Lecture 9: Pain Pharmacology Flashcards
What is the key difference between an anesthetic and an analgesic?
Anesthetics involve depressing all CNS characteristics, aka loss of all sensory modalities. Usually accompanied by LOC.
Analgesics are pain only, no LOC.
What is the gate-control theory?
Non-painful stimuli shut the gate to painful stimuli, preventing pain sensation from traveling to the CNS.
non opiod medications are called ___
what are their uses (3)
Adjuvant medications
- medications that enhance the efficacy of primary medications
- can also be used WITHOUT opiods
- can be used as a first-line treatement before considering opiods.
what is the prototype for all neuropathic pain meds. what is its MOA. what is its downfall
lidocaine
blocks Na+ channels
no oral admin
what are corticosteriods and how are they administered
glucocorticoids commonly used as an anti-inflammatory, administered orally and injectable
What are the side effects of corticosteroids?
Adrenal suppression
Appetite stimulation/weight gain
Cataracts formation
Impaired glucose metabolism
Edema
CHF
Osteoporosis
PUD
Bleeding
Mood changes
Steroid Psychosis
Joint degradation/atrophy at injection site with repeated injections.
What is the mechanism of action of corticosteroids?
Inhibition of phospholipase A2, which decreases the production of arachidonic acid and the inflammatory mediators.
What are the two pathways NSAIDs target?
COX-1
COX-2
What is the MoA of an NSAID?
Inhibition of the COX pathway. Subsequently inhibits prostaglandin formation.
Inhibits urate crystal phagocytosis (gout)
What does COX-1 inhibition commonly cause?
GI issues
Some prostaglandins are protective to mucosa which inhibit acid erosion
What does COX-2 inhibition commonly cause?
Decreases prostaglandins which therefore decrease inflammation, pain, fever
ALSO causes platelet aggregation and vasoconstriction, which is why celebrex has a cardiac black box warning.
(NSAIDS AND TYLENOL)
What is the PK of an NSAID?
absorption: Low pH causes absorption by intestinal and gastric mucosa.
distribution: Binds to albumin
metabolized: hepatically and conjugated to inactive metabolites,
Exccretion: renal excretion.
how does NSAIDS cause renal toxicity
prostaglandins are used to vasodilate the afferent arterioles in the glomeruli.
nsaids decrease prostaglandins
unnopposed constriction of arterioles = decreased renal perfusion = renal failure.
What lab test should I order before giving someone NSAIDs?
Renal function test, to check GFR
(BMP)
What are the other names for tylenol?
Acetaminophen/Paracetamol.
Scientific name: N-acetyl-p-aminophenol (APAP)
What is the MoA for Tylenol?
It is a selective COX inhibitor that generally targets COX-2.
Metabolites of APAP bind to TRPA-1 receptors (receptors for pain, stretch, temp), suppressing signal transduction of dorsal horn which supresses the pain/temp/stretch.
Why is tylenol an antipyretic?
COX enzyme reduction decreases formation for prostaglandin H2, which decreases prostaglandin E2 in hypothalamus (responsible for thermoregulation) which decreases temp
What is the max dose of tylenol in adults?
it was 4000mg/day but they recently decreased this to 3000mg/day
What kind of toxicity does excessive tylenol cause?
Hepatotoxicity
What two conditions can cause hepatotoxicity with tylenol?
High dosages and/or low glutathione, which is caused by excessive ETOH.
What kind of lab test should I order prior to tylenol use?
Liver function tests. (LFT) every 6 months
What are other non-opioid medications?
Lidocaine patch/cream (complete block of Na+ in neuron membrane = less pain)
Antispasmodics (decreased myofascial spasticity)
Compounding pharmacy topicals
Membrane stabilizers
what is the difference between opioids and opiates
opiates are natural opium alkaloids and semi-synthetics whereas opioids are morphine-like synthetics
the term opioids are used for both.
How do opiates work in general? howe do opioids work?
Alkaloid opiates mimic the action of endogenous endorphins (enkephalins) that are normally produced for analgesia by attaching to opioid receptors.
opiates act as ligands to attach to G-protein coupled (opioid) receptors in the brainstem/medial thalamus, spinal cord, and gastrointestinal regions.
What kind of receptor interaction are opioids?
Ligands binding to G-Protein coupled receptors.
What are the 3 opioid receptor subtypes?
Mu (u)
Kappa (k)
Delta
What is the main opioid receptor subtype? what does it control
Mu: responsible for analgesia, respiratory depression, GI SE, sedation, and pruritis.
What do kappa receptor subtypes control?
Analgesia, but mainly the consciousness effects, like hallucinations, euphoria, etc.
What do delta receptor subtypes control?
Analgesia possible.
Might offset respiratory depression from mu receptor subtypes.
What NTs does an opioid affect? How?
GABA inhibition, which inhibits substance P(pain).
Activates dopamine(causes euphoria).
Activation of receptor inhibits adenylate cyclase, decreases intracellular cAMP. Overall effect is reducing flow of nociceptive(pain) flow.
What are the two types of Mu receptors? What do they control?
Mu1 is responsible for analgesia and physical dependence.
Mu2 causes euphoria, respiratory depression, and constipation.
What are NMDA receptors? What is the significance?
Responsible for memory, enhances response to pain stimuli, suppresses CNS sensitization.
Antagonizing the NMDA receptors can help decrease tolerance to opioids. (Methadone)
What exactly is opium?
Dried milky latex from the opium poppy plant.
What are the 5 schedules of controlled substances? What are most opioids under?
Schedule 1-5, with schedule 1 being the most dangerous/addictive substances, such as LSD, heroin, cocaine, ecstasy, cannabis.
Most opioids are schedule II.
What are the pros and cons of short acting opioids?
Pros:
Good starter drug
Good for PRN use
Commonly prescribed
Cons:
Quick tolerance
Easy to abuse bc commonly prescribed
Highs and lows
What are the pros and cons of long-acting opioids?
Pros:
Sustained releases, long acting
Cons:
High risk for abuse
Not for opioid naive patients
What are the general SE of opioids?
Constipation, drowsiness, pruritis, respiratory depression, Hyperhidrosis, mental blunting, edema, dental loss, hypotestoteronism
What two medications are commonly used as adjuvants for opioids?
Ibuprofen and APAP/tylenol
What is the difference between dependence and addiction?
Dependence is when discontinuing an opioid causes withdrawal effects.
Addiction is when there is a psychological dependence and preoccupation with obtaining a supply despite harm to themselves or others. High incidence of recidivism.
Is tolerance inevitable?
Yes, due to neuroadaptation of the receptor.
When does pseudoaddiction occur?
Patients with both malignant and chronic pain. Most often seen in under-treatment of pain.
What are some drugs we give for opioid withdrawal?
Methadone
Clonidine
Suboxone