OTC Drugs Flashcards
(54 cards)
T or F. OTC drugs include supplements, minerals, etc.
F! Very little regulation; hard to be certain of concentration, buyer beware!
Primary afferents
neurons that detect sensory info in the periphery (skin, GI tract, etc.)
- they synapse onto secondary afferents in SC which pass sensory info to brain
Polymodal Nociceptors
- pain detected by primary afferents called nociceptors
- polymodal nociceptors: detect many types of painful stimuli (thermal, mechanical, chemical, electrical)
- different types of painful stimuli are detected by specific receptors expressed on polymodal nociceptors
TRP channels
- transient receptor potential channels
- temperature sensitive ligand-gated ion channels
- TRPM8 = activated at temps below 10 edgress C (cold)
- TRPV1 = activated at temps above 43 degrees C (hot)
TRPV1 and TRPM8 receptors can also be activated by ligands
- TRPV1 by capsaicin
- TRPM8 by menthol
Why is inflammation associated with pain?
- bc our innate immune system release substances that bind to nociceptors that cause pain
- receptors respond to inflammatory molecules (bradykinin, cytokines, prostaglandins)
Arachidonic acid
- fatty acid present in phospholipids of cell membranes
- freed from the phospholipid molecule by the enzyme phospholipase A2
- key inflammatory mediator
- what guides non-specific inflammation that happens in response to an infection
- metabolized by COX1 and COX2
(Cyclooxygenase) COX1 and COX2 metabolize arachidonic acid into …
prostaglandins, prostacyclin, and thromboxane
5-lipoxygenase (LOX) metabolized arachidonic acid into …
various leukotrienes (another inflammatory mediator
These drive inflammation because (3)
prostaglandins and leukotrienes
- they are potent vasodilators
- they are pyrogenic (fever)
- they attract immune cells (leukotactic) and coordinate the immune response
These are the enzymes that convert arachidonic acid into precursors of prostaglandins
COX1 and COX2
COX1 is primary expressed in …
non-inflammatory cells (blood vessels, platelets, gastric mucosa)
COX2 is primarily expressed in …
inflammatory cells
What do Aspirin and other NSAIDs inhibit? What’s the result?
both COX isoforms
- this decreases prostaglandin production that inhibits inflammation and reduces pain
- inhibitors 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?
due to inhibition of COX1 enzymes in gastric mucosa
- inhibition of COX1 decrease bicarbonate secretion – more H+
- chronic use = gastric ulceration, upper GI bleeding, renal failure
What was developed to bypass gastric toxicity?
specific COX2 inhibitors (ex: celecoxib)
- effective at reducing inflammation in chronic inflammatory disease (less so for acute pain)
- suggests that mechanisms beyond blocking inflammation drives analgesic effect
- associated with higher risk of cardiovascular toxicity (not available OTC)
This drug is a weak COX1 and COX2 inhibitor … what was later found about it?
Acetaminophen
- inhibits a third COX isoform (COX3); found most abundantly in cerebral cortex
- an analgesic and antipyretic agent; lacks anti-inflammatory effects (unlike NSAIDs)
Acetaminophen
- negligible toxicity at therapeutic doses
- overdose or patients with liver damage = liver damage and death
- preferred drug primarily in children
- if enzymes become overwhelmed by high doses, liver engages secondary pathways that involve SIP enzymes (class 1 metabolism) that leads to reactive intermediates that can eventually lead to toxic compounds leading to liver cell death
Albert Niemann
- German chemist who isolated cocaine from coca leaves
- numbed his tongue
- introduced cocaine as a topical anesthetic for ophthalmological surgery
Due to the addictive and toxicity issues with cocaine, synthetic substitutes were developed:
procain, lidocaine, and bupivicaine = most widely used topical anesthetics
- most contain a hydrophobic (Aromatic) moiety, a linker region, and a substituted amine
- linker region determines its pharmacological properties; how long it works, how well, how fast
**having both properties important!! Amphiphilic! Dissolve equally in water and fat
Procain
there is an ester link (none of the others have this) - leave this susceptible to plasma esterase which can hydrolyze this link, bc of this, duration of action is much shorter than other drugs ; positive side: sometimes you need short term anaesthetic (dentist numbing gums prior to injection of longer anaesthetic like bupivacaine)
Local anaesthetic binding
- bind reversible to a specific site within pore of Na+ channels
- block ion movement through this pore
- site in which anaesthetics bind is only accessible intracellularly (anesthetics must cross cell membrane)
- hydrophobicity increases both potency and duration of the action bc the more hydrophobic they are, they more able they are to cross fatty plasma membrane and enter cell which is now more hydrophilic to then get access to pore binding site intracellularly
T or F. Local anesthetics have higher affinity for the open conformation of the sodium channel s they preferentially block neurons that are active
T! so in other words, nociceptors when there’s pain! even they block all sensation and can cause motor paralysis (depending on where applied and conct’n); this is why they don’t!
Capsaicin
- agonist for the TRPV1 receptor
- active ingredient in chilli peppers
- initial application = moderate burning pain (less pain overtime)
- chronic activation of TRPV1 receptors leads to desensitization and loss of TRPV1+ nociceptors (analgesia)
