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Spring 2024 Therapeutics 3 > Final Non-Opiates > Flashcards

Final Non-Opiates Flashcards

1
Q

What are the categories of non-opioids?

A

Salicylates (aspirin)

Arylpropionic Acids (ibuprofen, naproxen)

Arylacetic Acids (indomethacin, diclofenac, ketorolac, etodolac)

Enolic Acids (Piroxicam, Meloxicam)

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2
Q

What are the 4 uses of NSAIDs?

A

Analgesic
Anti-inflammatory
Antipyretic (fever)
Prophylactic (reduce MI risk) -aspirin

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3
Q

What are the 4 components of the inflammatory response?

A

Rubor, Tumor, Calor, Dolor

(redness, swelling, heat, pain)

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4
Q

What are the 3 stages of the inflammatory response?

A

Acute
Subacute
Chronic

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5
Q

What happens in the Acute Phase of the inflammatory response?

A

Vasodilation
(increased permeability of blood vessels)

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6
Q

What happens in the Subacute Phase of the inflammatory response?

A

Infiltration
(of neutrophils which causes inflammation, pain, and mast cell degranulation)

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7
Q

What happens in the Chronic Phase of the inflammatory response?

A

Proliferation

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8
Q

Recruitment of which molecule contributes to inflammatory pain?

A

Eicosanoids

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9
Q

Eicosanoids are metabolites of what?

A

Arachidonic acid

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10
Q

Why do NSAIDs want to block COX-2?

A

To reduce prostaglandin formation and reduce inflammation + pain

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11
Q

NSAIDs are COX inhibitors in what pathway?

A

Arachadonic acid pathway

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12
Q

What is the cascade that occurs after an injury occurs, leading to release of molecules involved in tissue repair?

A

Tissue injury
Leads to Activation of H Protein Couples Receptors
These couple with Phospholipase A2 (PLA2)
This creates Arachadonic Acid
Arachadonic Acid leads to COX-1 and COX-2

COX-1:
-Thromboxane (TXA2) release in platelets
-PGE2 + PGI2 release in mucosa (protects stomach lining)

COX-2:
-PGE2 in nociceptors and platelets

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13
Q

What substances released into the mucosa by COX-1 after tissue injury protect the stomach lining?

A

PGE2 (prostaglandin)
PGI2 (prostacyclin)

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14
Q

What substance creates Arachadonic Acid?

A

Phospholipase A2 (PLA2)

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15
Q

Arachadonic Acid is a substrate for what?

A

COX-1
COX-2
5-LOX (lipoxygenase)

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16
Q

What is the only NSAID that irreversibly inhibits COX 1/2?

A

Aspirin

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17
Q

What is the MOA of aspirin?

A

-Irreversibly inhibits COX 1/2 by acetylation of COX

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18
Q

What affect does aspirin have on COX-2 function?

A

Modifies COX-2 activity through acetylation

-This turns off the ability of COX-2 to produce prostaglandin but turns on the ability to produce protective lipid mediators

(Less prostaglandin, More protective lipid mediators)

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19
Q

What is the MOA of NSAIDs other than aspirin?

A

Competitive, reversible inhibitors of COX 1/2

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19
Q

What is the most common use of aspirin?

A

Prophylactic for anti-coagulation

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20
Q

True or False: Aspirin tolerance is a big problem

A

FALSE - there is no tolerance development to the analgesic affects of aspirin

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21
Q

Why should children not be treated with aspirin?

A

Risk of developing Reye’s Syndrome

-if child’s fever is of viral origin

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22
Q

What is the typical half-life of salicylates vs aspirin?

A

Salicylates: 6-20hr

Aspirin: 15min (but duration longer due to irreversible inhibition)

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22
Q

How fast is aspirin absorbed?

A

Rapidly

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23
Q

How can we increase the excretion of aspirin from the body?

A

Excretion increases with increased urinary pH (make more basic)
(ex:bicarb)

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24
Q

What are the symptoms of salicylism/aspirin poisoning?

A

Mild:
Vertigo, Tinnitus

CNS:
Respiratory Alkalosis (hyperventilation)
Metabolic Acidosis (low blood pH)

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25
Q

What is the treatment for salicylism/aspirin poisoning?

A

Reduce salicylate load

*Increase urinary excretion by increasing pH with Dextrose or Sodium Bicarbonate

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26
Q

What are the arylpropionic acid NSAIDs?

A

Ibuprofen (Advil)

Naproxen (Aleve)

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27
Q

What is the MOA of arylpropionic acids?

A

REVERSIBLE cyclooxygenase inhibitors

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28
Q

What are the half-lives of the two common arylpropionic acids?

A

Ibuprofen: 2hr

Naproxen: 14hr

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29
Q

What are the Arylacetic Acid Derivatives?

A

Diclofenac (Voltaren)
Indomethacin (Indocin)
Sulindac (Clinoril)

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30
Q

Which Arylacetic Acid Derivative is available as a gel?

A

Diclofenac

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31
Q

What is a concerning side effect of diclofenac (Voltaren)?

A

Peptic Ulcer

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32
Q

What drug can be used to reduce the risk of developing a peptic ulcer while taking Diclofenac?

A

Misoprostol (PGE1 analog)

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33
Q

Which Arylacetic Acid Derivative is a potent reversible inhibitor of PG biosynthesis?

A

Indomethacin (Indocin)

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34
Q

What side effects are we worried about with Indomethacin (Indocin)?

A

*High incidence and severity of side effects

-Acute gouty arthritis

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35
Q

What is the less toxic derivative of indomethacin?

A

Sulindac (Clinoril)

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36
Q

What are the Enolic Acids?

A

Meloxicam
Piroxicam

“oxicam” drugs

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37
Q

What are the Enolic Acids used to treat?

A

Arthritis

*great joint penetration

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38
Q

What is the MOA of meloxicam?

A

COX-2 selective at low doses

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39
Q

What are the half-lives of the two enolic acids?

A

Meloxicam= 20 hours

Piroxicam= 57 hours***

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40
Q

What are the side effects of NSAIDs?

A

Renal Function Issues
(inhibition of renal PGE2 synthesis can cause increased sodium reabsorption and peripheral edema)

Increased bleeding risk
(inhibition of platelet aggregation)

Inhibition of uterine motility
(promethazine)

GI distress and ulcers

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41
Q

Which NSAID can be used to delay preterm labor by inhibiting uterine motility?

A

Promethazine

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42
Q

What are the uses for acetaminophen?

A

Analgesic

Antipyretic

**limited anti-inflammatory activity

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43
Q

True or False: Acetaminophen is an NSAID

A

FALSE

-limited anti-inflammatory activity

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44
Q

What are the advantages of acetaminophen over NSAIDs?

A

No GI toxicity

Can use in children

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45
Q

What are the disadvantages of acetaminophen compared to NSAIDs?

A

Overdose may lead to fatal hepatic necrosis
(hepatotoxic)

Causes more vasoconstriction than NSAIDs

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46
Q

The risk of hepatic necrosis with acetaminophen increases with what?

A

Alcohol

(increases toxic acetaminophen metabolites [NAPQI])

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47
Q

What drug is used to treat the increase in toxic acetaminophen metabolites (NAPQI) associated with hepatic necrosis?

A

n-acetylcysteine

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48
Q

What are the selective COX-1/2 inhibitors and what side effects are they associated with?

A

Aspirin/ Acetaminophen/ Non-Salycilate NSAIDs

-Stomach ulcers
-GI bleeds

49
Q

What is the selective COX-2 inhibitor and what are its side effects?

A

Rofecoxib (Vioxx)

Reduces ulcers and GI bleeds

*Withdrawn due to chance of blood clots, strokes, and heart attacks

50
Q

Who should not take NSAIDs?

A

Patients with:
-Chronic Kidney Disease
-Peptic Ulcer Disease
-History of GI Bleed

51
Q

All NSAIDs carry what risk?

A

Cardiovascular risk in patients with coronary heart disease

Highest risk: Diclofenac
Lowest risk: Naproxen

52
Q

When used at high doses, all NSAIDs can interfere with what?

A

Bone healing

53
Q

NSAIDs can cause what?

A

Asthma exacerbations

54
Q

Local anesthetics are what kind of drugs?

A

Sodium Channel Blockers

55
Q

What are the local anesthetics?

A

Lidocaine
Bupivacaine
Benzocaine

56
Q

Which sodium channel blocker local anesthetic has a higher allergy risk?

A

Benzocaine
(esters)

57
Q

Which sodium channel is being targeted for analgesia?

A

NaV1.7

58
Q

A gain of function / loss of function mutation in the sodium channel NaV1.7 leads to what?

A

Gain of Function: Severe neuropathic pain

Loss of Function: Congenital insensitivity to pain

59
Q

What psychiatric drugs are also sodium channel blockers?

A

Anticonvulsants:
-Lamotrigine
-Carbamazepine

Tricyclic Antidepressants:
-Amitriptyline

60
Q

SNRIs have what function?

A

Increase norepinephrine levels

61
Q

SNRIs act on what receptors in the spinal cord?

A

Alpha 2A- adrenergic receptors

62
Q

Which SNRI’s are used for pain and what type of pain are they used for?

A

Duloxetine: Peripheral neuropathy
Venlafaxine: Diabetic neuropathy

Milnacipran *lacks sodium channel function

63
Q

What two calcium channel blockers may be possible analgesics?

A

Gabapentin

Pregabalin

64
Q

What are the clinical pearls of the two analgesic calcium channel blockers?

A

a2 delta- Cav1,2 selective
Not metabolized
No drug-drug interactions
Half life= 4-8hr

65
Q

How do calcium channel blockers work to produce analgesia?

A

Blocking calcium reduces glutamate release which reduces firing

(calcium channels opening typically triggers the release of glutamate)

66
Q

What is the recommended dosing for acetaminophen (Tylenol) in adults?

A

325-1000mg PO q 4-6h prn

67
Q

What is the MAX dose of acetaminophen in adults?

A

3-4 g/day

68
Q

What is the recommended dosing for acetaminophen (Tylenol) in kids?

A

10-15 mg/kg PO q4h prn

69
Q

What is the MAX dose of acetaminophen (Tylenol) in kids?

A

75 mg/kg/day
OR
3-4 g/day

70
Q

Acetaminophen is the GOLD STANDARD treatment for which disease state?

A

Osteoarthritis

(less side effects in geriatric patients than NSAIDS)

71
Q

What do NSAIDs have a black box warning for?

A

GI bleeding

72
Q

Who should NSAIDs be used with caution in?

A

Geriatric patients

(Beers List)

73
Q

Systemic use of NSAIDS should be avoided in which disease states?

A

Cardiac history (can use topical)
Liver disease
Chronic kidney disease

74
Q

What is the recommended dosing of aspirin in adults?

A

325mg-1000mg po q4-6h PRN

75
Q

What is the MAX dose of aspirin used in adults?

A

4g/day

76
Q

What is the recommended dosing of aspirin in kids?

A

DO NOT USE IN KIDS Under 18)
-Reyes Syndrome

77
Q

What patients should avoid taking aspirin?

A

Patients taking blood thinners or antiplatelets

Children

78
Q

What is the Adult dosing of Ibuprofen?

A

200-800 mg po q6-8h prn

79
Q

What is the MAX dose of ibuprofen in adults?

A

3200 mg/day

80
Q

What is the Child dosing of Ibuprofen?*

A

(>6 months old): 5-10 mg/kg po q4-6h prn

81
Q

What is the MAX dose of Ibuprofen in children?

A

40 mg/kg/day or 2400mg

*whichever is less

82
Q

Besides tablet/capsule, what other form does aspirin come in?

A

Suppository

83
Q

Besides tablet/capsule, what other forms does ibuprofen come in?

A

Suspension
IV solution

84
Q

Besides tablet/ capsule, what other forms does diclofenac come in?

A

IV solution
Suppository
Topical gel
Topical solution
Opthalmic solution
Patch

85
Q

Besides capsules/tablets, what other forms does Naproxen come in?

A

Suspension

86
Q

Besides tablets, what other forms of ketorolac are available?

A

IV/IM solution
Nasal spray
Opthalmic solution

87
Q

What are the clinical pearls for ketorolac?

A

Max duration is 5 days

Increased GI bleeding risk when longer!

88
Q

What differentiates Celecoxib (Celebrex) from other NSAIDs?

A

COX 2 selective

-less GI toxicity

89
Q

Which of the following options offer a not po option?
Aspirin
Ibuprofen
Diclofenac
Naproxen
Ketorolac
Celebex

A

Aspirin (Suppository)

Ibuprofen (IV)

Diclofenac (IV, Suppository, Gel, Topical solution, Ophthalmic solution, Patch)

Ketorolac (IV/IM solution, nasal sprat, ophthalmic solution)

90
Q

Which of the following have an oral solution/suspension?
Tylenol
Bayer
Motrin
Voltaren
Aleve
Toradol
Celebrex

A

Tylenol
Motrin
Aleve

91
Q

What are the gabapentinoids?

A

Gabapentin (Neurontin)

Pregabalin (Lyrica)

92
Q

What pain are gabapentinoids useful for?

A

-Fibromyalgia
-Neuropathy
-Post-op pain

Nerve pain

93
Q

What is the MAX dose of gabapentin (Neurontin)?

A

3600 mg/d

94
Q

What is the MAX dose of pregabalin (Lyrica)?

A

600 mg/d

95
Q

What are the side effects of the gabapentinoids?

A

Sedation
Dizziness
Edema

96
Q

What are the SNRIs used for pain?

A

Venlafaxine (Effexor)

Duloxetine (Cymbalta)

97
Q

What types of pain are SNRI’s used for?

A

Fibromyalgia

Neuropathy
nerve pain

98
Q

What is the max dose of Venlafaxine?

A

225 mg/day

99
Q

What is the max dose of Duloxetine?

A

60 mg/day

100
Q

When do we avoid using Duloxetine?

A

CrCl < 30 ml/min

101
Q

What are the TCAs used for pain?

A

Amitriptyline (Elavil)

Nortriptyline (Pamelor)

102
Q

When are the TCA’s used for pain?

A

LAST LINE
-because of SE

103
Q

What are the muscle relaxants used to treat pain?

A

Cyclobenzaprine (Amrix, Fexmid)
Baclofen (Lioresal))
Methocarbamol (Robaxin)
Carisoprodol (Soma)
Tizanidine (Zanaflex)

104
Q

What pain are muscle relaxants used for?

A

Musculo-skeletal pain/spasms

105
Q

How long should muscle relaxants be used for?

A

SHORT TERM
<3 weeks

106
Q

Which antiepileptic is used in pain treatment?

A

Carbamazepine (Tegretol)

107
Q

What type of pain is an antiepileptic used for?

A

Neuropathic pain

108
Q

Which drug auto induces CYP metabolism of itself?

A

Carbamazepine (Tegretol)

109
Q

When do we use the antiepileptic (Carbamazepine) for pain?

A

LAST LINE

*many side effects

110
Q

What topical agents are available for pain management?

A

Lidocaine

Capsacian

111
Q

What are the instructions for applying a lidocaine patch?

A

Apply 1 patch to affected area daily and remove 12 hours later

112
Q

How does capsacian work?

A

Counter-irritant
-irritates spot when you put it on which tricks the brain to not focus on other pain

113
Q

What are the clinical pearls of capsacian?

A

-Do not get medicine into eyes (burning)
-Wash hands after applying
-Some formulations available OTC

114
Q

Older adults an increased risk of what with NSAIDs?

A

GI bleeding

Peptic Ulcer Disease

115
Q

How should elderly patients take NSAIDs?

A

Avoid chronic use unless alternative not available

*If taking, take gastroprotective agent too

-Avoid short-term scheduled use

116
Q

Which NSAID has the highest risk for adverse effects?

A

Indomethacin

*avoid in elderly

117
Q

Which are the 3 worst skeletal muscle relaxants to take in older adults?

A

Carisoprodol
Cyclobenzaprine
Methocarbamol

118
Q

Which muscle relaxants are the better ones to use in the elderly?

A

Baclofen
Tizanidine

119
Q

Why are SNRIs, TCAs, and Carbamazepine in the Beers Criteria?

A

Exacerbate or cause SIADH (syndrome of inappropriate antidiuretic hormones)

May cause hyponatremia
*monitor sodium

120
Q

Why are opioids/benzodiazepines in the beers criteria?

A

Increase risk of overdose and AE

*avoid use

121
Q

Which pain medications CAN be used in the elderly to minimize side effects?

A

Topical agents (lidocaine, diclofenac, capsaicin)

Acetaminophen
SNRIs
Gabapentinoids

Spring 2024 Therapeutics 3 (24 decks)

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