Lecture 12 - OTC Analgesics Flashcards
neurons that detect sensory information in the periphery
primary afferents
primary afferents synapse onto _____ in the spinal cord which pass sensory information up to the brain
secondary afferents
take motor commands from the brain and send them to the periphery
motor efferents
pain is detected by a specific class of primary afferents called:
nociceptors
detect many types of painful stimuli (thermal, mechanical, chemical, etc)
polymodal nociceptors
where are nociceptors found?
nociceptors densely innervate every surface of our body
different types of painful stimuli are detected by specific receptors expressed on:
polymodal nociceptors
temperature sensitive ligand-gated ion channels
transient receptor potential (TRP) channels
TRPM8 is activated at:
temperatures below 10 degrees
TRPV1 is activated at:
temperatures above 43 degrees
released from surrounding immune cells following tissue injury or infection
inflammatory molecules (ie: bradykinin, cytokines, prostaglandins)
what is arachidonic acid?
a fatty acid present in phospholipids of cell membranes
arachidonic acid is freed from the phospholipid molecule by:
the enzyme phospholipase A2
a key inflammatory mediator
arachidonic acid
the enzymes cyclooxygenase-1 and cyclooxygenase-2 metabolize arachidonic acid into:
prostaglandins (PG) and thromboxanes (Tx)
what are some of the functions of prostaglandins and thromboxanes?
- inflammation
- body temperature regulation
- platlet aggregation
- renal function
- etc
- potent vasodilator
- pyrogenic (fever)
- attract immune cells (leukotactic) and coordinate the immune response
- involved in producing gastric mucous
these are all characteristics of:
prostaglandin E2 (PGE2)
signals to platlets to form clots and causes vasoconstriction
thromboxane A2 (TXA2)
true or false: expression of cyclooxygenase enzymes is tissue specific
true
COX1 is primarily expressed in _____, whereas COX2 is expressed in _____
non-inflammatory cells, inflammatory cells
enzyme activity is either _____ or _____
constitutive (always on), inducible (must be activated by stimulus)
aspirin and other non-selective NSAIDs inhibit:
both COX1 and COX2
what is the effect of inhibiting of COX1 and COX2?
- decreases prostaglandin production that inhibits inflammation and reduces pain
- supresses prostaglandin synthesis in the brain
how does daily NSAID use help those at risk of a stroke or heart attack?
prevents platlet aggregation (particularly aspirin)
most NSAIDs inhibit the ______ of the cyclooxygenase enzymes
catalytic site (where arachidonic acid binds)
acetylsalicylic acid (aspirin) is an:
irreversible inhibitor (covalently binds to the catalytic site of COX1 and COX2)
how is the long half-life of aspirin explained?
it is an irreversible inhibitor of COX1 and COX2, meaning it has to be broken down and new COX enzymes have to be used
non-selective NSAIDs are associated with:
gastric toxicity (due to inhibition of COX1 enzymes in gastric mucosa)
chronic use of NSAIDs can result in:
gastric ulceration, upper GI bleeding, and renal failure
a highly efficacious non-selective NSAID recommended for short term use post-surgically; however, chronic use produces long term gastric issues
ketoralac
to bypass the gastric toxicity, _____ have been developed
specific COX2 inhibitors
certain COX2 inhibitors are also associated with higher risk of:
cardiovascular toxicity
inhibits a third COX isoform (COX3) found most abundantly in the cerebral cortex
acetominophen
an analgesic and antipyretic agent that lacks anti-inflammatory effects
acetominophen
what was the first local anesthetic discovered?
cocaine
German chemist, Albert Niemann, introduced cocaine as a:
topical anesthetic for ophthalmological surgery
list examples of topical anesthetics that look like cocaine, but lack the addictive and toxic side effects
- procain
- lidocaine
- bupivicane
most local anesthetics contain a:
hydrophobic (aromatic) moiety, a linker region (ester), and a substituted amine
what portion of a topical anesthetic (synthetic cocaine substitutes) determines the pharmacological properties of the molecule?
the linker region
local anesthetics bind to a specific site within the:
pore of sodium channels (block ion movement through the pore)
the site of the Na+ channels at which local anesthetics bind to is only accessible:
intracellularly (anesthetics must cross the membrane)
all neurons require sodium channels for action potential propogation. so, local anesthetics block:
all sensation and cause motor paralysis in the area
local anesthetics have a higher affinity for:
the open conformation of the sodium channel (so they preferentially block active neurons)
are the effects of local anesthetics reversible?
yes
capsaicin is an agonist for:
the TRPV1 receptor
initial application of capsaicin cream causes:
moderate burning pain
chronic activation of TRPV1 receptors due to application of capsaicin cream leads to:
desensitization and loss of TRPV1 nociceptors, leading to analgesia
