MSK Exam 2

Jin - 12 questions | Fisher 32 questions | Miskle 8 questions | 52 Total Questions

decreases the awareness to pain while raising the pain threshold

analgesics

designed to inhibit or reduce inflammatory in animals and man

anti-inflammatory

decreases the temperature in a feverish individual but not in a normal temperature individual

antipyretics

a normal beneficial process that begins immediately after injurty to facilitate repair and return the tissue to normal function

inflammatory process

the inflammatory process is initated by stimulus including what?

physical trauma, radiation, chemicals, heat, infection, and hypersensitivity

The important chemical mediators that involves the pain response, vascular permeability, and chemotaxis

prostaglandins and leukotrienes

_______ ____ is an unsaturated fatty acid that is the substrate for the production of compounds (metabolites) that contribute to the inflammatory response

arachidonic acid

metabolites of arachidonic acid are also known as

eicosanoids

What catalyzes the intracellular release of arachidonic acid from phospholipids?

Phospholipase A

What is the rate determining step in biosynthesis of prostaglandins from arachidonic acid

cyclooxygenase (COX1 and COX2)

Prostaglandins are naturally occuring ____-carbon cyclopentano-fatty acid derivatives

20 carbon

NSAIDs have a major mechanism of action to [increase/decrease] Prostaglandin production by [facilitating/inhibiting] one or both of the cyclooxygenase isoforms (COX-1 and COX-2)

1. decrease

2. inihbiting

Aspirin is the ______ form of o-hydroxy benzoic acid (salicylic acid)

aceylated

Aspirin inhibits the biosynthesis of ________ at the ________ stage.

1. prostaglandins

2. cyclooxygenase

Aspirin is the ONLY NSAID that ______ modifies COX by acetylating Ser__ of COX1 and Ser___ of COX2.

1. Covalently

2. Ser 530

3. Ser 516

The phenolic and carboxylic acid of aspirin and derivatives must be ____.

ortho

What happens to aspirin in humid conditions?

hydrolyzes to salicylic acid and acidic acid under humid conditions

Describe what it means when a structure in ortho.

The substituent is located directly next to the primary existing group on the ring.

salicylamide is NOT acidic, NOT a salicylate, NOT an ester. What side effect is less likely to happen? Who would be the best to use this medication? How is the anti-inflammatory activity?

Lack of GI irritation

People with aspirin hypersensitivity can use it

Minimal anti-inflammatory activity - analgesic and antipyretic activity mostly

In arylacetic acids, the center of acidity is usually located one carbon atom ______ to a flat surface (represented by what?)

carbon atom adjacent

represented by an aromatic or heteroaromatic ring

What is the most potent NSAID?

Indomethacin

What are common side effects of Indomethacin

GI tract, CNS, Ear (tinnitus)

Only the __-(+)-isomer has antiinflammatory activity for ibuprofen.

S

Sort the following based on inflammatory activity (potent to less potent)

aspirin, ibuprofen, indomethacin

(potent) indomethacin > ibuprofen > aspirin (less potent)

True or false. Naproxen is recommended for pregnant or lactating women and children under 16.

False.

Ketoprofen [facilitates/inhibits] the synthesis of leukotrienes and leukocyte migration into inflamed joint as well as [facilitating/inhibiting] the biosynthesis of prostaglandins.

inhibits

inhibiting

Nabumetone is a non-acidic prodrug because it has a _____ in the structure.

Ketone

Nabumetone is a prodrug that transforms into the active metabolite _____.

6-methoxynaphthalene-2-acetic acid

Ketoralac is more effective as an ______ than as an ______.

analgesic

anti-inflammatory

Ketorolac is contraindicated in patients currently recieving ____ or _____ due to the cumulative risk of inducing serious side effects.

Aspirin

NSAIDs

Diclofenac belongs to arylacetic acids but is also considered as a homolog of _________ _____.

N-arylanthranilic acid

Diclofenac inhibits _____ and the _______ pathway resultin in [increased/decreased] production of leukotriene.

COX and the Lipoxygenase pathway

decreased production

Diclofenac [facilitates/inhibits] arachidonic acid reliese and stimulation of its uptake, resulting in a [increase, reduction] of arachidonic acid availability.

inhibits

reduction

What is the first and now the only selective COX2 inhibitor on the market?

Celecoxib (Celebrex)

Adverse effects of selective COX-2 inhbitors include:

[increased/decreased] risk of CV events

increased

In APAP metabolism, hepatic proteins undergo conjugate _____ resulting in hepatice necrosis of renal failure

ADDITION

acetanilide, acetaminophen, and phenacetin are what class?

aniline and p-aminophenol derivatives

Celecoxib (Celebrex), Rofecoxib, Valdecoxib, and Lumiracoxib are what class?

Selective COX 2 inhibitors

Opiate vs Opioid:

drugs derived from opium - morphine, codiene, and their semi synthetic analogs

opiate

Opiate or Opioid:

peptides in brain that had morphine-like pharmacologic activity that include natural and synthetic compounds and peptides

Opioid

Endorphins (peptide) act on what receptor?

mu

dynorphins (peptide) act on what receptor?

kappa

enkephalins (peptide) act on what receptor?

delta

What is the key agonist on mu?

Morphine

What is the key antagonist on mu?

naloxone and naltrexone

What is the main opioid receptor found in the cortex?

kappa

What is the main opioid receptor found in the limbic system?

mu

what is the main opioid receptor found in the brain stem?

mu

what is the main opioid receptor found in the spinal cord?

mu

what is the main opioid receptor found in the nociceptors?

mu

True or false. Opioid receptors are G-protien coupled receptors

True

Examples of full agonist drugs acting on opioid receptors?

Morphine, codiene, oxycodone, fentanyl, heroine

Example of a partial agonist drug acting on opioid receptors?

buprenorphine

What is special about nalbuphine on how they act on opioid receptors?

agonist-antagonist acting

at the kappa - agonist

at the mu - antagonist

Even though buprenorphine is a partial agonist, explain how it is effective in treatment for opioid use disorder.

it is more potent thatn morphine with no euphoric effect. it binds much tighter to the receptor (higher affinity) than morphine so it can displace it (if its in the system)

Example of an antagonist on opioid receptors.

Naloxone

What CYP converts codiene into the active metabolite?

CYP2D6

What CYP converts codiene into the inactive version?

CYP3A4

Morphine is what class…

Phenanthrenes

Pentazocine is what class…

Benzomorphans

Fentanyl is what class

Phenylpiperidines

Methadone is what class?

Diphenylheptanes

Tramadol is what class?

Phenylpropylamines

Meperidine binds mu but it primarily targets ____.

Kappa

At [low/high] doses loperamide behaves like a calcium-calmodulin antagonist and calcium channel blocker.

High

What keeps loperamide from crossing the BBB?

efflux by p-glycoprotein in the intestinal wall and blood brain barrier

high first pass effect

Which is responsible for therapetuic effects of methadone, S or R.

R-methadone - 10 fold greater affinity for mu opioid receptor

S-methadone ______ the re-uptake of serotonin and NE.

prevents

Side effects of S-methadone due to binding to the hERG.

QT-prolongation

Tramadol has an _____ effect on opioid receptors.

indirect

Tramadol is a racemic mixture, the [+-] enantomer inhibits serotonin reuptake while the [+-] enatomer inhibits NE reuptake

positive

negative

Both enantamers of tramadol are agonists of the ____ receptor.

mu

Naloxone is a pure competitive opioid ______ with a high affinity of for the ____-opioid receptor

antagonist

mu

LECTURE SEPARATER: END JIN

LECTURE SEPARATER: START FISHER

MOA: Morphine is an Agonist at ____ and _____ opioid receptors

mu and kappa

What is the main metabolism that morphine undergoes?

UGT2B7 NOT CYP

At what CrCl does morphine require dose adjustment? Contraindicated level?

Adjustment - 50

Contraindication - 30

Morphine metabolizes into metabolites M3G which is ____ and M6G which is ____.

inactive

active

Why is morphine best for liver disease?

CYP metabolized opioids fail in liver disease. Those that go through phase 1 fail, morphine only goes through phase 2 (UGT) metabolism

What are four categories of drugs that interact with majority of opioids?

CNS DEPRESSANTS

• BZDs

• antidepressants

• Gabapentinoids

• SKMRs

Morphine is neurotoxic in severe renal impairment due to ______ of the ____ metabolite. What is so dangerous about this?

accumulation of the M3G metabolite

causes seizures, myoclonus, and death

Morphine has the most ____ release of the opioids causing itching and hypotension

histamine

Codeine metabolizes into morphine via CYP____.

2D6

MOA: Methadone is an ____ at the mu receptor, _____ at the NMDA receptor, _____ serotonin and NE reuptake (weakly)

Agonist

antagonist

inhibits

What CYP pathways does methadone use in metabolism?

2B6, 3A4, 2D6, 2C19, 2C9

At what CrCl does methadone require dose adustment?

10

What is the inactive metabolite of Methadone?

EDDP

What is the main concern for drug interactions for methadone?

QTc-prolonging drugs

What are other DDI that methadone has?

anti-infectives

antidepressants

BZDs, SKMRs

Alcohol

gabapentinoids

amiodarone

Methadone is [lipophilic/hydrophilic] and has a [short/long] and variable half-life

lipophilic

long

What is the MAX dose of methadone for a patient converting from another opioid

40mg TDD

what is the max dose of methadone for an opioid naive patient

2.5mg q8h

MOA: Tramadol is a Weak ___ receptor agonist + _____ reuptake of serotonin and norepinephrine

mu

inhibits

What CYPs are used for tramadol metabolism

2D6, 3A4, 2B6

At what point is dose adjustment recommended for CrCl for tramadol?

30

What is the active metabolite of tramadol

M1

Which CYP is required for SNRI and little MOR activity in tramdol?

CYP2D6

Tramadol pearls (SSSHH)

increases S_____ ____

S_____ S_____

H_______

H_______

increases seizure risk

serotonin syndrome

hypoglycemia

hyponatremia

Tramadol DDIs

bupropion

TCAs, SSRIs, SNRIs

Gabapentinoids

BZDs

Alcohol

SKMRs