Pharmacology

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Citation

AMA Citation
Pharmacology. In: Abdi S, Chopra P, Smith H. Abdi S, Chopra P, Smith H Eds. Salahadin Abdi, et al.eds. Pain Medicine Board Review New York, NY: McGraw-Hill; . http://accessanesthesiology.mhmedical.com/content.aspx?bookid=1471&sectionid=85199818. Accessed April 23, 2018.

MLA Citation
. "Pharmacology." Pain Medicine Board Review Abdi S, Chopra P, Smith H. Abdi S, Chopra P, Smith H Eds. Salahadin Abdi, et al. New York, NY: McGraw-Hill, , http://accessanesthesiology.mhmedical.com/content.aspx?bookid=1471&sectionid=85199818.

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Pharmacology

Which of the following is true regarding seizures as one of the multiple side effects from the use of opioids?

(A) Morphine and related opioids can cause seizure activity when moderate doses are given

(B) Seizure activity is more likely with meperidine, especially in the elderly and with renal dysfunction

(C) Seizure activity is mediated through stimulation of N-methyl-d-aspartate (NMDA) receptors

(D) Naloxone is very effective in treating seizures produced by morphine and related drugs including meperidine

(E) Seizure activity is most likely related with the fact that opioids stimulate the production of γ-aminobutyric acid (GABA)

(B) Extremely high doses of morphine and related opioids can produce seizures, presumably by inhibiting the release of GABA (at synaptic level).

Normeperidine a metabolite of meperidine is prone to produce seizures and tends to accumulate in patients with renal dysfunction and in the elderly.

Naloxone may not effectively treat seizures produced by meperidine.

Which of the following is true regarding respiratory depression related to the use of opioids?

(A) Opioid agonists, partial agonists, and agonist/antagonists produce the same degree of respiratory depression

(B) Opioids produce a leftward shift of the CO₂ response curve

(C) Depression of respiration is produced by a decrease in respiratory rate, with a constant minute volume

(D) Naloxone partially reverses the opioid-induced respiratory depression

(E) The apneic threshold is decreased

(E) Opioids produce a dose-dependant respiratory depression by acting directly on the respiratory centers on the brainstem. Partial agonist and agonist-antagonist opioids are less likely to cause severe respiratory depression, as are the selective K-agonist.

Therapeutic doses of morphine decrease minute ventilation by decreasing respiratory rate (as oppose to tidal volume).

Opioids depress the ventilatory response to carbon dioxide; the carbon dioxide-response curve shows a decrease slope and rightward shift.

The apneic threshold is decreased and also the increase in ventilatory response to hypoxemia is blunted by opioids.

Naloxone can effectively and fully reverse the respiratory depression from opioids.

The use of which of the following opioids would produce the greatest incidence of delayed respiratory depression?

(A) 25 μg intravenous (IV) fentanyl (bolus)

(B) 4 mg IV morphine (bolus)

(C) 5 μg IV sufentanil (bolus)

(D) 8 mg epidural, preservative free morphine

(E) 0.05 mg intrathecal, preservative free morphine

(D) Delayed respiratory depression is likely to occur with larger dose of epidural opioids, particularly morphine which is hydrophilic and therefore subject to spread in the cerebrospinal fluid (CSF), reaching the respiratory center in the brainstem.

Intrathecal doses of morphine produce only a uniphasic pattern of respiratory depression.

Opioids in general reduce the sympathetic output and produce a dose-dependant bradycardia, EXCEPT

(A) morphine

(B) fentanyl

(C) meperidine

(D) sufentanil

(E) alfentanil

(C) High doses of any opioid reduce sympathetic output allowing the parasympathetic output to predominate. The heart rate decreases by stimulation of the vagal center, especially with high-doses.

Meperidine because of its similarity to atropine may elevate the heart rate after IV administration.

What is the main mechanism by which opioids produce analgesia?

(A) Coupling of opioid receptors to sodium and potassium ion channels, therefore inhibiting neurotransmitter release (presynaptic) and inhibiting neuronal firing (postsynaptically)

(B) Coupling of opioid receptor to potassium and calcium channels, inhibiting neurotransmitter release (presynaptic), and inhibiting neuronal firing (postsynaptically)

(C) Coupling of opioid receptors to sodium and calcium channels, inhibiting neurotransmitter release (presynaptic), and inhibiting neuronal firing (postsynaptically)

(D) Coupling of opioid receptors to potassium and calcium channels, inhibiting neuronal firing (presynaptically), and inhibiting neurotransmitter release (postsynaptically)

(E) All the options are true

(B) Opioid receptors are coupled to G proteins, able to affect most of the time, protein phosphorylation via a second messenger, thereby altering the conductance of potassium and calcium ion channels. This is believed to be the main mechanisms by which endogenous and exogenous opioids produce analgesia.

The opening of potassium channels—the most well documented—will inhibit the release of neurotransmitters, including substance P and glutamate if the receptors are presynaptic. And will inhibit neuronal firing by hyperpolarization of the cell if the receptors are postsynaptic on the neurons.

Main mechanics of spinal opioid analgesia is via

(A) activation of presynaptic opioid receptors

(B) activation of postsynaptic opioid receptors

(C) activation of opioid receptors on the midbrain

(D) activation of opioid receptors on the RVM

(E) all of the above

(A) The different type of opioid receptors contribute in different proportions to the total opioid receptors in the spinal cord. μ-Receptors constitute 70%, δ-receptors 24% and κ-receptors 6%. The main mechanism of spinal opioid analgesia is through presynaptic activation of opioid receptors.

Opioid receptors are synthesized in small diameter DRG cell bodies and transported centrally and peripherally. They are mainly (70%) located presynaptically on small diameter nociceptive primary afferents (C and A-δ fibers).

Opioids act on what type of receptors targets?

(A) μ-, δ-, κ-, And ORL receptors

(B) Voltage-dependent sodium channels

(C) α_2B-Adrenoreceptors

(D) NMDA receptors

(E) All of the above

(E) Opioids produce analgesia primarily through interaction with μ-receptors. The activation of κ- and δ-receptors also causes analgesia.

The ORL receptor is a member of the opioid receptors, although ligands do not have the same high affinity for this type of receptors, but effects of high-affinity ligands, such as antinociception, proprioception/hyperalgesia, allodynia and no effect have been reported.

Analysis has shown that some opioid actions are not mediated by opioid receptors, morphine can inhibit voltage-dependant sodium (Na) current, meperidine can block voltage-dependant sodium (Na) channels. Meperidine also has agonist activity at the α_2B-adrenoreceptor subtype.

Methadone, meperidine, and tramadol inhibit serotonin and norepinephrin reuptake. High concentrations of opioids, including morphine, fentanyl, codeine, and naloxone directly inhibit NMDA receptor.

Which of the following statements is true regarding the use of oxycodone?

(A) Analgesic efficacy is not comparable with that of morphine

(B) Typically has been used in combination with nonopioids

(C) Not available as a long-acting preparation

(D) Lower bioavailability than that of morphine

(E) Consistently shows a higher induced rate of hallucinations and itching when compared with morphine

(B) Oxycodone a semisynthetic derivative of thebaine and has analgesic efficacy comparable with that of morphine, with a median oxycodone to morphine dose ratio of 1 to 15.

Oxycodone has been typically used in combination with nonopioids (acetaminophen, aspirin) and a long-acting preparation is available, which has popularized its use in cancer patients.

It has a higher bioavailability than that of morphine (approximately 60%).

There are not consistent observations on reduced rate of hallucinations and itching when compared with morphine.

One important characteristic of methadone that has to be considered when prescribing it on an outpatient basis:

(A) Usually there is a low chance for interactions on patients taking multiple medications

(B) Withdrawal symptoms are as severe as with morphine

(C) Rarely used in opioid addiction

(D) Sedation and respiratory depression can outlast the analgesic action

(E) Allows rapid titration

(D) Methadone unlike morphine is metabolized through N-demethylation by the liver cytochrome P-450 enzyme, which activity can vary widely in different people.

Methadone should be administered with caution in patients receiving multiple medications, specially antivirals and antibiotics.

Methadone's withdrawal symptoms tend to be less severe than morphine's, this and its long duration of action, good oral bioavailability, and high potency made it the maintenance drug or detoxification treatment of opioid addiction.

Methadone has biphasic elimination. A long β-elimination phase (ranges from 30 to 60 hours) producing sedation and respiratory depression can outlast the analgesic action which equates the α-elimination phase (6-8 hours).This biphasic pattern explains why methadone is required once a day for opioid maintenance therapy and every 4 to 8 hours for analgesia.

Rapid titration is not possible, making this drug more useful for stable type of pain.

What property of methadone makes it a good option for opioid rotation, when tolerance develops?

(A) Serotonin agonist

(B) α_2B-Adrenoreceptor agonist

(C) μ-Agonist

(D) NMDA agonist

(E) NMDA antagonist

(E) When tolerance to opioids, usually after use over long periods of time, opioid rotation, resting period off opioids, and addition of an NMDA antagonist are a number of strategies available.

Opioid rotation, switching from one opioid to another may be helpful because of partial cross tolerance between opioids. Because methadone has NMDA receptor antagonist properties, makes it a good choice.

Methadone is: μ- and δ-antagonist, NMDA inhibitor, inhibitor of serotonin and norepinephrine reuptake.

Which one of the following is the only opioid with prolonged activity not achieved by controlled-released formulation?

(A) Oxycodone

(B) Fentanyl

(C) Morphine

(D) Codeine

(E) Methadone

(E) Methadone is the only opioid with prolonged activity not achieved by controlled-release formulation.

Oxycodone can be formulated as controlled-release. Codeine half-life is 2 to 4 hours.

Which of the following opioids is used in the office-based treatment of addiction?

(A) Naloxone

(B) Morphine

(C) Tramadol

(D) Buprenorphine

(E) Meperidine

(D) Buprenorphine is a semisynthetic opioid with partial activity at the μ-receptor and very little activity at the κ- and δ-receptors.

It has high affinity but low intrinsic activity at the μ-receptor and has a pharmacologic ceiling owing to its partial agonist activity.

It is available in the United States to be used in the office-based treatment of addiction.

It can be given for withdrawal of heroin or methadone, or used as a maintenance of addicts.

Pharmacologic properties of fentanyl that make it an ideal drug for transdermal and transmucosal administration is

(A) high lipid solubility, high molecular weight, and high potency

(B) low lipid solubility, high molecular weight, and high potency

(C) low lipid solubility, low molecular weight, and low potency

(D) high lipid solubility, low molecular weight, and high potency

(E) high lipid solubility, low molecular weight, and low potency

(D) Fentanyl is a potent mu agonist, with high lipid solubility, low molecular weight and high potency, making it an ideal drug for transdermal and transmucosal administration.

92% of fentanyl delivered transdermally reaches the circulation as unchanged fentanyl.

Transmucosal route at the buccal and sublingual mucosa skips the first pass effect and overall bioavailability is 50%.

Opioids can have drug interactions with

(A) tricyclic antidepressants (TCAs)

(B) selective serotonin reuptake inhibitor (SSRIs)

(C) monoamine oxidase inhibitors (MAOIs)

(D) metoprolol

(E) all of the above

(E) Opioids can have interactions with multiple medications, including all the medications mentioned above.

One of the most remarkable interactions occurs if meperidine and MAOIs are combined, severe respiratory depression or excitation, arrhythmias, delusions, hyperpyrexia, seizures and coma can be seen.

Which of the following is a long and cumbersome research tool for substance abuse and is very good but not very practical in the setting of a busy pain clinic?

(A) Screening Tool for Addiction Risk (STAR)

(B) Severity of Opiate Dependence Questionnaire (SODQ)

(C) Screening Instrument for Substance Abuse Potential (SISAP)

(D) Addiction Severity Index (ASI)

(E) Prescription Drug Use Questionnaire (PDUQ)

(D) The Addiction Severity Index (ASI) is especially effective for evaluating the need for substance-abuse treatment. It is a 200-item, hour-long assessment of seven potential problem areas designed to be administered by a trained interviewer.

An opioid specific five-question self-administered tool which can be completed in less than 5 minutes to help predict patients at high-risk for exhibiting aberrant opioid-related behavior is

(A) Prescription Drug Use Questionnaire (PDUQ)

(B) Opioid Risk Tool (ORT)

(C) Screener and Opioid Assessment for Patients with Pain (SOAPP)

(D) Screening Instrument for Substance Abuse Potential (SISAP)

(E) Severity of Opiate Dependence Questionnaire (SODQ)

(B) The Opioid Risk Tool (ORT) is a five-question self-administered assessment that can be completed in less than 5 minutes and used on a patient's initial visit. Personal and family history of substance abuse; age; history of preadolescent sexual abuse; and the presence of depression, attention-deficit disorder (ADD), obsessive-compulsive disorder (OCD), bipolar disorder, and schizophrenia are assessed. The ORT accurately predicted which patients were at the highest and the lowest risk for exhibiting aberrant, drug-related behaviors associated with abuse or addiction.

The opioid which is largely metabolized by CYP3A4 is

(A) morphine

(B) fentanyl

(C) methadone

(D) hydromorphone

(E) oxymorphone

(B)

Which of the following is correct regarding patients who are prescribed and taking hydrocodone and found to have different opioid in their urine drug-testing results?

(A) Norfentanyl, which is expected

(B) Hydrocodeine, which is expected as a normal metabolite

(C) Hydromorphone, which is expected as a normal metabolite

(D) Hydromorphone, which is unexpected and patient is probably taking another opioid

(E) Hydrocodeine, which is unexpected and patient is probably taking another opioid

(D)

An opioid-specific instrument which may be useful in predicting opioid misuse and is available as a 5-, 14-, or 24-item questionnaire as well as a revised version designed to be less susceptible to overt deception than the original version is

(A) Prescription Drug Use Questionnaire (PDUQ)

(B) Opioid Risk Tool (ORT)

(C) Screener and Opioid Assessment for Patients with Pain (SOAPP)

(D) Screening Instrument for Substance Abuse Potential (SISAP)

(E) Severity of Opiate Dependence Questionnaire (SODQ)

(C) Screener and Opioid Assessment for Patients with Pain (SOAPP) is a survey tool used to predict opioid abuse and is available as a 5-, 14-, 24-item questionnaire. Although the five-item questionnaire [SOAPP V LO-SF (5Q)] is less sensitive and specific than the longer version, it may suffice for use in primary care settings. The SOAPP-SF is scored by adding up the ratings of each of the five questions. The SQ SOAPP uses a cutoff score of 4 or above (of a possible 20) with a score of more than 4, indicating that the subject may have a potentially increased risk of opioid abuse.

A classic example of an opioid partial agonist is

(A) naltrexone

(B) butorphanol

(C) nalbuphine

(D) buprenorphine

(E) pentazocine

(D)

A popular mnemonic for following relevant domains of outcome in pain management for patients on long-term opioid therapy is the so-called 4 A's which include all the following, EXCEPT

(A) analgesia

(B) activities of daily living

(C) adverse events

(D) affect

(E) aberrant drug-taking behaviors

(D)

A popular pain assessment scale which is utilized by preverbal toddler and nonverbal children through age 7 years who may be treated with opioids is

(A) CRIES

(B) APPT

(C) FACES

(D) FLAC C

(E) N-PASS

(D)

The opioid which has some component of metabolism by CYP1A2 is

(A) morphine

(B) fentanyl

(C) methadone

(D) hydromorphone

(E) oxymorphone

(C)

The opioid which is a metabolite of oxycodone via 3-0-demethylation is

(A) hydrocodone

(B) morphine

(C) codiene

(D) hydromorphone

(E) oxymorphone

(E)

Which of the following two opioids are inherently, pharmacologically, and relatively long-acting?

(A) Morphine and oxycodone

(B) Morphine and oxymorphone

(C) Oxycodone and fentanyl

(D) Methadone and levorphanol

(E) Methadone and oxymorphone

(D)

Oral transmucosal fentanyl citrate (OTFC) is applied against the buccal mucosa. The percentage of the total dose which is absorbed from the gastrointestinal (GI) tract but escapes hepatic and intestinal first-pass elimination is

(A) 25%

(B) 33%

(C) 50%

(D) 65%

(E) 75%

(A)

OTFC is applied against the buccal mucosa. The total apparent bioavailability is

(A) 25%

(B) 33%

(C) 50%

(D) 65%

(E) 75%

(C)

The fentanyl buccal tablet (FBT) utilizes an effervescent drug delivery system and achieves an absolute bioavailability of

(A) 25%

(B) 33%

(C) 50%

(D) 65%

(E) 75%

(D)

After intramuscular administration of fentanyl citrate, the time to onset of analgesia is roughly

(A) 1 to 3 minutes

(B) 7 to 15 minutes

(C) 15 to 30 minutes

(D) 20 to 40 minutes

(E) 30 to 50 minutes

(B)

The oral bioavailability of morphine is roughly

(A) 10% to 20%

(B) 25% to 35%

(C) 35% to 45%

(D) 40% to 55%

(E) 50% to 60%

(B)

In humans, methadone acts as

(A) an agonist-antagonist

(B) a pure μ-agonist

(C) a μ-agonist but also with significant actions at the δ-opioid receptor

(D) a μ-agonist but also with significant actions at the κ-receptor

(E) a μ-, δ-, and κ-agonist

(B)

A tool which documents a quantitative assessment of various opioid-adverse effects is the

(A) Pain Assessment and Documentation Tool (PADT)

(B) Translational Analgesic Score (TAS)

(C) SAFE score

(D) Numerical Opioid Side Effect (NOSE)

(E) Severity of Opioid Dependence Questionnaire (SODQ)

(D)

Which of the following is the best opioid to administer for analgesia in a patient with chronic kidney disease stage V?

(A) Codeine

(B) Meperidine

(C) Morphine

(D) Fentanyl

(E) Propoxyphene

(D)

Which of the following is the most prescribed opioid in the United States, which also undergoes O-demethylation to dihydromorphine and its major metabolites excreted into the urine are dihydrocodeine and nordihydrocodeine?

(A) Codeine

(B) Dihydrocodeine

(C) Hydrocodone

(D) Hydromorphone

(E) Morphine

(C)

Which of the following is essentially responsible for opioid-induced respiratory depression?

(A) μ-Receptor

(B) δ-Receptor

(C) κ-Receptor

(D) σ-Receptor

(E) ORL 1 receptor

(A)

Propoxyphene napsylate has a higher maximum daily dose than propoxyphene hydrochloride because

(A) propoxyphene napsylate is less potent than propoxyphene hydrochloride

(B) propoxyphene napsylate is less toxic than propoxyphene hydrochloride

(C) propoxyphene napsylate is cleared faster than propoxyphene hydrochloride

(D) the napsylate salt tends to be absorbed more slowly than the hydrochloride

(E) the napsylate salt makes propoxyphene less active

(D)

When considering opioid rotation to methadone, which of the following is the most appropriate next step?

(A) Maintain the equianalgesic dose

(B) Reduce the dose by 10% to 25%

(C) Reduce the dose by 25% to 50%

(D) Reduce the dose by 50% to 75%

(E) Reduce the dose by 75% to 90%

(E)

When considering opioid rotation to fentanyl, which of the following is the most appropriate step?

(A) Maintain the equianalgesic dose

(B) Reduce the dose by 10% to 25%

(C) Reduce the dose by 25% to 50%

(D) Reduce the dose by 50% to 75%

(E) Reduce the dose by 75% to 90%

(A)

The equianalgesic conversion ratio of oral oxymorphone to intravenous morphine is

(A) 1 to 1

(B) 1 to 2

(C) 1 to 3

(D) 1 to 4

(E) 1 to 5

(A)

By approximately what percentage is codeine ineffective as an analgesic in the Caucasian population owing to genetic polymorphisms in CYP2D6 (the enzyme necessary to O-methylate codeine to morphine)?

(A) 2%

(B) 5%

(C) 10%

(D) 25%

(E) 33%

(C)

Which of the following is the correct statement regarding the pharmacologic properties of NSAIDs?

(A) They readily cross the blood-brain barrier

(B) Their chemical structure consists of aromatic rings connected to basic functional groups

(C) They act mainly in the periphery

(D) They have a high renal clearance

(E) They are not metabolized by the liver

(C) The NSAIDs are weak organic acids, consisting in one or two aromatic rings connected to an acidic functional group. They do not cross the blood-brain barrier, are 95% to 99% bound to albumin, are extensively metabolized by the liver and have low renal clearance (< 10%).

NSAIDs act mainly in the periphery, but they may have a central effect. COX-2 induction within the spinal cord may play an important role in central sensitization. The acute antihyperalgesic action of NSAIDs has been show to be mediated by the inhibition of constitutive spinal COX-2, which has been found to be upregulated in response to inflammation and other stressors.

What are the advantages of COX-2 inhibitors versus NSAIDs?

(A) Protective renal effects

(B) Less GI side effects

(C) Protective cardiovascular effects

(D) Inhibits production of thromboxane A2

(E) Increases production of lipooxygenase

(B) Coxibs do not have any advantages in terms of renal effects.

COX-2 inhibitors are associated with less GI toxicity than standard NSAIDs but they are more expensive.

There is a possible increased risk of myocardial infarction (MI) and thrombotic stroke events associated with the continuosly long-term use of coxibs. Those concerns led to rofecoxib and valdecoxib being withdrawn from the market in the year 2004 and 2005, respectively.

Regular NSAIDs inhibit the synthesis of TXA2 by inhibiting COX-1, which is spared with the use of COX-2 inhibitors.

Which of the following best fits the pharmacologic mechanisms of action of "traditional" NSAIDs?

(A) Inhibition of phospholipase A2

(B) Inhibition of COX-2

(C) Inhibition of lipoxygenase

(D) Inhibition of arachidonic acid

(E) Inhibition of prostaglandin G/H synthase enzymes

(E) NSAIDs inhibits the prostaglandin G/H synthase enzymes, colloquially known as the COX, therefore inhibiting the synthesis of prostaglandin E, prostacyclin, and thromboxane. NSAIDs inhibit the production of not only COX-2 but also COX-1.

Steroids inhibit phospholipase A2.

The main role of prostaglandins in pain is

(A) as important primary pain mediators

(B) sensitization of central nociceptors

(C) sensitization of peripheral nociceptors

(D) facilitation of the production of pain mediators (ie, bradykinin, somatostatin, histamine)

(E) stimulation of κ-receptors on the spinal cord

(C) Prostaglandins are not important primary pain mediators, they do cause hyperalgesia by sensitizing peripheral nociceptors (to mechanical an chemical stimulation) to the effects of pain mediators, such as bradykinin, somatostatin, and histamine, producing hyperalgesia. They do so by lowering the threshold of the polymodal nociceptors of C fibers.

NSAIDs act mainly in the periphery, but they may have a central effect. COX-2 induction within the spinal cord may play an important role in central sensitization. The acute antihyperalgesic action of NSAIDs has been shown to be mediated by the inhibition of constitutive spinal COX-2, which has been found to be upregulated in response to inflammation and other stressors.

The effects of NSAIDs on the kidneys function or renal function may include

(A) increase in renal blood flow

(B) promotion of salt and water excretion

(C) chronic interstitial nephritis

(D) increased glomerular filtration rate (GFR)

(E) chronic papillary necrosis

(C) In the kidney, prostaglandins help to maintain GFR and blood flow.

They also contribute to the modulation of renin release, excretion of water, and tubular ion transport. In patients with normal renal function NSAID-induced renal dysfunction is extremely rare.

Risk factors for NSAID-induced renal dysfunction are:

Prolonged and excessive NSAID use
Older patients
Chronic renal dysfunction
Congestive heart failure
Ascites
Hypovolemia
Treatment with nephrotoxic drugs (aminoglycosides and vancomycin)

In these scenarios NSAIDs may decrease rapidly the GFR, release of renin, which can progress to renal failure. Sodium, water retention, hyperkalemia, hypertension, acute papillary necrosis, chronic interstitial nephritis, and nephrotic syndrome can also occur.

Coxibs (COX-2 inhibitors) have similar renal effects and it should be closely monitored, as is required for conventional NSAIDs.

Platelet dysfunction secondary to the use of NSAIDs is a known effect, in long-term treatment with standard NSAIDs. What laboratory value is most compatible with these effects?

(A) Prolonged prothrombin time (PT)

(B) Prolonged partial thromboplastin time (PTT)

(C) Prolonged activated clotting time (ACT)

(D) Severely prolonged bleeding time

(E) Below the upper limits of normal to mildly prolonged bleeding time

(E) Platelets are very susceptible to COX inhibition, which also inhibits the endogenous procoagulant thromboxane. Long-term use of standard NSAIDs produces a consistently prolonged bleeding time, but the prolongation is mild and values tend to remain below the upper limits of normal.

The duration of aspirin effect is related to the turnover rate of COX in different target tissues, because aspirin

(A) competitively inhibits the active sites of COX enzymes

(B) nonirreversibly inhibits COX activity

(C) irreversibly inhibits COX activity

(D) noncompetitively inhibits the active sites of COX enzymes

(E) acetylates COX-1

(C) Aspirin covalently acetylates COX-1 and COX-2, irreversibly inhibiting COX activity. This makes the duration of aspirin's effects related to the turnover rate of COX in different target tissues.

NSAIDs competitively inhibit the active site of COX enzymes which relates its duration more directly to the time course of drug disposition.

The unique sensitivity of platelets to inhibition by low doses of aspirin (as low as 30 mg/d) is related to

(A) first pass of aspirin through the liver

(B) presystemic inhibition of platelets in the portal circulation

(C) irreversible inhibition of COX

(D) constitutively expression of COX-1 in platelets

(E) good oral absorption

(B) The unique sensitivity of platelets to inhibition by low doses of aspirin, as low as 30 mg/d is related to their presystemic inhibition in the portal circulation before aspirin is deacetylated to salicylate on first pass through the liver.

Aspirin irreversibly inhibits COX activity, making the aspirin's effect related to the turnover rate of COX in different target tissues. Enzyme turnover is most notable in platelets because they are anucleated with a marked limited capacity for protein synthesis. Therefore the inhibition of platelet COX-1 (COX-2 is expressed only in megakaryocytes) last for the lifetime of the platelet, 8 to 12 days (10 days average) after therapy has been stopped.

In general NSAIDs are well absorbed orally, but that is not the reason for high platelet sensitivity to ASA.

How long before surgery NSAIDs are advised to be stopped?

(A) 12 hours

(B) 2 to 3 days

(C) 7 days

(D) 10 days

(E) 14 days

(B) The antiplatelet effect of NSAIDs is rapidly reversible, 24 hours cessation is probably sufficient, although 2 to 3 days cessation is advised.

Aspirin because of its irreversible antiplatelet effect should be stopped 10 days before elective surgery.

Which of the following NSAIDs is as effective as morphine?

(A) Ketoprofen

(B) Indomethacin

(C) Ibuprofen

(D) Ketorolac

(E) Diclofenac

(D) Ketorolac is one of the few NSAIDs that the FDA approved for parenteral use. It is highly efficacious, with efficacy close to that of morphine and other opioids for simple outpatient procedures to major operations.

Ketorolac's side effects, like other NSAIDs include GI bleeding, other bleeding problems, and reversible renal dysfunction (Possibly related with use of high doses or failure to recognize its contraindications).

Nonunion, deleterious effects in bone osteogenesis during bone repair are some other side effects, more likely to occur if ketorolac was administered after surgery, compared with no use of NSAIDs. Decreased posterior spine fusion rates have been demonstrated in rat models, with the long-term use of indomethacin, but even the short-term administration of NSAIDs may possibly significantly affect spinal fusion. These findings have not been confirmed in humans, but many surgeons prefer to avoid the use of NSAIDs in the postoperative period of bone fusion, especially in the spine. COX-2 inhibitors can have similar effects, which is unlikely with short-term perioperative use in humans. No human studies to date document that coxibs have these negative effects in bone healing.

Rare side effect of NSAIDs is

(A) GI side effects

(B) platelet dysfunction

(C) potentially fatal hepatic necrosis

(D) renal dysfunction/failure

(E) all of the above

(C) All are well-known and not uncommon side effects of NSAIDs. Borderline increases of one or more liver tests, may occur in up to 15% of patients taking NSAIDs, approximately 1% of patients taking NSAIDs have shown notable increases in alanine aminotransferase (ALT) or aspartate aminotransferase (AST) (X3 or more the upper limit of normal). These findings may progress, remain unchanged, or be transient with continuing therapy. Rare cases of severe hepatic reactions, including jaundice and fatal fulminant hepatitis, liver necrosis, and hepatic failure (some with fatal outcome), have been reported with NSAIDs.

Which of the following is (are) true regarding oxcarbazepine?

(A) It has more adverse effects than carbamazepine

(B) It is a sodium channel blocker

(C) Oxcarbazepine's dose adjustment is unnecessary for renal insufficiency

(D) Its most frequent adverse effects is weight loss and dizziness

(E) none of the above

(B) Oxcarbazepine [10, 11-dihydro-10-oxo-5H-debenz (b, f) azepine-5-carboxanide] is an analogue of carbamazepine with a keto group at the 10 carbon position. It is roughly 50% protein bound in the plasma. The dose should be at least cut by half if the patient has significant renal insufficiency.

The most frequent adverse effects experienced include dizziness and vertigo, weight gain and edema, GI symptoms, fatigue, and allergic-type reactions. Cross-allergy to carbamazepine occurs in about 25% of patients and may be severe.

Which of the following is a typical adverse effect of pregabalin?

(A) Constipation

(B) Dizziness

(C) Blurred vision

(D) Dry mouth

(E) All of the above

(E)

Which of the following is (are) false regarding gabapentin?

(A) It is a first-line drug for the treatment of PHN and PDN (painful diabetic neuropathy)

(B) Its dose should be reduced in renal insufficiency

(C) It blocks NMDA receptors

(D) It is thought to inhibit voltage-dependent calcium channels

(E) It has a chemical structure similar to that of GABA

(C) A structural analogue of GABA is considered by many practitioners to be a first-line drug for treatment of PHN and PDN because of its tolerability and efficacy. Dose should be reduced in renal dysfunction. Dose increases are usually made every 3 to 4 days.

Which of the following is true about zonisamide?

(A) It is a sulfonamide drug

(B) It is a sodium channel blocker

(C) It is 40% to 50% protein bound

(D) It may potentially lead to renal calculi

(E) All of the above

(E)

Which of the following is true about antiepileptic drugs (AED)?

(A) AEDs have analgesic effect in all subjects with neuropathic pain

(B) If one AED is ineffective, it is not necessary to try another one

(C) Newer AEDs have more side effects than older ones

(D) AEDs could be combined with antidepressants to treat neuropathic pain

(E) All of the above

(D)

The antidepressant with the least anticholinergic and least sedating effect is

(A) trazodone

(B) desipramine

(C) imipramine

(D) doxepin

(E) amitriptyline

(B) Anticholinergic side effects are generally very significant for TCAs.

Which of the following antidepressant agent selectively inhibits serotonin reuptake with minimal effect on norepinephrine reuptake?

(A) Duloxetine

(B) Protriptyline

(C) Paroxetine

(D) Amoxapine

(E) Desipramine

(C) Antidepressants which selectively inhibit serotonin with minimal effects on norepinephrine reuptake are referred to as SSRIs (eg, paroxetine). Protriptyline, desipramine, and amoxapine are secondary amine TCAs. Duloxetine inhibits both norepinephrine and serotonin (SNRIs).

The most common adverse effects associated with TCA are (is)

(A) anticholinergic effects

(B) seizures

(C) arrhythmias

(D) hepatotoxicity

(E) nephrotoxicity

(A) Side effects of antidepressants include anticholinergic effects, antihistaminergic effects, α₁-aderenergic receptor bloackade, and cardiac effects. Individual may possess significant side effects in one specific area (eg, doxepin is a strong antihistaminergic agent). As a generalization, the most common adverse effects associated with TCAs are anticholinergic in nature.

The least common adverse effects associated with TCA are (is)

(A) dry mouth

(B) seizure

(C) urinary retention

(D) blurred vision

(E) aconstipation

(B)

Compared to TCAs, SSRIs

(A) are more effective in the treatment of pain

(B) have more side effects

(C) have less side effects

(D) have more serious consequence of overdosage

(E) none of the above

(C)

Which of the following is false regarding tramadol?

(A) It has opioid characteristics

(B) There is a dose limit of 400 mg/d

(C) It is a centrally acting analgesic

(D) No effect on norepinepherine or serotonin

(E) Inhibits the reuptake of norepinephrine and serotonin

(D) Tramadol hydrochloride is a centrally acting analgesic which is thought to provide analgesia via at least two mechanisms: some analgesia may be derived from the relatively weak interaction of tramadol with the μ-opioid receptor. The second and major mechanism, which is thought to account for at least 70% of tramadol' s analgesic activity, is via inhibiting the reuptake of norepinephrine and serotonin.

The benzodiazepine which is used to treat various neuropathic pain syndromes is

(A) diazepam

(B) midazolam

(C) clonazepam

(D) flunazepam

(E) lorazepam

(C) Clonazepam is a benzodiazepine—which binds to the GABA_B receptor (other benzodiazepines bind to the GABA_A receptor) and has been utilized to treat various neuropathic pain syndrome and lower extremity muscle conditions.

Which of the following about carisoprodol is true?

(A) Naloxone may be a useful antidote to its toxicity

(B) Flumazenil may be a useful antidote to its toxicity

(C) It is safe to use as a long-term treatment of musculoskeletal disorders

(D) It is a GABA_B receptor agonist

(E) It has no abuse potential

(B) Carisoprodol may be useful for the short-term treatment of acute musculoskeletal disorders, especially in combination with acetaminophen, aspirin, or NSAIDs. Carisoprodol is primarily metabolized in the liver to several metabolites, including meprobamate. This metabolic conversion, although relatively small, has been postulated to be the reason that carisoprodol may have abuse potential. The formation of meprobamate from carisoprodol is by N-dealkylation via CYP2C19. Poor metabolizers of mephenytoin have a diminished ability to metabolize carisoprodol and therefore may be at increased risk of developing concentration-dependent side effects (eg, drowsiness, hypotension, CNS depression) at "usual" adult doses.

Although the precise mechanisms of action of carisoprodol (as well as meprobamate) are uncertain, one theory is that they act as indirect agonists at the GABA_A receptor, yielding CNS chloride ion channel conduction effects similar to benzodiazepines. Therefore, flumazenil may be a potentially useful antidote to carisoprodol toxicity.

Which of the following is true regarding tizanidine?

(A) It is structurally related to clonipine

(B) It is GABA_B receptor agonist

(C) It is GABA_A receptor agonist

(D) Its excretion occurs primarily through the liver

(E) It is α₂ agonist

(E) Tizanidine is an imidazoline derivative that is structurally related to clonidine. Its action is primarily derived from agonism at the α₂-adrenoreceptor.

Metabolism of tizanidine occurs primarily in the liver through oxidative processes, and metabolites of the parent compound have no known pharmacologic activity. Excretion of tizanidine and its metabolites occurs primarily via the kidneys (53%-66%).

Which of the following is a false statement about ziconotide?

(A) It is derived from conus sea snail venom

(B) It is the synthetic form of cone snail peptide (conotoxin)

(C) It is effective when given intravenously or orally

(D) It is N-type calcium channel blocker

(E) Its common side effects are dizziness, confusion, and headache

(C)

Which of the following is true regarding capsaicin?

(A) It is a member of the vanilloid family which binds to the TRPV1 receptor

(B) It is commercially available in 0.025% and 0.075% concentrations

(C) It is the active component of chili peppers

(D) It depletes presynaptic substance P

(E) All of the above

(E)

The following are some of the side effects of lidocaine 5% patches, EXCEPT

(A) methemoglobin

(B) edema

(C) erythema

(D) abnormal sensation

(E) exfoliation

(A)

Calcitonin may be used as an adjuvant drug for all the following, EXCEPT

(A) phantom limb pain

(B) sympathetically maintained pain

(C) cancer bone pain

(D) postoperative pain

(E) osteoporosis pain

(D)

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