly
 carisoprodol (Soma)
• Skeletal muscle relaxant that is subject to
abuse
• Not a controlled substance now, but efforts
are being made to make it controlled
• Causes drowsiness and dizziness
• Do not take with alcohol
 cyclobenzapine (Flexeril)
• Treats muscle spasms associated with acute
musculoskeletal conditions
• Pharmaceutically related to TCAs
• Onset of action is within 1 hour
 metaxalone (Skelaxin)
• Relaxes muscles through general CNS
depression
• May cause drowsiness
• Notify physician of signs/symptoms of
jaundice
 Discussion
Most muscle relaxants are not
controlled substances, so why are
they highly abused?
 Discussion
Most muscle relaxants are not
controlled substances, so why are
they highly abused?

Answer: due to the relaxing feeling

that patient has from taking them
 Nonnarcotic Analgesics
• Used for mild-to-moderate pain,
inflammation and fever
• Can treat somatic pain or visceral pain
 Nonnarcotic Analgesics
• Used for mild-to-moderate pain,
inflammation and fever
• Can treat somatic pain or visceral pain
• Somatic: dull, throbbing pain from skin,
muscle, or bone
• Visceral: sharp, stabbing pain from organs
 Inflammation
• Prostaglandins can cause inflammation,
tissue damage, and fever

• Inhibiting the enzyme needed to synthesize

prostaglandins relieves inflammation, pain,
and fever
 NSAIDs
• Nonsteroidal anti-inflammatory drugs have
analgesic, anti-inflammatory, and
antipyretic properties

• Salicylates is one subclass of NSAIDs

 Salicylates
• Have analgesic, antipyretic and anti-
inflammatory properties
• Reduces fever by increasing blood flow to
the skin
• Inhibits PG synthesis
• Opens stomach up to ulceration
• Aspirin (ASA) is the most common
 Therapeutic Uses of Salicylates
• Arthritis
• Inflammation of arthritis and rheumatism
• Menstrual cramps
• Muscular aches and pain
• Pain and fever of influenza or other
infections
• Simple headache
 Salicylate Dispensing Issues

Warning!
• Should not be used in patients:
– After surgery
– With hemophilia
– With asthma, nasal polyps, chronic sinusitis,
and bleeding ulcers
– During pregnancy
 Salicylate Dispensing Issues

Warning!
• Should not be taken with:
– methotrexate
– warfarin (Coumadin)
 Salicylate’s Side Effects
• GI upset
• Tinnitus
• Platelet changes
 Salicylate Intoxication Effects
• Tinnitus
• Dizziness
• Headache
• Mental confusion
Salicylate Sever Intoxication Effects

• Hyperpnea • Nausea
• Acid-base disturbances • Vomiting
• Petechial hemorrhages • Delirium
• Hyperthermia • Convulsions
• Coma
 Reye’s Syndrome
• Aspirin should not be given to children due to risk
of Reye’s Syndrome
• Effects of Reye’s Syndrome on the body:
– Mental changes
– Coma
– Seizures
– Relaxed muscles
– Dilated pupils
– Respiratory failure
 Aspirin and the
Cardiovascular System
• Low-dose aspirin can be given to adults to
reduce risk of heart attack and stroke by
altering platelet aggregation needed for
clotting
 acetaminophen (Tylenol)
• APAP has analgesic and antipyretic effects
• Does not cause GI irritation, bleeding,
alteration of platelet adhesiveness or
potentiation of oral anticoagulants
• Be cautious of liver damage:
– High risk in alcoholics
– >4 g/day can cause damage
 Therapeutic Uses of APAP
• Patients with peptic ulcers
• Taking a uricosuric agent for gout
• Taking oral anticoagulants
• With clotting disorders
• At risk for Reye’s syndrome
• Intolerant to aspirin
• With post-surgical pain
 Mixed Analgesics
• Chronic use can lead to kidney failure
• For APAP – risk of liver toxicity
• For ibuprofen – risk of GI bleeding
• As a Pharm Tech, caution needs to be taken
when calculating dosages of both narcotic
and nonnarcotic ingredients
 Drug List
Nonnarcotic Analgesics

Salicylates:
• aspirin (acetylsalicyclic acid)
• buffered aspirin (Ascriptin, Bufferin)
Antipyretic Analgesics:
• acetaminophen (Tylenol)
 Forms of Arthritis
• Osteoarthritis

• Bursitis

• Rheumatoid Arthritis
 Osteoarthritis
• Degenerative joint disease that results in
loss of cartilage elasticity and thickness
• Bones begin to wear and become deformed
• Commonly affected joints:
– Sternoclavicular joint, spine, hips, knees,
fingers, and great toes
– Knees and fingers are especially affected
 Osteoarthritis
• Characterized by progressive pain, stiffness,
limitation of motion, and deformed joints

• Generally appears after age 40

 Bursitis
• Inflammation of a bursa

• Bursa is a saclike pouch filled with synovial

fluid located at a site of friction
 Rheumatoid Arthritis
• Autoimmune disease that attacks connective
tissue
• Characterized by inflammation of the joint’s
synovial membrane
• Bone and cartilage reabsorption occurs
leaving bone-to-bone contact which can
lead to joint fusion
 Rheumatoid Arthritis
• Macrophages are present in joints and
release interleukin I and tumor necrosis
factor
• These chemicals stimulate destructive
growth of the synovial membrane
• COX-1 and COX-2 also play a critical role
in the inflammatory process
 Characteristics of R.A.
• Fatigue, anorexia, weight loss, and fever
• Pain originates from bone, tendon,
ligament, and muscle
• Symmetric morning stiffness lasting longer
than 60 minutes
• Small joints of the fingers are usually the
first joints affected
 Criteria for Diagnosis
• Joint tenderness or pain on motion
• Morning stiffness
• Presence of RF
• Soft-tissue swelling in a 1st joint, followed
within 3 months by swelling in a 2nd joint
• Sterile turbid synovial fluid
• X-ray changes showing erosions
 Therapy for R.A.
• Aimed at relieving pain, maintaining or
improving mobility and minimizing
disability

• May include medications, physical therapy,

and patient education
 NSAIDs
• Relieve inflammation and swelling and
therefore pain

• Effects on fever last longer than APAP

 Therapeutic Uses of NSAIDs
• Inflammation and pain of arthritis and rheumatism
• Headache
• Menstrual cramps
• Backache
• Muscle aches
• Flu
• Fever
 NSAIDS
• Inhibit PG synthesis in tissues

• Primary side effect is GI upset

 Discussion
Why do NSAIDs cause GI upset?
 Discussion
Why do NSAIDs cause GI upset?

Answer: PGs are responsible for

increased mucosal blood flow, mucus
production, and decreasing free acid
in the GI tract
 NSAID’s Side Effects
• Nausea • Acute renal failure
• Heartburn • Fluid retention
• Abdominal cramps • Hypertension
• Ulcers • Hyperkalemia
• Indigestion • Liver abnormalities
• Bone marrow
depression
• Tinnitus and others
 Interactions with NSAIDs
• Other NSAIDs including ASA
• Beta blockers
• Cyclosporine
• Digoxin
• Diuretics
• Methotrexate (MTX)
• Oral hypoglycemics
• Warfarin
 Tips for NSAID Users
• Take with food
• Use antacids
• Do not use gastric irritants (ETOH)
• Stop NSAID before any surgical procedure
• Use the lowest possible dose
• Be aware of side effects
• Take sufficient fluids
• If sensitive to ASA, avoid NSAIDs
 Conventional NSAIDs
• Several are available OTC
 Drug List
Drugs for Arthritis and
Related Disorders
Conventional NSAIDs
• diclofenac (Cataflam, Solaraze, Voltaren)
• diclofenac-misoprostol (Arthrotec)
• diflunisal (Dolobid)
• etodolac (Lodine)
• fenoprofen (Nalfon)
 Drug List
Drugs for Arthritis and
Related Disorders
Conventional NSAIDs
• flurbiprofen (Ansaid)
• ibuprofen (Advil, Motrin)
• indomethacin (Indocin)
• ketoprofen (Orudis KT, Oruvail)
• ketorolac (Toradol)
 Drug List
Drugs for Arthritis and
Related Disorders
Conventional NSAIDs
• meclofenamate
• mefenamic acid (Ponstel)
• meloxicam (Mobic)
• nabumetone (Relafen)
• naproxen (Aleve, Anaprox, Naprosyn)
 Drug List
Drugs for Arthritis and
Related Disorders
Conventional NSAIDs
• oxaprozin (Daypro)
• piroxicam (Feldene)
• sulindac (Clinoril)
• tolmetin (Tolectin)
 ibuprofen (Advil, Motrin)
• Controls fever well and can be alternated
with APAP
• OTC: liquids and 200 mg solids
• Rx: 400 mg, 600 mg, and 800 mg solids
(tablets)
 COX-2 Inhibitors
• Only block the COX-2 enzyme which is
induced during inflammation
 Therapeutic Uses of
COX-2 Inhibitors

• Rheumatoid arthritis
• Osteoarthritis
• Menstrual cramps
• Acute pain
 Drug List
Drugs for Arthritis and
Related Disorders
COX-2 Inhibitors
• celecoxib (Celebrex)
• valdecoxib (Bextra)
– (removed from market 4/05)
 celecoxib (Celebrex)
• Was the 1st COX-2 inhibitor to be approved
and is the only remaining one on the market
• GI upset is primary side effect
• Take with food
 celecoxib Dispensing Issues

Warning!
• Beware of cross-sensitivity with
sulfonamides
• May cause increased cardiovascular risk
 celecoxib Dispensing Issues

Warning!
• Look-alike and Sound-alike drugs:
– Celebrex (pain and inflammation)
– Cerebyx (seizures)
 Drug List
Drugs for Arthritis and
Related Disorders
Other
• tramadol (Ultram)
• tramadol-acetaminophen (Ultracet)
 tramadol (Ultram)
• Binds to opiate receptors and inhibits
norepinephrine and serotonin reuptake

• Used for moderate-to-severe pain

• tramadol has a high abuse potential

 tramadol’s Side Effects
• Dizziness
• Vertigo
• Nausea
• Constipation
• Headache
 tramadol Dispensing Issues

Warning!
• Look-alike and Sound-alike drugs:
– Toradol (ketorolac)
– tramadol (Ultram)
 Disease-Modifying Antirheumatic
Drugs (DMARDs)

• Used to modify disease progression

• Considered to be second-line treatments

 Drug List

DMARDs

• adalimumab (Humira)
• anakinra (Kineret)
• auranofin (Ridaura)
• aurothioglucose (Solganal)
• azathioprine (Imuran)
• cyclophosphamide (Cytoxan)
 Drug List

DMARDs

• etanercept (Enbrel)
• hydroxychloroquine (Plaquenil)
• infliximab (Remicade)
• leflunomide (Arava)
• methotrexate (Rheumatrex)
• penicillamine (Cuprimine)
 adalimunab (Humira)
• Blocks tumor necrosis factor which
stimulates bone and cartilage deterioration

• Given SQ every week

• Increases risk of infections and cancer

 cyclophosphamide (Cytoxan)
• Depresses bone marrow which increases
risk of infection

• Patient should stay well hydrated during

therapy
cyclophosphamide’s Side Effects
• GI upset
• Ulcers
• Liver toxicity
• Reproductive organ failure
• Hair loss
 etanercept (Enbrel)
• Biologically engineered protein that inhibits
tumor necrosis factor

• For moderate-to-severe RA

• Must be stored in the refrigerator and

diluted immediately before injection
 leflunomide (Arava)
• Interferes with the proliferation of
lymphocytes

• Retards progression of RA, reduces pain

and joint swelling, and improves functional
ability
 leflunomide’s Side Effects
• Diarrhea
• Rash
• Alopecia
• Elevated liver enzymes
• Increased infections
 Discussion
Why does depression of the bone
marrow lead to increased risk of
infection?
 Discussion
Why does depression of the bone
marrow lead to increased risk of
infection?

Answer: depressing bone marrow

depresses the formation of leukocytes
which weakens the immune system
 Gouty Arthritis
• Usually affects single joints; the great toe
usually being the first affected
• Causes joint to be painful, swollen, and red
• Usually inherited
 Gout
• Patient has overproduction or improper
excretion of uric acid
• Uric acid builds up in the body and deposits
in the joints
• Medications that compete with uric acid for
kidney excretion should be avoided
 Drugs Avoided in Gout Patients
• Cytotoxic agents
• Diuretics
• Ethanol
• Nicotinic acid
• Salicylates (ASA)
 Drug List

Drugs for Gouty Arthritis

• colchicine – Acute Attack Therapy

• allopurinol (Zyloprim) – Chronic Therapy
• indomethacin (Indocin) – Chronic Therapy
• probenecid-colchicine (Col-Probenecid) –
Chronic Therapy
• sulfinpyrazone (Anturane) – Chronic Therapy
 colchicine
• Drug of choice for acute gout attacks

• Reduces uric acid production

• There is a high potential for phlebitis

 allopurinol (Zyloprim)
• Used to prevent gout attacks

• Liver function should be monitored

• Should not be taken with diuretics