Lecture 6: Analgesics Flashcards
1
Q
What are drugs that treat inflammation and/or fever?
A
Aspirin and NSAIDs
2
Q
What are drugs that block sensation?
A
Topical anesthetics
3
Q
What are drugs that block pain?
A
- Acetaminophen
* Capsaicin cream
4
Q
What are the two classes of pharmaceutical drugs?
A
- Those that are prescription only
* Those are directly available to the consumer
5
Q
Why is there a huge diversity of products?
A
Because there is only a limited number of approved active ingredients, but they recombine the amounts
6
Q
What is Analgesics?
A
Pain killing
7
Q
What are some medications used for Analgesics?
A
- Tylenol
- Advil
- Motrin
- Robax
- Anacin
- Excedrin
8
Q
What are some typical Decongestants?
A
- Sudafed
- Mucinex
- Coricidin
- Dristan
9
Q
What are some common Cough, sleep, allergy medications?
A
- Buckley’s
- Benylin
- Dimetapp
- Robitussin
- NyQuil
- Claritin
10
Q
What is Efficacy?
A
The ability to evoke a response or produce an effect
11
Q
What are Primary Afferents?
A
Neurons that detect sensory information in the periphery
12
Q
Where do Primary Afferents take sensory information?
A
From the periphery to the spinal cord
13
Q
What do Primary Afferents synapse onto?
A
Secondary afferents in the spinal cord
14
Q
What do Secondary Afferents do?
A
The carry sensory information from from the spinal cord to the brain
15
Q
What do Efferent fibers do?
A
Take commands from the brain and send them to the periphery
16
Q
Which part of the spinal cord do Primary Afferents enter?
A
They enter through the Dorsal horn
17
Q
What helps to modulate the incoming primary afferents?
A
The descending signals sent by the pain system
18
Q
What can activate the descending pathway?
A
Opioids and acetaminophen
19
Q
What is the pathway of the modulating pain Efferents?
A
Parts of the brain synapse at PAG, then RVM, and then to the dorsal horn in the spinal cord
20
Q
What is pain detected by?
A
Nociceptors
21
Q
What are Nociceptors?
A
A specific class of primary afferents that detect pain
22
Q
What are Polymodal Nociceptors?
A
Nociceptors that detect many types of painful stimuli
23
Q
What are different types of painful stimuli detected by?
A
Specific receptors expressed on polymodal nociceptors
24
Q
What are the receptors on nociceptors linked to?
A
Intracellular pathways that activate signalling that cause the generation of an action potential into the CNS
25
What cause the different types of pain sensations perceived?
The combination of what signalling gets activated
26
What are Transient Receptor Potential (TRP) channels?
Temperature sensitive ligand-gated ion channels
27
What are different types of TRP channels tuned to respond to?
Very specific temperatures
28
What is TRPM8 activated by?
Temperature below 10ºC
29
What is TRPV1 activated by?
Hot temperatures above 43ºC
30
Aside from temperature what can TRPV1 and TRPM8 be activated by?
Ligands
31
Which TRP does menthod activate?
TRPM8
32
Which TRP does Capsaicin activate?
TRPV1
33
What do other receptors respond to?
Inflammatory molecules
34
What are inflammatory molecules released from?
Surrounding immune cells following tissue injury or infection
35
What are examples of inflammatory molecules?
* Bradykinin
* Cytokines
* Prostaglandins
36
What is the Axon Reflex?
Increased pain sensitivity due to inflammation
37
What is Hyperalgesia?
Increased pain sensitivity in a region
38
What would aim to such down the increased sensitivity of pain signals?
* Opioids
* Cannabinoids
* Noradrenaline
39
How does Bradykinin work?
It bind to the B2 receptor which activates PKC and phosphorylates the TRPV1 channel which enhances the ability of TRPV1 to open and cause depolarization
40
What is Arachidonic acid?
A fatty acid present in phospholipids of cell membranes
41
How is Arachidonic acid freed from the phospholipase molecule?
By the enzyme Phospholipase A2
42
What does Phospholipase A2 do?
Frees arachidonic acid from the phospholipase molecule
43
What is Arachidonic acid key in?
Inflammatory mediation
44
What is Arachidonic acid converted into by COX1 and COX2?
Prostandoids
45
What do COX1 and COX2 do to Arachidonic acid?
They convert it to Prostanoids
46
What are Prostanoids?
A family of signalling molecules
47
What are some Prostanoids?
* Prostaglandins
* Prostacyclin (PGI2)
* Thromboxane (TXA2)
48
What are Prostaglandins associated with?
Inflammation
49
What is different about COX2?
It is the inducible form of the COX enzyme
50
Where does COX2 occur?
Only in areas of inflammation
51
When is COX1 expressed?
It is constitutively expressed (expressed all the time)
52
Since COX1 is constitutively expressed, what does it do?
It facilitates baseline production of certain prostaglandins like PGI2 which protects certain organs and facilitates mucus secretion
53
What is COX2 induced by?
Inflammation
54
What is the site of Aspirin and NSAIDs?
COX1 and COX2 enzymes
55
What does the Prostanoid pathway do generally?
It is either inflammatory (COX2) or it is protective
56
What does the enzyme 5-lipoxygenase (LOX) do to arachidonic acid?
It metabolizes arachidonic acid into various leukotrienes
57
How do Prostaglandins and Leukotrienes drive inflammation?
They are vasodilators, pyrogenic (fever inducing) and attract immune cells
58
Where are Prostaglandins and leukotrienes especially pyrogenic?
When they reach the thalamus
59
What happens with immune cells once they are attracted by prostaglandins?
They can be induced to attract COX2
60
Where is COX1 primarily expressed?
In non-inflammatory cells (blood vessels, platelets, gastric mucosa)
61
Where is COX2 mainly expressed?
In inflammatory cells
62
What do non-selective NSAIDs target?
Both COX pathways
63
What do COX2 specific NSAIDs target?
The COX2 pathway
64
Where are the cells that express the inducible COX2 pathway found?
Cells that respond to inflammatory stress like macrophages, synoviocytes, endothelial cells, kidneys
65
What do Aspirin and other non-selective NSAIDs do?
Inhibit both COX isoforms
66
What happens when aspirin and nsaids inhibits both COX isoforms?
Prostaglandin production decreases, inhibiting inflammation and reducing pain and fever
67
How do Aspirin and other NSAIDs reduce fever?
By inhibiting the COX pathway they suppress prostaglandin synthesis in the brain that is stimulated by pyrogens
68
Which COX pathway would it be bad to inhibit?
COX1 because it is supposed to be constitutively active
69
Why are Non-selective NSAIDs associated with gastric toxicity?
Because they inhibit COX1 which is supposed to constitutively active and produce mucus in the stomach, bicarbonate, and blood flow
70
What can chronic use of non-specific NSAIDs do?
Cause gastric toxicity like gastric ulceration, upper GI bleeding and renal failure
70
What can chronic use of non-specific NSAIDs do?
Cause gastric toxicity like gastric ulceration, upper GI bleeding and renal failure
70
What can chronic use of non-specific NSAIDs do?
Cause gastric toxicity like gastric ulceration, upper GI bleeding and renal failure
71
How can the gastric toxicity due to non-specific NSAIDs be bypassed?
Specific COX2 inhibitors have been developed
72
What do COX2 inhibitors do?
They reduce inflammation in chronic inflammatory diseases, but are less effective at treating acute pain
73
What are specific COX2 inhibitors also associated with?
Higher risk of Cardiovascular toxicity
74
What does Acetaminophen inhibit?
COX3
75
Where is COX3 found most abundantly?
In the cerebral cortex
76
What is the difference between the effects of acetaminophen and NSAIDs?
Acetaminophen lacks the anti-inflammatory effects
77
What are the effects of Acetaminophen?
It is an analgesic and antipyretic agent
78
Which enzymes does Acetaminophen block?
COX1 and COX3
79
How can Acetaminophen be toxic?
When taking by overdose in patients it can lead to liver damage and death
80
What are the most widely used topical anesthetics?
* Procaine
* Lidocaine
* Bupivacaine
81
What do most local anesthetics contain?
* Hydrophobic (aromatic) moiety
* A linker region
* Substituted amine (hydrophilic region)
82
What is the hydrophilic region of a topical anesthetic?
The substituted amine
83
What does the nature of the linker region of a topical anesthetic do?
Determine pharmacological properties
84
What does an ester linker region mean?
Because they are hydrolyzed easily they are able to get rid of in the body so they have a shorter affect
85
What is the effector mechanism of local anesthetics?
They bind reversibly to an intracellular site within the pore of sodium channels and block ion movement through the pore
86
What must anesthetics do in order to block a pore?
They must cross the cell membrane
87
Why does hydrophobicity increase the potency and duration of action of an anesthetic?
Because the Na+ channel binding pocket it hydrophobic and anesthetic must cross the hydrophobic cell membrane
88
What do all local anesthetics do?
Block all sensation and can cause motor paralysis
89
What do local anesthetics have higher affinity for?
The open conformation of the sodium channel, so they preferentially block neurons that are active (nociceptors when there is pain)
90
What are different types of painful stimuli detected by?
Specific receptors on polymodal nociceptors
91
What is the active ingredient in chilli pepper?
Capsaicin
92
What is Capsaicin an agonist for?
The TRPV1 receptor
93
What does capsaicin do to TRPV1 receptors?
It activates normal signalling TRPV1
94
What does initial application of Capsaicin do?
Gives a sense of burning
95
What does chronic activation of TRPV1 induced by capsaicin do?
Cause desensitization of TRPV1 which blocks its ability to transmit afferent information. Basically blocks its function to signal for pain leading to analgesia
95
What does chronic activation of TRPV1 induced by capsaicin do?
Cause desensitization of TRPV1 which blocks its ability to transmit afferent information. Basically blocks its function to signal for pain leading to analgesia
