Medications to treat pain and inflammation Flashcards
Opioids, NSAIDs and Acetaminophen, RA and OA drugs
What is the role physical therapists can play in combatting the opioid epidemic
Patient education on use and looking out for side effects
List the different types of pain
Nociceptive
Neuropathic
Inflammatory
Non-inflammatory/non-neuropathic
What is nociceptive pain
Somatic - well localized (lots of receptors) in soft tissue and bone
Visceral - diffuse and vague - hollow organs and blood vessels
What is neuropathic pain
Pain to Brain, SC, or peripheral nerves as tingling, burning or electrical
What is inflammatory pain
Inflammatory markers cause local damage to tissue and lead to nociceptive pain
What is non-inflammatory/non-neuropathic pain
Wide spread pain with no definitive tissue or no known injury
What types of pain medications should be given for:
Nociceptive pain
- mild to moderate: acetaminophen, NSAIDs
- moderate to severe: opioids
What types of pain medications should be given for:
neuropathic pain
Antidepressants, antiseizure
What types of pain medications should be given for:
Inflammatory
NSAIDs & other medications to decrease inflammation
What types of pain medications should be given for:
Noninflammatory/nonneuropathic pain
NSAIDs, acetaminophen & other modalities
What are the three families of endogenous opioids
Endorphins
Enkephalins
Dynorphins
Where are the opioid receptors located
In the CNS and the peripheral tissue
List the 3 types of opioid receptors
Mu
Kappa
Delta
What is the primary therapeutic effect for the opioid receptors:
Mu
Kappa
Delta
Spinal and Supra spinal analgesia for all 3
T or F: there are different categories of opioids
True: agonists, antagonists, and mixed agonist-antagonists
Strong agonist (opioids)
Used to treat severe pain and have a high affinity for the Mu receptor
Ex) fentanyl, hydromprpjone, meperidine, methadone, morphine (MS Cotin)
Mild to moderate agonists (opioids)
Stimulate the opioid receptors (Mu) but do not have as high affinity or efficacy as the strong agonists and are more effective at treating moderate pain
Ex) codeine
Mixed agonist-antagonists (opioids)
- what do they bind to
Most bind to Kappa as AGONIST and Mu as ANTAGONIST
Mixed agonists-antagonist
- function
Produce adequate analgesia with less risk of side effects (reduced risk of OD compared to Mu agonists but increased psychotropic effects)
Antagonists (opioids)
Used to treat addiction and overdose since they bind to all opioid receptors (w/higher affinity for Mu)
- do not produce analgesia
Ex) naloxone (Narcan)
Physical therapy and Naloxone Availability
Made available in 2019 by the APTA house of delegates
What is the preferred route for opioids
Oral
What are the different ways to administer opioids
Oral Rectal (if N/V) IV (slowly) IM SQ Intrathecal Transdermal - avoid GI and constipation Iontophoresis Lozenges
What is the PCA
An IV set up that allows patients to self-administer a pre-set dose (demand dose) and has a lockout interval so patients have to wait for the next dose. First dose is the loading dose and it is larger than the demand to get desired plasma concentration established.
What are the 3 options for administration of PCA
IV - most common
Epidural PCA - directly into epidural space
Regional PCA - directly into a joint, near a peripheral nerve or into a wound (no systemic effects)
Why is PCA a good option?
Maintains drug levels within a well-defined therapeutic window
What are the potential problems with PCA
Operating errors (misprogramming, misplacing the key) Patient errors (lack of comprehension) Mechanical problems (failure to deliver on demand, malfunctions)
Where are opioids metabolized and eliminated
Liver metabolized
Kidneys eliminated
What is the mechanism of action for opioids
They act on neuronal receptors in the SC (decrease ascending pain pathway) brain (increase activity of decreased pain pathway), and periphery (decrease excitability of sensory nerves) at the same time
What do opioid G proteins act on
- Calcium channels (decrease entry & decrease NT)
- K+ channels (loss of K to hyperpolarize mem & cause more exit K+)
Intracellular signal pathways (inhibit - CAMP so can’t excite me round to transmit painful impulses)
True or false : opioids eliminate pain
False - they alter the perception of the pain causing a floating or euphoric feeling
What kind of pain are opioids good for
Constant moderate to severe pain (acute or chronic - cancer and sickle cell anemia but NOT msk pain)
How do you dose opioids
- Start with mild agonists orally
- Stronger agonists orally
- Stronger agonists parenterally
How can you ensure oral administration of opioids is most effective
Take it at on a regular schedule, not when you need it because otherwise it takes 20-30 minutes to kick in
Adverse effects of opioids
- sedative properties
- respiratory depression
- postural hypotension
- GI Distress (N/V)
- Constipation
- urinary retention
Rehab concerns with opioids
Want therapy to be at peak effects, but be cautious as it is also peak for side effects (monitor alertness, RR, and BP)
Define addiction
An individual repeatedly ingests certain substances for mood-altering and pleasurable experiences (different than tolerance and physical dependence) that had a psychological and psychiatric component
Define drug misuse
Use of a drug that falls outside of its intended purpose (taking a second sleeping pill, using a strong opioid for a mild ailment)
Define drug abuse
Prolonged tendency to seek out drugs that result in negative consequences (take more opioids than recommended to get “high”, take opioids without a prescription)
Define tolerance
The need to progressively increase the dosage of a drug to achieve a therapeutic effect when the drug is used for prolonged periods from receptor downregulation and desensitization
Tolerance & Opioids
1) when does it begin
2) when do you have to increase dose
3) how long does it last
1) behind after the first dose
2) 2-3 weeks out
3) lasts 1-2 weeks after drug is removed (Craving persists though)
Physical dependence & opioids
1) what is it
2) when does it begin
3) peak
4) length
- onset of withdrawal symptoms once drug is abruptly removed
2) severe cases, 6-10 hours after last dose
3) peak 2-3 days after
4) 5 days for PHYSICAL symptoms (psychological persists)
Symptoms of opioid withdrawal
- body aches
- diarrhea
- fever, sweating
- goose flesh, shivering
- insomnia, uncontrollable yawning
- irritability
- leg cramps/tremors
- loss of appetite, stomach cramps
- nausea/vomiting
- runny nose, sneezing
- tachycardia
- weakness/fatigue
What is opioid induced hyperalgesia
Fail to respond to opioids or report increased pain when given opioids, even before tolerance develops - not fully understood but probably genetics
Where are the most common drugs involved in prescription opioid overdose deaths
Methadone, oxycodone (OxyCotin), hydrocodone (Vicodin)
What is medical assisted treatment (MAT)?
Examples
- use of less addictive/strong opioids to bridge the gap rather than quitting cold turkey
- buprenorphine: mixed agonist and antagonist
- methadone (agonist but less side effects)
- naltrexone (long term IM injections)
What do NSAIDs do
- decrease inflammation
- relieve mild to moderate pain
- decrease elevated body temp associated with fever
- decrease blood clotting by inhibiting platelet aggregation
What produces the prostaglandin precursor in the body
Produced by everything except RBCs and have a normal pathological function
What is the biosynthesis of eicosanoids
There are two pathways, LOX which yields leukotrienes and COX that yields prostaglandins and thromboxane –> ASA and NSAIDS act on the cox system
Why do we care about eicosanoid biosynthesis
If cells are subject to trauma, it increases production of prostaglandins, leading to pain, fever, inflammation, dysmenorrhea and thrombus formation
What are the two subtypes of COX enzymes and what do they do
COX-1: always present and produce prostaglandins for normal cellular activity
COX-2: Produced by injured cells to mediate pain and other aspects of the inflammatory response
Basic function of Nonselective NSAID
Inhibits both COX-1 and COX-2, decreasing pain/inflam via COX-2 and also dec normal protective prostaglandins causing Stomach and kidney damage
Basic function of COX-2 Inhibitor
decrease pain and inflammation w/o negative COX-1 gastric and renal side effects
What is the dose of OTC vs prescription NSAIDs
OTC is 1/3 the dose of prescription
What is the OG NSAID
Acetylsalicyclic acid (ASA) = Asprin
What is the clinical application of aspirin-like drugs
Treat mild-moderate pain (OA,RA, dysmenorrhea, minor sx),inflammation and fever (except for those in children), vascular disorders, and prevention of cancer
What is Reye syndrome
A neurological problem that can occur when aspirin is taken in children
ASA influence on vascular disorders
It inhibits platelet induced thrombus formation and may prevent the onset or recurrence of MI, TIA and stroke
What are the adverse effects of Aspirin-like drugs
GI problems (Stomach discomfort, upper GI hemorrhage and ulceration)
CV problems (increased BP to then increase platelet formation)
Inhibit healing of fractures
Hepatotoxicity
Problems with kidney function
What are the symptoms of overdose of aspirin and aspirin-like drugs
Tinnitus Headache Trouble hearing Confusion GI Issues
ASA vs other NSAIDs (ie ibuprofen)
Same: anti-inflammatory and analgesia
Dif: non-aspirin have less GI effects (still have them) and are less toxic to liver and kidneys
What are COX-2 Inhibitors
Comparable to nonselective NSAIDs w/lower incidence of GI distress (altho still occurs) and have an increased risk of upper respiratory tract infections, and CV events
Do COX-2 drugs increase the risk of MI/CVA? Why or why not?
Yes because it decreases the prostaglandins that cause vasodilation and prevent thrombosis, now at an increased risk of developing a clot
NSAID pharmacokinetics
- ASA absorbed in stomach and small intestine w/8-90% bound to plasma proteins
- ASA metabolized in the BLOODSTREAM
- ASA excreted in the kidneys
Acetaminophen vs NSAIDs
Same in analgesic and antipyretic (fever) properties HOWEVER acetaminophen does not have the anti-inflammatory or anticoagulant effects
(also acetaminophen can treat fever in children and NSAIDs cannot)
What was the first drug used to treat OA
Acetaminophen
What is the mechanism of action of acetaminophen
It is not fully understood how it inhibits the cox enzymes without leading to anti-inflammatory or anticoagulant effects
How is acetaminophen metabolized
In the liver, it is metabolized to NAPQI which forms with GSH to form mercapturic acid to be eliminated
BUT if NAPQI accumulates it is toxic to the liver and can be fatal
What drug is combined with opioid after surgery? Why?
Acetaminophen to try and use less opioids to control the pain. Can be taken in combo or w/one extended release opioid w/acetaminophen in b/t to hold over
-cet or -tab
acetaminophen and opioid combos
Acetaminophen pharmacokinetics
Absorbed in upper GI tract
- plasma protein binding is highly variable
- metabolized in liver
- excreted inu rine
Mm spasms vs spasticity
Spasticity is due to CNS injury w/a velocity dependent mm stretech reflex whereas mm spasms are from MSK injury w/involuntary tension of specific mm
What is diazepam mechanism for MSK
Increases the inhibitory effects of GABA, esp on the alpha motor neuron, to cause generalized sedative effects w/mm relaxation (also used as anti-anxiety agent)
T or F: Diazepam produced tolerance and physical dependence
True!
What are polysynaptic inhibitors
may decrease polysnaptic reflex activity in the SC used for ST relief of mm spasms in acute MSK injuries
What are the side effects of polysynaptic inhibitors
Drowsiness, dizziness, nausea, H/A, vomiting
What are 2 examples of polysynaptic inhibitors and how do they work
- Cyclobenzaprine (flexeril): increase seratonin activity in the BS
- Carisoprodol (soma): may affect GABA-A, producing sedation similar to diazepam
What are two types of drugs to treat MSK mm spasms
Diazepam
Polysynaptic Inhibitors
What is Dantrolene Sodium (Dantrium)
A peripherally acting antispasticity agent that inhibits Ca+ release from the sarcoplasmic retic in skeletal mm –> dec. mm contraction and enhanced relaxation
What are the side effects of dantrolene sodium
mm weakness and hepatotoxicity
What is Botox
a peripherally acting antispasticity agent that works at the neuromuscular junction to prevent ACh release so the mm can’t contract
What is the clinical use of Botox
- treat localized mm dystonia
- can be injected into bladder detrusor mm to treat neurogenic bladder
- relief lasts about 3 months
- reduce spasticity enough so joint and mm can be stretched
Limitations and adverse effects of BoTox
- not a cure
- only lasts up to 3 mo and can only treat 1-2 mm groups at a time
- CAN SPREAD (low incidence) causing systemic effects like difficulty speaking/swallowing and respiratory disress
What is Tizanidine (zanaflex)
A centrally acting antispasticity agent primarily used to control spasticity resulting from spinal lesions by binding to alpha-2 adrenergic agonists (dec excitory NT)
What is the concern w/tizanidine
possibly can slow down neural recovery in acute phase of CVA and TBI`
What are the side effects of tizanidine
sedation, dizziness, and dry mouth
What is Baclofen
A centrally acting antispasticity agent that binds preferentially to GABA-B receptors, acting as an agonist to decrease alpha motor neuron activity in the SC
What are the side-effects of baclofen
drowsiness, fatigue, and mm weakness
T or F: Tolerance can occur w/baclofen
True - and then when you increase the dose to adjust, it can lead to increased drowsiness
What are the indications for intrathecal baclofen
severe, intractable spasticity
- long term treatment
What is are the positives and negatives of intrathecal baclofen
- allows for increased drug effectiveness w/much smaller drug doses
- leads to functional movements
negatives: pump malfunction and tolerance
What is dizaepam
Centrally acting antispaticity agent that works on both skeletal mm spasms and spasticity of CNS origin
Pharmacokinetics of mm relaxants
- oral most common route so absorbed by GI
- metabolized in the liver
- excreted in the kidneys
What are the rehab concerns w/mm relaxants
- Long term use is not practical as it leads to sedation and addictive properties
- PT can help Pts adjust to sudden changes
What are 3 ways to reduce mm excitability
- Act on SC
- Act at neuromuscular junction
- act directly w/in skeletal mm fiber
What is RA
A chronic, systemic autoimmune disorder that is primarily synovitis causing pain, stiffness, and inflammation in smaller –> larger joints
T or F: RA is constantly exacerbated
FALSE! It has periods of exacerbation and remission that is overall progressive
T or F: RA is more common in young men
False it is more common in women and older patients
What are the 2 goals of drug therapy for RA
- decrease joint inflammation
2. arrest the progression of the disease
What 3 groups of drugs used for RA
NSAIDs and glucocorticoids to decrease jt inflammation
DMARDs to slow disease progression
What are glucocorticoids
Anti-inflammatory agents to decrease joint inflammation and decrease pain and progression of RA BUT there are high adverse effects from high doses of steroids if used alone
How are glucocorticoids utilized in treating RA
Early on they control pain and inflammation and “bridge” to when DMARDs begin
- then help during exacerbations by increasing dosing at that time
Mechanism of Action of Glucocorticoids
Bind to specific genes that regulate inflammatory process and inhibit pro-inflammatory substances and increase anti-inflammatory substances
What are the adverse effects of glucocorticoids
- catabolic breakdown (mm, bone, ligaments, skin)
- increased risk of infection
- increase in mood changes
- hypertension
- hyperglycemia
- increased appetite and weight gain
What are the two categories of DMARDs
traditional (non-biological) and biological
both control synovitis
How are DMARDs used in RA
use two or more to attack disease from multiple MoA
What is the order of DMARD prescription for RA
- Methotrexate
- TNF-alpha inhibitor
- other DMARDs substituted for TNF-alpha
Rehab concerns for those w/RA
Side effects of gluco (weakness, osteoporosis/osteopenia), side effects of DMARDs (N/H, increased risk of infection)
What is osteoarthritis
Intrinsic defect in remodeling of the joint cartilage and underlying bone where it is being broken down faster than it can be repaired
T or F: Pharmacological management is the first line of defense for OA
FALSE - it should be PT, weight loss, and joint replacement in advanced stages
What are the two pharmacological treatment goals/categories for OA
- pain relief
- Disease-modifying osteoarthritic drugs (DMOADs)
How is analgesia given for OA
- 1st a patch
- Acetaminophen first
- NSAIDs better once moderate to severe pain
What is viscosupplementation OA
- a DMOD injected into the joint space to replace synovium and liit articular destruction, lasting 6mo –> 1 year
What are glucosamine and chondroitin sulfate
Nonprescription dietary supplements used to assist w/OA as they are needed for production of cartilage and synovial fluid
