Lecture 10 - Analgesics

Question 1

neurons that detect sensory information in the periphery (ie: skin, GI tract) are called ___

Answer 1

primary afferents

Question 2

primary afferents synapse onto ____ in the ____ which pass sensory information up to the ____

Answer 2

secondary afferents, spinal cord, brain

Question 3

pain is detected by a specific class of primary afferents called ____

Answer 3

nociceptors

Question 4

different types of painful stimuli are detected by ____ expressed on ____

Answer 4

specific receptors, polymodal nociceptors

Question 5

detect many types of painful stimuli

Answer 5

polymodal nociceptors

Question 6

temperature sensitive ligand-gated ion channels

Answer 6

transient receptor potential (TRP) channels

Question 7

can TRP receptors also be activated by ligands?

Answer 7

yes

ex: TRPV1 –> capsaicin, TRPM8 –> menthol

Question 8

what temperatures are TRPM8 receptors activated at?

Answer 8

<10 degrees

Question 9

what temperatures are TRPV1 receptors activated at?

Answer 9

> 43 degrees

Question 10

some receptors respond to inflammatory molecules such as:

Answer 10

• bradykinin
• cytokines
• prostaglandins

Question 11

inflammatory molecules are released from surrounding ____ following tissue injury or infection

Answer 11

immune cells

Question 12

a fatty acid produced by phospholipids and present in phospholipids of all cell membranes

Answer 12

arachidonic acid

Question 13

arachidonic acid is freed from the phospholipid molecule by the enzyme ____

Answer 13

phospholipase A2

Question 14

the enzymes cyclooxygenase-1 and -2 (COX1 and COX2) metabolize arachadonic acid into ___ and ___

Answer 14

prostaglandins (PG) and thromoxanes (Tx)

Question 15

• signals platlets to form a clot
• causes vasoconstriction
  these are qualities of ____

Answer 15

thromboxane A2 (TXA2)*

Question 16

• potent vasodilator
• pyrogenic (increases core body temp - fever)
• leukotactic (attracts immune cells)
• involved in producing gastric mucous
  these are all qualities of ____

Answer 16

prostaglandin E2 (PGE2)

Question 17

COX1 is primarily expressed in _____ cells, whereas COX2 is expressed in _____ cells

Answer 17

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

Question 18

enzyme activity is either _____ or _____

Answer 18

constitiutive (always on), inducible (activated by a stimulus)

Question 19

inhibits both COX1 and COX2

Answer 19

aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs)

Question 20

what are the effects of inhibiting COX1 and COX2?

Answer 20

• decreases prostaglandin production (inhibits inflammation and reduces pain)
• antipyretic action (reduces fever)

Question 21

daily NSAID use can prevent ____ in those at risk of a stroke or heart attack

Answer 21

platlet aggregation

Question 22

which site on the COX enzymes do NSAIDs inhibit?

Answer 22

the catalytic site (where arachadonic acid binds)

Question 23

acetylsalicylic acid (Aspirin)

Answer 23

a non-competitive, irreversible inhibitor, covalently binds to the catalytic site of COX1 and COX2

Question 24

what is a negative side effect of NSAID use?

Answer 24

gastric toxicity (due to inhibition of COX1 enzymes in gastric mucosa), extreme cases can lead to: ulceration, upper GI bleeding, and renal failure

Question 25

ketoralac (toradol)

Answer 25

a highly effacious non-selective NSAID recommended for short term use (ex: post-surgical) to avoid gastric toxicity

Question 26

specific COX2 inhibitors are also associated with higher risk of ____, however, these are not over the counter

Answer 26

cardiovascular toxicity

Question 27

acetaminophen

Answer 27

an analgesic and antipyretic that inhibits COX3, lacks anti-inflammatory effects

Question 28

where is the COX3 enzyme found?

Answer 28

the cerebral cortex

Question 29

what are the effects of overdosing on acetaminophen?

Answer 29

can lead to liver damage and death

Question 30

what drug was used as the first topical anesthetic for eye surgery? why is it no longer in use?

Answer 30

cocaine, no longer in use due to its addictive properties and other toxicity issues

Question 31

the three most widely used topical anesthetics

Answer 31

procain, lidocaine, bupivicaine

Question 32

what are the three main regions found on all local anesthetics?

Answer 32

• a hydrophobic (aromatic) region
• a linker region
• a substituted amine

Question 33

which area on a topical anesthetic determines its pharmacological properties?

Answer 33

the linker region

Question 34

local anesthetics bind ____ to a specific site within the pore of ____ channels and block ion movement through this pore

Answer 34

reversibly, Na+

Question 35

why do local anesthetics have a hydrophobic region?

Answer 35

to cross the cell membrane to bind intracellularly

Question 36

hydrophobicity of the local anesthetic increases both the ____ and ____ of action

Answer 36

potency, duration

Question 37

local anesthetics block all sensation and cause ____ in the area (depending on where you put it and the concentration)

Answer 37

motor paralysis

Question 38

local anesthetics have higher affinity for the _____ of the so sodium channel

Answer 38

open conformation

Question 39

capsaicin

Answer 39

an agonist for the TRPV1 receptor. initial application causes burning pain, but over time causes pain relief

Question 40

chronic activation of TRPV1 receptors leads to ____ and ____ leading to analgesia

Answer 40

desensitization, loss of TRPV1 nociceptors

Question 41

is capsaicin treatment reversible?

Answer 41

yes!