Analgesics: Opioids, NSAIDs, & Steroidal Anti-Inflammatories Flashcards
What is allodynia?
Pain due to a stimulus that does not normally provoke pain
What is hyperalgesia?
Increased pain from a stimulus that normally provokes pain
What is hypoalgesia?
Diminished pain in response to a normally painful stimulus
What is neuralgia?
Pain in the distribution of a nerve or nerves
What is neuritis?
Inflammation of a nerve or nerves
What is nociception?
The neural process of encoding noxious stimuli
What is a nociceptor?
A high threshold sensory receptor of the peripheral somatosensory nervous system that is capable of transducing and encoding noxious stimuli
What is nociceptive pain?
Pain that arises from actual or threatened damage to non-neural tissue and is due to the activation of nociceptors
What is neuropathic pain?
Pain caused by a lesion or damage or disease of the neurons or somatosensory nervous system
What is the WHO analgesic ladder?
-Step 1: Mild pain
-Step 2: Moderate pain
-Step 3: Severe pain
-Step 4: Acute, chronic, and palliative
What medications or treatment is used for step 1 on the WHO analgesic ladder?
-PT
-OT
-Non-opioid analgesics
-NSAIDs
-Adjuvant pain medications
What medications or treatment is used for step 2 on the WHO analgesic ladder?
-PT/OT
-Weak opioids
-Psychology, behavioral therapy, etc.
What medications or treatment is used for step 3 on the WHO analgesic ladder?
-Strong opioids
-PT/OT
-Psychology, behavioral therapy, etc.
What medications or treatment is used for step 4 on the WHO analgesic ladder?
-PT
-OT
What treatments can be used at every step on the WHO analgesic ladder?
-NSAIDs
-PT/OT
-Acupuncture
-Massage
-TENS
What is adjuvant pain medications?
Medications that are not typically used for pain but may be helpful for its management
What are some examples of adjuvant pain medications?
-Anti-depressants
-Anti-seizure medications
-Muscle relaxants
-Sedatives
-Anti-anxiety medications
-Botulinum toxin
What are medications that help to alter the perception of pain in the brain?
-Opioids
-TCAs
-SSRI
-SNRIs
-⍺-2 agonists
What are medications that help to modulate the ascending/descending pain pathway?
-TCAs
-SSRIs
-SNRIs
What are medications that limit the transmission of pain in the peripheral nerves?
-LAs (ask Dr. Pattipatti what this is)
-Opioids
-⍺-2 agonists
What are medications that limit the transduction of peripheral nociceptors?
-LAs
-Capsaicin
-Anticonvulsants
-NSAIDs
-ASA (what is this?)
-Acetaminophen
-Nitrate
What are examples of TCAs and SSRIs?
-Amitriptyline
-Noritryptiline
-Duloxetine
What are examples of topical agents?
-Capsaicin
-Lidocaine patch
What are examples of opioids?
-Tramadol
-Tapentadol
-Hydrocodone
-Oxycodone
-Methadone
What are examples of NMDA inhibitors?
-Ketamine
-Amantidine
-Memantine
What are examples of anticonvulsant agents?
-Pregabalin
-Gabapentin
-Carbamazepine
Where does opioids come from? What is the history of its use?
-Exudate from the opium poppy
-Has been used for 2,000-6,000 years
-Known to relieve pain, diarrhea, and produce euphoria
-Serturner isolated and puriphied morphine in 1803
-Semisynthetic compounds (Heroin- 1874)
-Fully synthetic opioids (Meperidine- 1939)
-Medicinal and recreational uses firmly established
Where are endogenous opioids derived from?
Peptides
Where are endorphins derived from? What types of endorphins are there? What receptors do they work on?
-Derived from proopiomelanocortin (POMC)
-2 types of β-endorphins: β-endorphin-1 and β-endorphin-2
-Primarily µ agonist and also has 𝛿 action
Where are enkephalins derived from? What types are there? What receptors do they work on?
-Derived from proenkephalin
-Met-ENK
-Leu-ENK
-Met-ENK: µ and 𝛿 agonist
-Leu-ENK: 𝛿 agonist
Where are dynorphins derived from? What types are there? What receptors do they work on?
-Derived from prodynorphine
-DYN-A
-DYN-B
-Potent 𝜿 agonist and also have µ and 𝛿 action
What are the 3 opioid receptors? What therapeutic effects does agonists of these receptors create?
-Mu (µ)
-Kappa (𝜿)
-Delta (𝛿)
-Creates spinal and supraspinal analgesia
What are other effects of µ agonists?
-Sedation
-Respiratory depression this is why opioid overdose can cause death
-Constipation
-Inhibits neurotransmitter release (ACh, dopamine)
-Increases hormonal release (prolactin, growth hormone)
What are other effects of 𝜿 agonists?
-Sedation
-Constipation
-Psychotic effects
What are other effects of 𝛿 agonists?
-Increases hormonal release (growth hormone)
-Inhibits neurotransmitter release (dopamine)
What are opioid receptor agonists?
Activate one or more opioid receptors
What are opioid receptor antagonists?
Occupy receptors and prevent agonist binding (e.g. Naloxone)
What are opioid mixed receptor agonist-antagonists?
Agonist activity at one type of receptor and antagonist activity at another type of receptor (e.g. Buprenorphine)
What is the difference between and opioid and an opiate?
-Opioid: any naturally occurring, semi-synthetic, or fully synthetic compound that binds to opioid receptors and share the properties of one or more of the naturally occurring endogenous opioids
-Opiate: any naturally occurring opioid derived from opium
What are examples of strong opioid receptor agonists? What receptor do they primarily interact with?
-Strong agonists are used to treat severe pain
-Interact primarily with µ receptors
-Fetanyl (Duragesic, Sublimaze)
-Morphine (MS Contin)
-Hydromorphone (Dilaudid)
-Oxymorphone (Numorphan)
-Meperidine (Demerol)
-Methadone (Dolophine)
-Oxycodone (Oxycontin)
What are examples of mild to moderate opioid receptor agonists?
-These are used for mild to moderate pain
-Codein
-Hydrocodone (Hycodan)
What are examples of mixed opioid receptor agonist-antagonist?
-Some of these bind to 𝜿 receptors while block or partially block µ receptors making them µ receptor antagonists or partial agonists
-Buprenorphine (Buprenex)
-Nalbuphine (Nubain)
What are examples of opioid receptor antagonists?
-Particular affinity for µ
-Naloxone (Narcan)
-Naltrexone (ReVia, Vivitrol)
What are other uses of Naltrexone?
-Can be used in conjunction with behavioral therapy to maintain an opioid-free state for recovering opioid addicts
-Can be used in treating alcohol dependence
What is the mechanism of action of opioids?
-Bind to opioid receptors
-Two well established direct G-protein coupled actions
-They close voltage gated Ca2+ channels on presynaptic nerve terminals which reduces neurotransmitter release (glutamate and substance P)
-They open K+ channels on postsynaptic neurons and hyperpolarize them and inhibit postsynaptic neurons
What are the sites of putative action of opioid analgesics?
-Primary afferent nociceptor terminals
-Dorsal horn
-Ventral posterolateral nucleus (VPL) of the thalamus
-Possibly in the amygdala as well
What are the key pharmacological actions of morphine and other opioid agents?
-Analgesia
-Respiratory depression
-Spasm of smooth muscle of the gastrointestinal (GI) and genitourinary (GU) tracts, including the biliary tract (bile ducts)
-Pinpoint pupils (miosis)
What is a way to determine if someone if overdosing from opioids or another drug?
If someone’s pupils are constricted/has pinpoint pupils, they are overdosing from opioids
What are the CNS effects of opioids?
-Analgesia
-Euphoria
-Sedation
-Respiratory depression
-Cough suppression
-Miosis
-Truncal rigidity
-Nausea and vomiting
-Body temperature
-Sleep disturbances
What are the effects of opioids on the cardiovascular system?
-Typically no significant effects
If there are effects:
-Bradycardia
-Hypotension
-Increased cerebral blood flow
-Increased intracranial pressure (opioids contraindicated in brain injury patients)
What are the effects of opioids on the gastrointestinal system?
Constipation
What are the effects of opioids on the biliary tract?
Biliary colic (blockage of bile ducts- contraction of biliary smooth muscles)
What are the effects of opioids on the renal system?
-Decreased renal function
-Anti-diuretic effect
-Urinary retention
What are the effects of opioids on the endocrine system?
-Decreased testosterone with chronic use
-Decreased libido, energy, and mood
-Dysmenorrhea or amenorrhea in women
What are the effects of opioids on the skin?
-Pruritis (itchy feeling of the skin)
-Produce flushing and warming of the skin accompanied sometimes by sweating, urticaria (itchy red bumps), and itching
-Peripheral histamine release
What is the duration of action of fentanyl?
1 hour
What is the duration of action of methadone?
8 hours
What is the duration of action of morphine?
4 hours
What is the duration of action of oxycodone?
4 hours
What is the duration of action of codeine?
4 hours
What is the duration of action of hydrocodone?
4 hours
What is the duration of action of tramadol?
4 hours
What is the duration of action of buprenorphine?
5 hours
What is the duration of action of naloxone?
2 hours
What is the duration of action of naltrexone?
24 hours
What are the clinical used for opioids?
-Analgesia
-Acute pulmonary edema
-Cough
-Diarrhea
-Anesthesia
What are the signs & symptoms of opioid overdose?
-Euphoria
-Unconsciousness
-Respiratory depression
-Miosis
-Pulmonary edema
-Seizures
-Hypothermia
-Death
What is the opiate toxicity triad?
-CNS depression (coma)
-Respiratory depression (cyanosis)
-Pupillary miosis
What are adverse effects with chronic opioid use?
-Hypogonadism
-Immunosuppression
-Increased feeding
-Increased growth hormone secretion
-Withdrawal effects
-Tolerance, dependence
-Abuse, addiction
-Hyperalgesia
-Impairment while driving
What does a person develop tolerance for on opioids?
-Analgesic effect
-Sedating effect
-Respiratory depressant effects
-Antidiuretic, emetic, and hypotensive effects
What tolerance does not develop on opioids?
-Mitotic effect
-Convulsant effect
-Constipating effect
What is physical dependence of opioid use?
An invariable accompaniment of tolerance to repeated administration pf an opioid of the µ type
What are symptoms of withdrawal to opioids?
-Rhinorrhea
-Lacrimation
-Yawning
-Chills
-Gooseflesh
-Hyperventilation
-Hyperthermia
-Mydriasis
-Muscular aches
-Vomiting
-Diarrhea
-Anxiety
-Hostility
What is psychological dependence of opioids or other drugs?
Addiction
What are benefits of patient controlled anesthesia?
-May allow better pain control with fewer side effects
-Requires patient awareness and cognitive ability
-Increases patient satisfaction
What are special concerns for rehab with opioids?
-Schedule therapy when drugs reach peak
-Consider respiratory depression
-Constipation: pts may be uncomfortable
-Withdrawal symptoms or addiction
What are non-opioid analgesics?
-Non-steroidal anti-inflammatory drugs (NSAIDs)
-Acetaminophen (Tylenol)
What are the primary therapeutic effects of NSAIDs?
-Analgesic
-Anti-inflammatory
-Antipyretic (reduces body temp.)
-Anticoagulant
-Anticancer (colorectal cancer)
What are prostaglandins (PGs)?
-Small lipid compounds produced in almost all cells
-Cells begin to synthesize PGs in response to damage
What are the function of PGs?
-In the hypothalamus: thermoregulation
-Responsible for coagulation
-PGs can exaggerate pain
-Promote inflammation
-Abnormal coagulation
How are PGs synthesized?
Prostaglandings are made by an enzymatic reaction where cyclooxygenase (COX-1, COX-2) converts arachidonic acid into prostaglandins
What is the mechanism of action of NSAIDs?
NSAIDs inhibit cyclooxygenase (COX-1, COX-2) from converting arachidonic acid to prostaglandins
What are non-selective NSAIDs? What are examples of them?
-Inhibit COX-1 and COX-2
-Diclofenac
-Ibuprofen
-Naproxen
What are COX-2 selective NSAIDs? What are examples of them?
-Specifically inhibit COX-2
-Celecoxib (Celebrex)
-Rofecoxib
Why if Rofecoxib banned?
Due to cardiovascular side effects
What are the functions of the prostaglandins that COX-1 produces?
-PGs that mediate homeostatic functions
-Constitutively expressed
-Homeostatic protection of gastric mucosa
-Platelet activation
-Renal functions
-Macrophage differentiation
What are the functions of the prostaglandins that COX-2 produces?
-PGs that mediate inflammation, pain, and fever
-Induced mainly in sites of acute inflammation by cytokines
-Pathologic inflammation
-Pain
-Fever
-Dysregulated proliferation
What are common NSAIDs?
-Aspirin
-Ibuprofen
-Naproxen
-Indomethacin
-Meloxicam
-Diclofenac
-Celecoxib
What are common side effects of NSAIDs?
-Nausea and vomiting
-Diarrhea
-Constipation
-Decreased appetite
-Rash
-Dizziness
-Headache
-Drowsiness
What are side effects associated with chronic use of NSAIDs?
-Kidney failure
-Liver failure
-Ulcers
What are uncommon side effects of NSAIDs?
-Prolonged bleeding after injury or surgery
-Fluid retention/edema
What is the benefit of selective COX-2 NSAIDs vs non-selective NSAIDs?
-May decrease pain & inflammation with less toxicity (less gastritis)
-Better for long term use
What are the benefits of acetaminophen?
-Analgesic and antipyretic effects
-No gastric irritation
-No anticoagulant effects
-No anti-inflammatory effects
What are side effects of acetaminophen if taken in high doses?
Liver toxicity
What are indications for acetaminophen?
-Frequently 1st drug used to control pain in early stages of OA and other MSK conditions that do not have an inflammatory
-Children and teenagers
What is a contraindication for acetaminophen?
-Reyes syndrome
-This syndrome is a rare but serious condition that causes confusion, swelling in the brain, and liver damage
What is the mechanism of action of acetaminophen?
-Not fully understood
-Inhibits cyclooxygenase (COX)
-Unclear why it does not exert anticoagulant & anti-inflammatory effects: thought to preferentially inhibit CNS PG production vs peripheral
Why can high doses of acetaminophen cause liver toxicity?
-Acetaminophen metabolizes into a toxic intermediate
-It is quickly detoxified and eliminated via the urine
-High doses can result in accumulation of the toxic intermediate with subsequent toxicity to liver proteins
What are common acetaminophen + opioid combinations?
-Lortab, Lorcet: hydrocodone + acetaminophen
-Darvocet: propoxyphene + acetaminophen
-Percocet: oxycodone + acetaminophen
What are physical therapy considerations for patients on NSAIDs or acetaminophen?
-Pain masking
-GI effects
-Cardiovascular risks
-Renal effects
-Hepatotoxicity
-Therapy timing
-Patient education
-Monitoring side effects
What are steroidal anti-inflammatory drugs (SAIDs)?
-Glucocorticoids
-Derived from cholesterol
What three 1° adrenal steroids does the adrenal cortex produce?
-Glucocorticoids (cortisol, corticosterone)
-Mineralocorticoids (aldosterone)
-Sex hormones
What are the physiological functions of glucocorticoids?
-Control glucose metabolism
-Controls the body’s ability to deal with stress
-Decrease inflammation
-Suppress the immune system
What is the precursor to steroids?
Cholesterol
What is the mechanism of action of glucocorticoids?
-Act on inflammatory cells
-Drug binds to glucocorticoid receptors in cytoplasm
-Drug-receptor complex travels to nucleus of the cell and alters gene expression
-Decreases expression of inflammatory proteins
-Increases expression of anti-inflammatory proteins
What is the clinical use of glucocorticoids?
-Endocrine conditions: normalize adrenal cortical hypofunction
-Nonendocrine conditions: RA, tenosynovitis, myositis, collagen disease
How are glucocorticoids for nonendocrine conditions such as RA or tenosynovitis administered?
Injections into specific tissues to help localize effects
What are some common glucocorticoids?
-Cortisone
-Dexamethasone
-Prednisone
-Hydrocortisone
What glucocorticoid is typically used for anaphylaxis?
Dexamethasone
What are methods of administering glucocorticoids?
-Oral: systemic
-Injections: local
-Dose packs: provide large dose but tapers off over 4-5 day period
What are adverse effects of glucocorticoids?
-Adrenocortical suppression
-Peptic ulcers
-Drug induced Cushing Syndrome
-Adrenal crisis/shock
-Breakdown of supporting tissues
-Decreases body’s ability to absorb calcium and can lead to osteoporosis
What are side effects of glucocorticoids?
-Headache
-Irregular heartbeat
-Sweating
-Dizziness
-Irritability
How does breakdown of supporting tissues occur from glucocorticoid use?
-Bone, ligaments, tendons, and skin are subject to a wasting effect from prolonged use
-Inhibits the genes responsible for production of collagen and other tissue components by increasing the expression of substances that promote breakdown of bone, muscle, etc.
-Interferes with muscle protein synthesis
-Can cause skeletal muscle atrophy
What are the signs & symptoms of drug induced Cushing Syndrome?
-Roundness and puffiness in the face
-Fat deposition and obesity in the trunk
-Muscle wasting in extremities
-Hypertension
-Osteoporosis
-Increased body hair
-Glucose intolerance
What are signs & symptoms of adrenal crisis/shock?
-Vasodilation of the organs
-Vascular collapse
-Severe hypotension
-Pain in legs, low back, abdomen
-Low BP, syncope
-Vomiting and diarrhea
-Hyperkalemia
-Hyponatremia
How can glucocorticoids lead to osteoporosis?
-Shifts the balance of bone metabolism leading to increased breakdown
-Stimulates osteoclast-induced bone resorption
-Inhibits osteoblast-induced bone formation
What are other side effects of glucocorticoids?
-Salt/water retention
-Increased infection
-Gastric ulcers due to decreased good PGs in stomach
-Glucose intolerance
-Glaucoma-effect vitreous humor drainage
-Adrenal suppression
What are PT considerations for glucocorticoid use?
-Increased risk of fractures, falls, and infection
-Strengthening exercises to maintain muscle mass
-Encourage weight bearing activities such as walking
-Inspection for skin breakdown
-Monitor blood pressure
