L6 OTC Analgesics Flashcards
Neurons that detect sensory info in the periphery are called:
Primary afferents
Where do primary afferents synapse?
Onto secondary afferents in the spinal cord which then pass sensory info up to the brain
Pain is detected by a specific class of primary afferents called _________
Pain is detected by a specific class of primary afferents called nociceptors
What are polymodal nociceptors?
receptor that responds to many types of painful stimuli
(thermal, mechanical, chemical, electrical)
What channels are temperature sensitive ligand-gated ion channels?
Transient Receptor Potential (TRP) channels
- different types of TRP channels are tuned to respond to very specific temperatures
- TRPM8 - activated in cold temperatures (<10C)
- TRPV1 - activated at hot temperatures (>43C)
What ligands can activate TRPV1 and what ligand can activate TRPM8?
- TRPV1 - activated at hot temperatures = can be activated by capsaicin
- TRPM8 - activated at cold temperatures = can be activated by menthol
What are three examples of inflammatory molecules that would be released during an immune response?
- Bradykinins
- Cytokines
- Prostaglandins
What is arachidonic acid?
A fatty acid present in phospholipids of cell membranes
- Freed from the phospholipid molecule by the enzyme phospholipase A2
- key inflammatory mediator
- Metabolized by 3 enzymes
The enzymes _______ and _______ metabolize arachidonic acid into prostaglandins, protacyclins and thromboxanes
The enzymes cyclooxygenase-1 and -2 metabolize arachidonic acid into prostaglandins, protacyclins and thromboxanes
The enzymes cyclooxygenase-1 and -2 (COX1 and COX2) metabolize arachidonic acid into:
The enzymes cyclooxygenase-1 and -2 metabolize arachidonic acid into prostaglandins, protacyclins and thromboxanes
The enzyme 5-lipoxygenase (LOX) metabolizes arachidonic acid into:
Various leukotrienes
The enzyme __________ metabolizes arachidonic acid into various leukotrienes
The enzyme 5-lipoxygenase metabolizes arachidonic acid into various leukotrienes
How do prostoglandins and leukotrienes drive inflammation?
- They are potent vasodilators
- they are pyrogenic
- they attract immune cells (leukotactic) and coordinate the immune response
______ is primarily expressed in non-inflammatory cells (blood vessels, platelets, gastric mucosa)
COX-1 is primarily expressed in non-inflammatory cells (blood vessels, platelets, gastric mucosa)
________ is expressed mainly in inflammatory cells
Cox-2 is expressed mainly in inflammatory cells
COX-1 is primarily expressed in ________ whereas COX-2 is expressed mainly in ________
COX-1 is primarily expressed in non-inflammatory cells (blood vessels, gastric mucosa, platelets) whereas COX-2 is expressed mainly in inflammatory cells
Aspirin and other non-selective NSAIDS inhibit:
Both Cox isoforms (COX1 and COX2)
Block Arachidonic Acid binding site to prevent conversion to prostaglandins
What is the effect of aspirin and Non-selective NSAIDS?
- Aspirin and other non-selective NSAIDS inhibit both COX isoforms thereby decreasing prostaglandin production = inhibits inflammation and reduces pain
- Also suppress prostaglandin synthesis in the brain that is stimulated by pyrogens and reduce fever (antipyretic action)
Why are non-selective NSAIDS associated with gastric toxicity?
Inhibition of COX1 enzymes in the gastric mucosa decreases:
- mucus secretion,
- bicarbonate secretion and
- blood flow
What was developed in an attempt to bypass the gastric toxicity resulting from non-selective NSAIDS?
Specific COX2 inhibitors were developed
(eg celecoxib)
Specific COX2 inhibitors are effective at reducing _______ but not at _________.
What does this suggest?
Specific COX2 inhibitors are effective at reducing inflammation but not at treating acute pain
- Suggests that mechanisms beyond blocking inflammation drives analgesic effects
What is a side-effect of Selective COX2 Inhibitors?
higher risk of cardiovascular toxicity (therefore you cannot buy these OTC)
What is acetaminophen?
- A weak COX1 and COX2 inhibitor.
- Inhibits a third COX isoform (COX3) found most abundantly in the cerebral cortex.
- Analgesic and antipyretic
- Lacks Anti-inflammatory effects
What can result from an overdose on acetaminophen?
Liver damage
- Acetaminophen is normally metabolized in the liver
What are three alternatives to cocaine?
- Lidocaine
- Bupivicaine
- Procain
Most local anesthetics contain a _______ moiety, a _______ and a __________.
What part of the molecule determines its pharmacological properties?
Most local anesthetics contain a hydrophobic (aromatic) moiety, a linker region and a hydrophilic substituted amine
- The LINKER REGION determines the pharmacological properties
How do local anesthetics work to reduce pain? Why is hydrophobicity relevant?
Local anesthetics bind reversibly to a specific site within the pore of sodium channels and block ion movement through this pore thus blocking the ability for the neuron to fire
- ONLY accessible intracellularly (anesthetics must pass the PM)
- Hydrophobicity increases both the potency and duration of action
How does capsaicin block pain?
Capsaicin is an agonist for the TRPV1 receptor
- Activates TRPV1 receptors eventually leading to desensitization and loss of TRPV1+nociceptors leading to analgesia
