OTC Analgesics Flashcards
what do OTC drugs not include?
supplements
what are the 2 kinds of pharmaceutical drugs?
prescription and over the counter (OTC)
what neurons detect sensory info in the periphery?
primary afferents
what do primary afferents synapse onto?
secondary afferents (in spinal cord)
where do secondary afferents send info to?
brain
what do motor efferents do?
send motor info from brain to periphery (muscles)
what are nocireceptors?
specific class of primary afferents that detect pain
what do polymodal nociceptors detect?
thermal, mechanical, chemical and electrical pain
where are nociceptors found?
on every surface of our body
how are different stimuli detected by polymodal nociceptors?
specific receptors are expressed on polymodal nociceptors
what are transient receptor potential (TRP) channels?
temperature sensitive ligand-gated channels
what do TRPM8 and TRPV1 detect?
M8: <10ºC
V1: >43ºC
what ligands activate TRPM8 and TRPV1 receptors?
TRPM8: menthol (cool)
TRMV1: capsaicin (chili peppers-hot)
what are inflammatory molecules? what can they bind to?
released from immune system after injury or infection; nociceptors
what is arachidonic acid?
fa in all phospholipids of pmemb and a key inflammatory mediator (2)
how is arachidonic acid freed from a phospholipid molecule?
by phospholipase A2 enzyme
what 2 enzymes metabolize arachidonic acid into prostaglandins, prostacyclins and thromboxanes?
cyclooxygenase 1 and 2 (COX1 and COX2)
what enzyme metabolizes arachidonic acid into leukotrienes?
5-lipoxygenase
what do prostaglandins and leukotrienes do? (3)
drive inflammation (vasodilators, pyrogenic, leukotactic-attract immune cells)
what cells is COX1 expressed in?
non-inflammatory cells (blood vessels, platelets, gastric mucosa)
what cells is COX2 expressed in?
inflammatory cells
what are NSAIDS?
aspirin or other non-selective anti-inflammatory drugs
what do NSAIDS do generally?
treat inflammation
how do NSAIDS work?
block COX1 and 2 (mainly) to inhibit production of pro-inflammatory prostaglandins and leukotrienes, reducing pain
what is the antipyretic action of NSAIDS?
suppression of prostaglandin synthesis in brain (stimulated by pyrogens) to reduce fever (COX 2&3)
what are non-selective NSAIDS associated with? why?
gastric toxicity; inhibit COX1 in gastric mucosa
what can chronic use of non-selective NSAIDS cause? (3)
gastric ulceration, upper GI bleeding and renal failure
how can gastric toxicity from NSAIDS be bypassed?
using specific COX2 inhibitors (reduce inflammation in chronic inflammatory disease)
what is a con of specific COX2 inhibitors?
incr risk of cardiovascular toxicity
what does specific COX2 inhibitors reducing inflammation but not pain suggest?
other mechanisms drive analgesic effects beyond blocking inflammation
what is acetaminophen? (2)
an analgesic and antipyretic (no anti-inflammatory effects/not an NSAID)
how does acetaminophen work?
a weak COX1 and 2 inhibitor (does not work like other NSAIDS), inhibits COX3 in cerebral cortex
what are the side effects of acetaminophen?
overdose w/ liver impairments leads to liver damage or death
what was the first anesthetic drug discovered?
cocaine
how did Albert Niemann discover the anesthetic properties of cocaine in the late 19th century?
isolated cocaine from cocoa leaves and it numbed his tongue (used as a topical anesthetic for ophthalmoplegic surgery)
what are the 3 most common topical anesthetics?
procain, lidocaine and bupivacaine
what 3 functional groups do most local anesthetic contain?
hydrophobic aromatic moiety (ring), linker region and subs. amine (hydrophilic)
what does the nature of the linker region of local anesthetics determine?
pharmacological properties (how long, well and fast it works)
what does the ester linkage in local anesthetics (procaine) allow for? (2)
easy hydrolysis by plasma esterase and a short duration of action
how do topical anesthetics work?
bind reversibly to site in pore of Na channels (block ion movement) - only accessible intracellularly
what do topical anesthetics do?
block active neurons (ex: nociceptors when there is pain) thus blocking all sensation/causing motor paralysis
how does the hydrophobicity of topical anesthetics affect its action? why?
incr potency and duration; Na channel binding pocket is hydrophobic and must cross pmemb
how do local anesthetics preferentially block active neurons?
have a high affinity for open conf. of Na channels (can bind to pore easier)
what is capsaicin?
agonist for TRPV1 receptor (active ingredient in chili peppers, causes burning pain)
what does chronic activation of TRPV1 receptors (by capsaicin) cause?
desensitization and loss of TRPV1+ nociceptors leading to analgesia
what does capsaicin do in a cell? (4)
prolonged opening of TRPV1 channels causes influx of cations, Ca overload, mitochondrial dysfunction and nerve ending dies off
what is capsaicin most effective at treating?
burning or inflammatory pain from arthritis
what do 3 OTC treatments for pain target?
inflammation/fever (NSAIDS), non-specific sensory pathways (topical anesthetics), and nociceptors (capsaicin cream)
