Module 2 MSK (Pharm 2 Exam)

what are the common drug classes for MSK conditions?

• muscle relaxants

• opions

• NSAIDs

• Acetaminophen

• steroids

• local anesthetics

what are the two groups of skeletal muscle relaxants drugs?

• antispasticity agents: used for UMN problems when the muscle is always being told to contract… hypertonic muscle firing problem

• antispasm agents: protect against acute tissue stretch

*diazepem falls under both of these so is used to treat both

why are skeletal muscle relaxants commonly used in rehab populations?

• address hyperexcitable skeletal muscles

• spasticity— for pain, improve movement, positioning, ADLs

• acute spasm— for pain

• goal: reduce hyperexcitability/normalize excitability, not eliminate muscle activity

what is muscle spasticity versus an acute muscle spasm?

• spasticity: a velocity dependent exaggerated stretch reflex that leads to a loss of supraspinal inhibition and results from CNS conditions such as CVA, cerebral palsy, and multiple sclerosis.

• acute muscle spams: a painful and localized tonic, involuntary contraction that may be protective or pahtological. they are associated with MSK injuries such as muscle strain so they can be treated with PT and rest so medication use is short term only

what is the MOI of centrally acting antispasm drugs (polysnaptic inhibitors)?

not well defined but believed there is a global decrease in CNS excitability the results in sedative effects

when are centrally acting antispasm drugs (polysnaptic inhibitors) used?

as adjuncts to rest and physical therapy for the short term relief of muscle spasms associated with acute, painful MSK injuries.

what are the adverse effects of centrally acting antispasm drugs (polysnaptic inhibitors)?

drowsiness, dizziness, nausea, lightheadedness, tolerance, and withdrawal symptoms

what are the centrally acting antispasm drugs (polysnaptic inhibitors) to know?

cyclobenzaprine (Flexiril)

carisoprodol (Soma)

metaxalone (Skelaxin)

which drug is used for both antispasms and antispasticity?

diazapam (Valium)

what is the MOI of diazepam (Valium)?

• enhances GABA mediated inhibition to decrease CNS activity

• reduces alpha motor neuron activity

• reduce spasticity

when sould diazepam (Valium) specifically be used?

• extensivtly in treatment of muscle spasms associated with acute low back pain

• spasticity management of spinal cord lesions and cerebral palsy

what are the adverse effects of diazepam (Valium)?

sedation, tolerance, physical dependence, and withdrawal

what is the MOI of centrally acting antispasticity drugs?

increase GABA activity in the CNS

what are the centrally acting antispasticity drugs to know?

Baclofen

Gabapentin

Diazapam

what is the MOI of alpha 2 adrenergic agonists as centrally acting antispasticity drugs?

inhibit excitatory neurotransmitter reducing transmissions to alpha motor neurons

what is the alpha 2 adrenergic agonists we should know that acts as a centrally acting antispasticity drugs?

tizanidine (Zanaflex)

discuss the difference in how Baclofen (Lioresal) and intrathecal Baclofen is administered?

Baclofen (Lioresal) is administed orally, while intrathecal Baclofen is delivered via a pump

what is the MOI of Baclofen (Lioresal) versus intrathecal Baclofen?

Baclofen (Lioresal) is a GABA receptor agonist so it…

• inhibits spinal reflex transmission

• is most effective for SC lesions

• is the drug of choice for MS

Intrathecal Baclofen is used for severe, intractable spasticity by being delivered directly into the subarachnoid space at a lower dose due to its higher specificity

what are the adverse effects of Baclofen (Lioresal) versus intrathecal Baclofen?

Baclofen (Lioresal): transient drowsiness that is disapperaing in a few days, confusion/hallucinations in the elderly or those who’ve had a CVA

Intrathecal Baclofen:

• pump malfunction that increases delivery leading to overdose, respiratory distress, decreased cardiav function, or coma.

• pump malfunction that decreases delivery leading to withdrawel, fever, confusion, delerium, and seizures

• tolerance

what is the MOI of peripherally acting antispascticity drugs?

they act directly at the NM junction or muscle

what are the peripherally acting antispascticity drugs?

Botulinum Toxin

Dantrolene Sodium

what is the MOI of dantrolene sodium (Dantrium)?

it is the only muscle relaxant that act directly on skeletal muscle by inhibiting calcium release from the SR so there is less calcium available for actin and myosin crossbridge formation

when is dantrolene sodium (Dantrium) used?

to treat severe spasticity, regardless of underlying pathology. it is NOT prescribed for muscle spams due to MSK injury

what are the adverse effects of dantrolene sodium (Dantrium)

weakness and hepatoxicity

what is the MOI of Botulinum Toxin?

blocks Ach release via a targeted muscle injection that lasts about 3 months

how does Botulinum Toxin help with spasciticy managament?

CP, stroke, TBI, SCI

enhances ADLs by enabling UE extensor in flexor spasticity, improves hygeine, dressing, etc

how does Botulinum Toxin help improve movement?

reduces spastic dominance to allow for better gait and taks performance

facilitates voluntary motor control during rehab

how does Botulinum Toxin support orthopedic intervention?

enhances stretching and serial casting

prevents contractures, reduces surgical need

improves orthotic tolerance

_________ is a general term that includes aspirin and related compounts. so aspirin is known as ______________. what does this mean?

salicylate; acetylsalicylic acid (ASA)

it can be irritating to the stomach (produce ulcers)

what are the therapeutic actions of Salicylate analgesic drugs (Aspirin)?

• Analgesic and Anti-inflammatory: pain relief of mild to moderate pain and anti-inflammatory by inhibiting release of prostaglandins from damaged tissue

• Antipyretic: reduce fever by action on the hypothalamus, and vasodilation and sweating to increase heat loss

• Anti-platelet: “blood thinner” inhibiting thromboxane that normally causes platelet aggregation prevents clot formation used for MI and CVA, post surgical prevention of DVT

Aspirin should not be used with children due to its link with ____________ which is increased serum levels of ammonia that can cause encephalitis and liver damage.

Reye’s syndrome

how does Aspirin have so many therapeutic effects?

it intereferes with the biosynthesis of prostaglandins

when are prostaglandins created?

1. cells experience damage

2. disruption of homeostasis

how are prostaglandins created?

1. cell membrane phospholipids are converted to arachadonic acid

2. the COX enzyme convert arachidonic acid to prostaglandins and thromboxane

what are the effects of prostaglandins?

• inflammation

• increase sensitivity of nociceptors

• fever

• thrombus formation

how does Aspirin and other NSAIDs have an effect of prostaglandin and what are the effects?

they inhibit the COX enzyme leading to decreased inflammation, pain, fever, and clotting

what are the 2 types of COX enzymes?

1. COX-1 is a component of normal cell activity that produces benign prostaglandins

2. COX-2 is produced in emergency situations so it produces prostaglandins that tend to mediate pain and be associated with inflammation

NSAIDs are eighther non-selective (effecting both COX forms) or selectively inhibit COX-2. what is the result of most NSAIDs being non-selective?

while they inhibit both COX forms, the primary beneficial effect is due to inhibition of COX 2. however, most side effects are due to the inhibition of COX-1 which leads to bleeding in the stomach and kidneys

what are the nonselective NSAIDs to know?

acetylsalicylic acid (Aspirin)

ibuprofen (Advil, Motrin)

Naproxen (Aleve)

what is the clinical application for how non-selective NSAIDs help with pain and inflammation?

• effective for mild-moderate pain

• particarly effective in MSK and joint disorders

• used for primary dysmenorrhea

• postoperative pain management

• reduce opioid requiremets post-surgery

what is the clinical application for how non-selective NSAIDs help with fever?

• they are the primary antipyretic in adults

• aspirin is contraindicated in children

• ibuprofen is commonly used across all age groups

what is the clinical application for how non-selective NSAIDs help with vascular disorders?

• antiplatelet effective via inhibition of thromboxane

• reduces risk of MI

• helps prevent ITA and ischemic stroke in selected patients

what is the clinical application for how non-selective NSAIDs help with cancer prevention?

• strong evidence for decreased colorectal cancer risk

• possible protection against GI cancers and non-GI cancers due to COX-2 inhibition which decreases prostaglandin mediated cell proliferation and antiplatet effects limiting tumor-promoting signaling

what is the primary adverse effect of non-selective NSAIDs?

GI damage due to loss of protective COX-1 prostaglandins

what are the cardiovascular adverse effect of non-selective NSAIDs?

can increase blood pressure and thrombotic risk due to inhibition of specific prostaglandins which may lead to an increased risk of heart attack and stroke in individuals with HTN and other risk factors

what are the renal/hepatic adverse effect of non-selective NSAIDs?

generally safe in healthy individuals but there is a rare hepatotoxicity at high doses or renal injury risk with dehydration, kidney disease, HF, and diabetes

discuss COX-2 selective NSAIDs?

• they selectively inhibit COX-2 in order to decrease the side effects of the nonselective but are not necessarily more effective at reducing pain and inflammation

• they may also be prescribed for individuals at risk of prolonged bleeding because they spare thrombonxanes produced by COX-2 to allow for normal platelet activity

• they inhibit a specific prostaglandin that promotes vasodilation and inhibits clotting. therefore, they tip the balance toward vascoconstriction and clotting. thus, they may increase the risk of heart attack or stroke

what is the COX-2 selective NSAID to know?

celecoxib (Celebrex)

t/f acetaminophen (Tylenol) is an NSAID

false because it has no anti-inflammatory or anti-platelet effects

compare acetaminophen (Tylenol) with NSAIDs

• they have similar pain relef and fever reduction techniques

• acetaminophen does not cause any GI irritation

• there is a major risk for dose dependent hepatotoxicity that is increased with overdose (>3000 mg/d), alcohol use, liver disease

• acetaminophen is widely used for mild-moderate pain in noninflammatory conditions

• acetaminophen is safe for children and adolescents for fever treatment

discuss opioid analgesics

• historically called narcotics due to sleep inducing effect and being derived from opium

• relieve pain by binding to opiate receptor sites in the brain to block pain impulses from ascending neural pathways

• used to treat moderate to severe pain, preop/postop pain relief, sedation, and maintain general anesthesia

• there are strong agonists, mild to moderate agonists, mixed antagonists, and antagonists

what is tolerance as seen with opiods?

the need to progressively increase the dosage of a drug to achieve a therapeutic effect when the drug is used for prolonged periods

what is physical dependence as seen with opiods?

• defined as the onset of withdrawel symptoms when the drug is abruptly removed

• in severe cases, symptoms occur within 6-10 hours of the last dose

• symptoms typically last around 5 days, peaking at 2-3 days

• this is NOT addiction which is psychological

what are withdrawal symptoms?

body aches, diarrhea, fever, gooseflesh, insomnia, irritability, loss of appetite, nausea/vomiting, runny nose, shivering, sneezing, stomach cramps, sweating, tachycardia, uncontrollable yawning, weakness/fatigue

what is the MOA of opiods on the spinal cord?

opiod receptors are concentrated neurons in the dorsal honr. the opioids act on 2 ways…

1. act on the presynaptic terminals of specific first order nociceptive afferents by binding to the receptors and decreasing release of pain-mediating neurotransmitters such as substance p.

2. act on the postsynaptic terminals of secondary afferents by inhibing pain transmissions by hyperpolarizing the postsynaptic neuron, making it less excitable

what is the MOA of opiods on the brain (suprasinal effects)?

they disinhibit (activate) descending pain pathways from the periaqueductal gray matter by…

1. binding to specific receptors in the midbrain and removing inhibition of descending pathways that decrease nociception

2. increase activity of descending pathways the travel through the ventromedial medulla to reach the dorsal horn of the SC

3. neurons in the descending pathways release seratonin and norepinephrine onto dorsal horn synapses and inhibit the ability of these synapses to transmit nociceptive impulses. tothe brain