Lecture 7 - Pain, NSAIDs, Migraine Flashcards
1
Q
What is pain?
A
An unpleasant sensory and emotional experience associated w/ actual or potential tissue damage
2
Q
What does pain cause?
A
Endocrine and metabolic abnormalities
3
Q
What is acute pain?
A
Lasts less than 6 months and subsides once healing is accomplished
4
Q
What is chronic pain?
A
- Constant and prolonged, lasting longer than 6 months
- Usually involves altered anatomy and neural pathways
5
Q
What is the pain theory?
A
- Severe, unrelieved acute pain results in abnormally enhanced physiological responses that lead to pronounced and progressively increased pathophysiology
- Increased pathophysiology causes increased significant organ dysfunction => increased morbidity and mortality
6
Q
Which systems are most affected by the pathophysiology of pain?
A
- Cardiovascular and respiratory systems
- Immune system becomes repressed, predisposing trauma patients to wound infections and sepsis
7
Q
What are the 2 causes of chronic pain syndrome?
A
1) Acute, unrelieved pain
2) Neuro-muscular disorders
8
Q
Which nerves can send pain signals, and what does this tell us?
A
- Almost every nerve
- Shows that pain is a perception b/c the signal might not be different, but that’s how the brain perceives it
9
Q
What are the 2 types of pain nerve fibers and which type of pain do they transmit?
A
1) A-delta – fast, sharp pain
2) C – second pain, dull
10
Q
What are the 4 processes of pain?
A
- Transduction
- Transmission
- Modulation
- Perception
11
Q
What is transduction?
A
- Local biochemical changes in nerve endings that generate a signal
12
Q
What are nociceptors?
A
Free nerve endings w/ the capacity to distinguish btwn noxious and innocuous stimuli
13
Q
What happens when a nociceptor is exposed to mechanical, thermal, or chemical stimuli?
A
Tissue damage occurs and substances are released which facilitates the movement of the pain impulse to the spinal cord
14
Q
Does every stimulation to a nociceptor cause pain?
A
Yes
15
Q
What are the primary known substances released from the traumatized tissue that cause pain?
A
- Bradykinin
- Serotonin
- Substance P
- Histamine
- Prostaglandin
16
Q
What type of pain are corticosteroids used for and what do they do?
A
- Cancer pain
- Interfere w/ production of prostaglandins
17
Q
What is transmission?
A
Movement of the signal from the site of pain to the spinal cord and brain
18
Q
Where is pain processed?
A
Central structures of the brain
19
Q
___ are needed to continue the pain impulse from the spinal cord to the brain
A
Neurotransmitters
20
Q
Why are opioids effect analgesics?
A
B/c they block the release of NT, which prevents the pain impulse from entering the brain
21
Q
Which pain nerve fibre is myelinated?
A
A-delta
22
Q
What is the thickness of A-delta fibres and what does this mean?
A
- Relatively thick
- Allow pain stimulus to be transferred very fast
23
Q
What is the purpose of a-delta fibres?
A
To make the body withdraw immediately from the painful and harmful stimulus to avoid further damage
24
Q
Does pain from a-delta fibres radiate?
A
No
25
How can pain from a-delta fibres be overcome?
Infiltration of the affected area or nerve w/ a local anesthetic
26
When does slow pain begin?
Immediately after fast pain
27
What is the body's response to slow pain?
Immobilization (guarding, spasm, or rigidity) so healing can occur
28
Does slow pain radiate?
Yes, it poorly localized
29
What is an effective treatment for slow pain?
Opioids
30
What is perception?
- Synthesis and analysis in the brain
| - End result of transmission
31
Where does perception occur and what does this mean?
Cortical structures, so behavioural strategies and therapy can be applied to decrease pain
32
What do the somatosensory and cingulate cortices control?
- Sensory discrimination
| - Emotional response -- fear, anxiety, panic, and subjective experience
33
What does the reticular formation control?
- Increases arousal
- Emotional response
- Somatic and autonomic motor reflexes
34
What is modulation?
Changing or inhibiting pain impulses in the descending tract (brain -> spinal cord)
35
How is modulation accomplished?
- Descending fibres release substances called endogenous opioids or endorphins which can inhibit transmission of noxious stimuli
- Endorphins also work at the nerve junction to slow pain impulses
36
What type of antidepressants does cancer pain respond to and why?
- Antidepressants that interfere w/ reuptake of serotonin and NE
- Increases the availability to inhibit noxious stimuli
37
_____ pathways modify ____ nociceptive info
Efferent; afferent
38
What does failure of inhibition lead to?
Neuropathic pain
39
When are endorphins released?
When a pain impulse reaches the brain
40
Which type of cells do endorphins excite and which type do they inhibit?
- Excite cells in midbrain (PAG, periaqueductal gray matter) and medulla
- Inhibit cells in spinal cord
41
What activates the descending pain modulation system (the system that decreases pain)?
- Stress
- Fear
- Hunger, thirst
- Fatigue
- Prolonged motor activity
- Hypnosis
42
What are the 3 categories of pain?
1) Nociceptive
2) Neuropathic
3) Visceral
43
What is nociceptive pain?
Injury, trauma, infection
44
What is neuropathic pain?
Initiated or caused by a primary lesion or dysfunction in the nervous system
45
What is visceral pain?
Arising from an internal organ (ex: MI, appendicitis, small bowel obstruction)
46
What are common feelings of neuropathic pain?
Fire or electricity
47
Where does neuropathic pain normally occur?
- Feet, legs, and hands
| - Trigeminal neuropathy occurs in face
48
What is hyperalgesia?
Intense pain in response to mildly painful stimulus (pinprick)
49
What is allodynia?
Pain in response to completely innocuous stimulus (touch)
50
What can cause neuropathic pain?
- Injury (amputation w/ subsequent phantom limb pain)
- Scar tissue from surgery
- Nerve entrapment (carpal tunnel)
- Damaged nerves (diabetic neuropathy)
51
In neuropathic ____ and _____ are spontaneous and repetitive
Depolarization and transmission
52
Can a treatment for nociceptive pain also be used for neuropathic pain?
No
53
What are common causes of headaches?
- Neck and jaw tension
- Nasal pressure
- Caffeine withdrawal
- Lack of sleep
- Eye strain
54
What are characteristics of NSAIDs?
- Analgesic (anti-pain)
- Antipyretic
- Anti-inflammatory (except acetaminophen!!)
55
What is the common mechanism of NSAIDs that elicits its effects?
Inhibition of COX enzymes, which convert arachidonic acid into prostaglandins; so therefore inhibits prostaglandins
56
What is the function of COX-1 enzyme?
Maintenance of stomach lining, so don't want to inhibit it
57
Where is COX-2 enzyme found and what is its function?
- Immune cells
| - Responsible for pain, inflammation, and fever
58
Where is COX-3 enzyme found?
Brain and heart
59
What causes inflammation?
- Infectious agents
- Ischemia
- Antigen/antibody reaction
- Thermal and other damage
60
What are the 3 phases of inflammation?
1) Acute transient - local vasodilation and increased capillary permeability
2) Delayed subacute - infiltration of leukocytes and phagocytes
3) Chronic proliferative - tissue degeneration and fibrosis
61
Which phases of inflammation do NSAIDs control?
1st phase
62
What would injection of prostaglandins cause?
- Local inflammation, increased blood flow, and severe pain
| - Cause uterine cramping, so injection used to cause abortion
63
What effect would morphine have on uterine cramping?
At low doses, morphine increases smooth muscle contraction, so would make uterine cramping worse
64
What are some other effects of prostaglandins?
- Critical to platelet aggregation and formation of clots
| - Important in modulating stomach acidity and mucous lining
65
What are the 2 mechanisms of action for aspirin?
1) Irreversibly acetylates COX enzymes, so its effect lasts as long as it takes to replace the enzyme
2) A minor metabolite of ASA, gentisic acid, is a competitive inhibitor of COX enzymes, thus its effect depends upon clearance
66
Which NSAID destroys COX enzymes?
ASA
67
What effect does caffeine have on all non-opioid analgesic drugs?
Will increase analgesic effect
68
What is the required dose of caffeine for a coanalgesic effect?
60-120 mg
69
Why should drugs be taken w/ ice water?
Ice water causes the stomach open its sphincter into the intestine, where the drug is absorbed
70
____ overdose is a very common overdose in children
Salicylate
71
What are signs and symptoms of salicylate toxicity?
- Tinnitus (ringing in the ears) -- first sign of aspirin overdose
- Marked increase in metabolic rate -- initial hyperventilation and metabolic acidosis (overproduction of CO2), then severe hypoglycemia
72
What is the immediate danger of salicylate toxicity?
Hyperthermia, dehydration, and hypoglycemia
73
What is the treatment for salicylate toxicity?
- Parenteral fluids and glucose
- Parenteral sodium bicarbonate solution
- Acetazolamide to make urine pH > 7
- Activated charcoal (only effective w/in 2 hours)
- Hemodialysis for severe overdoses
74
What are the 3 types of salicylates?
- Methylsalicylate
- Bismuth salicylate
- Aspirin
75
What are the classes of NSAIDs?
- Salicylates
- Propionic acid
- Diclofenac
- Indomethacin
76
What are the types of propionic acid?
Ibuprofen and naproxen
77
Ibuprofen has similar effects to ____
Other non-selective COX inhibitors
78
How often can naproxen be dosed?
Only twice a day
79
What is an advantage and disadvantage to diclofenac?
- High potency
| - High GI bleeding risk
80
What is diclofenac mostly used for?
Inflammatory pain, or gel is used for muscular/joint pain
81
What is indomethacin used for?
Gout pain and swelling
82
What is the primary problem w/ non-selective COX inhibitors?
GI side effects
83
What does inhibition of COX-1 cause?
- PGE2 and PGI2 (products of COX-1) suppresses acid production, increase gastric blood flow, and increase mucin secretion
- Therefore, COX-1 inhibition causes increased acid production, decreased mucous protection, as well as local effects of drugs
84
What is misoprostol?
A prostaglandin analog, similar structure and function
85
What is misoprostol used for?
To supply the stomach w/ prostaglandin effect that is lost w/ non-selective COX inhibitors
86
What is the most common side effect of misoprostol?
Diarrhea
87
What is Reye's syndrome?
- Fatal hepatic encephalopathy in children w/ viral infections (flu or chicken pox)
- Associated w/ ASA
88
What are some adverse effects of NSAIDs?
- Reye's syndrome
| - Hypertension, angina
89
What causes most of the side effects of non-selective COX inhibitors?
Inhibition of COX-1
90
What effects are caused by inhibition of COX-2?
Analgesic, anti-pyretic, and anti-inflammatory
91
What are characteristics of acetaminophen?
- Analgesic
- Anti-pyretic
* **NOT ANTI-INFLAMMATORY
92
What is the drug of choice in children w/ pain or fever?
Acetaminophen
93
Does acetaminophen stack w/ NSAIDs?
No
94
What are signs and symptoms of acetaminophen overdose?
- Severely increased serum transaminase levels
- Hepatic encephalopathy
- Jaundice (by this time, treatment is likely too late)
* No signs and symptoms recognizable to the average person
95
Which gender is more likely to get migraines?
- Boys > girls
| - Women > men
96
What are symptoms of migraines?
- Unilateral or bilateral, throbbing, nausea
- Often preceded w/ aura
- Variable duration, hours to days
- Variable incidence
97
What are common migraine triggers?
- Weather
- Missing a meal
- Stress
- Alcohol
- Various types of foods
- Menses
98
What is the first line therapy for acute headaches?
Non-opioid analgesics (NSAIDs)
99
What are ergot alkaloids?
Non-specific serotonin agonists
100
What is normally the cause of side effects of ergot alkaloids?
Arteriolar constriction
101
What should be watched w/ ergot alkaloids?
- Liver disease
- Rebound headache w/ frequent use
- CV disease from arteriolar constriction
* Poor peripheral circulation
102
What is a common side effect of ergot alkaloids?
Raynaud's (discolouration of fingers)
103
What are triptans?
Agonist of 5-HT1 receptor
104
What are the side effects of triptans?
Similar to ergot alkaloids, but safer
105
What are triptans used for?
Migraines, also help relieve nausea
106
What should be watched w/ triptans?
- Concurrent MAOI or SSRi antidepressants, causes serotonin syndrome
- Not concurrently w/ ergot alkaloids (24 hr washout)
107
What is the most commonly used preventive for migraines and why?
- Propranolol and other beta-blockers
| - Regulates blood flow and decreases blood pressure
108
What are side effects of propranolol?
Tiredness, dizziness, exacerbate asthma
109
What are side effects to amitryptiline?
Dry mouth and eyes; drowsiness
110
Does amitryptiline work directly on migraines?
May not, but will decrease stress and symp. NS stimulation
111
What is gabapentin?
Anticonvulsant
112
What is candesartan?
Angiotensin 2 receptor antagonist
113
Why is it believed that dietary supplements help w/ migraines?
Don't have a positive or negative effect, while many other foods have a negative effect
