HW

Question 1

Buprenorphine

Answer 1

Opioid agonist-antagonist
● High affinity for u-receptor
Routes: IV, Sublingual, Transdermal
● Used to treat chronic pain; higher doses can antagonize the effect of other opioids→ difficulty in treating acute on chronic pain
● Large dose opioid full agonists are needed to overcome its effect due to the high affinity for receptors.

Question 2

magnesium sulfate

Answer 2

Analgesic properties related to regulation of calcium influx into cells & antagonism of NMDA receptors in the CNS
● Systemically administered
○reduction in postoperative opioid requirements approximately equal to ketorolac
○ reports of neurotoxicity, disorientation, and continuous periumbilical burning following injections of neuraxial magnesium

● direct intrathecal administration
○ enhanced antinociceptive effects, an increase in the median duration of analgesia, decrease in opioid consumption by 25%.
○ dose of neuraxial magnesium that confers optimal analgesia with fewest possible side effects remains unclear increased the time to first analgesic request, reduced morphine consumption, and reduced early postoperative pain scores.
○ No increased risk of hypotension, bradycardia, or sedation, but risk of
clinically relevant neurologic injury does exist.

Question 3

Pentazocine:
name its action

tell me about metabolism and ceiling effect?

Answer 3

Possesses weak agonist actions as well as weak antagonist actions
Agonist effects are antagonized by naloxone
80% hepatic first pass metabolism for oral dose
Inactive glucuronide conjugates are excreted in the urine
Ceiling effect at IM dose of 30mg

Question 4

Pentazocine- potency comparable to?

Answer 4

Comparable to codeine in potency

Question 5

pentazocine,

cardiovascular effects?

is it dysphoric or euphoric?

Answer 5

Dysphoria including fear of impending death is associated with pentazocine limiting dependency
Increase concentration of catecholamines leading to increased heart rate, systemic blood pressure, pulmonary artery blood pressure and left ventricular end-diastolic pressure

Question 6

Butorphanol:

receptors?

intranasal route used for?

respiratory depression?

Answer 6

STADOL
Highly lipophilic opioid, synthetic opioid
partial kappa receptor agonist; 
Delta receptor agonist 
weak mu receptor antagonist

more potent than morphine in producing analgesia

causes respiratory depression
intranasal route used in treatment of migraines and post-operative pain
effective in treating post op shivering but MOA is unknown

IV onset =immediate
IV: peak 30 – 60 min
Duration 3 – 4 hours
Epidural single dose: 2 – 4 mg: 
infusion rate: 0.2 – 0.4 mg/h
80% protein binding

Low incidence of dysphoria

Increase heart rate, systemic blood pressure, pulmonary artery blood pressure and cardiac output similar to pentazocine

Question 7

Nalbuphine

Answer 7

Acts as both agonist and antagonist at the opioid receptor
Synthetic Opioid
Has the ability to reverse respiratory depression resulting from opioid use while maintaining analgesia
Analgesic response = to that of morphine
IV or IM
Peak: 1– 3 min (IV), 30 mins (IM)
Duration: 2 – 3 hr (IV), 3.5 – 5 hr (IM)
Equal to morphine in analgesic potency
Agonist reversed by naloxone
Ceiling effect at 30 mg IM
-dysphoria
DOES NOT increase heart rate, systemic blood pressure, pulmonary artery blood pressure and arterial filling pressures
Ideal for sedation in patients undergoing cardiac cath
10 – 20mg can be used to reverse ventilatory depression of fentanyl while maintaining analgesia
Lowers efficacy of subsequent agonists therefore not ideal intraoperatively when agonists are to be used post-operatively

Question 8

Nalorphine

Answer 8

Equally potent to morphine
Not useful due to high dysphoria
High incidence of dysphoria may reflect activity on σ (sigma) receptors
Antagonist actions displace other opioid agonists from µ (mu) receptors

Question 9

Bremazocine

Answer 9

Benzomorphan derivative
Twice a potent as morphine
Has NOT shown respiratory depression or physical dependence in animals
Speculated to work on κ(kappa) receptors
Naloxone fails to reverse sedation from this drug due to naloxone not working is evidence Bremazocine acts on sites other that µ (mu) receptors

Question 10

Dezocine

Answer 10

analgesic potency=morphine
IV 5 – 10 mg onset 15 min
Elimination primary in urine as glucuronide conjugate
High affinity for µ(mu) receptors
Moderate affinity for δ(delta) receptors
Interaction at δ(delta) receptors facilitates the effect of agonist activity at µ (mu) receptors
Minimal dysphoria reflecting low affinity for σ (sigma) receptors.

Question 11

Meptazinol

Answer 11

Partial opioid agonist with relative selectivity at Mu1 receptors
Respiration depression does not occur with analgesic doses
100 mg Meptazinol IM = 8 mg morphine IM
Rapid onset
Duration < 2 hours
Bioavailability orally < 10%
Metabolizes to inactive glucuronide conjugates
Excreted by kidneys
20 – 25% protein binding
No physical dependence
S/E: miosis is slight, constipation is absent, N/V
Not a substitute for opioid agonist in pts with physical dependent on opioids

Question 12

Opioid antagonists (Naloxone, Naltrexone, Nalmefene, Methylnaltrexone, Alvimopan):

Answer 12

Minor changes in the structure of an opioid agonist can convert the drug into an opioid antagonist at one or more of the opioid receptor sites
Naloxone, naltrexone, and nalmefene are pure m opioid receptor antagonists with no agonist activity. These drugs can displace the opioid agonist at the receptor site

Question 13

Naloxone: 1 – 4 mcg/kg

Answer 13

Opioid antagonist (nonselective antagonist at all three opioid receptors)
Blocks opioid receptor sites and reverses respiratory depression and opioid analgesia.
Duration of drug is less than most opioid agonist, therefore may need to re-dose
IV onset: 2 mins and IM onset 5 mins
Peak: 5 – 15 mins
Duration of action: 20 – 60 mins (one book says 30 – 45 min) due to rapid removal from the brain. You will most likely need to give more than one dose depending on duration of opioid agonist
Selective when used to treat opioid-induced depression of ventilation and opioid overdose
5 mcg/kg/hour infusion prevents depression of ventilation without altering analgesia produced by neuraxial opioids
Metabolized primarily in the liver with an elimination half-time of 60 – 90 minutes
Parental dose is far more potent than oral dose due to the first pass effect
Giving naloxone slowly over 2 – 3 minutes decreases incidence of nausea and vomiting
It causes an increase in sympathetic nervous system activity (tachycardia, hypertension, pulmonary edema, and cardiac dysrhythmias) due to sudden perception of pain with reversal of opioid agonist
It can cross the placenta and cause acute withdrawal in neonate with opioid dependent mother
It produces dose-related improvement in myocardial contractility in hypovolemic and septic shock
The occasional observation that high doses of naloxone seem to antagonize the depressant effect of inhaled anesthetics may represent drug-induced activation of the cholinergic arousal system in the brain, independent of any interaction with opioid receptors

Question 14

Naltrexone

Answer 14

similar to naloxone but higher oral efficacy and long duration of action.
Duration of action is approx. 24 hours
Given to patients addicted to opioids to prevent euphoric effects of opioids
Naltrexone, in contrast to naloxone, is highly effective orally, producing sustained antagonism of the effects of opioid agonist for as long as 24 hours
It has found a role in the treatment of alcoholism, possibly by reducing the pleasure associated with ethanol intoxication

Question 15

Nalmefene

Answer 15

Long acting parenteral opioid antagonist
Nalmefene is a pure opioid antagonist and is equally as potent as naloxone
The recommended dose is 15 – 25 mcg administered every 2 – 5 minutes until desired effect is achieved (max dose is 1 mcg/kg)
Prophylactic administration of nalmefene significantly decreases the need for antiemetics and antipruritic medications in patients receiving IV patient-controlled analgesia with morphine
The primary advantage of nalmefene over naloxone is its longer duration of action
Metabolized by hepatic conjugation and less than 5% excreted unchanged in urine
Acute pulmonary edema has occurred after IV administration
Should not be administered to opioid-dependent patients

Question 16

Methylnaltrexone

Answer 16

Methylnaltrexone is a quaternary opioid receptor antagonist and is highly ionized (doesn’t cross BBB easily)
Is active at peripheral rather than central opioid receptors due to its failure to penetrate the CNS sufficiently
It reverses the decrease in gastric emptying seen with morphine and also decreases incidence of nausea potentially without effecting the CNS effects of morphine (still get pain response, but don’t have side effects of nausea and vomiting)

Question 17

Alvimopan

Answer 17

Alvimopan is a newer m-selective oral peripheral opioid antagonist
Metabolism relies on gut flora and has about 6% oral bioavailability
Approved for treatment of post-op ileus and potentially for opioid induced constipation
There is concern for potential increase in cardiovascular events with long-term use

Question 18

Oxymorphone

Answer 18

About 10 times as potent as morphine
Seems to cause more nausea and vomiting
The potential for physical dependence is great
Oral oxymorphone IR (immediate release) produces maximum plasma concentrations in 30 minutes with associated rapid onset of analgesia

Question 19

Oxycodone

Answer 19

Commonly used orally for treating acute pain
Twice as potent as oral morphine and has similar duration of analgesic action
Abuse potential is great

Question 20

Hydrocodone

Answer 20

Commonly used oral opioid for treating acute pain
Similar in potency to oral morphine and similar duration of analgesic action
High abuse potential

Question 21

Methadone

Answer 21

Synthetic opioid agonist that produces analgesia in the setting of chronic pain syndromes
Highly effective by the oral route
The efficient oral absorption, prompt onset of action, and prolonged duration of action of methadone render this an attractive drug for suppression of withdrawal symptoms in physically dependent of person such as heroin addicts

Question 22

Propoxyphene

Answer 22

Structure is similar to methadone
Oral dose of 90 – 120mg has similar CNS effects of 60mg of codeine and 650mg of aspirin
Only clinical use is to tx mild to moderate pain not relieved by aspirin
Does not possess anti-inflammatory/antipyretic effects. Antitussive effects are insignificant
Completely absorbed after oral administration due to extensive first pass hepatic metabolism
demethylation norpropoxyphene
Most common side effects: vertigo, sedation, nausea, and vomiting
OD signs/symptoms: seizures, arrhythmias, and respiratory depression
Abuse is similar to codeine
IV administration severely damages veins and limits abuse by this route
Administration with alcohol = SEVERE drug induced respiratory depression
Voluntarily withdrawn from US market in 2010

Question 23

Heroin

Answer 23

Synthetic opioid produced by acetylation of morphine
Claimed to not have addictive potential
Rapid penetration of heroin into the brain due to its lipid solubility and chemical structure
Hydrolyzed by active metabolites monoacetylmorphine and morphine
Compared with morphine, parenteral heroin has:
Rapid onset
Less opioid induced nausea
Greater potential for physical dependency
Due to Heroin’s liability for physical dependence, it is not available legally for clinical use in the US

Question 24

Clonidine: (neuraxial administration)

Answer 24

Selective partial 𝞪2 receptor agonist
Chronic cancer, noncancer, and postop pain
Epidural dose 75 – 100㎍
Spinal Dose 10 – 50㎍
Synergism with opioids → decreased opioid requirement
Black Box Warning: Neuraxial clonidine with OB → Hemodynamic instability, hypotension, and bradycardia

Question 25

Dexmedetomidine: (neuraxial administration)

Answer 25

High affinity 𝛂2 receptors
Synergism with local anesthetics → prolonging sensory and motor block and improved postop analgesia
decreased intraoperative anesthetics with prevention of awareness and improved post op analgesia
Fewer systemic and hemodynamic side effects than clonodine

Question 26

Neostigmine: (neuraxial administration)

Answer 26

Inhibits acetylcholinesterase and prevents breakdown of acetylcholine
Antinociceptive effects (blockade of painful stimulus) due to stimulation of muscarinic cholinergic receptors
Intrathecal effects:
In combination with local anesthetics or opioids, use prolongs duration of analgesia and improves hemodynamic stability
Reduces amount of morphine needed to provide therapeutic effects
Dose: 10 – 100 mcg
Increases incidence of nausea to 50% to 100%
Reduces ED50 of Sufentanil by 25%
Epidural effects:
Dose 100 – 200 mcg
Reduced adverse effects compared to intrathecal route
Potentiates analgesic effectiveness of opioids and clonidine in the laboring patient
Higher doses can result in mild sedation
Not associated with an increased risk of nausea and vomiting; However, has been associated with sedation due to the high doses used to achieve other therapeutic effects
Meta-analysis showed a marginal improvement of perioperative and peripartum analgesia when compared with placebo
Stimulates bronchial smooth muscle which can lead to bronchospasm
Due to significant side effects, it is an unpopular choice for neuraxial adjuvant therapy

Question 27

Ketamine: (neuraxial administration)

Answer 27

Action: analgesic effects from noncompetitive antagonism of NMDA receptors (Glutamate, Aspartate, and Neurokinin)
Combination of epidural ketamine with local anesthetic and/or opioid infusions results in improved analgesia without significantly increasing adverse effects.
Ketamine acts synergistically with opioid, dopaminergic, serotonergic, and a-amino- 3 hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)
Reported side effects of epidural ketamine include sedation, headache, and transient burning back pain during injection with doses greater than 0.5 mg/kg
There are limited human studies on the use of intrathecal ketamine due to the potential risk of neurotoxicity from its preservative benzalkonium chloride

Question 28

Midazolam

Answer 28

Benzodiazepine that produces analgesic effects by binding to GABA receptors and reducing spinal cord excitability (Cl- ions enter into cell → hyperpolarization)
Some high density GABA-A receptors are found in lamina II of dorsal horn of spinal cord (suggests a possible role in pain modulation)
Benzodiazepines have been shown to also act on pain receptors
Since GABA-A receptors are found in dorsal horn, benzo’s are likely to mediate their analgesic effects by increasing inhibition of nociceptive neurons here
Adding midazolam with bupivacaine in epidural/spinal procedures proves better analgesic effects than just bupivacaine alone
Midazolam added to fentanyl-ropivacaine in epidurals can also decrease PONV (MOA not fully understood)
No sedation reported at 1 – 2 mg (typical induction dose), but is reported at higher doses
Midazolam is more effective in the treatment of somatic pain than visceral pain and can be added with opioids and clonidine for additive effects
Intrathecal administration of midazolam also reduces postoperative analgesic needs

Question 29

Droperidol

Answer 29

Is effective in reducing pruritus and postoperative nausea and vomiting
May be administered by IV, IM, epidural and intrathecal route
Long-term administration of intrathecal droperidol has proved to be an excellent antiemetic in patients with nonmalignant pain
It has been suggested that droperidol exerts direct action on the brainstem chemoreceptor trigger zone
Lack of laboratory data to support safety of neuraxial droperidol which may potentially cause neurotoxicity

Question 30

Adenosine

Answer 30

It is a central acting non-opioid analgesic appeared to be effective in the treatment of neuropathic pain enhancing spinal norepinephrine release
Has antinociceptive activity at adenosine A1 receptors located in the laminae 1 and 2 of the dorsal horn of the spinal cord, adenosine receptors are located in the superficial layers of the dorsal horn.
Intrathecal administration of adenosine in human volunteers has no reported clinical toxicity
May also be given IV, as intramuscular
Intrathecal adenosine does not inhibit acute pain but is effective in treating allodynia and hyperalgesia
Combination of an opioid, with intrathecal adenosine did not prolong analgesia during labor
Intrathecal trials of adenosine 500 – 2000 ug in human volunteers was shown to show a decrease in allodynia in phase 1 clinical trials
Intrathecal adenosine is not associated with hypotension, motor blockade or sedation
The only side effect observed was transient lumbar pain after a dose of 2000 ug 99-101

Question 31

Zinconotide:

Answer 31

Synthetic, derived from an omega conotoxin found in the venom of the marine snail
Selective antagonist
Acts on neuronal (N-type) voltage-sensitive calcium channels within presynaptic neuronal terminals in the dorsal horn → inhibits nerve transmission
Directly inhibits norepinephrine release → decreased mean and diastolic pressure
Narrow therapeutic window
Route:
IV - should be titrated starting at 0.1 mcg/hr
Intrathecal - only nonopioid approved for neuropathic pain
Side effects:
Neuropsychiatric - at high dosages
Intrathecal administration: Dizziness, confusion, ataxia, abnormal gait and memory impairment
Suicidality

Question 32

Xen 2174

Answer 32

Conopeptide derived from a marine snail
Inhibits norepinephrine transport and activate noradrenergic inhibitory pathways → antihyperalgesic, antiallodynic and antinociceptive effects

Question 33

CGX-1160

Answer 33

Conopeptide
Produces analgesia by activation of neurotensin receptor type 1 (NTR1)
Safe for patients with neuropathic pain r/t spinal cord injury
Said to have significant efficacy and superior therapeutic index to ziconotide
Not currently in clinical use

Question 34

Octreotide spinal

Answer 34

Synthetic Octapeptide
Spinal administration produces analgesia
5 years study of intrathecal administration to cancer patients resulted in reduced pain without adverse effects. Another study however showed that at doses > 20 mcg, absence of safety signals
Its role remains undefined in clinical practice

Question 35

Baclofen

Answer 35

GABA-B receptor agonist
Analgesia produced postsynaptically Via GABA-B: increase K conductance —> hyperpolarization. And presynaptically inhibits Ca+ conductance= release of glutamate and substance P
Intrathecal administration superior effect to systemic administration (i.e. 25 to 200 mcg/day Intrathecally through a programmable pump)
Efficacy for chronic pain syndrome related to Multiple Sclerosis and CRPS type I. For somatic pain, treats low back pain with compression syndrome. Specifically used for spasticity and dystonia (Cerebral palsy, spastic posttraumatic spinal cord injury). Relieves central pain syndrome in those patients. Increased efficacy to both nociceptive and neuropathic pain when used with morphine and/or clonidine. Knee arthroplasty study using baclofen as adjuvant spinal bupivacaine reduced opioid use in PACU, less pain for 48 – 72 hours post-op and lessened severity of pain at 3 months after total knee arthroplasty.
S/E: Drowsiness, sedation, nausea, headache, weakness, then rhabdomyolysis and multiple organ failure (in severe cases)

Question 36

Calcitonin

Answer 36

Naturally occurring hormone
Can reduce pain at bony sites
Epidural and intrathecal dose = 100 International unit
S/E: N/V and nervousness (side effects typically exists about 30% when mixed with Bupivacaine)

Question 37

Gabapentin

Answer 37

Acts on voltage-gated Ca++ channels and inhibits glutamate release at the dorsal horn of the spinal cord
PO gabapentin is approved as an anticonvulsant and treats neuropathic pain
Poorly penetrates BBB
Not well absorbed in the GI tract

Question 38

Magnesium Sulfate:

Answer 38

Analgesic properties related to regulation of calcium influx into cells & antagonism of NMDA receptors in the CNS
Systemically administered
show reduction in postoperative opioid requirements approximately equal to that of ketorolac
reports of neurotoxicity, disorientation, and continuous periumbilical burning following injections of neuraxial magnesium
direct intrathecal administration
enhanced antinociceptive effects, an increase in the median duration of analgesia, decrease in opioid consumption by 25%.
dose of neuraxial magnesium that confers optimal analgesia with fewest possible side effects remains unclear
increased the time to first analgesic request, reduced morphine consumption, and reduced early postoperative pain scores.
No increased risk of hypotension, bradycardia, or sedation, but risk of clinically relevant neurologic injury does exist.

Question 39

NSAIDS

Answer 39

NSAIDS are among the most commonly prescribed drugs in the world
Cause COX inhibition and decreased synthesis of prostaglandin.
NSAIDS affect COX-1 which affects platelet aggregation
Associated with a spectrum of Upper GI complications (Ulcers, GI bleeds) Patients with gastrointestinal risks should take a COX-2 selective agent or a non-selective NSAID
Associated with increased risk of cardiovascular adverse events (MI, hypertension, heart failure), AHA recommends using the lowest effective dose
When NSAID therapy is required with patients at risk for CV complications, Naproxen is the drug of choice.
The effects of NSAIDs on renal function are changes in excretion of sodium, changes in tubular function, potential for interstitial nephritis and reversible kidney failure; the risk for kidney injury is increased in hypovolemic patients

Question 40

Acetaminophen:

Answer 40

Tylenol, also known as paracetamol, N-acetyl-p-aminophenol, and nAPAP

• Antipyretic and analgesic but has little, if any, antiinflammatory action
• Leading cause of acute liver failure in the United States, and nearly half of acetaminophen associated cases are due to unintentional overdose
• Central analgesic effect that is mediated through activation of descending serotonergic pathways
• Inhibits COX-3 and, at the spinal cord level, has been shown to antagonize neurotransmission by N-methyl-d-aspartate (NMDA), substance P, and nitric oxide pathways
• First-line analgesic in osteoarthritis and particularly valuable for patients in whom aspirin is contraindicated
• Total daily doses should not exceed 4,000 mg (2,000 mg per day for chronic alcoholics).
• Can be given PO or IV (Ofirmev)
• IV paracetamol provides around 4 hours of effective analgesia for about 37% of patients with acute postoperative pain
• Significant opiate sparing effect
• Damage to the liver results from one of acetaminophen’s metabolites, N-acetyl-p- benzoquinoneimine (NAPQI), NAPQI leads to liver failure by depleting the liver’s natural antioxidant glutathione and directly damaging liver cells, leading to liver failure
• Acetylcysteine is administered as an antidote and acts as a precursor for glutathione and can neutralize NAPQI directly

Question 41

Aspirin

Answer 41

Aspirin is the oldest and most widely used medicinal compound in the world

• Derivative of salicylic acid
• Rapidly metabolized in the plasma (e.g. by plasma esterases), erythrocyte, and liver, to salicylate in vivo
• General analgesic by blocking the action of the COX enzymes and thus prevents the production of prostaglandins
• Irreversibly inactivates COX, leading to prolonged inhibition of platelet aggregation
• The mechanism of NSAID toxicity in overdose is related to both their acidic nature and their inhibition of prostaglandin production

Question 42

Steroids

Answer 42

Glucocorticoids have been used to reduce inflammation and tissue damage for conditions such as inflammatory bowel disease and rheumatoid arthritis
Glucocorticoids have the most powerful antiinflammatory characteristics of all steroids.
Its anti-inflammatory action decreases production of inflammatory mediators that otherwise amplify and pain perception (steroids decrease pain sensation)
Corticosteroids are a subgroup of compounds known as adrenocorticoids, primary corticosteroid is hydrocortisone (standard against which pharmacologic properties of synthetic corticosteroids are judged)
Mineralocorticoids are adrenal cortical hormones, they have a greater effect on water and electrolyte balance; the main endogenous hormone is aldosterone
Nearly all routes of administration can be used for corticosteroids.
Patients can be treated with corticosteroids for pain relief
Patients treated with dexamethasone experienced less post-op pain, required less post-op opioids, and had shorter PACU stays
Dexamethasone also prolongs local anesthetic block durations, interscalene blocks using ropivacaine and bupivacaine
Epidural injection of corticosteroids has been used to treat back pain

Question 43

Lidocaine

Answer 43

Lidocaine produces analgesia by suppressing the activity of sodium channels in neurons that respond to noxious stimuli.
IV lidocaine is useful in treatment of acute pain syndromes like post-op pain, burn pain, and cancer pain.
Orally administered lidocaine has poor bioavailability
Half-life is 1.5 – 2 hours; only 10% of the drug is excreted unchanged by the kidneys, therefore renal impairment has minimal effect on half-life.
At low doses, CNS symptoms include light-headedness, dizziness, tinnitus, vertigo, blurred vision, and altered taste
Seizures occur at higher doses
Cardiovascular side effects include hypotension, bradycardia, and cardiovascular collapse, can lead to cardiac arrest
Can be given locally, IV, regionally, or topically
Topical application of 5% applied as a gel or a patch relieves pain and reduces pain intensity with a fast onset (within 30 minutes); most common side-effects include mild skin reactions; topical route alone is not sufficient for adequate post-op pain management

Question 44

Capsaicin

Answer 44

Capsaicin is a transient receptor potential vanilloid (TPRV1) channels agonist TPRV1 receptors release substance P
Causes initial burning
Continued release of substance P depletes capsaicin, leads to decreased C fiber activation
Capsaicin is the major pungent ingredient of hot chili peppers and other botanicals
Can be applied topically as a cream or patch, used to treat pain from arthritis, myalgias, arthralgies, and neuralgias

Question 45

Ketamine

Answer 45

subanesthetic doses (0.15 – 1mg/kg) used as an adjunct for post op pain in opioid dependent patients
NMDA blocker therefore “modulates sensitization induced both by the incision and tissue damage and by perioperative analgesic such as opioids”
may prevent opioid induced hyperalgesia in patients receiving high doses of opioids for post op pain
clinical use is limited due to adverse effects such as: dizziness, blurred vision, nausea and vomiting. Commonly causes emergence delirium

Question 46

Dexmedetomidine:

Answer 46

Precedex is a highly selective, central α2 agonist
Used for: sedative, pro-anesthetic & pro-analgesic (decrease MAC and dose of opioids), and shivering
It also minimizes opioid-induced muscle rigidity, lessens postoperative shivering, causes minimal respiratory depression, and has hemodynamic stabilizing effects
Use of Precedex with PCA obtained superior analgesic without additional sedation and less nausea

Question 47

Clonidine:

Answer 47

Clonidine:
The use of low doses of clonidine proved to be a useful adjunct analgesic when given neuraxially and in combination with peripheral nerve blocks
Clonidine acts as a selective partial α2 receptor agonist

Question 48

morphine

Answer 48

PROTYPE opioid agonist (if it wasn’t for histamine release than fentanyl wouldn’t have replaces it)
Mu1 and Mu2 receptor site
Slow onset (penetrates CNS slowly)
More effective in relieving continuous dull pain than sharp intermittent pain.
Can be used IM, IV, SubQ, oral, intrathecal, and epidural routes
PO undergoes significant first-pass which limits the bioavailability by 25%
Least lipophilic
Undergoes phase 2 conjugation in the liver
M6G is an active metabolite. (more potent than morphine)
Causes histamine release, resulting in puritis. Sufficient histamine is released in patients may have decreased SVR, hypotension, and tachycardia.
Use caution in renal patients (higher plasma and CSF concentrations reflecting in a smaller Vd)
Depressed the vomiting center in the medulla
S/E: constipation, increase tone and peristaltic activity of the ureter, vasodilation, dysphoria rather than euphoria
GREATER potency and slower speed of offset in women

Question 49

Codeine:

Answer 49

Codeine:
Prodrug
Morphine is the active compound
Suppresses cough at 15 mg
Considered weak opioid
Generally not used for treatment of severe pain
10% of the administered dose of codeine is O-demethylated to morphine, which accounts for its analgesia
Good antitussive, less potent antitussive compared to morphine
Codeine is often combined with acetaminophen for analgesia

Question 50

Hydromorphone:

Answer 50

Hydromorphone:
Derived from morphine in the 1920’s, has a similar profile to that of morphine but is more potent
Due to rapid elimination and redistribution, oral dosing of Q4H is needed to maintain adequate plasma concentrations for analgesia
Large doses have been reported to cause agitation and myoclonus
Oral, rectal, and parenteral use
Because of its lipid solubility it is sometimes used instead of morphine for epidural or spinal administration when a wide area of analgesia is needed
Similar analgesia and side effect profile as morphine and has a FASTER onset
MORE euphoric than morphine
Because of known active metabolites, recommended in patients with renal failure
Available in high potency and sustained release preparations

Question 51

Methadone:

Answer 51

Methadone:
Primarily used for relief of chronic pain, treatment of opioid abstinence syndromes, and treatment of heroin addiction
Well absorbed orally and produces less euphoria
Racemic mixture of two optical isomers
Long half life
Prolonged effect in part due to extensive protein binding (90%)
Advantage of high bioavailability and no active metabolites.
Disadvantages include accumulation and longer time to reach steady state than
other opiods

Question 52

Meperidine:

Answer 52

Meperidine:
Synthetic mu-receptor opioid agonist (has atropine-like antispasmodic effect)
Used to reduce shivering from general and epidural anesthesia by stimulating kappa receptor which reduces or eliminates visible shivering
After demethylation in the liver, it is partially metabolized to normeperidine (which is half as analgesic as meperidine), which lowers the seizure threshold and induces CNS excitability characterized by: tremors, muscle twitches, and seizures.
Normeperidine’s half-life is significantly longer than Meperidine
Caution in renal failure and cancer patients, and has known interactions with MAOIs
Hyperthermia, seizures, and death have been reported with use, so use has declined in the recent years due to having safer and more convenient options
S/E: decreased contractility, mydriasis, tachycardia (due to “atropine like actions”), depresses ventilation more than morphine
But it is shorter acting and less potent than morphine
Crosses placental barrier

Question 53

Alfentanil:

Answer 53

Alfentanil: (dose for intubation: 30 mcg/kg)
Was the first opioid used in modern anesthesia practice
1/5 the potency of fentanyl and 1/3 the duration: more rapid onset but shorter duration than fentanyl (even though it is less lipid soluble)
Effective epidurally but the short duration of analgesia makes it an unpopular choice
Rapid onset and short duration make it ideal for blunting a brief stimulus (tracheal intubation)
Crosses BBB because it is mostly unionized
Metabolized by liver within 60 minutes (through oxidative N-dealkylation and O-demethylation in cytochrome P-450) and the inactive metabolites are excreted through urine
Has a great patient to patient variability with a high coefficient variant
Erythromycin prolongs metabolism and causes prolonged respiratory depression and sedation
Should NOT USE in patients with untreated Parkinson’s Disease (opioid decrease dopaminergic transmission)

Question 54

Fentanyl:

Answer 54

Fentanyl:
Most widely used opioid analgesic in anesthesia
Has many routes: IV, intrathecal, epidural, PCA, patches
Highly effective by oral route
75 – 125 more potent than morphine
Patches: deliver 75 – 100 mcg/hr, peaks at 18 hours, dose is stable during presence of patch, however, after removal there is a 17 hour half-life, but true elimination of fentanyl is about 3 hours (continued reabsorption from the SQ depot during elimination makes it appear longer)
Patch is worn for 3 consecutive days
Bradycardia and depression of ventilation is a concern
Increases ICP in head injuries by 6 – 9 mmHg
Short duration of action and produces a profound dose-dependent analgesia, ventilatory depression, and sedation
High lipid solubility allows for rapid tissue uptake
Highly protein bound (79 – 89%)
Undergoes significant first-pass uptake in the lungs with temporary accumulation before release and is terminated by redistribution
Cleared by hepatic blood flow (metabolized by N-dealkylation and hydroxylation) and inactive metabolites are eliminated in urine and bile
More than 80% leaves plasma after IV injection in less than 5 minutes but plasma concentration is maintained by slow reuptake from inactive tissue sites (reason for prolonged half-life)
Elimination is prolonged in elderly and neonates

Question 55

Remifentanil:

Answer 55

Remifentanil: (induction: 0.5 – 1 mcg/kg)
- MORE potent than alfentanil
Great for retrobulbar block direct laryngoscopy and L&D (less neonatal depression)
Phenylpiperidines
- Mu, Kappa, and Delta Agonist
- Route: IV
- Onset: 1 min, Peak: 1 min, Duration of action: 5 – 10 min
- Maintenance: 0.05 – 2 mcg/kg/min (dose reaches a steady state within 10 minutes of infusion)
Dose based on ideal body weight
Primarily excreted from kidneys
Propofol has a synergistic effect
- Its rapid onset, ultra-short duration, titratability, and simple metabolism make it very convenient for perioperative situations
- Moderately lipophilic, piperidine-derived opioid with ester link
- Easily and rapidly metabolized by blood and tissue esterases
- Small Vd
Less tissue absorption (rapid clearance)
- Metabolized by hydrolysis catalyzed by general esterase enzymes to less active compound
- Not influenced by changes in cholinesterase so Succinylcholine metabolism does not influence remifentanil breakdown
- Potential for respiratory depression, muscle rigidity- bolus dosing not recommended
- Rapid recovery after discontinuation of infusion
- Rapid emergence - develop and start a plan for alternative analgesic therapy in post op period
- Potential for glycine neurotoxicity so should not be administered epidurally or intrathecally

Question 56

Sufentanil:

Answer 56

Sufentanil:
- MOST POTENT opioid agonist used in anesthesia
Decreases cerebral metabolic oxygen demands
Phenylpiperidines
- Mu, Kappa, and Delta Agonist
- Route: IV/Intrathecal
- Onset: 1 – 3min, Duration: dose dependent, Half-life: 6 h
- Induction: 1 – 30 mcg/kg
- Maintenance: 0.005 – 0.015 mcg/kg/min
- Epidural single dose: 25 – 50 mcg
- Epidural infusion rate: 10 – 50 mcg/h
- Subarachnoid single dose: 5 – 10 mcg
- MOST potent of the phenylpiperidines
- Used in cardiac or other major surgical procedures
- High lipophilic/potency, shorter elimination half-life than fentanyl
- Hepatic clearance
- Metabolism > minimal amounts being excreted unchanged in the urine
- The effects of age on the distribution and elimination of sufentanil are reflected in a decrease in the initial volume of distribution for the elderly = increased respiratory depression
5 – 10 more potent than Fentanyl
Rapid penetration to BBB
High protein binding
First pass pulmonary uptake (about 60%) after rapid IV administration

MOST POTENT: sufentanil > fentanyl > remifentanil > alfentanil

Question 57

tramadol

Answer 57

Racemic mixture of 2 enantiomers
- PO Onset: 60 min
PO Peak: 120 min
PO Duration: 9 H
- Synthetic Codeine analog
- Weak Mu receptor agonist with analgesic effects produced by inhibition of norepi and serotonin neuronal reuptake as well as presynaptic stimulation of 5-hydroxytryptamine release
- + enantiomer binds to the mu receptor and inhibits serotonin uptake, - enantiomer inhibits norepi uptake and stimulated a2 adrenergic receptors
- Treats mild to moderate pain (3 mg/kg) but is useful in treating chronic pain as well
- Can cause seizures and possibly exacerbate them in patients with predisposing factors, LOWERS seizure threshold
- Not entirely reversed by naloxone, but tramadol respiratory depression can be reversed
- Overdose - most of toxicity is related to the amine uptake inhibition rather than to opioid effects
Low potential for developing tolerance, dependence, and abuse
Doesn’t cause respiratory depression
INTERACTS with coumadin
Zofran can interfere with analgesic affects

Question 58

Ketorolac (Toradol):

Answer 58

Ketorolac (Toradol):
COX inhibitor
IV or IM NSAID
Treats mild- moderate pain
Used in minor procedures where avoiding opioids is desired
30 – 60mg IM or IV
Onset 30mins
4 – 6 hours duration
Avoid in atopic or asthmatic, renal, GI dysfunction, intracranial surgery, or bleeding disorder patients

Question 59

Ibuprofen:

Answer 59

Ibuprofen:
Analgesic and antipyretic
Similar to Ketorolac
400 – 800 mg IV over 30 mins
Onset is 30 mins
Duration 4 – 6 hours
Precautions and contraindications similar to ketorolac

MOST POTENT PO MEDS:
hydromorphone > oxymorphone > oxycodone > hydrocodone = PO morphine > tramadol > codeine