OTC Analgesics

Question 1

what do OTC drugs not include?

Answer 1

supplements

Question 2

what are the 2 kinds of pharmaceutical drugs?

Answer 2

prescription and over the counter (OTC)

Question 3

what neurons detect sensory info in the periphery?

Answer 3

primary afferents

Question 4

what do primary afferents synapse onto?

Answer 4

secondary afferents (in spinal cord)

Question 5

where do secondary afferents send info to?

Answer 5

brain

Question 6

what do motor efferents do?

Answer 6

send motor info from brain to periphery (muscles)

Question 7

what are nocireceptors?

Answer 7

specific class of primary afferents that detect pain

Question 8

what do polymodal nociceptors detect?

Answer 8

thermal, mechanical, chemical and electrical pain

Question 9

where are nociceptors found?

Answer 9

on every surface of our body

Question 10

how are different stimuli detected by polymodal nociceptors?

Answer 10

specific receptors are expressed on polymodal nociceptors

Question 11

what are transient receptor potential (TRP) channels?

Answer 11

temperature sensitive ligand-gated channels

Question 12

what do TRPM8 and TRPV1 detect?

Answer 12

M8: <10ºC
V1: >43ºC

Question 13

what ligands activate TRPM8 and TRPV1 receptors?

Answer 13

TRPM8: menthol (cool)
TRMV1: capsaicin (chili peppers-hot)

Question 14

what are inflammatory molecules? what can they bind to?

Answer 14

released from immune system after injury or infection; nociceptors

Question 15

what is arachidonic acid?

Answer 15

fa in all phospholipids of pmemb and a key inflammatory mediator (2)

Question 16

how is arachidonic acid freed from a phospholipid molecule?

Answer 16

by phospholipase A2 enzyme

Question 17

what 2 enzymes metabolize arachidonic acid into prostaglandins, prostacyclins and thromboxanes?

Answer 17

cyclooxygenase 1 and 2 (COX1 and COX2)

Question 18

what enzyme metabolizes arachidonic acid into leukotrienes?

Answer 18

5-lipoxygenase

Question 19

what do prostaglandins and leukotrienes do? (3)

Answer 19

drive inflammation (vasodilators, pyrogenic, leukotactic-attract immune cells)

Question 20

what cells is COX1 expressed in?

Answer 20

non-inflammatory cells (blood vessels, platelets, gastric mucosa)

Question 21

what cells is COX2 expressed in?

Answer 21

inflammatory cells

Question 22

what are NSAIDS?

Answer 22

aspirin or other non-selective anti-inflammatory drugs

Question 23

what do NSAIDS do generally?

Answer 23

treat inflammation

Question 24

how do NSAIDS work?

Answer 24

block COX1 and 2 (mainly) to inhibit production of pro-inflammatory prostaglandins and leukotrienes, reducing pain

Question 25

what is the antipyretic action of NSAIDS?

Answer 25

suppression of prostaglandin synthesis in brain (stimulated by pyrogens) to reduce fever (COX 2&3)

Question 26

what are non-selective NSAIDS associated with? why?

Answer 26

gastric toxicity; inhibit COX1 in gastric mucosa

Question 27

what can chronic use of non-selective NSAIDS cause? (3)

Answer 27

gastric ulceration, upper GI bleeding and renal failure

Question 28

how can gastric toxicity from NSAIDS be bypassed?

Answer 28

using specific COX2 inhibitors (reduce inflammation in chronic inflammatory disease)

Question 29

what is a con of specific COX2 inhibitors?

Answer 29

incr risk of cardiovascular toxicity

Question 30

what does specific COX2 inhibitors reducing inflammation but not pain suggest?

Answer 30

other mechanisms drive analgesic effects beyond blocking inflammation

Question 31

what is acetaminophen? (2)

Answer 31

an analgesic and antipyretic (no anti-inflammatory effects/not an NSAID)

Question 32

how does acetaminophen work?

Answer 32

a weak COX1 and 2 inhibitor (does not work like other NSAIDS), inhibits COX3 in cerebral cortex

Question 33

what are the side effects of acetaminophen?

Answer 33

overdose w/ liver impairments leads to liver damage or death

Question 34

what was the first anesthetic drug discovered?

Answer 34

cocaine

Question 35

how did Albert Niemann discover the anesthetic properties of cocaine in the late 19th century?

Answer 35

isolated cocaine from cocoa leaves and it numbed his tongue (used as a topical anesthetic for ophthalmoplegic surgery)

Question 36

what are the 3 most common topical anesthetics?

Answer 36

procain, lidocaine and bupivacaine

Question 37

what 3 functional groups do most local anesthetic contain?

Answer 37

hydrophobic aromatic moiety (ring), linker region and subs. amine (hydrophilic)

Question 38

what does the nature of the linker region of local anesthetics determine?

Answer 38

pharmacological properties (how long, well and fast it works)

Question 39

what does the ester linkage in local anesthetics (procaine) allow for? (2)

Answer 39

easy hydrolysis by plasma esterase and a short duration of action

Question 40

how do topical anesthetics work?

Answer 40

bind reversibly to site in pore of Na channels (block ion movement) - only accessible intracellularly

Question 41

what do topical anesthetics do?

Answer 41

block active neurons (ex: nociceptors when there is pain) thus blocking all sensation/causing motor paralysis

Question 42

how does the hydrophobicity of topical anesthetics affect its action? why?

Answer 42

incr potency and duration; Na channel binding pocket is hydrophobic and must cross pmemb

Question 43

how do local anesthetics preferentially block active neurons?

Answer 43

have a high affinity for open conf. of Na channels (can bind to pore easier)

Question 44

what is capsaicin?

Answer 44

agonist for TRPV1 receptor (active ingredient in chili peppers, causes burning pain)

Question 45

what does chronic activation of TRPV1 receptors (by capsaicin) cause?

Answer 45

desensitization and loss of TRPV1+ nociceptors leading to analgesia

Question 46

what does capsaicin do in a cell? (4)

Answer 46

prolonged opening of TRPV1 channels causes influx of cations, Ca overload, mitochondrial dysfunction and nerve ending dies off

Question 47

what is capsaicin most effective at treating?

Answer 47

burning or inflammatory pain from arthritis

Question 48

what do 3 OTC treatments for pain target?

Answer 48

inflammation/fever (NSAIDS), non-specific sensory pathways (topical anesthetics), and nociceptors (capsaicin cream)