Pharmacotherapy in Chronic Pain

Question 1

Pharmacotherapy can effectively reduce pain at the spinal level through:

a) Primary afferent inputs ( A and C fibers)
b) Second-order neuron projecting to the brain or within the spinal cord
c) Interneurons
d) Descending controls ( excitatory or inhibitory)
e) All of the above

Answer 1

E. All of the above

Question 2

Neurotransmitters released in the spinal cord by primary afferents and excitatory interneurons are:

a) Glutamate
b) Purinergic
c) Peptidinergic
e) All of the above.

Answer 2

e) All of the above.

Question 3

GABA and glycine are inhibitory neurotransmitters released in the dorsal horn. True or False.

Answer 3

True

Question 4

Noradrenaline and serotonin are released from the terminals of descending modulatory fibers arising from the midbrains. True or False.

Answer 4

True

Question 5

Central sensitization has been described in the literature as:

a. as a pathological precursor of dysregulated nociception that sustains pain symptoms long after the initial insult to the body’s nervous system, which may transition from a localized pain problem to a generalized pain disorder.
b. an increased response of CNS neurons which inform of pain when faced with inputs coming from low threshold mechanoreceptors.
c. CNS can change, distort, or amplify pain, increasing its degree, duration, and spatial extent in a manner that no longer directly reflects the specific qualities of peripheral noxious stimuli, but rather the particular functional states of circuits in the CNS
d. All of the above

Answer 5

d. All of the above

Question 6

2. Central sensitization top down mechanisms encompasses all of the following EXCEPT:
   a. Altered processing in brain
   b. Malfunctioning of descending anti-nociceptive mechanisms
   c. Release of pro-inflammatory cytokines
   d. Increased pain facilitatory pathways & temporal summation (wind-up)

Answer 6

c. Release of pro-inflammatory cytokines «< bottom-up mechanism

Question 7

Bottom-up mechanism in central sensitization includes:

a) Release of pro-inflammatory cytokines
b) Activation of spinal cord glia with COX-2 and prostaglandin E expression
c) increased responsiveness to mechanical pressure, chemical substances, light, sound, cold, heat and electrical stimuli
e) All of the above

Answer 7

e) All of the above

Question 8

Hyperalgesia and Allodynia are results of the bottom-up mechanism of central sensitization. True or False.

Answer 8

True.

Question 9

Cognitive-related brain areas, sensory signaling systems, and emotional-related brain inputs to body-self neuromatirx. True or False.

Answer 9

True.

Question 10

In the Pain Neuromatrix model, pain can affect brain areas related to stress-regulation programs involving cortisol, noradrenaline and endorphin levels, and immune system activities. True or False.

Answer 10

True.

Question 11

Correct use of analgesics include:

a) Analgesics should be given at regular intervals and orally administered
b) Analgesics should be prescribed according to pain intensity as evaluated by a scale of intensity of pain
c) Dosing of pain medication should be adapted to the individual
d) All of the above.

Answer 11

d) All of the above.

Question 12

According to the American College of Physicians and Pain Society, For most patients the first-line mediation options are acetaminophen or non steroidal anti- inflammatory drugs (NSAIDs). True or False.

Answer 12

True. ( Chou et al, 2007)

Question 13

Combination prescription pain relievers that contain more than 325 mg of acetaminophen per tablet, capsule, or other dosage units should no longer be prescribed because of the risk of liver damage.
True or False.

Answer 13

True ( 1/14/2014, FDA.gov)

Question 14

The following is true of acetaminophen:

a) Good because has no GI irritation (primarily acts centrally)
b) No anti-inflammatory or anticoagulant effects
c) High doses can be toxic to the liver
d) All of the above

Answer 14

d) All of the above

Question 15

When your patient is taking Tylenol or paracetamol, always screen for:

a) jaundice
b) easy bruising
c) abdominal pain
d) all of the above

Answer 15

d) all of the above

Question 16

When present the following factors should signal an increase monitoring for adverse effects of acetaminophen:

a) Age >= 25 y/o and high BMI
b) Female smoking
c) DM
d) All of the above

Answer 16

d) All of the above

Question 17

Acetaminophen acts on central sensitization by:

a) activating PAG which activates serotonergic & noradreneric neurons that activate areas in medulla & pons
b) at the spinal level, inhibits action on nociceptive inputs
c) centrally, reinforce descending inhibitory pathways
d) inhibits COX-2
e) All of the above.

Answer 17

E. all of the above

Question 18

Acetaminophen has both analgesic and antipyretic properties. True or False.

Answer 18

True

Question 19

NSAIDs are analgesic (mild to moderate pain, including bone pain) anti-inflammatory, anti-pyretic, anti-coagulant.; and non-addicting. True or False.

Answer 19

True.

Question 20

NSAIDs have negative effects on the GI system, can cause ARF; or increased bleeding and prothrombin effects. True or False.

Answer 20

True

Question 21

NSAIDs may impede bone growth. True or False

Answer 21

True

Question 22

NSAID inhibit COX-2, therefore, decrease prostaglandins. True or False.

Answer 22

True

Question 23

Which is induced when the cell is injured, and synthesis mediates pain & inflammation? COX -1 or COX-2.

Answer 23

COX-2

Question 24

NSAID inhibits ______ , normally occurring in cells, which uses prostaglandins to maintain cellular function/protection: stomach, kidneys, platelets.

Answer 24

COX-1

Question 25

Which is true of NSAIDS? a) Anti-inflammatory dose often higher than analgesic dose b) Should be used continuously until inflammation is resolved, avoiding yoyo effect c) Non-addictive d) All of the above.

Answer 25

d) All of the above.

Question 26

COX-2 selective drugs characteristics include: a) Inhibit synthesis of PGs in pain, inflammation b) Spare production of beneficial PGs in stomach, kidney, platelets c) May decrease pain & inflammation with less toxicity but Increase risk of heart attack and stroke d) All of the above

Answer 26

d) All of the above

Question 27

The following are examples of OTC NSAIDs except: a) Ibuprofen( Advil, Motrin) c) naproxen sodium (Aleve) d) Acriptin ( Aspirin, Ecotrin) e) Mobic, Naproxen, Toradol

Answer 27

e) Mobic, Naproxen, Toradol

Question 28

NSAIDs are effective in central sensitization primarily by peripheral prostaglandin inhibition by: a) attenuating sensitization of peripheral nociceptors thereby reducing central hyper excitability. b) attenuating afferent nociceptive activity c) stopping C-fiber mediated central sensitization d) all of the above.

Answer 28

d) all of the above.

Question 29

Anti-inflammatory agents released by adrenal gland that affect glucose metabolism, stress and immune function are called ______________.

Answer 29

Glucocorticoids/Corticosteroids

Question 30

__________ are anti-inflammatory adjunctives that limit the production of factors that attract leukocytes; decreases expression of inflammatory proteins (cytokines, enzymes, etc.); and increases expression of the anti-inflammatory protein.

Answer 30

Glucocorticoids

Question 31

________ are anti-inflammatory adjunctives with catabolic effect , breaks down collagen to make amino acid, transports to liver; can cause muscle wasting and weakness,water retention, increased infection, gastric ulcers.

Answer 31

Glucocorticoids

Question 32

Your patient has a long history of corticosteroid use, the following considerations during rehabilitation must be taken: a) Avoid overstressing tissues; skin breakdown precaution b) Encourage wt bearing c) increase monitor of BP and signs of infection d) all of the above

Answer 32

d) all of the above

Question 33

_______ alter pain perception but not anesthetic and are indicated for mod-severe acute and chronic pain.

Answer 33

Opioids

Question 34

Name three endogenous opiates:

Answer 34

endorphins, enkephalins, dynorphins

Question 35

Which opioid receptor can cause respiratory distress?

Answer 35

Mu opioid receptor

Question 36

Which opioid receptor has only analgesics effect?

Answer 36

Delta

Question 37

Which opioid receptor can also cause dysphoria & psychomimetic effects?

Answer 37

Kappa

Question 38

__________ are antagonists the displace agonist from opioid receptors.

Answer 38

naloxone, naltrexone

Question 39

Which type of opioids are preferred due to increased adherence, less addiction and have longer onset and duration? Give examples.

Answer 39

Long-acting opioids ( LAOs): | Morphine, oxycodone (oxycotin), methadone, fentanyl transdermal patch

Question 40

Which opioids are more addicting?

Answer 40

Short-acting ( SAOs): | Codeine, meperidine, morphine, hydromorphone, oxycodone

Question 41

Opioids act on: a) Spinal cord ( dorsal gray matter) b) Brain ( medial thalamus, hypothalamus) c) presynaptic nerve terminals and post synaptic neurons d) all of the above.

Answer 41

d) all of the above.

Question 42

How does opioids affect respiration?

Answer 42

decreased sensitivity of respiratory receptors so greater dec in oxygen and greater accumulation of carbon dioxide is needed to trigger the respiratory center

Question 43

Rehab considerations with opioids include a) Time therapy sessions to take advantage of the pain relief provided by the drug b) Hypoxia & hypercapnia may occur w/ exercise due to decreased respiratory rate c) Muscle aches and pain may be symptoms of withdrawal rather than somatic disorder d) all of the above

Answer 43

d) all of the above

Question 44

Where are endogenous opioid receptors found in the CNS?

Answer 44

Dorsal horn: • Lamina II, III, VIII, IX • Presynaptic Aδ & C-fibers • Postsynaptically on interneurons & projection neurons Thalamus, PAG, Limbic system • Activation of μ-receptors has inhibitory effects, including presynaptic inhibition of primary afferents and postsynaptic projection neurons

Question 45

How do opiods work in the medulla?

Answer 45

• Excites OFF cells (μ-opioid agonist) • Supresses ON cells (δ-opioid agonist) Creates neural inhibition by blocking either by: • blocking release of neurotransmitter or • hyperpolarization of cell via alterations in the Ca/K channels • (Nijs et al Expert Pharm 2011)

Question 46

What is a state of nociceptive sensitization caused by | exposure to opioids?

Answer 46

Opioid Induced Hyperalgesia (OIH)

Question 47

What are effects of OIH?

Answer 47

a) Seems to wane in the absence of disease progression b) Unexplained pain c) Reports or diffuse allodynia unassociated with the original pain •d) Increased levels of pain with increasing dosages

Question 48

Skeletal Muscle Relaxors Indications for use include:

Answer 48

a) Normalize muscle exitability to decrease pain and improve motor function ( spasticity) b) selective decrease skeletal muscle excitabitliy (spasm)

Question 49

Skeletal muscle relaxers act on____________

Answer 49

inhibiting polysynaptic reflex arc in spinal cord

Question 50

What are some of the disadvantages of skeletal muscle relaxers?

Answer 50

``` Disadvantages: • Not useful for chronic pain (tolerance develops) • Many require monitoring liver function • Drowsiness • Lack of quality evidence ```

Question 51

________ is a benzodiazepine agent; developed originally as an anti-anxiety drug that increases’s inhibitory effects of GABA in the brain and spinal cord, and causes sedation

Answer 51

Diazepam (Valium)

Question 52

Antideprssants can be used to dec pain because of which similar pathways?

Answer 52

serotonin & norepinephrine.

Question 53

Which nutritional supplements should be avoided because they enhance General side effects: Nervousness, sleeping disorders, headache,drowsiness, nausea, vomiting or diarrhea of SSRI?

Answer 53

L-tryptophan & St Johns Wort

Question 54

Tricyclic anti-depressants & SSRI has decreased dosage for analgesic vs. depression but has cardivascular side effects including:

Answer 54

HTN Postural hypotension Arrhythmia

Question 55

Which SNRI serotonin-norepinephrine reuptake inhibitors is approved by FDA for chronic widespread FM?

Answer 55

Cymbalta

Question 56

How does Tricyclic antidepressants cause analgesic effects on diabetic neuropathy, postherpetic neuralgia, tension HA, migraine, FM, & LBP?

Answer 56

Inhibit NA & 5-HT reuptake ==> lleading to increased activity in pain descending modulating pathways and increased analgesia

Question 57

What is the action of SSRI (serotonin-reuptake inhibitor) drugs to pain pathways?

Answer 57

Activate serotonergic descending pathways, which recruit opioid peptide containing interneurons in the dorsal horn

Question 58

How does SNRI help with pain?

Answer 58

SNRI activate noradrengeric descending pathways tougher w/ seotonergic pathways • Serotonin enhances spinal processing • Norepinephrine acts to inhibit activity

Question 59

Which is used to treat OA, FM and NP pain that acts similar to tricyclic antidepressants?

Answer 59

Tramadol by binding μ opioid receptors | as an agonist and weakly inhibits uptake of serotonin and norepinephrine

Question 60

Examples of anticonvulsants that are often prescribed in chronic neuropathic pain?

Answer 60

Gabapentin and pregabalin

Question 61

How does gabapentin and pregabalin work?

Answer 61

Gabapentin dec glutamate, norepinephrine and substance P | Pregabalin decreases Ca2 influx and release of glutamate, norepinephrine and substance P

Question 62

Gabapentin is toxic to kidney while pregabalin is toxic to ___________

Answer 62

Liver

Question 63

In White et al's systematic review of pharmacologic treatment of LBP, the following are true: a) Opioid is more effective in decreasing pain than disability b) Opioid, when compared to NSAIDs is no better in decreasing pain and disability c) Antidepressants is effective regardless of type e) All of the above

Answer 63

e) All of the above

Question 64

When prescribed and monitored correctly,NSAID are effective and safe in the treatment if LBP. True or False according to systematic review by While et al, Spine , 2011. True or False.

Question 65

The following neurotransmitters are excitatory or inhibitory? Glutamate (Glu) Acetylcholine (ACh) Histamine Dopamine (DA) Norepinephrine (NE); also known as noradrenaline (NAd) Epinephrine (Epi); also known as adrenaline (Ad)

Answer 65

Excitatory

Question 66

The following neurotransmitters are excitatory or inhibitory ? gamma-Aminobutyric acid (GABA) Serotonin (5-HT) Dopamine (DA)

Answer 66

Inhibitory

Question 67

Which neurotransmitter is either excitatory or inhibitory?

Answer 67

Dopamine