non-opioids Flashcards
NSAIDS
Full name of NSAIDS______ are ________nhibitors
- Prevent binding of _______ to ______enzyme
- Inhibit the biosynthesis of ________
Common ____, _____ and ______effects
NSAIDS
Nonsteroidal anti-inflammatory drugs (NSAIDs) are cyclooxygenase (COX) inhibitors
- Prevent binding of arachidonic acid to COX enzyme
- Inhibit the biosynthesis of prostaglandins
Common analgesic, anti-inflammatory and antipyretic effects
COX enzyme exists in two forms:
- _____
- _____
COX enzyme exists in two forms:
- COX – 1 isoenzyme
- COX – 2 isoenzyme
NSAIDs are either:
- _____
- _____
NSAIDs are either:
- Non-selective
- COX – 2 selective (coxibs)
COX – 1 isoenzyme
- _____ expressed
- Involved in ____ physiologic functions
- Maintenance of ____ function
- ____ protection of the ___ tract
• Production of ______
COX – 1 isoenzyme
- Constitutively expressed
- Involved in numerous physiologic functions
- Maintenance of renal function
- Mucosal protection of the GI tract
• Production of thromboxane A2
COX - 2 isoenzyme
- Expression induced by ____
- Role in:
- ____
- ____
- _____
COX - 2 isoenzyme
- Expression induced by inflammatory mediators
- Role in:
- Mediation of pain
- Inflammation
- Fever
NON-SELECTIVE NSAIDs
Limited use in the perioperative setting
- ____ toxicity
- ___ dysfunction
___ healing is delayed with NSAIDs
• Safe in the setting of _____
____ (_____) is most commonly used perioperatively
- Dosing ___IV or IM Q __h
- Reduce dosing in patients with ____ function
NON-SELECTIVE NSAIDs
Limited use in the perioperative setting
- Gastrointestinal toxicity
- Platelet dysfunction
Bone healing is delayed with NSAIDs
• Safe in the setting of primary bone healing
Toradol (ketorolac) is most commonly used perioperatively
- Dosing 30mg IV or IM Q 6h
- Reduce dosing in patients with renal function
COX – 2 INHIBITOR
____ (_____) only available COX – 2 for use
- Have less _____ toxicity
- Increased _____ risk
Commonly given as part of ____ (_____) protocols
Dosing
- ____mg PO preoperatively
- ___mg. __ID x ____ days postoperatively
COX – 2 INHIBITOR
Celebrex (celecoxib) only available COX – 2 for use
- Have less gastrointestinal toxicity
- Increased cardiovascular risk
Commonly given as part of enhanced recovery after surgery (ERAS) protocols
Dosing
- 400 mg PO preoperatively
- 200 mg BID x 5 days postoperatively
NSAIDS PK
All NSAIDs are weak \_\_\_\_ Low Vd (\_\_\_\_) Plasma half-life is widely \_\_\_
Gastrointestinal absorption occurs ___
____ protein binding
_____ metabolizes most NSAIDs
Eliminated primarily by ___ and ____
All NSAIDs are weak acids Low Vd (.1-.3 L/kg) Plasma half-life is widely variable
Gastrointestinal absorption occurs rapidly
Increased protein binding
Liver metabolizes most NSAIDs
Eliminated primarily by renal and biliary excretion
NSAIDS side effects
Platelet function primarily through COX – 1
GI:
____ complications range from _____to ____such as _____ and _____
- Risk factors include:
- ____
- _____
- _____
- ______
NSAIDS side effects
Platelet function primarily through COX – 1
GI:
Gastrointestinal complications range from mild ulcers to serious incidents such as perforation and bleeding
- Risk factors include:
- Elderly
- Helicobacter pylori infection
- History of previous ulcer
- Concomitant use of aspirin, anticoagulants or corticosteroids
NSAIDS side effects
CV
- Increased risks of ____, _____ and _____
- In patients with CV risks, _____ is NSAID of choice
NSAIDS side effects
CV
- Increased risks of myocardial infarction, heart failure and hypertension
- In patients with CV risks, naproxen is NSAID of choice
NSAIDS side effects
Renal
- Changes in renal function include:
- ____ excretion, ____ function, interstitial ___ and reversible failure
- Risk factors
- Congestive ____, established ____ disease, history of ____, hypertension, _____ and significant ____
- _____ from any cause increases the potential of renal injury
NSAIDS side effects
Renal
- Changes in renal function include:
- Sodium excretion, tubular function, interstitial nephritis and reversible failure
- Risk factors
- Congestive heart failure, established renal disease, history of diabetes, hypertension, atherosclerosis and significant hypoalbuminemia
- Hypovolemia from any cause increases the potential of renal injury
NSAIDS other side effects
Liver
• Elevations in ______ levels and liver failure have been reported
Pulmonary
• Use of _____ in patients with history of ________
Hypersensitivity with NSAIDs rarely occurs. However:
• _____ + ____+ _____ = Risk of ___
Drug-Drug Interactions
- Increased bleeding with _____ agents
- Decreased _____ and _____ clearance secondary to _____ inhibition and altered ____ flow
NSAIDS other side effects
Liver
• Elevations in transaminase levels and liver failure have been reported
Pulmonary
• Use of COX - 2 in patients with history of aspirin-exacerbated disease
Hypersensitivity with NSAIDs rarely occurs. However:
• allergic rhinitis + nasal polyps + asthma = Risk of Anaphylaxis
Drug-Drug Interactions
- Increased bleeding with antiplatelet agents
- Decreased digoxin and lithium clearance secondary to prostaglandin inhibition and altered renal flow
ASPIRIN
____ and most _____ medicinal compound in the world
Derivative of ______
Rapidly metabolized by
• ____, ____ and ____
Two main uses
- _____
- _____
ASPIRIN
Oldest and most widely used medicinal compound in the world
Derivative of salicylic acid
Rapidly metabolized
• Plasma esterases, erythrocytes and liver
Two main uses
- General analgesic
- ”Irreversible” platelet inhibitor
ASPIRIN
OVERDOSE
Toxicity related to drug ____ and ____
Symptoms include:
- ___, ____, ____ pain, ____ impairment, ___ depression,
- Higher doses can result in ____acidosis, ___ failure, CNS ___ (____, ____, ____), and ____ with respiratory ____
_____ increases salicylate elimination
ASPIRIN
OVERDOSE
Toxicity related to drug acidity and prostaglandin inhibition
Symptoms include:
- Nausea, vomiting, abdominal pain, hearing impairment, CNS depression,
- Higher doses can result in metabolic acidosis, renal failure, CNS changes (agitation, confusion, coma), and hyperventilation with respiratory alkalosis
Urine alkalinization increases salicylate elimination
ACETAMINOPHEN
Has ___ and ____ properties
• Central analgesic effect through:
- Activation of _____ pathways
- Antagonism of ___, ___ and _____ pathways
• No _____ actions
Excellent oral bioavailability
- Dosing ____-____mg Q _-_h
- Total not to exceed ____mg/____h (____mg for chronic alcoholics)
An intravenous preparation (____) is available for clinical use
- ____mg IV Q __h
- Total not to exceed _____mg/___h
ACETAMINOPHEN
Has analgesic and antipyretic properties
• Central analgesic effect through:
- Activation of serotonergic pathways
- Antagonism of NMDA, substance P and nitric oxide pathways
• No anti-inflammatory actions
Excellent oral bioavailability
- Dosing 325-650mg Q 4-6h
- Total not to exceed 4,000mg/24h (2,000mg for chronic alcoholics)
An intravenous preparation (Ofirmev) is available for clinical use
- 1,000mg IV Q 6h
- Total not to exceed 4,000mg/24h
Acetaminophen PK
Metabolized in the _____
Leading cause of acute ____ failure in US
• Chronic usage of < ____g not associated with liver damage
Damage to the liver result from a metabolite:
- ______ leads to liver failure by depleting ____, a natural ___
- Treatment aimed at ____ acetaminophen (____) and replacing ____ (_____ administration)
Acetaminophen PK
Metabolized in the liver
Leading cause of acute liver failure in US
• Chronic usage of < 2g not associated with liver damage
Damage to the liver result from a metabolite:
- N-acetyl-p-benzoquinoneimine leads to liver failure by depleting glutathione, a natural antioxidant
- Treatment aimed at removing acetaminophen (charcoal) and replacing glutathione (acetylcysteine administration)
GABAPENTIN
Gabapentin is a structural analogue of ____
• Acts on ___-dependent ____ channels inhibiting ____
Approved as an _____ medication
• Has demonstrated some efficacy in ____ pain
Used as part of multimodal pain management in ______ protocols
• Generally accepted to be effective in reducing ____ ____ pain and _____ consumption
GABAPENTIN
Gabapentin is a structural analogue of gamma-aminobutyric- acid (GABA)
• Acts on voltage-dependent calcium channels inhibiting glutamate
Approved as an anticonvulsant medication
• Has demonstrated some efficacy in neuropathic pain
Used as part of multimodal pain management in enhanced recovery after surgery (ERAS) protocols
• Generally accepted to be effective in reducing immediate postoperative pain and opioid consumption
Gabapentin PK
Absorption is _____ to a relatively small part of the ____
• Absorption can be impaired by _____
Exhibit ____ protein binding and excreted _____ significant metabolism
Gabapentin PK
Absorption is limited to a relatively small part of the duodenum
• Absorption can be impaired by antacids
Exhibit minimal protein binding and excreted without significant metabolism
GABAPENTIN
Dosing
- Preoperatively _____mg ____ h before surgery
- _____mg Q__h x ____days
Side-Effects include:
• ___, _____ or _____ and ______ disturbances
GABAPENTIN
Dosing
- Preoperatively 1,200mg 1-2 h before surgery
- 600mg Q8h x 14days
Side-Effects include:
• Sedation, dizziness or headache and visual disturbances
LIDOCAINE
Lidocaine is an _____ local anesthetic
- Weak ____
- pKa slightly _____ physiologic pH
Infusions are routinely used as part of a ______plan to supplement _____
Mechanism of action ______
- May involve ____ channels
- Block priming of ____ _____
LIDOCAINE
Lidocaine is an amide local anesthetic
- Weak base
- pKa slightly above physiologic pH
Infusions are routinely used as part of a multimodal pain management plan to supplement general anesthesia
Mechanism of action not certain
- May involve sodium channels
- Block priming of polymorphonuclear granulocytes
LIDOCAINE
Pharmacokinetics
- Undergoes first-pass extraction in the _____
- Metabolized in the ____
- Metabolism prolonged in patients under ____
Dosing
- ____ bolus dose
- _____ infusion
LIDOCAINE
Pharmacokinetics
- Undergoes first-pass extraction in the lungs
- Metabolized in the liver
- Metabolism prolonged in patients under general anesthesia
Dosing
- 1.5 mg/kg bolus dose
- 1-2 mg/kg/hour infusion
LIDOCAINE
_____ for all surgical procedures
- Reduces ___ and speeds up _____in ____ cases
- Decreases ___, improves functional outcomes in ____, ____ and major ____ cases
_____ is a concern; however, at doses given during _____ protocols serum levels are well below ____
_____ at risk patients is advised
LIDOCAINE
Not beneficial for all surgical procedures
- Reduces pain and speeds up return of bowel function in laparoscopic cases
- Decreases pain, improves functional outcomes in prostatectomy, thoracic and major spine cases
Accumulation is a concern; however, at doses given during ERAS protocols serum levels are well below toxicity
Monitoring at risk patients is advised
MAGNESIUM SULFATE
Analgesic properties related to:
- Regulation of _____ influx into cells
- Antagonism of ____ receptors in CNS
Dosing
- ____ bolus
- _____ infusion
Studies show a decrease in ____ consumption and pain
Side-effects included ____ and _____
MAGNESIUM SULFATE
Analgesic properties related to:
- Regulation of calcium influx into cells
- Antagonism of NMDA receptors in CNS
Dosing
- 30-50 mg/kg bolus
- 10 mg/kg/h infusion
Studies show a decrease in opioid consumption and pain
Side-effects included bradycardia and hypotension
CAPSAICIN
______channel agonist
• Activation releases high-intensity ___ and release ____
The major pungent ingredient of ____ and ____
Applied _____ for ____ and ____
Available over the counter in:
• ____, _____ and _____ creams and/or _____
CAPSAICIN
Transient receptor potential vanilloid (TRPV1) channel agonist
• Activation releases high-intensity impulses and release substance P
The major pungent ingredient of chili peppers and botanicals
Applied topically for neuralgia and neuropathies
Available over the counter in:
• 0.025%, 0.075% and 0.25% creams and/or transdermal patches
KETAMINE
____ antagonist modulates ____
- Induced by ____ and ____
- Role in preventing opioid-induced ____
Dosing
•_____ prior to surgical incision
Side-effects
- ______
- ____, _____, _____
KETAMINE
NMDA antagonist modulates central sensitization
- Induced by incision and tissue damage
- Role in preventing opioid-induced hyperalgesia
Dosing
• 0.5-1 mg/kg prior to surgical incision
Side-effects
- Psychomimetic
- Dizziness, blurred vision, nausea and vomiting
DEXMEDETOMINDINE
_____agonist
• Blunts _____
Dosing
• _____
Side-effects include:
- _____
- _____
DEXMEDETOMINDINE
Selective alpha – 2 agonist
• Blunts central sympathetic response
Dosing
• 0.5 – 2 ug/kg
Side-effects include:
- Hypotension
- Bradycardia
PERIPHERAL OPIOIDS
Analgesic effects are mediated by ______receptors
Peripherally acting opioids can reduce:
• Plasma _____, ____, ____ neuropeptides, immune ____ and tissue _____
Role in ____ and _____disease
PERIPHERAL OPIOIDS
Analgesic effects are mediated by peripheral opioid receptors
Peripherally acting opioids can reduce:
• Plasma extravasation, vasodilation, proinflammatory neuropeptides, immune mediators and tissue destruction
Role in arthroplasty and inflammatory bowel disease
