SM 236a, 240a, 244a - Pharmacology, Opioids, and Pain I, II, III

Question 1

Describe the action of buprenorphine on the mu opioid receptor

Answer 1

• Partial mu agonist = ceiling on agonism
• Binds the mu opioid receptor with high affinity
• Prevents other opioids from binding
  
  • Makes naloxone reversal difficult in OD
• Use for opioid maintenance to treat addiction

Question 2

What are the neurologic effects of opioid use?

Answer 2

• Analgesia
• Miosis
  
  • Even in patients who are tolerant

Question 3

What factors might increase a patient’s risk of UGI bleed when taking NSAIDs?

Answer 3

• Daily, long term use
• High doses of NSAIDs
• Combining NSAIDs with ASA
  
  • ASA = aspirin
• Age
• Prior PUD or UGI bleed
• Anticoagulant use
• Alcohol or steroid use

Question 4

Which NSAID is okay to use in patients with CV disease?

Answer 4

ASA (aspirin)

Question 5

Butorphanol is classified as a mu opioid receptor…

A. Agonist

B. Antagonist

C. Agonist/Antagonist

D. Partial agonist

Answer 5

C. Agonist/Antagonist

• Analgesia is kappa mediated
  
  • Does not have as much pain relieve as mu agonists, but fewer GI effects
• Can trigger withdrawl
  
  • Do not use in opioid tolerant patients

Question 6

What is Misoprostol?

Answer 6

• An agent that helps to protect the stomach lining from damage from NSAIDs
• Note – also causes diarrhea

Question 7

​A patient with oropharyngeal cancer is requiring management of pain due to tumor erosion into his mandible. A long duration opioid is desired in order to avoid his having to take medication frequently. Due to difficulty in swallowing, however, he can only consume liquids or tablets that are crushed and placed in applesauce. The best option is

1. Sustained release morphine pills
2. Sustained release oxycodone pills
3. Hydromorphone pills
4. Methadone
5. Fentanyl lollipop

Answer 7

d. Methadone

Sustained release pills lose their duration when you crush them

Fentanyl lollipop is for acute pain; fast acting, short duration

Methadone is inherently long-acting; it has a long half life

Question 8

Which opioids inhibit serotonin reuptake, leading to intense euphoria?

Answer 8

Merperidine

Tramadol

Question 9

What is the difference between drug dependence and drug addiction?

Answer 9

• Dependence
  
  • The patient will have physical withdrawal if the drug is stopped
• Addiction
  
  • A psychological diagnosis involving misuse/abuse of the drug

Question 10

What is the relevant metabolite of merperidine?

What are its effects?

Answer 10

Normeperidine

• 10 hour half life
• Causes CNS hyperactivity and seizures
• Cleared by the kidney
  
  • Do NOT use in pts with renal failure

Question 11

What is tolerance?

Answer 11

When prolonged use of a drug requires higher doses to achieve the same effect

Question 12

How do opioid receptors vary person to person?

Answer 12

• Different density of mu, kappa, and delta receptors
  
  • Due to different DNA
• Different variants of mu, kappa, and delta subgroups
  
  • Due to splice variation
  • These splice variants have different affinities

Result: Different opioids work differently for different people!

If a patient is having side effects but no analgesia, change the opioid

Question 13

Increasing glycine and GABA in the CNS would have what effect on pain perception?

Answer 13

Glycine and GABA work through the descending pain pathway to intercept ascending nociceptive signals

More glycine and GABA = More descending action = decreased pain perception

Note: Prostaglandins inhibit the release of glycine and GABA

NSAIDs inhibit prostaglandins, and therefore increase glycine and GABA in the CNS

Question 14

What is the role of COX-1 in protecting our stomach lining?

Answer 14

• Increase Mucous layer thickness
• Decrease pH gradient
• Increase Bicarbonate secretion
• Increase Mucosal blood flow

Question 15

Naloxone is classified as a mu opioid receptor…

A. Agonist

B. Antagonist

C. Agonist/Antagonist

D. Partial agonist

Answer 15

B. Antagonist

Used for heroine/opioid overdose

Question 16

Nonsteroidal antiinflammatory drugs exert their analgesic effect by

1. Binding to prostaglandin receptors in peripheral inflamed tissue
2. Inhibiting the action of prostaglandins on peripheral nerves
3. Inhibiting the formation of prostaglandins
4. Inhibiting the formation of arachidonic acid
5. Inhibiting lipooxygenase

Answer 16

c. Inhibiting the formation of prostaglandins

Question 17

Where does the sensory neuron (pain fiber) synapse with the secondary (central) neuron)?

Answer 17

Substantia gelatinosa (in the dorsal horn)

Question 18

Morphine is classified as a mu opioid receptor…

A. Agonist

B. Antagonist

C. Agonist/Antagonist

D. Partial agonist

Answer 18

A. Agonist

Question 19

What are the metabolites of oxycodone?

What provides analgesia – the parent drug or the metabolites?

Answer 19

Relevant metabolite = oxymorphone

14x more potent than oxycodone

Both the parent drug and the metabolie provide analgesia

Question 20

Which somatosensory pathway is involved with pain, temperature, and crude touch?

Answer 20

Anterolateral pathway (including spinothalamic tract)

Question 21

Describe the pain pathway from the site of tissue injury to the brain

Answer 21

• Injured tisssue
  
  • Prostaglandin, bradykinin, leukotriene
• Sensitized nociceptor detects pain, fires an action potential
• Pain travels up a sensory neuron to the dorsal horn
• Sensory neuron synapses with the secondary neuron in the dorsal horn
• Secondary neuron carries the pain signal to the brain

Question 22

What protects our stomach lining from the acidic lumen?

Answer 22

Mucous layer containing HCO3

Question 23

Which NSAIDs will not interfere with clotting?

Answer 23

COX2 selective NSAID

Ex: Celecoxib

Question 24

Naltrexone is classified as a mu opioid receptor…

A. Agonist

B. Antagonist

C. Agonist/Antagonist

D. Partial agonist

Answer 24

B. Antagonist

Used to treat addiction

Question 25

Why do NSAIDs work even when there is no inflammation?

Answer 25

NSAIDs prevent prostaglandin synthesis * Prostaglandins are relesed in peripherl tissues due to inflammation, but **they are also contituitively present in the CNS** * ​They normally work to amplify pain in the ascending pathway. * Sensitize the second degree neurons to substance P and glutamate * Inhibit the descending pathway by preventing glycine and GABA release * **NSAIDs will prevent prostaglandins from having these effects on the CNS**

Question 26

Which NSAID will not increase a patient’s bleeding risk during surgery?

Answer 26

Celecoxib COX2 selective inhibitor =\> will not interfere with platelet function

Question 27

A patient comes to you suffering from pain following knee surgery 3 days ago. He reports that the opioid pain medication that he received from the orthopedic surgeon causes nausea and dysphoria but does nothing for his pain. He notes that a different opioid medication that he had from a prior surgery works well, and he requests you prescribe this for him instead. What would the scientific justification be for prescribing this different opioid?

Answer 27

Different patients have splice variation in their mu, kappa, and delta receptrs Different opioids have different affinities for these splice variants Therefore, some opioids work better for some patients than others

Question 28

What is the most common IV NSAID?

Answer 28

Ketorolac (no oral potency) Same as ibuprofen, but ibuprofen is oral

Question 29

What is pain?

Answer 29

Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage

Question 30

What is an opioid?

Answer 30

All drugs, both natural and synthetic, that bind to opioid receptors * All opiates are opioids, but not all opioids are opiates

Question 31

A transplant recipient is in the recovery room following a renal transplant surgery. The attending surgeon cancels the resident’s order to give a single dose of ketorolac for pain. The best reason for canceling the order is 1. Ketorolac can cause microemboli in the new kidney 2. Ketorolac can reduce blood flow to the new kidney 3. Ketorolac can reduce sodium reabsorption in the new kidney 4. Ketorolac can prolong postoperative ileus (cessation of peristalsis that occurs postop) 5. Ketorolac can cause respiratory depression

Answer 31

b. Ketorolac can reduce blood flow to the new kidney Ketorolac is an NSAID NSAIDs inhibit prostaglandin synthesis, and will therefore prevent vasodilation in the afferent arteriole of the kidney

Question 32

What sensations utilize the anteriolateral somatosensory pathways?

Answer 32

Pain, temperature, crude touch

Question 33

Which NSAID may cause tinnitus (ringing in the ears)?

Answer 33

Aspirin (ASA)

Question 34

Describe the mechanism of tramadol

Answer 34

* 2 mechanisms * M1 metabolite is a mu opioid receptor agonist * Parent drug blocks reuptake of 5-HT (serotonin) and norepinephrine * Use caution if the patient is on other SSRIs

Question 35

A patient in the ICU is recovering from a surgical resection of dead bowel. The patient is septic and requires hemodialysis three times a week. He is being given meperidine every 3 hours for control of his pain and to supplement his sedation. After two days on this regimen, you are called to his bedside because of seizures. The most appropriate therapy would be 1. Naloxone to treat the meperidine induced seizure 2. Benzodiazepines to treat the meperidine metabolite induced seizure 3. Naloxone to control effects of delayed meperidine clearance 4. Nalbuphine to antagonize the effect of the opioid while providing some analgesia 5. Urgent dialysis to remove the accumulated meperidine

Answer 35

b. Benzodiazepines to treat the meperidine metabolite induced seizure Normeperidine is a seizure-inducing metabolite of meperidine, normally cleared by the kidney The seizures have nothing to do with the opioid recepotors, and should be treated as you would treat any seizure (with benzos)

Question 36

What are the mechanisms of NSAID GI toxicity?

Answer 36

* Direct gastric irritation * Most NSAIDs are weak acids * Decreased cytoprotection via inhibition of COX1 * Decreased mucous layer thickness * Increased pH gradient * Decreased bicarb secretion * Decreased mucosal blood flow

Question 37

Describe the inflammatory prostaglandin synthesis pathway. Include the relevant enzymes and intermediates. NSAIDS inhibit the synthesis of which of these intermediates?

Answer 37

* Cell injuory or other trigger causes **phospholipid release** * Phospholipid -\> **Arachadonic acid** * *Phospholipase A2* * Arachadonic acid -\> **Prostaglandin H2** * *Cyclooxygenase (COX)* * NSAIDs act here to inhibit COX * Prostaglandin H2 -\> **Tissue-specific prostaglandin** * **​***Tissue specific PG synthase*

Question 38

How do prostaglandins enhance pain in the CNS? Describe the mechanism

Answer 38

Prostaglandins act at the synapse between the nociceptor and the second-degree neuron in the dorsal horn * Enhance substance P and glutamate release * Sensitize the second degree neuron to substance P and glutamate * Decrease glycine and GABA release from the descending pathway * Descending pathway cannot effectively modulate the ascending pathway These three mechanisms result in **hyperalgesia** (Prevented by NSAIDs)

Question 39

What do all NSAIDs have in common?

Answer 39

They inhibit cyclooxygenase (COX), the enzyme that makes prostaglandins

Question 40

Which opioids might cause seizures?

Answer 40

* Morphine * M-3-G metabolite produced by the liver may produce hyperalgesia, allodyina, myclonus, and **seizure** * Merperidine * Normeperidine metabolite has a 10 hour half life * Cleared by the kidney - do not use in pts with renal failure * Causes CNS hyperreactivity and seizures

Question 41

What are the differences between high lipohilicity opioids adn low lipophilicity opioids?

Answer 41

* High lipophilicity * Fast onset, short duration * Fentanyl, meperidine * Low lipophilicity * Slow onset, long duration * Morphinne, hydromorphone

Question 42

Hydromorphone is classified as a mu opioid receptor… ## Footnote A. Agonist B. Antagonist C. Agonist/Antagonist D. Partial agonist

Answer 42

A. Agonist

Question 43

How do opioids affect the ascending pain pathway? How do opioids affect the descending pain pathway?

Answer 43

* Ascending * Opioids inhibit cellular adenylyl cyclase, which increases K+ currents and decreases Ca2+ currents * This causes **hyperpolarization of the neuron, and therefore decreased pain transmission** * Acts on the pre-synaptic and post-synaptic neurons in the dorsal horn * Descending * Opioids inhibit the inhibitors of the descending pathway * Normally, inhibitory neurons prevent the descending pathway from affecting ascending pain transmission * Opioids **inhibit the GABA releasing inhibitory neurons in the periaqueductal grey and elsewhere** * **This allows the descending pathway to block the ascending pain signals**

Question 44

Arachidonic acid is the precursor for which two substances? Which enzymes are involved?

Answer 44

* **Arachidonic acid -\> Prostaglandin H2** * *Cyclooxygenase (COX)* * This is the pathway relevant to the pain pathway * Arachidonic acid -\> Leukotriene * *Lipooxygense*

Question 45

Which COX enzyme is involved in inflammation?

Answer 45

COX2 * Appears when inflammation/injury occurs - it is responsible for pain * Most tissues * Constitutitively active in some tissues * CNS, kidney, uterus * This means that selective COX2 inhibitors are not protective against kidney injury

Question 46

What is dependence? How is it different from tolerance?

Answer 46

* **Dependence** * Patient will have **withdrawal if the drug is stopped** * The patient is _physically_ dependent on the drug * Tolerance * **Increased dose required for the same effect**

Question 47

What are the effects of opioid use on the heart?

Answer 47

Not many! – considered a hemodynamically stable class of drugs

Question 48

Which COX enzyme is constitutively present in the GI tract, platelets, and kidneys?

Answer 48

COX1 A selective COX2 inhibitor will have fewer GI effects, and will not affect coagultion However, the kidneys also have COX2 - will be affected (and potentially injured) by a selective COX2 inhibitor

Question 49

Which NSAID is contraindicated in a child with a viral syndrome? Why?

Answer 49

Aspirin (ASA) Risk of Reye's syndrome: Hepatic injury and encephalopathy

Question 50

Meperidine is classified as a mu opioid receptor… ## Footnote A. Agonist B. Antagonist C. Agonist/Antagonist D. Partial agonist

Answer 50

A. Agonist

Question 51

Why are NSAIDs contraindicated in severe asthmatics?

Answer 51

Blocking COX leads to increased lipoxygenase activity, resulting in increased leukotriene synthesis Leukotrienes are involved in allergic/asthmatic inflammation

Question 52

What neurotransmitters are released from the 1st degree neuron in the dorsal horn in order to synapse with the second degree neuron?

Answer 52

Substance P and Glutamate Note: Their release is enhanced by prostaglandins (And therefore inhibited by NSAIDs)

Question 53

Which NSAID can be given topically? When is this most useful?

Answer 53

Diclofenac Used on superficial joints, fewer systemic side effects

Question 54

What are the hematologic effects of ASA?

Answer 54

ASA irreversibly acetylates COX in platelets (and elsewhere) * The platelets will never be able to make more COX – in order to have normal platelets again, the patient needs to make more platelets * Platelets do not have nuclei, and therefore cannot make new COX * It will take 7-10 days for clotting to return to normal * This means that even low doses of aspirin are cardioprotective (will prevent thrombosis) *Note: other NSAIDs irreversibly bind COX, so the anti-coagulative effect does not last as long*

Question 55

Which part of the body has the most opioid receptors outside of the CNS?

Answer 55

GI tract - enteric nervous system

Question 56

How do prostaglandins affect nociceptive nerve endings? Describe the mechanism

Answer 56

Prostaglandin E binds to the nociceptive nerve endings * -\> Increased Na+ influx into the neuron * -\> Increase resting membrane potential (closer to threshold) * - \> Nociceptor is more likely to fire an action potential and transmit a pain signal to the brain

Question 57

The brainstem ventilation nuclei contains opioid receptors. What is the implication of this?

Answer 57

Opioids will act on the ventilation system of the brain to decrease respiratory drive

Question 58

What are the therapeutic effects of opioids on the respiratory system?

Answer 58

Anti-tussive action Prevent hyperventilation from pain and anxiety Helps to avoid increased in bronchomotor tone in asthma

Question 59

What are the GI effects of opioid use?

Answer 59

Slowed peristalsis -\> constipation Nausea/vomiting

Question 60

What is the half life of Naloxone? Why is this relevant?

Answer 60

Naloxone has a short half life - 1 hour * Naloxone is used as a rescue drug for opioid use, but **the rescue may not last as long as the drug that was overdosed**

Question 61

What are the major side effects of NSAIDs?

Answer 61

* Stomach/duodenal ulcer * Decreased clotting * Decreased blood flow to kidneys * Edema and hypertension * In at-risk patients only (CV risks) * Reports of hepatic dysfunction

Question 62

Which area of the brain is considered our “emotional” center?

Answer 62

Amygdala Note - contains opioid receptors

Question 63

List the relevant mu opioid receptor antagonists

Answer 63

* Naloxone * Use if overdose * Naltrexone * Use to treat addiction

Question 64

Which drug is put in opioid pills to prevent IV abuse? How does this work?

Answer 64

Naloxone - competitive antagonist at the mu opioid receptor * Naloxone has very poor oral availability * It won't interfere with whatever is in the pill, if taken orally * However, if a person tries to crush up a pill and inject it, **there will be no mu agonist effect**

Question 65

What are the relevant metabolites of hydrocodone? What provides analgesia?

Answer 65

Hydrocodone metabolized to **hydromorphone** Ongoing debate as to which one provides analgesia

Question 66

What is the role of the periaqueductal grey in the central modulation of pain?

Answer 66

Periaqueductal gray **inhibits pain transmission** in the dorsal horn via a relay in the **rostral ventral medulla**

Question 67

NSAIDs prevent the synthesis of what substance?

Answer 67

Prostaglandin H2 Prostaglanins sensitize peripheral pain nerve endings (allodynia) and enhance pain transmission in the CNS (hyperalgesia)

Question 68

How is naloxone administered?

Answer 68

IV only Basically zero oral availability

Question 69

A 25 year old patient with no significant past medical history presents to your office for a routine introductory checkup. During your history, you learn that as an athlete, he uses 200mg of OTC (over the counter) ibuprofen three times per day every day for various muscle aches, and has done so for the past year. Further evaluation at this visit should include (select the best answer): 1. Drug screening for opioids 2. Drug screening for other NSAIDs 3. Thyroid stimulating hormone levels 4. Examination for hearing loss 5. Stool guiac for blood

Answer 69

e. Stool guiac for blood

Question 70

List the relevant mu opioid receptor agonists

Answer 70

My OH My, Can He Feel Me Toot? * Morphine * Oxycodone * Hydrocodone * Merperidine * Codeine * Hydromorphone * Fentanyl * Methadone * Tramadol **Note: If it starts with an N or a B, it is not a pure agonist** * Antagonists: Naloxone, Naltrexone* * Agonist/Antagonist: Nalbuphine* * Partial agonist: Buprenorphine*

Question 71

How do NSAIDs affect blood pressure?

Answer 71

NSAIDs increases blood pressure over time in people who have been treated for hypertension People with normal blood pressure to begin with are unaffected

Question 72

List the relevant mu opioid receptor partial agonist

Answer 72

Buprenorphine

Question 73

What is the action of naloxone on the mu opioid receptor?

Answer 73

Competitive antagonist

Question 74

How does the inhibition of prostaglandin synthesis affect our perception of pain peripherally? Centrally? Which drug does this?

Answer 74

NSAIDs inhibit prostaglandin syntehsis * Peripheral effect * Prostaglandins sensitize pain nerve endings by increasing Na+ influx, thus bringing the resting membrane potential closer to threshold -\> more AP firing -\> more pain signals * **NSAIDS inhibit the synthesis of prostaglandins, which prevents sensitization of these nociceptive nerve endings** * **​**They do not become excitable, and therefore do not transmit excessive pain signals * Central effect * At the synapse of the nociceptive neuron in the dorsal horn, prostaglandins increase substance P and glutamate from the 1st degree neuron and sensitize the 2nd degree neuron * They also inhibit the descending pathway by decreasing glycine and GABA release * **Inhibiting the synthesis of protaglandins prevents the enhanced substance P and glutamate release from the 1st degree neuron, prevents senitization of the 2nd degree neuron, and allows the descending pathway to block the ascending pain signal**

Question 75

Which somatosensory pathway is involved with proprioception, vibration, and fine touch?

Answer 75

Posterior column-medial lemniscal pathway

Question 76

What are the signs of opioid overdose? How is it treated?

Answer 76

* Respiratory depression or arrest * Perform CPR, support ventilation * Sedation * Unresponsive * Miosis Administer **Naloxone**

Question 77

How does the descending pathway modulate pain?

Answer 77

Activation of the descending pathway results in the **release of pain inhibitors** * Serotonin, norepinephrine * Endorphins * Enkephalins * Dynorphin Opiois help activate the descending pathway by removing the inhibition that normally acts on the descending pathway

Question 78

NSAID or Opioid? ## Footnote **Blocks transmission of pain**

Answer 78

Opioid

Question 79

What is the mechanism of action of NSAIDs?

Answer 79

COX inhibition * Without COX, arachidonic acid is not converted to prostaglandin H2 * This prevents the synthesis of tissue-specific **prostaglandins**, which normally work to sensitize peripheral pain nerve endings and enhance pain transmission in the CNS

Question 80

What opioid would be best for patients with pre-existing GI problems?

Answer 80

Fentanyl transermal patch Does note need to be absorbed by the GI tract

Question 81

How do NSAIDs affect the kidney?

Answer 81

NSAIDs inhibit prostaglandin synthesis, and therefore will interefere with afferent arteriole dilation during low-flow states This can lead to kidney injury * Decreased perfusion -\> ischemia * Especially bad when a patient has low blood volume, low blood pressure, or low cardiac output * **Both COX1 and COX2 are active in the kidney, so a COX2 selective inhibitor will not protect the kidney from decreased perfusion**

Question 82

Nalbuphine is classified as a mu opioid receptor… ## Footnote A. Agonist B. Antagonist C. Agonist/Antagonist D. Partial agonist

Answer 82

C. Agonist/Antagonist * Analgesia is kappa mediated * Does not have as much pain relieve as mu agonists, but fewer GI effects * Can trigger withdrawl * Do not use in opioid tolerant patients

Question 83

A patient with knee osteoarthritis asks you if acetaminophen can be as helpful for his pain as NSAIDs, which treat inflammation. You explain that it can be as effective because acetaminophen (select the best answer): 1. Blocks the formation of prostaglandins similarly to NSAIDs 2. Unlike NSAIDs, works by blocking the binding of prostaglandins to cells 3. Blocks COX-2 in the central nervous system 4. Activates opioid receptors 5. Is a nonspecific medication pain with no known mechanism

Answer 83

e. Is a nonspecific medication pain with no known mechanism But can be aseffective as NSAIDs in mild osteoarthritis pain

Question 84

Meperidine is classified as a mu opioid receptor… ## Footnote A. Agonist B. Antagonist C. Agonist/Antagonist D. Partial agonist

Answer 84

A. Agonist

Question 85

Which nerve fibers are affected by opioids?

Answer 85

Pain fibers - not touch or motor fibers

Question 86

What are the symptoms of opioid withdrawal?

Answer 86

Sympathetic overdrive + diarrhea and abdominal crampin * Anxiety * Insomnia * Diaphoresis * Yawning * Rhinnorhea * Lacrimation * HTN * Tachycardia * Hyperventilation

Question 87

What is vicoden?

Answer 87

Hydrocodone + acetaminophen

Question 88

Which opioid is most likely to cause histamine release? What is the result?

Answer 88

Morphine Itching, rash, hypotension

Question 89

Describe the metabolism of codeine

Answer 89

10% metabolized to morhine via CYP2D6 * Codeine does not provide analgesia - the morphine metabolite does * Codeine does not have a high affinity for the mu opioid receptor * It is considered a **weak opioid** * People with CYP2D6 mutations will not get pain relief from codeine

Question 90

What effects are modulated by the kappa opioid receptor?

Answer 90

* Mild analgesia * Less than Mu * Some respiratory depression * Less than Mu * Psychomimetic effects * Not euphoria

Question 91

What are the effects of prostaglandins on our perception of pain?

Answer 91

Prostaglandins... * Sensitize pain nerve endings * -\> Allodynia * Enhance pain transmission in the CNS * -\> Hyperlgesia

Question 92

What is the #1 cause of death related to opioid use?

Answer 92

Respiratory depression

Question 93

What is allodynia?

Answer 93

When touch causes pain

Question 94

Which drug blocks prostaglandin in the brain?

Answer 94

Acetaminophen

Question 95

What are the adverse effects of opioids on the respiratory system?

Answer 95

Respiratory depression * Activation of the mu opioid receptor inhibits the ventrilatory response to hypercapnia * The patient will breathe if prompted, but the natural ventilatory response is not there * **Risk of death because patient may forget to breathe**

Question 96

When pain transmission reaches the brain, which part of the brain does it go to?

Answer 96

Thalmus Note - the thalmus contains opioid receptors

Question 97

What is a narcotic?

Answer 97

* Any substance that induces sleep * Any substance which acts on opioid receptors * Any illicit substance Not descriptive! Has a connotation of misuse, abuse, and addiction

Question 98

NSAID or Opioid? ## Footnote **Prevents amplification of pain signal**

Answer 98

NSAIDs Note - NSAIDs do not block transmission; signals can still get through, but they are not amplified; no hyperalgesia

Question 99

What are the hematologic effects of non-ASA NSAIDs?

Answer 99

non-ASA NSAIDs reversibly bind COX * COX is necessry for the synthesis of TXA2, which is necessary for platelet aggregation and vasoconstriction * NSAIDs will therefore interfere with coagulation * Coagulation will return to normal after a few half lives Note: ASA irreversibly acetylates COX; that platelet will never work again. Effect lasts 7-10 days after mediation is stopped

Question 100

What are the most common uses for fentanyl?

Answer 100

* IV * During operations and ICU anesthesia * Usually only in patients that are closely monitored * Transdermal * Sustained release for chronic pain * Given as a patch or lollipop

Question 101

What is hyperalgesia?

Answer 101

Amplification of pain

Question 102

A patient you prescribed a combination drug of diclofenac/misoprostol calls you noting excellent pain relief but also the onset of marked diarrhea shortly after taking their first dose of the medication. Your next best step would be to 1. Reassure the patient that is is a side effect of the diclofenac 2. Reassure the patient that this is a side effect of the misoprostol 3. Advise the patient that he needs to go to the ED to evaluate for an ulcer 4. Advise the patient that this is an allergic response and to stop the medication 5. Advise the patient that this can be managed by taking the medication with food

Answer 102

b. Reassure the patient that this is a side effect of the misoprostol

Question 103

What is the precursor for prostaglandin in human tissue?

Answer 103

Arachidonic acid

Question 104

What causes “double pain?”

Answer 104

Sharp, initial pain due to A-delta (fast) fibers Subsequent thobbing pain due to C (slow) fibers

Question 105

What is an opiate?

Answer 105

A drug derived from opium Does **not** include synthetic drugs that act by the same mechanism * All opiates are opioids, but not all opioids are opiates

Question 106

What are the indications or buprenorphine?

Answer 106

Opioid maintenance for drug addiction (an alternative to methodone) * Has some indications for chronic pain, but most often use other agents for this

Question 107

People taking opioids for a long time can become tolerant to… But they will not become tolerant to…

Answer 107

* Tolerant to * Euphoria * Sedation * Analgesia * Respiratory depression * Will not become tolerant to * Miosis * Constipation

Question 108

Which opioid receptor is most strongly involved in analgesia?

Answer 108

Mu

Question 109

A mother brings in her 4-year-old child who is suffering from flu type symptoms (malaise, vomiting, diarrhea) and who has a temperature of 103^o F. The resident in the Emergency Department writes for aspirin to control the fever, but the attending changes the order to acetaminophen. The best reason for this change is 1. Risk of salicylate poisoning in a dehydrated patient 2. Risk of NSAID induced renal injury in a dehydrated patient 3. Risk of hepatic injury and encephalopathy from the aspirin 4. Risk of gastric bleeding 5. Risk of hematuria

Answer 109

c. Risk of hepatic injury and encephalopathy from the aspirin Aspirin is contraindicated in a child with viral syndrome; risk of Reye's syndrome

Question 110

What effects are modulated by the mu opioid receptor?

Answer 110

* Analgesia * Euphoria * Respiratory depression * Miosis * GI effects * Dependence

Question 111

Which areas of the brain contain opioid receptors? What are the functions of these areas?

Answer 111

TAP - BASS * **Thalmus** - pain * **Amygdala** - emotions * **Periaqueductal grey** - descending pain pathway * **Brainstem ventilation nuclei** - respiratory drive * **Area postrema** - vomiting * **Spinal trigeminal nucleus** - deep/crude touch, pain, and temperature * **Substantia gelatinosa** - synapse between sensory neuron and secondary neuron Note: **GI tract also contains opioid receptors**

Question 112

Which area of the brain modulates the descending pain pathway?

Answer 112

Periaqueductal grey

Question 113

What is the role of COX1 in platelet activation?

Answer 113

COX1 aids the formation of TXA2, which is necessary for platelet aggregation and vasoconstriction Note - non-selective NSAIDs inhibit COX1, and therefore will inhibit coagulation

Question 114

What is a nociceptor?

Answer 114

The receptive portion of a peripheral neuron that senses pain

Question 115

List the relevant mu opioid receptor agonist/antagonist

Answer 115

Nalbuphine

Question 116

What are the advantages of hydromorphone over morphine?

Answer 116

* Hydromorphone has a better side effect profile * Less likely to cause seizure * H3G isn't as dangerous as M3G * Less pruitis, sedation, nausea, and vomiting * More potent