Week 3: Nonopioid Analgesics Flashcards by Ashley Campbell

How do peripherally acting analgesics work?

Act at the sensory input level by blocking transmission of the impulse to the brain

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Peripheral administration of drugs can potentially optimize drug concentrations at the site of origin of pain while leading to _______ (higher/lower) systemic levels and _______ (fewer/more) adverse systemic effects and _______ (fewer/more) drug interactions

Lower
Fewer
Fewer

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What 3 types of pain depend on some degree of peripheral activation of primary sensory afferent neurons?

-Nociceptive
-Inflammatory
-Neuropathic

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Inhibiting the actions of these 5 inflammatory mediators represents a strategy for the development of analgesics

-Prostanoids
-Bradykinin
-Adenosine triphosphate (ATP)
-Histamine
-Serotonin

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Combinations of agents that act via different mechanisms may be particularly useful (multimodal analgesia

True or false

True

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Which drugs are among the most commonly prescribed drugs in the world

NSAIDs (nonsteroidal anti-inflammatory drugs)

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Aspirin and several other selective and nonselective cyclooxygenase inhibitors belong to what class of drugs

NSAIDs

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3 main properties of NSAID’s

-Common analgesic
-Anti-inflammatory
-Antipyretic properties

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How do NSAID’s work?

Inhibits the biosynthesis of prostaglandins by preventing the substrate arachidonic acid from binding to the cyclooxygenase (COX) enzyme active site

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NSAIDs work by inhibiting the biosynthesis of ____________ by preventing the substrate __________ from binding to the _________________ enzyme active site

prostaglandins
arachidonic acid
cyclooxygenase (COX)

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What two isoenzymes does the COX enzyme exist as

-COX 1
-COX 2

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What is the COX-1 isoenzyme responsible for?

-Maintenance of normal renal function in the kidneys
-Mucosal protection in the GI tract
-Production of proaggregatory thrombozane A2 in the platelets

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COX-2 can be induced by inflammatory mediators in many tissues and has a role in the mediation of ______, ______, and ______

pain, inflammation, and fever

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________ (increased/decreased) cardiovascular risk has been associated with COX-2 inhibitors

Increased

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What is the only COX-2 selective inhibitor available for clinical use?

Celecoxib

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What are some benefits of Celecoxib?

-Improved quality of analgesia
-Reduced incidence of GI side effects
-No platelet inhibition

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All NSAIDs are weakly acidic chemical compounds and share similarities in pharmacokinetic properties

True or false?

True

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How fast is GI absorption of NSAIDs?

15-30 mins

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What organ metabolizes most NSAIDs

Liver

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Where are most NSAIDs excreted

Urine and bile

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How does reduced renal function affect NSAIDs

Prolongs half-life; dose should be lowered proportionally in patients with impaired kidney function

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How does moderate to severe liver disease affect NSAIDs

Impairs NSAID metabolism, increasing potential for toxicity

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NSAID side effects

-Hypertension
-Can exacerbate, induce HF
-Thrombotic events (more likely in COX-2)

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Respiratory

NSAID side effects

-Nasal polyps
-Rhinitis
-Dyspnea
-Bronchospasm
-Angioedema
-May exacerbate asthma

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Hepatic NSAID side effects

Hepatitis

GI NSAID side effects

-Gastropathy (can be asymptomatic) -Gastric bleeding -Esophageal disease -Pancreatitis

Hematologic NSAID side effects

-Increased intraoperative bleeding d/t platelet inhibition/dysfunction (COX-2 dont affect) -Potentiates anticoagulation effect

Dematologic NSAID side effects

-Urticaria -Erythema multiforma -Rash

GU NSAID side effects

-Renal insufficiency -Sodium/fluid retention -Papillary necrosis -Interstitial nephritis

CNS NSAID side effects

-Headache -Aseptic meningitis -Hearing disturbances

Skeletal NSAID side effects

Potential to inhibit bone growth/healing/formation

Pharmacologic interactions NSAID side effects

Displace albumin-bound drugs and can potentiate their effects (e.g. warfarin)

Hypersensitivity reactions to NSAIDs rarely occur, and they are more common in individuals with _______ or _________

Nasal polyps, asthma

What kind of NSAID is Ketorolac?

Nonselective NSAID

What kind of NSAID is ibuprofen?

Nonselective NSAID

What kind of NSAID is Ketoprofen?

Nonselective NSAID

What kind of NSAID is Naproxen?

Nonselective NSAID

What kind of NSAID is aspirin?

Nonselective NSAID

What kind of NSAID is celecoxib

COX-2 agent

Acetaminophen has antipyretic and analgesic effects true or false

true

Acetaminophen has little, if any, antiiflammatory action true or false

true

Acetaminophen is found in many over-the-counter and prescription products true or false

true

Which drug is the leading cause of acute liver failure in the US?

Acetaminophen

Nearly half of acetaminophen-associated acute liver failure is do to what?

Unintentional overdose

How does damage to the liver from acetaminophen occur?

Results from one of acetaminophen's metabolites, NAPQI (N-acetyl-p-benzoquinoeimine)

How does acetaminophen's metabolite, NAPQI lead to liver failure?

Depletes the liver's natural antioxidant, glutathione and directly damages liver cells

What is the treatment for acetaminophen induced liver failure?

Acetylcysteine is administered as an antidote and acts as a precursor for glutathione (antioxidant) and can neutralize NAPQI directly

What is treatment for acetaminophen induced liver failure aimed at?

Removing the paracetamol from the body and replacing glutathione (antioxidant)

Does oral acetaminophen have excellent bioavailability?

Yes

Total daily dose of acetaminophen should not exceed what?

4,000 mg

Can acetaminophen be given IV?

Yes, an IV preparation of acetaminophen is currently available for clinical use

Which kind of steroid has the most powerful anti-inflammatory characteristic of all steroids?

Glucocorticoids

Which kind of steroids are adrenal cortical steroid hormones that have a greater effect on water and electrolyte balance?

Mineralcorticoids

What is the main endogenous hormone?

Aldosterone

How do corticosteroids in multimodal analgesia protocols contribute to postop recovery?

Minimize opioid doses and therefore side effects

Dexamethasone has been found to ______ (prolong/shorten) local anesthetic block duration

prolong

How have corticosteroids been used to treat back pain?

Epidural injections, mainly due to nerve root irritation

What is the only proven efficacy of epidural steroid injections?

Their ability to speed resolution of leg pain "sciatica" in patients with acute intervertebral disc herniation and associated radicular pain

Dexamethasone is given in doses over _____mg/kg It is dose dependent whether giving for anti-nausea vs pain/anti-inflammatory

0.1mg/kg

Side effects for steroids tend to occur with ________ (single/repeat) dosing

repeat

Dermatologic and soft tissue Corticosteroid side effects

-Skin thinning and purpura -Cushingold appearance -Alopecia -Acne -Hirsutism (excessive hair growth in women) -Striae -Hypertrichosis (excessive hair growth inappropriate places)

Eye Corticosteroid side effects

-Posterior subcapsular cataract -Elevated intraocular pressure/glaucoma -Exophthalmos (protruding eyes)

CV Corticosteroid side effects

-Hypertension -Change in serum lipoproteins -Premature atherosclerotic disease -Arrhythmias with pulse infusions

GI Corticosteroid side effects

-Gastritis -Pancreatitis -Steatohepatitis -Peptic ulcer disease -Visceral perforation

Renal Corticosteroid side effects

-Hypokalemia -Fluid volume shifts

GU and Reproductive Corticosteroid side effects

-Amenorrhea/infertility -Intrauterine growth retardation (fetus grows slower, is smaller at birth)

Bone Corticosteroid side effects

-Osteoporosis -Avascular necrosis (bone tissue dies d/t loss of blood supply)

Muscular Corticosteroid side effects

Myopathy (muscle weakness)

Neuropsychiatric Corticosteroid side effects

-Euphoria -Dysphoria/depression -Insomnia/akathisia (inner restlessness) -Psychosis -Pseudo tumor cerebri (increased ICP without brain tumor)

Endocrine Corticosteroid side effects

-DM -Hypothalmic-pituitary-adrenal insufficiency

What is hypothalmic-pituitary-adrenal-insufficiency

Steroids mimic body's natural cortisol, leading to a negative feedback loop that signals the body to stop producing its own cortisol, leading to adrenal glands to stop producing enough cortisol

Infectious disease Corticosteroid side effects

-Heightened risk of typical infections -Opportunistic infections -Herpes zoster

What kind of anesthetic is lidocaine

Nonopioid systemic local anesthetic

How does lidocaine produce analgesia?

By suppressing the activity of sodium (Na+) channels in the neurons that respond to noxious stimuli, thereby preventing nerve conduction and pain transmission

How are intravenous lidocaine infusions being used

Intra-op for pain management

What are the 2 gabapentinoids?

Gabapentin (Neurontin) Pregabalin (Lyrica)

How do gapapentinoids work?

Bind to alpha 2 delta subunits of the voltage-gated calcium (Ca2+) channels in the CNS (near GABA)

What is gabapentin used for?

Analgesic effectiveness in: -Diabetic neuropathy -Post-herpetic neuralgia -Neuropathic pain

When used for a dose sparing effect, how much gabapentin is typically used in the preop holding area

300-900mg PO smaller doses in elderly (can be very sedating)

How does pregabalin typically work

reduces hyper-excitability of dorsal horn neurons

How is pregabalin metabolized and excreted?

-Not metabolized -Excreted by kidneys

Dose for Lyrica

150-600mg/day in 2-3 doses

What are the 4 centrally acting nonopioid analgesics

-Clonidine -Dexmedatomidine -Ketamine -Magnesium

How does clonidine work

Acts as a selective partial alpha2-receptor agonist

What is neuraxial clonidine an effective analgesic for?

-Chronic cancer and noncancer pain -Postop pain (epidural, intrathecal)

Epidural dose for clonidine

Epidural: 75-150mcg

Intrathecal dose for clonidine

Intrathecal: 30-60mcg

Neuraxially administered opioids and alpha-2 agonists exibit________

Synergism

Addition of clonidine to opioids for postop analgesia as a continuous epidural infusion reduces opioid requirements by _____-______%

20-60%

Clonidine is a useful adjunt for ______ epidural analgesia

Labor

Neuraxial clonidine is indicated for the treatment of intractable pain in ______ patients unresponsive to maximum dose of opioids

cancer

Dexmedetomidine has a _______ (higher/lower) affinity for alpha-2 receptors than clonidine

higher

How does dexmedetomidine work?

Potent alpha2-receptor agonist

Does dexmedetomidine produce analgesia as efficiently as clonidine?

Yes

Dexmedetomidine is associated with _________ (more/fewer) side effects as clonidine

fewer

Dexmedetomidine is associated with fewer _________ and _______ side effects than clonidine

hemodynamic, systemic

A dose of 3mcg of intrathecal dexmedetomidine is equipotent to ___mcg of clonidine

30mcg

Epidural dexmedetomidine exhibits _________ with local anesthetics

synergism

Epidural dexmedetomidine exhibits increasing density of motor block true or false

true

Epidural dexmedetomidine _________ (shortens/prolongs) the duration of both sensory and motor block

prolongs

Dexmedetomidine improves postop analgesia true or false

true

SE of dexmedetomidine include

-Hypotension -Bradycardia

Do alpha2-receptor agonists reduce MAC requirements?

Yes

What kind of doses of ketamine are used as an adjunt to provide postoperative pain relief in opioid dependent patients?

Subanesthetic doses (<0.5mg/kg)

What can be used as an adjunct to provide postop pain relief in opioid dependent patients?

Ketamine

What ways can ketamine be used

Bolus Infusion

How does ketamine work

NMDA receptor antagonist

What is the analgesic dose of ketamine while limiting side effects

<0.5mg/kg

How does magnesium work as an analgesic

NMDA recetor antagonist

How can magnesium be administered

Bolus Infusion

Dose of magnesium

30-50mg/kg (2g for adults) loading dose 6-20mg/kg/h infusion

What are some things to look out for with magnesium administration

-Renal function -Hypotension (fast bolus) -Potentiation of neuromuscular blocking agents

Centrally acting nonopioid analgesics Various neuraxial drug administration via the INTRATHECAL and EPIDURAL route remains an important treatment option for the provision of anesthesia and analgesia in

-Acute -Cancer -Chronic pain

Ketorolac adult dosing

15-30mg IV q6h

Ketorolac peds dosing

0.5mg/kg IV q6h (MAX 15mg)

Acetaminophen dosing

325-650mg PO q4-6h (MAX 3,000-4,000mg daily)

Week 3: Nonopioid Analgesics Flashcards

(116 cards)