Analgesics and NSAIDs Flashcards
Which pathway produces the toxic metabolite in paracetamol overdose?
A N-hydroxylation
B Glucoronidation
C Conjugation with glutathione
D Sulfation
A
Explanation
N-hydroxylation forms the NAPQI toxic metabolite, which leads to liver failure
Normally acetaminophen is metabolized via glucuronidation (40% to 67%), sulfation (20–40%), and N-hydroxylation/rearrangement/GSH conjugation (less than 15%). With excessive dosing of acetaminophen, the glucuronide and sulfate conjugation pathways become saturated, and increasing amounts of acetaminophen then undergoes N-hydroxylation (CYP-mediated) to form NAPQI, which is a toxic metabolite.
Regarding aspirin, which of the following statements is correct?
A It has a pKa of 6.5
B In moderate doses it increases respiratory rate
C Alkalinising the urine will decrease excretion
D It is a reversible inhibitor of cyclo-oxygenase
B
Explanation
Aspirin has a pKa of 3.5. It is an irreversible inhibitor of cyclo-oxygenase and, at moderate doses, causes an increased respiratory rate. In higher doses a respiratory alkalosis occurs followed by a metabolic acidosis. Alkalinising the urine will increase excretion of aspirin. Aspirin effects last the life of platelets which is 8-10 days. Aspirin demonstrates capacity limited clearance at low doses. I.e. saturable elimination at low doses
Regarding ketamine, which of the following statements is correct?
A It is a cardiovascular stimulant via a central mechanism
B It causes a brief period of increased respiratory rate
C It possesses no analgesic properties
D It decreases cerebral blood flow
A
Explanation
Ketamine is closely related to phencyclidine. It produces a dissociative amnesic anaesthetic state characterised by: catatonia, amnesia, and analgesia without the loss of consciousness (hypnosis). It binds to the NMDA receptor. It stimulates the cardiovascular system (+inotropy) via the central sympathetic nervous system. It causes a decrease in respiratory rate but preserves respiratory reflexes and produces bronchodilation. Ketamine inhibits histamine release. CNS effects include an increase in blood flow to the brain, brain oxygen consumption and intracranial pressure. Side effects include agitation and emergence phenomenon in children.
Which of the following is FALSE regarding the pharmakokinetics of morphine?
A Enterohepatic circulation of morphine represents a large proportion of the excretory process.
B Drug concentration in muscle may be much lower but this tissue still serves as the main reservoir because of its greater bulk.
C Metabolism is mainly in the liver (polar metabolites: glucuronides)
D Small amount of unchanged drug may be found in the urine
A
Explanation
Morphine has a high first pass metabolism; therefore the oral dose may need to be greatly increased (as compared to the parenteral dose) to achieve a therapeutic effect. Although all opioids bind to plasma proteins with varying affinity, the drug rapidly leaves the blood compartment and localises in tissues that are highly perfused e.g. brain, liver, kidneys and spleen. Drug concentration in muscle may be much lower but this tissue still serves as the main reservoir because of its greater bulk. Metabolism is mainly in the liver (polar metabolites: glucuronides) and excretion via the kidneys. Small amount of unchanged drug may be found in the urine. In addition, glucuronide metabolites are found in bile, but enterohepatic circulation represents only a small proportion of the excretory process.
Ketamine is chemically related to which of the following?
A Phencyclidine
B LSD
C Thiopentone
D Propofol
A
Explanation
Ketamine is closely related to phencyclidine. It produces a dissociative amnesic anaesthetic state characterised by: catatonia, amnesia, and analgesia without the loss of consciousness (hypnosis). It binds to the NMDA receptor. It stimulates the cardiovascular system (+inotropy) via the central sympathetic nervous system. It causes a decrease in respiratory rate but preserves respiratory reflexes and produces bronchodilation.Ketamine inhibits histamine release . CNS effects include an increase in blood flow to the brain, brain oxygen consumption and intracranial pressure. Side effects include agitation and emergence phenomenon in children.
A high degree of tolerance can be expected to all these effects of morphine EXCEPT?
A Analgesia
B Miosis
C Cough supression
D Nausea
B
Explanation
Tolerance does not occur with miosis, constipation and convulsions
There is only a moderate degree of tolerance to bradycardia
High tolerance to analgesia, euphoria, mental clouding, sedation, respiratory depression, antidiuresis, nausea and vomiting and cough suppression
Why is methadone is used in the treatment of narcotic addiction?
A It does not produce constipation
B It is a phenylpiperadine class narcotic agonist
C Tolerance and physical dependence develop more slowly with methadone
D It produces a short withdrawl when ceased
D
Explanation
Methadone produces a milder but longer withdrawal when stopped than morphine. It has proven to be beneficial in treating chronic pain when morphine has failed. Pethidine is a phenylpiperadine class narcotic agonist. A side effect of methadone is constipation. Methadone is widely used in the treatment of opioid abuse. Tolerance and physical dependence develop more slowly with methadone than with morphine. The withdrawal signs and symptoms occurring after abrupt discontinuation of methadone are milder, although more prolonged, than those of morphine. These properties makes methadone useful drug for detoxification and for maintenance of chronic relapsing heroin addict.
Methadone is not a phenylpiperadine. It is a phenylheptylamine.
What effects do kappa receptors mediate?
A Slows gastrointestinal transit
B Antidepressant effects
C Respiratory depression
D Physical dependence
A
Explanation
Kappa receptors mediate supraspinal analgesia, spinal analgesia, psychotomimetic effects, slow gastrointestinal transit, inhibit ADH release, cause miosis, sedation and dysphoria
Mu receptors - decreases respiration, supraspinal and spinal analgesia, sedation, slow GIT transit, modulation of hormone and neurotransmitter release, causes physical dependence, miosis and euphoria,
Delta receptors - supraspinal and spinal analgesia, and modulation of hormone and neurotransmitter release
Redarding allopurinol, which of the following statements is correct?
A It is metabolised by xanthine oxidase
B It has no side effects
C It is useful in acute gout
D It has a low oral bioavailability
A
Explanation
Allopurinol is not useful in acute attacks but rather the period between attacks of gout. It can cause a gouty arthritis when initially started.
You need to take colchicine and NSAIDS concurrently. It has a bioavailability of 80%, its half life 1-2 hrs and is metabolized by xanthine oxidase but the resulting compound, alloxanthine, retains the capacity to inhibit xanthine oxidase and has a long enough duration of action so that allopurinol can be given once a day. Side effects include GIT intolerance, depression of bone marrow, hepatic toxicity and renal disease.
By inhibiting xanthine oxidase, those purine ribonucleotides not incorporated into nucleic acids are NOT oxidised to uric acid.
Like uric acid, allopurinol is metabolised by xanthine oxidase, but the resulting compound, alloxanthine, retains the capacity to inhibit xanthine oxidase and has a long enough duration of action so that allopurinol is given only once a day
Regarding paracetamol toxicity which of the following statements is correct?
A Enhanced with cimetidine
B Toxic metabolite is due to sulphanation
C Toxicity is related to glutathione consumption
D N-acetylation produces the toxic metabolite
C
Explanation
Acetaminophen is conjugated to harmless glucuronide and sulfate metabolites when taken at normal doses. If abnormal doses are taken the metabolic pathways are overwhelmed and a P450-dependant system converts some of the drug to NAPQI, a reactive intermediate. NAPQI is conjugated with glutathione to a third harmless product if the stores of glutathione are adequate. If the stores are exhausted, the NAPQI combines with essential hepatic cell proteins causing hepatic cell death. Administration of other sulhydryl donors e.g. acetylcysteine may be life saving. Enzyme inducers may increase acetaminophen toxicity because they increase phase I metabolism more than phase II thus resulting in increased production of NAPQI
Note: the toxic pathway is N-hydroxylation, not N-acetylation.
Regarding paracetamol, which of the following statements is correct?
A It is only given orally
B It is highly protein bound
C It is hydrophobic
D It doesn’t cause hyperuricaemia
D
Explanation
Paracetamol can be given orally, IVI and rectally. It is slightly protein bound. Half-life is 2-3hrs and is relatively unaffected by renal fucntion.
The experimental value of octanol water partition co-efficient (log Pow) of paracetamol is 0.46 at temperature 25 degC. This value indicates that paracetamol is hydrophilic in nature.
Regarding ibuprofen, select the correct answer
A It causes more gastric side effects than aspirin
B It has a low bioavailability
C It is not effective in closing the patent ductus arteriosis in the preterm infant
D It is a non selective COX inhibitor
D
Explanation
Ibuprofen is more than 99% protein bound, is rapidly cleared and has a terminal half-life of 1-2hrs. It is a reversible inhibitor of COX1 and COX 2. GIT irritation and bleeding do occur, but with less frequency than aspirin. Its bioavailability is 50-73%. It may cause closure of the patent ductus arteriosis
Regarding dextropropoxyphene, which of the following statements is correct?
A When combined with paracetamol is a strong anti inflammatory
B Overdose causes death from hepatotoxicity
C It is a strong opiod
D It is structurally related to methadone
D
Explanation
Dextropropoxyphene is a centrally acting, synthetic opioid analgesic structurally related to methadone. Combination with paracetaomol produces extra pain relief but no anti-inflammatory actions. The potency of the drug is about two thirds that of codeine.
Note: Overdose results in hepatoxicity (due to paracetamol) and CNS depression (due to opioid overdose). However, death due to overdose is usually because of Cardio-respiratory depression.
Regarding opioid agonists and antagonists, which is INCORRECT?
A Codeine is a strong opioid agonist
B Naloxone is a pure antagonist
C Buprenorphine is an agonist-antagonist opioid
D Nalmefene is available only in IVI preparation
A
Explanation
Codeine is a partial agonist. It is less efficacious than morphine. It can antagonize strong agonists.
Buprenorphine is a partial mu agonist and a kappa antagonist.
Naloxone and naltexone are pure antagonists.
Nalmefene, the newest of the opioid antagonists is only available in IVI preparation.
Note:
Nalmefene is available in an oral formulae 10mg, however it is not PBS listed (as of 2015) in Australia
The current textbook says that is only available as an IVI formulae. For exam purposes this would have to be true
Extra: Codeine’s predominant analgesic effect comes from metabolism to morphine via CYP2D6.
Regarding dextropropoxyphene, which of the following statements is false?
A It produces greater pain relief when used with paracetamol
B It should never be used in patients with renal failure
C It has no anti-inflammatory properties
D It is structurally similar to methadone
B
Explanation
Dextropropoxyphene is a centrally acting, synthetic opioid analgesic structurally related to methadone. Combination with paracetaomol produces extra pain relief but no anti-inflammatory actions. The potency of the drug is about two thirds that of codeine. In patients with renal failure it should be used with caution as since higher concentration or delayed excretion may occur.
An old question. The never statement is false: it can be used but with caution
Later TB editions state that due to its low analgesic properties and misuse, it has been withdrawn
Regarding ketamine, which of the following statements is correct?
A It is a bronchoconstrictor
B It increases respiratory rate initially
C It can cause agitation and an emergence phenomina in children
D It has no cardiovascular effects
C
Explanation
Ketamine is closely related to phencyclidine. It produces a dissociative amnesic anaesthetic state characterised by: catatonia, amnesia, and analgesia without the loss of consciousness (hypnosis). It binds (inhibits) to the NMDA receptor. It stimulates the cardiovascular system (+inotropy) via the central sympathetic nervous system. It causes a decrease in respiratory rate but preserves respiratory reflexes and produces bronchodilation. Ketamine inhibits histamine release. CNS effects include an increase in blood flow to the brain, brain oxygen consumption and intracranial pressure. Side effects include agitation and emergence phenomenon in children.
Extra: Ketamine is partially water-soluble and highly lipid soluble, low protein binding 12%, metabolised in the liver to an active (although less potent metabolite-norketamine) and renally excreted. The effects of a single bolus injection is terminated by redistribution to inactive tissue sites
Extra:McGraw text: “Unpleasant emergence reactions after administration are the main factor limiting ketamine’s use. Such reactions may include vivid colorful dreams, hallucinations, out-of-body experiences, and increased and distorted visual, tactile, and auditory sensitivity. These reactions can be associated with fear and confusion, but a euphoric state may also be induced, which explains the potential for abuse of the drug. Children usually have a lower incidence of and less severe emergence reactions.”
Regarding Methadone, which of the following is true?
A It has a lower bioavailability than morphine
B It binds to opioid and non opioid receptors
C Withdrawal symptoms are less prolonged than with morphine
D Half life of methadone 12-24hrs
B
Explanation
Methadone is well absorbed from the GIT tract. Its bioavailability far exceeds that of morphine. It is an agonist at the mu receptors and an antagonist at the non opioid receptors including NMDA and monoaminergic reuptake receptors. These receptor properties may explain methadone’s ability to treat chronic pain and cancer patients when regular opioids have failed. It has a long half life of 25-52hrs.
Tolerance and physical dependence develop more slowly with methadone than with morphine. Withdrawal symptoms following an abrupt stopping of methadone produce milder but more prolonged symptoms than morphine withdrawal. Theses properties make methadone a useful drug for detoxification and for maintenance for the chronic relapsing heroin addict.
For detoxification of a heroin addict, methadone (5-10mg) is given 2-3 times daily for 3 days. Duration of action is 4-8 hrs. Upon discontinuing methadone, the patients experiences a mild but endurable withdrawal syndrome.
To which of the following does opioid tolerance not occur?
A Cough suppression effect
B Hypotensive effect
C Respiratory depression effect
D Miotic effect
D
Explanation
Opioid tolerance developes to the analgesic, sedating and respiratory depressant effects. Tolerance also develops to the antidiuretic, emetic, cough suppression and hypotensive effects but not to the miotic, convulsant and constipating actions
Explanation:
Opioids when used chronically, the patient will develop tolerance to its effects. Tolerance will develop to the physiological effects of opioids and euphoric, analgesic effects. However, no matter how often/long you use opioids or how high the dose is, you will not get a physiological tolerance to miosis of the pupil, you will still get constipated and you can still convulse. Your body cannot over come these side effects (cannot build a tolerance to them)
Regarding ibuprofen, which of the following statements is correct?
A It has a half life 2 hours
B Urinary excretion of unchanged drug is 20%
C Eating the drug with food significantly lowers its bioavailability
D It is a strong organic acid
A
Explanation
Ibuprofen, like most NSAIDS is absorbed well orally and food does not substantially change its bioavailability. All but one are weak organic acids- nabumetone. Ibuprofen has a half life of 2hrs and is urinary excretion of unchanged drug is <1%. Interestingly, Ibuprofen in doses <600mg QID has analgesic and no anti-inflammatory properties.
Regarding naloxone, which of the following statements is correct?
A It has a half life of less than one hour
B It has a half life of between 2 and 3 hours
C It has a half life of between 3 and 4 hours
D It has a half life of between 1 and 2 hours
D
Explanation
Naloxone has a duration of action of 1-2 hours when given by injection and 10 hours when taken via the oral route. Although naloxone is well absorbed via the oral route it undergoes rapid first pass metabolism. There is no tolerance to the antagonistic action of these agents, nor does withdrawal after chronic administration precipitate an abstinence syndrome.
MIMS reports the half-life of Naloxone to be about 60min in adults with a range of 30-80 minutes, and about 3hrs in neonates
The current TB states that Naltrexone has a half-life of 10hrs. The elimination half-life is 60-90min
Which opioid analgesic has the longest duartion of analgesia?
A Morphine
B Codeine
C Methadone
D Buprenorphine
D
Explanation
Buprenorphine= 4-8hrs
Methadone= 4-6hrs
Morphine= 4-5hrs
Codeine= 3-4hrs
Note: that the half life of methadone 25-52 hrs, but the duration of action is only 4-8hrs
Which is true regarding common opioid analgesics?
A Morphine has analgesic effects on mu, kappa and delta receptors
B Sufentanil can be given orally and intravenously
C Alfentanil has the shortest duration of analgesia
D Codeine is a weak full mu receptor agonist
D
Explanation
Morphine has analgesic effects on the mu receptor. Although it is an agonist to kappa and delta receptors as well, there is doubt as to the actual analgesic action it produces at these receptor sites. Morphine has analgesia duration of 4-5hrs. Codeine is a weak full mu receptor agonist. Sufentanil is a mu, kappa and delta receptor agonist. Methadone is a mu receptor agonist. Sufentanil can only be given parenterally. Remifentanil has the shortest duration of analgesia-0.05hrs. Buprenorphine has the longest duration of analgesia-4-8hrs. Alfentanil has analgesia duration of 0.25-0.75hrs.
Extra:
Kappa receptors mediate supraspinal analgesia, spinal analgesia, psychotomimetic effects, slow gastrointestinal transit, inhibit ADH release, cause miosis, sedation and dysphoria
Mu receptors - decreases respiration, supraspinal and spinal analgesia, sedation, slow GIT transit, modulation of hormone and neurotransmitter release, causes physical dependence, miosis and euphoria
Delta receptors - supraspinal and spinal analgesia, and modulation of hormone and neurotransmitter release
Extra:
The most recognized full agonist opioids are heroin, morphine, codeine, oxycodone, meperidine, and fentanyl
Source: full opioid agonists and Tramadol: Pharmacological and clinical considerations. Edinoff etal
Which of the following is TRUE regarding the pharmakokinetics of morphine?
A No amount of unchanged drug is be found in the urine
B Morphine has a high first pass metabolism
C Enterohepatic circulation of morphine represents a large proportion of the excretory process.
D 60% bound to plasma proteins
B
Explanation
Morphine has a high first pass metabolism; therefore the oral dose may need to be greatly increased (as compared to the parenteral dose) to achieve a therapeutic effect. Although all opioids bind to plasma proteins with varying affinity, the drug rapidly leaves the blood compartment and localises in tissues that are highly perfused e.g. brain, liver, kidneys and spleen. Drug concentration in muscle may be much lower but this tissue still serves as the main reservoir because of its greater bulk. Metabolism is mainly in the liver (polar metabolites: glucuronides) and excretion via the kidneys. Small amount of unchanged drug may be found in the urine. In addition, glucuronide metabolites are found in bile, but enterohepatic circulation represents only a small proportion of the excretory process.
Which of the following opioids have only INACTIVE metabolites?
A Oxycodone
B Morphine
C Codeine
D Methadone
D
Explanation
Morphine=hydromorphone.
Codeine= morphine
Oxycodone= oxymorphone.
Pethidine = norpethidine
Unlike codeine, morphine, hydromorphone, pethidine or oxycodone-methadone has no active metabolites and is therefore a good choice for patients at risk for toxicity from metabolite accumulation
Extra:
Morphine is primarily conjugated to morphine-3-glucuronide (M3G), a compound with neuroexcitatory properties. 10% of morphine is metabolised to morphine-6-glucuronide (M6G), an active metabolite with analgesic potency of four to six times that of its parent compound. These relative polar metabolites have limited ability to cross the BBB and probably do not contribute significantly to the usual CNS effects of a single dose of morphine. More importantly, accumulation of these metabolites may produce unexpected adverse effects in patients with renal failure or when exceptionally large doses of morphine are administered or high doses are administered over long periods. This can result in M3G-induced CNS excitation (seizures) or enhanced and prolonged opioid action produced by M6G.
Which of the following statements regarding Naloxone is false?
A Naloxone has equal affinity for mu, kappa and delta receptors
B Tolerance to naloxone does not develop
C Naloxone is a pure antagonist
D Intravenous administration reverses opioid effects in 1-2min
A
Explanation
Naloxone is a pure antagonist. It has a very high affinity for mu receptors and a lower affinity for the other receptor binding sites but can also reverse agonists at deltas and kappa sites. Naloxone has a half life of 1-2 hours when given by injection and 10 hours when taking via the oral route. Although naloxone is well absorbed via the oral route it undergoes rapid first pass metabolism. IVI administration reverses opioid toxicity in 1-3 minutes. There is no tolerance to the antagonistic action of these agents, nor does withdrawal of naloxone after chronic administration precipitate an abstinence syndrome
Have a better explanation? Submit your own
Peak blood concentration of acetaminophen following oral route is achieved in?
A 30-60min
B 10-15min
C 10-30min
D 20-40min
A
Explanation
Peak blood concentration of acetaminophen following oral route is usually achieved in 30-60min. IVI route takes 15min, however the analgesic effect does not last as long via the IVI route
Opioid metabolism includes the following
A Morphine metabolites are able to cross the blood brain barrier and do not contribute to the significant CNS effects that are seen with morphine.
B Remifentanil is rapidly hydrolysed by common blood esterases into morphine
C There are no active metabolites of morphine
D Codeine undergos hepatic metabolism by the P450 system
D
Explanation
The opioids are largely converted to polar metabolites (mostly glucuronides), which are then excreted by the kidney. 10% of morphine is metabolised to morphine 6 glucuronide, an active metabolite with 4-6x the potency of its parent compound.
Note, these metabolites are not readily able to cross the blood brain barrier and do not contribute to the significant CNS effects that are seen with morphine. Nevertheless accumulation of these metabolites can produce unwanted side effects in patients with renal failure and when large doses of morphine are given over long periods.
Although both heroin and remifentanil are metabolized by blood and non-specific tissue esterases, they do not result in the same metabolites. Heroin is ultimately metabolized to morphine (which then undergoes hepatic metabolism), whereas remifentanil is metabolized to a carboxylic acid derivative (remifentanil acid) which is excreted by the kidneys.
Hepatic oxidation is the prime route of degradation for the phenylpiperidine opioids (remifentanyl, fentanyl, alfentanyl, and sufentanyl). This leaves only a small amount of parent drug for renal excretion. There are no active metabolites of fentanyl
Codeine, oxycodone and hydrocodone undergo hepatic metabolism by the P450 system resulting in metabolites of grater potency.
The NSAID with the least gastro-intestinal upset is
A Ibuprofen
B Aspirin
C Indomethacin
D Naproxen
A
Explanation
Ibuprofen in doses of 2.4g a day are anti-inflammatory. Doses less than this are analgesic and not anti-inflammatory.
Indomethacin at normal doses cause the usual GIT side effects including pancreatitis.
Naproxen’s incidence of GIT bleeding is double that of ibuprofen
Ketoprofen is not superior to other NSAIDS in clinical effectiveness. GIT complications are common
Aspirin causes about double the gastric ulcers as compared to ibuprofen at normal doses
Extra:
The relative risk of upper gastrointestinal complications for aceclofenac, celecoxib and ibuprofen is low (<2). Diclofenac, meloxicam and ketoprofen are intermediate (2–4) while naproxen, indomethacin and diflunisal have a higher relative risk (4–5). The highest pooled relative risk is associated with piroxicam (7.4) and ketorolac (11.5).
Source: Peptic ulcer disease and non-steroidal antiinflammatory drugs. Dirini M et al
An elderly patient on Lithium develops gout. He is given a drug to help with the pain of gout but develops lithium toxicity. Which is the likely causative drug?
A Paracetamol
B Indomethacin
C Colchicine
D Aspirin
B
Explanation
Renal clearance of lithium is reduced by 25% with thiazide diuretics and the dose may need to be reduced by a similar amount. A similar reduction occurs with the newer NSAIDS. There is no issue with Aspirin however. Paracetamol is also safe. All neuroleptics with the possible exception of clozapine may produce more severe extrapyradimal side effects when combined with lithium
NSAIDs. This includes every drug in the non-steroidal anti-inflammatory drug category except Aspirin and Sulindac. If you have a patient on Lithium who is taking significant ongoing doses of ibuprofen, indomethicin, naproxen, or even the new Cox-2 inhibitors such as Celebrex, more aggressive monitoring of Lithium levels is warrented. Lithium level can double. The mechanism is not entirely clear, but may relate to the inhibition of prostaglandins leading to interference with Lithium excretion.
Extra: Textbook list
Important drug interactions with lithium
ACE inhibitors- decreased renal clearance (RC)
Angiotensin II blockers - decreased RC
Diuretics (thiazides)- decreased RC
Haloperidol- occasional neurotoxicity
Methyldopa- increased risk of neurotoxicity
NSAIDS- decreased RC
Theophylline- increased RC with reduced effect of Lithium
Which of the following opioid analgesia has weak binding at the mu receptors, serotonergic like effects, a risk of seizures and is only partially reversed by naloxone?
A Buprenorphine
B Tramadol
C Methadone
D Fentanyl
B
Explanation
Tramadol is a centrally acting analgesic whose main mechanism of action is blockade of serotonin reuptake. Because it is only partially reversed by Naloxone, it is believed to be a weak mu-receptor agonist. Toxicity includes an association with seizures. Another risk is the development of serotonin syndrome, especially if SSRI are being administered,
A patient with renal failure presents in severe pain. Which opioid is recommended?
A Fentanyl
B Morphine
C Codeine
D Oxycodone
A
Explanation
Hepatic oxidative metabolism is the primary route of degradation of the phenylpiperidine opioids (fentanyl) and eventually leaves only small quantities of the parent compound unchanged for excretion. No active metabolite of fentanyl has been reported.
Source: medscape
Recommendations for Opioids in Renal Impairment
Opioid
Recommended Use
Codeine - Not recommended due to accumulation
Fentanyl - Appears safe, but renal dosage adjustment may be necessary
Hydrocodone/oxycodone - Use cautiously; adjust dosage
Hydromorphone - Use cautiously; adjust dosage
Methadone - Appears safe; however, renal dosage adjustment may be necessary
Meperidine - Not recommended due to metabolites
Morphine - Not recommended due to metabolites
Tramadol - Not recommended
Which NSAID is a COX-2 selective inhibitor?
A Meloxicam
B Indomethacin
C Naproxen
D Peroxicam
A
Explanation
Celecoxib, meloxicam, ( rofecoxib, valdecoxib-removed from the market)
Cox-2 inhibitors have analgesic, antipyretic and anti-inflammatory effects similar to those of the non-selective NSAIDS but with an approximate halving of the gastro-intestinal adverse effects. Cox 2 inhibitors at usual dose do no inhibit platelet aggregation; in contrast they do inhibit prostacyclin synthesis in vascular endothelium. As a result COX-2 inhibitors do not offer the same cardio protective of the traditional nonselective NSAIDs, which has resulted in some patients taking a low dose aspirin in combination with a COX-2 regimen to maintain this effect,
Which has negligible first pass metabolism?
A Morphine
B Hydromorphone
C Hydrocodone
D Codeine
D
Explanation
According to oral:parenteral potency ratio
Morphine: low
Fentanyl: low
Hydromorphone: low
Hydrocodone: medium
Oxycodone: medium
Codeine: high
Certain analgesics such ads codeine and oxycodone are effective orally because they have reduced first pass metabolism. Morphine is extensively metabolised visa the oral route, making the oral dose requirements much higher than the parenteral dose to elicit a therapeutic effect.
Not a great question but based on a recall- so left as is
other sources:
A: Like codeine, oxycodone retained at least 1/2 of its analgesic activity when administered orally. We hypothesize that the high oral/parenteral relative potency ratios of codeine and oxycodone relative to morphine and its congeners are not due to more efficient absorption after oral administration, but rather that methylation at position 3 in codeine and oxycodone protects these drugs from rapid first-pass metabolism.
Source
J Pharmacol EXp Ther 1978 Oct;207(1):92-100.
B: Analgesic studies of codeine and oxycodone in patients with cancer. I. Comparisons of oral with intramuscular codeine and of oral with intramuscular oxycodone.
Codeine, in contrast to morphine, is two-thirds as effective orally as parenterally, both as an analgesic and as a respiratory depressant. It has therefore a highly oral-parenteral potency ratio (due to lower first-pass metabolism in the liver) (Goodman & Gilman, 1985). www.inchem.org
Paracetamol is a simple analgesic commonly given in the emergency department. What is the time to peak serum concentration after administration?
A 0.5 – 1.0 hours
B 1.0 – 1.5 hours
C 2.0 – 2.5 hours
D 1.5 – 2.0 hours
A
Explanation
Source: https://litfl.com/pharm-101-paracetamol/
The oral dose of morphine is higher than the parenteral dose required to produce a given analgesic effect, because:
A Morphine has a high first pass metabolism
B Morphine undergoes enterohepatic circulation
C Morphine has zero order kinetics
D Morphine has active metabolites
A
Explanation
Source: https://litfl.com/pharm-101-morphine/
Which is the most potent opioid analgesic?
A Morphine
B Fentanyl
C Buprenorphine
D Oxycodone
B
Explanation
Potency is defined as the dose required to produce 50% of the drug’s maximal effect. Fentanyl is usually given in the dose range 25-100mcg, compared to 2.5-10mg for morphine, 2.5-5mg for oxycodone, and buprenorphine 200-400mcg
Source: https://litfl.com/pharm-101-fentanyl/
Buprenorphine is a partial agonist. Which of the following may occur if it is given to a patient on long-term morphine treatment?
A It will have a synergistic effect
B It will have no analgesic effect
C It will produce profound respiratory depression
D It may precipitate a withdrawal syndrome
D
Explanation
Partial agonist: Produce a lower response when all receptors are occupied compared to full agonists. (out of TB: partial agonists produce a lower response , at full receptor occupancy , than do full agonists). Produce concentration-effect curves resembling those with a full agonist in presence of a non-competitive antagonist (i.e. reduced Emax). Competitively inhibit responses produced by full agonists e.g. buprenorphine and morphine can reduce analgesia and induce withdrawal symptoms if given to opioid-dependent patients.
A medication that is an antagonist at the mu receptor, produces little respiratory depression is:
A Buprenorphine
B Tramadol
C Naltrexone
D Methadone
C
Explanation
Tramadol, buprenorphine and methadone are opioid agonists. Naltrexone is a mu receptor antagonist.
A patient presents following an overdose with tinnitus, headache and hyperventilation. Which medication has he likely ingested in toxic quantities?
A Aspirin
B Paracetamol
C Tramadol
D Ibuprofen
A
Explanation
Aspirin toxicity causes “salicylism”, with features of hyperthermia, fever and vomiting accompanying headache, tinnitus, and dizziness.
Source: https://litfl.com/pharm-101-aspirin/
What pathway is responsible for the production of NAPQI in paracetamol ingestion?
A Glucuronidation
B Hydroxylation
C Methylation
D Sulfation
B
Explanation
In overdose, glucuoronidation and sulphation pathways are saturated and paracetamol is broken down by phase I hydroxylation reaction which forms NAPQI (N-acetyl-pbenzoquinone imine). More NAPQI is formed, depleting glutathione stores and eventually causing accumulation of this toxic metabolite
A patient is prescribed a xanthine oxidase inhibitor. Which of the following drugs might he have been prescribed?
A Colchicine
B Ibuprofen
C Corticosteroid
D Allopurinol
D
Explanation
The preferred and standard of care therapy for gout during the period between acute episodes is allopurinol, which reduces total uric acid body burden by inhibiting xanthine oxidase.
Which NSAID is reported to have the lowest gastro-intestinal upset
A Celecoxib
B Naproxen
C Diclofenac
D Ibuprofen
A
Explanation
The incidence of upper GI bleeding in over-the-counter Naproxen use is low but still double that of over-the-counter ibuprofen (perhaps due to a dose effect).
Some surveys suggest that indomethacin and tolmetin are the NSAIDs associated with the greatest toxicity, while salsalate, aspirin, and ibuprofen are least toxic
Meloxicam inhibits COX-2 over COX-1. It is associated with fewer clinical GI symptoms and complications than piroxicam, diclofenac, and naproxen
The provided text states that celecoxib is associated with fewer endoscopic ulcers than most other NSAIDs. It also indicates that meloxicam is associated with fewer clinical GI symptoms and complications than piroxicam, diclofenac, and naproxen. However, a direct comparison of celecoxib and meloxicam in terms of GI upset is not explicitly provided.
Source: Katzung pharmacology 15ed
Which drug is an irreversible cox-2 inhibitor
A Aspirin
B Clopidogrel
C Ticagrelor
D Ibuprofen
A
Explanation
Aspirin is not a COX-2 inhibitor; it’s a non-selective COX inhibitor. While it irreversibly inhibits COX enzymes, this action is not specific to COX-2; it affects both COX-1 and COX-
Which of the NSAIDS has the least gastro-intestinal side effects?
A Diclofenac
B Celecoxib
C Aspirin
D Indomethacin
B
Explanation
All NSAIDs, including aspirin, are about equally efficacious with a few exceptions-Tolmetin seems not to be effective for gout, and aspirin is less effective thanother NSADIS for ankylosing spondylitis. Therefore, NSAIDS tend to be differentiated on the basis of toxicity and cost effectiveness.
Some surveys suggest that indomethacin and tolmetin are the NSAIDs associated with the greatest toxicity, while aspirin and ibuprofen are least toxic. The selective COX2 inhibitors were not included in these surveys.
For patients with renal insufficiency, nonacetylated salicylates may be best. Diclofenac and sulindac are associated with more liver function test abnormalities than other NSAIDs. The relatively expensive selective COX-2 Inhibitor celecoxib is probably safest for patients at high risk of GI bleeding but may have a higher risk of cardiovascular toxicity.: in this subpopulation of patients, they aremore cost effective despitetheirhighacquisition costs.
The choice of NSAIDS thus require a balance of efficacy., cost effectiveness, safety and numerous personal factors (eg other drugs being used, concurrent illness, compliance) so that there is no best NSAID for all patients. There may be one or two best NSAIDS for a specific person
Celecoxib is associated with fewer endoscopic ulcers than most other NSAIDs. However, it also notes that the older NSAIDs (compared to celecoxib) have a correlation between the amount of enterohepatic circulation and the degree of GI irritation. The TB also mentions that newer NSAIDs, as a group, tend to cause less GI irritation than aspirin
