Pain and opioids, NSAIDS and steroidal anti-inflammatory drugs Flashcards
What is nociception?
neural process of encoding noxious stimuli
What is neuralgia?
pain in the distribution of nerve(s)
What is allodynia?
pain because of a stimuli that doesn’t normally provoke a pain
What is hyperalgesia?
more pain from a stimulus that normally provokes pain
What is neuropathic pain?
pain because of damage of the neurons or somatosensory nervous system
What are the drugs considered as adjuvants?
antidepressants
anticonvulsant
antispasmodic
muscle relaxant
bisphosphate
corticosteroid
What are the drugs considered as weak opioids?
codeine
tramadol
low dose morphine
What are the drugs considered as strong opioids?
morphine
fentanyl
oxycodone
hydromorphone
buprenorphine
WHO Analgesic Ladder
What is step 1 for mild pain?
a non-opioid
+/- adjuvant
WHO Analgesic Ladder
What is step 2 for moderate pain?
a weak opioid
+/- non-opioid
+/- adjuvant
WHO Analgesic Ladder
What is step 3 for severe pain?
strong opioid
+/- non-opioid
+/- adjuvant
WHO Analgesic Ladder
What is the +/- indicating?
That combining an opioid and non-opioid is effective but not combining drugs of the same class
What are the types of drugs used for pain treatment?
It’s a picture sry :(
What are the classifications of pain medications?
- opioid analgesics (HARD ASS DRUGS)
- non-opioid analgesics (NSAIDs)
What are the endogenous opioid peptides
Endorphins
- derived from POMC
Enkephalins
- derived from proenkephalin
Dynorphine
- derived from prodynorphine
Opioid receptors
What is the primary therapeutic effect of all opioid receptors?
spinal and supraspinal analgesia
Opioid receptors
What is the other effects of Mu(μ)?
sedation
respiratory depression
constipation
stops neurotransmitter release (ACh and dopamine)
increases hormonal release (prolactin)
Opioid receptors
What is the other effects of Kappa (k)?
sedation
constipation
psychotic effects
Opioid receptors
What is the other effects of delta (δ)?
increases hormonal release
inhibits neurotransmitter release
What is the effect of a strong agonist on the body?
have high affinity (relationship) for certain receptors
- believed to interact primarily with Mu opioid receptors in the CNS
What is the effect of a mild-to-mod agonist on the body?
still considered agonist that stimulate opioid receptors
- but do not have as high affinity or efficacy
What drugs are more effective in treating mild-mod pain?
codeine and hydrocodone
What is the characteristic of mixed agonist-antagonists?
show some agonist and antagonist-like activity at the same time
- drugs have the ability to act differently at specific classes of receptors
What are antagonist?
block all receptors that loves the Mu variety
What is the mechanism of the antagonists?
they wont produce analgesia but will displace opioid agonist from the receptors = block effects
What is the primary function of antagonist?
To treat opioid overdoses and addiction
What is the primary agent used to treat opioid overdose?
Naloxone
Morphine - brand name
MS contin
Methadone - Brand name
dolophine
Oxycodone - brand name
oxycontin
Hydromorphone - brand name
Dilaudid
Fentanyl - brand name
duragesic
sublimaze
Hydrocodone - brand name
Hycodan
Buprenorphine - brand name
Buprenex
Naloxone - brand name
Narcan
Naltrexone - brand name
ReVia
Vivitrol
Mechanism of Action of Opioids
What does the opioid drug bind to?
the opioid receptors which are Gi/0 protein-couple receptors
Mechanism of Action of Opioids
What is the presynaptic effects?
They close the voltage-gated Ca2+ channels @ presynaptic nerve terminals
= decrease transmitter release (glutamate and substance-P)
Mechanism of Action of Opioids
What is the postsynaptic effects?
they open the K+ channels of the postsynaptic neurons and hyperpolarize them
= inhibit postsynaptic neurons
What are the CNS effects of opioids?
- analgesia
- euphoria
- sedation
- respiratory depression
- cough suppression
- miosis
- truncal rigidity
- nausea
- vomitting
- body temp
- sleep disturbances
Peripheral effects of Opioids
Cardiovascular system effects
- no significants on CVs
- bradycardia
- hypotension
- increased cerebral blood flow
- increased intracranial pressure
Brady - except Meperidine-tachycardia due to anticholinergic effects
Intracranial pressure - contraindicated in brain injury
Peripheral effects of Opioids
Gastrointestinal system effects
constipation
- opioids don’t develop the tolerance to constipating effects
Peripheral effects of Opioids
Biliary tract effects
Biliary colic
- contraction of biliary smooth muscles
Peripheral effects of Opioids
Renal effects
- decreased renal function
- antidiuretic effect
- urinary retention
Peripheral effects of Opioids
Endocrine effects
- decreased testosterone with chronic use
- decreased libido, energy and mood
- dysmenorrhea or amenorrhea in women
Peripheral effects of Opioids
Pruritis effects
Produce flushing and warming of the skin + sweating, urticaria and itching
- increased peripheral histamine release
What is the major cause of opioid overdose?
Respiratory failure
What are the adverse effects with acute use of opioid drug?
- respiratory depression
- nausea/vomiting
- pruritus
- urticaria
- constipation
- urinary retention
- delirium
- sedation
- myoclonus
- seizures
What are the adverse effects with chronic use of opioid drug?
- hypoganodism
- immunosuppresion
- increased feeding
- increased growth hormone secretion
- withdrawal effects
- tolerance and dependence
- abuse
- addiction
- hyperalgesia
- impairment of ADLs
How is a high degree of tolerance developed in regard to opioids?
What is not developed?
develop to the analgesic (no pain), sedating (high af) and respiratory depressants (relaxing) effects of the agonists
it can also be to the antidiuretic, emetic and hypotensive effects
Not to the miotic, convulsant and constipating actions
What does COX-1 produce?
produces prostaglandins that mediate homeostatic functions
- constitutively expressed
What does COX-2 produce?
Produces prostaglandins for inflammation, pain and fever
- induced mainly in sites of inflammation by cytokines
What is the mechanism of action for NSAIDs?
inhibiting COX
What is the effects of COX-1 inhibition?
peptic ulcers
GI bleeding
What is the effects of COX inhibition?
Na and water retention
Hypertension
Hemodynamic acute kidney injury
What is the effects of COX-2 > COX-1 inhibition?
Stroke
MI
What are the non-selective NSAIDs for COX1 and COX2?
Diclofenac
Ibuprofren
Naproxen
What are the COX2-selective NSAIDs?
Celecoxib
Rofecoxib
What is the mechanism of action of acetaminophen?
not fully understood but does inhibit the COX enzyme
a theory:
- it inhibits CNS PG production but has little effect on peripheral cyclooxygenase activity
- analgesia and antipyretic effect probably 2 PG inhibition
What are the important side effects of NSAIDs?
- kidney failure
- liver failure
- Ulcers
- prolonged bleeding after injury or surgery
- cause fluid retention = edema = swelling of ankles
What are the therapeutic effects of NSAIDs?
- analgesic
- anti-inflammatory
- antipyretic
- anticoagulant
- anticancer
All therapeutic effects through inhibition of prostaglandins
What is the precursor to steroid synthesis?
Cholesterol
Glucocorticoids produces what substances?
cortisol
corticosterone
Mineralocorticoids produces what substance?
Aldosterone
What is the function of mineralocorticoids?
Fluid retention and electrolyte balance
Clinical use of corticosteroids
What is the endocrine conditions?
used to normalize adrenal cortical hypofunction
- used as a diagnostic tool to evaluate hormal disorders
Clinical use of corticosteroids
What is the nonendocrine conditions?
different conditions for anti-inflammatory or immunosuppressive effects
- primary nonendocrine conditions will see: RA, myositis, tenosynovitis and collagen diseases
What are the adverse effects of corticosteroids?
- adrenocortical suppression
- peptic ulcers
- drug-induced cushing syndrome
- adrenal crisis/shock
- breakdown of supporting tissues
- decreases body’s ability to absorb calcium which can lead to osteoporosis and delayed wound healing
